Chiasma : Overview

Chiasma Overview

August 2020 | NASDAQ: CHMA

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 company's expectations relating to MYCAPSSA for the long- term maintenance treatment in patients with acromegaly who have responded to and tolerated treatment with octreotide or lanreotide, statements regarding the plans for and the commercialization of MYCAPSSA, including its pricing, reimbursement, payer mix and market adoption, statements regarding the data from the open label extension of the CHIASMA OPTIMAL trial, statements regarding the size and composition of the U.S. market for MYCAPSSA, the commercial or therapeutic potential of MYCAPSSA, including its ability to become a standard of care, and anticipated market acceptance of MYCAPSSA, statements concerning the company's expectations regarding the manufacturing supplement it submitted to the FDA and expectations regarding the availability of product supply, statements regarding the timing and success of commercial launch of MYCAPSSA in the United States and plans related to the number of customer-facing employees and the timing of their hiring, and statements concerning the timing of top-line results from the MPOWERED trial. 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. Management's expectations and, therefore, any forward-looking statements in these slides and the accompanying presentation 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 manufacturing supplement to the NDA the company submitted to the FDA, the results of any inspections of the company's third-party manufacturers, the company's reliance on third parties to manufacture API and commercial octreotide capsules, the company's ability to retain requisite regulatory approvals for the commercial launch of octreotide capsules in the United States, the timing and costs involved in establishing a commercial organization, and the impact the ongoing COVID-19 pandemic may have on the company's business, including its expected development, manufacturing, regulatory and commercialization timelines for MYCAPSSA. These and other potential risks, uncertainties and other important factors are described under the heading "Risk Factors" in our Form 10-Q for the quarter ended June 30, 2020 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 has been approved by the FDA for the long-term maintenance treatment in patients with acromegaly who have responded to and tolerated treatment with octreotide or lanreotide, but remains an investigational drug outside the U.S.

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MYCAPSSA FDA Approved June 26, 2020

MYCAPSSA is a somatostatin analog indicated for long-term maintenance treatment in acromegaly patients who have responded to and tolerated treatment with octreotide or lanreotide.

Full prescribing information available at www.MYCAPSSA.com	3

Chiasma Overview

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Commercial biopharma company

Focused on oral treatment options for patients facing significant challenges with injectables

Financial Position

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MYCAPSSA® is now approved as the first and only oral SSA (somatostatin analog) therapy; potential to become the new standard of pharmacological care

Attractive U.S. commercial opportunity ~8,000 acromegaly patients* on first line SSA injectables

Acromegaly patients on SSA injectables face significant treatment challenges Differentiated rare disease commercial launch

~$87M in cash, equivalents, securities and restricted cash as of June 30, 2020

Additional aggregate ~$100M in underwritten equity offering and revenue interest financing tranche funded in July

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Novel technology platform that enables oral delivery of select peptides Potentially attractive opportunities in therapeutic areas with no oral therapies

* Company estimate based on available data

Acromegaly U.S. Market Overview

Acromegaly is a rare disease most often caused by a benign pituitary tumor and

characterized by an excess of growth hormone and insulin-like growth factor-1 hormone. Treatment options include surgery, medication and radiation or a combination of these.

If untreated, acromegaly may cause

Altered facial	Enlargement of the	Type 2	Intense	Joint	Respiratory	Cardiac	Cerebrovascular	Enlarged
appearance	hands and feet	diabetes	headaches	pain	disorders	disease	disease	organs

Octreotide and lanreotide	Potential addressable	~90% of these patients are
injections are broadly used as	patient population of	treated at fewer than 1,000
z
first-line pharmacological	~8,000 patients in	medical centers
treatments	the U.S.*

The global market for SSAs in the treatment of acromegaly is estimated at ~$800 million with U.S. estimated at ~$400 million

*Company estimate based on available data.

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Injections Carry Significant Treatment Burdens1

Pain	70%	experience pain during injection; half of these
experienced continuing pain days later
Injection Site	Hardness (48%), nodules (38%), swelling (28%), bruising
Reactions	(16%) and inflammation (7%)
Suboptimal	52%	report symptoms worsen toward the end of the
Symptom Control	monthly dosing interval
Emotional Impact	36%	feel loss of independence due to chronic
injections
Lost Workdays	16%	regularly miss work for injections (averages 11
days/year)

1Strasburger et al. Patient reported outcomes of parenteral somatostatin analogue injections in 195 patients with acromegaly. Eur J Endocrinol. 2016	6
Mar;174(3):355-62.

MYCAPSSA®

First and only FDA-approved oral SSA for acromegaly; developed using TPE

Expected Drivers for a Differentiated and Targeted Q4 2020 U.S. Launch

SSA-treated acromegaly patients are readily identifiable and are managed by a small number of endocrinologists

Priced competitively - significant advancement for payers, patients, and the healthcare system

Octreotide is well known and has been used for

~30 years

Solution for patients who prefer oral treatment options

Strong and informed acromegaly patient community

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Commercial Launch Strategy

Acromegaly Market Overview

~1,000 Target Accounts

Pituitary

Centers

Regional Referral

Centers

High Volume Community

Endocrinologists

Other Community Endocrinologists

~90% of patients receiving injectable SSA

therapies are treated at fewer than 1,000 medical practices

Promotional Strategy

Initial sales team focused on top tier clinical accounts now in the field

Promote MYCAPSSA, identify and enroll patients, adapt programs and resources

Expand to ~ 45-person sales, market access and patient services team as conditions normalize for full U.S. launch

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Top Tier Commercial and Medical Leaders in Place

Anand Varadan | Chief Commercial Officer

• Built commercial organization and successfully launched orphan oncology drug for Karyopharm Therapeutics as CCO (2018 to 2019)
• General Management at Amgen in U.S. and internationally across numerous therapeutic areas (1999-2015)

Derek Brown | Head of Marketing

• Led the global team responsible for the commercialization of Ultomiris® (Alexion) in two ultra-rare hematology diseases (PNH and aHUS) and held commercial leadership roles at Boehringer Ingelheim

Jim Dion | Head of Sales

• Held Sales leadership roles at Tercica and Synageva; Ipsen; Head of US Patient Services at Akcea
• Launched Somatuline Depot at Ipsen

Scott McConnell | Head of Medical Affairs

• Built and led multiple Medical Affairs organizations at Kaleido Biosciences, Alkermes, and Cubist Pharmaceuticals / Merck & Co.

Dan Thornton | Head of Market Access and Patient Services

• Held Market Access roles, including leadership roles, at Flexion Therapeutics, Shire, Targanta Therapeutics, Therion Biologics, Biogen Idec, and Johnson & Johnson

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Comprehensive Multichannel Digital Campaign

MYCAPSSA is the first and only FDA-approved oral somatostatin analog (SSA) for appropriate patients with acromegaly, providing effective and consistent biochemical control while freeing patients from the burden of injections.

Engage HCPs

Peer to Peer

Paid Search

Paid Social

Programmatic Display

Point of Decision

Activate Patients

Paid Search

Patient Ambassadors

Paid Social

Programmatic Display

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Pricing Designed to Support Broad Payer Coverage

	Commercial		Medicare
	25%
MYCAPSSA: Compelling Value for Payers	57%

• Oral option seen as a critical unmet need
• SSAs already reimbursed and in payers' budget
• MYCAPSSA pricing designed to facilitate broad access

Wholesale Acquisition Cost (WAC)	Intended to deliver
of $5,152 for 28-day supply at 40 mg	significant value to
starting dose (linear pricing for 60 mg	patients and healthcare
and 80 mg)	system

Payer

Mix*

Medicaid

/Other

18%

Anticipate payers will cover MYCAPSSA comparably to SSA injectables

*Company estimates based on 2019 claims data.

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Chiasma Access and Patient Support

Help patients with acromegaly get started on MYCAPSSA and

support them throughout their treatment

Chiasma case managers offer personalized patient support

Dedicated

Patent Care

Specialist

Financial	Specialty
pharmacy
Assistance
interactions
	Benefits
	Investigation

Coordination with Physician Offices

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MYCAPSSA Adapts Well to Telemedicine

Minimizes the need for office visits

Telehealth	A prescription	Mobile phlebotomy	Home delivery
consultation with	communicated over	for labs	and oral
the clinician	the phone or internet		administration

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OUR SCIENCE

TPE technology and MYCAPSSA clinical trials

Validated TPE Delivery Technology Platform

TPE enhances oral bioavailability,

allowing for oral formulations of injectable-only therapies

Capsules with TPE technology have an enteric coating to

protect against degradation in the stomach.

Once in the small intestine, the capsule dissolves and releases the TPE formulation.

TPE technology induces the reversible expansion of tight junctions between intestinal epithelial cells, a natural process to absorb nutrients.

Capsules containing TPE allow drug therapies to enter systemic circulation while excluding toxins, bacteria and viruses.

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MYCAPSSA® Phase 3 Trials for U.S. and Europe

CH-ACM-01open-label Phase 3 trial completed in 2014

CHIASMA OPTIMAL Phase 3 trial, met primary and all secondary endpoints completed in 2019

MPOWERED Phase 3 trial top-line data expected to be released in Q4 2020

• Robust safety database included in U.S. approved label
• Designed to reflect real-world clinical practice
• Basis for U.S. approval
• Rigorous placebo- controlled trial
• Designed for EMA approval
• Comparative trial vs. injectable standard of care*

*octreotide and lanreotide	17

CHIASMA OPTIMAL Phase 3

Multinational, Randomized, Placebo-Controlled Study

Eligibility Criteria:	Double-blind placebo-	Open Label Extension
 Average IGF-1 ≤ 1.0 x ULN	controlled (DPC) (36 Weeks)

• Confirm active disease (IGF-1 ≥ 1.3 x ULN) post last surgery

Primary Endpoint

• Proportion of patients who maintain biochemical response
  (average of week 34 and 36 IGF ≤ 1.0 x ULN )

Pre-defined Withdrawal Criteria (Both Arms)

• IGF-1≥1.3 x ULN for 2 consecutive visits on the highest dose of oral and exacerbation of clinical signs/symptoms
• Early terminated patients followed up to 36 weeks on injections, per protocol

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Primary & All Secondary Endpoints Met

Endpoints	Octreotide (N=28)	Placebo (N=28)	P-value
	MAINTENANCE of CONTROL
Mean IGF-1 at end of oral treatment	0.97 x ULN	1.69 x ULN
	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 x ULN	Median >36 weeks	Median = 16 weeks	<0.001
Time to IGF-1 ≥ 1.3 x ULN
Reversion to prior injectable	25%	68%	0.003

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Octreotide Capsules Demonstrated as Safe & 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	2	7.1	1	3.6
discontinuation
TEAEs of special interest	15	53.6	26	92.9
(acromegaly symptoms)

TEAE: Treatment-emergent adverse event

SAE: Serious adverse event20

TEAEs of special interest: e.g. headache, perspiration, joint pain, fatigue, soft tissue swelling

CHIASMA OPTIMAL 48-Week Open Label Extension Data

• The mean of the IGF-1levels for the population of all MYCAPSSA treated patients that completed the 36-week,double-blind placebo controlled (DPC) CHIASMA OPTIMAL trial and continued into the OLE (n=19) were maintained within normal limits at the end of the 48-weekOLE period.
• 90% of patients enrolled into the OLE that were treated with MYCAPSSA during the DPC phase of the study (n=20) completed the 48-weekOLE period.
• All patients that enrolled into the OLE as responders to MYCAPSSA (IGF-1within normal limits, n=14) completed the 48-week OLE period and 93% maintained their response within the normal limits at the end of this period.
• The safety profile observed during OLE was generally consistent with the safety of MYCAPSSA noted in the 36-week CHIASMA OPTIMAL trial with no new patterns noted with the increased duration of exposure.

8/10/2020

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MPOWERED Phase 3

Multinational, Randomized, Non-inferiority Study

Eligibility Criteria:

• IGF-1<1.3 x ULN and GH <2.5 ng/mL

Primary Endpoint

• The proportion of patients who are biochemically controlled throughout the RCT phase. A patient will be considered biochemically controlled if their IFG -1 Time Weighted Average (TWA), during the RCT phase is < 1.3 x ULN

Randomization Completed:

• 63% responder rate per protocol as of January 2020

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	22
cabergoline.

MYCAPSSA® Patents Timeline

Strong U.S. and EU Patent Position

September 2029

Expiration of Formulation Patent (U.S. & EU)

February 2036

Expiration of U.S. Issued Dosing Patent (EU patent approval pending)

June 2020	June 2027
U.S. Marketing Approval	Expiration of U.S. Orphan Exclusivity,
	assuming granted by FDA

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.	23

Key Milestones

	Timing (Est.)	Anticipated Key Milestones		Status
	Q1:2020	MYCAPSSA Octreotide Capsule NDA Acceptance from the FDA
	Mid-2020	MYCAPSSA CHIASMA OPTIMAL Phase 3 Study Data Presentation
	Mid-2020	MYCAPSSA PDUFA Approval (June 2020)
	Mid-2020	Publish CHIASMA OPTIMAL Phase 3 Study Data
	in Peer Reviewed Journal
	Q4:2020	MYCAPSSA API Manufacturing Supplement Decision/
	Commercial Supply Availability
	Q4:2020	MYCAPSSA U.S. Launch
	Q4:2020	MPOWERED Phase 3 Study Top-Line Data
	1H:2021	Planned MYCAPSSA EMA Regulatory Submission
	2021 and	Revenue Growth and Advance Pipeline Utilizing TPE Technology
	beyond

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Financial Summary

(In thousands, except per share data)	Qtr. Ended June	Qtr. Ended June
30, 2019	30, 2020
General & Administrative	$2,644	$10,665
Research & Development	$5,522	$9,672
Net Loss	$(7,840)	$(21,128)
Net Loss Per Basic Share	$(0.25)	$(0.50)
Weighted Average Common Shares Outstanding - Basic	31,598	42,268

	Dec. 31, 2019	June 30, 2020
Cash, Cash Equivalents & Marketable Securities	$92,375	$67,087*

• Excludes: (1) $20.0 million of restricted cash; (2) $25.0 million received from Healthcare Royalty Partners in July as part of a revenue interest financing agreement of up to $75.0 million; and (3) $75.0 million from completed equity offering in July

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Management Team

Raj Kannan	Mark J. Fitzpatrick	William Ludlam, M.D., Ph.D.	Anand Varadan
Chief Executive Officer	President (Principal	Clinical Development	Chief Commercial Officer
	Financial Officer)	& Medical Affairs

Drew Enamait	Lee Giguere	Shoshie Katz	Gary Patou, M.D.	David Schubert
Finance & Administration	General Counsel	VP, Regulatory & Quality;	Strategic Clinical	SVP, Regulatory & Quality
		Israel Site Head	Advisor

Board of Directors

Dave Stack	Raj Kannan	Todd Foley	Bard Geesaman, M.D., Ph.D.
Chairman of the Board	CEO & Director	Director	Director
Roni Mamluk, Ph.D.	Scott Minick	John A. Scarlett, M.D.	John F. Thero
Director	Director	Director	Director

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2020 - A Transformational Year

Commercial Stage

Company

Clinical Stage

Company

Platform Company with Validated TPE Technology

Well positioned for a robust launch of first commercial asset

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Thank You

August 2020 | NASDAQ: CHMA