Cullinan Therapeutics, Inc. · NASDAQ:CGEM

Cullinan Therapeutics — Investor Presentation (June 2024)

48 slides from Cullinan Therapeutics's investor presentation, June 2024

  1. Slide 1: Corporate Overview

    CORPORATE OVERVIEW June 2024 © CULLINAN THERAPEUTICS, INC. ALL RIGHTS RESERVED.

  2. 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

  3. Slide 3: Our Mission: Create new standards of care for patients

    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 cl

  4. Slide 4: Poised for multiple value-creation opportunities in the near-term

    Poised for multiple value-creation opportunities in the near-term CLN-619 Zipalertinib CLN-978 3 other clinical Pan cancer EGFR inhibitor for EGFR CD19xCD3 TCE for SLE stage programs anti-MICA/B mAb ex20ins NSCLC ▪ First-in-class potential ▪ First-in-class potential in ▪ Best-in-class potential ▪ CL

  5. Slide 5: CLN-619

    CLN-619 MICA/B-directed mAb © CULLINAN THERAPEUTICS, INC. ALL RIGHTS RESERVED.

  6. Slide 6: CLN-619: Engages both innate and adaptive immune cells

    CLN-619: Engages both innate and adaptive immune cells IMMUNE EVASION RESTORATION OF IMMUNOSURVEILLANCE ENHANCEMENT BY CHECKPOINT INHIBITION (CPI) CLN-619 Single-Agent MoA CLN-619 Plus CPI MoA CLN-619 Multiple Modes of Action (MoAs) 1 Prevention of MICA/B shedding 2 Antibody-dependent cellular cytot

  7. Slide 7: 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 Key inclusion criteria 3+3 dose escalation All cohorts • Adults (≥18 y) with locally advanced Monotherapy or metastatic solid tumors CLN-619 IV Q3W Continue for Endpoints (0.1, 0.3,

  8. Slide 8: 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 CLN-619 monotherapy (n=22) (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 (

  9. Slide 9: Pembrolizumab combination: Objective responses in CPI-unresponsive tumor types

    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 Gas

  10. Slide 10: Pembrolizumab combination: Characteristics of responders

    Pembrolizumab combination: Objective responses in patients with tumor types typically unresponsive to CPI therapy Characteristics of responders No. of prior CPI Responsive Tumor type Prior CPI Best response DoR, wks lines of therapy Tumor NSCLC, ALKr 2 No No PR 12.7 Gastric, HER2+ 3 No No PR 8.9+ (o

  11. 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 CLN-619 monotherapy (n=22) (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 (

  12. Slide 12: Updated monotherapy efficacy shows durability of clinical benefit

    Updated monotherapy efficacy shows durability of clinical benefit, including objective responses across multiple tumor types Endometrial Adenoid Cystic Carc * Breast * Ovarian * Pancreatic • Total treated: N=42 Parotid Gland Mediastinal Intimal Sarc * * Endometrial * Cervical Cervical * • Dose ≥1 mg

  13. Slide 13: 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 Characteristics of patients with response or SD ≥18 wks No. of prior lines of Tumor type Best response DoR, wks therapy Responders (n=3) Mucoepidermoid parotid 2 CR 71 Endometrial (serous, MMRp) 5 PR 31 E

  14. Slide 14: NSCLC with oncogenic mutations experienced clinical benefit

    Patients with NSCLC harboring oncogenic mutations experienced clinical benefit with both monotherapy and combination therapy • 8 of the 11 patients with NSCLC were RECIST evaluable; of these, 6 had oncogenic mutations • 3 of the 6 patients with oncogenic mutations experienced clinical benefit • 2 PR

  15. Slide 15: Durable partial response in EGFRm NSCLC with liver metastasis

    Durable partial response in EGFRm NSCLC with liver metastasis BASELINE Cycle 4 Day 1 Cycle 7 Day 1 Cycle 10 Day1 32mm 14mm 8mm 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, gefit

  16. Slide 16: CLN-619 was well tolerated as monotherapy and in combination

    CLN-619 was well tolerated as a monotherapy and in combination with pembrolizumab Any-grade TEAEs in ≥15% of patients or grade ≥3 TEAEsa in ≥5% of patients in either group CLN-619 + pembrolizumab (n=22) CLN-619 monotherapy (n=42) • Treatment-related AEs reported in TEAEs, n (%) Any grade Grade ≥3 An

  17. Slide 17: 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

  18. Slide 18: CLN-619 + Chemotherapy

    CLN-619 + Chemotherapy Chemotherapy induces cell stress leading to upregulation of MICA/B and can HYPOTHESIS simultaneously have positive immuno-modulatory properties • Platinums and taxanes • Chemotherapy leads to • Several chemotherapeutic upregulate MICA/B increased infiltration/ agents are known

  19. Slide 19: CLN-619 current development plan in solid and hematologic tumors

    CLN-619 current development plan in solid and hematologic tumors CERVICAL CANCER Monotherapy (10 mg/kg) Monotherapy ENDOMETRIAL (3 mg/kg, 10 mg/kg) CANCER Combination with Checkpoint Inhibitor (3 mg/kg, 10 mg/kg) PLATINUM- Combination with Chemotherapy RESISTANT (3 mg/kg, 10 mg/kg) OVARIAN CANCER NS

  20. Slide 20: CLN-978

    CLN-978 CD19xCD3 T cell Engager © CULLINAN THERAPEUTICS, INC. ALL RIGHTS RESERVED.

  21. Slide 21: CD19 CAR-T generated immune system reset and durable remissions in autoimmune patients

    CD19 CAR-T cell therapy generated immune system reset and durable, treatment-free remissions in autoimmune patients Immune system reset: selected SLE PD data Observations • Mueller et al. (2024) treated 15 autoimmune patients (SLE, IIM, & SSc)1 with autologous CD19 CAR T • SLE and IIM patients had c

  22. Slide 22: CAR T cell therapy: Promising outcomes but multiple challenges

    CAR T cell therapy: Promising outcomes but multiple challenges may limit broad uptake in autoimmune diseases Cell therapy limitations • Available cellular therapies all require lymphodepleting chemotherapy, which has been associated with increased risk for infection, infertility, and secondary malig

  23. Slide 23: TCE and CAR-T cells have comparable efficacy in NHL

    TCE and CAR-T cells have comparable efficacy in similar NHL patient populations* YESCARTA1 KYMRIAH2 LUNSUMIO3 Axi-cel Tisa-cel Mosunetuzumab Target/Modality CD19 CAR T CD19 CAR T CD20 TCE (IV) ZUMA-5 Phase 2 ELARA Phase 3 GO29781 Phase 2 Study / pt pop R/R FL 3L+ R/R FL 3L+ R/R FL 3L+ ORR / CR (%) 9

  24. Slide 24: Initial Clinical Proof of Concept for CD19xCD3 T Cell Engagers in Autoimmune Diseases

    Initial Clinical Proof of Concept for CD19xCD3 T Cell Engagers in Multiple Autoimmune Diseases Clinical efficacy in 6/6 patients with RA Observations • Bucci et al. (2024) showed effective treatment of 6/6 patients with severe RA refractory to multiple disease-modifying therapies using only a brief

  25. Slide 25: CLN-978: A novel CD19 T cell engager

    CLN-978: A novel CD19 T cell engager designed to deliver T cell directed potency with off-the-shelf convenience CLN-978 3 2 4 1 CLN-978 potently triggers redirected lysis of CD19-expressing target cells in vitro and in vivo 𝛼-CD3 𝛼-CD19 𝛼-HSA (scFv) (scFv) (VHH) 2 Engineered to achieve very high…

  26. Slide 26: Targeting CD19 achieves broader B cell coverage than CD20 or BCMA

    Targeting CD19 achieves broader coverage of the B cell compartment compared to CD20 or BCMA Stem cell Pro-B cell Pre-B cell Immature B cell Mature B cell Memory B Cell Plasmablast Plasma cell CD19 CD20 BCMA ➢ CD19 directed therapies afford significant potential for deep and broad B cell depletion as

  27. Slide 27: CLN-978 pre-clinical highlights in NHPs

    CLN-978 pre-clinical highlights: Subcutaneous dosing achieved rapid, deep and sustained B cell depletion with attenuated cytokine release in NHPs Deep, sustained peripheral B cell Subcutaneous dosing attenuated cytokine release in NHPs depletion after a single dose in NHPs IL-6 TNFα 2.5 IV SC Absolu

  28. Slide 28: Deep B cell depletion in tissues following SC administration

    Deep B cell depletion in bone marrow, spleen and lymphoid tissues following SC administration of CLN-978 in cynomolgus monkeys Bone Marrow Spleen Lymphoid Tissues Bone marrow Spleen Lymphoid tissue 80 80 80 80 15 15 15 15 60 60 60 60 cells Percent CD20+ cells Percent CD20+ cells Vehicle Percent CD20

  29. Slide 29: CLN-978 in B-NHL: Clinically active at starting dose with favorable safety

    CLN-978 in B-NHL: Clinically active at starting dose with favorable safety Clinical observations from B-NHL study (as of 5 April 2024) Disease Characteristics and Efficacy Observations Treatment Emergent Adverse Events1 Prior Duration of Best ID Diagnosis Response Non-Hematological Hematological CRS

  30. Slide 30: Subject #3 case study: mantle cell lymphoma

    Subject #3 case study: 68-year-old patient with mantle cell lymphoma Baseline PET-CT After 7 doses of CLN-978 ▪ 7.4 x 1.7 cm mass in left mandible and adjacent musculature was palpable on physical exam at baseline ▪ Investigator reported mass was no longer appreciated on exam 96 hours following the

  31. Slide 31: Rapid, deep and sustained B cell depletion in B-NHL patients

    Rapid, deep and sustained B cell depletion was demonstrated in B-NHL patients following CLN-978 dosing Peripheral blood TBNK flow assay Data cut-off 20 March 2024 Last dose CLN978 Subject 1 ▪ Rapid, deep and sustained B cell depletion was demonstrated in 2 of 2 subjects with measurable B cells at ba

  32. Slide 32: CLN-978-SLE-001 planned study design

    CLN-978-SLE-001 planned study design PA R T A : D O S E E S C A L AT I O N PAR T B : D O S E E X PAN S I O N Study Population PLANNED DESIGN FEATURES PLANNED DESIGN FEATURES Objectives 1. SLE patients • Step-wise escalation to determine target • Exploration of 2 or more dosing schedules Primary Obje

  33. Slide 33: Systemic Lupus Erythematosus: High Unmet Need Creates Market Opportunity

    Systemic Lupus Erythematosus (SLE)1: High Unmet Need Creates a Compelling Market Opportunity High Unmet Need U.S. SLE Market Opportunity – 2024 Estimate ▪ Systemic disease characterized by 163,000 Diagnosed patients (18-70 y/o) autoantibodies produced by B cells, leading to multiple affected organ s

  34. Slide 34: Substantial number of addressable autoimmune diseases

    Substantial number of addressable autoimmune diseases Opportunity to Address Multiple B Cell Mediated Autoimmune Diseases <50,000+ U.S. Patients 50,000 - 500,000 U.S. Patients 500,000+ U.S. Patients NMOSD SLE Multiple Sclerosis Pemphigus vulgaris Myasthenia gravis Rheumatoid arthritis Autoimmune hem

  35. Slide 35: CLN-978 program: Summary and next steps

    CLN-978 program: Summary and next steps ▪ CLN-978 development refocused exclusively on autoimmune diseases ▪ CD19 is the optimal target for autoimmune diseases • CLN-978 represents a potential first in class opportunity with the following differentiated benefits: • Off-the-shelf convenience and subc

  36. Slide 36: Zipalertinib

    ZIPALERTINIB (CLN-081/TAS6417) EGFRex20ins inhibitor © CULLINAN THERAPEUTICS, INC. ALL RIGHTS RESERVED.

  37. Slide 37: Exon 20 insertions are 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 E G F R M U TAT E D N S C L C 1 U.S. EXON 20 INCIDENCE Other 9% U.S. Lung cancer incidence1: Ex20 234,580 12% NSCLC1: 80%-85% Ex19 Deletion 47% L858R Exon 202-4: 32% 1.5%-2.0%

  38. Slide 38: 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 KEY DATA FROM PH 1/2A STUDY @ 100 MG BID Distinct chemical scaffold 41% confirmed overall rate of response (16/39) HER2-sparing 12-mo

  39. Slide 39: Zipalertinib: Superior safety and efficacy at 100mg BID

    Zipalertinib: Superior safety and efficacy observed at 100mg BID dose level in REZILIENT1 Phase 1/2a cohorts <65 mg 100 mg 150 mg Total (N=23) (N=39) (N=11) (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

  40. Slide 40: Update on patients in prior chemo + amivantamab cohort of REZILIENT1

    Update on initial patients treated in the prior chemo + amivantamab cohort of REZILIENT1 REZILIENT11 REZILIENT22 REZILIENT33 Pivotal Phase 2b cohorts Key Parallel Phase 2 cohorts 1L Randomized Phase 3 (initiated Q4 2022) (initiated Q3 2023) Prior chemo only Active brain mets (+/- prior treatment) Zi

  41. Slide 41: 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 (%)

  42. Slide 42: Zipalertinib after prior amivantamab shows similar efficacy

    Zipalertinib treatment after prior amivantamab shows similar efficacy to Phase 1/2a results in patients receiving prior chemo alone post chemo and Ami +/- other Phase 1/2a results ex20ins treatment (post chemo)1 Data cut-off 12 January 2024 (N=39) (N=18*) Data cut-off 12 January 2024 ORR (confirmed)

  43. Slide 43: Best Percentage Change from Baseline of Target Lesions

    Best Percentage Change from Baseline of Target Lesions 30 20 • Radiographic 10 tumor regression -1% -7% -7% -11% -14% -16% -19% -24% -28% -43% -43% -50% -60% -63% -74% -93% -100% 0 in all but 1 patient Reduction from Baseline in Target Lesions (%) -10 who died prior to 1st on study -20 imaging -30 -

  44. Slide 44: Time on treatment and activity

    Time on treatment and activity 0107-016 0602-011 0501-018 0201-005 0106-011 0104-023 0120-001 0602-013 0201-007 1304-001 0106-016 0107-019 0201-010 0201-009 Patients 0106-019 0102-005 0106-010 0102-006 Module C Ami Only 1109-001 1109-003 0601-008 Module C Ami+ex20ins Drug 1302-005 1204-002 0201-012

  45. Slide 45: No new safety signals observed in the post amivantamab population

    No new safety signals observed in the post amivantamab population AE Any Grade Grade 3 TRAE All Patients (N=31)​ All Patients (N=31)​ Overall Preferred Term​ Any Grade Grade 3​ Any TEAE 29 ( 93.5) Any TRAE​ 6 (19.4)​ Any TRAE 27 ( 87.1) Anemia​ 1 (3.2)​ TRAE of Any Grade in ≥10% of Patients Amylase

  46. Slide 46: 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 REZILIENT11 REZILIENT22 REZILIENT33 Pivotal Phase 2b cohorts Key Parallel Phase 2 cohorts 1L Randomized Phase 3 (initiated Q4 2022) (initiated Q3 2023

  47. Slide 47: 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 demons

  48. Slide 48: Thank You!

    THANK YOU! © CULLINAN THERAPEUTICS, INC. ALL RIGHTS RESERVED.

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