Kura Oncology Virtual Investor Event - KURA ONCOLOGY INC

Explicit Guidance:

• No specific financial guidance (revenue, earnings, margins, capex, etc.) or share count/dividend/buyback targets provided for Cura Oncology or Caspian Therapeutics.
• Clinical Timeline: Initiation of First-in-Human (FiH) trials in Healthy Volunteers targeted for "next year" (following the call date, implied FY2025/FY2026 transition); expectation to disclose initial Phase 1 data in "late 2028, possibly early 2029."
• Capital Allocation: $50 million financing raised (led by BDF Partners, with participation from Eli Lilly, T1D Fund, etc.) to fund KO7246 through IND-enabling studies and initial clinical proof-of-concept (POC).

Business-Segment Outlook:

• Cura Oncology: Will remain focused solely on its oncology business (AML, solid tumors), spinning out the diabetes program to Caspian.
• Caspian Therapeutics: Dedicated focus on developing menin inhibitors for diabetes (Type 1 and Type 2). Structure provides independent leadership while Cura retains ~50% ownership.
• Product Pipeline (KO7246): Primary objective is to establish safety, tolerability, and pharmacokinetic profiles for chronic administration. Secondary objective is to assess ability to restore endogenous insulin production.
• Pipeline Expansion: Caspian will advance not only KO7246 but also a second menin inhibitor candidate; the $50M financing supports both.

Market and Competitive Outlook:

• Mechanism Differentiation: KO7246 is positioned as uniquely capable of selectively expanding beta-cell mass without stimulating non-beta cell growth (unlike competitors like ICOVAMEN/BMF219 or GSK's MLL inhibitors).
• Competitive Landscape:
  • vs. Balameneb (BMS/BMS-986094): KO7246 is ~3x more potent in vitro; Balameneb showed no efficacy in MENIN-dependent models in Cura's assays, whereas KO7246 demonstrated robust activity.
  • vs. KO7246 (Caspian) vs. ICOVAMEN: ICOVAMEN lacked measurable MENIN-MLL inhibition in Cura's assay and showed no efficacy; KO7246 demonstrated selective beta-cell proliferation.
  • vs. Harmine (DERP1A inhibitor): Harmine stimulated non-beta cells and reduced the proportion of beta cells, highlighting KO7246's superior selectivity.
• Combination Potential: Strong scientific rationale for combination with GLP-1 receptor agonists to achieve synergy (increasing beta-cell number + enhancing function). Significant interest noted from standard-of-care diabetes drug producers.
• Target Population: Focus on patients with residual beta-cell capacity (identified via C-peptide levels). Targeting both Type 1 (T1D) and Type 2 (T2D) diabetes, with initial trials likely prioritizing stable patients (not rapid decliners).

Macro / Industry Outlook:

• Unmet Need: No current therapy exists that selectively expands beta-cell mass to restore endogenous insulin production.
• Regulatory/Safety Context: Anticipated to be a "chronic" drug class; expects a large therapeutic window based on prior AML menin inhibitor experience (Ziftomenib) and lack of class-specific metabolic toxicity.
• Regulatory Hurdles: Acknowledges the challenge of distinguishing T1D autoimmune destruction from beta-cell regeneration; potential need for future combination therapies to suppress autoimmunity.

Strategic Initiatives:

• Corporate Structure: Established Caspian Therapeutics as a separate entity with dedicated board oversight; Cura and Caspian operating under an intercompany services agreement for R&D access.
• Clinical Development:
  • Phase 0/Preclinical: Finalizing IND-enabling studies (toxicology, exposure, manufacturing) to support clinical dosing.
  • Phase 1: Designing trials to measure C-peptide (stimulated) as a primary marker of beta-cell regeneration, alongside HbA1c and glycemic control.
  • Patient Selection: Stratifying patients based on baseline C-peptide to identify "responders" vs. "non-responders" (linked to threshold beta-cell mass).
• Dosing Paradigm: Investigating whether chronic dosing or fixed short-course intermittent dosing is optimal; preclinical data suggests beta-cell mass expansion occurs within 28 days (T2D models) but human timelines may vary based on starting mass.
• Safety Optimization: KO7246 specifically designed with a higher tolerability bar than oncology agents; screened for lack of hERG interaction, CYP450 issues, and comprehensive GLP-compliant gene toxicity (found clean at high concentrations).

Risks and Headwinds to Outlook:

• Binary Response Risk: Preclinical data showed a "binary" response in rats (complete recovery in some, none in others); suggests a threshold effect where patients with insufficient residual beta cells may not respond.
• Dosing Uncertainty: Unknown if chronic vs. intermittent dosing is required; uncertainty regarding the speed of beta-cell regeneration in humans compared to rodents (humans may take longer).
• T1D Complexity: The autoimmune process destroying beta cells continues; success may require combination therapies to dampen autoimmunity alongside regeneration.
• Data Disclosure: Initial Phase 1 data from Healthy Volunteers may not be fully disclosed publicly; key data expected only in late 2028/early 2029.
• Competitor Toxicity: Industry peer (referenced generally) reported liver toxicity; Cura notes this appears to be class-specific for certain covalent inhibitors/other targets, not pure menin inhibition, but remains a monitoring point.

Management Tone on the Future:

• Confidence: High confidence in the "scientific basis" and "strong scientific hypothesis" regarding menin inhibition for beta-cell regeneration.
• Strategic Clarity: Confident in the separation of business lines to allow Caspian to focus on metabolic disease while Cura continues oncology work.
• Realism: Acknowledges the "million-dollar question" of dosing and the "variable response time" based on patient starting point; describes the approach as "stepwise" and cautious ("safety always comes first").
• Differentiation: Emphasizes that demonstrating selective beta-cell expansion without alpha-cell growth is a "unique and powerful" capability that no one else has achieved.

Miscellaneous:

• Additional Indications: Management indicated evaluation of "other chronic metabolic diseases" beyond T1D/T2D, though specific targets were not disclosed (mentioning "epigenetic regulation" as a broad field).
• Investor Sentiment: Noted that investors (Eli Lilly, T1D Fund, etc.) made their first beta-cell regeneration investments with this financing, signaling validation of the opportunity.
• Competitor Intelligence: Cura conducted direct head-to-head preclinical comparisons of KO7246 vs. Balameneb, ICOVAMEN, and Harmine, providing the data that distinguishes their candidate's mechanism and potency.
• Future Communications: Cura Oncology to provide Q3 earnings update; Caspian will operate with a "relatively lower profile" but plans to share progress as the program advances.