Core Insights - Kura Oncology has received a $30 million milestone payment following the dosing of the first patient in the KOMET-017 Phase 3 clinical trials for ziftomenib, an investigational oral menin inhibitor [1] - The KOMET-017 trials are designed to evaluate ziftomenib in combination with both intensive and non-intensive chemotherapy regimens for patients with newly diagnosed NPM1-mutated or KMT2A-rearranged acute myeloid leukemia [2] - Kura Oncology is focused on precision medicines for cancer treatment, with a pipeline targeting cancer signaling pathways and addressing hematologic malignancies and solid tumors [3] Company Overview - Kura Oncology is a clinical-stage biopharmaceutical company dedicated to developing precision medicines for cancer treatment [3] - The company is advancing ziftomenib, a menin inhibitor aimed at specific genetic drivers of acute myeloid leukemias, and is also exploring farnesyl transferase inhibition for solid tumors [3]

Group 1 - Kura Oncology is presenting updates on its farnesyl transferase program at the ESMO 2025 Congress, focusing on clinical data [2] - This presentation is the second part of a series, with the first part discussing preclinical data and rationale presented on September 16 [2] - The company has made available the webcast and slides from the previous presentation on its website [2] Group 2 - The presentation includes forward-looking statements regarding the company's future prospects [3]

Kura Oncology Conference Call Summary Company Overview - **Company**: Kura Oncology (NasdaqGS: KURA) - **Event**: Discussion of FTI clinical data at the ESMO 2025 Congress - **Date**: October 18, 2025 Key Points Industry and Product Focus - **Focus**: Farnesyltransferase inhibitors (FTIs), specifically KO-2806 (DARLI/Farnib) - **Target Indications**: Advanced HRAS-mutant solid tumors, renal cell carcinoma (RCC), and PIK3CA-mutant head and neck cancers [2][3][4] Clinical Data Highlights 1. **KO-2806 Monotherapy in HRAS-Mutant Tumors** - KO-2806 demonstrated encouraging safety and tolerability with manageable adverse events (AEs) such as neutropenia and anemia [11][12] - Monotherapy activity showed stable disease and partial responses in various tumor types, with a notable response rate at lower doses (5-8 mg) [14][16] - Patients exhibited durable responses, with some remaining on treatment for over 20 months [14][15] 2. **Combination Data with Cabozantinib in RCC** - KO-2806 combined with Cabozantinib showed a response rate of 33% to 50% in clear cell RCC patients, with a disease control rate of 80% to 100% [26][27] - The combination was well tolerated, with no significant overlapping toxicities observed [21][22] - Encouraging activity was noted even in patients previously treated with Cabozantinib, indicating potential for resensitization [26][27] 3. **Combination with PI3K Inhibitors in Head and Neck Cancer** - A phase I study combining Tipifarnib (another FTI) with alpelisib showed a nearly 50% response rate in patients with PIK3CA alterations [32][33] - The combination demonstrated robust antitumor activity and manageable safety profiles, addressing adaptive resistance mechanisms [37] Future Development Plans - Kura Oncology plans to complete dose escalation studies for KO-2806 in combination with Cabozantinib and Adagrasib in KRAS G12C-mutant patients [39][40] - The company aims to explore further combinations with PI3K inhibitors and share additional data in the coming year [39][40] Market Potential - The total addressable market for KO-2806 and FTIs is estimated to exceed 200,000 patients across various indications, highlighting significant growth opportunities [41] Additional Insights - The conference emphasized the importance of combining FTIs with targeted therapies to enhance patient outcomes and address challenges in current treatment paradigms [41][42] - The safety profile of KO-2806 is considered a key advantage, allowing for potential combinations with other therapies without significant dose-limiting toxicities [12][21] Conclusion Kura Oncology's ongoing clinical trials and data presentations at ESMO 2025 indicate promising developments in the use of KO-2806 and FTIs in treating various cancers, particularly in combination therapies that enhance efficacy while maintaining safety. The company is positioned to explore further opportunities in the oncology market, leveraging its innovative drug development strategies.

Darlifarnib (KO-2806) Monotherapy in HRAS-Mutant Solid Tumors - Darlifarnib (KO-2806) is a next-generation FTI with enhanced potency and optimized PK properties[18] - In the FIT-001 monotherapy study, encouraging anti-tumor activity was observed in HRAS-mutant solid tumors[25] - One patient with HRAS-mutant salivary gland carcinoma showed a 62.8% tumor shrinkage from baseline after 80 weeks on 5 mg KO-2806[28, 30] - A patient with advanced HRAS-mutant HNSCC showed a 60% tumor shrinkage at week 8 on 8 mg KO-2806[32, 35] Darlifarnib + Cabozantinib Combination in Renal Cell Carcinoma (RCC) - The combination of KO-2806 and cabozantinib demonstrated a manageable safety profile in RCC patients[48, 69] - In ccRCC patients, the ORR ranged from 33% to 50%, and the DCR ranged from 80% to 100%[50, 69] - One patient with ccRCC treated with KO-2806 5 mg + cabozantinib 60 mg showed a 44% reduction in tumor size at week 16[57, 60] - In ccRCC patients with prior cabozantinib exposure, ORR ranged from 17% to 50%[50, 69] Tipifarnib + Alpelisib Combination in HNSCC - The combination of tipifarnib and alpelisib was well-tolerated in PIK3CA-mutant R/M HNSCC patients[79, 91] - An ORR of 47% was observed at a dose of tipifarnib 1200 mg/day + alpelisib 250 mg/day[80, 81, 91] - One patient with PIK3CA R88Q mutation achieved PR with 81% reduction at week 4[85, 88]

Core Insights - Kura Oncology is advancing the use of farnesyl transferase inhibitors (FTIs) in combination with targeted therapies to overcome resistance mechanisms in cancer treatment [2][11] - Preliminary data from ongoing clinical trials indicate promising efficacy of darlifarnib, showing a 50% objective response rate and an 80% disease control rate in renal cell carcinoma when combined with cabozantinib [1][4] - The company is hosting a virtual investor event to discuss these findings and their implications for future cancer therapies [9][10] Clinical Data Highlights - Darlifarnib demonstrated a 50% objective response rate (ORR) and an 80% disease control rate (DCR) in renal cell carcinoma (RCC) patients in an ongoing dose-escalation trial [1][4] - The combination of tipifarnib and alpelisib showed a 47% ORR in heavily pretreated patients with PIK3CA-altered head and neck squamous cell carcinoma (HNSCC) [6][7] - The ongoing studies are assessing the optimal biologically active dose for combinations across various tumor types [6][4] Mechanism of Action - FTIs like darlifarnib block hyperactivated mTORC1 signaling in tumor endothelial cells, which is crucial for enhancing the efficacy of PI3Kα inhibitors [6][11] - The mechanism of FTIs addresses both innate and adaptive resistance pathways common in targeted oncology therapies [2][6] Future Directions - Kura Oncology plans to further evaluate darlifarnib in combination with PI3Kα inhibitors across different solid tumors [6][11] - A Phase 1b dose-expansion study is planned to determine the optimal dosing strategy for the combination therapies [6][4]

Company Overview - Kura Oncology is preparing for the FDA approval of ziftomenib, with a PDUFA date set for November 30, indicating confidence in obtaining a competitive label for relapsed/refractory NPM1-mutant AML [3]. Product Development - The company has received positive feedback from key opinion leaders (KOLs) regarding the efficacy, simplicity, compatibility, and safety of ziftomenib compared to competitors [3]. - Kura's commercial team is fully established and ready for market access and preapproval information exchanges [3]. Future Prospects - Kura Oncology is also advancing ziftomenib in combination with standard treatments for frontline indications, indicating a strategic focus on expanding its therapeutic applications [4].

Kura Oncology Conference Summary Company Overview - **Company**: Kura Oncology (NasdaqGS: KURA) - **Focus**: Development and commercialization of Ziftomenib for treating acute myeloid leukemia (AML) and gastrointestinal stromal tumors (GIST) [3][5] Key Points and Arguments Ziftomenib Development - **PDUFA Date**: The first PDUFA date for Ziftomenib is set for November 30, 2025, with expectations for FDA approval in the relapsed/refractory setting for NPM1-mutant AML [3][7] - **Efficacy and Safety**: Kura is encouraged by feedback from key opinion leaders (KOLs) regarding Ziftomenib's efficacy, simplicity, combinability, and safety compared to competitors [3][4] - **Combination Trials**: Kura is advancing Ziftomenib in combination with standard treatments, including intensive chemotherapy and venetoclax, with promising data expected to be reported at upcoming conferences [4][5] - **Market Potential**: Ziftomenib has the potential to impact up to 50% of AML patients across various treatment settings [4][5] Commercial Strategy - **Collaboration with Kyowa Kirin**: Kura has a partnership with Kyowa Kirin to support global development and commercialization, with Kura leading U.S. commercial strategy [5][16] - **Sales and Marketing Preparation**: Kura has established a commercial team and market access strategies, including agreements with specialty pharmacies and distributors [16][17] - **Competitive Positioning**: Kura plans to aggressively compete for market share in the NPM1-mutant relapsed/refractory market, emphasizing the importance of combination therapies [18][22] FDA Engagement - **Constructive Interaction**: Kura reports constructive engagement with the FDA, with no disruptions noted in the review process [8][9] - **Label Discussions**: The FDA will conduct its own independent review of efficacy and safety data, which may differ from Kura's assessments [10][11] Clinical Trials and Data - **COMET-017 Trial**: Kura has initiated the COMET-017 trial, which includes two parallel phase three trials for intensive and non-intensive settings, targeting approximately 1,200 patients [31][32] - **Accelerated Approval Potential**: The first top-line results for an accelerated endpoint are expected in 2028, contingent on enrollment progress [32][33] - **Physician Feedback**: Positive feedback from physicians indicates strong interest in Ziftomenib as a treatment option, particularly in combination with other therapies [35][37] FTI Program - **Darlafarnib**: Kura is making progress with its FTI program, particularly with Darlafarnib, which aims to address resistance to targeted therapies [5][42] - **Upcoming Data**: Data on Darlafarnib is expected to be presented at ESMO, focusing on its combination with cabozantinib [42][43] Additional Important Content - **NCCN Guidelines**: Kura plans to submit Ziftomenib for inclusion in NCCN guidelines immediately following FDA approval [26][27] - **Market Dynamics**: The competitive landscape in the AML treatment market is characterized by a need for combination therapies and early intervention strategies [21][22][23] This summary encapsulates the critical insights from Kura Oncology's conference, highlighting the company's strategic direction, clinical developments, and market positioning.

Core Insights - Ziftomenib is being evaluated in combination with approved FLT3 inhibitors for frontline treatment of acute myeloid leukemia (AML) [1][2] - FLT3 mutations are prevalent in approximately 30% of newly diagnosed adult AML patients and up to 50% in those with NPM1-mutated AML, highlighting the significance of FLT3 as a target [1] - The KOMET-007 clinical trial has commenced, focusing on ziftomenib's efficacy alongside cytarabine, daunorubicin, and quizartinib for newly diagnosed AML patients [1][2] Company Overview: Kura Oncology - Kura Oncology is a clinical-stage biopharmaceutical company focused on precision medicines for cancer treatment, with a pipeline targeting hematologic malignancies and solid tumors [4] - Ziftomenib, a menin inhibitor, is under development to address specific genetic drivers of acute myeloid leukemias [4] Company Overview: Kyowa Kirin - Kyowa Kirin is a Japan-based Global Specialty Pharmaceutical Company with over 70 years of experience in drug discovery and biotechnology innovation [5] - The company is committed to developing novel medicines and treatments for high unmet medical needs, including hematological diseases and rare diseases [5]

Core Insights - Ziftomenib is being evaluated in combination with approved FLT3 inhibitors for frontline treatment of acute myeloid leukemia (AML), addressing a significant unmet need in patients with FLT3/NPM1 co-mutations [1][2] - FLT3 mutations are prevalent in approximately 30% of newly diagnosed adult AML patients and up to 50% in those with NPM1-mutated AML, highlighting the importance of targeting this genetic alteration [1] - The KOMET-007 clinical trial has commenced, focusing on the safety and efficacy of ziftomenib combined with standard chemotherapy and quizartinib for newly diagnosed AML patients [1][2] Company Overview - Kura Oncology is a clinical-stage biopharmaceutical company dedicated to developing precision medicines for cancer treatment, with a focus on small molecule drug candidates targeting cancer signaling pathways [4] - Kyowa Kirin is a global specialty pharmaceutical company with over 70 years of experience in drug discovery and biotechnology innovation, aiming to develop novel therapies for high unmet medical needs [5] Clinical Development - Ziftomenib has received Breakthrough Therapy Designation from the FDA for treating adult patients with relapsed or refractory NPM1-mutated AML, indicating its potential significance in the treatment landscape [1] - The KOMET-007 trial will assess the combination of ziftomenib with intensive chemotherapy and quizartinib, with primary endpoints including complete remission and composite complete remission [2]

Core Insights - The first patient has been dosed in the KOMET-017 clinical trial, which evaluates ziftomenib, a menin inhibitor, for treating newly diagnosed acute myeloid leukemia (AML) patients with specific genetic mutations [1][2] Company Overview - Kura Oncology is a clinical-stage biopharmaceutical company focused on precision medicines for cancer treatment, with a pipeline targeting hematologic malignancies and solid tumors [3] - Kyowa Kirin is a Japan-based global specialty pharmaceutical company dedicated to drug discovery and biotechnology innovation, particularly in hematological diseases and rare diseases [5] Clinical Trial Details - The KOMET-017 trial consists of two Phase 3 studies: one assessing ziftomenib with intensive chemotherapy (cytarabine/daunorubicin) and the other with non-intensive chemotherapy (venetoclax/azacitidine) [2][3] - The intensive trial will evaluate minimal residual disease (MRD) negative complete response (CR) and event-free survival (EFS) as dual-primary endpoints, while the non-intensive trial will assess CR and overall survival (OS) [2][3] Market Potential - The trials aim to confirm the efficacy of ziftomenib in nearly half of newly diagnosed AML patients, addressing a significant unmet medical need for safe and effective treatment options [2][3] - The FDA's acceptance of MRD negative CR and CR as primary endpoints for accelerated approval is seen as a groundbreaking opportunity to expedite ziftomenib's availability to patients [2]