FULC | 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.
2
Q1 2024 Updates
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
3
Unlocking the Power of Small Molecules to Change the Course of Genetically Defined Rare Diseases
Diversified biotech | Losmapimod: first-to- | Pociredir: potential | Discovery efforts | |||||||||||
developing oral small | market potential in | best-in class oral small | validated by two | |||||||||||
molecules designed | facioscapulohumeral | molecule HbF inducer | clinical programs | |||||||||||
to modify gene | muscular dystrophy | for sickle cell disease | ||||||||||||
expression: Two wholly | (FSHD); granted | (SCD); granted Fast | Strong cash position | |||||||||||
owned clinical | Fast Track and | Track and Orphan | with runway into | |||||||||||
programs | Orphan Designations | Designations | 2027 | |||||||||||
Founded in 2015 | IPO in 2019 | Ticker: FULC |
4
Robust Small Molecule Pipeline Across Multiple Rare Diseases
Indication | Asset / MOA | Preclinical | Phase 1 | Phase 2 | Phase 3 | Collaborator |
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
5
f o r F a c i o s c a p u l o h u m e r a l
M u s c u l a r D y s t r o p h y ( F S H D )
Fast Track Designation
Orphan Drug Designation
FSHD: Debilitating Disease With No Approved Therapies
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*
FSHD | DMD | SMA | FA |
= 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
FSHD: Facioscapulohumeral muscular dystrophy; DMD: Duchenne muscular dystrophy, SMA: Spinal muscular atrophy; FA: Friedreich's ataxia
7 Hamel and Tawil, Neurologic Clinics, 2020; Himeda and Jones, Annual Review of Genomics and Human Genetics, 2019; Lally et al., Orphanet J Rare Dis, 2017; NORD; MDA. *Calculated based on prevalence rate 1:8,000 - 1:20,000 in Jia et al, 2021, Neuromuscular Disorders; assuming 333 million US population
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
RWS measures global upper extremity function | FSHD natural history demonstrates a ~3% RWS | |||||||||
decline year over year | ||||||||||
Total Reachable Workspace (Weighted) | ||||||||||
2.0 | ||||||||||
(%) | 1.0 | baseline | ||||||||
0.0 | ||||||||||
Year | ||||||||||
-1.0 | FSHD patient | |||||||||
per | -2.0 | |||||||||
decline/year | ||||||||||
Change | ||||||||||
-3.0 | ||||||||||
-4.0 | ||||||||||
-5.0 | ||||||||||
0 | 10 | 20 | 30 | 40 | 50 | |||||
Han et al, Muscle Nerve, 2015 | Weeks | Hatch et al, Neuromuscul Disord, 2019 | ||||||||
• | Reachable Workspace (RWS) is a quantification of upper | • Demonstrated sensitivity to disease progression | ||||||||
limb motion utilizing a contactless sensor-based system | in FSHD and in Duchenne/Becker muscular | |||||||||
• | RWS is evaluated using a series of protocol-directed arm | dystrophy | ||||||||
• A longitudinal study in a FSHD patient population* | ||||||||||
motions (with and without weights) assessing Relative | ||||||||||
Surface Area (RSA) across five quadrants (Q1-Q5) | exhibited annual declines in RWS of ~3% (measured | |||||||||
Q1-Q4) compared to baseline |
- RSA has been shown to correlate with abilities to perform activities of daily living (e.g., eating, self-care)
8 RWS: Reachable workspace. Han et al, Muscle Nerve, 2014; Han et al, Muscle Nerve, 2015; Hatch et al, AAN Annual Meeting, 2022; Hatch et al, Neuromuscul Disord, 2019; Kurillo et al, Technol Health Care, 2013; Mellion et al, AAN Annual Meeting, 2022
*N=16 patients
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
100 | Summed score of all 20 | ||||
Score | Rho = 0.7609** | NeuroQoL-UE questions | |||
80 | |||||
NeuroQoL | |||||
60 | |||||
40 | |||||
0.2 | 0.4 | 0.6 | 0.8 |
Total RSA
Spearman Correlation Coefficients for Reachable Workspace to NeuroQoL-UE
Total RSA | P-value | |
NeuroQoL-UE Raw | 0.7609 | 0.0001 |
Hatch et al, Muscle Nerve, 2021
9 UE: Upper Extremity; RSA: Relative Surface Area; Hatch et al., Muscle Nerve, 2021.
Whole Body Musculoskeletal MRI Enables Assessment of Muscle Health and Dystrophic Progression
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%
Fibrosis | ||||||
Fat tissue | Muscle Fat | |||||
Fraction (MFF) | ||||||
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%
10 | MFF: Muscle Fat Fraction; MFI: Muscle Fat Infiltration; MRI: Magnetic Resonance Imaging. Mellion, Tawil, et. al. Neurology. 2022; Mellion, Widholm, et. al. Neurology. 2022. |
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Fulcrum Therapeutics Inc. published this content on 13 May 2024 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 13 May 2024 11:19:15 UTC.