Kura Oncology, Inc. · NASDAQ:KURA
Kura Oncology — Q4 2024 Earnings Presentation
66 slides from Kura Oncology's earnings presentation, Feb 26, 2025
Slide 1: Corporate Presentation
CORPORATE PRESENTATION Our goal is to develop transformative therapies to extend and improve the lives of patients with cancer February 2025
Slide 2: Forward-Looking Statements
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, KO-2806 and tipifarnib, plans regarding
Slide 3: Kura is Advancing a Robust Pipeline of Therapeutic Product Candidates
KURA IS Ziftomenib: Potentially Best-in-Class Menin Inhibitor for AML ADVANCING Relapsed/refractory (R/R) and frontline acute myeloid Positive topline results from KOMET-001 study Kyowa Kirin collaboration funds expansive AML development A ROBUST leukemia (AML) market opportunity could exceed in R/R
Slide 4: Experienced Leadership Team and Board of Directors
Board of EXPERIENCED Directors LEADERSHIP TROY WILSON, PH.D., J.D. TEAM AND Chairman BOARD OF Troy Wilson, Ph.D., J.D. President & Chief Teresa Bair, J.D. Chief Legal Officer Francis Burrows, Ph.D. Chief Scientific Officer FAHEEM HASNAIN Lead Independent Director DIRECTORS Executive Officer HELEN CO
Slide 5: Maximize Value of Robust Therapeutic Pipeline
MAXIMIZE VALUE OF ROBUST THERAPEUTIC PIPELINE PROGRAM CLINICAL TRIAL RESEARCH DOSE ESCALATION DOSE OPTIMIZATION REGISTRATION-ENABLING REGULATORY SUBMISSION NPM1-mutant acute myeloid leukemia (AML)1 KMT2A-rearranged acute lymphoblastic leukemia (ALL) Monotherapy Non-NPM1-mutant / Non-KMT2A-rearranged
Slide 6: Anticipated Upcoming Milestones: Several Expected 2025 Data Read-outs
ANTICIPATED UPCOMING MILESTONES: SEVERAL EXPECTED 2025 DATA READ-OUTS ACROSS MULTIPLE PROGRAMS Ziftomenib Report topline results from KOMET-001 Phase 2 registration-directed trial in R/R NPM1-m AML FDA feedback on KOMET-017 registration-enabling protocol in 1L NPM1-m and KMT2A-r intensive and non-
Slide 7: Financial Highlights
FINANCIAL HIGHLIGHTS (NASDAQ: KURA) Cash, Cash Equivalents Anticipated Significant Shares and Marketable Securities Near-Term Milestones Outstanding $727.4M $420M 78.2M in potential near-term in cash, cash equivalents 24.3M options, RSUs, milestones, including and short-term investments PSUs, warran
Slide 8: Ziftomenib
MENIN AML GIST DIABETES ZIFTOMENIB POTENT, SELECTIVE MENIN INHIBITOR Targeted Investigational Menin Inhibitor for Newly Diagnosed and Relapsed/Refractory Acute Myeloid Leukemia (AML)
Slide 9: Up to 50% of AML Patients May Benefit from Menin Inhibitor Therapy
MENIN AML UP TO 50% OF AML PATIENTS MAY BENEFIT FROM MENIN PREVALENCE OF INHIBITOR THERAPY ZIFTOMENIB-ELIGIBLE PATIENTS AML is characterized by significant genetic Other mutations heterogeneity due to driver mutations, including NPM1m, FLT3m, IDH1/2m and KMT2A-r KMT2Ar 1-2 10-15% 5-10% Up to 50% of
Slide 10: Significant Unmet Need Remains for AML Patients
MENIN AML SIGNIFICANT UNMET NEED REMAINS FOR AML PATIENTS Acute Myeloid Leukemia (AML) Up to 70% of patients An estimated 20,800 new cases of AML diagnosed each year in the United States1 70% who achieve a first CR will see AML return within 3 years3 Median age at diagnosis is 69 years; majority of
Slide 11: Ziftomenib Targets the Menin Pathway, a Foundational Target in AML
MENIN AML ZIFTOMENIB TARGETS THE MENIN PATHWAY, A FOUNDATIONAL TARGET IN AML In ~35–40% of AML, leukemogenesis KMT2A (MLL) and NPM1 sit Inhibiting the menin-KMT2A is driven by either NPM1 mutations or upstream from major AML complex downregulates KMT2A rearrangements,1,2 which targets (i.e., FLT3, B
Slide 12: Investigating Ziftomenib Across the AML Continuum
MENIN AML INVESTIGATING ZIFTOMENIB ACROSS THE AML CONTINUUM IN UP TO 50% OF PATIENTS for Whom Menin-KMT2A Pathway is a Disease Driver 1L TREATABLE RELAPSED / REFRACTORY Targeted Tx if Non-Intensive Intensive (IC) or Non- Transplant/ Post-Transplant IC or NIC Tx or Transplant/ FLT3m, IDH1/2m therapy/
Slide 13: Significant Unmet Need for Newly Diagnosed AML Patients
MENIN FRONTLINE AML SIGNIFICANT UNMET NEED FOR NEWLY DIAGNOSED AML PATIENTS IN FIT AND UNFIT PATIENT POPULATIONS 1L FIT AML 1L UNFIT AML Many patients who are eligible to receive intensive Venetoclax/azacitidine (ven/aza) is the standard of chemotherapy (IC) are treated with an expectation care for
Slide 14: Phase 1 Combination Trial of Ziftomenib in Newly Diagnosed AML
MENIN FRONTLINE AML PHASE 1 COMBINATION TRIAL OF ZIFTOMENIB IN PATIENTS WITH NEWLY DIAGNOSED AML Ziftomenib/cytarabine/daunorubicin (7+3) combination Ziftomenib dosing begins Cytarabine administered on Daunorubicin administered on Dose escalation conducted in on Cycle 1 Day 8 and is Cycle 1 Day 1-7;
Slide 15: Phase 1 Combination Trial of Ziftomenib in Newly Diagnosed or R/R AML
MENIN FRONTLINE AML PHASE 1 COMBINATION TRIAL OF ZIFTOMENIB IN PATIENTS WITH NEWLY DIAGNOSED OR R/R AML Ziftomenib/venetoclax/azacitidine (Ven/Aza) combination Ziftomenib dosing begins on Cycle 1 Venetoclax administered per label Azacitidine administered per label on Day 8 and is continuous thereaft
Slide 16: Baseline Characteristics & Disposition
MENIN FRONTLINE AML BASELINE CHARACTERISTICS & DISPOSITION 1L AML (N=51) NPM1-m KMT2A-r All Patients 200 mg 400 mg 600 mg Total 200 mg 400 mg 600 mg Total (N=51) (n=8) (n=7) (n=9) (n=24) (n=10) (n=9) (n=8) (n=27) Median age, years (range) 60 (18–74) 65 (43–74) 66 (55–68) 66 (60–68) 66 (43–74) 53 (31
Slide 17: Safety and Tolerability of Ziftomenib with 7+3 in 1L AML
MENIN FRONTLINE AML SAFETY AND TOLERABILITY OF ZIFTOMENIB WITH 7+3 IN 1L AML (N=51) TEAEs in ≥ 30% of All Patients NPM1-m KMT2A-r All 200 mg 400 mg 600 mg Total 200 mg 400 mg 600 mg Total Patients (n=8) (n=7) (n=9) (n=24) (n=10) (n=9) (n=8) (n=27) TEAEs, n (%) (N=51) Safety profile of Any Grade 48 (
Slide 18: Safety and Tolerability of Ziftomenib with 7+3 in 1L AML (Grade ≥3)
MENIN FRONTLINE AML SAFETY AND TOLERABILITY OF ZIFTOMENIB WITH 7+3 IN 1L AML (N=51) Grade ≥3 TEAEs in ≥ 10% of All Patients NPM1-m KMT2A-r All 200 mg 400 mg 600 mg Total 200 mg 400 mg 600 mg Total Patients (n=8) (n=7) (n=9) (n=24) (n=10) (n=9) (n=8) (n=27) TEAEs, n (%) (N=51) One case (2%) of Gr3 Gr
Slide 19: Clinical Activity in All Response-Evaluable 1L Patients
MENIN FRONTLINE AML CLINICAL ACTIVITY IN ALL RESPONSE-EVALUABLE* 1L PATIENTS (N=46) Historically, only 33% of 7+3 treated newly diagnosed, adverse-risk AML patients achieve CRc, with a median overall survival of ~6 months1-2 NPM1-m KMT2A-r All Patients 200 mg 400 mg 600 mg Total 200 mg 400 mg 600 mg
Slide 20: 60-Yr-Old Female with Newly Diagnosed NPM1-m AML Treated with Ziftomenib and 7+3
MENIN FRONTLINE AML 60-YR-OLD FEMALE WITH NEWLY DIAGNOSED NPM1-m AML TREATED WITH ZIFTOMENIB Screening marrow: blasts 8%, CD34– NPM1+ (IHC), NPM1 AND 7+3 PCR 38% Day 21 marrow: 30% morphologic blasts, but now CD34+ NPM1– (IHC), NPM1 PCR 0.08% Days 22–24: Platelet count recovering, decision to hold o
Slide 21: Preliminary Clinical Outcomes in 1L NPM1-m AML Patients
MENIN FRONTLINE AML PRELIMINARY CLINICAL OUTCOMES IN 1L NPM1-m AML PATIENTS 200 mg For NPM1-m, after a median follow-up of 31 weeks (range 17–63): Median duration of CR was not reached 400 mg Median OS was not reached 5 NPM1-m patients received HSCT (200 mg n=3, 400 mg n=2); 2 went onto ziftomenib m
Slide 22: Preliminary Clinical Outcomes in 1L KMT2A-r AML Patients
MENIN FRONTLINE AML PRELIMINARY CLINICAL OUTCOMES IN 1L KMT2A-r AML PATIENTS 200 mg For KMT2A-r, after a median follow-up of 19 weeks (range 2–43): Median duration of CR was not reached 400 mg Median OS was not reached 10 KMT2A-r patients received HSCT (200 mg n=6, 400 mg n=3, 600 mg n=1); 5 went on
Slide 23: ANC and Platelet Recovery in CRc Responders
MENIN FRONTLINE AML ABSOLUTE NEUTROPHIL COUNT (ANC) AND PLATELET RECOVERY IN CRc RESPONDERS Higher ziftomenib doses did not impact or delay NPM1-m + KMT2A-r neutrophil and platelet count recovery 200 mg 400 mg 600 mg (n=17) (n=13) (n=12) Median (range) Days to ANC ≥ 0.5x109/L, Cycle 1 32 (20–40) 27
Slide 24: Conclusions from Ongoing KOMET-007 Study
MENIN FRONTLINE AML CONCLUSIONS FROM ONGOING KOMET-007 STUDY Ziftomenib combined Robust clinical activity We believe these data with 7+3 was well was demonstrated in both support advancement of tolerated across all dose NPM1-m and KMT2A-r ziftomenib with 7+3 in all 1L levels subtypes NPM1-m and KMT2
Slide 25: KOMET-017: Two Phase 3 Trials Under a Single Protocol
MENIN FRONTLINE AML KOMET-017 TWO PHASE 3 TRIALS UNDER A SINGLE PROTOCOL Provides Treatment Options to the Broadest Frontline AML Patient Pool KOMET-017-NIC KOMET-017-IC (NON-INTENSIVE COMBINATION) (INTENSIVE COMBINATION) ARM A Ziftomenib Ziftomenib 7+3 Induction Consolidation Venetoclax + Azacitidi
Slide 26: Non-Intensive Chemotherapy (NIC) Trial
MENIN FRONTLINE AML NON-INTENSIVE CHEMOTHERAPY (NIC) TRIAL Randomized, Double-Blind, Placebo-Controlled Study: Venetoclax + Azacitidine + Ziftomenib or Placebo Patient Population Ziftomenib AML with NPM1 mutation Venetoclax + Azacitidine Age 75+ or < 75 with medical comorbidities Randomized Non-Inte
Slide 27: Non-Intensive Chemotherapy (NIC) Trial: FDA Aligned on Modified Venetoclax Dosing
MENIN FRONTLINE AML NON-INTENSIVE CHEMOTHERAPY (NIC) TRIAL FDA Aligned Around Modified Venetoclax Dosing Regimen • Known myelosuppression with venetoclax + azacitidine from indicated dose and schedule has evolved in current clinical practice • Standard practice has moved towards minimizing venetocla
Slide 28: Intensive Chemotherapy (IC) Trial
MENIN FRONTLINE AML INTENSIVE CHEMOTHERAPY (IC) TRIAL Randomized, Double-Blind, Placebo-Controlled Study: 7+3/Consolidation + Ziftomenib or Placebo PROPOSED 3-ARM DESIGN TO CAPTURE MAINTENANCE INDICATION IN THE LABEL FOR NEWLY DIAGNOSED AML Primary Endpoints ARM A Ziftomenib CRMRD- 7+3 Induction Con
Slide 29: Intensive Chemotherapy (IC) Trial: Importance of the CRMRD- Endpoint
MENIN FRONTLINE AML INTENSIVE CHEMOTHERAPY (IC) TRIAL Importance of the CRMRD- Endpoint • Published data suggest CR MRD- may correlate better with long-term survival than morphologic CR alone • Literature highlights significant impact of NPM1-m MRD negativity on long-term survival and the implicatio
Slide 30: Ziftomenib Market Potential in Newly Diagnosed AML
MENIN FRONTLINE AML ZIFTOMENIB MARKET POTENTIAL IN NEWLY DIAGNOSED AML High Unmet Large Population & Potential Expansive Medical Need for Sustained Benefit Market Opportunity of patients who Potential for benefit Potential peak 12-24 Newly-diagnosed $36-40k Analog pricing, ~70% achieve a first CR wi
Slide 31: Ziftomenib Market Potential in Newly Diagnosed AML
MENIN FRONTLINE AML ZIFTOMENIB MARKET POTENTIAL IN NEWLY DIAGNOSED AML High Unmet Large Population & Potential Expansive Medical Need for Sustained Benefit Market Opportunity of patients who Potential for benefit Potential peak 12-24 Newly diagnosed $36-40k Analog pricing, ~70% achieve a first CR wi
Slide 32: Phase 1/2 Study of Ziftomenib in Relapsed/Refractory AML
MENIN R/R AML PHASE 1/2 STUDY OF ZIFTOMENIB IN RELAPSED/ REFRACTORY AML PHASE 1A PHASE 1B PHASE 1B PHASE 1B Dose Escalation Validation Cohorts Validation Cohorts Expansion Completed Completed Completed Enrollment Completed Expansion of 600 mg QD 50 mg 100 mg Cohort 1: 200 mg QD 1000 mg 600 mg ~ ~ QD
Slide 33: Ziftomenib Demonstrates Optimal Pharmaceutical Properties
MENIN R/R AML ZIFTOMENIB DEMONSTRATES OPTIMAL PHARMACEUTICAL PROPERTIES Ziftomenib demonstrates a dose-dependent increase in exposure up to RP2D at 600 mg Mean AUClast (ng/mL*hr) Ziftomenib is not a clinically meaningful CYP3A4 substrate • No dose adjustment of ziftomenib needed when administered wi
Slide 34: Ziftomenib Demonstrates Encouraging Safety Profile in Phase 1
MENIN R/R AML ZIFTOMENIB DEMONSTRATES ENCOURAGING SAFETY PROFILE IN PHASE 1 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 42.9% at 200 mg and 38.9% at 600 mg;
Slide 35: Ziftomenib Demonstrates Meaningful Clinical Activity as Monotherapy
MENIN R/R AML ZIFTOMENIB DEMONSTRATES MEANINGFUL CLINICAL ACTIVITY AS MONOTHERAPY Best Overall Response 600 mg DIFFERENTIATED CR RATES VS. SOC IN HEAVILY PRETREATED PATIENTS NPM1-m Phase 1a + 1b (n=20) 40% of NPM1-m CR 7 (35.0) MEDIAN patients MUTATION CR % mDOR PRIORS achieved CR/CRh 7 (35.0) a CR
Slide 36: Conclusions from KOMET-001 Phase 1 Clinical Trial
MENIN R/R AML CONCLUSIONS FROM KOMET-001 PHASE 1 CLINICAL TRIAL Ziftomenib displays an Clinical activity of Monotherapy encouraging safety ziftomenib monotherapy is data supportive and tolerability profile optimal at the of combination strategies 600 mg daily dose Reported events most often Positive
Slide 37: Ziftomenib Market Potential in R/R AML
MENIN R/R AML ZIFTOMENIB MARKET POTENTIAL IN R/R AML High Unmet Need in R/R Potential for Sustained Attractive NPM1-m AML Treatment Market Opportunity 20% 20% are primary ~6 mo Potential for safe and refractory; ~50% will Duration of well-tolerated ~50% relapse who achieved an initial CR1-5 Treatmen
Slide 38: Kyowa Kirin Strategic Collaboration
KYOWA KIRIN STRATEGIC COLLABORATION MAXIMIZING THE VALUE OF ZIFTOMENIB IN AML 38
Slide 39: Strategic Collaboration with Kyowa Kirin Positions Kura to Unlock Full Value of Ziftomenib
STRATEGIC Complementary expertise and vision to capitalize COLLABORATION on the full potential of ziftomenib in AML WITH KYOWA KIRIN POSITIONS Kura retains leadership and key strategic rights to ziftomenib in the U.S. to preserve strategic flexibility KURA TO UNLOCK THE FULL VALUE Enables broad deve
Slide 40: Summary of Collaboration Terms
SUMMARY OF SCOPE Broad development & commercialization of ziftomenib in acute leukemias, including both fit and unfit 1L indications, post-transplant COLLABORATION maintenance setting and combinations with targeted therapies TERMS UPFRONT PAYMENT Kura received $330M upon closing NEAR-TERM MILESTONES
Slide 41: Menin Inhibitor in GIST
MENIN AML GIST DIABETES ZIFTOMENIB MENIN INHIBITOR IN GIST Targeted Investigational Menin Inhibitor in Combination with Imatinib for Treatment of Gastrointestinal Stromal Tumors (GIST)
Slide 42: Significant Unmet Need Remains for GIST Patients
MENIN GIST SIGNIFICANT UNMET NEED REMAINS FOR GIST PATIENTS Gastrointestinal Stromal Tumor (GIST) Tumors can start anywhere in the GI tract, 4,000- Number of GIST cases diagnosed in but they occur most often in the stomach 6,000 the U.S. each year1 (about 60%) or the small intestine (about 35%) case
Slide 43: A Unique Opportunity for Ziftomenib in GIST
MENIN GIST A UNIQUE OPPORTUNITY FOR ZIFTOMENIB IN GIST SIGNALING PATHWAYS OF KIT-MUTATED GIST1 Ziftomenib + imatinib combination treatment showed robust antitumor activity in GIST PDX models representing the full GIST treatment continuum Ziftomenib + imatinib exerts antitumor activity by a synthetic
Slide 44: Ziftomenib Offers Potential to Shift the Treatment Paradigm in GIST
ZIFTOMENIB OFFERS POTENTIAL TO SHIFT THE TREATMENT PARADIGM IN GIST Ziftomenib may overcome resistance to imatinib ORR ~ ORR ~ 7% ORR ~ 5% ORR ~ 9% 60% 1L 2L 3L 4L PFS ~ 6 PFS ~ 4.8 PFS ~ 6.3 PFS ~ 19 months months months months Imatinib Sunitinib Regorafenib Ripretinib 1L Market Opportunity: 2L Mar
Slide 45: Ziftomenib + Imatinib Displays Durable Antitumor Activity in 1L GIST PDX Model
MENIN GIST ZIFTOMENIB + IMATINIB COMBINATION DISPLAYS DURABLE ANTITUMOR ACTIVITY IN 1L GIST PDX MODEL Imatinib monotherapy was tumoristatic, but the ziftomenib + imatinib combination induced deep regressions in all animals, including some CRs Cessation of dosing resulted in rapid regrowth in imatini
Slide 46: Ziftomenib and TKIs Synergize in Imatinib-Resistant PDX Models
MENIN GIST ZIFTOMENIB AND TKIs SYNERGIZE IN IMATINIB- RESISTANT PDX MODELS Robust and durable responses seen GS11331, KIT Ex11 del and V654A vehicle in Ex13 GIST PDX model with combo 2500 dosing stopped ziftomenib 2000 imatinib Mean TV (mm3) zifto + Both TKIs synergized with ziftomenib, 1500 imatini
Slide 47: Ziftomenib and TKIs Synergize in Imatinib-Resistant PDX Models
MENIN GIST ZIFTOMENIB AND TKIs SYNERGIZE IN IMATINIB- RESISTANT PDX MODELS Ziftomenib-imatinib combination antitumor activity is independent of KIT mutation type SYNTHETIC LETHAL ACTIVITY OBSERVED IN IMATINIB-RESISTANT EX17 GIST PDX MODELS GS5106, KIT/K642E, Y822K vehicle GS5108, homozygous KIT/Y823
Slide 48: Ziftomenib Market Potential in GIST
MENIN GIST ZIFTOMENIB MARKET POTENTIAL IN GIST Meaningful Potential for Attractive Unmet Need Sustained Benefit Market Opportunity Potential for ~4-6K Newly diagnosed cases of GIST each 24+ benefit / risk to $500M months support sustained year in the U.S.1 treatment -$1B peak Patients who Analog pri
Slide 49: Menin Inhibitors for Treatment of Diabetes
MENIN AML GIST DIABETES MENIN INHIBITORS FOR TREATMENT OF DIABETES Targeted Investigational Menin Inhibitor for Treatment of Diabetes
Slide 50: Diabetes Represents a Disease Epidemic
MENIN DIABETES PREVALENCE DIABETES REPRESENTS 38.4 million adults (11.6%) in the United States have diabetes • 29.7 million adults have diagnosed diabetes A DISEASE EPIDEMIC • 8.7 million adults have undiagnosed diabetes 97.6 million adults in the U.S. have prediabetes DIABETES AND PANCREATIC BETA-C
Slide 51: Menin Inhibitors Offer Unique Attributes for Diabetes
MENIN DIABETES MENIN INHIBITORS OFFER UNIQUE ATTRIBUTES FOR DIABETES Impact both insulin deficiency and insulin resistance Potential for a first-in-class regenerative medicine that can restore β-cell mass and improve insulin resistance Proof-of-concept studies with ziftomenib showed: • Effects on fa
Slide 52: Ziftomenib Reduces Blood Glucose and HbA1c in ZDF Rat Model
MENIN DIABETES ZIFTOMENIB REDUCES BLOOD GLUCOSE AND HbA1C LEVELS AND IMPROVES INSULIN SENSITIVITY IN ZDF RAT MODEL OF TYPE 2 DIABETES 4h fasting blood glucose HOMA-IR 35 500 30 400 25 *** **** HOMA-IR BG (mM) 20 **** 300 **** 15 **** 200 ns ns ns **** ns 10 **** **** 7 100 ** 5 **** **** *** 0 0 0 1
Slide 53: Ziftomenib Stimulates Insulin Production
MENIN DIABETES ZIFTOMENIB STIMULATES INSULIN PRODUCTION Ziftomenib significantly increased serum insulin levels and serum c-peptide levels, indicating significant improvement to steady-state β-cell function 4h fasting Insulin c-peptide on Day27 HOMA-B 5000 25 *** **** ns **** 2500 ns 4000 ns c-pepti
Slide 54: Ziftomenib Stimulates β-Cell Proliferation in Human Pancreatic Islet Microtissues
MENIN DIABETES ZIFTOMENIB STIMULATES β-CELL PROLIFERATION WITH MINIMAL EFFECTS ON NON-β-CELLS IN HUMAN PANCREATIC ISLET MICROTISSUES Ziftomenib stimulated the proliferation of β-cells specifically in donor samples • Ziftomenib: 1x (nM) or 5x (nM) • Harmine: 10 µM (effects are expected to be the same
Slide 55: Ziftomenib Treatment Restored β-Cell Mass in ZDF Rat Pancreas
MENIN DIABETES TAILS OF PANCREAS, DAPI + INSULIN Zifto Zucker-lean ZIFTOMENIB Vehicle TREATMENT RESTORED β-CELL MASS IN ZDF RAT PANCREAS INSULIN+ AREAS EXPANDED AFTER 42 DAYS OF ZIFTOMENIB TREATMENT ns; not significant; *, p<0.05; **; p<0.01, ***, p<0.005; ****, p<0.001 55
Slide 56: Menin Inhibition for Diabetes Development Plan
MENIN DIABETES MENIN INHIBITION FOR DIABETES DEVELOPMENT PLAN REPORT PRECLINICAL DATA HIGHLIGHTING POTENTIAL FOR MENIN INHIBITORS IN DIABETES NOMINATE NEXT-GEN MENIN INHIBITOR DEVELOPMENT CANDIDATE FOR EVALUATION IN DIABETES INITIATE IND-ENABLING STUDIES FOR DEVELOPMENT CANDIDATE FILE IND APPLICATIO
Slide 57: KO-2806: A Potent, Selective Companion Inhibitor to Targeted Therapies
KO-2806 A POTENT, SELECTIVE COMPANION INHIBITOR TO TARGETED THERAPIES Class-leading drug candidate to address innate and adaptive resistance to various classes of targeted therapies
Slide 58: Resistance Remains a Challenge for Many Classes of Targeted Therapies in Cancer
DESPITE ADVANCES, RESISTANCE REMAINS A CHALLENGE FOR MANY CLASSES OF TARGETED THERAPIES IN CANCER • Persistent mTORC1 activity seems to be a frequent and consistent non-genetic driver of inherent and adaptive resistance to multiple classes of targeted therapies (e.g., KRAS inhibitors, PI3Kα inhibito
Slide 59: KO-2806 Potentiates Antitumor Activity of Cabozantinib in ccRCC Models
KO-2806 POTENTIATES THE ANTITUMOR ACTIVITY OF CABOZANTINIB IN ccRCC MODELS The anti-angiogenic activity of cabozantinib is enhanced by addition of KO-2806 786-O CDX 786-O CDX KI-12-0073 PDX KI-12-0073 PDX ANGIOGENIC MARKERS IN 786-O CDX TUMORS 1000 1200 Tumor volume (mm3) Tumor volume (mm3) 800 800
Slide 60: KO-2806 Enhances Antitumor Efficacy of a KRAS G12C Inhibitor in NSCLC Models
ADDITION OF KO-2806 ENHANCES THE ANTITUMOR EFFICACY OF A KRASG12C INHIBITOR IN NSCLC MODELS Combination of KO-2806 with adagrasib causes tumor regressions through suppression of mTOR signaling in KRASG12C NSCLC xenografts NCI-H2122 Vehicle Adagrasib KO-2806 Combo (KRASG12C NSCLC) p-ERK1/2 (T202/204)
Slide 61: Combination with KO-2806 Enhances Depth and Duration of Response vs Adagrasib Alone
COMBINATION WITH KO-2806 ENHANCES DEPTH AND DURATION OF RESPONSE COMPARED TO ADAGRASIB ALONE NCI-H2030 NCI-H2030 (KRAS G12CNSCLC G12C (KRAS NSCLC) 3000 Vehicle KO-2806 Adagrasib Combination stop Change in tumor volume (%) dosing 3 3) 2500 (Best response on treatment) (mm (mm ) 2000 volume Tumorvolum
Slide 62: Tumors Progressing on Adagrasib Are Re-Sensitized by Addition of KO-2806
TUMORS PROGRESSING ON KRASG12C INHIBITOR, ADAGRASIB, ARE RE-SENSITIZED BY THE ADDITION OF KO-2806 Tumor regressions in the KO-2806 add-in group were comparable to the upfront combination of KO-2806 with adagrasib NCI-H2122 NCI-H2122 (KRASG12C NSCLC) 1000 (KRASG12C NSCLC Change in tumor volume (%) 10
Slide 63: FIT-001 Phase 1 First-in-Human Trial of KO-2806 in Advanced Solid Tumors
FIT-001 PHASE 1 FIRST-IN-HUMAN CLINICAL TRIAL OF KO-2806 IN PATIENTS WITH ADVANCED SOLID TUMORS PART 1A (MONOTHERAPY) PART 1A (COMBINATIONS) PART 1B (COMBINATIONS) DOSE ESCALATION DOSE ESCALATION DOSE EXPANSION OBJECTIVES PRIMARY SECONDARY Evaluate safety and tolerability of KO-2806 Evaluate the saf
Slide 64: Phase 1/2 Combination Trial of Tipifarnib and Alpelisib in HNSCC
KURRENT-HN PHASE 1/2 COMBINATION TRIAL OF TIPIFARNIB AND ALPELISIB IN PATIENTS WITH HNSCC Clinical collaboration to evaluate the first-generation FTI, tipifarnib, in combination with alpelisib for the treatment of patients with HNSCC whose tumors have PIK3CA mutations Under the collaboration, Kura s
Slide 65: Durable Clinical Response Observed in Patient with PI3Kα-Dependent HNSCC
KURRENT-HN DURABLE CLINICAL RESPONSE OBSERVED IN PATIENT WITH PI3Kα-DEPENDENT HNSCC 35yo, male, nonsmoker, HPV16 positive SCC of tonsil Stage III cT4N2M0; PD-L1 CPS = 60 Prior Treatments • CDDP/rad for 1 mo (Nov-Dec2019), BOR UNK • Cemiplimab/ISA101b (Jun-Nov2021), BOR PD PIK3CA R88Q mutation (44%)
Slide 66: Corporate Presentation
CORPORATE PRESENTATION Our goal is to develop transformative therapies to extend and improve the lives of patients with cancer February 2025