Cullinan Therapeutics, Inc. · NASDAQ:CGEM
Cullinan Therapeutics — Corporate Update (June 2024)
35 slides from Cullinan Therapeutics's corporate update, Jun 3, 2024
Slide 1: CLN-619 and Zipalertinib Updates at ASCO June 2024
CLN-619 and Zipalertinib Updates at ASCO June 2024
Slide 2: Important Notice and Disclaimers
Important Notice and Disclaimers This presentation contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. All statements other than statements of historical facts contained in this presentation, including statements regarding our strategy, fut
Slide 3: Agenda
Agenda Opening Remarks CLN-619 +/- pembrolizumab in patients with advanced solid tumors Zipalertinib in amivantamab pre-treated patients Unmet need and treatment landscape in EGFR mutated NSCLC Nadim Ahmed CEO, Cullinan Therapeutics Jeff Jones, MD CMO, Cullinan Therapeutics Alexander Spira, MD, PhD
Slide 4: Cullinan Therapeutics: Our Mission
CULLINAN THERAPEUTICS Our Mission: Create new standards of care for patients We use a unique R&D model of identifying high-impact targets and then applying the best modality to address each target We are rigorously advancing only highly-differentiated molecules, yielding a robust portfolio of clinic
Slide 5: Diversified portfolio leveraging novel technologies and differentiated mechanisms
Diversified portfolio leveraging novel technologies and differentiated mechanisms Program Modality/MOA IND- Enabling Phase 1 Phase 2 Phase 3 Status Zipalertinib (CLN-081/TAS6417) EGFRex20ins inhibitor CLN-049 FLT3xCD3 T-cell engager CLN-619 Anti-MICA/B antibody CLN-978 CD19xCD3 T-cell engager CLN-61
Slide 6: Cash supports progress into 2028; near-term value-creation opportunities
Cash of $435m* + gross proceeds of $280M from Q2 2024 equity raise supports progress into 2028 *As of March 31, 2024 (unaudited), includes cash equivalents, investments, and interest receivable Poised for multiple value-creation opportunities in the near-term Next milestone/ status Zipalertinib EGFR
Slide 7: CLN-619 Phase I Dose Escalation Data Update
CLN-619 Phase I Dose Escalation Data Update
Slide 8: Today's Update
Today’s Update Initial data from the CLN-619 + pembrolizumab dose escalation Updated observations from the CLN-619 monotherapy dose escalation Implications for future development
Slide 9: CLN-619 engages both innate and adaptive immune cells
CLN-619 engages both innate and adaptive immune cells CLN-619 Multiple MoAs TCR ADCC, antibody-dependent cellular cytotoxicity; ADCP, antibody-dependent cellular phagocytosis; CPI, checkpoint inhibitor; FcgR, Fc gamma receptor; MoA, mechanism of action; NKG2D, natural killer group 2D receptor; NK, n
Slide 10: CLN-619 studied as monotherapy and in combination with pembrolizumab
CLN-619 is being studied as monotherapy and in combination with a CPI, pembrolizumab Phase 1 study design NCT05117476 Corticosteroid, antihistamine, and antipyretic premedications for IRR prophylaxis were required 30–60 minutes before Cycle 1 Day 1 Patients in extension cohorts were required to prov
Slide 11: Enrolled patients had heavily pretreated advanced solid tumors
Enrolled patients had heavily pretreated advanced solid tumors; many had disease progression after prior treatment with a CPI CLN-619 + pembrolizumab (n=22) CLN-619 monotherapy (n=42) Age, y, median (range) 68.5 (38, 82) 62.5 (26, 83) Female, n (%) 11 (50.0) 25 (59.5) ECOG PS 1, n (%) 15 (68.2) 28 (
Slide 12: Pembrolizumab combination: Objective responses in tumor types typically unresponsive to CPI
Pembrolizumab combination: Objective responses in patients with tumor types typically unresponsive to CPI therapy 22 patients treated with CLN-619 + pembrolizumab; 18 patients were RECIST-evaluable for response* Confirmed responses (all PR) were observed at CLN-619 doses ≥ 3 mg/mg Tumor type Gastric
Slide 13: Pembrolizumab combination: Objective responses in tumor types typically unresponsive to CPI
Pembrolizumab combination: Objective responses in patients with tumor types typically unresponsive to CPI therapy Tumor type No. of prior lines of therapy Prior CPI CPI Responsive Tumor Best response DoR, wks NSCLC, ALKr 2 No No PR 12.7 Gastric, HER2+ 3 No Yes PR 8.9+ (ongoing) NSCLC, EGFRm exon 18/
Slide 14: Enrolled patients had heavily pretreated advanced solid tumors
Enrolled patients had heavily pretreated advanced solid tumors; many had disease progression after prior treatment with a CPI CLN-619 + pembrolizumab (n=22) CLN-619 monotherapy (n=42) Age, y, median (range) 68.5 (38, 82) 62.5 (26, 83) Female, n (%) 11 (50.0) 25 (59.5) ECOG PS 1, n (%) 15 (68.2) 28 (
Slide 15: Updated monotherapy efficacy shows durability of clinical benefit
Updated monotherapy efficacy shows durability of clinical benefit, including objective responses across multiple tumor types Total treated: N=42 Dose ≥1 mg/kg and RECIST evaluable: N=29 CBR = 41.4% (1 CR, 2 PR, 9 SD ≥18 weeks) Endometrial Adenoid Cystic Carc Breast Ovarian Pancreatic Parotid Gland M
Slide 16: Durable clinical benefit of CLN-619 monotherapy across tumor types
Durable clinical benefit of CLN-619 monotherapy has been observed across a range of tumor types Durable objective response observed in patients with disease progression after prior CPI Durable stable disease observed in a more extensive group of tumors, including gynecologic malignancies (cervical,
Slide 17: NSCLC patients with oncogenic mutations experienced clinical benefit
Patients with NSCLC harboring oncogenic mutations experienced clinical benefit with both monotherapy and combination therapy Mutation, histology EGFRm, Adeno None, Adeno ALKr, Adeno TP53, Squamous EGFRm, Adeno ALKr, Adeno STK11 APC, Adeno BRAF V600E, Adeno Time on treatment and clinical activity in
Slide 18: Durable partial response in EGFRm NSCLC with liver metastasis
Durable partial response in EGFRm NSCLC with liver metastasis BASELINE 32mm Cycle 4 Day 1 14mm Cycle 7 Day 1 8mm Cycle 10 Day1 8mm 69y patient with NSCLC (EGFR mutation: G719 X in exon18 + L861 in exon 21) Entered study after 6 prior lines of prior therapy, including cisplatin + etoposide, gefitinib
Slide 19: CLN-619 was well tolerated as monotherapy and in combination
CLN-619 was well tolerated as a monotherapy and in combination with pembrolizumab Treatment-related AEs reported in ≥10% of patients were fatigue (combination: 18.2%; monotherapy: 9.5%) and infusion related reactions (IRRs combination: 18.2%; monotherapy: 28.6%) Most IRRs were grade 1 or 2, occurred
Slide 20: Key Takeaways
Key Takeaways Objective responses were observed with CLN-619 + pembrolizumab in patients with tumor types typically unresponsive to pembrolizumab (e.g., NSCLC with ALKr and EGFRm) CLN-619 + pembrolizumab was well tolerated Longer follow-up for patients treated with CLN-619 monotherapy confirms durab
Slide 21: CLN-619 + Chemotherapy
CLN-619 + Chemotherapy Platinums and taxanes upregulate MICA/B expression in vitro Chemotherapy leads to increased infiltration/ activation of immune cells including CD8 T/NK cells in preclinical models Several chemotherapeutic agents are known inducers of immunogenic cell death Hypothesis Chemother
Slide 22: CLN-619 current development plan in solid and hematologic tumors
CERVICAL CANCER Monotherapy (10 mg/kg) ENDOMETRIAL CANCER Monotherapy (3 mg/kg, 10 mg/kg) NSCLC Adenocarcinoma priority EGFR or ALK Combination with Checkpoint Inhibitor (3 mg/kg, 10 mg/kg) Monotherapy (10 mg/kg) Combination with Checkpoint Inhibitor (10 mg/kg) R/R MULTIPLE MYELOMA Monotherapy (Phas
Slide 23: Zipalertinib Data Update
ZIPALERTINIB Data Update J cullinan’ THERAPEUTICS
Slide 24: Exon 20 insertion patients make up the largest unmet need segment of EGFR-mutated lung cancer
Patients with insertions at exon 20 make up the largest unmet need segment of the lung cancer population with EGFR mutations U.S. Lung cancer incidence1: 234,580 NSCLC1: 80%-85% Exon 202-4: 1.5%-2.0% of NSCLC ~2,800-4,000 patients Other 9% Ex19 Deletion 47% L858R 32% Ex20 12% EGFR MUTATED NSCLC1 U.S
Slide 25: Zipalertinib: Selective EGFR inhibitor with best-in-class potential
Zipalertinib (CLN-081/TAS6417): Selective EGFR inhibitor with best-in-class potential for NSCLC patients with exon20 mutations ZIPALERTINIB: UNIQUE DESIGN PROPERTIES Distinct chemical scaffold HER2-sparing High selectivity to mutant vs WT EGFR 41% confirmed overall rate of response (16/39) 12-month
Slide 26: Zipalertinib: Superior safety and efficacy at 100mg BID in REZILIENT1
Zipalertinib: Superior safety and efficacy observed at 100mg BID dose level in REZILIENT1 Phase 1/2a cohorts <65 mg (N=23) 100 mg (N=39) 150 mg (N=11) Total (N=73) ORR 8 (35%) 16 (41%) 4 (36%) 28 (38%) Median PFS 8 mo 12 mo 8 mo 10 mo Gr3+ Rash 0 0 1 (9%) 1 (1%) Gr3+ Diarrhea 0 0 2 (18%) 2 (3%) Dose
Slide 27: Update on initial patients in prior chemo + amivantamab cohort of REZILIENT1
Update on initial patients treated in the prior chemo + amivantamab cohort of REZILIENT1 REZILIENT33 Clinicaltrials.gov identifiers: 1NCT04036682, 2NCT05967689 and 3NCT05973773; * includes both approved and investigational exon20 therapies ** following 6-12 patient safety lead in. PACC = P-loop and
Slide 28: Enrolled patients were heavily pre-treated, nearly 50% with brain metastases
Enrolled patients were heavily pre-treated, and nearly 50% had history of brain metastases Characteristic All Patients (N=31) Age (years), median (range) 62.5 (39-77) Female 23 (74.2) Male 8 (25.8) ECOG Performance Status, N (%) 0 8 (25.8) 1 23 (74.2) Prior systemic cancer regimens, N (
Slide 29: Zipalertinib after prior amivantamab shows similar efficacy to Phase 1/2a
Zipalertinib treatment after prior amivantamab shows similar efficacy to Phase 1/2a results in patients receiving prior chemo alone Piotrowska Z, et al: JCO 2023 Disease Control Rate = (PR+SD) / response evaluable patients Data cut-off 12 January 2024 post chemo and Ami +/- other ex20ins treatment (
Slide 30: Best Percentage Change from Baseline of Target Lesions
Best Percentage Change from Baseline of Target Lesions Radiographic tumor regression in all but 1 patient who died prior to 1st on study imaging Zipalertinib was clinically active in patients who had received both amivantamab and other exon20ins drugs -100% -93% -74% -63% -60% -50% -43% -43% -28% -2
Slide 31: Time on treatment and activity
Time on treatment and activity Module C Ami Only Module C Ami+ex20ins Drug
Slide 32: No new safety signals observed in the post amivantamab population
No new safety signals observed in the post amivantamab population Grade 3 TRAE AE Any Grade Preferred Term All Patients (N=31) Grade 3 Any TRAE 6 (19.4) Anemia 1 (3.2) Amylase increased 1 (3.2) Lymphocyte decrease 1 (3.2) Hypoxia 1 (3.2) ILD 1 (3.2) Pneumonitis 1 (3.2) Folliculitis 1
Slide 33: REZILIENT program: zipalertinib development across multiple studies
REZILIENT program: zipalertinib development across multiple studies and indications, including 2 pivotal trials, in collaboration with Taiho Oncology REZILIENT33 Clinicaltrials.gov identifiers: 1NCT04036682, 2NCT05967689 and 3NCT05973773; * includes both approved and investigational exon20 therapies
Slide 34: Key Takeaways
Key Takeaways Zipalertinib shows promising anti-tumor activity in patients with exon20ins mutation NSCLC who have received prior treatment with amivantamab Objective response rate was similar to prior reports in patients with disease relapsed after prior platinum chemotherapy Zipalertinib demonstrat
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