Fulcrum Therapeutics, Inc. · NASDAQ:FULC
Fulcrum Therapeutics — Corporate Update (January 2025)
21 slides from Fulcrum Therapeutics's corporate update, Jan 13, 2025
Slide 1: Fulcrum Therapeutics January 13, 2025
Exhibit 99.1 January 13, 2025 FULC
Slide 2: Disclaimer and Notice
FULCRUM THERAPEUTICS 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 or implied statements regarding the development status of
Slide 3: Unlocking the Power of Small Molecules to Change the Course of Rare Diseases
Unlocking the Power of Small Molecules to Change the Course of Genetically Defined Rare Diseases Discovery & Strategic Focus Pociredir Cash Position • Developing oral small • Potential best-in class oral • Advancing discovery molecules designed small molecule HbF inducer programs for pipeline to mod
Slide 4: Small Molecule Pipeline Across Multiple Rare Diseases
FULCRUM THERAPEUTICS Small Molecule Pipeline Across Multiple Rare Diseases Indication Asset / MOA Preclinical Phase 1 Phase 2 Phase 3 Collaborator Clinical Programs Sickle Cell Disease Pociredir (HbF Induction) Discovery Programs DBA & Inherited Aplastic Anemias Novel HbF Inducers Fibrotic Disorders
Slide 5: Pociredir for Sickle Cell Disease
f or Si c k l e C ell D i s eas e Fast Track Designation Orphan Drug Designation
Slide 6: Sickle Cell Disease: Debilitating Disease with High Unmet Need
FULCRUM THERAPEUTICS Sickle Cell Disease: Debilitating Disease with High Unmet Need The Disease Global Impact § Genetic disorder caused by mutation in the Hemoglobin-Beta (HBB) gene § Results in abnormal sickle-shaped red blood cells that rupture or block blood vessels Debilitating Symptoms ~100K U.
Slide 7: Competitive Landscape in SCD
FULCRUM THERAPEUTICS Competitive Landscape in SCD Hydroxyurea HbF Inducers Pociredir – Fulcrum Therapeutics Current Standard of Care γ α BMS-986470 – Bristol Myers Squibb γ ITU-512 – Novartis α Ndec (decitabine + tetrahydrouridine) – Novo Nordisk / EpiDestiny SCD Treatment ® HbS Polymerization Inhib
Slide 8: Best-in-class Potential of Pociredir to Address Significant Unmet Need
FULCRUM THERAPEUTICS Best-in-class Potential of Pociredir to Address Significant Unmet Need for People Living With SCD Addresses underlying Ability to reduce VOC / Ability to be Safety & Tolerability disease pathology impact survival administered orally HbF Inducers PK Activators HbS Polymerization
Slide 9: Higher HbF Levels Result in Reduced Symptomology in SCD
FULCRUM THERAPEUTICS Higher HbF Levels Result in Reduced Symptomology in People Living with Sickle Cell Disease Typical SCD Patient SCD Patient with High HbF Levels Stroke Pulmonary hypertension 30% Asymptomatic Acute Chest Syndrome (ACS) presentation Reduced hemolysis Nephropathy Reduced anemia 20%
Slide 10: Even Modest Increases in HbF Reduce Mortality and Symptom Severity
FULCRUM THERAPEUTICS Even Modest Increases in HbF Reduce Mortality and Symptom Severity Each 1% increase in HbF is associated with HbF levels > mid-to-high 20% results in near 1 2 a 4%-8% reduction in VOCs abolition of VOCs 100 Analysis IRR (95% CI) Interpretation Cooperative Study of SCD (CSSCD) An
Slide 11: Targeting EED Results in HbF Increases
FULCRUM THERAPEUTICS Targeting EED Results in HbF Increases Identified EED as a Novel Drug Target of Polycomb Repressor Complex 2 CRISPR + Compound Screening Engine Experimentally screened candidate targets Allosteric PRC2 Activation Identified Targets that Regulate HbF H3K27me3 Computational Data M
Slide 12: Dose-dependent HBG mRNA Induction in Healthy Volunteers
FULCRUM THERAPEUTICS Dose-dependent HBG mRNA Induction in Healthy Volunteers Gamma Globin (HBG) mRNA Induction is both Time- and Dose-dependent in MAD Cohorts Off Treatment 10 2mg Pociredir p<0.0001 6mg Pociredir p<0.0001 10mg Pociredir 5 p<0.0001 20mg Pociredir 30mg Pociredir p<0.01 PBO 0 Day -1 Da
Slide 13: Pioneer Phase 1b Pociredir Clinical Trial in SCD Subjects
FULCRUM THERAPEUTICS Pioneer Phase 1b Pociredir Clinical Trial in SCD Subjects Study Population Study Design – Open-label** • Males and females with SCD, ages 18 – 65 years Cohort 1 (6 mg, n=10) 12-Week Treatment Period Patient Severity • ≥4 VOCs over 12 months or ≥2 VOCs over 6 Cohort 2 (2mg, n=2)
Slide 14: Pociredir Was Generally Well-tolerated with No Serious Treatment-related Adverse Events
FULCRUM THERAPEUTICS Pociredir Was Generally Well-tolerated with No Serious Treatment-related Adverse Events (Pioneer Ph1b – Open label data through 2023) § 23 Treatment Emergent Adverse Events (TEAEs) in Pociredir 10/16 (62.5%) patients Number of Patients with: (n=16) n (%) Ø 8/23 were treatment-re
Slide 15: Pioneer Phase 1b Clinical Trial Sites
FULCRUM THERAPEUTICS Pioneer Phase 1b Clinical Trial Sites Active Sites United States § UT Houston (PI: Idowu) § Queens Hospital Cancer Center (PI: Ferman) § University of Miami (PI: Alvarez) § University of North Carolina (PI: Little) § Jacobi Medical Center (PI: Rivlin) § Lynn Health Sciences Inst
Slide 16: Initial Pioneer Data Demonstrated Dose-dependent Increases in HbF
FULCRUM THERAPEUTICS Initial Pioneer Data Demonstrated Dose-dependent Increases in HbF Absolute %HbF Change from Baseline Off Treatment / Safety Follow-up 12 2mg Pociredir 10 6mg Pociredir 8 12mg Pociredir 6 4 2 0 0 14 28 42 56 70 84 98 112 Day U.S. FDA issued a full clinical hold for pociredir on F
Slide 17: Dose Dependent, Clinically Relevant and Consistent Increases in HbF
FULCRUM THERAPEUTICS Dose Dependent, Clinically Relevant and Consistent Increases in HbF 6mg*** 2mg*** 12mg*** Safety Safety Safety Follow-up Follow-up Follow-up 25 25 25 Subject 13 Subject 11 Subject 1 20 Subject 14* Subject 12** 20 20 Subject 2 Subject 15* Subject 3 15 15 15 Subject 7* 10 10 10 Su
Slide 18: Improvements in Biomarkers of Hemolysis and Anemia
FULCRUM THERAPEUTICS Improvements in Biomarkers of Hemolysis and Anemia from initial 6mg and 12mg Pioneer data Red Cell Distribution Width Absolute Reticulocyte Count Total Hemoglobin Total Bilirubin (RDW) Subject 7* Subject 7* 400 11.0 Subject 7* 25 4 Subject 8 10.5 Subject 8 Subject 8 10.0 Subject
Slide 19: Utilizing AI from AiCure to Increase Drug Adherence
FULCRUM THERAPEUTICS Utilizing Artificial Intelligence (AI) from AiCure to Increase Drug Adherence Improves Study Drug Adherence Robust Data Collection Real-Time Feedback to Clinical Trial Sites 19
Slide 20: Well-Positioned for Transformational Year in 2025
FULCRUM THERAPEUTICS Well-Positioned for Transformational Year in 2025 Pociredir: Best-in-class potential Preclinical Programs Cash Position ~$240 million as of December Oral small molecule HbF Advanced preclinical 31, 2024 inducer with demonstrated program for the potential proof-of-concept treatme
Slide 21: Thank You
THANK YOU
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