Olutasidenib (FT-2102), an IDH1m Inhibitor as a Single Agent or in - PowerPoint PPT Presentation

Olutasidenib (FT-2102), an IDH1m Inhibitor as a Single Agent or in Combination With Azacitidine, Induces Deep Clinical Responses With Mutation Clearance in Patients With Acute Myeloid Leukemia Treated in a Phase 1 Dose Escalation and Expansion Study Justin M. Watts, 1 Maria R. Baer, 2 Jay Yang, 3 Thomas Prebet, 4 Sangmin Lee, 5 Gary J. Schiller, 6 Shira N. Dinner, 7 Arnaud Pigneux, 8 Pau Montesinos, 9 Eunice S. Wang, 10 Karen P. Seiter, 11 Andrew H. Wei, 12 Stephane De Botton, 13 Montserrat Arnan, 14 Will Donnellan, 15 Brian A. Jonas, 16 P. Brent Ferrell, Jr., 17 Kim-Hein Dao, 18 Patrick Kelly, 19 Jennifer Sweeney, 19 Sanjeev Forsyth, 19 Sylvie Guichard, 19 Julie Brevard, 19 Patrick Henrick, 19 Hesham Mohamed, 19 Jorge E. Cortes 20 1 University of Miami Sylvester Comprehensive Cancer Center, Miami, FL; 2 University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD; 3 Karmanos Cancer Institute, Detroit, MI; 4 Yale University, New Haven, CT; 5 Weill Cornell Medicine, New York, NY; 6 David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA; 7 Northwestern University, Chicago, IL; 8 Centre Hospitalier Universitaire Bordeaux, Bordeaux, France; 9 Hospital Universitari i Politècnic La Fe, Valencia, Spain and CIBERONC, Instituto Carlos III, Madrid, Spain; 10 Roswell Park Comprehensive Cancer Center, Buffalo, NY; 11 New York Medical College, Valhalla, NY; 12 The Alfred Hospital and Monash University, Melbourne, Australia; 13 Institut Gustave-Roussy, Villejuif, France; 14 Institut Catala d’Oncologia - Hospital Duran i Reynals, Barcelona, Spain; 15 Sarah Cannon Research Institute at Tennessee Oncology, Nashville, TN; 16 University of 1 California, Davis Comprehensive Cancer Center, Sacramento, CA; 17 Vanderbilt University, Nashville, TN; 18 Oregon Health & Science University, Portland, OR; 19 FORMA Therapeutics, Inc., Watertown, MA; 20 Georgia Cancer Center, Augusta, GA

Introduction • IDH1 mutations occur in 7-14% of patients with AML and approximately 3-5% of patients with MDS • Olutasidenib (FT-2102) is a highly potent, orally active, selective inhibitor of IDH1m Olutasidenib (FT-2102)

Study Design Phase 1 Dose Expansion Key Inclusion Criteria Dose Escalation (RP2D) Objectives • AML or intermediate to very R/R high risk MDS with IDH1- Olutasidenib a Monotherapy Olutasidenib a R132 gene mutation 150 mg QD Primary 150 mg BID 300 mg QD • Relapsed/refractory (R/R) 150 mg BID • Safety and tolerability • Treatment naive (TN) R/R Secondary/Exploratory where standard therapy is Olutasidenib a contraindicated • Antileukemic activity 150 mg BID Olutasidenib a + Combination 150 mg QD • Adequate cardiac, renal, • Anti-MDS activity AZA b 75 mg/m 2 therapy 150 mg BID and hepatic function + • PK TN AZA b • ECOG PS 0-2 Olutasidenib a 75 mg/m 2 • Biomarkers 150 mg BID • Prior IDH1 inhibitors, + allowed in the combination AZA b 75 mg/m 2 arm Results of MDS cohort FPFV = September 1, 2016 ; Data Cutoff = September 12, 2019 presented in Session 637, Monday, December 9 a Olutasidenib PO given daily over continuous 28-day cycles. b AZA IV or SC given daily on Days 1-7 of each 28-day cycle. Abstract # 674

Demographics and Disease Characteristics Olutasidenib Olutasidenib + AZA Characteristic (N = 32) (N = 46) Age, median (range), years 72 (35-87) 67 (31-88) Female 16 (50) 24 (52) ECOG PS - 0 / 1 / 2, % 28/50/22 28/57/15 AML, n 26 39 Primary AML (de novo) 21 (81) 23 (59) Secondary AML 5 (19) 16 (41) Disease state TN (newly diagnosed) 4 (15) 13 (33) Relapsed 14 (54) 11 (28) Refractory 8 (31) 15 (39) Cytogenetic Risk, n Intermediate 9 22 Poor/Unknown 7/10 8/9 Prior regimens, median (range) a 2 (0-9) 2 (0-6) HMA (azacitidine/decitabine), n 12 10 IDH1m inhibitor, n 0 3 HSCT, n 2 3 Intensive Chemotherapy, n 17 23 MDS, n 6 7 TN (newly diagnosed) 2 (33) 5 (71) Relapsed/Refractory 4 (67) 2 (29) Prior regimens, median (range) a 1 (0-4) 0 (0-4) HMA (azacitidine/decitabine), n 4 2 All values n (%) unless otherwise specified. a Not inclusive of all types; patient could have received more than one type

Patient Disposition Olutasidenib Olutasidenib + AZA Characteristic (N = 32) (N = 46) 3 (9) 10 (22) Treatment ongoing, n (%) Discontinued from study treatment, n (%) 29 (91) 36 (78) Transplant (HSCT) 4 (13) 10 (22) Disease progression 12 (38) 11 (24) 1 (3) 5 (11) Investigator decision 1 (3) 0 Permanent withdrawal of consent 5 (16) 4 (9) Death Adverse event 3 (9) 3 (7) Other a 3 (9) 3 (7) 4.2 4.7 Median time on treatment, months a Other reasons include lack of response (for monotherapy and combination therapy groups); entering hospice, and alternative treatments (for combination therapy group)

Nonhematologic TEAEs (> 20%) Regardless of Causality Olutasidenib Olutasidenib + AZA TEAE, n (%) (N = 32) (N = 46) Any Grade Grade 3-4 Any Grade Grade 3-4 Nausea 15 (47) 0 32 (70) 4 (9) Fatigue 14 (44) 2 (6) 18 (39) 8 (17) Pyrexia 11 (34) 2 (6) 11 (24) 0 Diarrhea 8 (25) 1 (3) 21 (46) 2 (4) Pneumonia 8 (25) 5 (16) 8 (17) 5 (11) Vomiting 8 (25) 0 17 (37) 1 (2) Constipation 7 (22) 1 (3) 27 (59) 1 (2) Decreased appetite 7 (22) 0 11 (24) 1 (2) Dizziness 7 (22) 1 (3) 11 (24) 1 (2) Dyspnea 7 (22) 0 14 (30) 1 (2) Hypokalemia 7 (22) 2 (6) 16 (35) 3 (7) Headache 6 (19) 0 15 (33) 1 (2) Cough 5 (16) 0 18 (39) 1 (2) Hypertension 4 (13) 3 (9) 10 (22) 8 (17) Peripheral edema 2 (6) 0 10 (22) 0 Abdominal pain 1 (3) 0 10 (22) 1 (2) Asthenia 1 (3) 0 11 (24) 2 (4)

Hematologic TEAEs (> 20%) Regardless of Causality Olutasidenib Olutasidenib + AZA TEAE, n (%) (N = 32) (N = 46) Any Grade Grade 3-4 Any Grade Grade 3-4 Thrombocytopenia 9 (28) 9 (28) 21 (46) 19 (41) Neutropenia 3 (9) 2 (6) 14 (30) 13 (28) Leukocytosis 7 (22) 4 (13) 12 (26) 7 (15) Anemia 7 (22) 7 (22) 11 (24) 9 (20) Febrile neutropenia 7 (22) 7 (22) 15 (33) 13 (28)

DLTs and AEs of Special Interest • No DLTs observed in the dose escalation cohorts • IDH differentiation syndrome (IDH-DS) • 4 monotherapy patients (13%; grade 3, 3; grade 2, 1) and 6 combination therapy patients (13%; grade 3, 3; grade 2, 1; grade 1, 2) experienced an IDH-DS AE • Most (7) were observed during cycle 1 (2 in cycle 2 and 1 in cycle 5) • All cases resolved with treatment interruption/reduction, dexamethasone, and/or supportive treatment. No recurrences. • 2 of 4 monotherapy patients and 5 of 6 combination therapy patients achieved a response • QT prolongation • 3 combination therapy patients (7%) were reported to have QT prolongation; all events were transient, and patients resumed treatment with no recurrences • Liver • 5 of 32 patients in monotherapy and 5 of 46 patients in combination therapy had grade ≥ 3 LFT (ALT, AST, TB) abnormalities • 2 patients (1 monotherapy and 1 combination therapy) discontinued treatment due to these events

Clinical Response in Patients With AML Monotherapy Combination Therapy T T T T T Response, n (%) R/R TN Response, n (%) R/R TN (n=22) (n=4) (n=26) (n=13) T T T ORR 9 (41) 1 (25) ORR 12 (46) 10 (77) T T CR 4 (18) 0 CR 3 (12) 7 (54) CRh 3 (14) 0 CRh 1 (4) 0 T CRi/MLFS 2 (9) 1 (25) CRi/MLFS 8 (31) 3 (23) T SD 2 (9) 2 (50) SD 9 (35) 2 (15) 0 10 20 30 50 80 110 40 60 70 90 100 120 0 10 20 30 40 50 60 70 80 130 140 150 160 170 Weeks on Study Weeks on Study CR/CRh CRi SD First response T Transplant PD MLFS NE/ND Continuing on study

Survival in AML Median OS (95% CI), weeks 1.0 Monotherapy (R/R) 37.7 (10.7 - NR) Combination (R/R) 52.6 (18.3 - NR) 0.8 Combination (TN) NR (41.6 - NR) Survival Probability 0.6 0.4 Censored Olutasidenib Monotherapy – R/R 0.2 Olutasidenib + AZA Combination – R/R Olutasidenib + AZA Combination – TN 0.0 0 20 40 60 80 100 120 140 160 180 Time (weeks) No. of Subjects at Risk Monotherapy (R/R) 22 13 10 3 1 1 1 1 1 0 Combination (R/R) 26 16 11 6 0 0 0 0 0 0 Combination (TN) 13 11 10 5 3 0 0 0 0 0

Mutational Analysis of AML Patients • Of the 59 patients with AML with both local and central IDH1m results, central testing confirmed the presence of IDH1m at study entry in 56 (95%) of patients • 57 of 59 patients (97%) had ≥ 1 co-mutation and 23 of 59 patients (39%) had ≥ 3 co-mutations IDH1 Variants (Central Determination) Co-mutations Frequency (Central Determination) IDH1-R132L Patients with Mutation (%) IDH1-R132G 60 1 (2%) 3 (5%) 50 IDH1-R132S 40 8 (14%) 30 20 10 0 DNMT3A NPM1 SRSF2 NRAS RUNX1 ASXL1 FLT3 STAG2 IDH2 TET2 SMC1A SF3B1 U2AF1 PHF6 JAK2 MPL NF1 ASXL2 BCOR EED WT1 CBL CSF3R ETNK1 PTPN11 ATM TP53 IDH1-R132C IDH1-R132H 28 (50%) 16 (29%)