Olutasidenib (FT-2102) Induces Rapid Remissions in Patients with - PowerPoint PPT Presentation

Olutasidenib (FT-2102) Induces Rapid Remissions in Patients with IDH1-Mutant Myelodysplastic Syndrome: Results of Phase 1/2 Single-Agent Treatment and Combination with Azacitidine Jorge E. Cortes, 1 Eunice S. Wang, 2 Justin M. Watts, 3 Sangmin Lee, 4 Maria R. Baer, 5 Kim-Hein Dao, 6 Shira N. Dinner, 7 Jay Yang, 8 William B. Donnellan, 9 Anthony Schwarer, 10 Christian Recher, 11 Patrick Kelly, 12 Jennifer Sweeney, 12 Julie Brevard, 12 Patrick Henrick, 12 Sanjeev Forsyth, 12 Sylvie Guichard, 12 Hesham Mohamed, 12 Andrew H. Wei 13 1 Georgia Cancer Center, Augusta, GA; 2 Roswell Park Comprehensive Cancer Institute, Buffalo, NY; 3 Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, FL; 4 Weill Cornell Medicine, New York, NY; 5 University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD; 6 Oregon Health Sciences University, Portland, OR; 7 Northwestern University, Chicago, IL; 8 Karmanos Cancer Center, Detroit, MI; 9 Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; 10 Box Hill Hospital, Box Hill, VIC, Australia; 11 Institut Universitaire du Cancer de Toulouse Oncopole, CHU de Toulouse and Université de Toulouse III, Toulouse, France; 12 FORMA Therapeutics, Inc., Watertown, MA; 13 The Alfred Hospital and Monash University, Melbourne, VIC, Australia 1

Introduction • IDH1 mutations occur in approximately 4% of patients with MDS, yielding hypermethylated DNA and histones • Olutasidenib (FT-2102) is an oral highly potent and selective inhibitor of IDH1m with clinical activity in AML (ORR, 41%; monotherapy in R/R AML) Olutasidenib (FT-2102)

FT-2102 in MDS: Study Design Phase 1 Phase 2 Dose Dose Escalation Expansion Objectives Olutasidenib a Primary Key inclusion n = 6 • Phase 1 : Safety and 4 Monotherapy criteria: tolerability and 150 mg QD • Phase 2 : Efficacy (CR rate) • Intermediate to very 4 Olutasidenib + AZA 300 mg QD 150 mg BID high-risk MDS with cohorts Secondary and exploratory IDH1m 150 mg BID • Phase 1 : Clinical activity, • R/R Cohort 5 PK, biomarkers, mutation (Olutasidenib + AZA): • Treatment naive Olutasidenib a analysis Patients with R/R • Adequate cardiac, + • Phase 2 : Clinical activity, MDS and an renal, and hepatic AZA b safety and tolerability, PK, inadequate response function n = 7 biomarkers, mutation to or progression on • ECOG PS 0-2 analysis prior HMA 150 mg QD 150 mg BID n = 10 150 mg BID Results of Phase 1 AML cohort presented a Olutasidenib given daily over continuous 28-day cycles (RP2D 150 mg BID). in Session 616, Saturday, December 7 b AZA (75 mg/m 2 IV ) given daily on days 1-7 of each 28-day cycle. Abstract # 231

FT-2102 in MDS: Baseline Demographics and Disease Characteristics Olutasidenib Olutasidenib + AZA Characteristic (n = 6) (n = 17) Age, median (range), years 77 (66-87) 72 (59-82) ECOG PS 0/1/2, n 0/4/2 3/14/0 Time since initial diagnosis, median (range), months 17.8 (1.4-77.7) 13.8 (0.5-196.8) Disease state, n (%) R/R 4 (67) 12 (71) Treatment naive 2 (33) 5 (29) 0 4 (24) MDS risk category, n (%) Intermediate 5 (83) 10 (59) High Very high 1 (17) 3 (18) Cytogenetic risk category, n (%) Good/very good 1 (17) 9 (53) Intermediate 1 (17) 3 (18) Poor/very poor 2 (33) 2 (12) Unknown 2 (33) 3 (18) Prior regimens, median (range), n a 1 (0-4) 1 (0-4) Prior HMA, n (%) 4 (67) 11 (65) Duration of prior HMA, median (range), months 17.4 (3.6-45.2) 6.8 (0.2-37.0) Time between HMA and first olutasidenib dose, median (range), months 1.2 (0.3-64.0) 3.1 (1.2-17.0) a Not inclusive of all types; patient could have received > 1 type of prior regimen.

FT-2102 in MDS: Patient Disposition Olutasidenib Olutasidenib + AZA Characteristic (n = 6) (n = 17) Treatment ongoing, n (%) 2 (33) 10 (59) Treatment discontinued, n (%) 4 (67) 7 (41) Transplant 0 3 (18) Disease progression 3 (50) 1 (6) Death 0 1 (6) Adverse event 1 (17) 0 Other a 0 2 (12) Time on treatment, median, months 6.3 15 • The median time on treatment for all patients with MDS treated with olutasidenib (± AZA) was 8.0 months a Other reasons included alternative treatments.

FT-2102 in MDS: Clinical Activity Olutasidenib Olutasidenib + AZA (n = 6) (n = 16) a Investigator-Assessed Response, n (%) 3 (50) 9 (56) ORR b [95% CI] [11.8-88.2] [29.9-80.2] CR 4 (25) 2 (33) 5 (31) Marrow CR 1 (17) Clinical benefit (CB = SD ≥ 8 weeks) 1 (17) 5 (31) 1 (6) PD 1 (17) NE 1 (6) 1 (17) 2.8 (< 1 to 5.1) Time to first response, median (range), months 8.3 (< 1 to 9.7) Duration of overall response, median (range), 12.9 (< 1 to NR) NR (6.7-NR) months a Efficacy-evaluable population. One patient was excluded from efficacy analysis due to lack of R132X mutation. b ORR = CR + marrow CR + PR. NR, not reached

FT-2102 in MDS: Time on Treatment * • 12 of 22 patients (55%) achieved CR/marrow CR • 3 Patients proceeded to transplant • 12 Patients remain on treatment CR Marrow CR First response CB SCT PD Continuing on study NE Off treatment 0 10 20 30 40 50 60 70 80 90 100 110 120 Weeks on Study * This patient had R100X mutation, a non-R132 mutation, and was not included in the efficacy-evaluable set.

FT-2102 in MDS: Hematologic Improvement in Clinical Benefit and Marrow CR Olutasidenib + AZA Olutasidenib Response, n (%) (n = 16) a (n = 6) Patients with CB or marrow CR 2 (33) 10 (63) Patients with hematologic improvement 2 (100) 9 (90) Erythroid improvement Baseline hemoglobin < 11 g/dL 2 (100) 9 (90) Hemoglobin increased by ≥ 1.5 g/dL from baseline 2 (100) 4 (44) Platelet improvement Baseline platelet < 100 × 10 9 /L 2 (100) 7 (70) Any improvement 1 (50) 2 (29) Change > 30 × 10 9 /L (baseline, ≥ 20 × 10 9 /L ) 1 (50) 1 (14) At least 100% increase to > 20 × 10 9 /L (baseline, < 20 × 10 9 /L ) 0 1 (14) Neutrophil improvement Baseline neutrophils < 1 × 10 9 /L 1 (50) 8 (80) Increase > 0.5 × 10 9 /L and ≥ 100% increase from baseline 1 (100) 8 (100) a Efficacy-evaluable population. One patient was excluded from efficacy analysis due to lack of R132X mutation.

FT-2102 in MDS: TEAEs (> 20% Overall) Regardless of Causality Olutasidenib Olutasidenib + AZA Overall TEAE, n (%) (n = 6) (n = 17) (N = 23) Any Grade Grade 3/4 Any Grade Grade 3/4 Any Grade Hematologic Thrombocytopenia 2 (33) 2 (33) 7 (41) 4 (24) 9 (39) Neutropenia 1 (17) 1 (17) 6 (35) 6 (35) 7 (30) Nonhematologic Nausea 4 (67) 0 9 (53) 1 (6) 13 (57) Fatigue 4 (67) 1 (17) 6 (35) 2 (12) 10 (43) Arthralgia 4 (67) 1 (17) 5 (29) 0 9 (39) Constipation 1 (17) 0 8 (47) 0 9 (39) Dyspnea 2 (33) 0 5 (29) 1 (6) 7 (30) Vomiting 2 (33) 0 5 (29) 0 7 (30) Cough 1 (17) 0 5 (29) 0 6 (26) Dizziness 1 (17) 0 5 (29) 0 6 (26) Headache 2 (33) 0 4 (24) 0 6 (26) Diarrhea 1 (17) 0 4 (24) 1 (6) 5 (22) Hematuria 2 (33) 0 3 (18) 1 (6) 5 (22) Pain in extremity 3 (50) 0 2 (12) 1 (6) 5 (22) • IDH differentiation syndrome was observed in 3 patients (13%) • LFT (AST, AST, bilirubin) abnormalities were observed in 4 patients; 2 (G1, G3) continued dosing through the elevation, 1 (G3) improved with dose reduction, and 1 (G3) discontinued treatment after a positive re-challenge

FT-2102 in MDS: Mutations Consistent With Previous MDS Studies Baseline Co-Mutations R132L WT 50 5% 5% 45 Patients with co-mutations, % Median = 3 (range, 0-5) 14% 40 R132G, 17.6% R132G 35 R132C, 41.2% 32% 30 R132C 25 20 R132H, 58.8% 15 44% R132H 10 5 0 2 1 1 A R 1 2 1 2 1 S 3 2 3 1 2 P • 22 Mutations were identified in 17 patients F L X M G H F L P T A 5 X 3 A B 3 S X A X L T P N T F Z B U P A R C F A T R S M E 2 S U S T T C N N G A U A S C S E R N with samples available for central analysis S D • 3 Patients had multiple baseline IDH1 mutations

FT-2102 in MDS: Olutasidenib Induces IDH1 Mutation Clearance and Reduces 2-HG VAF 5 2-HG 4 Baseline Normalized Value • 44% of patients (4/9) 3 experienced mutation clearance (VAF < 1%) a 2 • Rapid reduction of 2-HG occurred by the end of 1 cycle 1 0 C1D1 C2D1 C3D1 C4D1 C5D1 C6D1 C7D1 C8D1 C9D1 VAF, n 16 11 4 4 5 4 3 2 3 2-HG, n 16 14 12 12 11 10 6 5 5 2-HG; 2 hydroxyglutarate; VAF, variant allele frequency a Only patients who received ≥ 3 cycles of treatment and ≥ 1 postbaseline VAF assessment were analyzed for mutation clearance.

FT-2102 in MDS: Conclusions • Olutasidenib is well tolerated as a single agent and in combination with AZA • Patients with MDS remained on treatment for a median of 8 months • Olutasidenib demonstrated preliminary clinical activity as a single agent and in combination with AZA in treatment-naive and relapsed/refractory patients with MDS: • 50% of patients treated with olutasidenib monotherapy achieved CR/mCR • 56% of patients treated with olutasidenib + AZA achieved CR/mCR • Clinical benefit with hematologic improvement was observed with olutasidenib monotherapy and olutasidenib + AZA in 17% and 31% of patients, respectively • Mutation clearance was observed in 44% of evaluable patients • Rapid and sustained reduction of 2-HG was seen by the end of cycle 1