Cullinan Therapeutics (CGEM) Status Update summary

Strategic approach and pipeline overview

• Focus on modality-agnostic, target-first R&D, enabling a diversified pipeline across oncology and immunology, with multiple clinical-stage programs and data catalysts expected through 2024 and early 2025.

• Expansion into autoimmune diseases with CLN-978, targeting systemic lupus erythematosus and other autoimmune indications, while oncology programs remain on track.

• Key assets include CLN-619 (pan-cancer anti-MICA/B mAb), CLN-978 (CD19xCD3 TCE), and zipalertinib (EGFR ex20ins inhibitor), each with upcoming clinical milestones.

• Pivotal Phase 2b and Phase 3 studies for zipalertinib are actively enrolling, with a 50/50 US profit share and significant milestone payments from Taiho Oncology.

• Recent $280M financing and $435 million in cash as of March 31, 2024, extend runway into 2028, supporting continued pipeline progress.

Key clinical updates and data readouts

• Multiple clinical data catalysts expected through 2024 and H1 2025, including CLN-619, CLN-978, zipalertinib, CLN-049, and CLN-418.

• CLN-619 plus pembrolizumab shows objective responses in tumor types typically unresponsive to checkpoint inhibitors, including NSCLC with ALKr and EGFRm.

• Durable responses and favorable safety observed with CLN-619 in both monotherapy and combination settings, with expansion cohorts in endometrial, cervical, and NSCLC.

• Zipalertinib demonstrates a 41% confirmed overall response rate and 12-month median progression-free survival in heavily pretreated NSCLC patients with EGFR exon 20 insertions.

• Efficacy and safety of zipalertinib in amivantamab-exposed patients remain strong, with a 39% response rate and no new safety signals.

Development and regulatory strategy

• Expansion cohorts for CLN-619 include both IO-exposed and IO-naive patients, focusing on those progressing after PD-1 therapy.

• Zipalertinib's regulatory path includes accelerated approval in relapsed settings and frontline studies in combination with chemotherapy.

• Biomarker and translational programs are ongoing to identify predictors of response, especially in ovarian cancer.

• Strategic flexibility maintained for potential partnerships, especially as more data matures.

• Strategic collaborations, notably with Taiho Oncology, enhance commercialization prospects and provide significant milestone and profit-sharing opportunities.