KURA ONCOLOGY VIRTUAL INVESTOR EVENT - KURA ONCOLOGY INC

Financial Performance:

• No specific Cura Oncology or Caspian Therapeutics revenue, earnings, or profit margin figures were disclosed, as Caspian is a newly spun-out entity focused on early-stage development rather than commercial sales.
• Caspian secured a $50 million financing round led by BDF Partners, with participation from the T1D Fund, Invis, Montanova, Eli Lilly & Company, and Cura Oncology.
• Proceeds are allocated to support KO-7246 through IND-enabling studies and initial clinical proof-of-concept, plus advancement of a second menin inhibitor candidate.
• Cura Oncology retains approximately 50% ownership of Caspian, providing stockholders with exposure to the new program's potential value.

Guidance and Future Outlook:

• Clinical Timeline: The company aims to initiate First-in-Human (FIH) trials with Healthy Volunteers next year (likely late 2028 or early 2029 for patient data disclosure).
• Development Strategy: Initial clinical goals focus on establishing safety, tolerability, pharmacokinetics (PK), and the ability to improve endogenous insulin production (via C-peptide).
• Long-term Goal: The objective is to restore functional beta-cell capacity in Type 1 and Type 2 diabetes patients, potentially leading to durable glucose control even after treatment cessation.
• Expansion: Management notes potential evaluation of other chronic metabolic diseases beyond T1D and T2D, leveraging the menin inhibition mechanism.

Business Segments and Product Lines:

• Caspian Therapeutics: A dedicated spin-off established to focus exclusively on diabetes, utilizing Cura's IP and research on menin inhibition.
• KO-7246: A potent, selective, oral menin inhibitor developed specifically for metabolic disease.
• Pipeline Progress: KO-7246 has advanced to IND-enabling studies (toxicology, manufacturing, supply) to support clinical entry.
• Secondary Candidate: Funding also supports the advancement of a second menin inhibitor candidate.
• Cura Oncology: Remains focused on its oncology business while retaining oversight and partial ownership of the Caspian program.

Market and Competitive Landscape:

• Competitive Differentiation: KO-7246 is reported to be ~3x more potent than competitor balamenib (IBR-052) in vitro and in leukemia models, while showing superior selectivity.
• Mechanism Comparison: Unlike ICOVAMENID (BMF-219), KO-7246 demonstrates bona fide menin-MLL inhibition and lacks the off-target CDK9 kinase inhibition that plagues ICOVAMENID.
• Complementary Landscape: The company positions KO-7246 as a synergistic addition to standard of care, particularly GLP-1 receptor agonists, rather than a direct replacement, noting potential upregulation of GLP-1 receptors as a secondary mechanism.
• Market Opportunity: Focuses on the unmet need for therapies that restore endogenous insulin production, distinct from current glucose-lowering agents.

Risks and Challenges:

• Patient Selection Complexity: Efficacy appears binary and threshold-dependent; preclinical data suggests only animals/patients with a minimum residual beta-cell mass will respond, necessitating rigorous patient stratification (likely via C-peptide levels).
• Autoimmunity in T1D: The underlying autoimmune destruction in Type 1 diabetes may limit the durability of beta-cell expansion, potentially requiring combination therapies with immunomodulators.
• Species Translation: Rodent beta-cells proliferate faster than human beta-cells; clinical efficacy in humans may require longer treatment durations.
• Non-Responders: In preclinical STZ models, non-responders were likely those with insufficient baseline beta-cell reserves, creating a challenge for patient recruitment in advanced stages of disease.
• Competitor Safety: While KO-7246 aims for a clean safety profile, competitors have faced issues (e.g., liver toxicity with covalent inhibitors or off-target effects), making safety validation critical for chronic use.

Management Commentary and Tone:

• Tone: Management expressed high confidence and optimism regarding the scientific rationale, emphasizing the unique ability to "rebuild" beta-cell mass and the durability of the effect.
• Strategic Clarity: Dr. Troy Wilson and Dr. Francis Burroughs framed the spin-off as a necessary step to align capital and leadership with the specific needs of metabolic disease development, distinct from oncology timelines.
• Cautious Optimism on Dosing: While preclinical data shows rapid regeneration, management avoided committing to a fixed short-course dosing paradigm in humans, citing the need to understand exposure-response and patient variability before determining chronic vs. intermittent dosing.

Analyst Questions and Answers:

• C-peptide Signals: Analysts asked about meaningful signal thresholds. Management confirmed that preservation or enhancement of C-peptide (endogenous insulin marker) is the primary proof-of-concept metric for both treatment and follow-up periods.
• Dosing Paradigm: Questions regarding chronic vs. intermittent dosing were addressed; management indicated the dosing strategy remains to be determined by clinical data but noted a potentially large therapeutic window based on AML experience.
• Competitor Comparison: Clarification was provided that KO-7246 is superior to balamenib in potency and that ICOVAMENID lacks the specific menin-MLL inhibition mechanism, instead acting as a broad kinase inhibitor.
• Patient Selection: Confirmed that trials will target patients with residual beta-cell capacity (identified via C-peptide) and that stable patients (not those in rapid decline) will be prioritized for initial T1D studies.
• Safety Design: Explained that KO-7246 was engineered for chronic use by eliminating interactions with CYP450 and hERG channels and achieving a clean Genotoxicity profile at high concentrations.
• Data from AML Patients: Management noted that while AML data is reassuring regarding safety, it does not provide direct diabetes efficacy data due to the lack of interest in diabetes endpoints among oncologists and the complications of transfusions in that population.

Other Key Points:

• Scientific Basis: Preclinical data in mouse (T2D), rat (T1D model), and human islet microtissues consistently showed KO-7246 increases beta-cell proliferation and insulin production without hyperglycemia or growth of non-beta cells.
• Durability: In rat models, blood sugar control remained restored for a month after treatment cessation, suggesting the functional benefit persists after the proliferation phase ends.
• Collaboration: Caspian will access Cura's R&D infrastructure and corporate capabilities via an intercompany services agreement.
• Investor Relations: This represents the first beta-cell regeneration investment by major partners like Eli Lilly and the T1D Fund.
• Future Updates: Cura Oncology plans to provide further updates in its upcoming Q3 earnings call.