Fulcrum Therapeutics : Corporate Presentation May 2024

F U L C R U M T H E R A P E U T I C S

Disclaimer and Notice

This presentation contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties, including express of implied statements regarding the development status of Fulcrum's product candidates, the potential advantages and therapeutic potential of Fulcrum's product candidates planned meetings with regulatory agencies and availability of clinical trial data. All statements, other than statements of historical facts, contained in this press release, including statements regarding Fulcrum's strategy, future operations, future financial position, prospects, plans and objectives of management, are forward-looking statements. The words "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential," "predict," "project," "should," "target," "will," "would" and similar expressions are intended to identify forward-looking statements, although not all forward- looking statements contain these identifying words. Any forward-looking statements are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in, or implied by, such forward- looking statements. These risks and uncertainties include, but are not limited to, risks associated with Fulcrum's ability to obtain and maintain necessary approvals from the FDA and other regulatory authorities; continue to advance its product candidates in clinical trials; initiate and enroll clinical trials on the timeline expected or at all; correctly estimate the potential patient population and/or market for Fulcrum's product candidates; replicate in clinical trials positive results found in preclinical studies and/or earlier-stage clinical trials of losmapimod, pociredir (formerly known as FTX-6058), and any other product candidates; obtain, maintain or protect intellectual property rights related to its product candidates; manage expenses; and raise the substantial additional capital needed to achieve its business objectives. For a discussion of other risks and uncertainties, and other important factors, any of which could cause Fulcrum's actual results to differ from those contained in the forward-looking statements, see the "Risk Factors" section, as well as discussions of potential risks, uncertainties and other important factors, in Fulcrum's most recent filings with the Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent Fulcrum's views as of the date hereof and should not be relied upon as representing Fulcrum's views as of any date subsequent to the date hereof. The Fulcrum anticipates that subsequent events and developments will cause Fulcrum's views to change. However, while Fulcrum may elect to update these forward-looking statements at some point in the future, the Fulcrum specifically disclaims any obligation to do so.

F U L C R U M T H E R A P E U T I C S

Losmapimod

FSHD

Pociredir

Sickle Cell Disease

Fulcrum Corporate

• Entered into a collaboration with Sanofi for ex-U.S. rights to develop and commercialize losmapimod
• • Terms include $80 million upfront payment, up to $975 million in additional milestone payments, and royalties on ex-U.S. sales starting in the low teens
  • Parties to share future global development costs 50/50
  • Fulcrum retains full U.S. commercialization rights
• Published results from the Phase 2b ReDUX4 clinical trial in The Lancet Neurology, reflecting losmapimod's favorable treatment effect compared to placebo as demonstrated by:
• • Functional outcomes as evaluated by reachable workspace
  • Structural outcomes of muscle through the measurement of muscle fat infiltration
  • Patient-reportedoutcomes
• On track to report topline data for the Phase 3 REACH clinical trial in the fourth quarter of 2024
• Activated additional clinical trial sites in the Phase 1b clinical trial in Sickle Cell Disease
• Appointed Patrick Horn, M.D., Ph.D., as Chief Medical Officer
• Cash runway into 2027

F U L C R U M T H E R A P

Clinical Programs

FSHD

SCD

Losmapimod (DUX4 Reduction)

Pociredir (HbF Induction)

(Ex-U.S.)

E U T I C S

Discovery Programs

Blood Disorders

Muscle Disorders

Cardiomyopathies

FSHD: Facioscapulohumeral muscular dystrophy; HbF: Fetal hemoglobin; SCD: Sickle cell disease

F U L C R U M T H E R A P E U T I C S

The Disease

Chronic, progressive genetic muscular disorder characterized by significant muscle cell death and fat infiltration into muscle tissue

Debilitating Symptoms

• Significant impairment of upper extremity function and mobility
• Many patients unable to work or live independently
• Approximately 20% of affected individuals become wheelchair-bound

Treatment Options

No approved therapies for FSHD

Population

Second most common adult muscular dystrophy affecting approximately 30,000 individuals in the US*

= 1,000 patients

Disease Progression

Implementing innovative clinical outcome measures and metrics is necessary to quantify disease progression

• Reachable workspace (RWS): Measure of disease progression
• Muscle fat infiltration (MFI): Measure of muscle health

F U L C R U M T H E R A P E U T I C S

Reachable Workspace Enables Quantification of Disease Progression ​

• RSA has been shown to correlate with abilities to perform activities of daily living (e.g., eating, self-care)

F U L C R U M T H E R A P E U T I C S

RWS correlates to FSHD Patient-reported Outcomes such as Neuro-QoL- Upper Extremity in Natural History Studies

Total RSA

Spearman Correlation Coefficients for Reachable Workspace to NeuroQoL-UE

Hatch et al, Muscle Nerve, 2021

F U L

Dystrophic Skeletal Muscle

Tissue in FSHD

Tissue infiltration contributes to the loss of function by altering biomechanical properties

Whole Body MRI Provides a Holistic and Quantitative

Assessment of Muscle Quality and Health

18 muscles are analyzed bilaterally

(36 total muscles analyzed)

C R U M T H E R A P E U T I C S

Muscle Fat

Infiltration (MFI)

Muscle Fat

Infiltration

(MFI)

50%

• Measurement of the diffuse fatty infiltration in the muscle
• MFI is an indicator of muscle quality and sensitive to early muscle fat replacement

0%

Muscle Fat

Fraction

(MFF)

100%

• Measurement of the overall amount of fat within the muscle
• MFF is an indicator of FSHD-affected muscles with a strong correlation to clinical function / disability

0%