Fulcrum Therapeutics, Inc. · NASDAQ:FULC
Fulcrum Therapeutics — Corporate Update (January 2023)
16 slides from Fulcrum Therapeutics's corporate update, Jan 4, 2023
Slide 1: Pipeline and Catalysts
Pipeline and Catalysts Wholly Owned Clinical Programs FSHD Losmapimod (DUX4 Inhibitor) Complete Phase 3 enrollment in 2H'23 SCD FTX-6058 (Oral HbF Inducer) Phase 1b data update in 4Q'23 Wholly Owned Discovery Programs Blood Disorder Neurologic Disorder IND expected in 2023* Muscle Disorder IND expec
Slide 2: Fast Track Designation Granted in December 2022
Fast Track Designation Granted in December 2022
Slide 3: FTX-6058: Potential Best-in-Class Therapeutic Profile
FTX-6058: Potential Best-in-Class Therapeutic Profile HbS Polymerization Inhibition P-selectin Inhibition HbF Induction Physiologic Disease Modification Anemia Amelioration Improved Disease Symptoms FTX-6058: Best-in-Class Profile Raises HbF level Potential to ameliorate disease pathology Convenient
Slide 4: FTX-6058 Phase 1b Clinical Trial
FTX-6058 Phase 1b Clinical Trial
Slide 5: Ongoing Phase 1b Clinical Trial in SCD Subjects
Ongoing Phase 1b Clinical Trial in SCD Subjects Cohort 1 (6 mg) Cohort 2 (2mg) Cohort 3 (12 mg) 4-Week Treatment Period -Week Treatment Extension Study Design Safety and tolerability Pharmacokinetic measurements %HbF protein and %F-cells Primary Secondary Target engagement Incidence of VOCs Biomarke
Slide 6: SCD Phase 1b Demographics
SCD Phase 1b Demographics 2 mg Cohort 6 mg Cohort Total Number of subjects enrolled, n 2 10 12 Average age, years (range) 37 (25, 48) 28 (21, 48) 30 (21, 48) Gender, Male (%) 1 (50%) 2 (20%) 3 (25%) Mean baseline HbF (range %) 4.0 (3.2, 4.8) 9.3 (3.7, 19.9) 8.4 (3.2, 19.9) Genotype, n (%) HbSS 2 (10
Slide 7: Overall FTX 6058 Was Generally Well Tolerated
Overall FTX 6058 Was Generally Well Tolerated Data analysis cutoff : December 21, 2022; 14 Treatment Emergent Adverse Events (TEAEs) in 7/12 (58%) subjects 2/14 TEAEs reported as possibly related to study drug (headache, lip numbness) Mild severity and non-serious 2/14 TEAEs characterized as VOCs (i
Slide 8: Instituted Observed Dosing and On-Treatment Analysis Following Initial Non-Adherence
Instituted Observed Dosing and On-Treatment Analysis Following Initial Non-Adherence Initial 6 subjects were either not fully adherent or not adherent to study drug Observed dosing was instituted in subjects 7-12 An on-treatment analysis was established to allow interpretation of efficacy (HbF) data
Slide 9: Non-Adherent Subject Switched to Observed Dosing Demonstrated HbF Induction
Non-Adherent Subject Switched to Observed Dosing Demonstrated HbF Induction Subjects were not included in the on-treatment analysis ----- Represents last day of on drug measurements Subject 4 (Switched to Observed Dosing at ~Day 53) Subject 5 Observed dosing
Slide 10: Adherent Subjects, On and Off Hydroxyurea, Reach Robust HbF Increases
Adherent Subjects, On and Off Hydroxyurea, Reach Robust HbF Increases HbF increase was robust (6.8%-9.5%) at day 84 No apparent response differences in HU vs non-HU treated subjects Potential for further HbF induction beyond 3 months Observed dosing was used to ensure adherence 6 mg with HU Subject
Slide 11: FTX-6058 (6 mg) Improved Biomarkers of Hemolysis
FTX-6058 (6 mg) Improved Biomarkers of Hemolysis Bilirubin decreases indicate less hemolysis Reductions in reticulocytes and increases in total hemoglobin indicate less anemia and healthier bone marrow function Total Bilirubin Absolute Reticulocyte Count Total Hemoglobin Reductions in RDW indicate R
Slide 12: FTX-6058 Appears to Have a Dose Dependent Increase in HbF
FTX-6058 Appears to Have a Dose Dependent, Clinically Relevant and Consistent Increase in HbF 6mg 2mg (ongoing) ----- Represents last day of on drug measurements
Slide 13: FTX 6058 Demonstrates Best-in-Class Potential
FTX 6058 Demonstrates Best-in-Class Potential All patients on treatment have responded Levels of HbF increase are clinically relevant among patients both on HU and off HU Consistency of response demonstrated across patients, independent of baseline HbF Dose response at 2 mg and 6 mg Overall FTX 6058
Slide 14: Next Steps: Complete Phase 1b to Enable Registration Dose Selection
Next Steps: Complete Phase 1b to Enable Registration Dose Selection Amend Protocol and Increase Number of Sites: Streamline PK Collection and Reduce Patient Burden Accelerate Enrollment Refine PK / PD Model: Select Optimal Therapeutic Dose Final Dose for Pivotal Trial Optimize Treatment Effect: Cont
Slide 15: FTX-6058: Differentiated HbF Inducer with Best-in-Class Potential
FTX-6058: Differentiated HbF Inducer with Best-in-Class Potential Demonstrated proof-of-concept Development path forward Best-in-Class Potential Completion of Phase 1b to Enable Registrational Dose Selection FDA Fast Track designation Composition of matter patent into 2040 Dose responsive target eng
Slide 16: Diversified, Differentiated Pipeline of Clinical Assets
Diversified, Differentiated Pipeline of Clinical Assets Enrollment for REACH Phase 3 trial to be completed in 2H 2023 Cash runway to late 2024 Well positioned to delivery on goals Losmapimod well-positioned to be first-to-market for patients living with FSHD Completion of Phase 1b to enable registra
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