Regulating Gene Expression to Treat the Root Cause of Disease - September 2020 - Seeking Alpha
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Regulating Gene Expression to
Treat the Root Cause of Disease
September 2020
1
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 statements regarding the development status of the Company’s product candidates, the potential advantages and therapeutic potential of our product candidates, the timing of regulatory filings, initiation and enrollment of clinical trials and the timing of availability of clinical trial data and the Company’s ability to fund its operations with cash on hand . All statements, other than statements of historical facts, contained in this presentation, including statements regarding the Company’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 the Company’s product candidates replicate in later clinical trials positive results found in earlier preclinical studies and early-stage clinical trials of losmapimod and its other product candidates; advance the development of its product candidates under the timelines it anticipates in current and future clinical trials; 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 the Company’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 the Company’s most recent filings with the Securities and Exchange Commission. In addition, the forward- looking statements included in this presentation represent the Company’s views as of the date hereof and should not be relied upon as representing the Company’s views as of any date subsequent to the date hereof. The Company anticipates that subsequent events and developments will cause the Company’s views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so. This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such data and estimates. In addition, projections, assumptions and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk. Neither Fulcrum nor its affiliates, advisors or representatives makes any representation as to the accuracy or completeness of that data or undertakes to update such data after the date of this presentation. FULCRUM THERAPEUTICS 2
Fulcrum Overview
Clinical stage biopharmaceutical company using systematic approach to identify
small molecules able to rebalance gene expression
Gene
Expression
▪ ~7,000 genetically defined diseases today
Gene
Expression ▪ We are building on decades of research
highlighting gene expression role in disease
▪ High-throughput product engine designed to
rapidly identify and validate drug targets that can
modulate gene expression and treat disease at its
root cause
▪ Focus on small molecules as therapeutic modality
Our vision is to treat genetically defined diseases by addressing their root cause
FULCRUM THERAPEUTICS 3
FulcrumSeek Screening
Intelligent drug discovery in disease relevant models through high dimensional data and machine learning
Discovery Engine Accelerated Drug
Computational Engine Discovery Programs
Targets with desired profile
Functional profiles of specificity, selectivity
and tolerability
Morphological profiles
Data-rich target
Identification of tissue- hypotheses and
Transcriptional profiles
relevant translatable
biomarkers
clinical
candidates
Machine
Characterization of lead
Learning
candidates to understand
potential issues (toxicity or
off-target activity)
Proprietary datasets in relevant cellular models
that recapitulate tissue and disease biology
FULCRUM THERAPEUTICS 4
Fulcrum Pipeline
Multiple clinical programs advancing in 2H 2020
DISCOVERY PRECLINICAL PHASE 1 PHASE 2 PHASE 3 STATUS
PROGRAM (PRODUCT CANDIDATE)
COVID-19 (losmapimod) Initiated Ph3 in Q3 2020
FSHD (losmapimod) Full data Q2 2021
Sickle Cell Disease (FTX-6058) Submit IND in Q3 2020
-Thalassemia (FTX-6058)
DISCOVERY SCREENING
Duchenne Muscular Dystrophy Target ID / Validation
Friedreich Ataxia Target ID / Validation
Myotonic Dystrophy 1 Target ID / Validation
α-Synucleinopathies Target ID / Validation
Undisclosed Neurological Disease Target ID / Validation
Undisclosed Pulmonary Disease Target ID / Validation
Undisclosed Cardiomyopathies Target ID / Validation
FULCRUM THERAPEUTICS Additional screens & FulcrumSeek planned for 2020 5
Robust Development Portfolio with Multiple Near-
term Catalysts
Losmapimod Losmapimod FTX-6058
Sickle Cell Disease
COVID-19 FSHD
& β-Thalassemia
▪ Rapid progress and strong ▪ ReDUX4 Phase 2 Interim ▪ IND Filing Q3 2020
KOL support Analysis 3Q 2020
▪ Phase 1 Initiation in SCD
▪ IND granted June 2020 ▪ ReDUX4 Phase 2 Topline Q4 2020
Data 1Q2021/ Full Data
▪ LOSVID Phase 3 initiated ▪ Ongoing preclinical
2Q2021
3Q 2020 investigation for β-
▪ Ongoing Phase 2 Open Thalassemia
▪ LOSVID Phase 3 Interim
Label Study
Analysis 4Q 2020
▪ Ongoing Open Label
▪ LOSVID Phase 3 Topline
Extension
Data 1Q 2021
FULCRUM THERAPEUTICS 6
Losmapimod for COVID-19
7
Potential to transform COVID-19 into a milder and
treatable disease
▪ Solid scientific rationale
▪ p38 MAPK pathway plays a key role severe
viral infections, including COVID-19
▪ Losmapimod could impact multiple
components of the disease and alleviate
COVID-19 morbidity and mortality
▪ Previous losmapimod clinical data demonstrate
potential activity against pathogenic processes
in COVID-19
▪ Extensively studied (>3600 subjects),
generally safe and well-tolerated
▪ Oral administration
▪ IND approved, Initiated Phase 3 Q3 2020
https://cdn.mos.cms.futurecdn.net/tHvWMA98Yymfmgq3jf4GX9-1200-80.jpg
FULCRUM THERAPEUTICS 8
Evidence Supports Multiple Impacts of p38 Inhibition on
COVID-19 Pathology
Restoration of the innate – Broad suppression of Correction of renin-angiotensin
adaptive immune balance inflammatory programs system dysfunction
Losmapimod significantly and rapidly Angiotensin II is elevated in COVID-19
Exaggerated reduced acute inflammatory biomarkers in patients and correlates with viral load and
acute immune clinical trials severity of lung injury
responses in hsCRP
older individuals
hinder adaptive
immunity to viral
challenge
Adaptive immune
response restored
following IL-6
treatment with
losmapimod in
older human p38 MAPK inhibition has been shown to
subjects reduce Ang II induced organ damage
FULCRUM THERAPEUTICS 9
Vukmanovic-Stejic M, et al., Journal of Allergy Clin Immunol 2018 Newby L, et al., Lancet 2014; GSK Clinical Data Grimes et al., JMCC 2020; Park J et.al, Hypertension. 2007
Evidence Supports Multiple Impacts of p38 Inhibition on
COVID-19 Pathology
Restoration of the innate – Broad suppression of Correction of renin-angiotensin
adaptive immune balance inflammatory programs system dysfunction
Losmapimod significantly and rapidly Angiotensin II is elevated in COVID-19
Exaggerated reduced acute inflammatory biomarkers in patients and correlates with viral load and
acute immune clinical trials severity of lung injury
responses in hsCRP
older individuals
hinder adaptive
immunity to viral
challenge
Adaptive immune
response restored
following IL-6
treatment with
losmapimod in
older human p38 MAPK inhibition has been shown to
subjects reduce Ang II induced organ damage
FULCRUM THERAPEUTICS 10
Vukmanovic-Stejic M, et al., Journal of Allergy Clin Immunol 2018 Newby L, et al., Lancet 2014; GSK Clinical Data Grimes et al., JMCC 2020; Park J et.al, Hypertension. 2007Evidence Supports Multiple Impacts of p38 Inhibition on
COVID-19 Pathology
Restoration of the innate – Broad suppression of Correction of renin-angiotensin
adaptive immune balance inflammatory programs system dysfunction
Losmapimod significantly and rapidly Angiotensin II is elevated in COVID-19
Exaggerated reduced acute inflammatory biomarkers in patients and correlates with viral load and
acute immune clinical trials severity of lung injury
responses in hsCRP
older individuals
hinder adaptive
immunity to viral
challenge
Adaptive immune
response restored
following IL-6
treatment with
losmapimod in
older human p38 MAPK inhibition has been shown to
subjects reduce Ang II induced organ damage
FULCRUM THERAPEUTICS 11
Vukmanovic-Stejic M, et al., Journal of Allergy Clin Immunol 2018 Newby L, et al., Lancet 2014; GSK Clinical Data Grimes et al., JMCC 2020; Park J et.al, Hypertension. 2007Phase 3 LOSVID Trial (n=~400)
Randomized, double-blind, placebo-controlled multi-center trial in hospitalized COVID-19
patients when administered concurrently with standard of care
▪ Primary endpoint:
▪ ~400 subjects randomized 1:1 to 15mg PO ▪ Proportion of progressors to critical illness, defined as
BID losmapimod or placebo for 14 days on death or respiratory failure (severe hypoxia) by day 28
top of standard of care
▪ Secondary endpoints:
▪ Stratified by age (50-64 or ≥65 years old) ▪ Clinical Status on Days 7 and 14 as measured on the
and need of oxygen at randomization 9-point WHO ordinal scale
▪ Small initial sentinel cohort for safety ▪ Total number of study days free of oxygen
supplementation
▪ Interim analysis after 50% complete for ▪ Length of hospitalization and ICU stay
futility and sample size re-estimation by
independent DMC ▪ Percentage of subjects discharged from the hospital
by days 14 and 28
▪ Topline data expected in Q1 2021 ▪ All-cause mortality
▪ Frequency and severity of AEs
FULCRUM THERAPEUTICS ▪ Viral Clearance 12Losmapimod for Facioscapulohumeral Muscular Dystrophy
(FSHD)
13Second Most Common Muscular Dystrophy with Significant
Disease Burden and No Current Treatment Options
Characterized by progressive Losmapimod Market Opportunity
muscle degeneration
Estimated US FSHD Population*
16,000-38,000
▪ Skeletal muscle replaced by fat
▪ Significant impairment of upper
extremity function and mobility
▪ Affects movement of face and
eventually the trunk and legs Estimated Global FSHD Population*
300,000-780,000
▪ Patients report chronic pain, “They told me that I was probably going
to die from muscular dystrophy at 30
anxiety and depression years old—that I would probably roll
over and suffocate myself in my sleep.”
▪ Approximately 2/3 of cases are
familial-inherited
“You know how many years it took to
get out of that? That’s a scary feeling.”
FULCRUM THERAPEUTICS *Deenen, JCW, et al. Neurology. 2014; Preston, MK et al. GeneReviews – FSHD. 2020 14DUX4 is the Root Cause of FSHD
Relationship Between DUX4 Expression and FSHD
Disease Presentation
Any reduction in DUX4 may provide a functional
benefit in FSHD patients
24 SEPTEMBER 2010 VOL 329 SCIENCE
FULCRUM THERAPEUTICS Fulcrum FSHD KOL Breakfast 2019 15Aberrant Expression of DUX4 Gradually Kills Skeletal
Muscle and Causes Significant Disability in FSHD Subjects
1 2 3
Pathogenic DUX4 Muscle death Progressive loss
expression in and fatty of function in
select myofibers replacement select muscles
Losmapimod has the potential to reduce pathogenic DUX4, which may preserve muscle, reduce fatty
replacement, slow muscle loss, and decrease disability
FULCRUM THERAPEUTICS 16Losmapimod Reduces DUX4 in vitro and in vivo
Fulcrum product engine identified p38α (MAPK) as key regulator of DUX4 expression
Extensive safety and tolerability – over 3,600 subjects dosed
Losmapimod (6 mpk b.i.d.) increased
Reduced DUX4 protein and DUX4-driven
Apoptosis markers reduced relative human cell content, consistent
gene expression in vitro
with decreased muscle cell death
Range of
Range of
concentrations
concentrations
observed in
observed in
phase 1 study at
phase 1 study at
15 mg BID dose
(~30-100 ng/mL or 15 mg BID dose
75-265 nM) (~30-100 ng/mL or
75-265 nM)
Terminal plasma concentration = 23 nM
FULCRUM THERAPEUTICS Company data; Oliva et al., 2019 17Integrated Development Strategy
▪ Refined clinical endpoints: DUX4, MRI, Muscle
Fulcrum Preparatory Studies
Function, PROs
▪ Safe and tolerable in FSHD subjects
Phase 1 ▪ Target engagement demonstrated
Complete ▪ Losmapimod penetrates FSHD muscle
Ongoing ReSOLVE Natural History Study ▪ Clinical endpoints: MRI, Muscle Function, PROs
▪ Molecular endpoint in muscle biopsy
Phase 2 Open Label Study ▪ MRI assessment of skeletal muscle
52 weeks dosing ▪ Clinical assessments of mobility
▪ Patient reported outcomes
▪ IA data suggest losmapimod may be reducing
Phase 2b ReDUX4
DUX4-driven gene expression
24 or 48 weeks dosing
▪ Anticipate topline ReDUX4 data in Q1 2021 and
Open Label Extension
full data in Q2 2021
FULCRUM THERAPEUTICS 18Capitalizing on Established and Novel Molecular, MRI
Imaging and Functional Endpoints
Endpoint Novel Modified Established
DUX4-Driven Gene
Tailored to FSHD and DUX4
Expression detection
Pathogenic DUX4 expression in Sensitivity and responsivity not yet
biopsied muscle clinically proven
Whole body
Musculoskeletal MRI
Composite regional and whole-body
Muscle death and fatty replacement assessment Fat fraction, Lean Muscle Volume,
Muscle Fat Infiltration from single muscle level
Clinical Outcome
Assessments
Patient Reported Real World Mobility Assessment FSHD TUG TUG
Outcomes Reachable Workspace Dynamometry
FSHD-RODs Motor Function Measure
Progressive loss of function in regions FSHD-HI 6 MWT
and individual muscles Spirometry
Patient Reported Outcomes PGIC
FULCRUM THERAPEUTICS 19Phase 2b ReDUX4 Trial (n=80)
Randomized, double-blind, placebo-controlled, multi-site international
15 mg twice per day for 24 or 48 weeks followed by an open label extension
▪ Primary endpoint: ▪ Exploratory endpoints:
▪ Change from baseline in DUX4 driven gene expression in ▪ Reachable Workspace (RWS)
skeletal muscle needle biopsy at 16 or 36 weeks, as ▪ FSHD-Timed up and Go (TUG)
measured by qRT-PCR in a panel of DUX4-regulated gene
transcripts ▪ Muscle Function Measure (MFM)
▪ Muscle Strength (Dynamometry)
▪ Secondary endpoints:
▪ PROs
▪ Safety and tolerability
▪ PK in blood ▪ Interim analysis on first 29 randomized
▪ Losmapimod concentration in skeletal muscle biopsies subjects in Q3 2020
▪ Target engagement in blood and in skeletal muscle biopsies ▪ Topline data on all subjects expected
▪ MRI Lean Muscle Volume & MRI Fat Fraction Q1 2021
▪ Full data on all subjects expected Q2
2021
FULCRUM THERAPEUTICS 20Targeting and Measuring DUX4-driven Gene Expression, the
Root Cause of FSHD, and its Impact on Functional Outcomes
• DUX4 controls transcription and is abnormally present in FSHD muscle in very low
amounts and for a very short time period
• DUX4 itself cannot be directly measured
• DUX4-driven gene expression is detectable at higher amounts and for longer time
• Using MRI-guided muscle biopsy, DUX4-driven gene expression is detected in 90-
100% of affected FSHD muscles (data from Seattle Wellstone and Fulcrum)
• Fulcrum developed a novel qPCR assay to measure DUX4-driven gene expression
in repeated muscle biopsies (before and after treatment)
• The assay uses 6 DUX4-regulated genes and 3 housekeeping genes
• Assessing losmapimod’s effect on the root cause of the disease by monitoring
numerous MRI and functional endpoints impacted in FSHD
FULCRUM THERAPEUTICS 21DUX4 Expression is Highly Variable
▪ MRI guided biopsy is utilized to identify
1000-fold Range of DUX4-driven gene those muscles most likely to express
expression found in IA Biopsies DUX4-driven gene expression
Top 25% 50% 75% 100%
100
>27.54 >24.61 >21.96
▪ MRI can accurately identify affected
80 muscle, but cannot determine level of
% of reference
DUX4-driven gene expression, which
60
varies by muscle and by tissue sample,
40 but is stable over time across the
population
20
0
30 28 26 24 22 20 18
▪ Pre-specified sensitivity analysis was
included in the IA to evaluate treatment
inverted(Ct)
effects on DUX4-driven gene expression
Average of 6 DUX4 driven genes related to 3 in muscle biopsies with the highest
housekeeping genes baseline level of DUX4-driven gene
expression
FULCRUM THERAPEUTICS 22Results of Interim Analysis of Primary Endpoint
Large reduction observed with losmapimod treatment in highest expressing muscle biopsies
Observed a 38-fold reduction in losmapimod arm and 5.4-fold reduction in placebo treated arm
IA Results IA Results
(Highest Expressing Muscle Biopsies) (All muscle biopsies)
1000 1000
+/- Max/Min (%of reference composite)
+/- Max/Min (%of reference composite)
Mean DUX4 composite
Mean DUX4 composite
100 100
Placebo (n=5) Placebo (n=14)
3.7-fold increase
10 5.4-fold decrease 10
Losmapimod (n=3) Losmapimod (n=15)
2.8-fold increase
35
35
1 38-fold decrease 1
Mean DUX4 composite
Mean DUX4 composite
30
30
0.1 Placebo (n=5) 0.1 Placebo (n=14)
+/- S.D.
Losmapimod (n=3)
+/- S.D.
25
Losmapimod (n=15)
25
Baseline Post-Baseline Baseline Post-Baseline
20
20
Highest expressing muscle biopsies represent the top quartile of Data from IA is displayed as inverted ΔCT values (relative to
biopsies assessed for baseline DUX4-driven gene expression housekeeping gene)
15
FULCRUM THERAPEUTICS 15 23
Baseline Post-Baseline Baseline Post-BaselineReDUX4 Interim Analysis Key Highlights
▪ Encouraging IA data suggests losmapimod may be reducing DUX4 driven gene
expression, the root cause of FSHD
▪ Observed a 38-fold reduction in losmapimod arm and 5.4-fold reduction in placebo treated arm in
highest expressing muscle biopsies
▪ Separation from placebo in the total population was not observed
▪ Muscle biopsies with higher DUX4-driven gene expression at baseline may be needed to observe a
reduction
▪ All FSHD patients likely have muscle regions with high to low baseline DUX4-driven gene
expression, and we believe that losmapimod has the potential to offer a benefit to all FSHD patients
▪ Interim analysis data is consistent with limited initial data from Open Label Study (OLS)
▪ Highest expressing biopsies demonstrated reduction of DUX4-driven gene expression
FULCRUM THERAPEUTICS 24Multiple Near-term Data Readouts
2020 2021
Q1 Q2 Q3 Q4 Q1 Q2
ReSolve Natural History Study
OLS Open Label Study
Full data in 2Q 2021
Phase 2b
ReDUX4 Topline data on primary endpoint in 1Q 2021
Full data in 2Q 2021
FULCRUM THERAPEUTICS 25FTX-6058 – Hemoglobinopathies - Sickle Cell Disease & Beta-
Thalassemia
26Fetal Hemoglobin Mitigates Mortality and Morbidity
Risks Associated with Sickle Cell Disease (SCD)
SCD Patient SCD Patient with High Fetal Hemoglobin (HbF)
RBC sickling
VOCs
Hemolysis
Stroke
Pancellular
HbF Asymptomatic
Acute Pulmonary 30%
Hypertension Expression presentation
Chest and
Syndrome
Induction Increased F-cells*
Nephropathy
20% Reduced Reduced VOCs
recurring
Osteonecrosis events Reduced hemolysis
(VOCs, ACS,
Hospitalization)
10%
Ulcer / Pain Reduced
mortality
HbF Level
FULCRUM THERAPEUTICS
*F-cells - fetal hemoglobin expressing cells
27FTX-6058 for Sickle Cell Disease
• Highly potent (< 1 nM) and selective small • Elevation of endogenous embryonic globin
molecule with clean off-target profile mRNA (hbb-bh1) in wild-type mice
• Superior pre-clinical activity relative to SOC and • Elevation of human fetal hemoglobin mRNA
competitor compounds (HBG1), protein (HbF), and F-cells in Townes
mouse model of SCD
• Potent upregulation of HBG mRNA and
pancellular induction of HbF protein in primary • Nonprovisional composition of matter
human erythroid cells patent application filed
• Clinically desirable globin profile (e.g., % HbF) in • 28-day GLP toxicology studies completed and
differentiated CD34+ cells from multiple healthy GMP material scale-up for Phase 1 is complete
and SCD donors
• PK and human dose projections support FTX-
6058 as an orally bioavailable, once-daily
treatment for SCD
FULCRUM THERAPEUTICS 28FTX-6058 Robustly Induces Fetal Hemoglobin in
CD34+ Cells from Healthy and SCD Donors
FTX-6058 Maximal %HbF
HbF Induction Induction
with FTX-6058
Donor
D144 1
30
Donor
D069 2
%HbF (HPLC)
D160 3
Donor
20
D224 4
Donor
D227 5
Donor
10 D466 6(SCD)
Donor (SCD)
0
Pre-treatment
Baseline %HbF Post-treatment
Maximal %HbF
▪ Observe an absolute 8 – 18% increase in HbF upon treatment with FTX-6058, which has the ability
to address mortality risk and recurring events in SCD patients
▪ Small increases in HbF (1 – 5%) have the potential to provide clinical benefits to all SCD patients
FULCRUM THERAPEUTICS 29FTX-6058 Selectively Upregulates Fetal Globin, with
No Observed Effect on Beta Globin Expression
In vivo pharmacology In vitro pharmacology
(Townes SCD mouse model) (Human CD34+ cells)
HBG1 HBB HBG1/2 HBB
1000 600 1000 600
****
** ****
****
**
800 800
(% of vehicle)
(% of vehicle)
(% of DMSO)
(% of DMSO)
400 400
600 Area 600
Area
Area
Area
400 400
200 200
200 200
0 0 0 0
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60
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Ve
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SCD Mice SCD Mice
Townes mouse model (28 days treatment): Human primary CD34+ cells (Donor 224):
Hydroxyurea was administered once daily at 100 mg/kg; 7 days of treatment and differentiation
FTX-6058 was administered twice per day at 5 mg/kg
FULCRUM THERAPEUTICS 30FTX-6058 Induces Pancellular Distribution of HbF Similar to
Hereditary Persistence of Fetal Hemoglobin
Hereditary Persistence of Fetal Hemoglobin FTX-6058 treatment results in ~80% F-cells
(HPFH) induces Pancellular HbF expression
HbF Protein: ~11% HbF Protein: ~30% HbF Protein: ~12% HbF Protein: ~30%
SCD Patient SCD Patient w HPFH DMSO 100 nM FTX-6058
(Asymptomatic)
Wood WG et al. J Med Gen, HbF flow cytometry: CD34+ cells differentiated and treated
14:237 1977 for 7 days; Gated and quantified for HbF+/CD235a+/CD71+
FULCRUM THERAPEUTICS 31Research and Discovery Collaborations
Fulcrum eligible to receive >$800M in milestone payments + upfront and R&D reimbursement
▪ Fulcrum to utilize its proprietary product engine to identify therapeutic targets that control the expression of genes known to impact
pathways relevant to the targeted disease states
▪ Partners responsible for all development & commercialization activities for any potential therapeutics identified
Therapeutic targets that control the expression of genes
Therapeutic targets that modulate genes associated with
Targets known to impact pathways relevant to the Targets genetically defined cardiomyopathies
targeted pulmonary disease
▪ Fulcrum receives $10M upfront payment & ▪ Fulcrum receives $12.5M at the close of the transaction &
reimbursement for all relevant research expenses reimbursement for all relevant research expenses
▪ Fulcrum eligible to receive: ▪ Fulcrum eligible to receive:
− R&D and commercial milestones up to $295M for first − R&D and commercial milestone payments and
Financial product commercialized Financial additional research reimbursement of up to $302.5
Terms − Up to $143.5M in additional milestones for all Terms million for first product
subsequent products commercialized − Up to $150M if MyoKardia chooses to develop and
− Tiered royalty payments on net sales ranging from commercialize any additional targets
mid-single to low double-digits
− Tiered royalty payments on net sales ranging from
mid-single to low double-digits
FULCRUM THERAPEUTICS 32Anticipated Milestones
Cash runway into Q1 2022
2020 2021
Q1 Q2 Q3 Q4 Q1 Q2
Phase 3
Losmapimod IND Filing Interim analysis in 4Q 2020
COVID-19 Topline data in 1Q 2021
Phase 2b
Topline data on primary endpoint in 1Q 2021
OLE
Losmapimod Full data in 2Q 2021
FSHD
Phase 2 Open Label Study
Full data in 2Q 2021
FTX-6058 IND-Enabling Studies Submit
Sickle Cell Disease IND
Phase I HV Trial
Complete
Ongoing
& β-Thalassemia
Advancing New Targets Identified with FulcrumSeek
Product Engine
Acceleron and MyoKardia Research & Discovery Collaborations
FULCRUM THERAPEUTICS 33
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