Full Press Release Details
Preliminary Data from KOMET-007 - January 30, 2024
WELCOME AND INTRODUCTION Troy Wilson, Ph.D., J.D. - President
& Chief Executive Officer, Kura Oncology
Forward-Looking Statements This presentation contains forward-looking
statements. Such statements include, but are not limited to, statements regarding our research, preclinical and clinical development activities, plans and projected timelines for ziftomenib, tipifarnib and KO-2806, plans regarding regulatory
filings, our expectations regarding the relative benefits of our product candidates versus competitive therapies, our expectations regarding the therapeutic and commercial potential of our product candidates, our expectations regarding our cash
runway, and our expectations regarding our intended use of the net proceeds from the private placement that closed on January 26, 2024. The words "believe," "may," "should," "will,"
"estimate," "promise," "plan", "continue," "anticipate," "intend," "expect," "potential" and similar expressions (including the negative thereof), are
intended to identify forward-looking statements. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Risks that contribute to the
uncertain nature of the forward-looking statements include: our preclinical studies and clinical trials may not be successful; the U.S. Food and Drug Administration (FDA) may not agree with our interpretation of the data from clinical trials of our
product candidates; we may decide, or the FDA may require us, to conduct additional clinical trials or to modify our ongoing clinical trials; we may experience delays in the commencement, enrollment, completion or analysis of clinical testing for
our product candidates, or significant issues regarding the adequacy of our clinical trial designs or the execution of our clinical trials may arise, which could result in increased costs and delays, or limit our ability to obtain regulatory
approval; the commencement, enrollment and completion of clinical trials and the reporting of data therefrom; the COVID-19 pandemic may disrupt our business and that of the third parties on which we depend, including delaying or otherwise disrupting
our clinical trials and preclinical studies, manufacturing and supply chain, or impairing employee productivity; our product candidates may not receive regulatory approval or be successfully commercialized; unexpected adverse side effects or
inadequate therapeutic efficacy of our product candidates could delay or prevent regulatory approval or commercialization; we may not be able to obtain additional financing; risks associated with market conditions and the satisfaction of closing
conditions related to the private placement; risks associated with our cash needs; and risks and uncertainties associated with our business and finances in general. Additional risks and uncertainties may emerge from time to time, and it is not
possible for Kura's management to predict all risk factors and uncertainties. All forward-looking statements contained in this presentation speak only as of the date on which they were made. Other risks and uncertainties affecting us are
described more fully in our filings with the Securities and Exchange Commission. We undertake no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made. This presentation
also contains statistical and clinical data obtained from and prepared by third parties. The recipient is cautioned not to give undue weight to such disclosures. Neither the Company nor any other person makes any representation as to the accuracy or
completeness of such data or undertakes any obligation to update such data after the date of this presentation. 3
Targeting Foundational Mutations has Transformed Deadly Hematologic
Cancers into Chronic Diseases Acute Promyelocytic Leukemia Acute Promyelocytic Leukemia (APL) APL arises from an abnormal fusion protein called PML/RAR , which is mechanistically similar to the menin-KMT2A complex in AML.
ATRA/ATO therapy is a combination treatment of all- trans retinoic acid (ATRA) and arsenic trioxide (ATO). The mechanism of action of ATRA/ATO therapy is differentiation of promyelocytes, immature white blood cells. ATRA/ATO
combinations have fundamentally transformed the treatment of APL. ATRA/ATO combinations demonstrate curative potential with 89% overall survival at 10 Years Gurnari: APL in Children, A Model of Precision Medicine and Chemotherapy-Free Therapy: IJMS
Targeting Foundational Mutations has Transformed Deadly Hematologic
Cancers into Chronic Diseases Multiple Myeloma Until the 2000's, there were few treatment options for multiple myeloma, and the median survival was 2-3 years. With the advent of immunomodulatory drugs (IMiDs) and
proteasome inhibitors (PIs) in the 2000's, the outcomes of patients are now significantly improving. Many patients can now live with their disease > 10 years. IMiDs have become a cornerstone of treatment for patients with
multiple myeloma and are used in combinations at all stages of disease. IMiD combinations increased 5yr OS from 35% to > 65%; class generated ~$15B in revenues at peak Holstein and McCarthy, Drugs (2017) 77(5), 505-520 Bird, S. and Pawlyn, C.
Blood (2023) 142(2): 131-140 5
ZIFTOMENIB OPPORTUNITY AND INTRODUCTION TO KOMET-007 INVESTIGATORS
Stephen Dale, M.D. - Chief Medical Officer, Kura Oncology
Ziftomenib Demonstrates Potential to Become a Cornerstone of AML Therapy
Targets foundational mutations at the core of up to 50% of AML cases Compelling clinical data support frontline opportunity Good tolerability profile, enabling continuous administration in combination with SOC Combinations
appear to mitigate the risk of differentiation syndrome No observed or predicted drug-drug interactions Encouraging preliminary evidence of clinical activity Strong investigator enthusiasm as evidenced by rapid enrollment
across studies First 20 patients enrolled in KOMET-007 combination trial in less than four months KOMET-001 monotherapy registrational trial expected to complete enrollment by mid-2024 7
KOMET-007 Investigators Amir Fathi, M.D. Amer Zeidan, MBBS
Program Director, Center for Leukemia, Interim Chief, Division of Hematologic Massachusetts General Hospital Cancer Center Malignancies, Director of Hematology Early Therapeutics Research, Yale Cancer Center Associate Professor of
Medicine, Harvard Medical School Associate Professor of Medicine (Hematology), Yale University 8
ZIFTOMENIB AS MONOTHERAPY / OPPORTUNITY IN COMBINATION Amir Fathi, M.D.
- Massachusetts General Hospital
KOMET-001 Phase 1/2 Study of Ziftomenib in Relapsed/Refractory AML
Phase 1a Phase 1b Phase 2 Phase 1b Dose Escalation Expansion Registration-Enabling Validation Cohorts (Ongoing) Completed Completed Completed Ongoing Expansion of 600 mg QD Cohort 1: 200 mg QD 50 mg 100 mg 1000 mg 600 mg QD QD QD QD Cohort 2: 600 mg
QD NPM1-m, KMT2A-r, Other NPM1-m NPM1-m NPM1-m or KMT2A-r OBJECTIVES Safety and tolerability Continue enrollment of Phase Primary endpoint: Safety and tolerability CR/CRh Pharmacokinetics 1b validation
cohort(s) Pharmacokinetics Early evidence of antitumor consistent with FDA's Project Clinical activity Secondary endpoints: activity Optimus Duration of CR/CRh Safety and tolerability
Transfusion independence Pharmacokinetics CR/CRh MRD negativity Adverse events Clinical activity CR, complete remission; CRh, complete remission with partial hematological recovery; FDA, United States Food and Drug
Administration; MRD, measurable residual disease; R/R, relapsed/refractory; RP2D, recommended phase 2 dose. 10 ~ ~
Dose-Proportional Increase in Ziftomenib Exposure Supports 600 mg Dose
AUC = area under the curve 11
Ziftomenib Demonstrates Encouraging Safety Profile in Phase 1b
Differentiation syndrome (DS) appears manageable in NPM1-m monotherapy patients with mitigation strategy 20% rate of mild to moderate DS Rates of DS in KMT2A-r monotherapy patients were 38.5% at 200 mg and 37.5% at 600 mg; potential
to mitigate in combination DS is an on-target AE and represents evidence of clinical activity No reports of drug-induced QTc prolongation Maintained count recovery suggests no drug-induced myelosuppression Fathi et al. EHA
2023 #LB2713 (preliminary data as of April 12, 2023) 12
Ziftomenib has Highly Differentiated Monotherapy Activity Best Overall
Response 600 mg Differentiated CR Rates vs. SOC in NPM1-m Phase 1a + 1b (n=20) 40% of NPM1 Heavily Pretreated Patients patients CR 7 (35.0) achieved a MEDIAN CR/CRh 7 (35.0) MUTATION CR % mDOR CR during PRIORS course of CRc 8 (40.0) NPM1m 8.2 mo*
35% study Ziftomenib 1 MRD negativity 4(50.0) FLT3m - 3 33% 600mg QD IDH 1/2 - 50% ORR 9 (45.0) Gilteritinib FLT3m 14.2% 14.8 mo 1 KMT2A-r Phase 1a + 1b (n=18) Enasidenib IDH2 19% 8.2 mo 2 CR/CRh 2 (11.1) Ivosidenib IDH1 25% 10.1 mo 2 CRc 3 (16.7)
*Median DoR for CRc without censoring at HSCT MRD negativity 3 (100.0) Source: USPI's ORR 3 (16.7) (preliminary data as of April 10, 2023) High activity, durable responses and favorable profile suggest potential for ziftomenib to become
a backbone therapy across the continuum of AML care 1 MRD was assessed for 6/8 CRc patients; 4 of those 6 patients (67%) tested were MRD negative 13 CRc includes CR, CRh, CRi, CRp; ORR includes CR, CRh, CRi, CRp, MLFS
Maximizing the Therapeutic Value of Menin Inhibitors Will Come Through
Combinations Clinical Activity - Enhanced relative to SOC Pharmacoeconomic Benefit - Safety/Tolerability - Minimal Fewer requirements for monitoring additive toxicity over SOC and hospitalization Quality of Life - Fewer
Drug-Drug Interactions - Minimal to none concomitant meds, less toxicity Resistance - Potential to address Synergistic MOA - Ideally, additive / innate and adaptive resistance to SOC synergistic to SOC MRD - Potential to
achieve greater depth of response Holstein and McCarthy, Drugs 77(5), 505-520 (2017); 14 Bird, S. and Pawlyn, C. Blood (2023) 142(2): 131-140
PRELIMINARY COMBINATION DATA FROM KOMET-007 TRIAL Amer Zeidan, MBBS
- Yale Cancer Center Disclosure: Honoraria or consultation fees provided by Kura Oncology
KOMET-007: Phase 1 Combination Trial of Ziftomenib in Patients with
Newly Diagnosed or R/R AML Ziftomenib/cytarabine/daunorubicin (7+3) combination Ziftomenib dosing will begin on Cycle 1 Day 8 and be administered continuously thereafter Cytarabine will be administered on C1 Day 1-7; administration
of an additional cycle based on C1 bone marrow biopsy results Daunorubicin will be administered on C1 Day 1- 3; administration of an additional cycle based on C1 bone marrow biopsy results Dose escalation conducted in patients with
adverse risk* *Age > 60 years and/or treatment-related AML and/or adverse risk cytogenetics per ELN 16 DL = ziftomenib dose level; zifto = ziftomenib; 7+3 = cytarabine/daunorubicin; RP2D = recommended Phase 2 dose; 1L = first-line; IC = intensive
KOMET-007: Phase 1 Combination Trial of Ziftomenib in Patients with
Newly Diagnosed or R/R AML Ziftomenib/venetoclax/azacitidine combination Ziftomenib dosing will begin on Cycle 1 Day 8 and be administered continuously thereafter Venetoclax will be administered per label in 28-day cycles with
adjustments to cycle length based on C1 bone marrow biopsy results Azacitidine will be administered per label on C1 Day 1-7 of each cycle with additional cycles based on bone marrow biopsy results DL = ziftomenib dose level; zifto =
ziftomenib; ven = venetoclax; ven = venetoclax; RP2D = recommended Phase 2 dose; NIC = non-intensive chemotherapy; 17 1L = first-line; R/R = relapsed/refractory
KOMET-007: Patient Demographics and Disposition First 20 Patients
Enrolled Relapsed/refractory patients with NPM1-m or KMT2A-r AML in combination with venetoclax/azacitidine Newly-diagnosed patients with adverse risk* NPM1-m or KMT2A-r AML in combination with cytarabine/daunorubicin (7+3)
80% (16/20) of patients remain on trial as of January 11, 2024, including 100% of patients with NPM1-m AML Cohorts R/R NPM1-m 1L NPM1-m R/R KMT2A-r 1L KMT2A-r Ven/Aza 7+3 Ven/Aza 7+3 All Age, years (Median, range) 55.5 (23, 77) 55.0 (41, 77) 65.5
(43, 74) 52.5 (23, 71) 49.0 (49, 49) 13 (65) 4 (57) 2 (50) 6 (75) 1 (100) Female (n, %) Genetic Subtypes [n (%)] NPM1-m 11 (55) 7 (100) 4 (100) N/A N/A KMT2A-r 9 (45) N/A N/A 8 (100) 1 (100) ECOG PS [n (%)] 0 4 (20) 1 (14) 3 (75) 0 0 1 11 (55) 5
(71) 0 5 (63) 1 (100) 2 5 (25) 1 (14) 1 (25) 3 (38) 0 Prior Therapies (Median, Range) N/A 2 (1,12) 0 2 (1,6) 0 Prior Antineoplastic Therapy [n (%)] Stem Cell Transplant 7 (47) 4 (57) N/A 3 (38) N/A Hypomethylating Agent (HMA) 8 (53) 4 (57) N/A 4
(50) N/A Venetoclax 10 (67) 5 (71) N/A 5 (63) N/A Menin Inhibitors 6 (40) 2 (29) N/A 4 (50) N/A Preliminary data as of January 11, 2024 18 *Age > 60 years and/or treatment-related AML and/or adverse risk cytogenetics per European LeukemiaNet
KOMET-007: Promising Safety and Tolerability Profile in Combination
Combinations mitigate risk of differentiation syndrome (DS) Grade 3 TEAEs ( 10%) n (%) Grade 3 Ziftomenib-Related AEs (All) n (%) Patients with Grade 3 TEAEs 18 (90) Patients with Grade 3 Ziftomenib-Related AEs
6 (30) Platelet count decreased 6 (30) Platelet count decreased 3 (15) Febrile neutropenia 5 (25) Anemia 1 (5) White blood cell count decreased 4 (20) Febrile neutropenia 1 (5) Pneumonia 3 (15) Leukopenia 1 (5) Hypoxia 2 (10) Neutrophil count 1 (5)
Neutrophil count decreased 2 (10) Thrombocytopenia 1 (5) Sepsis 2 (10) Thrombocytopenia 2 (10) No DS events reported No dose-limiting toxicities (DLTs) observed to date, including delayed hematologic count recovery No QTc
prolongation observed TEAEs consistent with underlying disease and backbone therapies Preliminary data as of January 11, 2024 19 TEAEs = Treatment-emergent adverse events
100% CR rate with Ziftomenib and 7+3 in 1L Patients with Adverse-Risk
AML* 1,2 Anticipated CR/CRi rate with 7+3 in all-comer 1L adverse risk patients: 32-33% 1L Adverse-Risk Group CR Rate n=5 (n) Overall (NPM1-m + KMT2A-r) 100% (5) NPM1-m only (n=4) 100% (4) KMT2A-r only (n=1) 100% (1) All patients
treated in initial dose cohort (200 mg) in combination with 7+3 Preliminary data as of January 11, 2024 1 Lancet et al. Blood. 2014 May 22;123(21):3239-46. 2 Lin et al. Blood Adv. 2021 Mar 23;5(6):1719-1728. 20 *Age > 60 years and/or
treatment-related AML and/or adverse risk cytogenetics per ELN
Ziftomenib + Ven/Aza with Pronounced Activity in Menin Inhibitor
Na ve Patients 1 ~35-45% CR/CRi is expected in ven-na ve relapsed/refractory patients 2 Anticipated response rate in KMT2A-r relapsed/refractory AML <10% ORR 53% ORR in mITT population (n=15, including six menin
experienced patients) 40% (6/15) of patients treated with ven/aza received prior treatment with a menin inhibitor Menin Inhibitor Na ve Group ORR CR/CRi Rate CR/CRh Rate n=9 (n) (n) (n) Overall (NPM1-m + KMT2A-r) 78% (7) 67% (6) 56% (5)
NPM1-m (n=5) 100% (5) 80% (4) 60% (3) KMT2A-r (n=4) 50% (2) 50% (2) 50% (2) All patients treated in initial dose cohort (200 mg) in combination with Ven/Aza Enrollment in 400 mg dose cohort ongoing Preliminary data as of January 11,
2024 1 Stahl, M. et al., Blood Advances 5(5), 1552-1564 (2021) 2 Issa, Syndax ASH Investor Event (Dec. 2023) 21 ORR includes CR, CRh, CRi, MLFS
Ziftomenib + Ven/Aza Able to Drive Responses in Venetoclax Failures 1-4
Expected response rates following ven/aza ~ 0-20% 4 Anticipated response rate in KMT2A-r R/R AML < 10% ORR Venetoclax Experienced Group ORR CR/CRi Rate CR/CRh Rate n=10 (n) (n) (n) Overall (NPM1-m + KMT2A-r) 40% (4) 30% (3) 30%
(3) NPM1-m (n=5) 60% (3) 40% (2) 40% (2) KMT2A-r (n=5) 20% (1) 20% (1) 20% (1) All patients treated in initial dose cohort (200 mg) in combination with Ven/Aza Enrollment in 400 mg dose cohort ongoing Preliminary data as of January
11, 2024 1 Zainaldin, C. et al., Lymphoma 63(13):3245-3248 (2022); 2 Chan, O. and Walker, A., Hematology 702-708 (2023); 3 Maiti A, et al., Haematologica. 2021; 106(3):894-898; 4 Issa, Syndax ASH Investor Event (Dec. 2023) 22 ORR includes CR, CRh,
Continued Use of Ziftomenib Following Successful Induction with 7+3
HSCT ziftomenib CR 7+3 WEEK 0 1 6 23 CYT Cohort: Frontline Ongoing post-HSCT DAU NPM1-m 7+3 ZIFTO Patient Characteristics CR after one cycle of induction (week 5-6) Demographics 66-year-old female Mutational profile NPM1m, CBL, IDH2, NRAS,
SRSF2 Maintained ziftomenib from induction through consolidation until conditioning for transplant (~5 months) Baseline bone marrow blasts 77% Post-transplant ziftomenib maintenance planned Best overall response CR Preliminary data
as of January 11, 2024 23 ~ ~
Ziftomenib Combinations Are Effective in Treating Aggressive Disease