UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM
CURRENT REPORT
Pursuant to Section 13 OR 15(d)
of The Securities Exchange Act of 1934
Date of Report (Date of earliest event reported):
(Exact name of registrant as specified in its charter)
| (State or other jurisdiction of incorporation) |
(Commission File Number) |
(IRS Employer Identification No.) |
| (Address of principal executive offices) | (Zip Code) |
Registrant’s telephone number, including area code:
N/A
(Former name or former address, if changed since last report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
| Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
| Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
| Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
| Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
Securities registered pursuant to Section 12(b) of the Act:
| Title of each class |
Trading Symbol(s) |
Name of each exchange on which registered | ||
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).
Emerging growth company
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
| Item 2.02 | Results of Operations and Financial Condition |
Although it has not yet finalized its full financial results for the fourth quarter and fiscal year ended December 31, 2024, Fulcrum Therapeutics, Inc., or Fulcrum, published an updated corporate presentation on its Website on January 13, 2025, which is attached as Exhibit 99.1 hereto, announcing that it expects to report that it had approximately $240 million of cash, cash equivalents and marketable securities as of December 31, 2024.
The information contained in this Item 2.02 of, and in Exhibit 99.1 attached to, this current report on Form 8-K is unaudited and preliminary and does not present all information necessary for an understanding of Fulcrum’s financial condition as of December 31, 2024. The audit of Fulcrum’s consolidated financial statements for the year ended December 31, 2024 is ongoing and could result in changes to the information set forth above.
The information in this Item 2.02, and in Exhibit 99.1 attached hereto, shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or the Exchange Act, or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such a filing.
| Item 7.01 | Regulation FD Disclosure. |
On January 13, 2025, Fulcrum published an updated corporate presentation on its website. Fulcrum is furnishing as Exhibit 99.1 to this current report on Form 8-K a copy of the slides from such presentation, which updated information is incorporated by reference herein.
The information in this Item 2.02, and in Exhibit 99.1 attached hereto, shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or the Exchange Act, or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such a filing.
| Item 9.01 | Financial Statements and Exhibits |
| (d) | Exhibits |
The following exhibit is furnished herewith:
| Exhibit No. |
Description | |
| 99.1 | Corporate Presentation dated January 13, 2025. | |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document). | |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| FULCRUM THERAPEUTICS, INC. | ||||||
| Date: January 13, 2025 | By: | /s/ Alex C. Sapir | ||||
| Name: Alex C. Sapir | ||||||
| Title: President and Chief Executive Officer | ||||||
Exhibit 99.1 January 13, 2025 FULC
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 Fulcrum's product candidates, the potential advantages and therapeutic potential of Fulcrum's product candidates, filings with regulatory agencies and availability of clinical trial data, effects of using AiCure, and Fulcrum’s preliminary unaudited cash position and cash runway. All statements, other than statements of historical facts, contained in this presentation, including express or implied 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 pociredir 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; and complete the audit of its 2024 financials. 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 presentation 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. While Fulcrum may elect to update these forward-looking statements at some point in the future, Fulcrum specifically disclaims any obligation to do so. Fulcrum's financial closing procedures for the fourth quarter and year ended December 31, 2024 are not yet complete. It is possible that the final cash position and cash runway guidance may differ from the preliminary unaudited year end cash position and cash runway disclosed herein between now and when results are finalized. 2
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 modify gene for sickle cell disease (SCD) sustainability expression in rare diseases with a focus on benign • Fast Track and Orphan • IND submission planned in hematology Designations Q4 2025 • Planned timing for Phase 1b • Cash position of ~$240M as PIONEER data disclosure of 12/31 with runway into at least 2027 − Cohort 3 (12 mg): mid-2025 − Cohort 4 (20 mg): YE 2025 HbF: Fetal hemoglobin 3
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 Cardiomyopathies DBA: Diamond-Blackfan anemia 4
f or Si c k l e C ell D i s eas e Fast Track Designation Orphan Drug Designation
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.S. individuals § Vaso-occlusive crises (VOCs) § Other complications, including stroke, neuropathy, and acute chest syndrome § Anemia / hemolysis § Reduced life expectancy >20 years; mortality 4.4 million worldwide rate up to 9x higher than general population 6 VOC: Vaso-occlusive crisis; CDC; WHO; UpToDate.
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 Inhibitors Adakveo – Novartis Selectin Inhibitors Anti-Polymerization ® Oxbryta – Pfizer (withdrawn) Inclacumab – Pfizer Osivelotor (GBT-601) – Pfizer PK Activators Gene Therapy Mitapivat (AG-348) – Agios ® Etavopivat (FT-4202) – Novo Nordisk Lyfgenia – Bluebird Bio ® Tebapivat (AG-946) – Agios Casgevy – Vertex Pharmaceuticals BEAM-101 – Beam Therapeutics HbS: Sickle hemoglobin. PK: Pyruvate kinase. 7 EDIT-301 – Editas Medicine (ceased development)
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 Inhibitors Selectin Inhibitors 8
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% Reduced recurring Reduced VOCs events Osteonecrosis Fewer recurring events 10% Progressively SCD Baseline 5% reduced Ulcer / pain HbF 5-10% mortality HbF Level By Raising HbF Levels, Pociredir Provides the Potential to Ameliorate Disease Pathology 9 VOC: Vaso-occlusive crisis; Powars, DR. Blood. 1984; Platt, OS. NEJM. 1994; Akinsheye, I. Blood. 2011.
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) Analysis 1: Baseline 75 0.94 (0.92 – 1% increase in HbF is associated HbF Approach N=1395 0.97) with 6% reduction in VOC rate N=1395 Analysis 2: Equal 50 observation time 0.96 (0.94 – 1% increase in HbF is associated approach 0.98) with 4% reduction in VOC rate N=1367 N=3056 25 Analysis 3: All 0.95 (0.94 – 1% increase in HbF is associated observation approach N=1367 0.97) with 5% reduction in VOC rate N=3056 0 0 10 20 30 40 50 Multicenter Study on Hydroxyurea (MSH) (N= 299) Imputed HbF (%) HbF analysis: 0.92 (0.89 – 1% increase in HbF is associated Probability of observing zero VOC/year by HbF Post-randomization 0.96) with 8% reduction in VOC rate Blue line = model prediction; Black line = observed VOC 1 Table adapted from Peter Bruun-Rasmussen. ASH 2024 (poster #1124). 10 2 Unpublished data from Fulcrum analysis of Picnic Health real-world dataset, n = 673; ≥ 2 years old ; Mean HbF = 8.6% Percent of patients with zero VOC per year
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 Mining HBG mRNA Computationally mined candidate targets HbF Protein H3K27me3 Propagation Pociredir is a Potent and Selective EED Binder EED Highly Selective H3K27me3 HBG mRNA Clean Off-target Profile pociredir pociredir HbF Protein Reduced H3K27me3 Propagation Composition of Matter Patent Expires 2040 11 EED: Embryonic Ectoderm; HbF: Fetal hemoglobin; HBG: Gamma globin gene (encodes mRNA for fetal hemoglobin)
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 Day 7 Day 14 SFU HBG Fold Induction in Healthy Volunteers Safety follow-up (SFU) samples were collected 7 – 10 days post 14-day treatment period; PBO: placebo; Data presented as geometric LS mean ratio (to placebo) with 95% confidence interval; mixed-effects model 12 for repeated measures (MMRM) analysis performed for Day 7 and Day 14; analysis of covariance (ANCOVA) utilized for SFU data;. HBG: hemoglobin gene; HBB: hemoglobin subunit beta gene HBG Fold Induction (Normalized to HBB)
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) 12-Week Treatment Period months or 12-Week Treatment Period Cohort 3 (12 mg, n=10) • ≥2 VOCs + at least 1 non-VOC severe acute event (ACS, sequestration, priapism) over 12 Cohort 4 (20 mg, n=10) 12-Week Treatment Period months or • ≥2 non-VOC severe acute events (ACS, sequestration, priapism) over 12 months or Key Study Endpoints • SCD end-organ disease severity (CKD or PAH) Secondary/Exploratory Primary HbF induction, hemolysis, and anemia: • Safety and tolerability assessments Concomitant Medications • % HbF (CE/HPLC) and % F-cells (flow • PK parameters cytometry) • Prior experience with hydroxyurea / Current • Absolute reticulocyte count hydroxyurea use excluded • Total hemoglobin • Unconjugated bilirubin • Other disease modifying therapies (crizanlizumab, L-glutamine) allowed **U.S. FDA lifted the clinical hold for pociredir on August 18, 2023. Reinitiated trial at the 12mg dose, to be followed by the 20mg dose. CE, capillary electropherisis ; CKD, chronic kidney disease ; HbF, fetal hemoglobin; HPLC, high-performance liquid chromatography ; PAH, pulmonary arterial hypertension ; 13 PD, pharmacodynamics; PK, pharmacokinetics; SCD, sickle cell disease; VOC, vaso-occlusive crisis. Active Completed
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-related TEAEs in 5/16 (31.3%) Any TEAE 10 (62.5) patients: (headache [x2], lip numbness, diarrhea, fatigue, # somnolence, nausea, tinnitus) Any treatment-related TEAE 5 (31.3) Any serious adverse event (SAE)* 4 (25.0) Any TEAE leading to treatment discontinuation 0 § 4/23 TEAEs (in 4 patients) were characterized as VOC Any lab-related TEAE 0 (pain crisis) per protocol definition Patients with TEAE (by Maximum Severity) Ø None reported as related to study drug Mild 4 (25.0) Ø Two VOCs occurred in patients documented non-adherent Moderate 5 (31.3) to study drug Severe 1 (6.3) Most Common TEAEs § Single SAE in patient on study drug* Pain crisis 4 (25.0) Headache 3 (18.8) Ø VOC with chest syndrome, reported as not related to study drug * In 3 (of 4) patients, SAE began prior to first dose of study drug TEAE: Treatment-emergent Adverse Event; SAE: Serious adverse event; VOC: Vaso-occlusive crisis 14 # All mild in severity, non-serious and resolved while patient remained on study drug
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 Institute (PI: Griffin) § Virginia Commonwealth University (PI: Smith) § Boston Medical Center (PI: Ribeil) § University of California Los Angeles (PI: Sehl) § Mississippi Center for Advanced Medicine (PI: Pennington) § University of Arkansas (PI: Birrer) § Lady of the Lake Hospital (PI: Stagg) § Inova Cancer Center (PI: Alan) South Africa § Wits Health Consortium (PI: Mahlangu) Onboarding Sites Nigeria United States § University of Illinois Chicago (PI: Molokie) South § Massachusetts General Hospital (PI: Azar) Africa § East Carolina University (PI: Liles) Nigeria § National Hospital, Abuja (PI: Ojika) § Barau Dikko Teaching Hospital (PI: Dogara) 15 § University of Ibadan (PI: Fasola) Clinical trial site status as of January 6, 2025
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 February 23, 2023 which was lifted August 23, 2023. Safety data collection continued with data cutoff of March 3, 2023. 16 Note: Summary data includes both subjects on and off hydroxyurea; Subject 15 ceased dosing on Day 22 and therefore, was only included in the analysis up to Day 14 Absolute %HbF Change from Baseline Mean (+/- SE)
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 Subject 8 Subject 9* 5 5 5 Subject 10* 0 0 0 0 14 28 42 56 70 84 98 112 0 14 28 42 56 70 84 98 112 0 14 28 42 56 70 84 98 112 Day Day Day Safety Safety Safety Follow-up Follow-up Follow-up 10 10 10 Subject 13 Subject 1 Subject 11 8 Subject 14* 8 Subject 2 8 Subject 12** Subject 15* Subject 3 6 6 6 Subject 7* 4 4 4 Subject 8 Subject 9* 2 2 2 Subject 10* 0 0 0 0 14 28 42 56 70 84 98 112 0 14 28 42 56 70 84 98 112 0 14 28 42 56 70 84 98 112 Day Day Day U.S. FDA issued a full clinical hold for pociredir on February 23, 2023. Safety data collection continued with data cutoff of March 3, 2023. *Subjects on stable dose of hydroxyurea; Note: Subject 15 ceased dosing on Day 22 17 ** Day 42 and day 84 data not available for subject 12; samples were received by the lab outside of stability window ***Data includes subjects with confirmed study drug adherence Absolute %HbF %HbF (HPLC) Change from Baseline
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 7* 300 3 9.5 Subject 8 20 9.0 200 2 8.5 8.0 Normal 15 Normal Normal 100 7.5 1 7.0 0 6.5 0 10 0 14 28 42 56 70 84 98 112 0 14 28 42 56 70 84 98 112 0 14 28 42 56 70 84 98 112 0 14 28 42 56 70 84 98 112 Day Day Day Day 400 11.0 25 4 10.5 Subject 13 10.0 Subject 13 300 Subject 13 3 9.5 Subject 14* 20 Subject 14* Subject 14* 9.0 Subject 15* 200 Subject 15* Subject 13 2 Subject 15* 8.5 Subject 14* 8.0 Normal Normal 15 Normal 100 Subject 15* 7.5 1 7.0 0 6.5 10 0 0 14 28 42 56 70 84 98 112 0 14 28 42 56 70 84 98 112 0 14 28 42 56 70 84 98 112 0 14 28 42 56 70 84 98 112 Day Day Day Day Reductions in RDW indicate RBCs Bilirubin decreases indicate Reductions in reticulocytes and increases in total hemoglobin indicate less anemia are becoming more uniform in shape less hemolysis and healthier bone marrow function 18 *Subjects on stable dose of hydroxyurea; Note: Subject 15 ceased dosing on Day 22 12 mg 6 mg RDW (%) RDW (%) Total Bilirubin (mg / dL) Total Bilirubin (mg / dL) Absolute Reticulocyte Count Absolute Reticulocyte Count 3 3 (x10 / uL) (x10 / uL) Hemoglobin (g/dL) Hemoglobin (g/dL)
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
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 treatment of DBA & inherited Estimated 2025 cash burn of aplastic anemias $55 - $65 million Potential to be broadly protective of SCD Foundation for pipeline Cash runway until at least symptomology sustainability in benign 2027 hematology Planned timing for Phase 1b IND submission planned in PIONEER data disclosure Q4 − cohort 3 (12 mg): mid-2025 − cohort 4 (20 mg): YE 2025 20
