KURA ONCOLOGY VIRTUAL INVESTOR EVENT - KURA ONCOLOGY INC

Financial Performance:

• Caspian Therapeutics secured a $50 million financing round led by BDF Partners, with participation from the T1D Fund, Invis, Montanova, Eli Lilly & Company, Cura Oncology, and other investors.
• Proceeds are earmarked to fund KO-7246 through IND-enabling studies, initial clinical proof of concept, and the advancement of a second menin inhibitor candidate.
• Cura Oncology retains approximately 50% ownership of Caspian, ensuring stockholder participation in potential future value.
• An intercompany services agreement allows Caspian to access Cura's research, development, and corporate infrastructure, optimizing resource allocation.

Guidance and Future Outlook:

• The immediate objective is completing IND-enabling studies (toxicology, exposure, manufacturing) to support an initial First-in-Human (FIH) clinical program.
• A Phase 1 trial in healthy volunteers is targeted for initiation next year to establish safety, tolerability, and pharmacokinetic profiles.
• Clinical data updates are anticipated in late 2028 or early 2029.
• The company aims to establish proof of concept regarding the restoration of endogenous insulin production (via C-peptide increases) in both Type 1 and Type 2 diabetes.
• Long-term vision includes exploring other chronic metabolic diseases beyond diabetes, leveraging menin's broad biological role.

Business Segments and Product Lines:

• Cura Oncology: Remains focused on its core oncology business (AML and solid tumors) while spinning off the diabetes program.
• Caspian Therapeutics: A dedicated entity formed to advance the KO-7246 menin inhibitor program in diabetes, with Dr. Rob Spencer as President/COO.
• KO-7246: A potent, selective, oral menin inhibitor designed specifically for metabolic disease, featuring optimized safety and pharmacokinetic profiles compared to prior oncology candidates.
• Pipeline: Beyond KO-7246, resources are allocated to advancing a second menin inhibitor candidate.

Market and Competitive Landscape:

• Mechanism Differentiation: KO-7246 demonstrates selective beta-cell proliferation without stimulating non-beta cells, contrasting with compounds like harmine (DERP1A inhibitor) which caused broader cell growth.
• Competitor Comparison: KO-7246 is ~3x more potent than balamenib (ICOBAMEN/ICOBIVMENIB) in vitro and showed superior activity in leukemia models; ICOBAMENIB showed no efficacy in MENIN-dependent models and exhibited off-target kinase inhibition (CDK9).
• Synergy Potential: The program is positioned as complementary to standard of care, particularly GLP-1 receptor agonists, with preclinical data suggesting synergistic effects.
• Market Need: Addresses a significant unmet need for therapies that restore endogenous beta-cell function rather than just managing glucose levels.

Risks and Challenges:

• Patient Selection: Efficacy is likely dependent on residual beta-cell mass; patients with insufficient remaining beta cells may not respond (as seen in non-responding rats).
• Autoimmunity in T1D: A challenge remains the underlying autoimmune destruction of newly regenerated beta cells, potentially requiring combination therapies with immunomodulators.
• Variable Response: Preclinical data showed binary responses (full recovery or no effect), suggesting a threshold effect based on baseline beta-cell reserves.
• Duration of Action: The optimal dosing paradigm (chronic vs. intermittent) remains undetermined and requires clinical validation.
• Safety: While menin inhibition appears generally safe in oncology, higher tolerability thresholds are required for chronic diabetes use, necessitating rigorous GLP-grade genotoxicity testing.

Management Commentary and Tone:

• Confidence: Management expressed strong confidence in the scientific rationale, citing consistent efficacy across mouse, rat, and human islet microtissue models.
• Strategic Clarity: The spin-off structure is framed as a strategic necessity to provide specialized leadership and capital for the diabetes program while allowing Cura to focus on oncology.
• Safety Profile: Emphasized that the KO-7246 design specifically mitigated off-target risks (SIP system, hERG, genotoxicity) to differentiate from other menin inhibitors facing safety hurdles.
• Tone: Cautiously optimistic; while preclinical data is compelling, the team acknowledged the need for rigorous human data to define dosing and patient stratification.

Analyst Questions and Answers:

• C-Peptide Targets: A meaningful signal is defined as preservation or enhancement of stimulated C-peptide levels compared to baseline during treatment or follow-up.
• Patient Stratification: Trials will likely stratify patients based on baseline C-peptide to ensure a sufficient residual beta-cell pool; "stable" patients with some endogenous insulin production are preferred.
• Dosing Paradigm: Management indicated the therapeutic window is likely large but the specific frequency (chronic vs. intermittent) is unknown until Phase 1 exposure-response data is analyzed.
• Durability: Preclinical data showed blood sugar control persisted one month after stopping treatment, suggesting durable functional benefits, though the exact duration in humans is unproven.
• Competitor Data: Management noted that data from other companies (e.g., Eli Lilly's Menin data or competitor trials) is either not fully disclosed or, in the case of ICOBAMENIB, does not support a pure MENIN-MLL mechanism.
• Combination Therapies: Potential exists for combining KO-7246 with immunomodulators for T1D or GLP-1 agonists for T2D to maximize beta-cell mass and function.

Other Key Points:

• Intellectual Property: Cura contributed KO-7246 and related IP to Caspian, retaining 50% ownership.
• Regulatory Path: The path forward involves establishing a safe and tolerable dosing regimen in healthy volunteers before advancing to patients.
• Differentiation from AML Drugs: Unlike oncology dosing where rapid clearance and high potency are key, KO-7246 was optimized for once-daily oral dosing with complete clearance between doses to meet higher chronic safety standards.
• Future Opportunities: Menin inhibition is described as a "gift that keeps on giving," with potential applications in other epigenetic regulation disorders beyond diabetes and oncology.