SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
Pursuant to Section 13 or 15(d)
of The Securities Exchange Act of 1934
Date of Report (Date of Earliest Event Reported): January 10, 2020
(Exact name of registrant as specified in its charter)
(State or other jurisdiction
140 Kendrick Street, Building C East
Needham, Massachusetts 02494
(Address of principal executive office) (Zip Code)
(Registrants telephone number, including area code)
460 Totten Pond Road, Suite 530
Waltham, Massachusetts 02451
(Former name or former address, if changed since last report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))
Securities registered pursuant to Section 12(b) of the Act:
Title of each class
Name of each exchange
on which registered
|Common Stock, $0.01 par value||CHMA||NASDAQ Global Select Market|
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company ☒
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☒
|Item 2.02|| |
Results of Operations and Financial Condition.
On January 10, 2020, Chiasma, Inc. (the Company) issued a press release (the Press Release) providing a year-end corporate update and preliminary 2020 outlook, which Press Release included the Companys preliminary approximate cash, cash equivalents and marketable securities as of December 31, 2019 (the Financial Information). The Financial Information is unaudited and does not present all information necessary for an understanding of the Companys financial condition as of December 31, 2019 and its results of operations for the twelve months ended December 31, 2019. A copy of the Press Release is furnished herewith as Exhibit 99.1.
The Financial Information set forth in Item 2.01 and Exhibit 99.1 is intended to be furnished and shall not be deemed filed for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the Exchange Act), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such a filing.
|Item 7.01|| |
A copy of the slide presentation that will be used by representatives of the Company in connection with investor meetings and presentations from time to time (the Corporate Presentation) is attached to this Current Report on Form 8-K as Exhibit 99.1. The Corporate Presentation is current as of January 10, 2020, and the Company disclaims any obligation to correct or update this material in the future.
The information set forth in Item 7.01 and Exhibit 99.1 is intended to be furnished and shall not be deemed filed for purposes of Section 18 of the Exchange Act or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such a filing.
|Item 8.01|| |
On January 10, 2020, the Company issued the Press Release, which announced, among other things, the Companys resubmission of its new drug application (NDA) to the United States Food and Drug Administration (FDA) seeking marketing approval for its investigational octreotide capsules product candidate, conditionally trade-named MYCAPSSA®, for the maintenance treatment of adults with acromegaly. Following the anticipated approval of the NDA by the FDA, the Company expects to submit two manufacturing supplements to the NDA to provide for an additional active pharmaceutical ingredient (API) manufacturer and an additional commercial-scale manufacturing site affiliated with the API manufacturer currently referenced in the NDA. These manufacturing sources were not included in the NDA resubmission in order to allow for further time for the additional API manufacturer not referenced in the NDA to resolve observations from a recent regulatory inspection and to allow the Company to seek the FDAs designation of the resubmission of the NDA as a Class 2 resubmission, which typically entails a six-month review period. The Company is currently procuring API from both sources in anticipation of an NDA approval and, subject to FDAs timely approval of the NDA and either of the manufacturing supplements, expects to have oral octreotide product available to support its planned commercial launch in the fourth quarter of 2020.
A copy of the Press Release is attached hereto as Exhibit 99.1 and is incorporated herein by reference.
Cautionary note on forward-looking statements
This Current Report on Form 8-K contains forward-looking statements, including, but not limited to, statements regarding the Companys intent to submit manufacturing supplements to its NDA to provide for an additional API manufacturer and for an additional commercial-scale manufacturing site of the API manufacturer currently referenced in the NDA following a potential NDA approval by the FDA and statements concerning the Companys expectations regarding the availability of oral octreotide product supply. These forward-looking statements are not promises or guarantees and involve substantial risks and uncertainties that can cause actual results to differ materially from those in such forward-looking statements. Such statements are subject to numerous important factors, risks and uncertainties, many of which are beyond the Companys control, that may cause actual events or results to differ materially from the Companys current expectations. For example, the review of any manufacturing supplement to the NDA to provide for an additional API manufacturer and an additional API manufacturing site will require FDA review and approval of the manufacturing process, facility, equipment and procedures in place at each manufacturer in accordance with the FDAs current good manufacturing practice requirements and may require additional regulatory inspections of each manufacturer, which could prevent or delay approval of any such manufacturing supplement to the NDA and prevent or delay commercial launch. In addition, even if the Company is able to obtain approval of the additional API manufacturer or additional API manufacturing site, there can be no guarantee that the Company will be able to secure API or commercial octreotide capsules in sufficient quantities, in a timely manner or at all and initiate the planned commercial launch of octreotide capsules. Managements expectations and, therefore, any forward-looking statements in this Current Report on Form 8-K could be affected by risks and uncertainties relating to a number of factors, including the following: the content and timing of decisions made by the FDA, including with respect to the NDA and any manufacturing supplements to the NDA we may submit to the FDA, the results of any inspections of the Companys third-party manufacturers, the Companys reliance on third parties to manufacture API and commercial octreotide capsules, and the Companys ability to obtain and retain requisite regulatory approvals for the commercial sale of octreotide capsules in the United States. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause the Companys actual results to differ from those contained in the forward-looking statements, see the section entitled Risk Factors in the Companys Annual Report on Form 10-K for the year ended December 31, 2018, and in subsequent filings with the Securities and Exchange Commission. All information in this Current Report on Form 8-K is as of the date hereof, and the Company undertakes no duty to update this information unless required by law.
|Item 9.01|| |
Financial Statements and Exhibits.
|99.1||Press release dated January 10, 2020.|
|99.2||Corporate presentation current as of January 10, 2020.|
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
|Date: January 10, 2020||Chiasma, Inc.|
|Mark J. Fitzpatrick|
Chiasma Provides Corporate Update and Previews 2020 Milestones
MYCAPSSA® NDA resubmitted to FDA; PDUFA decision expected mid-2020
MYCAPSSA® U.S. commercial launch planned for the fourth quarter of 2020
Top-line MYCAPSSA® MPOWERED Phase 3 results on track for the fourth quarter of 2020
Needham, MA January 10, 2020 Chiasma, Inc. (NASDAQ: CHMA), a clinical-stage biopharmaceutical company focused on improving the lives of patients with rare and serious chronic diseases, today reviewed its 2019 highlights and previewed its anticipated 2020 corporate milestones.
2019 Key Highlights:
MYCAPSSA New Drug Application (NDA) Resubmitted to FDA: On December 26, Chiasma resubmitted its NDA to the U.S. Food and Drug Administration (FDA) for its investigational octreotide capsules product candidate, MYCAPSSA, for the maintenance treatment of adults with acromegaly. The positive results from the CHIASMA OPTIMAL trial, which was conducted under a Special Protocol Assessment (SPA) agreement with the FDA, support the NDA resubmission. Chiasma expects a six-month review of the NDA resubmission. The NDA resubmission marks an important milestone in the companys effort to bring an oral somatostatin analog to patients.
Manufacturing Plans: Following anticipated NDA approval, and in order to have commercial supply of MYCAPSSA product for launch, Chiasma expects to submit two manufacturing supplements to provide for (i) an additional active pharmaceutical ingredient (API) manufacturer and (ii) an additional commercial-scale manufacturing site affiliated with the API manufacturer currently referenced in the NDA. Chiasma is currently procuring API from both sources in anticipation of NDA approval. Chiasma expects to have adequate product available to support its planned commercial launch in the fourth quarter of 2020, subject to FDAs timely approval of the NDA and either of the manufacturing supplements.
CHIASMA OPTIMAL Global Phase 3 Trial for Acromegaly Met the Primary and All Secondary Endpoints: In July, Chiasma announced that the primary endpoint of the CHIASMA OPTIMAL (Octreotide capsules vs. Placebo Treatment In MultinationAL centers) trial, the proportion of patients biochemically (IGF-1 £ 1.0 x ULN) controlled at the end of the trial, was achieved. Additionally, all four secondary endpoints were met. The CHIASMA OPTIMAL trial was conducted under an SPA agreement with the FDA and evaluated MYCAPSSA for the maintenance treatment of adults with acromegaly.
Three Posters Presented at ENDO 2019 Highlighted Significant Unmet Needs in U.S. Acromegaly Patients: Data presented concluded that patients currently treated on injectable somatostatin analog therapies experience a significant disease burden and treatment dissatisfaction even when biochemically-controlled using existing therapies.
MPOWERED Phase 3 Trial Completed Enrollment and Randomization: The MPOWERED (Maintenance of acromegaly Patients with Octreotide capsules compared With injections Evaluation of REsponse Durability) trial, designed to support approval of MYCAPSSA in the European Union for acromegaly, completed enrollment in June 2019. As of January 2020, the randomization was completed. Responders to the octreotide capsules were randomized per the protocol (IGF-1 < 1.3 x ULN) into the nine-month randomized controlled phase.
Chiasma appointed key leaders in medical affairs, market access, patient services and marketing: Chiasma began its transformation into a commercial-ready organization with the appointment of a commercially-experienced chief executive officer and the addition of experienced leaders in marketing, market access and patient services. Chiasma has also expanded its medical affairs function, including hiring a leader with strategic medical and scientific expertise.
2019 was a successful year for Chiasma, highlighted by the positive results from the Phase 3 CHIASMA OPTIMAL trial and the NDA resubmission, said Raj Kannan, Chief Executive Officer of Chiasma. Looking ahead, 2020 has the potential to be a transformational year for our company as we focus on executing a successful launch of the first oral somatostatin analog for the treatment of acromegaly.
Anticipated 2020 Milestones and Other Guidance:
MYCAPSSA NDA Acceptance: Chiasma anticipates that within 30 days of its NDA resubmission the FDA will determine whether the NDA is complete and ready for review and provide the review timeline.
ENDO 2020 Conference: Chiasma has been selected to present the CHIASMA OPTIMAL Global Phase 3 results in an oral presentation at the Endo 2020 conference. Additional abstracts have been submitted to the conference which is being held March 28-31, 2020 in San Francisco, CA.
Publication of CHIASMA OPTIMAL Phase 3 Results: Chiasma plans to submit the final results of the CHIASMA OPTIMAL trial to a peer-reviewed journal for expected publication in mid-2020.
MYCAPSSA PDUFA Decision: Chiasma expects a six-month review of the MYCAPSSA NDA resubmission and a PDUFA decision from the FDA in mid-2020.
MYCAPSSA U.S. Commercial Launch: Chiasma plans to launch MYCAPSSA in the United States in the fourth quarter of 2020, pending FDAs timely approval of the NDA and either of the planned manufacturing supplements to the NDA.
Top-line MPOWERED Phase 3 Results: Chiasma expects to report top-line results from the MPOWERED Phase 3 open-label trial of MYCAPSSA in the fourth quarter of 2020.
Pipeline Expansion Leveraging Transient Permeability Enhancer (TPE®) Technology: Chiasma plans to announce its indication and pipeline expansion plans to develop one or more oral therapies targeting rare and serious chronic diseases with unmet needs following the anticipated approval of MYCAPSSA for the maintenance treatment of adults with acromegaly.
Cash: As of December 31, 2019, Chiasma had approximately $92 million in cash, cash equivalents and marketable securities, which is expected to fund its operations, as currently planned, through at least 2020, including key milestones such as the planned FDA approval of MYCAPSSA, the anticipated U.S. commercial launch, and the release of top-line MPOWERED Phase 3 results.
Chiasma management will be available to meet with institutional investors and analysts at the 2020 LifeSci Advisors Corporate Access Event, which is being held from January 13-15, 2020, in San Francisco, CA.
CHIASMA OPTIMAL Trial Design
The CHIASMA OPTIMAL trial was a randomized, double-blind, placebo-controlled, nine-month Phase 3 clinical trial of octreotide capsules that was conducted under a SPA agreement with the FDA. The trial enrolled 56 adult acromegaly patients whose disease was biochemically controlled by injectable somatostatin analogs (average IGF-1 £ 1.0 × upper limit of normal (ULN)). The patients also had confirmed active acromegaly following their last surgical intervention based upon an elevated IGF-1 at that time of ³ 1.3 × ULN. Patients were randomized on a 1:1 basis, to octreotide capsules or placebo. Patients were dose titrated from 40 mg per day to up to a maximum of 80 mg per day, equaling two capsules in the morning and two capsules in the evening. Patients who met the predefined withdrawal criteria, or discontinued from oral treatment for any reason, in either treatment arm during the course of the trial were considered treatment failures and reverted to their original treatment of injections and monitored for the remainder of the trial. The primary endpoint of the trial was the proportion of patients who maintained their biochemical response at the end of the nine-month, double-blind, placebo-controlled period as measured using the average of the last two IGF-1 levels £ 1.0 × ULN (assessed at weeks 34 and 36). Hierarchical secondary endpoints that are expected to be considered by the FDA in evaluating the totality of evidence for octreotide capsules treatment include: proportion of patients who maintain GH response at week 36 compared to screening; time to loss of response: IGF-1 of 2 consecutive visits is > 1.0 × ULN; time to loss of response: IGF-1 of 2 consecutive visits is ³ 1.3 × ULN; and proportion of patients requiring rescue treatment.
MPOWERED Phase 3 Trial
Chiasma is also conducting an international Phase 3 clinical trial under a protocol accepted by the EMA for the companys octreotide capsules product candidate for the maintenance therapy of adult patients with acromegaly. The trial, referred to as MPOWERED, is a global, randomized, open-label and active-controlled, 15-month trial intended to support approval in the European Union. Chiasma completed enrollment of 146 adult acromegaly patients into the trial in June 2019, of which 92 patients who are responders to octreotide capsules per the protocol following a six-month run-in were randomized to either octreotide capsules or injectable somatostatin receptor ligands (octreotide LAR or lanreotide autogel) and are being followed for an additional nine months. The trial is designed to evaluate the proportion of patients who maintain their biochemical response to octreotide capsules and patient-reported outcomes in patients treated with octreotide capsules, compared to patients treated with standard of care injectable somatostatin receptor ligands. Chiasma expects to release top-line data from the MPOWERED Phase 3 clinical trial during the fourth quarter of 2020.
Acromegaly typically develops when a benign tumor of the pituitary gland produces too much growth hormone, ultimately leading to significant health problems. Common features of acromegaly are facial changes, intense headaches, joint pain, impaired vision and enlargement of the hands, feet, tongue and internal organs. Serious health conditions associated with the progression of acromegaly include type 2 diabetes, hypertension, respiratory disorders and cardiac and cerebrovascular disease. We believe that approximately 8,000 adult acromegaly patients are chronically treated with somatostatin analogs in the United States.
Chiasma is focused on improving the lives of patients who face challenges associated with their existing treatments for rare and serious chronic diseases. Employing its Transient Permeability Enhancer (TPE®) technology platform, Chiasma seeks to develop oral medications that are currently available only as injections. In July 2019, the company reported positive topline data from its CHIASMA OPTIMAL Phase 3 clinical trial for its octreotide capsules product candidate, conditionally trade named MYCAPSSA, for the maintenance therapy of adult patients with acromegaly in whom prior treatment with somatostatin analogs has been shown to be effective and tolerated. Prior to trial initiation, the company reached agreement with the FDA on the design of the trial through a special protocol assessment. In December 2019, Chiasma resubmitted to the FDA its NDA seeking marketing approval for MYCAPSSA in the United States. Chiasma is headquartered in Needham, MA with a wholly-owned subsidiary in Israel. MYCAPSSA, TPE and CHIASMA are registered trademarks of Chiasma. For more information, please visit the companys website at www.chiasma.com.
This release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding the companys development of octreotide capsules, conditionally named MYCAPSSA, for the treatment of acromegaly, the data from the CHIASMA OPTIMAL trial and whether the data and the rest of the regulatory submission will support the acceptance by the FDA of the companys NDA resubmission for octreotide capsules as complete and ready for review and ultimately regulatory approval, statements regarding the timing of regulatory review, including the acceptance of the NDA and the companys anticipated eligibility for a six-month PDUFA review cycle, and potential approval, statements concerning the nature of the FDAs review of any such NDA resubmission and whether the data submission will be sufficient to support regulatory approval, statements regarding the companys plan to submit manufacturing supplements for an additional API manufacturer and API manufacturing site following a potential NDA approval and the companys expectations regarding the availability of product supply, statements concerning the timing of potential commercial launch of MYCAPSSA in the United States, statements regarding the release of top-line date from the MPOWERED Phase 3 trial, statements concerning the commercial or therapeutic potential of MYCAPSSA, if approved, statements regarding the companys cash forecasts, including its expected cash and investment balances as of the end of 2019 and that it has sufficient existing cash and investments on hand to fund its operations through key milestones such as the planned FDA approval of MYCAPSSA, the anticipated U.S. commercial launch and the release of top-line MPOWERED Phase 3 data and that its cash and investments balance is sufficient to fund operations as currently planned through at least 2020, and statements concerning future announcements of indication and pipeline expansion plans. Such statements are subject to numerous important factors,
risks and uncertainties, many of which are beyond the companys control, that may cause actual events or results to differ materially from the companys current expectations. For example, there can be no guarantee that the FDA will agree that the NDA resubmission is a complete response to the FDAs April 2016 complete response letter or that MYCAPSSA qualifies for marketing approval in the United States based on the results from the CHIASMA OPTIMAL trial and other information contained in the NDA. Further, there can be no guarantee that, even if the NDA is approved, the company will submit manufacturing supplements to the NDA for an additional API manufacturer and additional API manufacturing site to provide commercial API supply or that the FDA will accept the filing of either supplement or approve such additional API manufacturer or additional API manufacturing site, in each case, in a timely manner or at all. Managements expectations and, therefore, any forward-looking statements in this press release could be affected by risks and uncertainties relating to a number of factors, including the following: the content and timing of decisions made by the FDA, including with respect to the NDA and any manufacturing supplements to the NDA we may submit to the FDA, the results of any inspections of the companys third-party manufacturers, the companys reliance on third parties to manufacture API and commercial octreotide capsules, the companys ability to obtain and retain requisite regulatory approvals for the commercial launch of octreotide capsules in the United States, and the timing and costs involved in establishing a commercial organization. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause the companys actual results to differ from those contained in the forward-looking statements, see the section entitled Risk Factors in Chiasmas Annual Report on Form 10-K for the year ended December 31, 2018, and in subsequent filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and Chiasma undertakes no duty to update this information unless required by law.
Vice President, Investor Relations and Corporate Communications
Chiasma Overview NASDAQ: CHMA January 2020 Chiasma Overview Exhibit 99.2
Forward-Looking Statements These slides and the accompanying presentation contain forward-looking statements and information. The use of words such as “may,” “might,” “will,” “should,” “expect,” “plan,” “anticipate,” “believe,” “estimate,” “project,” “intend,” “future,” “potential,” or “continue,” and other similar expressions are intended to identify forward-looking statements. These statements include, without limitation, those statements regarding the development and potential commercialization of octreotide capsules, conditionally named MYCAPSSA, for the treatment of acromegaly, the potential development of octreotide capsules for other indications and utilization of the TPE platform for other therapies, the data from the CHIASMA OPTIMAL trial and whether the data and the rest of the regulatory submission will support the acceptance by the FDA of Chiasma’s resubmission of its new drug application, or NDA, for octreotide capsules as complete and ready for review and ultimately regulatory approval, statements regarding the timing of NDA regulatory review, including the acceptance of the NDA resubmission and Chiasma’s anticipated eligibility for a six-month PDUFA review cycle, and potential approval, statements concerning the nature of the FDA’s review of any such NDA submission and whether the data submission will be sufficient to support regulatory approval, statements concerning the timing of potential commercial launch of MYCAPSSA in the United States and the release of topline date from the MPOWERED phase 3 trial, statements concerning the commercial or therapeutic potential of MYCAPSSA, if approved, and statements concerning future indication and pipeline expansion plans, and statements concerning the market potential of MYCAPSSA. All forward-looking statements are based on estimates and assumptions by Chiasma’s management that, although Chiasma believes them to be reasonable, are inherently uncertain. All forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those that Chiasma expects. For example, there can be no guarantee that the FDA will agree that the NDA resubmission is a complete response to the FDA’s April 2016 complete response letter or that MYCAPSSA qualifies for marketing approval in the United States based on the results from the CHIASMA OPTIMAL trial and other information contained in the NDA. Further, as Chiasma has disclosed, in order to have product availability of MYCAPSSA for a potential commercial launch in the fourth quarter of 2020, following anticipated approval of the NDA, Chiasma expects to submit two manufacturing supplements to its NDA for an additional active pharmaceutical ingredient, or API, manufacturer and for an additional commercial-scale manufacturing site of the API manufacturer currently referenced in the NDA, the review of which will require FDA review and approval of the manufacturing process, facility, equipment and procedures in place at each manufacturer in accordance with the FDA’s current good manufacturing practice requirements and may require additional regulatory inspections of each manufacturer, which could prevent or delay approval of any such supplement to the NDA and prevent or delay commercial launch. In addition, even if Chiasma is able to obtain approval of the additional API manufacturer or additional API manufacturing site, there can be no guarantee that Chiasma will be able to secure API or commercial octreotide capsules in sufficient quantities, in a timely manner or at all and initiate the planned commercial launch of octreotide capsules. These and other potential risks, uncertainties and other important factors are described under the heading “Risk Factors” in our Form 10-K for the year ended December 31, 2018 filed with the Securities and Exchange Commission, or SEC, as well as in Chiasma’s subsequent filings with the SEC. Undue reliance should not be placed on any forward-looking statement, which speak only as of the date on which it was made. Chiasma undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law. Unless otherwise noted, all references to acromegaly market sizes are Chiasma internal estimates. This presentation is intended only for communications with investors. MYCAPSSA is an investigational drug that has not been approved by the FDA or any other regulatory agency. The safety and efficacy of this drug candidate has not been established by any agency.
Chiasma: On A Mission to Improve Patients’ Lives If approved, the first oral SSA therapy in an injectable-only market Potential addressable market in acromegaly of ~$800M globally* NDA resubmitted December 26, 2019; planned Q4:2020 commercial launch Mycapssa has the potential to become the new standard of pharmacologic care Patent protection through early 2036 in U.S. Validated technology platform that enables oral delivery of select peptides Potentially attractive opportunities in select therapeutic areas with no oral therapies Biopharmaceutical company with a registration-ready lead asset Focused on patients who face challenges with their existing treatments Management team and board with significant experience ~$92M in cash, cash equivalents and marketable securities as of December 31, 2019 Financial Position * Company estimate
2020 – A Potentially Transformational Year Commercial Launch Anticipated Q4:2020 Timing Anticipated Key Milestones Q1:2020 Mycapssa Octreotide Capsule NDA Acceptance from the FDA Q1:2020 Mycapssa OPTIMAL Phase 3 Data Presentation at ENDO Mid-2020 Publish CHIASMA OPTIMAL Phase 3 data in Peer Reviewed Journal Mid-2020 Mycapssa PDUFA Decision Q4:2020 Mycapssa U.S. Launch Q4:2020 MPOWERED Phase 3 Top-Line Data 2020 Expand Pipeline Utilizing TPE Technology
Acromegaly U.S. Market Summary A rare and debilitating hormonal disorder caused by a benign pituitary tumor treated by surgery and pharmacologic therapy; prevalence estimated to be approximately 75 per million Somatostatin analog (SSA) injections are broadly used as first line pharmacologic treatment ~8,000 Acromegaly patients in the U.S. are on SSAs Prior trials with injectable octreotide LAR1 showed 42-57% maintenance IGF-1 response rate ~90% of patients treated within ~1,000 accounts Injections carry significant treatment burdens for patients (i.e., pain, injection site reactions, sub-optimal symptom control, loss of independence, etc.) Treatment burdens are increasingly being recognized by physicians The 2018 global market for SSAs in the treatment of acromegaly is estimated at ~$800 million with U.S. estimated at ~$400 million Price for SSAs range from $55,000 / year of treatment (Sandostatin) to $165,000 (Signifor) If approved, Mycapssa positioned to potentially become the first oral SSA Acromegaly represents an attractive commercial opportunity for Chiasma Sandostatin LAR prescribing information 2019
Current Injection Therapies Carry Significant Treatment Burdens1 Emotional Impact 36% feel loss of independence due to chronic injections Injection Site Reactions Hardness (48%), nodules (38%), swelling (28%), bruising (16%) and inflammation (7%) Lost Work Days 16% regularly miss work for injections (averages 11 days / year) Suboptimal Symptom Control 52% report symptoms worsen toward the end of the monthly dosing interval 32% controlled patients still complain about symptoms Pain 70% experienced pain during injection; half of these experienced continuing pain days later Ipsen’s Lanreotide Depot: 18 or 19 Gauge deep subcutaneous Reference: Insulin Needle: 30 Gauge Strasburger et al. Patient reported outcomes of parenteral somatostatin analogue injections in 195 patients with acromegaly. Eur J Endocrinol. 2016 Mar;174(3):355-62 Compelling need for an oral therapeutic option Novartis’ Octreotide LAR: 19 or 20 Gauge intramuscular cm
TPE® Delivery Platform …then absorbed intact at therapeutic levels. Peptide is protected by TPE® from degradation… TPE enhances oral bioavailability, potentially allowing for oral formulations of injectable-only therapies
Plasma Levels of Octreotide Comparable to SC Injection Data are mean ± SEM. * Octreotide subcutaneous (SC) injection = Sandostatin®, IR injection, Novartis. Octreotide SC (n=14) Octreotide Capsule (n=24) AUC(0-inf) (h´ng/mL) 13.7 (2.29) 17.0 (9.66) t1/2 (h) 2.27 (0.25) 2.66 (0.73) Data are Mean (SD) Higher AUC from oral octreotide demonstrates longer residence time 10.0 1.0 0.10 0.01 Plasma Octreotide ng/mL Time from Dosing (Hours) 0 4 8 12 16 20 24 Octreotide SC Injection, 0.1 mg Octreotide capsule, 20 mg Octreotide injection* Octreotide capsules
Mycapssa – Robust Clinical Database Phase 1 Trials 9 trials, 172 healthy subjects: No documented serious adverse events Abdominal discomfort was most commonly reported AE (~15%; octreotide related) Phase 3 Trials Phase 3 studies (CH-ACM-01, 302 MPOWERED, and 303 OPTIMAL); 151 + 146 + 28 patients with acromegaly treated with Mycapssa: Adverse events were consistent with the known safety profile of octreotide and disease burden of acromegaly No injection-related AEs No formulation-related AEs No signal for increased risk of GI infections No signal for increased inflammatory markers (WBC, CRP) No antibodies detected Cynomolgus Monkeys Toxicology studies for 1, 3, and 9 months No adverse macroscopic or microscopic changes were detected in GI or liver No signs of inflammation
Mycapssa Pivotal Trial Clinical Summary TPE enhances oral bioavailability potentially allowing for oral formulations of injectable-only peptide therapies CHIASMA OPTIMAL phase 3 trial under a SPA agreement met its primary endpoint and all secondary endpoints NDA resubmitted December 26, 2019; anticipated mid-2020 PDUFA date CHIASMA MPOWERED phase 3 trial (E.U.) top-line data expected to be released in Q4 2020 Focused U.S. commercial readiness planning underway
OPTIMAL Phase 3: Multinational, Randomized, Placebo-Controlled Study Open Label Extension Double-blind placebo-controlled (DPC) (36 weeks) Pre-defined Withdrawal Criteria (Both Arms) IGF-1 ≥1.3 x ULN for 2 consecutive visits on the highest dose and exacerbation of clinical signs / symptoms Early terminated patients followed up to 36 weeks on injections, per protocol Baseline Placebo N=28 N=28 36 weeks 34 Last Injection Screening IGF-1s 2x IGF-1s 50% 50% Withdrawal Octreotide Capsules Versus Placebo Treatment In MultinationAL Centers Primary Endpoint Proportion of patients who maintain biochemical response (average of week 34 and 36 IGF-1 ≤ 1.0 x ULN) Eligibility Criteria: Average IGF-1 ≤ 1.0 ´ ULN Confirm active disease (IGF-1 ≥ 1.3 x ULN post last surgery) Subject Disposition and Demographics 56 patients, 28 per group (octreotide capsules or placebo) 38% from the US All patients completed trial No missing primary endpoint data Baseline characteristics well balanced between the groups
Key Clinical Information from CHIASMA OPTIMAL Trial The mean IGF-1 of the octreotide capsules group (n = 28) at the end of treatment was maintained within the normal range (0.97 x ULN) while it was 1.69 x ULN in the placebo group 75% of patients on octreotide capsules achieved an IGF-1 <= 1.1xULN at end of treatment 75% of patients in the octreotide capsules group (n = 28) successfully completed the trial on oral therapy (i.e., did not rescue to prior injectable treatment) 90% of all patients who completed the trial in active arm elected to continue on octreotide capsules
OPTIMAL Phase 3: Primary and All Secondary Endpoints Met All enrolled patients completed the study Endpoints Octreotide (N=28) Placebo (N=28) P-value Primary Proportion Maintaining IGF-1 Response 58% 19% 0.008 Secondary Proportion Maintaining GH Response 78% 30% 0.001 Time to IGF-1 >1.0 × ULN Median > 36 weeks Median = 16 weeks < 0.001 Time to IGF-1 ≥1.3 × ULN Median > 36 weeks Median = 16 weeks < 0.001 Rescued to Prior Injectable 25% 68% 0.003
Octreotide Capsules Appeared Safe and Well Tolerated Octreotide Capsules Placebo Subjects with: n % n % At least one TEAE 28 100.0 27 96.4 Treatment-Related TEAE 18 64.3 15 53.6 SAEs 2 7.1 1 3.6 Treatment-Related SAEs 0 0.0 0 0.0 Severe TEAEs 3 10.7 7 25.0 TEAE Leading to Study Drug Discontinuation 2 7.1 1 3.6 TEAEs of Special Interest (acromegaly symptoms) 15 53.6 26 92.9 TEAE - Treatment-Emergent Adverse Events; SAEs – Serious Adverse Events; TEAEs of special interest: e.g. headache, perspiration, joint pain, fatigue, soft tissue swelling
MPOWERED: Multinational, Randomized, Non-inferiority Study Primary Endpoint: The proportion of patients who are biochemically controlled throughout the RCT phase. A patient will be considered biochemically controlled if their IGF-1 Time Weighted Average (TWA), during the RCT phase is < 1.3 × ULN. Key Secondary Endpoints: Proportion of patients who maintain or reduce the overall number of active acromegaly symptoms at the end of RCT Acromegaly Treatment Satisfaction Questionnaire (ACRO-TSQ) at the end of the RCT phase *Non-responders at selected centers will be offered the opportunity to determine if they can respond to a combination of oral octreotide and the drug cabergoline. Maintenance of Acromegaly Patients with Octreotide Capsules Compared With Injections – Evaluation of REsponse Durability Eligibility criteria: IGF-1 <1.3 x ULN and GH<2.5 ng/mL Last Injection Day (-28) Screening First Dose 6-Month Run-in Phase Responders Randomized to 9-Month Controlled Phase (RCT) Open Label Extension Follow for safety and efficacy 60% 40% Non-Responder Substudy* or Non-Responders Randomization Completed: 63% responder rate per protocol a/o January 2020
A Differentiated Rare Disease Commercial Launch Strategy Traditional Rare Disease Launch Challenges MYCAPSSA Expected Launch Advantages Patients can be hard to identify – investments needed for patient identification Doctors are critical stakeholders and may be unfamiliar with MOA or a NCE – investment and time needed for education Patients need to be educated on benefits – investment and time needed to build patient advocacy Payers need to find budget to pay for new orphan therapies – Mycapssa is for the most part a replacement of existing therapy, if approved Minimal investment needed for MOA or disease awareness, which allows for education to focus on the treatment burdens Physicians prefer SSA analogs as their standard of treatment choice Nurses and patients are key to switching behavior Significant room to improve patient experience - Competitors’ execution and pull-back in the market leaves gaps and creates dissatisfaction amongst patients and providers Robust data package from Chiasma OPTIMAL demonstrating patients maintain biochemical response on Mycapssa
90% of patients on oral octreotide who completed the OPTIMAL trial continued into the Open Label Extension Patients experience symptoms, often later in the injection cycle, that is increasingly being recognized by HCPs Strong precedents for oral preference to injectables from relevant analogues Patients1,2,3,4,5 Clinical programs involved many KOLs Strong familiarity with Chiasma and Mycapssa Ongoing planned initiatives on education KOLs Endos open and willing to inform patients of Mycapssa: ~57% will inform all of their patients ~39% will inform appropriate candidates Increasing acceptance of treatment burden Community Endos / HCPs6 Expected Key Drivers For A Successful Launch Strong relations with an active advocacy community that is well-established Ongoing planned engagements and sponsorships Patient Advocacy 1 Melmed S et al. J Clin Endocrinol Metab. 2015 Apr;100(4):1699-708. 2 Strasburger C et al. ENDO 2015 Poster PP09-4. 3 Patient Reported Outcome Data from Acromegaly Patients Treated with Injectable Somatostatin Analogues in Routine Clinical Practice. Presented at ENDO, Abstract #5468. March 23-26, 2019. 4 Relationship between Responses from Acromegaly Patients Treated with a Stable Dose of Injectable Somatostatin Analogues in Routine Clinical Practice and their Endocrinology Health Care Professional regarding treatment Outcomes. Presented at ENDO Abstract #5468, March 23-26, 2019. 5 Biochemically Controlled Acromegaly Patients on a Stable Dose of Injectable SSAs in Routine Clinical Practice Still Remain Symptomatic. Presented at ENDO, Abstract #8138, March 23-26, 2019. 6 U.S. Endocrinologists Self-Reported Current and Future Somatostatin Analog Prescribing Behaviors for the Medical Management of Acromegaly, Market Modelers. N=102 endocrinologists, Sept. 2015. . Scheduled to begin U.S. enrollment in early 2020 at > 40 sites for the first Disease State registry in acromegaly Goal is to collect real-world data on treatment burden and effectiveness of various treatments MACRO Registry – Management of Acromegaly
Pituitary Centers Regional Referral Centers High Volume Community Endocrinologists Other Community Endocrinologists ~1,000 Target Accounts Addressing the Acromegaly Market 1 Orphan, Addressable U.S. Acromegaly Market Opportunity ~90% Targeted Patients Population 1 Company estimates. 2 Weighted average cost for mid-range doses annually as provided by Red Book Online (July 10, 2019) rounded to nearest $1k. 3Tag & Associates, Inc. Dec 2018. Based on published medical and drug coverage policies of United Healthcare, Anthem, Aetna/Humana and Cigna. Estimated Payer Mix 1 Product Route July 2019 WAC $/Yr.2 Covered by Major Payers3 Sandostatin® (octreotide LAR) IM $55,000 Yes Somatuline® (lanreotide Depot) Deep SC $88,000 Yes Somavert® (pegvisomant) SC $158,000 Varies by plan Signifor® (pasireotide LAR) IM $165,000 Yes
Patients Are Our Focus Patients are Carrying the Burden Today Chiasma Case Managers Will Help Alleviate the Load Patient Education and Support Specialty Pharmacy Interface Medical Practice Interface Supply and Distribution Benefits Verification
Planned 2020 Approval and Launch Activities PDUFA Product Availability Prepare for Approval Scale Up/Launch Profile clinicians and patient flows Engage physicians, nurses, payers and patients on disease and treatment burden awareness Develop resources to facilitate switch Build supply chain Engage high-value accounts Ensure successful early starts Create referral networks Build full-scale launch organization Full Deployment Call on targeted accounts Build broad prescribing base Leverage referral networks Planning 30 to 50 Customer Facing Positions
Key Leaders Appointed SCOTT MCCONNELL VP Medical Affairs Previously Senior Director of Medical Affairs at Chiasma in 2015 & 2016; rejoined 2019 Former Medical Affairs roles at Kaledio Biosciences, Alkermes, and Cubist Pharmaceuticals / Merck & Co. Pharm.D. from Creighton University School of Pharmacy and Allied Health Professions; Clinical Residency at Basset Healthcare; Post-Doctoral Fellowship at The University of Arkansas for Medical Sciences DEREK BROWN VP Marketing Former Marketing roles at Alexion, which included leading the global team responsible for the commercialization of Ultomiris® in two ultra-rare hematology diseases (PNH and aHUS), and Boehringer Ingelheim Independent consulting experience with clinical-stage biopharmaceutical companies in rare and ultra-rare disease M.B.A. from The Tuck School of Business at Dartmouth; B.A. in Cellular Structure and Function and in Economics from Middlebury College DAN THORNTON VP Market Access and Patient Services Previously VP of Market Access and Patient Services at Chiasma in 2015 & 2016; rejoined 2019 Former Market Access roles at Flexion Therapeutics, Shire, Targanta Therapeutics, Therion Biologics, Biogen Idec, and Johnson & Johnson M.B.A. from The Wharton School; B.A. in Health Policy from Duke University ANAND VARADAN Commercial Strategic Advisor Previously Chief Commercial Officer at Chiasma in 2015 & 2016 Built commercial organization and successfully launched orphan oncology drug for Karyopharm Therapeutics as CCO (2018 to 2019) General Management at Amgen in US and internationally across numerous therapeutic areas (1999-2015) M.B.A. from The Simon Business School at the University of Rochester; B.A. in Zoology from George Washington University Raj Kannan Chief Executive Officer Over 25 years of industry experience from field sales, brand and payer marketing, managing country business units, to leading global business franchises Previously served as the Global Head of the Neurology and Immunology business franchise at Merck KGaA Held roles of increasing responsibility at Boehringer Ingelheim, including Global Marketing Head of the Cardiovascular Franchise in Germany
Mycapssa® Estimated Exclusivity Timeline* Mid-2020* U.S. Marketing Approval Mid-2027 Expiration of U.S. Orphan Exclusivity SEPTEMBER 2029 Expiration of Formulation Patent (U.S. & EU) FEBRUARY 2036 Expiration of U.S. Issued Dosing Patent (EU patent pending) NOTES: Generics may enter the market at the end of the patent exclusivity and our patents may be challenged at any time; If a generic challenger wins a patent challenge, the generic can enter the market after expiration of regulatory and orphan exclusivity. *For illustration purposes only: Timeline assumes mid-2020 PDUFA approval. Strong patent and exclusivity position
2020 – A Potentially Transformational Year Well positioned for potential launch of first commercial product in 2020 Clinical Stage Company Commercial Stage Company Platform Company with Validated TPE Technology
Thank you NASDAQ: CHMA January 2020