STIFEL 2026 HEALTHCARE CONFERENCE - CULLINAN THERAPEUTICS INC

Explicit Guidance:

• Cash Runway: $300+ million in cash as of end-September 2024, extending operations into 2029, assuming all current programs (autoimmune, oncology) progress as planned and including anticipated regulatory milestones from the ZipAlertny/Taiho partnership.
• PDUFA Dates:
  • Second-line indication for ZipAlertny: February 2027.
  • Frontline indication for ZipAlertny: Anticipated early 2027 (estimated 2 months post-application acceptance).
• Financial Milestones: Upcoming regulatory approvals for ZipAlertny will trigger $130 million in non-dilutive milestone payments from partner Taiho.
• Profit Sharing: Implementation of a 50-50 profit share in the U.S. market for ZipAlertny, expected to become effective "very quickly" upon launch, allowing reinvestment into T-cell engager programs.

Business-Segment Outlook:

• CLN978 (CD19 T-cell engager – Autoimmune):
  • Timeline: First multi-dose data (approx. 20 patients across SLE and RA) to be presented in December.
  • Follow-up: Minimum 6-month follow-up on single-dose cohorts for SLE and RA; durability tracking ongoing into 2027.
  • Sjogren's Disease: Expectation to present both single-target and multi-target dose data in December, including paired biopsy results to assess B-cell depletion in salivary glands.
  • Phase 2 Strategy: Planning to initiate Phase 2 studies in 2025 across multiple indications (SLE, RA, Sjogren's, Lupus Nephritis) to identify consistent dosing regimens and establish efficacy for registration.
  • Success Metrics: Targeting DORIS response in 30% of SLE patients (durable 6 months) and DAS28 response in 20% of RA patients (durable 4–5 months) with predominantly Grade 1/low Grade 2 CRS.
• Velanotamate (BCMA T-cell engager – Autoimmune):
  • Current Status: Global Phase 1/2 study in autoimmune cytopenias cleared IND (US/Australia); first data from China partner (Generics Bio) presented at ACR.
  • Timeline: Aiming to move rapidly into Phase 2 and other plasma-cell driven indications (Nephrology, Neurology, Endocrinology) based on Chinese Proof-of-Concept data, potentially without waiting for full completion of the initial cytopenia basket.
  • Strategy: Pursuing subcutaneous administration for future studies to enhance patient comfort, though IV data has shown favorable safety.
• CLN049 (FLT3 T-cell engager – Oncology):
  • Timeline: Pivotal Phase 2 study in relapsed/refractory AML is actively recruiting; focus on a 12 mcg/kg dose with two-step-up dosing.
  • Data Expectations: Upcoming ASH presentation to highlight 26% composite CR/CRh rate in the 12 mcg/kg cohort with durability follow-up of 4+ months; enrollment limited to patients with ≤2 prior lines to ensure efficacy testing.
• ZipAlertny (Tyrosine Kinase Inhibitor – NSCLC Exon 20):
  • Frontline Study: Primary analysis for PFS/OS anticipated before the end of 2024; initiation of RTOR submission expected soon, with PDUFA targeted for early 2027.
  • Commercial: Partner Taiho to handle commercialization; profit sharing begins upon product launch.

Market and Competitive Outlook:

• T-Cell Engager Landscape: Management views the competitive field as having "decreased" activity; competitors (Roche, Nevidus) have pivoted to other molecules or started anew from Phase 1, while Colnan aims to be the first to present multi-dose CD19 data and clear INDs for BCMA.
• Execution Advantage: Positioning to be the first company to present multi-dose CD19 data and clear INDs for BCMA in autoimmune settings, leveraging speed of execution (e.g., China partnership for GenexBio) to stay ahead of larger pharma pivots.
• Product Differentiation: Strategy to redefine standards of care by addressing different B-cell compartments (CD19 for broad depletion, BCMA for long-lived plasma cells), aiming for high commercial attractiveness.
• Regulatory Strategy: Exploring single-arm registration pathways for high-unmet-need populations (e.g., Lupus Nephritis) based on compelling efficacy data, similar to recent CAR-T precedents.

Macro / Industry Outlook:

• Autoimmune Therapy Standards: Anticipates a shift in treatment paradigms, particularly for heavily pre-treated RA and SLE patients where current options are insufficient; Colnan targets "deep treatment-free responses" not achievable by existing therapies.
• Regulatory Environment: Engaging in Real-Time Oncology Review (RTOR) for ZipAlertny, indicating a willingness to navigate accelerated pathways for high-need indications.
• Clinical Trial Dynamics: Acknowledges that clinical trials for new modalities are increasingly enrolling heavily pre-treated populations; management notes a strategic shift to limit Phase 2 AML enrollment to ≤2 prior lines to ensure a rigorous efficacy test.

Strategic Initiatives:

• Partnerships:
  • Taiho (ZipAlertny): Leveraging partner's lean commercial infrastructure for rapid US market entry; securing $130M in milestones and 50-50 US profit share to fund non-dilutive R&D.
  • Generics Bio (Velanotamate): Utilizing partner's ability to rapidly accrue patients in China for initial Phase 1 data; maintaining 50-50 split on milestones (implied) or upfront cash benefit of $20M compared to larger recent deals.
• Capacity & Indication Expansion:
  • Autoimmune: Expanding CLN978 and Velanotamate pipelines into nephrology, neurology, and endocrinology indications beyond initial rheumatic and cytopenia focus.
  • Lupus Nephritis: Specifically targeting enrollment of a cohort for Lupus Nephritis in the next phase of CLN978 development.
  • Dosing Optimization: Focusing on identifying multi-step-up dosing schemes to mitigate CRS (Cytokine Release Syndrome) risks and optimize therapeutic index for both CLN978 and Velanotamate.

Risks and Headwinds to Outlook:

• Safety (CRS): Potential for Cytokine Release Syndrome (CRS) remains a key risk; mitigation relies on optimized step-up dosing regimens. Previous data showed Grade 1-2 CRS, with one Grade 3 case that could have been mitigated by step-up dosing.
• Efficacy Durability: Uncertainty remains regarding the fraction of patients achieving durable treatment-free responses; targets vary by indication (30% in SLE vs. 20% in RA).
• Regulatory Pathway: Success relies on securing registration-enabling data; FDA flexibility is noted, but formal acceptance and PDUFA dates are contingent on application completion and agency review timing.
• Trial Recruitment: AML Phase 2 study enrollment is limited to ≤2 prior lines; management notes that patients in recent studies (post-ASH 2025) are heavily pre-treated, requiring careful patient selection to demonstrate efficacy.
• Timing Risks: Data for the frontline ZipAlertny study (OS analysis) is expected before end-of-year, but delays in trial maturation or regulatory feedback could impact 2027 PDUFA targets.

Management Tone on the Future:

• Confidence Level: High confidence ("super excited," "very pleased") regarding the clinical data trajectory, particularly for CLN978 multi-dose data and the strategic value of the Taiho partnership.
• Strategic Clarity: Strong conviction in the CD19/BCMA dual-target approach for autoimmunity and the feasibility of "treatment-free responses."
• Execution Focus: Emphasis on "speed" and "execution advantage" as key differentiators against larger competitors who have pivoted or slowed down.
• Financial Stability: Optimistic about cash runway extending to 2029 and the ability to reinvest non-dilutive capital from ZipAlertny milestones to sustain the T-cell engager pipeline.
• Hedges: Acknowledges that "there is probably not one single solution" for dosing and that durability targets depend on specific disease settings.

Miscellaneous:

• Dose Specifics: CLN978 multi-dose data will cover 20 mcg and 30 mcg doses; Velanotamate IV step-up starts at 3 mcg/kg; CLN049 pivotal dose is 12 mcg/kg (step-up from 1–1.5 mcg/kg).
• Patient Populations: CLN978 studies utilize "clean monotherapy" (patients off background therapy); Phase 2 RA studies may eventually broaden to earlier lines of treatment per investigator opinion.
• Biopsy Data: Plan to collect paired salivary gland biopsies for CLN978 Sjogren's study to correlate tissue B-cell depletion with symptom resolution.