Slide 1: RALLY-MF: Initial efficacy of a Phase 2 study of DISC-0974 in myelofibrosis anemia
RALLY-MF: Initial efficacy of a Phase 2 study of DISC-0974, an anti-hemojuvelin antibody, to treat anemia in myelofibrosis Naseema Gangat1*, Ayalew Tefferi1*, Prithviraj Bose2^, Elizabeth Hexner3^, Laura Michaelis4^, Aaron Gerds5#, Akriti Jain5#, Prioty Islam6#, Raajit Rampal6#, Ronan Swords7#, Mosh
Slide 2: Key Takeaway Points
Key Takeaway Points #1 #2 #3 Treatment with DISC-0974 Treatment with DISC-0974 DISC-0974 resulted in meaningful also resulted in was safe and generally hematologic responses improvement in patient- well tolerated regardless of baseline reported outcomes MF-directed therapy, independent of concomitan
Slide 3: Hepcidin is a key driver of myelofibrosis (MF) anemia
Hepcidin is a key driver of myelofibrosis (MF) anemia Hepcidin Levels Are Elevated in MF Anemia of MF ~12× higher than control and associated with severity of anemia and transfusion burden Est. # Patients • 25,000 patients (US) • ~87% have anemia; severe and require transfusion Etiology of Anemia •
Slide 4: DISC-0974 is an investigational first-in-class mAb that blocks hemojuvelin and decreases hepcidin
DISC-0974 is an investigational first-in-class mAb that blocks the co-receptor hemojuvelin and decreases hepcidin expression DISC-0974 BMP2/4/6 HJV BMPs ↓ HJV-dependent BMP signaling in the liver ALK2/3/6 Liver cell ↓ Hepcidin production P ↑ Mobilization of stored iron into circulation SMAD1/5/8 P S
Slide 5: RALLY-MF Phase 2: study design and eligibility
RALLY-MF Phase 2: study design and eligibility Study Population • Age ≥18 years, with primary, post-essential thrombocythemia or post-polycythemia vera MF • Anemia, defined as: o Non-transfusion dependence (nTD): baseline Hgb <10 g/dL on ≥3 assessments over 84 days prior to Screening, without RBC tr
Slide 6: RALLY-MF Phase 2: study endpoints
RALLY-MF Phase 2: study endpoints Study Endpoints Major Hematologic Response Minor Hematologic Response Baseline Transfusion Overall Response (Primary Endpoint) (Secondary Endpoint) nTD Mean Hgb ↑1.5 g/dL ≥12 weeks (rolling Mean Hgb ↑1 g/dL ≥12 weeks (rolling (Hgb <10 and 0 units transfused)* window
Slide 7: RALLY-MF Phase 2: participant disposition as of data cut
RALLY-MF Phase 2: participant disposition as of data cut nTD TD Low TD High Overall Participants treated 35 13 13 61 Participants evaluable for efficacy analysis, n (%)* 31 (88.6) 11 (84.6) 8 (61.5) 50 (82.0) Participants with follow-up through EOS (Day 169), n (%) 25 (71.4) 9 (69.2) 6 (46.2) 40 (65
Slide 8: RALLY-MF Phase 2: baseline and demographics
RALLY-MF Phase 2: baseline and demographics Characteristic nTD (n=35) TD Low (n=13) TD High (n=13) Overall (n=61) Age, median (range), years 70.0 (31, 83) 75.0 (60, 87) 73.0 (60, 87) 71.0 (31, 87) Male, n (%) 18 (51.4) 7 (53.8) 8 (61.5) 33 (54.1) Race, n (%) White 31 (88.6) 12 (92.3) 11 (84.6) 54 (8
Slide 9: DISC-0974 was safe and generally well tolerated
DISC-0974 was safe and generally well tolerated Preferred Term nTD (n=35) TD Low (n=13) TD High (n=13) Overall (n=61) Any TEAE, n (%) 33 (94.3) 12 (92.3) 11 (84.6) 56 (91.8) Related TEAE, n (%) 6 (17.1) 4 (30.8) 5 (38.5) 15 (24.6) SAE, n (%) 8 (22.9) 1 (7.7) 3 (23.1) 12 (19.7) AESIs, n (%) 2 (5.7) 0
Slide 10: DISC-0974 leads to sustained hepcidin reduction and iron mobilization
DISC-0974 leads to sustained hepcidin reduction and iron mobilization (A) Hepcidin by Transfusion Cohort (B) Iron by Transfusion Cohort 150 300 nTD Serum Hepcidin, ng/mL 125 TD Low Serum Iron, ng/mL 250 TD High Mean ± SEM Mean ± SEM 100 200 75 150 50 nTD 25 100 TD Low LLD TD High 0 50 0 29 57 85 113
Slide 11: 55% nTD participants achieved mean Hgb increase of 1.5 g/dL for ≥12 weeks
55% nTD participants achieved mean Hgb increase of 1.5 g/dL for ≥12 weeks; Hgb increase is maintained through optional continuation phase (A) nTD Hematologic Response (B) nTD Hgb Increase from Baseline through Optional Continuation Evaluable participants (n=31) Evaluable participants (n=31) Treatmen
Slide 12: 64% TD Low participants achieved ≥TI-16
64% TD Low participants achieved ≥TI-16*; Hgb increase is maintained through optional continuation phase (A) TD Low Hematologic Response (B) TD Low Hgb Increase from Baseline through Optional Continuation Evaluable participants (n=11) Evaluable participants (n=11) Treatment period Optional continuat
Slide 13: 50% TD High participants achieved ≥TI-12
50% TD High participants achieved ≥TI-12* TD High Hematologic Response Evaluable participants (n=8) Overall response 88 50% reduction in transfusion requirement Major response 50 TI ≥12 weeks 0 20 40 60 80 100 % of Responders Response Mean ± SD (days) Time to major response (n=4) 2±1 Duration of lon
Slide 14: Hgb increase associated with improvement in patient-reported outcomes
Hgb increase in nTD and TD Low participants is associated with improvement in patient-reported outcomes (A) nTD FACIT-Fatigue (B) TD Low FACIT-Fatigue 12 nTD - Major responders 12 TD Low - Major responders • nTD and TD Low participants experienced 9 clinically significant improvement in Δ FACIT-Fati
Slide 15: Hepcidin reduction, iron mobilization and response regardless of concomitant JAKi use
DISC-0974 leads to hepcidin reduction, iron mobilization, and hematologic response regardless of concomitant JAKi use (A) Hepcidin by JAKi (B) Iron by JAKi (C) Hemoglobin by JAKi (D) Hematologic Response by JAKi Evaluable participants (n=50) Evaluable participants (n=50) Evaluable participants (n=50
Slide 16: Limitations
Limitations • This is a Phase 2, single-arm study with ongoing follow-up for the nTD cohort and ongoing enrollment for the TD cohort 16
Slide 17: Conclusions
Conclusions • DISC-0974 was safe and generally well tolerated • DISC-0974 resulted in sustained ↓hepcidin and ↑serum iron in participants regardless of concomitant JAKi therapy or baseline transfusion requirement • DISC-0974 resulted in meaningful hematologic responses across cohorts: ✓ 55% of nTD p
Slide 18: Lay Summary
Lay Summary • Patients with myelofibrosis often have low red blood cell counts that are due in part to high levels of hepcidin, a hormone that controls how iron is used and stored in the body • Iron is essential for the body to produce red blood cells • This clinical study looked at whether an inves
Slide 19: Thank you
@ disc medicine Ds Thank you