CHARDAN HEALTHCARE CONFERENCE - PRELUDE THERAPEUTICS INC

Financial Performance:

• No specific Q4 financial results (revenue, earnings, or cash flow) disclosed; focus is on pre-revenue biotech development.
• Potential to secure $100 million in non-dilutive financing contingent on Insight Therapeutics exercising a partnership option.
• Capital allocation strategy centered on advancing three distinct clinical programs rather than generating immediate commercial revenue.

Guidance and Future Outlook:

• Timeline (H1 2027): Expect clarity on Insight's option exercise decision to unlock potential funding.
• Timeline (H2 2027): Anticipated disclosure of initial proof-of-concept (PoC) data for the CAT6A degrader program.
• CAT6A Program: IND clearance received; clinical enrollment expected to begin shortly.
• JAK2 Program: Advanced to the clinic in Q2 2026 (Note: Transcript date context implies future projection relative to "current" call).
• NCALR Program: Continued advancement as a third clinically validated target for Myeloproliferative Neoplasms (MPN).

Business Segments and Product Lines:

• CAT6A Degrader (Breast Cancer): Differentiated approach targeting CAT6A selectively (sparing CAT6B) to degrade the protein rather than inhibit it; aims for tumor regression vs. stasis seen with inhibitors.
• JAK2 Inhibitor (MPN): Utilizes structure-based design to target the V617F mutation deep pocket; claims 10x selectivity for mutant vs. wild-type with favorable pharmacokinetics.
• NCALR Program: Focused on the MPN community as a validated target; status advanced but no specific clinical data points provided in this segment during the call.

Market and Competitive Landscape:

• Competitors: Pfizer and Olema currently developing dual CAT6A/B inhibitors; Insight Therapeutics previously shelved a JAK2 program due to PK challenges.
• Differentiation: Prelude positions its CAT6A degrader as superior to dual inhibitors regarding therapeutic index (sparing CAT6B to reduce neutropenia) and efficacy (tumor regression vs. growth arrest).
• Market Strategy: Aims to move into frontline therapy for HR+ breast cancer by combining with CDK4/6 inhibitors, a combination competitors face toxicity hurdles in preventing.
• Target Audience: Breast cancer patients (CAT6A) and MPN patients (JAK2/NCALR).

Risks and Challenges:

• Toxicity Risk: Potential for neutropenia remains a critical hurdle; reliance on the hypothesis that sparing CAT6B will mitigate bone marrow toxicity compared to dual inhibitors.
• Clinical Uncertainty: Preclinical regression data in PDX/CDX models must translate to human efficacy; clinical success is not guaranteed.
• Funding Dependency: Future liquidity depends on the binary outcome of Insight exercising their partnership option ($100M).
• Competition: First-mover disadvantage for competitors (e.g., Pfizer) who may reach market first despite lower tolerability profiles.

Management Commentary and Tone:

• Tone: Confident and execution-focused; emphasizes "clinically validated targets" and a strategic pivot to three specific programs.
• Strategic Clarity: CEO and CSO articulate a clear path forward regarding the CAT6A degradation mechanism versus traditional inhibition.
• Technical Confidence: Strong belief in the biological rationale that degraders offer deeper target engagement and superior efficacy (regression vs. stasis) compared to inhibitors.

Analyst Questions and Answers:

• Q: CAT6A Biology & Differentiation: Management clarified CAT6A drives ER+ breast cancer; contrasted their selective degrader (sparing CAT6B) against Pfizer's dual inhibitor to avoid dose-limiting neutropenia.
• Q: Degrader vs. Inhibitor Efficacy: Confirmed preclinical data shows regression with degraders versus stasis with inhibitors; cited ability to maintain active dosing without "holidays" as a key efficacy driver.
• Q: Neutropenia Mitigation: Reiterated that while CAT6A is involved in bone marrow, preclinical models suggest sparing CAT6B significantly reduces toxicity, enabling combination with other myelosuppressive agents.
• Q: JAK2 Selectivity: Addressed selectivity comparisons (Prelude's 10x vs. competitors' 170x-500x); argued that a "flat" PK profile allows the lower 10x selectivity to be sufficient for therapeutic window, whereas competitors rely on high peak selectivity.

Other Key Points:

• Catalyst Schedule: The next 12-18 months are bifurcated: funding clarity in the first half and PoC data in the second half of 2027.
• Clinical Design: CAT6A trial protocol designed to assess monotherapy activity, safety, and early combination data with fulvestrant.
• Company Status: Currently pivoted post-SMARCA shelving; now fully resourced around three specific programs with no immediate commercial revenue streams.