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]

Kura Oncology Conference Call Summary Company Overview - **Company**: Kura Oncology (NasdaqGS: KURA) - **Focus**: Development of targeted therapies for cancer treatment, particularly through the use of Farnesyl Transferase Inhibitors (FTIs) and menin inhibitors. Key Points Industry and Product Pipeline - Kura is well-positioned to build on the success of Ziftomenib, currently under FDA review for NPM1-mutant relapsed/refractory Acute Myeloid Leukemia (AML) [3][4] - The menin inhibitor class could represent a market opportunity of $5 to $10 billion, with Kura aiming to capture a significant share [3] - The company is advancing its FTI program, specifically KO-2806 (Darlifarnib), which is designed to overcome drug resistance in various cancers [12][26] Preclinical Data and Mechanism of Action - KO-2806 has shown improved potency and reduced dosing requirements compared to its predecessor, Tipifarnib, making it suitable for combination therapies [12][13] - The FTI program targets Rheb, a protein involved in mTOR signaling, which is crucial for addressing resistance to multiple targeted therapies [8][18] - Preclinical studies indicate that KO-2806 enhances the efficacy of various therapies, including PI3K inhibitors, KRAS inhibitors, and anti-angiogenic TKIs, across multiple cancer types [26][27] Clinical Development Strategy - Kura is conducting several clinical trials, including: - A dose escalation trial for KO-2806 in RAS mutant tumors [30] - A combination trial of KO-2806 with Cabozantinib in renal cell carcinoma [31] - A trial combining Tipifarnib with Alpelisib in PIK3CA mutant head and neck squamous cell carcinoma [32] - The company anticipates presenting data at the upcoming ESMO meeting, focusing on safety, tolerability, and efficacy of these combinations [27][30] Market Opportunity - Kura estimates a patient population of over 200,000 annually in the U.S. for potential applications of FTIs in combination with other targeted therapies [34] - The company is optimistic about the commercial launch of Ziftomenib and ongoing studies, including the KOMET-001 phase three studies [35][36] Financial Position - Kura reported $630.7 million in cash and cash equivalents, with anticipated milestone payments of $375 million expected by year-end [36] Future Directions - Kura is exploring various clinical collaborations and partnerships to enhance the development of KO-2806 and its applications across different cancer types [60][61] - The company aims to demonstrate the additive efficacy of KO-2806 in combination therapies, addressing the challenge of proving its value alongside established agents [81] Additional Insights - The call highlighted the importance of demonstrating single-agent activity for future development, although Kura is currently focused on combination therapies [52] - The potential for KO-2806 to overcome resistance mechanisms associated with other combination regimens was also discussed, indicating a broad applicability of the FTI approach [81] This summary encapsulates the key points from the Kura Oncology conference call, focusing on the company's strategic direction, product pipeline, and market opportunities.