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As filed with the Securities and Exchange Commission on April 1, 2015

Registration No. 333-            

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM S-1

REGISTRATION STATEMENT

UNDER

THE SECURITIES ACT OF 1933

GELESIS, INC.

(Exact name of registrant as specified in its charter)

500 Boylston Street, Suite 1600

Boston, Massachusetts 02116

(617) 456-4718

(Address, including zip code, and telephone number, including area code, of registrant’s principal executive offices)

Yishai Zohar

Chief Executive Officer

Gelesis, Inc.

500 Boylston Street, Suite 1600

Boston, Massachusetts 02116

(617) 456-4718

(Name, address, including zip code, and telephone number, including area code, of agent for service)

Copies to:

Approximate date of commencement of proposed sale to public: As soon as practicable after this Registration Statement is declared effective.

If any of the securities being registered on this Form are to be offered on a delayed or continuous basis pursuant to Rule 415 under the Securities Act of 1933, check the following box.  ¨

If this Form is filed to register additional securities for an offering pursuant to Rule 462(b) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering.  ¨

If this Form is a post-effective amendment filed pursuant to Rule 462(c) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering.  ¨

If this Form is a post-effective amendment filed pursuant to Rule 462(d) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering.  ¨

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, or a smaller reporting company. See the definitions of “large accelerated filer,” “accelerated filer” and “smaller reporting company” in Rule 12b-2 of the Exchange Act.

CALCULATION OF REGISTRATION FEE

The registrant hereby amends this registration statement on such date or dates as may be necessary to delay its effective date until the Registrant shall file a further amendment which specifically states that this registration statement shall thereafter become effective in accordance with Section 8(a) of the Securities Act of 1933 or until the registration statement shall become effective on such date as the Securities and Exchange Commission, acting pursuant to said Section 8(a), may determine.

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The information in this prospectus is not complete and may be changed. We may not sell these securities until the Securities and Exchange Commission declares our registration statement effective. This prospectus is not an offer to sell these securities and it is not soliciting an offer to buy these securities in any state where the offer or sale is not permitted.

Subject to completion, dated April 1, 2015

             Shares

GELESIS, INC.

Common Stock

$         per share

This investment involves risk. See “Risk Factors” beginning on page 12.

We are an “emerging growth company” as that term is used in the Jumpstart Our Business Startups Act of 2012 and, as such, may elect to comply with certain reduced public company reporting requirements for future filings.

The underwriters have a 30-day option to purchase up to              additional shares of common stock from us.

Neither the Securities and Exchange Commission nor any state securities commission has approved of anyone’s investment in these securities or determined if this prospectus is truthful or complete. Any representation to the contrary is a criminal offense.

The underwriters expect to deliver the shares on or about                     , 2015.

The date of this prospectus is                     , 2015

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You should rely only on the information contained in this prospectus. We have not, and the underwriters have not, authorized any other person to provide you with different information. This prospectus is not an offer to sell, nor is it seeking an offer to buy, these securities in any state where the offer or sale is not permitted. The information in this prospectus is complete and accurate as of the date on the front cover, but the information may have changed since that date.

Through and including                     , 2015 (the 25th day after the date of this prospectus), all dealers that effect transactions in these securities, whether or not participating in this offering, may be required to deliver a prospectus. This is in addition to the dealers’ obligation to deliver a prospectus when acting as underwriters and with respect to their unsold allotments or subscriptions.

For investors outside of the United States: We have not, and the underwriters have not, done anything that would permit this offering or possession or distribution of this prospectus in any jurisdiction where action for that purpose is required, other than the United States. Persons outside of the United States who come into possession of this prospectus must inform themselves about, and observe any restrictions relating to, the offering of the shares of common stock and the distribution of this prospectus outside of the United States.

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RISK FACTORS

Investing in our common stock involves a high degree of risk. You should carefully consider the following risks and uncertainties, together with all other information in this prospectus, including our consolidated financial statements and related notes, before investing in our common stock. Any of the risk factors we describe below could adversely affect our business, financial condition or results of operations. The market price of our common stock could decline if one or more of these risks or uncertainties actually occur, causing you to lose all or part of the money you paid to buy our common stock. Additional risks that we currently do not know about or that we currently believe to be immaterial may also impair our business. Certain statements below are forward-looking statements. See “Special Note Regarding Forward-Looking Statements” in this prospectus.

Risks Related to Our Financial Position and Need for Capital

We are a clinical stage biotechnology company with a limited operating history and have not generated any product sales. We have incurred significant operating losses since our inception and anticipate that we will incur continued losses for the foreseeable future.

We are a clinical stage biotechnology company with a limited operating history on which to base your investment decision. Clinical development is a highly speculative undertaking and involves a substantial degree of risk. We were incorporated in February 2006. Our operations to date have been limited primarily to organizing and staffing our company and conducting research and development activities for Gelesis100. We have never generated any product sales. We have not obtained regulatory approvals for any of our product candidates.

We have funded our operations to date through proceeds from collaborations and issuance of common and convertible preferred stock, issuance of convertible and non-convertible debt and non-dilutive grants received from government agencies. We have incurred losses in each year since our inception, other than fiscal 2013. Our net loss was $17.7 million for the year ended December 31, 2014 and we had an accumulated deficit of $45.4 million as of December 31, 2014. Our prior losses, combined with expected future losses, have had and will continue to have an adverse effect on our stockholders’ deficit and working capital. We expect to incur increasing levels of operating losses over at least the next several years. We expect our research and development expenses to significantly increase in connection with our continued development of Gelesis100 and the development of our future product candidates, including Gelesis200 and any other product candidates that we may choose to pursue. In addition, if we obtain marketing approval for Gelesis100, we will incur significant sales and marketing expenses. Once we are a public company, we will incur additional costs associated with operating as a public company. Because of the numerous risks and uncertainties associated with developing our product candidates, we are unable to predict the extent of any future losses or when we will become profitable, if at all. Even if we do become profitable, we may not be able to sustain or increase our profitability on a quarterly or annual basis.

Our ability to become profitable depends upon our ability to generate product sales. To date, we have not generated any product sales of our lead product candidate, Gelesis100, and we do not know when, or if, we will generate any product sales from Gelesis100. We will not generate significant product sales unless and until we obtain regulatory approval of, and begin to sell, Gelesis100. Our ability to generate product sales depends on a number of factors, including, but not limited to, our ability to:

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We expect to incur significant sales and marketing costs as we prepare to commercialize Gelesis100. Even if we initiate and successfully complete our pivotal clinical trials of Gelesis100 and it is approved for commercial sale, Gelesis100 may not be a commercially successful product. We may not achieve profitability soon after generating product sales, if ever, and may be unable to continue operations without continued funding.

Even if this offering is successful, we will need to raise additional funding, which may not be available on acceptable terms, if at all. Failure to obtain this necessary capital when needed may force us to delay, limit or terminate our product development efforts or other operations.

We are currently advancing Gelesis100 through clinical development. Developing our hydrogel technology is expensive and we expect our research and development expenses to increase substantially in connection with our ongoing activities, particularly as we advance Gelesis100 in clinical trials. Depending on the status of regulatory approval or, if approved, commercialization of Gelesis100, as well as the progress we make in selling Gelesis100, we may require additional capital to fund operating needs thereafter. We may also need to raise additional funds sooner if we choose to pursue additional indications and/or geographies for Gelesis100 or otherwise expand more rapidly than we presently anticipate.

As of December 31, 2014, our cash was $2.6 million. In March 2015, the Company raised $18.0 million through the issuance of Series A-5 convertible preferred shares. We estimate that the net proceeds from this offering will be approximately $         million, based on an assumed initial public offering price of $         per share, the midpoint of the price range set forth on the cover of this prospectus, after deducting estimated underwriting discounts and commissions and estimated offering expenses payable by us. We expect that the net proceeds from this offering, together with our existing cash, will be sufficient to fund our current operations until at least                         . However, our operating plan may change as a result of many factors currently unknown to us, and we may need to seek additional funds sooner than planned, through public or private equity or debt financings, government or other third party funding, marketing and distribution arrangements and other collaborations, strategic alliances and licensing arrangements or a combination of these sources. In any event, we will require additional capital to obtain regulatory approval for, and to commercialize, Gelesis100 and our future product candidates. Even if we believe we have sufficient funds for our current or future operating plans, we may seek additional capital if market conditions are favorable or if we have specific strategic considerations.

If we are unable to obtain funding on a timely basis, we may be required to significantly curtail, delay or discontinue one or more of our research or development programs or the commercialization of any product candidate or be unable to expand our operations or otherwise capitalize on our business opportunities, as desired, which could materially affect our business, financial condition and results of operations.

Raising additional capital may cause dilution to our existing stockholders, restrict our operations or require us to relinquish rights.

We may seek additional capital through a combination of private and public equity and debt offerings, government or other third party funding, marketing and distribution arrangements and other collaborations, strategic alliances and licensing arrangements or a combination of these sources. To the

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extent that we raise additional capital through the sale of common stock or securities convertible or exchangeable into common stock, your ownership interest in our company will be diluted. In addition, the terms of any such securities may include liquidation or other preferences that materially adversely affect your rights as a stockholder. Debt financing, if available, would increase our fixed payment obligations and may involve agreements that include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures or declaring dividends. If we raise additional funds through collaborations, strategic partnerships and licensing arrangements with third parties, we may have to relinquish valuable rights to Gelesis100, our intellectual property or future revenue streams or grant licenses on terms that are not favorable to us.

Our ability to use our net operating loss carryforwards and certain tax credit carryforwards may be subject to limitation.

As of December 31, 2014, we had federal and state net operating loss carryforwards of $14.2 million and $10.3 million, respectively. Our federal net operating loss carryforwards begin to expire in 2026, and our state net operating loss carryforwards began to expire in 2015. Under Section 382 of the Internal Revenue Code of 1986, as amended, or the Code, changes in our ownership may limit the amount of our net operating loss carryforwards and research and development tax credit carryforwards that could be utilized annually to offset our future taxable income, if any. Any such limitation may significantly reduce our ability to utilize our net operating loss carryforwards and research and development tax credit carryforwards before they expire. We have completed a study to assess whether an ownership change for purposes of Section 382 has occurred, or whether there have been multiple ownership changes since our inception. The results of this study indicate that a cumulative change in ownership of our company greater than 50% has occurred, and, therefore, we have an annual limitation of the amount of net operating losses we can carryforward to offset future taxable income of approximately $0.3 million, and impaired federal and state net operating losses of approximately $9.1 million, federal research tax credits of $0.2 million, and state research tax credits of $0.1 million. This and any other limitations, whether as the result of this offering, prior private placements, sales of our common stock by our existing stockholders or additional sales of our common stock by us after this offering, could have a material adverse effect on the amount of net operating losses we can utilize to offset future taxable income.

Risks Related to Product Development, Regulatory Approval and Commercialization

We are dependent on the success of our hydrogel therapeutics, specifically our lead product candidate, Gelesis100, which is in clinical development. We cannot be certain that we will be able to obtain regulatory approval for Gelesis100 or any other product candidate.

We currently have one product candidate, Gelesis100, in clinical development. Our business depends on the successful clinical development, regulatory approval, and commercialization of Gelesis100 or other product candidates based on our hydrogel technology. We currently have no products for sale and may never be able to develop marketable products. Gelesis100, which is currently in clinical development for its initial indication as a treatment for weight loss in overweight and obese patients, will require substantial additional clinical development, testing and regulatory approval before we are permitted to commercialize it. Our second product candidate, Gelesis200, is still in pre-clinical development. The clinical trials of our product candidates are, and the manufacturing and marketing of our product candidates will be, subject to extensive and rigorous review and regulation by numerous government authorities in the United States and in other countries where we intend to test and, if approved, market our product candidates. Before obtaining regulatory approval for the commercial sale of any product candidate, we must demonstrate through pre-clinical testing and clinical trials that the product candidate is safe and effective for use in each target indication. This process can take many years and may include post-marketing studies and surveillance, which will require the expenditure of substantial resources beyond the proceeds we raise in this offering. Accordingly, even if we are able to obtain the requisite financing to continue to fund our development and clinical trials, we cannot assure you that Gelesis100 or any other of our future product candidates, including Gelesis200, will be successfully developed or commercialized.

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We believe that Gelesis100 and any other product candidates based on our hydrogel technology, including Gelesis200, will be regulated as medical devices because they do not achieve their primary intended purposes through chemical action within or on the body and are not dependent upon being metabolized for the achievement of their primary intended purposes. Additionally, we have engaged in discussions with CDRH, which has indicated that Gelesis100 will be regulated as a medical device. Before we can market or sell a new product regulated as a medical device in the United States, we must obtain marketing authorization under one of the three following regulatory pathways (i) Section 510(k) of the Federal Food, Drug, and Cosmetic Act, or FDC Act, (ii) a premarket approval application, or PMA, or (iii) de novo classification of our product. In the 510(k) clearance process, the FDA must determine that a proposed device is “substantially equivalent” to a device legally on the market, known as a “predicate” device, with respect to intended use, technology and safety and effectiveness, in order to clear the proposed device for marketing. Clinical data are sometimes required to support substantial equivalence. In the second pathway, the PMA process, the FDA must determine that a proposed device is safe and effective for its intended use based, in part, on extensive data, including, but not limited to, technical, pre-clinical, clinical trial, manufacturing and labeling data. The PMA process is typically required for products that are deemed to pose the greatest risk, such as life-sustaining, life-supporting or implantable devices. The third pathway is called de novo classification, which is generally used for low- to moderate-risk products that have not previously been classified by the FDA and therefore no predicate device is available. Devices not previously classified by the FDA are automatically placed into Class III; through the de novo process a manufacturer may request reclassification as a Class I or II device. If the FDA agrees to reclassify the device, it will then clear the device through the de novo process, and future devices of a similar nature may use the device cleared through the de novo process as a predicate device for a 510(k) submission. We currently intend to pursue the PMA pathway for Gelesis100. Obtaining a PMA is generally more costly and uncertain than the 510(k) clearance process or the de novo classification process and generally takes from one to three years, or even longer, from the time the application is submitted to the FDA until an approval is obtained.

We recently completed a clinical trial, the FLOW study, evaluating Gelesis100’s ability to induce weight loss in overweight and obese patients. In April 2014, we held a pre-submission meeting with the FDA to discuss the proposed clinical development plan and regulatory pathway to support marketing authorization in the United States. Based on these discussions and additional ongoing discussions with European notified bodies, we have initiated a larger clinical study, which is 6 months in duration and includes overweight and obese patients, including those with prediabetes and mild type 2 diabetes, which we refer to as the GLOW study. We anticipate that the GLOW study could, subject to the outcome of our discussions with European notified bodies, serve as the pivotal study for obtaining a CE Mark, which would permit Gelesis100 to be marketed in the European Economic Area for a weight loss indication for overweight and obese patients. In the United States, we expect the GLOW study will serve as proof of concept for weight loss in overweight and obese patients at 6 months. We received preliminary feedback from a centralized institutional review board, or IRB, that the GLOW study would be considered a nonsignificant risk, or NSR, study. In parallel, on March 4, 2015, we held a pre-submission meeting with the FDA to discuss the protocol and statistical analysis plan for the GLOW study. In advance of this pre-submission meeting, the FDA provided us with initial feedback in which it designated the GLOW study as a significant risk study. We are providing a detailed response, including limited protocol amendments per their request, to support a NSR designation. In addition, we are requesting a formal risk determination from the FDA and believe that, based on the discussions during our pre-submission meeting, we will receive NSR status for the GLOW study. If we do not receive NSR status, we will complete the GLOW study in the non-U.S. sites and expect no change in the scheduled readout of the GLOW study. We intend to use the data from both the FLOW and GLOW studies to design the pivotal study for Gelesis100 in the United States for a weight loss indication. Because we expect to include a broader patient population in the pivotal trial that includes patients that are treated for comorbidities common in overweight and obese populations, we believe that the pivotal trial will have a different risk profile from the GLOW study, and we intend to file for an Investigational Device Exemption, or IDE, for

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our FDA pivotal trial. There is no assurance that the data from either the FLOW or GLOW studies will provide support for a premarket submission.

Neither the FDA nor any European notified bodies are bound by any of the discussions that we have had with them to date regarding the scope of our clinical studies and the related endpoints that will be necessary to qualify as pivotal studies and to demonstrate safety and effectiveness for purposes of approval in the United States and Europe. The FDA is not obligated to follow the recommendations it provides to companies as a result of a pre-submission meeting. In addition, any changes to the safety profile of our product candidates, including the level and severity of any adverse events, could result in the FDA or European notified bodies requiring us to conduct additional clinical trials or change the primary endpoints of our clinical trials to support regulatory approval.

The FDA and certain European notified bodies may delay, limit or deny approval of Gelesis100, or other future product candidates, for many reasons, including, among others:

Any of these factors, many of which are beyond our control, could jeopardize our ability to obtain regulatory approval for and successfully market Gelesis100 or our other future product candidates, including Gelesis200. Moreover, because our business is almost entirely dependent upon Gelesis100 and its underlying hydrogel technology, any such setback in our pursuit of regulatory approval would have a material adverse effect on our business and prospects.

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Positive results from early clinical trials of Gelesis100 in weight loss and glycemic control are not necessarily predictive of the results of later clinical trials of Gelesis100.

Positive results in one of the two doses studied in our FLOW study that showed preliminary evidence of statistically significant weight loss in overweight and obese patients may not necessarily be predictive of the results in the GLOW study or any other required later clinical trials. If we cannot demonstrate more significant weight loss in the GLOW study or other later clinical trials than we did in the FLOW study, we may be unable to successfully develop, obtain regulatory approval for and commercialize Gelesis100 for that indication. For example, the placebo-adjusted total body weight loss in the 2.25 g arm of Gelesis100 was 2% in the FLOW study, but one of the two co-primary endpoints in the GLOW study will be placebo-adjusted weight loss of ³ 3%. Our GLOW study will be for a longer duration (6 months) and includes prediabetic and mild type 2 diabetic patients, to assess the effect of Gelesis100 on weight loss and improvement of certain glycemic parameters, as measured by the study’s secondary endpoints. The FLOW study was a 3 month study and, therefore, its results may not be predictive of the weight loss results that we will obtain in the GLOW study. In addition, although we observed improvement in certain glycemic parameters, such as insulin levels, insulin resistance, and fasting blood glucose levels, the FLOW study did not include any type 2 diabetic patients. Our ability to potentially include limited information regarding weight loss and safety in diabetic patients in approved labeling for Gelesis100 depends on our ability to replicate the improvements in glycemic parameters that were seen in a limited number of prediabetic patients in the FLOW study. Moreover, the more pronounced weight loss seen in the small subset of prediabetic patients was based on an analysis of a group that was not pre-specified, and such exploratory analysis may not be predictive of later trials. In addition, the FDA has stated that a study to support a claim or indication of diabetes management or glycemic control would need to be longer than six months in duration and would have to have HbA1c improvement as the primary endpoint. As our GLOW study is not designed to include these features, it could not support a claim or indication for diabetes management or glycemic control in prediabetic or type 2 diabetic populations and can only serve as a proof of concept study for glycemic control. The FLOW study was conducted at sites in Denmark, the Czech Republic, and Italy, and results gathered there may not be replicated in the GLOW study in which additional sites will be included. If we fail to produce positive results in the GLOW study relative to weight loss, the development timeline and regulatory approval and commercialization prospects for Gelesis100, and, correspondingly, our business and financial prospects, would be materially adversely affected.

Failures or delays in the commencement or completion of our planned clinical trials of Gelesis100 could result in increased costs to us and could delay, prevent or limit our ability to generate product sales and continue our business.

We initiated our GLOW study to assess the effect of Gelesis100 on body weight and glycemic control in overweight and obese patients, including those with prediabetes and mild type 2 diabetes, in November 2014 and expect to report data in the first half of 2016. However, we cannot assure you that the GLOW study will be completed on schedule, if at all. In addition, we designed the primary endpoints of this study based on ongoing conversations with the FDA and certain European notified bodies. Despite the guidance received from, and that which we expect to receive from the FDA, and the European notified bodies, both can change their positions on the acceptability of our trial designs or the clinical endpoints selected, which may require us to complete additional clinical trials or impose stricter approval conditions than we currently expect. Completion of a successful pivotal trial is a prerequisite to submitting a PMA application and, consequently, obtaining authorization to begin commercial marketing of Gelesis100. The commencement and completion of clinical trials, including the GLOW study, could be delayed or prevented for a number of reasons, including, among others:

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Clinical trials may also be delayed or terminated as a result of ambiguous or negative interim results. In addition, a clinical trial may be suspended or terminated by us, the FDA, European regulatory authorities, the IRBs or Ethics Committees at the sites where they are overseeing a clinical trial, a data and safety monitoring board, or DSMB, overseeing the clinical trial due to a number of factors, including, among others:

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If drug-device interaction studies, or DDI studies, show that there are interactions between Gelesis100 and certain drugs commonly prescribed for comorbidities in the obese and overweight population, patients using these drugs may be excluded from using Gelesis100, which could have a material adverse effect on our results of operations, financial condition and prospects.

Overweight and obesity are associated with a number of comorbidities, including but not limited to, type 2 diabetes, hypertension, heart disease, and hypercholesterolemia. The treatment of these comorbidities involves chronic administration of various classes of orally administered drugs, including but not limited to, metformin, oral antidiabetics, antihypertensives, antidyslipidemics, and oral anticoagulants. These drugs are absorbed systemically as they travel through the GI tract. In order to treat these patients with Gelesis100, we will be required to perform drug-device interaction studies both in vitro and, if necessary, in patients, to ensure that Gelesis100 does not impede or interfere with the pharmacokinetics or pharmacodynamics of these drugs. If these studies show that the pharmacokinetics of these drugs are affected by Gelesis100, patients using these drugs may be excluded from the product label, which could have a material adverse effect on our results of operations, financial condition and prospects.

We rely, and expect that we will continue to rely, on third parties to conduct any clinical trials for Gelesis100. If these third parties do not successfully carry out their contractual duties or meet expected timelines, we may not be able to obtain regulatory approval for or commercialize Gelesis100 and our future product candidates, including Gelesis200, and our business could be substantially harmed.

We enter into agreements with third party CROs to provide monitors for and to manage data for our ongoing clinical trials. We have and will rely heavily on these parties for execution of clinical trials for Gelesis100 and our future product candidates, including Gelesis200, and control only certain aspects of their activities. As a result, we have less control over the conduct, timing and completion of these clinical trials and the management of data developed through the clinical trials than would be the case if we were relying entirely upon our own employees. Communicating with outside parties, such as CROs, can also be challenging, potentially leading to mistakes as well as difficulties in coordinating activities. Outside parties may:

These factors may materially adversely affect the willingness or ability of third parties to conduct our clinical trials and may subject us to unexpected cost increases that are beyond our control. Nevertheless, we are responsible for ensuring that each of our trials is conducted in accordance with the applicable protocol, legal and regulatory requirements, and scientific standards, and our reliance on CROs does not relieve us of our regulatory responsibilities. We and our CROs are required to comply with Good Clinical Practices, or GCPs, which are regulations and guidelines enforced by the FDA and European notified bodies for any products in clinical development. The FDA enforces these GCP regulations through periodic inspections of clinical trial sponsors, principal investigators and trial sites. If we or our CROs fail to comply with applicable GCPs, the clinical data generated in our clinical trials may be deemed unreliable and the FDA or European notified bodies may require us to perform additional clinical trials before considering our marketing applications for approval. We cannot assure you that, upon inspection, the FDA will determine that any of our clinical trials comply with GCPs. In addition,

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our clinical trials must be conducted with product produced under the QSR requirements. Our failure or the failure of our CROs to comply with these regulations may require us to repeat clinical trials, which would delay the regulatory approval process and could also subject us to enforcement action, including civil and criminal penalties.

Although we design our clinical trials for Gelesis100 and will design our clinical trials for our future product candidates, including Gelesis200, CROs conduct and will conduct all of the clinical trials. As a result, many important aspects of our product development programs are outside of our direct control. In addition, the CROs may not perform all of their obligations under arrangements with us or in compliance with regulatory requirements, but we remain responsible and are subject to enforcement action that may include civil penalties up to and including criminal prosecution for any violations of FDA laws and regulations during the conduct of our clinical trials. If the CROs do not perform clinical trials in a satisfactory manner, breach their obligations to us or fail to comply with regulatory requirements, the development and commercialization of Gelesis100 and our future product candidates, including Gelesis200, may be delayed or our development program materially and irreversibly harmed. We cannot control the amount and timing of resources these CROs devote, or will devote, to Gelesis100 and our future product candidates, including Gelesis200. If we are unable to rely on clinical data collected by our CROs, we could be required to repeat, extend the duration of, or increase the size of our clinical trials and this could significantly delay approval and commercialization and require significantly greater expenditures by us.

If any of our relationships with these third party CROs terminate, we may not be able to enter into arrangements with alternative CROs. If CROs do not successfully carry out their contractual duties or obligations or meet expected timelines, if they need to be replaced or if the quality or accuracy of the clinical data they obtain is compromised due to the failure to adhere to our clinical protocols, regulatory requirements or for other reasons, any such clinical trials may be extended, delayed or terminated, and we may not be able to obtain regulatory approval for Gelesis100 or our future product candidates, including Gelesis200. As a result, our financial results and the commercial prospects for Gelesis100 and our future product candidates, including Gelesis200, in the subject indication would be harmed, our costs could increase and our ability to generate product sales could be delayed.

Gelesis100 has only been administered to a limited number of patients, and it may ultimately prove to be ineffective or unsafe.

We initiated our GLOW trial in November 2014. Ultimately, the results of our clinical trials to date, in which Gelesis100 has been well tolerated and induced clinically meaningful weight loss in overweight and obese patients, may prove to be incorrect. No assessment of the efficacy, safety or side effects of a product candidate can be considered complete until all clinical trials needed to support a submission for marketing approval are complete, and success in early-stage clinical trials does not mean that subsequent trials will confirm the earlier findings, or that experience with use of a product in large-scale commercial distribution will not identify additional safety or efficacy issues. If we find that Gelesis100 is not safe, or if its efficacy cannot be consistently demonstrated, we will not be able to commercialize, or may be required to cease distribution of, the product. In addition, although the GLOW study protocol incorporates guidance received from the FDA regarding potential use of the study to support approval, it does not incorporate the FDA’s guidance with respect to (i) the size of the study (ii) the appropriate demographic representation of the U.S. population and (iii) the inclusion of patients with comorbidities treated with drugs other than metformin, a drug commonly prescribed for type 2 diabetics. Therefore, our ability to obtain approval for Gelesis100 depends on the results from future studies that meet these criteria.

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Our product candidates may cause undesirable side effects that could delay or prevent their regulatory approval, limit the commercial profile of the approved labeling, or result in significant negative consequences following marketing approval, if any.

Undesirable side effects caused by our product candidates could cause us, the FDA or European regulatory authorities to interrupt, delay or halt clinical trials and could result in more restrictive labeling than anticipated or the delay or denial of regulatory approval by the FDA or European notified bodies. In our FLOW trial evaluating Gelesis100’s ability to induce weight loss in overweight and obese patients, the main adverse events, or AEs, in patients taking Gelesis100 were bloating, flatulence, abdominal pain, and diarrhea.

The safety data we have disclosed to date represent our interpretation of the data at the time of disclosure and are subject to our further review and analysis. There have been no serious adverse events, or SAEs, attributed to Gelesis100 in our clinical trials. However, SAEs that are not characterized by clinical investigators as possibly related to Gelesis100 or SAEs that occur in small numbers may not be disclosed to the public until such time the various documents submitted to the FDA as part of the approval process are made public. We are unable to determine if the subsequent disclosure of SAEs would have an adverse effect on our stock price. In addition, the FDA may not agree with our methods of analysis of the safety data from our clinical trials or our interpretation of the results.

In addition, based on feedback provided by the FDA, the magnitude of the effectiveness the FDA has indicated it would require for a pivotal study of Gelesis100 will be affected by the level and severity of AEs attributed to Gelesis100. Because the AEs seen in the FLOW trial were generally of mild intensity, occurred at different times during the course of the study, and resolved within one week, we believe that the co-primary endpoints sufficient to support U.S. regulatory approval would be (i) 3% weight loss difference between placebo and Gelesis100 groups with super superiority; and (ii) 5% weight loss in at least 35% of patients on Gelesis100 (regardless of placebo results) over a 6 month period. If the level or severity of AEs experienced by patients taking Gelesis100 increases or our prior clinical trial results are found to be inaccurate, the FDA may require more significant effectiveness in order to conclude that Gelesis100 has a benefit:risk profile acceptable to support approval.

If Gelesis100 receives marketing approval and we or others identify undesirable side effects caused by the product (or any other similar product) after the approval, a number of potentially significant consequences could result, including:

Any of these events could prevent us from achieving or maintaining market acceptance of Gelesis100 or any future product candidate and could substantially increase the costs of commercializing our product candidates and significantly impact our ability to successfully commercialize our product candidates and generate product sales.

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If we obtain FDA approval of Gelesis100 or any future products, we will be subject to ongoing and extensive regulatory requirements, and our failure to comply with these requirements could substantially harm our business.

If we obtain FDA approval of Gelesis100 or any future product candidates, including Gelesis200, we will be subject to ongoing FDA requirements and continued regulatory oversight and review, including routine inspections by the FDA of our manufacturing facilities and compliance with requirements such as the QSR, which establishes extensive requirements for quality assurance and control as well as manufacturing procedures; requirements pertaining to the registration of our manufacturing facilities and the listing of Gelesis100 with the FDA; continued complaint, adverse event and malfunction reporting; corrections and removals reporting; and labeling and promotional requirements. The promotional claims we will be able to make for Gelesis100 or any other future products will be limited to the approved indications for use. We may also be subject to additional FDA post-marketing requirements. If we are not able to maintain regulatory compliance, we may not be permitted to market our products and/or may be subject to enforcement by the FDA such as the issuance of warning or untitled letters, the imposition of fines, injunctions, and civil penalties; the recall or seizure of products; the imposition of operating restrictions; and the institution of criminal prosecution. In addition, if we obtain approval of Gelesis100 or any future product candidates, including Gelesis200, from European notified bodies, we will be subject to similar regulatory regimes. Adverse EU Competent Authority or FDA action in any of these areas could significantly increase our expenses and limit our product sales and profitability.

The FDA and other regulatory agencies actively enforce the laws and regulations pertaining to the advertising and promotion of medical devices. If we are found to have improperly promoted off-label uses, we may become subject to significant liability.

The FDA and European regulatory authorities strictly regulate the promotional claims that may be made about prescription products, such as Gelesis100, if approved. In particular, a medical device may not be promoted for uses that are not approved by the FDA or other regulatory agencies as reflected in the product’s approved labeling. For example, we will not be able to make claims for Gelesis100 pertaining to diabetes management or glycemic control in prediabetic and type 2 diabetic patients without approval of specific labeling regarding such use. The FDA has stated that our GLOW study of Gelesis100 as a treatment for weight loss in overweight and obese patients, even though it will include mild type 2 diabetic patients, will not provide information sufficient to obtain a claim or indication for diabetes management or glycemic control in this subset of patients. If we receive marketing approval for Gelesis100 as a treatment for weight loss in overweight and obese patients, physicians may nevertheless prescribe Gelesis100 to their patients in a manner that is inconsistent with the approved label. If we are found to have promoted such off-label uses, we may become subject to enforcement action by the FDA, including warning or untitled letters. In addition, the federal government has levied large civil and criminal fines against companies for alleged improper promotion and has enjoined companies from engaging in off-label promotion. The FDA has also requested that companies enter into consent decrees or permanent injunctions under which specified promotional conduct is changed or curtailed. If we cannot successfully manage the promotion of Gelesis100, if approved, we could become subject to significant liability, which would materially adversely affect our business and financial condition.

We are subject to healthcare laws and regulations, which could expose us to criminal sanctions, civil penalties, contractual damages, reputational harm and diminished profits and future earnings.

Healthcare providers, physicians and others will play a primary role in the recommendation and prescription of Gelesis100, if approved. Any future arrangements with third party payors will expose us to broadly applicable fraud and abuse and other healthcare laws and regulations that may constrain the business or financial arrangements and relationships through which we market, sell and distribute

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Gelesis100, if we obtain marketing approval. Restrictions under applicable federal and state healthcare laws and regulations include the following:

Ensuring that our future business arrangements with third parties comply with applicable healthcare laws and regulations could be costly. It is possible that governmental authorities will conclude that our business practices do not comply with current or future statutes, regulations or case law involving applicable fraud and abuse or other healthcare laws and regulations. If our operations, including anticipated activities to be conducted by our or a collaborator’s sales team, were found to be in violation of any of these laws or any other governmental regulations that may apply to us, we may be subject to significant civil, criminal and administrative penalties, damages, fines and exclusion from government funded healthcare programs, such as Medicare and Medicaid, any of which could substantially disrupt our operations. If any of the physicians or other providers or entities with whom we expect to do business are found not to be in compliance with applicable laws, they may be subject to criminal, civil or administrative sanctions, including exclusions from government funded healthcare programs.

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If Gelesis100 and our other product candidates are not regulated as medical devices, we will be subject to a significantly more time-consuming regulatory approval process in the United States and foreign jurisdictions, which could result in increased costs to us and could delay our development timeline. 

In the United States, the FDA regulates medical devices under the authority granted by the FDCA. Although Gelesis100 is designed to be ingested orally like a drug, it works mechanically, as opposed to via a chemical mode of action. Therefore, we believe that Gelesis100, and our other product candidates based on our hydrogel technology, including Gelesis200, will be regulated as medical devices. While CDRH has not raised any concern with regulating Gelesis100 as a medical device in our interactions to date, we cannot guarantee that the FDA and applicable foreign regulatory agencies will determine that Gelesis100 or any other product candidates that we may seek approval for are medical devices. If our product candidates are regulated as drugs and not as medical devices, we will be required to submit a New Drug Application to the FDA and comply with similar requirements in foreign jurisdictions and need to complete additional clinical trials, which will significantly increase the time, expense and uncertainty related to the process by which we will seek regulatory approval for our product candidates and our ability to generate product revenue will be delayed.

We are responsible for manufacturing Gelesis100 and our other product candidates, including Gelesis200, for our clinical trials. We need to scale up our capabilities to support the production of commercial level quantities of our product candidates. If we encounter failures or difficulties or cannot provide an adequate supply of our product candidates for our clinical trials or for commercialization, it could adversely affect the clinical development or regulatory approval of our product candidates or the production of Gelesis100 for commercialization.

We have developed proprietary processes and manufacturing technologies for the production of Gelesis100. Our wholly owned subsidiary Gelesis S.r.l. operates a manufacturing and research and development facility in southern Italy that produces Gelesis100 and Gelesis200 for our clinical trials. We are currently planning to double the output of this facility to meet the near term demands of our upcoming clinical trials. This facility is currently our sole supplier of Gelesis100 and Gelesis200. Although we believe that this facility, once expanded, is adequate for our clinical supply needs for the immediate future, if we encounter unexpected failures or difficulties in our manufacturing process or require amounts of Gelesis100 in excess of our current estimates we may be unable to manufacture sufficient supplies to support our clinical development, which will adversely affect our expected timeline for completion of our planned clinical trials and the expected timing of any regulatory approval.

In addition, in order to meet anticipated demand for commercial-scale quantities following regulatory approval, if obtained, we intend to construct a commercial-scale manufacturing line in North America, beginning in 2016. We do not expect that we will complete the construction of this line and receive regulatory approval for commercial production until 2018. Our preliminary cost estimates for the construction of this line are approximately $30 million. The new plant will utilize the processes that are currently used in our Italian facility with throughput increases, which we believe can be accomplished primarily through equipment scale and improved drying techniques. We do not have substantial experience in the construction of commercial-scale manufacturing lines, and there can be no assurance that we will succeed in increasing our historical production levels while meeting the required specifications for our product candidates. Therefore, even if we obtain regulatory approval of Gelesis100, our dependence on our ability to develop our own commercial-scale manufacturing lines, and any delays in the construction of those facilities may adversely affect our ability to develop and deliver our product candidates on a timely and competitive basis, if at all. Moreover, since we plan to seek regulatory approval through the PMA process, if we develop such commercial-scale manufacturing facilities after we obtain regulatory approval, we will need to seek a supplemental approval for our manufacturing location.

Any performance failure by us could delay or otherwise adversely affect the clinical development or regulatory approval of Gelesis100 or one or more of our product candidates or commercial sales, if

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approved for sale. We may encounter difficulties involving production yields, regulatory compliance, lot release, quality control and quality assurance, as well as shortages of qualified personnel. Approval of Gelesis100, as well as one or more of our product candidates, could be delayed, limited or denied if our manufacturing facilities do not complete successful inspections by the FDA or European regulatory authorities. Moreover, the ability to manufacture and supply our products adequately and in a timely manner is dependent on the uninterrupted and efficient operation of the manufacturing facilities, which is impacted by many manufacturing variables, including, but not limited to:

In addition, we may encounter delays and problems in manufacturing Gelesis100 and our other future product candidates, including Gelesis200, for a variety of reasons, including accidents during operation, failure of equipment, delays in receiving materials, natural or other disasters, political or governmental unrest or changes, social unrest, intentional misconduct or other factors inherent in operating complex manufacturing facilities. We may not be able to operate our respective manufacturing facilities in a cost-effective manner or in a time frame that is consistent with our expected future manufacturing needs. If we cease or interrupt production or if other third parties fail to supply materials, products or services to us for any reason, such interruption could delay progress on our programs, or interrupt the commercial supply, with the potential for additional costs and lost product sales. If this were to occur, we may also need to seek alternative means to fulfill our manufacturing needs.

We will also be subject to ongoing periodic inspection, which may be unannounced, by the FDA, corresponding state authorities and European regulatory authorities to ensure strict compliance with QSR requirements and other applicable government regulations and corresponding foreign standards. If we fail to maintain compliance or otherwise experience setbacks, we could be subject to enforcement action, including warning or untitled letters or civil or criminal penalties, the production of Gelesis100 or one or more of our product candidates could be interrupted or suspended, or our product could be recalled or withdrawn, resulting in delays, additional costs and potentially lost product sales.

Even if we are able to obtain the required regulatory approvals in the United States and the European Economic Area, there is no guarantee that we would be able to successfully commercialize Gelesis100 or our other product candidates.

Even if we obtain the required regulatory approval in the United States and the European Economic Area, our ability to generate product sales in the future will be dependent on our ability to market and sell Gelesis100 or our other future product candidates, including Gelesis200. The commercial success of Gelesis100, if approved by the FDA and/or European notified bodies, will depend upon the awareness

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and acceptance of Gelesis100 among the medical community, including physicians and patients. Market acceptance of Gelesis100, if approved, will depend on a number of factors, including, among others:

If Gelesis100 is approved but does not achieve an adequate level of acceptance by patients and physicians, we will not generate sufficient product sales of Gelesis100 to become or remain profitable. Our efforts to educate the medical community about the benefits of Gelesis100 may require significant resources and may never be successful.

In order to market Gelesis100, we may establish our own sales, marketing and distribution capabilities or we may enter into one or more strategic collaborations with third parties to sell, market and distribute Gelesis100. We have no experience in these areas and, if we have problems establishing these capabilities, the commercialization of Gelesis100 would be impaired.

We do not currently have infrastructure for the sales, marketing and distribution of our products. In order to market Gelesis100, if approved by the FDA or European notified bodies, we must build our sales, marketing, managerial and other non-technical capabilities or make arrangements with third parties to perform these services. We have no experience in these areas and developing these capabilities will require significant expenditures on personnel and infrastructure. While we may enter into collaborations with one or more third parties to sell, market and distribute Gelesis100, we may not be able to maintain such an arrangement or enter into any future arrangement on acceptable terms, if at all. Any collaboration we enter into may not be effective in generating meaningful product royalties or other revenues for us. If we are unable to establish adequate sales, marketing and distribution capabilities, whether independently or with third parties, or if we are unable to do so on commercially reasonable terms, our business, results of operations, financial condition and prospects will be materially adversely affected.

Even if Gelesis100 is approved for commercialization, we expect that our success will be dependent on the willingness of patients to pay out-of-pocket, should they not be able to obtain third party reimbursement. If there is not sufficient patient demand for Gelesis100, our financial results and future prospects will be harmed.

We cannot be certain that third party reimbursement will be available for Gelesis100, and, if reimbursement is available, the amount of any such reimbursement. As a result, we expect that our success

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will be dependent on the willingness of patients to pay out-of-pocket for Gelesis100. The decision by a patient to elect to undergo treatment with Gelesis100 may be influenced by a number of factors, such as:

Our financial performance will be materially harmed if we cannot generate significant patient demand for Gelesis100.

Competing technologies could emerge, including pharmaceuticals, devices, and surgical procedures, that adversely affect our opportunity to generate product sales of Gelesis100.

The biotechnology, pharmaceutical and medical device industries are intensely competitive and subject to rapid and significant technological change. We have competitors in a number of jurisdictions, many of which have substantially greater name recognition, commercial infrastructures and financial, technical and personnel resources than we have. Competitors may invest heavily to quickly discover and develop novel products that could make Gelesis100 obsolete or economically disadvantageous. Any new product that competes with an approved product may need to demonstrate compelling advantages in efficacy, convenience, tolerability and safety to be commercially successful. Other competitive factors could force us to lower prices or could result in reduced sales. In addition, new products developed by others could emerge as competitors to Gelesis100. If we are not able to compete effectively against our competitors, our financial condition and operations will suffer.

Our potential competitors in the obesity market include drugs that are FDA-approved and currently marketed for the treatment of obesity. Gelesis100 will primarily compete with orlistat, phentermine/topiramate, naltrexone/bupropion, and lorcaserin, four orally administered, marketed pharmaceutical products in the United States for the treatment of obesity, and several older products, indicated for short-term administration, including phentermine, phendimetrazine, benzphetamine and diethylpropion. Orlistat is marketed in the United States by Roche Group under the brand name Xenical and over-the-counter under the brand name alli, at half the prescribed dose, by GlaxoSmithKline. In September 2012, Vivus, Inc. launched its combination product, phentermine/topiramate, under the trade name Qsymia and in September 2014, Orexigen Therapeutics, Inc. received FDA approval of naltrexone/bupropion which is marketed under the brand name Contrave in the United States. In December 2014, Orexigen announced that it had received a positive opinion recommending the granting of marketing approval for naltrexone/bupropion under the name Mysimba in the EU. In June 2013, Arena Pharmaceuticals, Inc. and Eisai, Inc. launched lorcaserin, which is marketed in the United States under the name Belviq. Gelesis100 will also compete with injectable pharmaceutical obesity therapies, such as those in development by Zafgen, Inc. and Novo Nordisk. In December 2014, Novo Nordisk received FDA approval for its injectable drug, Saxenda, and is expected to launch Saxenda in the first half of 2015. Neurosearch A/S is also pursuing a pharmaceutical treatment for obesity. In addition, other potential approaches which utilize various implantable devices or surgical tools are in development, by companies such as Allergan, Inc., Boston Scientific Corporation, EnteroMedics, Inc., GI Dynamics, Inc., Johnson & Johnson and Medtronic, Inc.

Many of our competitors have significantly greater financial, technical, manufacturing, marketing, sales and supply resources or experience than we have. Competing products could present superior treatment alternatives, including by being more effective, safer, less expensive or marketed and sold more effectively

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than any products we may develop. Competitive products may make any products we develop obsolete or noncompetitive before we recover the expense of developing and commercializing our product candidates. Such competitors could also recruit our employees, which could negatively impact our level of expertise and our ability to execute our business plan.

Risks Relating to Our Intellectual Property Rights

If we are unable to adequately protect our proprietary technology or maintain issued patents that are sufficient to protect Gelesis100 or our other product candidates, others could compete against us more directly, which would have a material adverse impact on our business, results of operations, financial condition and prospects.

Our commercial success will depend in part on our success in obtaining and maintaining issued patents and other intellectual property rights in the United States and elsewhere and protecting our proprietary technology. If we do not adequately protect our intellectual property and proprietary technology, competitors may be able to use our technologies and erode or negate any competitive advantage that we may have, which could harm our business and ability to achieve profitability.

We have five families of patents and patent applications which cover composition of matter, methods of use and methods of production for our product candidates, including Gelesis100 and Gelesis200. Uses of Gelesis100 for treating obesity and reducing caloric intake are currently protected in the United States by an issued patent with the priority date of August 10, 2007. Corresponding patents have also been granted or allowed in Europe, Russia, China, Australia, and Mexico. A divisional patent application covering Gelesis100 composition of matter has also been granted in Europe. This patent family is also pending in additional territories around the world. Two recent international patent families and two U.S. provisional applications are also pending. These families are directed to methods for enhancing glycemic control, methods for producing a polymer hydrogel, and methods for treating obesity in a subject involving oral administration of a specific form of cross-linked modified cellulose at particular doses, respectively. We expect to have coverage in the United States, Europe and several other territories until at least 2027, with possible extended coverage from pending applications should they be granted.

We cannot provide any assurances that any of our patents have, or that any of our pending patent applications that mature into issued patents will include, claims with a scope sufficient to protect Gelesis100 or our other product candidates. Other parties have developed technologies that may be related or competitive to our approach and may have filed or may file patent applications and may have received or may receive patents that may overlap or conflict with our patent applications, either by claiming the same methods or formulations or by claiming subject matter that could dominate our patent position. The patent positions of biotechnology, pharmaceutical and medical device companies, including our patent position, involve complex legal and factual questions and, therefore, the issuance, scope, validity, and enforceability of any patent claims that we may obtain cannot be predicted with certainty. Patents, if issued, may be challenged, deemed unenforceable, invalidated, or circumvented. U.S. patents and patent applications may also be subject to interference proceedings, ex parte reexamination, inter partes review proceedings, post-grant review proceedings, and challenges in district court. Patents may be subjected to opposition, post-grant review, or comparable proceedings lodged in various foreign, both national and regional, patent offices. These proceedings could result in either loss of the patent or denial of the patent application or loss or reduction in the scope of one or more of the claims of the patent or patent application. In addition, such proceedings may be costly. Thus, any patents that we own may not provide any protection against competitors. Furthermore, an adverse decision in an interference proceeding can result in a third party receiving the patent right sought by us, which in turn could affect our ability to develop, market or otherwise commercialize Gelesis100.

Furthermore, though an issued patent is presumed valid and enforceable, its issuance is not conclusive as to its validity or its enforceability, and it may not provide us with adequate proprietary protection or

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competitive advantages against competitors with similar products. Competitors may also be able to design around our patents. Other parties may develop and obtain patent protection for more effective technologies, designs or methods. We may not be able to prevent the unauthorized disclosure or use of our technical knowledge or trade secrets by consultants, vendors, former employees and current employees. The laws of some foreign countries do not protect our proprietary rights to the same extent as the laws of the United States, and we may encounter significant problems in protecting our proprietary rights in these countries. If these developments were to occur, they could have a material adverse effect on our sales.

Our ability to enforce our patent rights depends on our ability to detect infringement. It is difficult to detect infringers who do not advertise the components of their products. Moreover, it may be difficult or impossible to obtain evidence of infringement in a competitor’s or potential competitor’s product. Any litigation to enforce or defend our patent rights, even if we were to prevail, could be costly and time-consuming and would divert the attention of our management and key personnel from our business operations. We may not prevail in any lawsuits that we initiate and the damages or other remedies awarded if we were to prevail may not be commercially meaningful.

In addition, proceedings to enforce or defend our patents could put our patents at risk of being invalidated, held unenforceable, or interpreted narrowly. Such proceedings could also provoke third parties to assert claims against us, including that some or all of the claims in one or more of our patents are invalid or otherwise unenforceable. If any of our patents covering Gelesis100 are invalidated or found unenforceable, our financial position and results of operations would be materially and adversely impacted. In addition, if a court found that valid, enforceable patents held by third parties covered Gelesis100, our financial position and results of operations would also be materially and adversely impacted.

The degree of future protection for our proprietary rights is uncertain, and we cannot ensure that:

We rely upon unpatented trade secrets, unpatented know-how, and continuing technological innovation to develop and maintain our competitive position, which we seek to protect, in part, by confidentiality agreements with our employees and our collaborators and consultants. We also have agreements with our employees and selected consultants that obligate them to assign their inventions to us and have non-compete agreements with some, but not all, of our consultants. It is possible that technology relevant to

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our business will be independently developed by a person that is not a party to such an agreement. Furthermore, if the employees and consultants who are parties to these agreements breach or violate the terms of these agreements, we may not have adequate remedies for any such breach or violation, and we could lose our trade secrets through such breaches or violations. Further, our trade secrets could otherwise become known or be independently discovered by our competitors.

Under our amended and restated master agreement, we have granted One S.r.l., the original owner of our core patent rights, a license to practice the patent rights for noncommercial, research purposes, and we have agreed under certain circumstances to grant limited commercial rights as well. While we believe that the rights we have granted are reasonably limited and not competitive with our core business, there can be no guarantee that the third party’s activities will not in any way overlap or interfere with the development or commercialization of Gelesis100 or our other product candidates, if approved. Additionally, there is always the possibility that we may become dependent on obtaining access to third party intellectual property in the future.

Under the original master agreement and its amendments, we acquired certain patent rights that cover Gelesis100 and our other hydrogel-based product candidates from One S.r.l. Our amended and restated master agreement imposes various obligations on us, including a requirement to make certain milestone and royalty payments and to prosecute and maintain the patent rights. Under this agreement, we granted One S.r.l. a non-exclusive license to practice the patent rights for noncommercial, research purposes, and we have agreed under certain circumstances to grant an additional non-blocking license for the development and commercialization of certain drug delivery products that do not include any composition of matter that is claimed by the patent rights.

Our agreement to grant any future non-blocking license to One S.r.l., excludes products relating to obesity, weight loss, diabetes, metabolic diseases, GI disorders, laxatives and liquid removal. While we believe that the scope of any non-blocking license we might grant to One S.r.l. is clearly distinct from our field of interest, there can be no guarantee that a disagreement will not arise over a particular product area, or that such a disagreement could not materially and adversely impact our business.

One S.r.l. and the inventors of the patent rights are bound by non-competition provisions in our amended and restated master agreement, which prohibit them from developing, manufacturing or commercializing any product or process related to diet, weight loss, food products or obesity during the term of our amended and restated master agreement and for a year after its termination. Additionally, the inventors have agreed to assign to us certain future technology relating to food products that they develop during the term of our amended and restated master agreement, as well as other improvements to our existing intellectual property rights that result from activities they perform under our amended and restated master agreement. There can be no guarantee, however, that One S.r.l. or the inventors will not attempt to act contrary to such obligations or that, if they do, we would succeed in a legal action to stop them from doing so.

We may be required to enter into additional license(s) to third party intellectual property that we find necessary or useful to our business, or that the third party owner asserts we are infringing. In such a case, even if we are successful in obtaining terms that are commercially reasonable, such a future licensor might also allege that we have breached our license agreement and may accordingly seek to terminate our license with them, or may insist on the right to terminate such a license at will. If successful, any such termination could result in our loss of the right to use the licensed intellectual property, which could materially adversely affect our ability to develop and commercialize a product candidate or product, if approved, as well as harm our competitive business position and our business prospects.

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We may infringe the intellectual property rights of others, which may prevent or delay our product development efforts and stop us from commercializing or increase the costs of commercializing Gelesis100 or our other product candidates, if approved.

Our success will depend in part on our ability to operate without infringing the intellectual property and proprietary rights of third parties. We cannot assure you that our business, products and methods do not or will not infringe the patents or other intellectual property rights of third parties.

The medical device, pharmaceutical and biotechnology industries are characterized by extensive litigation regarding patents and other intellectual property rights. Other parties may allege that Gelesis100 or the use of our technologies infringes patent claims or other intellectual property rights held by them or that we are employing their proprietary technology without authorization. Patent and other types of intellectual property litigation can involve complex factual and legal questions, and their outcome is uncertain. Any claim relating to intellectual property infringement that is successfully asserted against us may require us to pay substantial damages, including treble damages and attorney’s fees if we are found to be willfully infringing another party’s patents, for past use of the asserted intellectual property and royalties and other consideration going forward if we are forced to take a license. In addition, if any such claim were successfully asserted against us and we could not obtain such a license, we may be forced to stop or delay developing, manufacturing, selling or otherwise commercializing Gelesis100 or our other product candidates.

Even if we are successful in these proceedings, we may incur substantial costs and divert management time and attention in pursuing these proceedings, which could have a material adverse effect on us. If we are unable to avoid infringing the patent rights of others, we may be required to seek a license, defend an infringement action or challenge the validity of the patents in court, or redesign our products. Patent litigation is costly and time consuming. We may not have sufficient resources to bring these actions to a successful conclusion. In addition, intellectual property litigation or claims could force us to do one or more of the following:

Any of these risks coming to fruition could have a material adverse effect on our business, results of operations, financial condition and prospects.

We may be subject to claims challenging the inventorship or ownership of our patents and other intellectual property.

We may also be subject to claims that former employees, collaborators, or other third parties have an ownership interest in our patents or other intellectual property. For example, each of our patents and patent applications names one or more inventors affiliated with other institutions, any of whom may assert an ownership claim. Litigation may be necessary to defend against these and other claims challenging inventorship or ownership. If we fail in defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights, such as exclusive ownership of, or right to use, valuable intellectual property. Such an outcome could have a material adverse effect on our business. Even if we are successful in defending against such claims, litigation could result in substantial costs and be a distraction to management and other employees.

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Obtaining and maintaining our patent protection depends on compliance with various procedural, document submission, fee payment and other requirements imposed by governmental patent agencies, and our patent protection could be reduced or eliminated for non-compliance with these requirements.

The U.S. Patent and Trademark Office, or U.S. PTO, and various foreign governmental patent agencies require compliance with a number of procedural, documentary, fee payment and other provisions during the patent process. There are situations in which noncompliance can result in abandonment or lapse of a patent or patent application, resulting in partial or complete loss of patent rights in the relevant jurisdiction. In such an event, competitors might be able to enter the market earlier than would otherwise have been the case.

We may be involved in lawsuits to protect or enforce our patents, which could be expensive, time-consuming, and unsuccessful.

Competitors may infringe our patents. To counter infringement or unauthorized use, we may be required to file infringement claims, which can be expensive and time-consuming. In addition, in an infringement proceeding, a court may decide that a patent of ours is not valid, is unenforceable and/or is not infringed, or may refuse to stop the other party from using the technology at issue on the grounds that our patents do not cover the technology in question. An adverse result in any litigation or defense proceedings could put one or more of our patents at risk of being invalidated or interpreted narrowly and could put our patent applications at risk of not issuing.

Interference proceedings provoked by third parties or brought by us may be necessary to determine the priority of inventions with respect to our patents or patent applications. An unfavorable outcome could require us to cease using the related technology or to attempt to license rights to it from the prevailing party. Our business could be harmed if the prevailing party does not offer us a license on commercially reasonable terms. Our defense of litigation or interference proceedings may fail and, even if successful, may result in substantial costs and distract our management and other employees. We may not be able to prevent misappropriation of our intellectual property rights, particularly in countries where the laws may not protect those rights as fully as in the United States.

Furthermore, because of the substantial amount of discovery required in connection with intellectual property litigation, there is a risk that some of our confidential information could be compromised by disclosure during this type of litigation. There could also be public announcements of the results of hearings, motions or other interim proceedings or developments. If securities analysts or investors perceive these results to be negative, it could have a material adverse effect on the price of our common stock.

Issued patents covering our product candidates could be found invalid or unenforceable if challenged in court.

If we initiated legal proceedings against a third party to enforce a patent covering our product candidate, the defendant could counterclaim that the patent covering our product candidate is invalid and/or unenforceable. In patent litigation in the United States, defendant counterclaims alleging invalidity and/or unenforceability are commonplace. Grounds for a validity challenge include alleged failures to meet any of several statutory requirements, including lack of novelty, obviousness or non-enablement. Grounds for unenforceability assertions include allegations that someone connected with prosecution of the patent withheld relevant information from the U.S. PTO, or made a misleading statement during prosecution. Third parties may also raise similar claims before administrative bodies in the United States or abroad, even outside the context of litigation. Such mechanisms include re-examination, post grant review and equivalent proceedings in foreign jurisdictions, e.g., opposition proceedings. Such proceedings could result in revocation or amendment of our patents in such a way that they no longer cover our product candidates or competitive products. The outcome following legal assertions of invalidity and unenforceability is unpredictable. With respect to validity, for example, we cannot be certain that there is

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no invalidating prior art, of which we and the patent examiner were unaware during prosecution. If a defendant were to prevail on a legal assertion of invalidity and/or unenforceability, we would lose at least part, and perhaps all, of the patent protection on our product candidates. Such a loss of patent protection would have a material adverse impact on our business.

We do not seek to protect our intellectual property rights in all jurisdictions throughout the world and we may not be able to adequately enforce our intellectual property rights even in the jurisdictions where we seek protection.

Filing, prosecuting and defending patents on product candidates in all countries and jurisdictions throughout the world would be prohibitively expensive, and our intellectual property rights in some countries outside the United States could be less extensive than those in the United States. In addition, the laws of some foreign countries do not protect intellectual property rights to the same extent as federal and state laws in the United States. Consequently, we may not be able to prevent third parties from practicing our inventions in all countries outside the United States, or from selling or importing products made using our inventions in and into the United States or other jurisdictions. Competitors may use our technologies in jurisdictions where we have not obtained patent protection to develop their own products and further, may export otherwise infringing products to territories where we have patent protection, but enforcement is not as strong as that in the United States. These products may compete with our products, and our patents or other intellectual property rights may not be effective or sufficient to prevent them from competing.

Many companies have encountered significant problems in protecting and defending intellectual property rights in foreign jurisdictions. The legal systems of certain countries, particularly certain developing countries, do not favor the enforcement of patents and other intellectual property protection, particularly those relating to biopharmaceuticals and medical devices, which could make it difficult for us to stop the infringement of our patents or marketing of competing products in violation of our proprietary rights generally. Proceedings to enforce our patent rights in foreign jurisdictions could result in substantial costs and divert our efforts and attention from other aspects of our business, could put our patents at risk of being invalidated or interpreted narrowly, could put our patent applications at risk of not issuing and could provoke third parties to assert claims against us. We may not prevail in any lawsuits that we initiate and the damages or other remedies awarded, if any, may not be commercially meaningful. Accordingly, our efforts to enforce our intellectual property rights around the world may be inadequate to obtain a significant commercial advantage from the intellectual property that we develop or license.

If we do not obtain additional protection under the Hatch-Waxman Amendments and similar foreign legislation by extending the patent terms for Gelesis100, our business may be materially harmed.

Depending upon the timing, duration, specifics and method of FDA marketing approval of Gelesis100, one of our U.S. patents may be eligible for limited patent term restoration under the Drug Price Competition and Patent Term Restoration Act of 1984, referred to as the Hatch-Waxman Amendments. The Hatch-Waxman Amendments permit a patent restoration term of up to five years as compensation for patent term lost during product development and the FDA regulatory review process. However, we may not be granted an extension because of, for example, failing to apply within applicable deadlines, failing to apply prior to expiration of relevant patents or otherwise failing to satisfy applicable requirements. In addition, we will only be eligible for patent extension if we receive PMA approval from the FDA. Moreover, even if we are eligible for an extension, the applicable time period or the scope of patent protection afforded could be less than we request. If we are unable to obtain patent term extension or restoration or the term of any such extension is less than we request, our competitors may obtain approval of competing products following our patent expiration, and our ability to generate product sales could be materially adversely affected.

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Changes in U.S. patent law could diminish the value of patents in general, thereby impairing our ability to protect our products.

The United States has recently enacted and is currently implementing the America Invents Act of 2011, wide-ranging patent reform legislation. Further, the U.S. Supreme Court has ruled on several patent cases in recent years, either narrowing the scope of patent protection available in certain circumstances or weakening the rights of patent owners in certain situations. In addition to increasing uncertainty with regard to our ability to obtain future patents, this combination of events has created uncertainty with respect to the value of patents, once obtained. Depending on decisions by the U.S. Congress, the federal courts and the U.S. PTO, the laws and regulations governing patents could change in unpredictable ways that would weaken our ability to obtain new patents or to enforce our existing patents or future patents.

We may be subject to damages resulting from claims that we, our employees, consultants or third parties we engage to manufacture our products have wrongfully used, or disclosed alleged trade secrets of our competitors or are in breach of non-competition or non-solicitation agreements with our competitors.

Many of our employees were previously employed at pharmaceutical companies and other medical device companies, including our potential competitors, in some cases until recently. We may be subject to claims that we, our employees, consultants or third parties have inadvertently or otherwise used or disclosed alleged trade secrets or proprietary information of these former employers or competitors. In addition, we may be subject to claims that we caused an employee to breach the terms of his or her non-competition or non-solicitation agreement. Litigation may be necessary to defend against these claims. Even if we are successful in defending against these claims, litigation could result in substantial costs and could be a distraction for our management. If our defense to those claims fails, in addition to paying monetary damages, we may lose valuable intellectual property rights or personnel. Any litigation or the threat thereof may adversely affect our ability to hire employees or contract with third parties. A loss of key personnel or their work product could have an adverse effect on our business, results of operations and financial condition.

Risks Related to Our Business and Strategy

We will need to develop and expand our company, and we may encounter difficulties in managing this development and expansion, which could disrupt our operations.

As of December 31, 2014, we had 14 full-time employees and 7 consultants and, in connection with becoming a public company, we expect to increase the number of our administrative employees. We also plan to expand the scope of our operations including the development of a commercial-scale manufacturing line and hiring manufacturing staff. To manage our anticipated development and expansion, we must continue to implement and improve our managerial, operational and financial systems, expand our facilities and continue to recruit and train additional qualified personnel. Also, our management may need to divert a disproportionate amount of its attention away from its day-to-day activities and devote a substantial amount of time to managing these development activities. Due to our limited resources and the limited experience of our management team in managing a company with such anticipated growth, we may not be able to effectively manage the expansion of our operations or recruit and train additional qualified personnel. This may result in weaknesses in our infrastructure, give rise to operational mistakes, loss of business opportunities, loss of employees and reduced productivity among remaining employees. The physical expansion of our operations may lead to significant costs and may divert financial resources from other projects, such as the development of Gelesis100 and our other product candidates. If our management is unable to effectively manage our expected development and expansion, our expenses may increase more than expected, our ability to generate or increase our product sales could be reduced, and we may not be able to implement our business strategy. Our future financial performance and our ability to commercialize Gelesis100, if approved, and compete effectively will depend, in part, on our ability to effectively manage the future development and expansion of our company.

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Our future success depends on our ability to retain our chief executive officer, and to attract and keep senior management and key scientific personnel.

Our success depends, in part, on our continued ability to attract, retain and motivate highly qualified management, clinical and scientific personnel. We are highly dependent upon our senior management, particularly Yishai Zohar, our Chief Executive Officer and President, as well as other employees and consultants. Although none of these individuals has informed us to date that he intends to retire or resign in the near future, the loss of services of any of these individuals or one or more of our other members of senior management could delay or prevent the successful development of our future product candidates.

Although we have not historically experienced unique difficulties attracting and retaining qualified employees, we could experience such problems in the future. For example, competition for qualified personnel in the biotechnology, pharmaceutical and medical device field is intense, and we face competition for the hiring of scientific and clinical personnel from other biotechnology and pharmaceutical companies, as well as universities and research institutions. In addition, the consultants and advisors, including scientific and clinical advisors, upon whom we rely to assist us in formulating our research development and commercialization strategy, may be employed by employers other than us and may have commitments under consulting or advisory contracts with other entities that may limit their availability to us. In addition, we will need to hire additional personnel as we expand our clinical development and commercial activities. We may not be able to attract and retain quality personnel on acceptable terms, if at all.

We may not be successful in our efforts to identify or discover additional product candidates.

The success of our business depends primarily upon our ability to identify, develop and commercialize products using our proprietary hydrogel technology. Although Gelesis100 is currently in clinical development and Gelesis200 is in pre-clinical development, our research programs may fail to identify other potential product candidates for clinical development for a number of reasons. Our research methodology may be unsuccessful in identifying potential product candidates or our potential product candidates may be shown to have harmful side effects or may have other characteristics that may make the products unmarketable or unlikely to receive marketing approval.

If any of these events occur, we may be forced to abandon our development efforts for a program or programs, which would have a material adverse effect on our business and could potentially cause us to cease operations. Research programs to identify new product candidates require substantial technical, financial and human resources. We may focus our efforts and resources on potential programs or product candidates that ultimately prove to be unsuccessful.

Our employees may engage in misconduct or other improper activities, including violating applicable regulatory standards and requirements or engaging in insider trading, which could significantly harm our business.

We are exposed to the risk of employee fraud or other misconduct. Misconduct by employees could include intentional failures to comply with the regulations of the FDA and European notified bodies, provide accurate information to the FDA and applicable non-U.S. regulators, comply with healthcare fraud and abuse laws and regulations in the United States and abroad, as well as the Foreign Corrupt Practices Act, or FCPA, report financial information or data accurately or disclose unauthorized activities to us. In particular, sales, marketing and business arrangements in the healthcare industry are subject to extensive laws and regulations intended to prevent fraud, misconduct, kickbacks, self-dealing and other abusive practices. These laws and regulations restrict or prohibit a wide range of pricing, discounting, marketing and promotion, sales commission, customer incentive programs and other business arrangements. Employee misconduct could also involve the improper use of, including trading on, information obtained in the course of clinical trials, which could result in regulatory sanctions and

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serious harm to our reputation. We intend to adopt a code of conduct, but it is not always possible to identify and deter employee misconduct, and the precautions we take to detect and prevent this activity may be ineffective in controlling unknown or unmanaged risks or losses or in protecting us from governmental investigations or other actions or lawsuits stemming from a failure to comply with these laws or regulations. If any such actions are instituted against us, and we are not successful in defending ourselves or asserting our rights, those actions could have a significant impact on our business, including the imposition of significant fines or other sanctions.

We face potential product liability exposure and, if claims are brought against us, we may incur substantial liability.

The use of Gelesis100 in clinical trials and the sale of Gelesis100, if approved, exposes us to the risk of product liability claims. Product liability claims might be brought against us by patients, healthcare providers or others selling or otherwise coming into contact with Gelesis100. For example, we may be sued if any product we develop allegedly causes injury or is found to be otherwise unsuitable during product testing, manufacturing, marketing or sale. Any such product liability claims may include allegations of defects in manufacturing, defects in design, a failure to warn of dangers inherent in the product, negligence, strict liability and a breach of warranties. Claims could also be asserted under state consumer protection acts. If we become subject to product liability claims and cannot successfully defend ourselves against them, we could incur substantial liabilities. In addition, regardless of merit or eventual outcome, product liability claims may result in, among other things:

We maintain product liability insurance coverage for our clinical trials with a $1.0 million annual aggregate coverage limit. Nevertheless, our insurance coverage may be insufficient to reimburse us for any expenses or losses we may suffer. Moreover, in the future, we may not be able to maintain insurance coverage at a reasonable cost or in sufficient amounts to protect us against losses, including if insurance coverage becomes increasingly expensive. If we obtain marketing approval for Gelesis100, we intend to expand our insurance coverage to include the sale of commercial products at that time; however, we may not be able to obtain this product liability insurance on commercially reasonable terms, if at all. Significant judgments have been awarded in class action lawsuits based on drugs and medical devices that had unanticipated side effects. The cost of any product liability litigation or other proceedings, even if resolved in our favor, could be substantial, particularly in light of the size of our business and financial resources. A product liability claim or series of claims brought against us could cause our stock price to decline and, if we are unsuccessful in defending such a claim or claims and the resulting judgments exceed our insurance coverage, our financial condition, business and prospects could be materially adversely affected.

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In order to satisfy our obligations as a public company, we will need to hire additional qualified accounting and financial personnel with appropriate public company experience.

As a newly public company, we will need to establish and maintain effective disclosure and financial controls and institute changes in our corporate governance practices, which will cause us to incur significant legal, accounting and other expenses, particularly once we are no longer an “emerging growth company,” that we did not incur as a private company. The Sarbanes-Oxley Act, the Dodd-Frank Wall Street Reform and Consumer Protection Act, the listing requirements of the Nasdaq Stock Market and other applicable securities rules and regulations impose various requirements on public companies, including establishment and maintenance of effective disclosure and financial controls and corporate governance practices. Given the limited public company experience of our management team, we will need to hire additional accounting and financial personnel with appropriate public company experience and technical accounting knowledge, and it may be difficult to recruit and maintain such personnel. Even if we are able to hire appropriate personnel, our existing operating expenses and operations will be impacted by the direct costs of their employment and the indirect consequences related to the diversion of management resources from product development efforts. The rules and regulations associated with being a public company are often subject to varying interpretations, in many cases due to their lack of specificity, and, as a result, their application in practice may evolve over time as new guidance is provided by regulatory and governing bodies. This could result in continuing uncertainty regarding compliance matters and higher costs necessitated by ongoing revisions to disclosure and governance practices.

Our internal computer systems, or those of our third party CROs or other contractors or consultants, may fail or suffer security breaches, which could result in a material disruption of our Gelesis100 development programs.

Despite the implementation of security measures, our internal computer systems and those of our third party CROs and other contractors and consultants are vulnerable to damage from computer viruses, unauthorized access, natural disasters, terrorism, war and telecommunication and electrical failures. While we have not experienced any such system failure, accident, or security breach to date, if such an event were to occur and cause interruptions in our operations, it could result in a material disruption of our programs. For example, the loss of clinical trial data for Gelesis100 could result in delays in our regulatory approval efforts and significantly increase our costs to recover or reproduce the data. To the extent that any disruption or security breach results in a loss of or damage to our data or applications or other data or applications relating to our technology or product candidates, or inappropriate disclosure of confidential or proprietary information, we could incur liabilities and the further development of Gelesis100 could be delayed.

We may acquire businesses or products, or form strategic alliances, in the future, and we may not realize the benefits of such acquisitions.

We may acquire additional businesses or products, form strategic alliances or create joint ventures with third parties that we believe will complement or augment our existing business. If we acquire businesses with promising markets or technologies, we may not be able to realize the benefit of acquiring such businesses if we are unable to successfully integrate them with our existing operations and company culture. We may encounter numerous difficulties in developing, manufacturing and marketing any new products resulting from a strategic alliance or acquisition that delay or prevent us from realizing their expected benefits or enhancing our business. We cannot assure you that, following any such acquisition, we will achieve the expected synergies to justify the transaction.

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Unfavorable global economic conditions could adversely affect our business, financial condition or results of operations.

Our results of operations could be adversely affected by general conditions in the global economy and in the global financial markets. The 2008 global financial crisis caused extreme volatility and disruptions in the capital and credit markets. A severe or prolonged economic downturn, such as the 2008 global financial crisis, could result in a variety of risks to our business, including, weakened demand for any of our future products and our ability to raise additional capital when needed on acceptable terms, if at all. A weak or declining economy could also result in supply disruption or cause our customers to delay making payments for our services. Any of the foregoing could harm our business and we cannot anticipate all of the ways in which the current economic climate and financial market conditions could adversely impact our business.

If we fail to comply with environmental, health and safety laws and regulations, we could become subject to fines or penalties or incur costs that could have a material adverse effect on the success of our business.

We are subject to numerous environmental, health and safety laws and regulations, including those governing laboratory procedures and the handling, use, storage, treatment and disposal of hazardous materials and wastes. Our operations involve the use of hazardous and flammable materials, including chemicals and biological materials. Our operations also produce hazardous waste products. We cannot eliminate the risk of contamination or injury from these materials. In the event of contamination or injury resulting from our use of hazardous materials, we could be held liable for any resulting damages, and any liability could exceed our resources. We also could incur significant costs associated with civil or criminal fines and penalties.

Although we maintain workers’ compensation insurance to cover us for costs and expenses we may incur due to injuries to our employees resulting from the use of hazardous materials, this insurance may not provide adequate coverage against potential liabilities. We do not maintain insurance for environmental liability or toxic tort claims that may be asserted against us in connection with our storage or disposal of biological, hazardous or radioactive materials.

In addition, we may incur substantial costs in order to comply with current or future environmental, health and safety laws and regulations. These current or future laws and regulations may impair our research, development or production efforts. Failure to comply with these laws and regulations also may result in substantial fines, penalties or other sanctions, which could have a material adverse effect on our operations.

Changes in federal, state, local or foreign tax law or interpretations of existing tax law, or adverse determinations by tax authorities, could increase our tax burden or otherwise adversely affect our financial condition, results of operations or cash flows.

We are subject to taxation at the federal, state and local levels in the U.S. and other countries and jurisdictions. Our future effective tax rate could be affected by changes in the composition of earnings in jurisdictions with differing tax rates, changes in statutory rates and other legislative changes, changes in the valuation of our deferred tax assets and liabilities, or changes in determinations regarding the jurisdictions in which we are subject to tax. From time to time, the U.S. federal, state and local and foreign governments make substantive changes to tax rules and their application, which could result in materially higher taxes than would be incurred under existing tax law or interpretation and could adversely affect our profitability, financial condition, results of operations or cash flows. State and local tax authorities have also increased their efforts to increase revenues through changes in tax law and audits. Such changes and proposals, if enacted, could increase our future effective income tax rates. We are subject to ongoing and periodic tax audits and disputes in various jurisdictions. An unfavorable outcome from any tax audit could result in higher tax costs, penalties and interest, thereby adversely impacting our financial condition, results of operations or cash flows.

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Risks Related to this Offering and Ownership of Our Common Stock

Market volatility may affect our stock price and the value of your investment.

Following this offering, the market price for our common stock is likely to be volatile, in part because our common stock has not been previously traded publicly. In addition, the stock market in general and the market for biotechnology and pharmaceutical companies in particular has experienced extreme volatility that has often been unrelated to the operating performance of particular companies. The market price of our common stock may fluctuate significantly in response to a number of factors, most of which we cannot control including, among others:

An active trading market for our common stock may not develop, and you may not be able to resell your shares at or above the initial public offering price.

Prior to this offering, there has been no public market for shares of our common stock. Although we are applying to have our common stock listed on The NASDAQ Global Market, an active trading market for our shares may never develop or be sustained following this offering. The initial public offering price of our common stock was determined through negotiations between us and the underwriters. This initial public offering price may not be indicative of the market price of our common stock after this offering. In the absence of an active trading market for our common stock, investors may not be able to sell their common stock at or above the initial public offering price or at the time that they would like to sell.

Our executive officers, directors, principal stockholders and their affiliates will continue to exercise significant control over our company after this offering, which will limit your ability to influence corporate matters and could delay or prevent a change in corporate control.

Immediately following the completion of this offering, and disregarding any shares of common stock that they may purchase in this offering, the existing holdings of our executive officers, directors, principal

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stockholders and their affiliates, will represent beneficial ownership, in the aggregate, of approximately     % of our outstanding common stock, assuming no exercise of the underwriters’ option to acquire additional common stock in this offering and assuming we issue the number of shares of common stock as set forth on the cover page of this prospectus. As a result, these stockholders, if they act together, will be able to influence our management and affairs and control the outcome of matters submitted to our stockholders for approval, including the election of directors and any sale, merger, consolidation, or sale of all or substantially all of our assets. These stockholders acquired their shares of common stock for substantially less than the price of the shares of common stock being acquired in this offering, and these stockholders may have interests, with respect to their common stock, that are different from those of investors in this offering and the concentration of voting power among these stockholders may have an adverse effect on the price of our common stock. In addition, this concentration of ownership might adversely affect the market price of our common stock by:

See “Principal Stockholders” in this prospectus for more information regarding the ownership of our outstanding common stock by our executive officers, directors, principal stockholders and their affiliates.

Sales of a substantial number of shares of our common stock in the public market could cause our stock price to fall.

If our existing stockholders sell, or indicate an intention to sell, substantial amounts of our common stock in the public market after the lock-up and other legal restrictions on resale discussed in this prospectus lapse, the market price of our common stock could decline. Based upon the number of shares of common stock, on an as-converted basis, outstanding as of December 31, 2014, upon the completion of this offering, we will have outstanding a total of              shares of common stock, assuming no exercise of the underwriters’ option to purchase additional shares. Of these shares, as of the date of this prospectus, approximately              shares of our common stock, plus any shares sold upon exercise of the underwriters’ option to purchase additional shares, will not be subject to lock-up agreements. The representatives of the underwriters, however, may, in their sole discretion, permit our officers, directors and other stockholders who are subject to these lock-up agreements to sell shares prior to the expiration of the lock-up agreements.

The lock-up agreements pertaining to this offering will expire 180 days from the date of this prospectus. After the lock-up agreements expire, based upon the number of shares of common stock, on an as-converted basis, outstanding as of December 31, 2014, up to an additional              shares of common stock will be eligible for sale in the public market, of which              shares are held by directors, executive officers and other affiliates and will be subject to certain limitations of Rule 144 under the Securities Act of 1933, as amended, or the Securities Act.

In addition, as of December 31, 2014,             shares of common stock that are either subject to outstanding options or reserved for future issuance under our equity incentive plans will become eligible for sale in the public market to the extent permitted by the provisions of various vesting schedules, the lock-up agreements and Rule 144 and Rule 701 under the Securities Act. If these additional shares of common stock are sold, or if it is perceived that they will be sold, in the public market, the market price of our common stock could decline.

After this offering, the holders of approximately              shares of our common stock will be entitled to rights with respect to the registration of their shares under the Securities Act, subject to the lock-up

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agreements described above. Registration of these shares under the Securities Act would result in the shares becoming freely tradable without restriction under the Securities Act, except for shares purchased by affiliates. Any sales of securities by these stockholders could have a material adverse effect on the market our common stock.

If we are unable to successfully remediate the existing material weakness in our internal control over financial reporting, the accuracy and timing of our financial reporting may be adversely affected.

In preparing our consolidated financial statements as of and for the year ended December 31, 2014, we and our independent registered public accounting firm identified control deficiencies in the design and operation of our internal control over financial reporting that constituted a material weakness in our internal control over financial reporting. A material weakness is a deficiency, or a combination of deficiencies, in internal control over financial reporting such that there is a reasonable possibility that a material misstatement of our financial statements will not be prevented or detected on a timely basis. The material weakness identified resulted from the fact that we do not have sufficient financial reporting and accounting staff with appropriate training in generally accepted accounting principles in the United States, or GAAP, and SEC rules and regulations to perform an adequate level of review of accounting and financial reporting information or maintain adequate controls related to the risk assessment and information components of the control framework, and there was insufficient oversight of the financial reporting process by those charged with governance due to a lack of internal resources. As such, our controls over financial reporting were not designed or operating effectively and, as a result there were adjustments required in connection with closing our books and records and preparing our December 31, 2014 consolidated financial statements.

The material weakness in our internal control over financial reporting was attributable to our lack of sufficient financial reporting and accounting personnel with the technical expertise to appropriately segregate the preparation and review of the accounting and financial information that is reflected in our consolidated financial statements, and a lack of oversight in the financial reporting process by those charged with governance. In response to this material weakness, we plan to hire additional personnel with public company financial reporting expertise to build our financial management and reporting infrastructure and further develop and document our accounting policies and financial reporting procedures. However, we cannot assure you that we will be successful in pursuing these measures or that these measures will significantly improve or remediate the material weakness described above. We also cannot assure you that we have identified all of our existing material weaknesses, or that we will not in the future have additional material weaknesses. We have not yet remediated our material weakness, and the remediation measures that we intend to implement may be insufficient to address our existing material weakness or to identify or prevent additional material weaknesses.

Neither we nor our independent registered public accounting firm has performed an evaluation of our internal control over financial reporting during any period in accordance with the provisions of the Sarbanes-Oxley Act. In light of the control deficiencies and the resulting material weakness that were identified as a result of the limited procedures performed, we believe that it is possible that, had we and our independent registered public accounting firm performed an evaluation of our internal control over financial reporting in accordance with the provisions of the Sarbanes-Oxley Act, additional material weaknesses and significant control deficiencies may have been identified. However, for as long as we remain an “emerging growth company” as defined in the JOBS Act, we intend to take advantage of the exemption permitting us not to comply with the requirement that our independent registered public accounting firm provide an attestation on the effectiveness of our internal control over financial reporting.

If we fail to remediate the material weakness or to meet the demands that will be placed upon us as a public company, including the requirements of the Sarbanes-Oxley Act, we may be unable to accurately report our financial results, or report them within the timeframes required by law or stock exchange regulations. Failure to comply with Section 404 of the Sarbanes-Oxley Act could also potentially subject us to sanctions or investigations by the SEC or other regulatory authorities. There is no assurance that we will be able to

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remediate the material weakness in a timely manner, if at all, or that in the future, additional material weaknesses will not exist or otherwise be discovered. If our efforts to remediate the material weakness identified are not successful, or if other material weaknesses or other deficiencies occur, our ability to accurately and timely report our financial position could be impaired, which could result in late filings of our annual and quarterly reports under the Exchange Act, restatements of our consolidated financial statements, a decline in our stock price, suspension or delisting of our common stock from the NASDAQ Global Market, and could adversely affect our reputation, results of operations and financial condition.

We will have broad discretion in how we use the proceeds of this offering. We may not use these proceeds effectively, which could affect our results of operations and cause our stock price to decline.

We will have considerable discretion in the application of the net proceeds of this offering. We intend to use the net proceeds from this offering to advance the clinical development of Gelesis100 as a treatment to induce weight loss in overweight and obese patients, to advance the clinical development of Gelesis200 as a treatment to improve glycemic control in prediabetic and diabetic patients, to continue the development of our other product candidates and to fund new and ongoing research and development activities, working capital and other general corporate purposes, which may include funding for the hiring of additional personnel, capital expenditures and the costs of operating as a public company. As a result, investors will be relying upon management’s judgment with only limited information about our specific intentions for the use of the balance of the net proceeds of this offering. We may use the net proceeds for purposes that do not yield a significant return or any return at all for our stockholders. In addition, pending their use, we may invest the net proceeds from this offering in a manner that does not produce income or that loses value.

After the completion of this offering, we may be at an increased risk of securities class action litigation.

Historically, securities class action litigation has often been brought against a company following a decline in the market price of its securities. This risk is especially relevant for us because biotechnology, pharmaceutical and medical device companies have experienced significant stock price volatility in recent years. If we were to be sued, it could result in substantial costs and a diversion of management’s attention and resources, which could harm our business.

Anti-takeover provisions in our charter documents and under Delaware law could make an acquisition of us, even one that may be beneficial to our stockholders, more difficult and may prevent attempts by our stockholders to replace or remove our current management.

Provisions in our amended and restated certificate of incorporation and amended and restated bylaws may delay or prevent an acquisition of us or a change in our management. These provisions include a classified board of directors, a prohibition on actions by written consent of our stockholders and the ability of our board of directors to issue preferred stock without stockholder approval. In addition, because we are incorporated in Delaware, we are governed by the provisions of Section 203 of the Delaware General Corporation Law, which limits the ability of stockholders owning in excess of 15% of our outstanding voting stock to merge or combine with us. Although we believe these provisions collectively provide for an opportunity to obtain greater value for stockholders by requiring potential acquirers to negotiate with our board of directors, they would apply even if an offer rejected by our board were considered beneficial by some stockholders. In addition, these provisions may frustrate or prevent any attempts by our stockholders to replace or remove our current management by making it more difficult for stockholders to replace members of our board of directors, which is responsible for appointing the members of our management. See “Description of Capital Stock—Anti-Takeover Effects of Provisions of our Amended and Restated Certificate of Incorporation, our Amended and Restated Bylaws and Delaware Law” for more information.

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We are an “emerging growth company,” and as a result of the reduced disclosure and governance requirements applicable to emerging growth companies, our common stock may be less attractive to investors.

We are an “emerging growth company,” as defined in the JOBS Act, and we intend to take advantage of certain exemptions from various reporting requirements that are applicable to other public companies that are not emerging growth companies including, but not limited to, not being required to comply with the auditor attestation requirements of Section 404, reduced disclosure obligations regarding executive compensation in our periodic reports and proxy statements, and exemptions from the requirements of holding a nonbinding advisory vote on executive compensation and stockholder approval of any golden parachute payments not previously approved. If we choose not to comply with the auditor attestation requirements of Section 404 of the Sarbanes-Oxley Act, our auditors will not be required to attest to the effectiveness of our internal control over financial reporting. As a result, investors may become less comfortable with the effectiveness of our internal controls and the risk that material weaknesses or other deficiencies in our internal controls go undetected may increase. In addition, the JOBS Act provides that an emerging growth company can take advantage of an extended transition period for complying with new or revised accounting standards. This allows an emerging growth company to delay the adoption of certain accounting standards until those standards would otherwise apply to private companies. If we choose to provide reduced disclosures in our periodic reports and proxy statements while we are an emerging growth company, investors would have access to less information and analysis about our executive compensation, which may make it difficult for investors to evaluate our executive compensation practices. We cannot predict if investors will find our common stock less attractive because we will rely on these exemptions. If some investors find our common stock less attractive as a result, there may be a less active trading market for our common stock and our stock price may be more volatile. We may take advantage of these reporting exemptions until we are no longer an “emerging growth company.” We will remain an “emerging growth company” until the earlier of (1) the last day of the fiscal year (a) following the fifth anniversary of the completion of this offering, (b) in which we have total annual gross revenue of at least $1.0 billion, or (c) in which we are deemed to be a large accelerated filer, which means the market value of our common stock that is held by non-affiliates exceeds $700 million as of the prior June 30th, and (2) the date on which we have issued more than $1.0 billion in non-convertible debt during the prior three-year period.

If we fail to maintain an effective system of internal control over financial reporting, we may not be able to accurately report our financial results or prevent fraud. As a result, stockholders could lose confidence in our financial and other public reporting, which would harm our business and the trading price of our common stock.

Effective internal controls over financial reporting are necessary for us to provide reliable financial reports and, together with adequate disclosure controls and procedures, are designed to prevent fraud. Any failure to implement required new or improved controls, or difficulties encountered in their implementation could cause us to fail to meet our reporting obligations. In addition, any testing by us conducted in connection with Section 404 of the Sarbanes-Oxley Act of 2002, or any subsequent testing by our independent registered public accounting firm, may reveal deficiencies in our internal controls over financial reporting that are deemed to be material weaknesses or that may require prospective or retroactive changes to our financial statements or identify other areas for further attention or improvement. Inferior internal controls could also cause investors to lose confidence in our reported financial information, which could have a negative effect on the trading price of our common stock.

We will be required to disclose changes made in our internal controls and procedures on a quarterly basis, and our management will be required to assess the effectiveness of these controls annually, beginning with the year ending December 31, 2016. However, for as long as we are an “emerging growth company” under the JOBS Act, our independent registered public accounting firm will not be required to attest to the effectiveness of our internal controls over financial reporting pursuant to Section 404. We could be an “emerging growth company” for up to five years. An independent

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assessment of the effectiveness of our internal controls could detect problems that our management’s assessment might not. Undetected material weaknesses in our internal controls could lead to financial statement restatements and require us to incur the expense of remediation.

The rules governing the standards that must be met for our management to assess our internal control over financial reporting pursuant to Section 404 of the Sarbanes-Oxley Act are complex and require significant documentation, testing and possible remediation. These standards require that our audit committee be advised and regularly updated on management’s review of internal control over financial reporting. Our management may not be able to effectively and timely implement controls and procedures that adequately respond to the increased regulatory compliance and reporting requirements that will be applicable to us as a public company. If we fail to staff our accounting and finance function adequately or maintain internal control over financial reporting adequate to meet the demands that will be placed upon us as a public company, including the requirements of the Sarbanes-Oxley Act, our business and reputation may be harmed and our stock price may decline. Furthermore, investor perceptions of us may be adversely affected, which could cause a decline in the market price of our common stock.

If you purchase our common stock in this offering, you will incur immediate and substantial dilution in the book value of your shares.

You will suffer immediate and substantial dilution in the net tangible book value of the common stock you purchase in this offering. Based on the initial public offering price of $         per share, the midpoint of the price range set forth on the cover of this prospectus, purchasers of common stock in this offering will experience immediate dilution of $         per share, representing the difference between our pro forma as adjusted net tangible book value per share of the common stock as of December 31, 2014 and the assumed initial public offering price. In addition, investors purchasing common stock in this offering will contribute     % of the total amount invested by stockholders since inception but will only own     % of the shares of common stock outstanding. In the past, we issued options to acquire common stock at prices significantly below the initial public offering price. In addition, future sales and issuances of our common stock or rights to purchase common stock, including pursuant to our equity incentive plans, could result in additional dilution of the percentage ownership of our stockholders and could cause our stock price to fall. To the extent these outstanding options are ultimately exercised, investors purchasing common stock in this offering will sustain further dilution. See “Dilution” for a more detailed description of the dilution to new investors in the offering.

We do not intend to pay dividends on our common stock and, consequently, your ability to achieve a return on your investment will depend on appreciation in the price of our common stock.

We do not currently intend to pay cash dividends on our common stock and we do not plan do so in the foreseeable future. We currently anticipate that we will retain future earnings, if any, for the development, operation and expansion of our business. Therefore, the success of an investment in shares of our common stock will depend upon any future appreciation in their value. There is no guarantee that shares of our common stock will appreciate in value or even maintain the price at which you purchased them.

If securities or industry analysts do not publish or cease publishing research or reports or publish misleading, inaccurate or unfavorable research about us, our business or our market, our stock price and trading volume could decline.

The trading market for our common stock will be influenced by the research and reports that securities or industry analysts publish about us, our business, our market or our competitors. We do not currently have and may never obtain research coverage by securities and industry analysts. If no or few securities or industry analysts cover our company, the trading price and volume of our stock would likely be negatively impacted. If we obtain securities or industry analyst coverage and if one or more of the

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analysts who covers us downgrades our stock or publishes inaccurate or unfavorable research about our business, or provides more favorable relative recommendations about our competitors, our stock price would likely decline. If one or more of these analysts ceases coverage of us or fails to publish reports on us regularly, demand for our stock could decrease, which could cause our stock price or trading volume to decline.

Our employment and consultant agreements with our named executive officers may require us to pay severance benefits to any of those persons who are terminated in connection with a change of control of us, which could harm our financial condition or results.

Our named executive officers are parties to employment and consultant agreements providing for aggregate cash payments of up to approximately $0.4 million for severance and other benefits, in the event of a termination of employment in connection with a change of control of our company. The payment of these severance benefits could harm our financial condition and results. In addition, these potential severance payments may discourage or prevent third parties from seeking a business combination with us.

Our bylaws designate a state or federal court located within the State of Delaware as the sole and exclusive forum for certain types of actions and proceedings that may be initiated by our stockholders, which could limit our stockholders’ ability to obtain a preferred judicial forum for disputes with us or our directors, officers or other employees.

Our bylaws will provide that, unless we consent in writing to the selection of an alternative forum, the sole and exclusive forum for (i) any derivative action or proceeding brought on our behalf, (ii) any action asserting a claim of breach of a fiduciary duty owed by any director, officer or other employee to us or our stockholders, (iii) any action asserting a claim arising pursuant to any provision of Delaware General Corporation Law, our certificate of incorporation (including any certificate of designations for any class or series of our preferred stock) or our bylaws, in each case, as amended from time to time, or (iv) any action asserting a claim governed by the internal affairs doctrine shall be a state or federal court located within the State of Delaware, in all cases subject to the court’s having personal jurisdiction over the indispensable parties named as defendants. Any person or entity purchasing or otherwise acquiring any interest in shares of our capital stock is deemed to have received notice of and consented to the foregoing provision. This forum selection provision may limit a stockholder’s ability to bring a claim in a judicial forum that it finds favorable or cost-effective for disputes with us or our directors, officers or other employees, which may discourage such lawsuits against us and our directors, officers and employees.

We may not achieve the intended benefits of having an exclusive forum provision if it is found to be unenforceable.

We have included an exclusive forum provision in our bylaws as described above. However, the enforceability of similar exclusive jurisdiction provisions in other companies’ bylaws or certificates of incorporation has been challenged in legal proceedings, and it is possible that, in connection with any action, a court could find the exclusive jurisdiction provision contained in our bylaws to be inapplicable or unenforceable in such action. Although in September 2014 the Delaware Court of Chancery upheld the statutory and contractual validity of exclusive forum-selection bylaw provisions, the validity of such provisions is not yet settled law under the laws of Delaware. Furthermore, the Delaware Court of Chancery emphasized that such provisions may not be enforceable under circumstances where they are found to operate in an unreasonable or unlawful manner or in a manner inconsistent with a board’s fiduciary duties. Also, it is uncertain whether non-Delaware courts consistently will enforce such exclusive forum-selection bylaw provisions. If a court were to find our choice of forum provision inapplicable to, or unenforceable in respect of, one or more of the specified types of actions or proceedings, we may incur additional costs associated with resolving such matters in other jurisdictions and we may not obtain the benefits of limiting jurisdiction to the courts selected.

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SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS

This prospectus contains forward-looking statements concerning our business, operations and financial performance and condition, as well as our plans, objectives and expectations for our business operations and financial performance and condition. Any statements contained herein that are not statements of historical facts may be deemed to be forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as “aim,” “anticipate,” “assume,” “believe,” “contemplate,” “continue,” “could,” “due,” “estimate,” “expect,” “goal,” “intend,” “may,” “objective,” “plan,” “predict,” “potential,” “positioned,” “seek,” “should,” “target,” “will,” “would,” and other similar expressions that are predictions of or indicate future events and future trends, or the negative of these terms or other comparable terminology. These forward-looking statements include, but are not limited to, statements about:

These forward-looking statements are based on our management’s current expectations, estimates, forecasts and projections about our business and the industry in which we operate and our management’s beliefs and assumptions. These forward-looking statements are not guarantees of future performance or development and involve known and unknown risks, uncertainties and other factors that are in some cases beyond our control. As a result, any or all of our forward-looking statements in this prospectus may turn out to be inaccurate. Factors that may cause actual results to differ materially from current expectations include, among other things, those listed under “Risk Factors” and discussed elsewhere in this prospectus. Potential investors are urged to consider these factors carefully in evaluating

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the forward-looking statements. These forward-looking statements speak only as of the date of this prospectus. Except as required by law, we assume no obligation to update or revise these forward-looking statements for any reason, even if new information becomes available in the future. You should, however, review the factors and risks we describe in the reports we will file from time to time with the SEC after the date of this prospectus. See “Where You Can Find More Information.”

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USE OF PROCEEDS

We estimate that the net proceeds from our issuance and sale of              shares of our common stock in this offering will be approximately $        , assuming an initial public offering price of $          per share, the midpoint of the price range set forth on the cover page of this prospectus, after deducting estimated underwriting discounts and commissions and estimated offering expenses payable by us. If the underwriters exercise their option to purchase additional shares in full, we estimate that the net proceeds from this offering will be approximately $        .

A $1.00 increase (decrease) in the assumed initial public offering price of $         per share, the midpoint of the price range set forth on the cover page of this prospectus, would increase (decrease) the net proceeds from this offering by approximately $        , assuming that the number of shares offered by us, as set forth on the cover page of this prospectus, remains the same and after deducting the estimated underwriting discounts and commissions and estimated offering expenses payable by us. We may also increase or decrease the number of shares we are offering. Each increase (decrease) of 1.0 million in the number of shares we are offering would increase (decrease) the net proceeds to us from this offering, after deducting the estimated underwriting discounts and commissions and estimated offering expenses payable by us, by approximately $         million, assuming the assumed initial public offering price stays the same.

We intend to use the net proceeds from this offering to fund:

This expected use of the net proceeds from this offering represents our intentions based upon our current plans and business conditions. As of the date of this prospectus, we cannot predict with certainty all of the particular uses for the net proceeds to be received upon the closing of this offering or the amounts that we will actually spend on the uses set forth above. The amounts and timing of our actual expenditures may vary significantly depending on numerous factors, including the progress of our development efforts, the status of and results from preclinical studies and any ongoing clinical trials or clinical trials we and they may commence in the future, as well as any collaborations that we may enter into with third parties for our product candidates and any unforeseen cash needs. As a result, our management will retain broad discretion over the allocation of the net proceeds from this offering. We may also use a portion of the net proceeds of this offering for the acquisition of, or investment in, technologies, solutions or businesses that complement our business, but we have no present commitments or agreements to enter into any such transaction.

Pending our use of the net proceeds from this offering, we intend to invest the net proceeds in a variety of capital preservation investments, including short-term, investment grade, interest bearing instruments and U.S. government securities.

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DIVIDEND POLICY

We do not intend to pay cash dividends to holders of our common stock in the foreseeable future. Any future determination as to the declaration and payment of dividends, if any, will be at the discretion of our board of directors and will depend upon then existing conditions, including our financial condition, operating results, contractual restrictions, restrictions imposed by applicable law, capital requirements, business prospects and other factors our board of directors may deem relevant.

In 2012, to satisfy certain tax obligations incurred by our stockholders in connection with the distribution of equity interests of Gelesis, LLC to our stockholders and option holders, we elected to declare and pay a cash dividend of approximately $215,000 to our stockholders and approximately $120,000 to option and warrant holders under our 2006 Plan.

In January 2015, Gelesis, LLC, an intellectual property holding company controlled by us and our stockholders, was reorganized into a wholly owned subsidiary of Gelesis in connection with the issuance of an aggregate of 331,829 shares of our common stock to our stockholders. See “Business—Gelesis, LLC Reorganization.”

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CAPITALIZATION

The following table sets forth our unaudited cash and capitalization as of December 31, 2014:

The pro forma and pro forma as adjusted information below is illustrative only, and our capitalization following the closing of this offering will be adjusted based on the actual initial public offering price and other terms of this offering determined at pricing. You should read this information together with our financial statements and related notes appearing elsewhere in this prospectus and the information set forth under the headings “Selected Consolidated Financial Data” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations.”

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A $1.00 increase (decrease) in the assumed initial public offering price of $         per share, the midpoint of the estimated price range set forth on the cover page of this prospectus, would increase (decrease) each of total stockholders’ deficit, cash and total capitalization on a pro forma as adjusted basis by approximately $         million, assuming that the number of shares offered by us, as set forth on the cover page of this prospectus, remains the same and after deducting estimated underwriting discounts and commissions and estimated offering costs payable by us.

The number of shares shown as issued and outstanding in the table above is based on 7,317,772 shares of common stock outstanding as of March 15, 2015 as if the March 2015 debt and equity transactions had occurred on 12/31/14 and excludes:

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DILUTION

If you invest in our common stock, your interest will be diluted immediately to the extent of the difference between the initial public offering price per share you will pay in this offering and the pro forma as adjusted net tangible book value per share of our common stock immediately after this offering.

Our net tangible book value (deficit) as of December 31, 2014 was $(16.1) million, or $(2.30) per share of common stock. The net tangible book value per share represents the amount of our total tangible assets less total liabilities, divided by the number of shares of common stock outstanding as of December 31, 2014.

Our pro forma net tangible book value on December 31, 2014 was $(49,000), or $(0.00) per share of common stock. Pro forma net tangible book value represents total tangible assets less total liabilities and assumes the automatic conversion of the warrants for Series A-1, Series A-3 and A-4 convertible preferred stock into warrants for common stock upon the closing of this offering, the conversion of our convertible promissory notes into Series A-5 convertible preferred stock in March 2015, the receipt of gross proceeds of $18.0 million upon the issuance of Series A-5 convertible preferred stock in March 2015 and the write off of the related derivative liability which results in a reduction in total liabilities of $16.0 million. Pro forma net tangible book value per share represents pro forma net tangible book value divided by the total number of shares outstanding as of December 31, 2014, after giving effect to the automatic conversion of all outstanding shares of our convertible preferred stock into an aggregate of 27,056,623 shares of common stock (including 6,851,626 shares upon conversion of Series A-5 convertible preferred stock issued in March 2015) upon the closing of this offering.

After giving further effect to adjustments relating to this offering, our pro forma as adjusted net tangible book value as of December 31, 2014 would have been          million, or $         per share. The adjustments made to the pro forma net tangible book value per share to determine pro forma as adjusted net tangible book value per share are the following:

The initial public offering price per share will significantly exceed the pro forma as adjusted net tangible book value per share. Accordingly, new investors who purchase shares of common stock in this offering will suffer an immediate dilution of their investment of $         per share. The following table illustrates the increase in pro forma as adjusted net tangible book value of $         per share and the dilution (the difference between the initial public offering price per share and pro forma as adjusted net tangible book value per share) to new investors:

If the underwriters exercise their option to purchase additional shares in full, the pro forma as adjusted net tangible book value will increase to $         per share, representing an immediate dilution of $         per share to new investors, assuming that the initial public offering price will be $         per share, the midpoint of the range set forth on the cover page of this prospectus.

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A $1.00 increase (decrease) in the assumed initial public offering price of $         per share, the midpoint of the range set forth on the cover page of this prospectus, would increase (decrease) the pro forma as adjusted net tangible book value by $         million, the pro forma as adjusted net tangible book value per share by $         per share, and the dilution in pro forma as adjusted net tangible book value per share to investors in this offering by $         per share, assuming that the number of shares offered by us, as set forth on the cover page of this prospectus, remains the same and after deducting the estimated underwriting discounts and commissions and estimated offering expenses payable by us.

We may also increase or decrease the number of shares we are offering. An increase of 1.0 million shares in the number of shares offered by us, as set forth on the cover page of this prospectus, would increase our pro forma as adjusted net tangible book value per share after this offering by approximately $         million and decrease the dilution to investors participating in this offering by approximately $         per share, assuming that the assumed initial public offering price remains the same, and after deducting the estimated underwriting discounts and commissions and the estimated offering expenses payable by us. Similarly, a decrease of 1.0 million shares in the number of shares offered by us, as set forth on the cover page of this prospectus, would decrease the pro forma as adjusted net tangible book value per share after this offering by approximately $         million and increase the dilution to investors participating in this offering by approximately $         per share, assuming that the assumed initial public offering price remains the same, and after deducting the estimated underwriting discounts and commissions and the estimated offering expenses payable by us.

If shares are issued in connection with the exercise of all outstanding options and warrants for common stock with exercise prices less than $        , the midpoint of the price range set forth on the cover page of this prospectus, you will experience further dilution of $         per share. As of December 31, 2014, we had outstanding options and warrants to purchase a total of              shares of our common stock with exercise prices less than $         per share.

The following table summarizes, as of December 31, 2014, on a pro forma as adjusted basis as described above, the differences between the number of shares of common stock purchased from us, the total consideration paid to us, and the average price per share paid by existing stockholders and by investors purchasing shares of common stock in this offering. The calculation below is based on an assumed initial public offering price of $         per share, the midpoint of the estimated price range set forth on the cover of this prospectus, before the deduction of the estimated underwriting discounts and commissions and estimated offering expenses payable by us:

The tables above assume no exercise of options to purchase shares of common stock outstanding as of December 31, 2014. At December 31, 2014, there were 5,652,818 shares of common stock issuable upon exercise of outstanding options with a weighted average exercise price of $0.88 per share.

The number of shares shown as issued and outstanding in the table above is based on 6,985,943 shares of common stock outstanding as of December 31, 2014 and excludes:

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If the underwriters exercise their option to purchase additional shares in full, the number of shares held by new investors will increase to         , or     % of the total number of shares of common stock outstanding after this offering.

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SELECTED CONSOLIDATED FINANCIAL DATA

The following tables show selected consolidated financial data as of, and for the periods ended on, the dates indicated. We derived the selected consolidated statement of operations data for the years ended December 31, 2013 and 2014 and the consolidated balance sheet data as of December 31, 2013 and 2014 from our audited consolidated financial statements appearing elsewhere in this prospectus. Our historical results are not necessarily indicative of the results to be expected in the future and results of interim periods are not necessarily indicative of the results for the entire year. You should read the following selected consolidated financial data in conjunction with our financial statements, the notes to the consolidated financial statements and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” included elsewhere in this prospectus. The selected consolidated financial data included in this section are not intended to replace the consolidated financial statements and the related notes included elsewhere in this prospectus.

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MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION

AND RESULTS OF OPERATIONS

You should read the following discussion and analysis of our financial condition and results of operations together with the section entitled “Selected Consolidated Financial Data” and our consolidated financial statements and related notes appearing in this prospectus. Some of the information contained in this discussion and analysis or set forth elsewhere in this prospectus, including information with respect to our plans and strategy for our business and related financing, includes forward-looking statements that involve risks and uncertainties. As a result of many factors, including those factors set forth in the “Risk Factors” section of this prospectus, our actual results could differ materially from the results described in or implied by the forward-looking statements contained in the following discussion and analysis.

Overview

We are a biotechnology company focused on the development of first-in-class products to induce weight loss and improve glycemic control in overweight and obese patients. Our product candidates are based on our proprietary hydrogel technology that works mechanically, as opposed to via a chemical mode of action, and exclusively in the gastrointestinal, or GI, tract rather than systemically or through surgical intervention. We believe our product candidates, if approved, have the potential to address the obesity and diabetes epidemics safely and effectively while optimizing convenience and ease of use.

Our lead product candidate, Gelesis100, is an orally administered capsule that contains small hydrogel particles designed to employ multiple mechanisms along the GI tract to induce weight loss and improve glycemic control. These hydrogel particles are engineered to rapidly absorb and release water at specific locations in the GI tract. We have completed a 3 month proof of concept, or POC, 128-patient, randomized, double-blind, placebo-controlled, parallel-group clinical trial for Gelesis100 that demonstrated statistically significant weight loss in overweight and obese patients, including prediabetics. Gelesis100 exhibited a safety profile that was similar to that of placebo with no serious adverse events observed. In November 2014, we initiated a 168-patient, randomized, double-blind, placebo-controlled, parallel-group, 6 month clinical trial to study the ability of Gelesis100 to induce weight loss and improve glycemic control in overweight and obese patients, including those with prediabetes and mild type 2 diabetes. We expect to report data from this trial in the first half of 2016. Although Gelesis100 is an orally administered capsule, we anticipate it will be regulated as a medical device.

Since our inception in 2006, we have devoted substantially all of our resources to licensing and acquiring technology, research and development, and raising capital. We do not have any products approved for sale and have not generated any revenue from product sales. We have funded our operations to date through proceeds from collaborations and issuance of common and convertible preferred stock, issuance of convertible and non-convertible debt and non-dilutive grants received from government agencies.

We expect to continue to incur significant expenses and increasing operating losses for at least the next several years. We expect our expenses and capital requirements will increase substantially in connection with our ongoing activities, as we:

We will not generate product sales unless and until we successfully complete clinical development and obtain regulatory approval for our product candidates. Additionally, we currently utilize third-party

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contract research organizations, or CROs, to carry out our clinical development activities, and we do not yet have a commercial organization. If we obtain regulatory approval for any of our product candidates, we expect to incur significant expenses related to developing our internal commercialization capability to support product sales, marketing and distribution. Accordingly, we will seek to fund our operations through public or private equity or debt financings or other sources, potentially including collaborative commercial arrangements.

Because of the numerous risks and uncertainties associated with product development, we are unable to predict the timing or amount of increased expenses or when or if we will be able to achieve or maintain profitability. Even if we are able to generate product sales, we may not become profitable. If we fail to become profitable or are unable to sustain profitability on a continuing basis, then we may be unable to continue our operations at planned levels and be forced to reduce or terminate our operations.

Financial Operations Overview

Revenues

To date, we have not generated any product sales. Our limited revenues have been derived from a license and collaboration agreement and grants from government agencies. The license and collaboration agreement was executed in June 2012 and terminated effective November 2013.

Under previously approved grants from the Puglia Region in Italy and an Italian economic development agency, we are reimbursed for certain qualifying capital investments and expenses incurred for research and development work performed in Italy and other countries in the European Union.

Research and Development Expenses

Research and development expenses consist primarily of costs incurred for the development of our product candidates, which include:

Research and development costs are expensed as incurred. Costs for certain development activities are recognized based on an evaluation of the progress to completion of specific tasks using information and data provided to us by our vendors, CROs and clinical sites.

We cannot determine with certainty the duration and completion costs of the current or future clinical studies of our product candidates or if, when, or to what extent we will generate sales from the commercialization of any of our product candidates if they receive regulatory approval. The successful development of our product candidates is highly uncertain and may never result in approved products. The duration, costs, and timing of clinical studies and development of our product candidates will depend on a variety of factors, including:

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A change in the outcome of any of these variables with respect to the development of a product candidate could mean a significant change in the costs and timing associated with the development of that product candidate. For example, if the FDA, or another regulatory authority were to require us to conduct clinical studies beyond those that we currently anticipate will be required for the completion of clinical development of a product candidate, we could be required to expend significant additional financial resources and time on the completion of clinical development.

We plan to increase our research and development expenses for the foreseeable future as we continue the development of Gelesis100 and Gelesis200. Our current planned research and development activities include the following:

To date, substantially all of our research and development efforts have been related to the development of Gelesis100. We do not allocate personnel-related costs, costs associated with our general research platform improvements, depreciation or other indirect costs to specific programs.

General and Administrative Expenses

General and administrative expenses consist primarily of salaries and related costs for personnel, including stock-based compensation and travel expenses for our employees in executive, operational, finance and human resource functions. Other general and administrative expenses include facility-related costs and professional fees for directors, accounting and legal services and expenses associated with obtaining and maintaining our intellectual property.

We anticipate that our general and administrative expenses will increase in the future as we increase our headcount to support our continued research and development and potential commercialization of our product candidates. We also anticipate increased expenses related to audit, legal, regulatory, and tax-related services associated with maintaining compliance with exchange listing and Securities and Exchange Commission requirements, director and officer liability insurance, investor relations costs and other costs associated with being a public company. Additionally, if and when we believe a regulatory approval of Gelesis100 appears likely, we anticipate an increase in staffing and related expenses as a result of our preparation for commercial operations, especially as it relates to the sales and marketing of our product candidates.

Other (Income) Expense, Net

Gains (losses) from change in the fair value of warrants.    We have issued warrants for the purchase of preferred stock that contain redemption features that are not solely within our control. Therefore, we have classified these warrants as liabilities that we remeasure to fair value at each reporting period and we record changes in fair value of the warrants as a component of other income (expense), net.

We use the Black-Scholes option pricing model, or Black-Scholes, to estimate the fair value of the warrants. We base the estimates in Black-Scholes, in part, on subjective assumptions, including stock price volatility, risk-free interest rate, dividend yield, and the fair value of the preferred stock underlying the warrants.

Interest expense.    Interest expense consisted of interest accrued in connection with our convertible notes and loans.

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Results of Operations

Comparison of the Years Ended December 31, 2013 and 2014