Kura Oncology ASH 2025 Update Summary Company Overview - **Company**: Kura Oncology (NasdaqGS: KURA) - **Event**: ASH 2025 update call - **Key Product**: Ziftomenib (branded as Comzifti) Industry Context - **Focus**: Acute Myeloid Leukemia (AML) treatment, specifically targeting NPM1 mutant and KMT2A rearranged AML - **Significance**: First ASH conference where ziftomenib is approved, highlighting its potential in AML treatment Core Points and Arguments 1. **Ziftomenib Approval**: Ziftomenib is now approved and available as 200 mg capsules, marking a significant milestone for Kura Oncology and its partners [4][5][6] 2. **Combination Therapy**: The combination of ziftomenib with azacitidine and venetoclax shows promising results in both newly diagnosed and relapsed/refractory AML settings [3][17] 3. **Efficacy Data**: - In newly diagnosed NPM1 mutant AML, the complete response (CR) rate was 73%, with an overall response rate of 89% [11][12] - In relapsed/refractory settings, CR rates were 27% for NPM1 mutant patients and 6% for KMT2A rearranged patients, with overall response rates of 66% and 41% respectively [22][26] 4. **Safety Profile**: The safety profile of ziftomenib in combination with azacitidine and venetoclax was favorable, with low rates of myelosuppression and adverse events such as differentiation syndrome and QTc prolongation [16][20][25] 5. **MRD Negativity**: The minimal residual disease (MRD) negativity rates were 68% at a threshold of 0.1% and 44% at 0.01% in newly diagnosed patients, indicating deepening responses over time [12][61] 6. **Clinical Development Plans**: Kura Oncology is committed to further developing ziftomenib in combination therapies and has a robust clinical development plan, including the ongoing COMET-017 trial [28][29] Additional Important Insights 1. **Patient Demographics**: The median age of patients in the studies was around 75 years, with a significant portion being older and unfit for intensive therapies [8][19] 2. **Long-term Treatment**: The combination therapy allows for prolonged treatment without significant dose reductions, which is crucial for maintaining response and preventing relapse [72][78] 3. **Comparative Efficacy**: The data suggests that ziftomenib may offer enhanced efficacy compared to other menin inhibitors, particularly in terms of MRD negativity and durability of response [40][61] 4. **Future Directions**: Kura Oncology aims to be the first approved menin inhibitor in the newly diagnosed setting, with ongoing trials designed to evaluate the effectiveness of ziftomenib in various patient populations [30][29] Conclusion Kura Oncology's ziftomenib demonstrates significant promise in treating AML, particularly in combination with established therapies. The favorable safety profile and high response rates position it as a potential leader in the evolving landscape of AML treatment. The company is focused on advancing its clinical trials to solidify its role in frontline therapy for AML patients.

Ziftomenib + Ven/Aza in Newly Diagnosed NPM1-m AML - In newly diagnosed NPM1-m AML patients, the combination of ziftomenib 600 mg QD with Ven/Aza resulted in a composite complete remission (CRc) rate of 86% (32/37), with a complete remission (CR) rate of 73% (27/37)[35] - Among CRc responders in newly diagnosed NPM1-m AML, 68% (17/25) achieved MRD negativity at a threshold of ≤01% and 44% (11/25) at a threshold of ≤001%[36] - In newly diagnosed NPM1-m AML, 68% (27/40) of patients remained alive and continued on study after a median follow-up of 261 weeks[40] Ziftomenib + Ven/Aza in R/R NPM1-m or KMT2A-r AML - In R/R NPM1-m AML patients, the combination of ziftomenib 600 mg with Ven/Aza resulted in an overall response rate (ORR) of 65% (31/48) and a CRc rate of 48% (23/48)[57] - In R/R KMT2A-r AML patients, the combination of ziftomenib 600 mg with Ven/Aza resulted in an ORR of 41% (13/32) and a CRc rate of 28% (9/32)[57] - Among R/R NPM1-m AML patients without prior venetoclax exposure, the CRc rate was 70% (16/23) and the ORR was 83% (19/23)[58] - Among R/R KMT2A-r AML patients without prior venetoclax exposure, the CRc rate was 60% (6/10) and the ORR was 70% (7/10)[58] - For R/R NPM1-m AML, the median duration of CRc was 399 weeks after a median follow-up of 274 weeks[61] - For R/R KMT2A-r AML, the median duration of CRc was 124 weeks after a median follow-up of 169 weeks[64]

Core Insights - The combination of ziftomenib with venetoclax and azacitidine shows promising clinical activity in treating acute myeloid leukemia (AML) with NPM1 mutations, achieving an 86% composite complete remission (CRc) rate in newly diagnosed patients and a 65% overall response rate (ORR) in relapsed/refractory cases [1][2][5] - Ziftomenib has a favorable safety profile, with low rates of myelosuppression and manageable side effects, supporting its potential integration into treatment regimens for AML [4][7][8] - Ongoing registrational trials for ziftomenib are expected to further establish its role in both front-line and relapsed/refractory settings for AML [2][8][13] Summary by Category Clinical Efficacy - In newly diagnosed NPM1-m AML, 86% of patients achieved CRc, with 68% of responders attaining molecular minimal residual disease (MRD) negativity [1][3] - In relapsed/refractory NPM1-m AML, the ORR was 65%, and in venetoclax-naïve patients, it increased to 83% [2][11] - For KMT2A-r AML, the ORR was 41%, with 70% in venetoclax-naïve patients [1][11] Safety Profile - The triplet combination of ziftomenib, venetoclax, and azacitidine was well tolerated, with low rates of ziftomenib-related myelosuppression [4][7] - Adverse events included one case of grade 2 differentiation syndrome and one case of grade 3 QTc prolongation, both managed without treatment discontinuation [4][7] Ongoing Development - Kura Oncology is conducting registrational trials for ziftomenib in both intensive chemotherapy-eligible and -ineligible patients [1][2] - The company is also activating sites for pivotal trials, indicating confidence in the drug's potential as a foundational treatment for AML [8][13]

Core Insights - The combination of ziftomenib with venetoclax and azacitidine shows promising clinical activity in treating acute myeloid leukemia (AML) with NPM1 mutations and KMT2A rearrangements, with high rates of complete remission and molecular negativity [2][3][8] Group 1: Clinical Efficacy - In newly diagnosed NPM1-m AML, 86% achieved composite complete remission (CRc) and 73% achieved complete remission (CR), with 68% of CRc responders attaining molecular minimal residual disease (MRD) negativity [1][2] - In relapsed/refractory (R/R) NPM1-m AML, the overall response rate (ORR) was 65%, and in venetoclax-naïve patients, the ORR was 83% [1][2] - For R/R KMT2A-r AML, the ORR was 41%, with 70% in venetoclax-naïve patients [1][2] Group 2: Safety Profile - The triplet combination of ziftomenib, venetoclax, and azacitidine was well tolerated, with low rates of ziftomenib-related myelosuppression and no increase in toxicity beyond venetoclax/azacitidine alone [1][4][7] - Adverse reactions included differentiation syndrome and QTc prolongation, but these were managed without treatment discontinuation [4][7] Group 3: Ongoing Development - Kura Oncology is conducting registrational trials for ziftomenib in both intensive chemotherapy-eligible and -ineligible patients [1][2][8] - The ongoing KOMET-007 Phase 1a/1b trial is evaluating ziftomenib's efficacy across multiple AML subtypes, reinforcing its potential as a foundational treatment option [1][8][12] Group 4: Company Information - Kura Oncology is focused on precision medicines for cancer treatment, with KOMZIFTI (ziftomenib) being the first oral menin inhibitor approved for adult patients with R/R AML harboring NPM1 mutations [12][28] - Kyowa Kirin collaborates with Kura Oncology, emphasizing their commitment to innovative treatments for high unmet medical needs [29]

Core Insights - The article highlights the identification of Kura Oncology as a promising small-cap biotech opportunity following the author's successful investment in Nuvation Bio, emphasizing the search for reasonably priced companies with long-term growth potential [1]. Group 1: Company Analysis - Kura Oncology is positioned as a small-cap biotech firm that may offer exponential growth potential, aligning with the author's investment strategy focused on fundamental analysis of businesses, financials, and valuations [1]. - The author expresses a belief that educated investors can outperform the market by understanding basic accounting and financial principles, which is relevant for evaluating companies like Kura Oncology [1]. Group 2: Investment Strategy - The investment strategy involves identifying companies that are reasonably priced and have steady long-term growth prospects, which is a key focus for the author in their analysis of Kura Oncology [1]. - The article suggests that small- and mid-cap companies, such as Kura Oncology, can present significant investment opportunities if analyzed correctly [1].

Core Viewpoint - Kura Oncology is hosting a virtual analyst and investor event on December 8, 2025, to discuss data on the triplet combination of ziftomenib, venetoclax, and azacitidine for treating acute myeloid leukemia [1][2] Company Overview - Kura Oncology is a biopharmaceutical company focused on precision medicines for cancer treatment, with a pipeline targeting cancer signaling pathways and addressing hematologic malignancies and solid tumors [3] - The company has developed KOMZIFTI™, an FDA-approved oral menin inhibitor for adults with relapsed or refractory NPM1-mutated acute myeloid leukemia [3]

Core Insights - The article highlights the background and expertise of Brendan, who has a strong foundation in organic synthesis and experience in both pharmaceutical and biotech sectors [1] Group 1: Background and Experience - Brendan completed a Ph.D. at Stanford University in organic synthesis in 2009 [1] - He worked for Merck, a major pharmaceutical company, from 2009 to 2013 [1] - His experience includes working with biotech startups such as Theravance and Aspira before joining Caltech [1] Group 2: Entrepreneurial Ventures - Brendan was the first employee and co-founder of 1200 Pharma, which spun out of Caltech and secured significant investment in the 8 figures [1] - He remains an active investor, focusing on market trends, particularly in biotechnology stocks [1]

Core Insights - Kura Oncology has completed its first U.S. commercial sale of KOMZIFTI™ (ziftomenib), marking a significant milestone for the company [1] - The sale triggers a $135 million milestone payment from Kyowa Kirin, expected to be received by Kura before year-end [1] - KOMZIFTI was approved by the U.S. FDA on November 13, 2025, for treating adults with relapsed or refractory NPM1-mutated acute myeloid leukemia [1][2] Company Overview - Kura Oncology is focused on precision medicines for cancer treatment, with a pipeline of small molecule drug candidates targeting cancer signaling pathways [2] - The company is commercializing KOMZIFTI™, a once-daily oral menin inhibitor, and is advancing research in menin inhibition and farnesyl transferase inhibition [2]

Core Insights - KOMZIFTI (ziftomenib) is the first and only once-daily oral menin inhibitor approved by the FDA for adults with relapsed or refractory acute myeloid leukemia (AML) with a susceptible NPM1 mutation, now commercially available in the U.S. [1][2] - The drug has been included in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines as a Category 2A recommended treatment option for this patient population [1][3] Company Overview - Kura Oncology, Inc. is a biopharmaceutical company focused on precision medicines for cancer treatment, with KOMZIFTI being a key product in its pipeline [19] - Kyowa Kirin Co., Ltd. is a global specialty pharmaceutical company with a long history in drug discovery and biotechnology innovation, collaborating with Kura on the commercialization of KOMZIFTI [20] Clinical Data - KOMZIFTI received full FDA approval on November 13, 2025, based on the KOMET-001 clinical trial, which demonstrated a 21.4% complete response (CR) or complete response with partial hematologic recovery (CRh) rate and a median duration of response of 5 months [2] - The clinical trial involved 112 patients with R/R AML and NPM1 mutation, with differentiation syndrome (DS) occurring in 26% of patients [8][14] Treatment Guidelines - The inclusion of KOMZIFTI in the NCCN Guidelines highlights its potential impact on patients with R/R NPM1-mutated AML and reflects the commitment to patient access [3] - KOMZIFTI is also being developed for front-line treatment of AML with various mutations, indicating its potential to benefit a broader patient population [5] Safety Information - KOMZIFTI has a boxed warning for differentiation syndrome, which can be fatal, and requires monitoring and management protocols [6][7] - Adverse reactions reported in clinical trials include serious reactions in 79% of patients, with the most common being infections and differentiation syndrome [14][16]

Core Viewpoint - Kura Oncology has received FDA approval for ziftomenib, marking a significant milestone for the company in its oncology portfolio [1]. Group 1: Company Overview - The conference call is led by Greg Mann, Senior Vice President of Investor Relations and Corporate Affairs at Kura Oncology [1]. - Key executives participating in the call include Dr. Troy Wilson (President and CEO), Dr. Mollie Leoni (Chief Medical Officer), and Brian Powl (Chief Commercial Officer) [2]. Group 2: FDA Approval Details - The call is focused on discussing the FDA approval of ziftomenib, with supporting materials available on the company's website [1]. - Dr. Eunice Wang, a notable expert in leukemia, is a guest speaker for the call, indicating the importance of the approval in the context of leukemia treatment [2].