Kura Oncology Virtual Investor Event - KURA ONCOLOGY INC

Financial Performance:

• Caspian Therapeutics secured $50 million in financing to fund IND-enabling studies and initial clinical proof-of-concept for KO7246.
• The financing round was led by BDF Partners, with participation from the T1D Fund, Invis, Montanova, Eli Lilly & Company, Cura Oncology, and other investors.
• Cura Oncology retains approximately 50% ownership in Caspian Therapeutics, providing Cura stockholders with exposure to the potential value of the diabetes program.
• Cura will contribute KO-7246 and related intellectual property to Caspian under a specific development agreement.
• An intercompany services agreement allows Caspian to leverage Cura's existing R&D infrastructure, directing Caspian's resources toward clinical development.

Guidance and Future Outlook:

• Caspian's primary short-term objective is to complete IND-enabling studies, including toxicology and manufacturing, to support the first-in-human (FIH) trial.
• Initial clinical assessment is projected to begin in Healthy Volunteers (HV) next year, with data on dose, exposure, and tolerability expected in late 2028 or early 2029.
• The clinical strategy focuses on establishing safety, tolerability, and pharmacokinetics for chronic administration in patients with Type 1 and Type 2 diabetes.
• Management anticipates the program will demonstrate a durable functional benefit where insulin production persists after treatment cessation, based on preclinical rodent data.
• Long-term goals include defining the dosing paradigm (chronic vs. intermittent) and identifying patient subgroups with sufficient residual beta cell mass for optimal response.

Business Segments and Product Lines:

• Cura Oncology: Continues to focus exclusively on its oncology pipeline while spinning out the diabetes program into Caspian.
• Caspian Therapeutics: A dedicated entity formed to advance KO7246, a potent, selective oral menin inhibitor designed for metabolic disease.
• KO7246: Shows potent menin inhibition with superior selectivity; preclinical data demonstrates beta cell expansion, increased insulin production, and sustained glucose control in mouse, rat, and human islet models.
• Mechanism: The drug acts by inhibiting the menin protein, a "brake" on beta cell division, thereby allowing the body to regenerate its insulin-producing capacity.
• Competitor Comparison: KO7246 is reported to be approximately three times more potent than Balameneb (ICOVAMEN) in vitro and displays superior efficacy in menin-dependent models; ICOVAMEN showed no efficacy in these models and non-specific kinase inhibition (e.g., CDK9).

Market and Competitive Landscape:

• KO7246 targets a significant unmet need for therapies that restore endogenous beta cell function, contrasting with current standard of care (e.g., GLP-1 agonists) that primarily manage symptoms.
• The mechanism is viewed as highly complementary to GLP-1 receptor agonists, potentially offering synergistic effects by increasing beta cell mass while improving cell function.
• Management notes that KO7246's selectivity for beta cells without proliferating alpha or other islet cells distinguishes it from other agents like harmine (DPP4 inhibitor).
• No other current therapy is confirmed to selectively expand beta cell mass; successful demonstration of this in humans would establish a unique competitive advantage.
• Management believes menin inhibition has a clean safety profile compared to covalent inhibitors in the class, with no observed liver toxicity in prior AML trials.

Risks and Challenges:

• Patient Selection: A critical challenge is identifying patients with sufficient residual beta cell mass (baseline C-peptide levels) to respond to the therapy, as shown by the binary responder/non-responder phenotype in STZ rat models.
• Autoimmunity: In Type 1 diabetes, the underlying autoimmune process continues to destroy beta cells; the strategy may eventually require combination therapies to address both regeneration and immune suppression.
• Dosing Paradigm: It remains uncertain whether the therapy requires chronic administration or if a fixed short course is sufficient for durable benefit; this must be determined in Phase 1 trials.
• Timeline: Clinical results regarding proof-of-concept in humans are not expected until late 2028 or early 2029, presenting a long development horizon.
• Variable Response: Preclinical data indicates a wide variability in response times and magnitudes, likely dependent on the starting beta cell mass.

Management Commentary and Tone:

• Management expressed high confidence in the scientific foundation, citing consistent efficacy across mouse, rat, and human microtissue models.
• The tone was optimistic regarding the "durable" nature of the effect, noting that blood sugar control persisted even after beta cell proliferation ceased and treatment stopped.
• Dr. Troy Wilson and the team emphasized the strategic separation of the diabetes program into Caspian to provide focused leadership and capital, while ensuring Cura shareholders retain 50% equity.
• Management acknowledged the "threshold" nature of the response in preclinical models, suggesting a "sliding doors" moment where early intervention is critical.

Analyst Questions and Answers:

• Meaningful Signal: Management indicated that preservation or enhancement of stimulated C-peptide levels compared to baseline (during treatment or follow-up) would constitute a meaningful proof-of-concept signal.
• Combination Therapy: Francis Burroughs confirmed a strong scientific rationale for combining KO7246 with GLP-1 agonists, noting menin's potential to upregulate GLP-1 receptors and complement the existing mechanism.
• Dosing Paradigm: While preclinical data suggests rapid beta cell mass increase (quadrupling in T2D models in 28 days), management stated the exact dosing schedule (continuous vs. intermittent) is an open question to be resolved in FIH studies.
• Competitive Positioning: Rob Spencer clarified that while Balameneb is a menin inhibitor, KO7246 demonstrates higher potency and a cleaner profile regarding non-menin kinase inhibition, unlike ICOVAMEN.
• Safety Profile: Management highlighted that the KO7246 design specifically excluded interactions with the hERG channel and SLC transporters, and passed full GLP-grade genotoxicity testing, addressing safety concerns for chronic use.
• Patient Subtypes: For Type 1 diabetes, the company plans to target patients who are in a relatively stable phase of the disease (not rapidly declining) to ensure a clear signal of beta cell regeneration.

Other Key Points:

• The EASD data presentation highlighted that in Type 2 diabetic mice, KO7246 combined with Semaglutide provided both rapid initial glucose lowering and sustained effects via beta cell expansion.
• In Type 1 diabetic rat models (STZ), KO7246 restored blood glucose in "responders" (those with sufficient remaining beta cells) and maintained control for at least one month post-treatment.
• Human islet microtissue studies confirmed that KO7246 selectively increased beta cell proliferation without stimulating non-beta cells, unlike the comparator compound harmine.
• Management noted that previous AML trials with menin inhibitors showed no obvious metabolic tolerability issues, supporting the safety of chronic dosing in diabetics.
• While the immediate focus is T1D and T2D, management hinted at other potential chronic metabolic indications driven by menin's role in epigenetic regulation.