Jefferies Healthcare Conference June 7, 2016 NASDAQ: CHMA
Forward-Looking Statements These slides 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. For example, all statements we make regarding our plans to meet with the FDA and our plans for our MPOWERED trial are forward looking. All forward-looking statements are based on estimates and assumptions by our management that, although we believe 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 we expected. These statements are also subject to a number of material risks and uncertainties that are described under the heading Risk Factors in our Quarterly Report on form 10-Q for the quarter ended March 31, 2016 filed with the Securities and Exchange Commission on May 12, 2016 as well as discussions of potential risks, uncertainties and other important factors in Chiasma s subsequent filings with the Securities and Exchange Commission. Any forward-looking statement speaks only as of the date on which it was made. We undertake no obligation to publicly update or revise any forwardlooking statement, whether as a result of new information, future events or otherwise, except as required by law. 1
Overview Focus: Improving the lives of patients facing challenges associated with their existing treatments for rare and serious chronic diseases Experienced management team and board $134M in cash, cash equivalents and marketable securities as of March 31 Clinically validated technology platform that enables oral delivery of certain peptides and small molecules Broad set of potential market opportunities Chiasma s lead product candidate may be the first oral somatostatin analog (SSA) in a $2.2 billion injectable market Initial indication is adult patients with the rare disease acromegaly with future potential for a neuroendocrine tumor indication Reassessing U.S. pathway following April 2016 Complete Response Letter Initiated Phase 3 in March 2016 to support EMA submission 2
TPE is a Novel Technology for Oral Peptide Therapies Peptide is protected by TPE from degradation then absorbed intact at therapeutic levels. 3
TPE Technology Platform Product Candidate Considerations Over $30 billion spent on 60+ peptide and small protein (<20kDa) products; approximately 100 additional candidates in late-stage clinical trials Technical Considerations Commercial Considerations Poor oral bioavailability Highly potent (up to a few mg per dose) Broad window for dosing amount & timing Proven efficacy & safety profile Today s standard of care: injections only Significant unmet need for oral Chronic usage Freedom to operate High return on investment Ideal pipeline candidate 4
Lead Product: Mycapssa for Acromegaly Rare disease caused by excessive secretion of growth hormone (GH) stemming from a benign pituitary tumor that leads to excess of insulin-like growth factor-1 (IGF-1) 69,000 (1) patients worldwide Symptoms include enlarged hands, feet and internal organs, altered facial features, headache, joint pain and increased perspiration Significant comorbidities lead to premature death if untreated Most patients first undergo surgery to remove or reduce the size of their pituitary tumor Patients not cured by surgery typically receive life-long somatostatin analog injections to achieve suppression of GH & IGF-1, but (1) Source: Acromegaly Epidemiology abstracts and publications 1980-2016 5
Current Injection Therapies Carry Treatment Burdens (1) Lanreotide Depot: 18 or 19 Gauge deep subcutaneous Pain Injection Site Reactions 70% experienced pain during injection; half of these experienced continuing pain days later Hardness (48%), nodules (38%), swelling (28%), bruising (16%) and inflammation (7%) Octreotide LAR: 19 or 20 Gauge intramuscular cm Reference: insulin needle: 30 Gauge Suboptimal Symptom Control Emotional Impact Work Days 52% report symptoms worsen toward the end of the monthly dosing interval 32% controlled patients still complain about symptoms 36% feel loss of independence due to chronic injections 16% regularly miss work for injections (averages 11 days/year) (1) Source: Strasburger et al, Patient reported outcomes of parenteral somatostatin analogue injections in 195 patients with acromegaly, Eur J Endocrinol, 12/18/15 EJE-15-1042 6
$2.2 Billion Market for Somatostatin Analogs Global Injectable Somatostatin Analog Sales (1) $1.8B 34% $1.9B 34% $2.0B 34% $2.1B $2.2B 34% 34% Acromegaly (2) Lanreotide (20%) (5%) Immediate Release ($ in millions) 50% 49% 49% 49% 51% NET (2) Long- Acting Release (75%) Octreotide (80%) 16% 17% 17% 17% 15% Other indications (2) 2011 2012 2013 2014 2015 2015 Share by Analog Type (1) Sources: (1) Financial reports and filings Novartis & Ipsen 2010 2016 (2) Company estimates 7
Mycapssa Phase 1 Activity Supported Progression to Phase 3 Phase 1 study in 16 healthy subjects; cross-over design 4 3 Dosing Initiated No Treatment GH (ng/ml) 2 1 Significant Growth Hormone (GH) inhibition recorded in all 16 subjects tested (P<0.05) 0-1 -0.5 0 0.5 1 1.5 2 Time (hr) Data are Mean ± SE Source: Tuvia S, et al. J Clin Endocrinol Metab. 2012 8
Phase 3: Multicenter, Open-Label, Baseline-Controlled, Dose-Escalation Trial Design* Key study questions: Will patients respond to an oral therapy? Can responses on oral be sustained? Do patients prefer oral therapy? Baseline period on injections Titrate patients to an effective dose Patient choice to continue on oral Screening N=155 Last Injection Day (-28) Baseline First Dose Day (-14) Day 0 2x daily Core 7 mo. Extension 13 mo. N=151 N=110 N=102 N=88 N=82 Discontinuation (N=49): Dose (24), AE (18), Other (7) * As reviewed with the FDA. 9
Phase 3: Patient Responses Sustained on Mycapssa Primary endpoint defined as biochemical response (GH and IGF-1) at 7 months FDA agreed at End of Phase 2 meeting on descriptive statistics rather than p-value Pituitary experts pre-specified a population response 50% for a successful product 75% of the patients who completed dose escalation were responders 100 80 60 40 20 0 89 % of All Subjects Dosed 65 62 Baseline 7 months 13 months Time-weighted average response rate at 7 months was 72% Safety profile of Mycapssa was consistent with injections (AEs included nausea, diarrhea, headaches and joint pain) and without adverse injection-site reactions No new or unexpected safety signals were observed Sources: Melmed S. et al, J Clin Endocrinol Metab. 2015 Apr;100(4):1699-708 Fleseriu M, et al, Longitudinal assessment of response to treatment with oral octreotide capsules in patients with acromegaly: Post-hoc analysis of a phase 3 trial. Poster presented at ECE 2016; May 2016; Munich, Germany 10
Phase 3: Strong Biochemical Response to Mycapssa 3.0 Growth Hormone 2.5 IGF-1 GH ng/ml 2.5 2.0 1.5 1.0 0.5 + + + + + Response <2.5 ng/ml IGF-1 X ULN 2.0 1.5 1.0 0.5 + + + + + Response <1.3xULN 0 Baseline First Dose End Dose Esc. 7 mo. 13 mo. 0 Baseline First Dose End Dose Esc. 7 mo. 13 mo. Responder Non-Responder Average GH and IGF-1 response comparable to injections Source: Melmed S. et al, J Clin Endocrinol Metab. 2015 Apr;100(4):1699-708 11
Phase 3: Improved Acromegaly Symptom Response Symptom Incidence and Severity of Symptoms Through 13 Months Reduced incidence and severity of symptoms in responders on octreotide capsules Asthenia Headache Joint pain Baseline End of Trial Baseline End of Trial Baseline End of Trial 80% of patients had symptoms entering the trial Excess Baseline Perspiration End of Trial Swelling of Extremities Baseline End of Trial Severity Severe Moderate Mild 80% of patients who entered fixed-dose portion of trial had improved or maintained acromegaly symptom response at end of treatment Reduced breakthrough symptoms reported by responders Patients, % 100 90 80 70 60 50 40 30 20 10 0 0 10 20 30 40 50 60 % of Patients Reporting Symptoms Change in Reported Symptoms in Patients Maintained on Octreotide Capsules P=0.019 Baseline 79.1-14% P=0.002 End of 13 Mo. Treatment 68.2 62.7-23% P=0.005 48.2 44.5-31% 30.9 1 Symptom 2 Symptoms 3 Symptoms Sources: (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 Symptoms Burden 12
U.S. Regulatory Status NDA submitted to FDA in June 2015 and accepted in August 2015, with a PDUFA date set for April 15, 2016 On April 15, Chiasma received Complete Response Letter from FDA, communicating: 1. During a recent site inspection, certain deficiencies were conveyed to the representative of one of Chiasma s suppliers that would need to be resolved before approval 2. The Agency did not believe the NDA provided substantial evidence of efficacy to warrant approval, and strongly recommended that Chiasma conduct a randomized, double-blind and controlled trial that enrolls patients from the United States and be of sufficiently long duration to ensure that control of disease activity is stable at the time point selected for the primary efficacy assessment; and The FDA did not note any safety concerns related to Mycapssa in its letter End-of-Review meeting expected to take place in June 13
Pivotal E.U. Phase 3 Trial Now Underway Key study questions: How does the sustained response compare on oral vs. injection? How do acromegaly symptoms compare on oral vs. injection? How does quality of life compare on oral vs. injection? Approx. 150 patients to be enrolled 6-Month Run-in Phase 60% 9-Month Randomized Controlled Phase Extension Up to Launch Responders Screening Last Injection Day (-28) First Dose Non-Responders 40% Non-Responder Substudy* or Follow for safety and efficacy * 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. 14
E.U. Regulatory Status MPOWERED protocol accepted by the EMA in October 2015 Leveraging EMA s hybrid application pathway for potential product approval Trial initiated in March 2016 with plans to include approximately 25 U.S. and approximately 35 international clinical sites EMA has conditionally accepted tradename Mycapssa Currently targeting a Marketing Authorization Application in 2019 15
Experienced Leadership Management Team Role Key Affiliations Mark Leuchtenberger Roni Mamluk, Ph.D. Mark Fitzpatrick Gary Patou, M.D. Anand Varadan Tara McCarthy President & Chief Executive Officer Chief Development Officer Chief Financial Officer Head of Clinical Chief Commercial Officer General Counsel Board of Directors Dave Stack, Chairman Mark Leuchtenberger Ansbert Gadicke, M.D. Bard Geesaman, M.D. Ph.D. Jim Tobin Key Affiliations F2, F3 John (Chip) Scarlett, M.D. Scott Minick Todd Foley John Thero Key Affiliations 16
Q1 Financial Overview (In thousands, except per share data) March 31, 2016 For the Quarter Ended March 31, 2015 Marketing, General & Administrative 9,994 1,931 Research & Development 7,226 2,219 Net Loss Attributable to Common Stockholders ($17,180) ($4,342) Net Loss Per Basic Share ($0.71) ($59.73) Wtd. Avg. Common Shares Outstanding - Basic 24,238 73 (In thousands) March 31, 2016 Dec. 31, 2015 Cash, Cash Equivalents & Marketable Securities $134,299 $148,754 As of Now revisiting all areas of investment and resourcing 17
Overview Focus: Improving the lives of patients facing challenges associated with their existing treatments for rare and serious chronic diseases Experienced management team and board $134M in cash, cash equivalents and marketable securities as of March 31 Clinically validated technology platform that enables oral delivery of certain peptides and small molecules Broad set of potential market opportunities Chiasma s lead product candidate may be the first oral somatostatin analog (SSA) in a $2.2 billion injectable market Initial indication is adult patients with the rare disease acromegaly with future potential for a neuroendocrine tumor indication Reassessing U.S. pathway following April 2016 Complete Response Letter Initiated Phase 3 in March 2016 to support EMA submission 18
Jefferies Healthcare Conference June 7, 2016 NASDAQ: CHMA