Cullinan Therapeutics, Inc. · NASDAQ:CGEM

Cullinan Therapeutics — Investor Presentation (February 2025)

57 slides from Cullinan Therapeutics's investor presentation, Feb 27, 2025

  1. Slide 1: Corporate Overview

    CORPORATE OVERVIEW February 2025 © 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 express or implied statements regardin

  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 CD19xCD3 TCE for Pan cancer EGFR inhibitor for clinical programs SLE and RA anti-MICA/B mAb EGFR 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: Modality-agnostic approach drives rigorous advancement of highly-differentiated molecules

    Modality-agnostic approach drives rigorous advancement of highly- differentiated molecules to create new standards of care for patients Our unique R&D model enabling potential best-in-class molecules Advancing differentiated Deep scientific expertise to Applying best modality to molecules to maximiz

  7. Slide 7: Growing global prevalence of autoimmune diseases

    Growing global prevalence of autoimmune diseases despite treatment advances underscores need for treatments that deliver durable remissions OPPORTUNITY FOR OTHER B CELL MEDIATED CURRENT DEVELOPMENT FOCUS AUTOIMMUNE DISEASES Systemic Combined ~21.4M Idiopathic Combined ~13M patients globally Myasthen

  8. Slide 8: Applying Cullinan's research model to autoimmune diseases

    Applying Cullinan’s research model to accelerate research for patients with autoimmune diseases Best modality to address Differentiated, patient- High-impact targets optimal target friendly molecules What role do B cells play in What does research tell us is the How do we design the optimal autoimmu

  9. Slide 9: Autoimmune diseases driven by dysregulated B cells

    Autoimmune diseases are thought to be caused by an overly active immune response, mainly driven by dysregulated B cells Adaptive immunological memory resides in subsets of B cells BONE MARROW S E C O N D A RY LY M P H O I D O R G A N S A N D C I R C U L AT I O N Stem Pro-B Pre-B Immature Naïve Memor

  10. Slide 10: B cells play key roles in pathogenic processes

    B cells play key roles in pathogenic processes in autoimmune diseases, making them an attractive, well-validated therapeutic target Antibody production Cytokine production B cells develop into plasma blasts and plasma cells that Important source of cytokines release autoantibodies, which are pathoge

  11. Slide 11: Deep and durable B cell depletion could drive immune reset

    Treatments that achieve deep and durable B cell depletion could drive immune reset Therapies that achieve durable immune reset could provide meaningful improvements over current immunosuppressive therapies Before Treatment After Treatment After B cell Reconstitution Monoclonal antibody mediated B ce

  12. Slide 12: Applying Cullinan's research model to autoimmune diseases

    Applying Cullinan’s research model to accelerate research for patients with autoimmune diseases High-impact targets Best modality to address Differentiated, patient- optimal target friendly molecules What does research tell us is What role do B cells play in How do we design the optimal the best way

  13. Slide 13: Targeting CD19 achieves broader coverage than CD20 or BCMA

    Targeting CD19 achieves broader coverage of the B cell compartment compared to CD20 or BCMA for deeper, more durable B cell depletion Stem Pro-B Pre-B Immature Naïve Memory Short-lived Long-lived Plasmablast Cell Cell Cell B Cell B cell B cell Plasma Cell Plasma Cell CD19 CD20 BCMA • CD19 directed t

  14. Slide 14: B cell depletion resulted in sustained drug free remissions

    Therapies achieving B cell depletion resulted in sustained drug free remissions for B cell malignancies A N T I - C D 1 9 T C E L L E N G A G E R S E S TA B L I S H E D P R O O F - O F - C O N C E P T F O R DISEASE-MODIFYING T CELL REDIRECTING THERAPIES HEM-ONC IMM NHL RA 1997 2001 2021 2024 1st gen

  15. Slide 15: T cell engagers: protein constructs redirecting T cells

    T cell engagers: protein constructs engineered to redirect T cells to eliminate malignant or autoreactive cells expressing a specific cell surface target HOW T CELL ENGAGERS WORK Cytotoxic Cytotoxic proteins T cell • Bispecific TCEs are designed to bring together a cytotoxic granzyme and perforin T

  16. Slide 16: Data show proof of concept for TCEs in autoimmune diseases

    Data show proof of concept for TCEs to meaningfully improve upon standard of care across certain autoimmune diseases B L I N AT U M O M A B : C D 1 9 - D I R E C T E D T C E I N R A A N D S S c CD19-DIRECTED TCE IN SLE (N=6) B cell depletion in RA (n=6) B cell depletion in SSc (n=1) SLE peripheral b

  17. Slide 17: Optimal modality: TCEs for deep and durable B cell depletion

    Optimal modality: TCEs provide high therapeutic potential for deep and durable B cell depletion in a convenient, off-the-shelf treatment option mAbs TCEs CAR T Lower efficacy; limited tissue penetration High efficacy; B cell depletion in tissue High efficacy; B cell depletion in tissue Symptomatic r

  18. Slide 18: Applying Cullinan's research model to autoimmune diseases

    Applying Cullinan’s research model to accelerate research for patients with autoimmune diseases High-impact targets Best modality to address Differentiated, patient- optimal target friendly molecules What role do B cells play in What does research tell us is the How do we design the optimal autoimmu

  19. Slide 19: CLN-978 combines the optimal target and modality

    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 O T E N T I 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

  20. Slide 20: Preclinical: SC dosing of CLN-978 achieved deep B cell depletion

    In preclinical studies, subcutaneous dosing of CLN-978 achieved rapid, deep and sustained B cell depletion in blood and tissue with attenuated cytokine release PRECLINICAL HIGHLIGHTS Deep, sustained peripheral B cell depletion after single dose in NHPs Deep B cell depletion in bone marrow, spleen an

  21. Slide 21: B-NHL patients: sustained B cell depletion with CLN-978

    In a study of B-NHL patients, CLN-978 achieved sustained B cell depletion with promising clinical results R A P I D , D E E P A N D S U S TA I N E D B C L I N I C A L LY A C T I V E AT 3 0 μ g S C W E E K LY S TA R T I N G C E L L D E P L E T I O N D E M O N S T R AT E D D O S E F O R N H L PAT I E

  22. Slide 22: CLN-978 is well differentiated relative to other CD19 TCEs

    CLN-978 is well differentiated relative to other CD19 TCEs in development* P O T E N T I A L A D VA N TA G E S O F C L N - 9 7 8 1 Broader B cell lineage depletion due to very high affinity binding to CD19 αCD3 CD3 binder for T cell (scFv) redirected B cell lysis Wider therapeutic index due to “cyto

  23. Slide 23: Applying Cullinan's research model to autoimmune diseases

    Applying Cullinan’s research model to accelerate research for patients with autoimmune diseases High-impact targets Best modality to address Differentiated, patient- optimal target friendly molecules What role do B cells play in What does research tell us is the How do we design the optimal autoimmu

  24. Slide 24: CLN-978-SLE-001 global study design

    CLN-978-SLE-001 global 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 Cohort 4 (optional; n=3) 1. SLE meeting 2019 • Day 1: 10 micrograms EULAR/ACR criteria Further exploration of 2 or more dosing schedules • Day 8: 45 micrograms Objectives 2. O

  25. Slide 25: SLE: High unmet need in complex disease

    Systemic Lupus Erythematosus (SLE): High unmet need in complex disease with few approved therapies, limited efficacy and chronic immunosuppression SLE - SELECT MARKET OPPORTUNITY HIGH UNMET NEED 2 0 2 4 E S T I M A T E ( U S , E U 5 , J P, A U ) 430,000 • Systemic disease characterized by autoantibo

  26. Slide 26: Rheumatoid Arthritis second indication for CLN-978

    Rheumatoid Arthritis (RA) second indication for CLN-978 CLN-978 initial study to be developed in No transformational therapies expected from collaboration with institutions that pioneered industry RA development pipeline initial POC study of anti-CD19 TCE in RA • Current therapies result in chronic

  27. Slide 27: RA: Large pool of highly refractory patients

    Rheumatoid Arthritis (RA): Large pool of highly refractory patients RA - SELECT MARKET OPPORTUNITY HIGH UNMET NEED 2 0 2 4 E S T I M A T E ( U S , E U 5 , J P, A U ) • Rheumatoid arthritis (RA) is a chronic inflammatory disease that mainly affects the joints with pathogenesis associated 5,300,000 Di

  28. Slide 28: CLN-978 potential as disease-modifying treatment across autoimmune diseases

    CLN-978 has potential to address high unmet need as a disease-modifying treatment across a broad range of autoimmune diseases Best modality to address Differentiated, patient- High-impact targets optimal target friendly molecules Practical advantages of TCEs include: Development in autoimmune diseas

  29. Slide 29: CLN-619

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

  30. Slide 30: CLN-619: Engages both innate and adaptive immune cells

    CLN-619: Engages both innate and adaptive immune cells RESTORATION OF ENHANCEMENT BY CHECKPOINT IMMUNE EVASION IMMUNOSURVEILLANCE INHIBITION (CPI) CLN-619 Single-Agent MoA CLN-619 Plus CPI MoA C L N - 6 1 9 M U LT I P L E M O D E S O F A C T I O N ( M O A S ) 1 2 3 4 Prevention of MICA/B shedding An

  31. Slide 31: CLN-619 studied as monotherapy and with pembrolizumab

    CLN-619 is being studied as monotherapy and in combination with a CPI, pembrolizumab Phase 1 study design Key inclusion criteria 3+3 dose escalation NCT05117476 All cohorts Monotherapy • Adults (≥18 y) with locally advanced CLN-619 IV Q3W Endpoints or metastatic solid tumors Continue for (0.1, 0.3,

  32. Slide 32: 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 (

  33. Slide 33: Pembrolizumab combination: objective responses in CPI-unresponsive tumors

    Pembrolizumab combination: Objective responses in patients with tumor types typically unresponsive to CPI therapy Tumor type Gastric, HER2+ NSCLC, EGFRm NSCLC Prostate • 22 patients treated with NSCLC, ALKr Ovarian CLN-619 + pembrolizumab; NSCLC * 18 patients were RECIST- Head and Neck * Skin evalua

  34. Slide 34: 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

  35. Slide 35: 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 (

  36. Slide 36: 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 * Parotid Gland Mediastinal Intimal Sarc * Endometrial * Cervical * • Total treated: N=42 Cervical Endometrial *

  37. Slide 37: Durable clinical benefit of CLN-619 monotherapy

    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 Tumor type No. of prior lines of therapy Best response DoR, wks Responders (n=3) Mucoepidermoid parotid 2 CR 71 Endometrial (serous, MMRp) 5 PR 31 E

  38. Slide 38: NSCLC patients with oncogenic mutations experienced clinical benefit

    Patients with NSCLC harboring oncogenic mutations experienced clinical benefit with both monotherapy and combination therapy Time on treatment and clinical activity in patients with NSCLC Combination therapy Mutation, histology EGFRm, Adeno • 8 of the 11 patients with NSCLC were RECIST evaluable; of

  39. Slide 39: Durable partial response in EGFRm NSCLC with liver metastasis

    Durable partial response in EGFRm NSCLC with liver metastasis BASELINE C Y C L E 4 D AY 1 C Y C L E 7 D AY 1 C Y C L E 1 0 D AY 1 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 +

  40. Slide 40: CLN-619 was well tolerated

    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) TEAEs, n (%) Any grade Grade ≥3 Any grade Grade ≥3 Fatigue 8 (36.4) 0

  41. Slide 41: Key takeaways

    Key takeaways Objective responses were observed with CLN-619 + pembrolizumab in patients with tumor CLN-619 + pembrolizumab types typically unresponsive to pembrolizumab (e.g., was well tolerated NSCLC with ALKr and EGFRm) Based on these findings, new monotherapy and Longer follow-up for patients tr

  42. Slide 42: CLN-619 + chemotherapy

    CLN-619 + chemotherapy HYPOTHESIS C L I N I C A L R AT I O N A L E Chemotherapy induces cell stress leading to upregulation of MICA/B and can simultaneously Why combine CLN-619 with chemotherapy? have positive immuno-modulatory properties • Platinums and taxanes upregulate MICA/B expression in vitro

  43. Slide 43: CLN-619 in relapsed and refractory multiple myeloma

    CLN-619 in relapsed and refractory multiple myeloma CLN-619’s Potential in r/r Part 1 Dose Escalation Design Multiple Myeloma 3+3 cohort escalation Scientific rationale: • NK cells act as important regulators of MM progression and their suppressive activity against MM cells has been confirmed 6 mg/k

  44. Slide 44: CLN-619 current development plan

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

  45. Slide 45: Zipalertinib

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

  46. Slide 46: Exon 20 insertions: 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 Ex20 U.S. lung 9% 12% cancer incidence2: 234,580 NSCLC1: 80%-85% Ex19 Deletion 47% L858R 1.5%-2.0% of NSCLC 32% Ex

  47. Slide 47: 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 INTERIM DATA @ 100 MG BID Distinct chemical scaffold ~40% Confirmed ORR in Ph 1/2a and pivotal Ph 2b cohort post amivantamab (ESMO

  48. Slide 48: Zipalertinib: safety and efficacy at RP2D in Phase 1/2a

    Zipalertinib: Superior safety and efficacy observed at RP2D 100 mg BID dose level in the Phase 1/2a component of REZILIENT11 <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 (

  49. Slide 49: Interim ESMO 2024 data update after prior amivantamab

    Interim ESMO 2024 data update in patients with EGFR ex20ins NSCLC after prior amivantamab treatment REZILIENT11 REZILIENT22 REZILIENT33 Pivotal Phase 2b Phase 2 Parallel Cohort Study 1L Randomized Phase 3 (met primary endpoint) (initiated Q3 2023) Prior chemo only Active brain mets (+/- prior treatm

  50. Slide 50: Enrolled patients 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

  51. Slide 51: Zipalertinib after prior amivantamab shows similar efficacy

    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) 9 (50.0) 3 (25.0) 12 (40.0) Confirmed ORR Data cut-off 12 January 2024 [26.0–74.0] [5.5–57.2] [22.7–59.4] 1 (5.6) 1 (3.3) CR

  52. Slide 52: Best percentage change from baseline of target lesions

    Best percentage change from baseline of target lesions 20% 10% 0% Best reduction from baseline (10%) • Radiographic tumor in target lesions (%) (20%) regression in all but 2 Avg. (30%) patients who died prior (40%) to 1st on study imaging (50%) • Zipalertinib was clinically (60%) active in patients

  53. Slide 53: No new safety signals in post amivantamab population

    No new safety signals observed in the post amivantamab population AE Any Grade Grade 3 TRAE Ami only Ami + other ex20ins Total TRAE Grade ≥3 Ami only Ami + other ex20ins Total TRAE ≥10%, n (%) (n=28) (n=17) (N=45) (≥2 patients), n (%) (n=28) (n=17) (N=45) Rash 12 (43) 5 (29) 17 (38) Anemia 2 (7) 2 (

  54. Slide 54: January 2025 REZILIENT1 update: met primary endpoint of ORR

    January 2025 REZILIENT1 update: pivotal Phase 2b study in 2L+ met primary endpoint of ORR REZILIENT11 Pivotal Phase 2b REZILIENT1 pivotal Phase 2b study in 2L+ met its primary endpoint of overall (met primary endpoint) response rate - announced January 2025 Prior chemo only The safety profile was ge

  55. Slide 55: REZILIENT program: broad development across multiple studies

    REZILIENT program: zipalertinib broad 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 (met primary endpoint) (initiated Q3 20

  56. Slide 56: Taiho zipalertinib collaboration provides financial and strategic benefits

    Taiho zipalertinib collaboration provides Cullinan with financial and strategic benefits Upfront Payment $275 million to Cullinan received in 2022 in exchange for providing 50% of U.S. and 100% of ex-U.S. rights to Taiho1 Milestone Payments Cullinan is eligible to receive up to $130 million in payme

  57. Slide 57: Thank You

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

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