Cullinan Therapeutics, Inc. · NASDAQ:CGEM

Cullinan Therapeutics — Investor Presentation (September 2024)

51 slides from Cullinan Therapeutics's investor presentation, Sep 17, 2024

  1. Slide 1: Corporate Overview

    CORPORATE OVERVIEW September 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-978 CLN-619 Zipalertinib Additional clinical CD19xCD3 TCE for SLE Pan cancer EGFR inhibitor for EGFR programs and RA anti-MICA/B mAb ex20ins NSCLC  First-in-class potential in  First-in-class potential  Best-in-class potential

  5. Slide 5: CLN-978

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

  6. Slide 6: 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

  7. Slide 7: 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

  8. Slide 8: TCEs achieve deep and durable B cell depletion and provide off-the-shelf option

    TCEs achieve deep and durable B cell depletion and provide a convenient, off-the-shelf treatment option mAbs CAR T ADVANTAGES ADVANTAGES • Off-the-shelf • High efficacy • Favorable safety profile • Potentially disease modifying • B cell depletion in tissue DISADVANTAGES mAbs TCEs CAR T • Immune rese

  9. Slide 9: Targeting CD19 achieves broader coverage of the B cell compartment

    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

  10. Slide 10: CLN-978 combines the optimal target (CD19) and modality (TCE)

    CLN-978 combines the optimal target (CD19) and modality (TCE) for a highly differentiated, potentially best-in-class asset CLN-978 CLN-978 CD19 X CD3 T CELL ENGAGER P R A C T I C A L A D VA N TA G E S I N A U T O I M M U N E D I S E A S E S High affinity, enabling lysis of target cells Therapeutic m

  11. Slide 11: CLN-978 is well differentiated relative to other CD19 TCEs in development

    CLN-978 is well differentiated relative to other CD19 TCEs in development* Route of Asset Company Stage of Dev. (Indication) Key SLE Trial Attributes Additional Autoimmune Indications Admin. Approved (ALL) Blinatumomab Amgen SC SLEDAI ≥ 8 with LN None Disclosed Est. SLE Start: Aug '24 SLEDAI ≥ 8 CLN

  12. Slide 12: CLN-978 pre-clinical highlights: subcutaneous dosing 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 80000 IV SC

  13. Slide 13: Deep B cell depletion in bone marrow, spleen and lymphoid tissues

    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 15 80 60 Vehicle Percent CD20+ cells Percent CD20+ cells 60 0.1 mg/kg Percent CD20+ cells 10 1 mg/kg 4

  14. Slide 14: 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

  15. Slide 15: Subject #3 case study: patient with 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

  16. Slide 16: 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

  17. Slide 17: 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

  18. Slide 18: Systemic Lupus Erythematosus: High Unmet Need Creates a 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

  19. Slide 19: Opportunity for CLN-978 across a range of outcomes in SLE

    Due to CAR T cell therapy limitations, opportunity exists for CLN-978 across a range of outcomes in SLE Anti-malarials Corticosteroids NSAIDs Immunosuppressives Opportunity Gap Immunomodulatory BLyS CD19 Therapy Anti-IFN-1 CAR T Current Standards of Care Lower efficacy Higher efficacy Symptomatic re

  20. Slide 20: Rheumatoid Arthritis (RA) to be second indication for CLN-978

    Rheumatoid Arthritis (RA) to be second indication for CLN-978 • Initial study to be developed in collaboration with leading institutions that pioneered initial proof-of- concept study of a CD19 TCE in RA © CULLINAN THERAPEUTICS, INC. ALL RIGHTS RESERVED. 20

  21. Slide 21: Rheumatoid Arthritis: Large pool of highly refractory patients

    Rheumatoid Arthritis (RA): Large pool of highly refractory patients High Unmet Need U.S. RA Market Opportunity – 2024 Estimate  Rheumatoid arthritis (RA) is a chronic inflammatory disease that mainly affects the joints with 1,723,000 Diagnosed patients (>=18 years of age) pathogenesis associated wi

  22. Slide 22: Large group of refractory RA patients who fail available DMARDs

    Large group of refractory RA patients who fail available DMARDS; Long term potential to compete against multiple biologics ~1,100,000 Methotrexate patients on therapy • No transformational therapies expected from TNF Inhibitors RA development pipeline. • Current therapies result in chronic immune IL

  23. Slide 23: 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 Rheumatoid arthritis Pemphigus vulgaris Myasthenia gravis Multiple Sclerosis Autoimmune hem

  24. Slide 24: 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 subcut

  25. Slide 25: CLN-619

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

  26. Slide 26: 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

  27. Slide 27: 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,

  28. Slide 28: 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 (

  29. Slide 29: 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

  30. Slide 30: 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

  31. Slide 31: 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 (

  32. Slide 32: 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

  33. Slide 33: 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

  34. Slide 34: 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

  35. Slide 35: 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

  36. Slide 36: 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

  37. Slide 37: 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

  38. Slide 38: 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

  39. Slide 39: 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

  40. Slide 40: Zipalertinib (CLN-081/TAS6417)

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

  41. Slide 41: Exon 20 insertions make up the largest unmet need in 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 incidence2: Ex20 234,580 12% NSCLC1: 80%-85% Ex19 Deletion 47% L858R Exon 203-5: 32% 1.5%-2.0%

  42. Slide 42: 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 @ 100 MG BID Distinct chemical scaffold ~40% Confirmed ORR in Ph 1/2a and pivotal Ph 2b cohort post amivantamab HER2-sparing

  43. Slide 43: Zipalertinib: Safety and efficacy at RP2D 100 mg BID in REZILIENT1

    Zipalertinib: Superior safety and efficacy observed at RP2D 100 mg BID dose level in REZILIENT1 Phase 1/2a <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 R

  44. Slide 44: Update on initial patients in the prior chemo + amivantamab cohort

    Update on initial patients treated in the prior chemo + amivantamab cohort of REZILIENT1 REZILIENT11 REZILIENT22 REZILIENT33 Pivotal Phase 2b Phase 2 Parallel Cohort Study 1L Randomized Phase 3 (fully enrolled SEP 2024) (initiated Q3 2023) Prior chemo only Active brain mets (+/- prior treatment) Zip

  45. Slide 45: 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 Ami onlya Ami + other ex20insb Total Characteristics, n (%) (n=28) (n=17) (N=45) Median age, y (range) 62 (36–85) 63 (33–77) 62 (33–85) Female 20 (71) 14 (82) 34 (76) Race Asian 13 (46) 7 (41) 20 (44) White 13

  46. Slide 46: Zipalertinib after prior amivantamab shows similar efficacy to Phase 1/2a

    Zipalertinib treatment after prior amivantamab shows similar efficacy to Phase 1/2a results Ami only Ami + other ex20ins Total Statistics, n (%) [95% CI] (n=18*) (n=12) (N=30) Data cut-off 12 January 2024 9 (50.0) 3 (25.0) 12 (40.0) Confirmed ORR [26.0–74.0] [5.5–57.2] [22.7–59.4] 1 (5.6) 1 (3.3) CR

  47. Slide 47: Best reduction from baseline

    Best Percentage Change from Baseline of Target Lesions 20% 10% • Radiographic tumor regression in all but 0% 2 patients who died (10%) prior to 1st on study Best reduction from baseline imaging (20%) in target lesions (%) (30%) Avg. • Zipalertinib was clinically active in (40%) patients who had (50%

  48. Slide 48: 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 Ami Ami + other Ami Ami + other Total TRAE Grade ≥3 Total TRAE ≥10%, n (%) only ex20ins only ex20ins (N=45) (≥2 patients), n (%) (N=45) (n=28) (n=17) (n=28) (n=17) Rash 12 (43) 5 (29) 17 (38) Anemia 2 (7) 2 (

  49. Slide 49: 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 Phase 2 Parallel Cohort Study 1L Randomized Phase 3 (fully enrolled SEP 2024) (initiated Q3 2023)

  50. Slide 50: 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 demon

  51. Slide 51: Thank You

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

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