Cullinan Therapeutics, Inc. · NASDAQ:CGEM

Cullinan Therapeutics — Investor Presentation (April 2025)

87 slides from Cullinan Therapeutics's investor presentation, Apr 16, 2025

1. Slide 1: Full Corporate Overview

   FULL CORPORATE OVERVIEW April 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: Investment Highlights

   Investment Highlights CLN-978: CLN-619: ZIPALERTINIB: CD19xCD3 T cell engager (TCE) in Stabilizes unique target, MICA/B, De-risked partnered program in broad development for autoimmune diseases on the tumor cell surface to promote lysis development for NSCLC EGFR exon20 by innate and adaptive immune

5. Slide 5: Diversified pipeline across immunology and oncology

   Diversified pipeline leveraging novel technologies and differentiated mechanisms across immunology and oncology Immunology Program IND- Geographic Phase 1 Phase 2 Phase 3 Status Modality/MOA Enabling Rights SLE global study; initial CLN-978 Systemic lupus erythematosus data in SLE in Q4 2025 CD19xCD

6. Slide 6: 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

7. Slide 7: CLN-978

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

8. Slide 8: Modality-agnostic approach drives rigorous advancement of 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

9. Slide 9: 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

10. Slide 10: 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

11. Slide 11: 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

12. Slide 12: 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

13. Slide 13: 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

14. Slide 14: 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

15. Slide 15: Targeting CD19 achieves broader coverage of B cell compartment

    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

16. Slide 16: 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

17. Slide 17: T cell engagers redirect T cells to eliminate target 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

18. Slide 18: Data show proof of concept for TCEs in autoimmune disease

    Data show proof of concept for TCEs to meaningfully improve upon standard of care across certain autoimmune diseases BLINATUMOMAB: CD19-DIRECTED TCE IN RA AND CD19-DIRECTED TCE IN SLE (N=6) SSc B cell depletion in RA (n=6) B cell depletion in SSc (n=1) SLE peripheral blood CD19+ B cell counts (n=3)

19. Slide 19: 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

20. Slide 20: 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

21. Slide 21: CLN-978 combines 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 POTENTIAL ADVANTAGES IN AUTOIMMUNE DISEASES High affinity, enabling lysis of target cells Therapeutic modality with low CD19 target exp

22. Slide 22: Preclinical subcutaneous dosing 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

23. Slide 23: B-NHL study: sustained B cell depletion with promising results

    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 CLINICALLY ACTIVE AT 30μg SC WEEKLY STARTING C E L L D E P L E T I O N D E M O N S T R AT E D DOSE FOR NHL PATIENTS I N B - N H L PAT I E N T S Rapid

24. Slide 24: CLN-978 differentiated relative to other CD19 TCEs

    CLN-978 is well differentiated relative to other CD19 TCEs in development* POTENTIAL ADVANTAGES OF CLN-978 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 “cytokine window” 2 αCD19 H

25. Slide 25: 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

26. Slide 26: CLN-978-SLE-101 global study design

    CLN-978-SLE-101 global study design PART A: DOSE ESCALATION 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. One or more of

27. Slide 27: 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

28. Slide 28: Rheumatoid Arthritis second indication for CLN-978

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

29. Slide 29: CLN-978-RA-101 initial Phase 1 design

    CLN-978-RA-101 initial Phase 1 design P H A S E 1 D O S E E S C A L AT I O N Cohort 5 (optional; n=3) • Day 1: 10 micrograms • Day 8, 15, 22: 45 micrograms Study Population Cohort 4 (optional; n=3) Objectives • Day 1: 10 micrograms Primary Objective: 1. RA meeting 2010 EULAR/ACR criteria • Day 8: 45

30. Slide 30: 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

31. Slide 31: CLN-978 potential across a broad range of 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

32. Slide 32: CLN-619

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

33. Slide 33: MICA/B serves as a warning signal to the immune system

    MICA/B serves as a warning signal to the immune system to eliminate potentially dangerous cells NKG2D activation results in Malignant transformation lysis of stressed cell NK Cell Viral infection MICA MICB NKG2D Cell stress Radiation Stressed T Cell Cell TCR MHC Normal Stressed Cell Cell Normal cell

34. Slide 34: MICA/B are potentially pan-cancer therapeutic targets

    MICA/B are compelling and potentially pan-cancer therapeutic targets MICA/B are the most highly expressed NKG2D ligands MICA/B ligands have a favorable across 32 different tumor types (TCGA)1 expression profile as a therapeutic target • MICA/B are the most consistently and highly expressed NKG2D lig

35. Slide 35: CLN-619: Potential first-in-class MICA/B targeting antibody

    CLN-619: Potential first-in-class MICA/B targeting antibody CLN-619’S POTENTIAL CLN-619 DESIGN D I F F E R E N T I AT I O N First-in-class potential • Only clinical-stage MICA/B antibody Multiple modes of action: • Inhibits MICA/B shedding • Mediates ADCC and ADCP • Enhances NKG2D receptor binding S

36. Slide 36: CLN-619 engages 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

37. Slide 37: 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,

38. Slide 38: 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 (

39. Slide 39: Pembrolizumab combination: objective responses

    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

40. Slide 40: 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

41. Slide 41: 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 (

42. Slide 42: 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 *

43. Slide 43: 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

44. Slide 44: Monotherapy efficacy: Durable complete response

    Monotherapy efficacy: Durable complete response 83-year-old male patient with mucoepidermoid parotid cancer. Prior systemic therapy before relapse included anti-PD1 antibody therapy with 30 month sustained PR before PD (last dose 4 months before study entry) BASELINE CYCLE 4 CLN-619 CYCLE 7 CLN-619

45. Slide 45: Monotherapy efficacy: Confirmed partial response

    Monotherapy efficacy: Confirmed partial response in a patient with pulmonary metastases BASELINE CYCLE 4 CLN-619 76 year-old patient with endometrial cancer, relapsed after platinum chemotherapy + trastuzumab, doxorubicin, and anastrazole. Progressed at 9-months during immediate prior therapy with p

46. Slide 46: 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

47. Slide 47: 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 +

48. Slide 48: CLN-619 well tolerated as monotherapy and 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) TEAEs, n (%) Any grade Grade ≥3 Any grade Grade ≥3 Fatigue 8 (36.4) 0

49. Slide 49: 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

50. Slide 50: 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

51. Slide 51: 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

52. Slide 52: CLN-619 current development plan in solid and hematologic tumors

    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

53. Slide 53: Zipalertinib

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

54. Slide 54: Exon 20 insertion patients have poorer outcomes

    Patients with exon 20 insertion mutations have poorer outcomes than other more common EGFR mutations 20% Survival is inferior to Patients with exon 20 Real-world outcomes from platinum- patients with sensitive insertion mutations based chemotherapy in the front- mutations receive little benefit line

55. Slide 55: Approved therapies for 2nd line+ leave a large unmet need

    Safety, tolerability and durability of currently approved therapies for 2nd line+ leave a large unmet need Amivantamab *Mobocertinib • IV-dosing • Weekly for 4 weeks (split dose over 2 days, 1st week) Route of Administration1 • Then every 2 weeks • Oral • Premedicate with antihistamines and antipyre

56. Slide 56: Exon 20 insertions largest unmet need segment in EGFR NSCLC

    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

57. Slide 57: 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

58. Slide 58: Superior safety and efficacy at RP2D 100 mg BID

    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 (

59. Slide 59: REZILIENT1 Phase 1/2a: change in target lesions by dose level

    Zipalertinib REZILIENT1 Phase 1/2a: Best percentage change from baseline in target lesion dimensions and confirmed response by dose level ≤65 mg BID 100 mg BID 150 mg BID Overall N (%) N = 23 N = 39 N = 11 N = 73 Confirmed PR1, n (%) 8 (35%) 16 (41%) 4 (36.4%) 28 (38.4%) SD 14 (60.9%) 22 (56.4%) 6 (

60. Slide 60: Differentiated safety and tolerability profile at 100 mg BID

    Differentiated safety and tolerability profile of zipalertinib at 100 mg BID Dose BID ≤65 mg (N = 23) 100 mg (N = 39) 150 mg (N = 11) Overall (N = 73) AE Term, n (%) All grade1 Grade ≥ 𝟑𝟑 All grade Grade ≥ 𝟑𝟑 All grade Grade ≥ 𝟑𝟑 All grade Grade ≥3 Rash 19 (83) 0 32 (82) 0 7 (64) 1 (9) 58…

61. Slide 61: 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

62. Slide 62: 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

63. Slide 63: Efficacy after prior amivantamab similar 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) 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

64. Slide 64: 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

65. Slide 65: 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 (

66. Slide 66: January 2025 REZILIENT1 update: pivotal Phase 2b met primary endpoint

    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

67. Slide 67: 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

68. Slide 68: Taiho 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

69. Slide 69: CLN-049

    CLN-049 FLT3xCD3 T cell Engager © CULLINAN THERAPEUTICS, INC. ALL RIGHTS RESERVED.

70. Slide 70: Significant unmet need in adult AML

    Significant unmet need in adult AML • The only curative therapy is intensive chemotherapy +/- stem cell transplantation • Curative therapy remains out of reach for most US AML Incidence 20,8001 AML patients: 85% patients >60 years old are ineligible for intensive chemotherapy • Recent treatment adva

71. Slide 71: FLT3: An optimal target for AML immunotherapy

    FLT3: An optimal target for AML immunotherapy Validation: FLT3 plays a key role in promoting leukemic cell 1 proliferation and survival. Tyrosine kinase inhibitors (XOSPATA®, RYDAPT®) treat 20-30% of AML by targeting only mutant FLT3 Potential for treatment of broad AML population: Targeting the ext

72. Slide 72: Compelling biological rationale for FLT3 targeted approach in AML

    Compelling biological rationale for FLT3 targeted therapeutic approach in AML Most AML patients express FLT3 on blast cell surface1 Limited expression of FLT3 mRNA in normal tissues1 Florescence Activated Cell Sorting (FACS) Analysis RNA >10 10 3 8 MFI ratio FLT32 6 4 2 0 1 27 53 79 105 131 157 183

73. Slide 73: CLN-049: Novel T cell engager targeting FLT3

    CLN-049: A novel T cell engager targeting FLT3 in Phase 1 for r/r AML or MDS and in Phase 1 for MRD in AML CLN-049’S POTENTIAL CLN-049 DESIGN D I F F E R E N T I AT I O N Wide therapeutic window • Two FLT3-binding Fab arms allow for higher avidity binding to AML cells, potentially increasing efficac

74. Slide 74: CLN-049 mechanism allows broad FLT3 dependent AML blast killing

    CLN-049 mechanism potentially allows for broad FLT3 dependent AML blast killing Redirects lysis of AML cells expressing mutant 1 or wildtype FLT3 2 Functionally monovalent CD3 binding domains 2 prevent T cell activation in absence of target cells 1 3 Two FLT3 binding domains drives potent eliminatio

75. Slide 75: CLN-049 preclinical data supports mechanism and AML cell elimination

    CLN-049 preclinical data supports mechanism of FLT3-dependent T cell activation and broad AML cell elimination resulting in improved survival Potent redirected lysis of AML cell lines with No T cell activation by CLN-049 in the absence 1 wildtype or mutant FLT3 2 of target cells Potent elimination o

76. Slide 76: CLN-049 Phase 1 multiple ascending dose design

    CLN-049 Phase 1 multiple ascending dose design in r/r AML or MDS Intravenous dosing module progressing R E L A P S E D / R E F R A C T O R Y A M L A N D H Y P O M E T H Y L AT I N G A G E N T ( H M A ) - R / R M D S Accelerated Titration Standard Titration Single Patient Cohort Escalation 3 + 3 Coho

77. Slide 77: CLN-049 Phase 1 study design in MRD in AML

    CLN-049 Phase 1 study design in measurable residual disease in AML Dose Escalation Dose Expansion Accelerated Titration Standard Titrations Further exploration of one or more dosing schedules based on clinical activity and PK/PD observations from dose escalation Single Patient Cohort Escalation i3 +

78. Slide 78: CLN-617

    CLN-617 Collagen-binding IL-12 and IL-2 fusion protein © CULLINAN THERAPEUTICS, INC. ALL RIGHTS RESERVED.

79. Slide 79: CLN-617: IL-2 and IL-12 combined in a single molecule

    CLN-617: Combination of synergistic cytokines, IL-2 and IL-12, into a single molecule designed to simulate natural responses CLN-617 has been designed with three key differentiating principles in mind 1 Cytokines are autocrine/paracrine in 2 A protein injected locally will not stay 3 Natural respons

80. Slide 80: Systemic IL-2 and IL-12 efficacy limited by toxicity

    Systemic IL-2 and IL-12 each have validated efficacy but toxicity has limited utility SYSTEMIC INTERLEUKIN 2 (IL-2) SYSTEMIC INTERLEUKIN 12 (IL-12) • Clinical validation: Aldesleukin is an IL-2 • Clinical validation: Multiple trials in humans product that has been approved for the have demonstrated

81. Slide 81: IL-2 and IL-12 are highly synergistic

    IL-2 and IL-12 are highly synergistic • IL-2 and IL-12 mediate orthogonal signaling pathways1,2 • Both IL-2 and IL-12 upregulate each other’s receptors, leading to a synergistic feed-forward pathway3-5 • The two cytokines synergize to enhance production of anti-tumor cytokines, proliferation of effe

82. Slide 82: Preclinical data shows CLN-617 is retained in the tumor

    Preclinical data shows CLN-617 is retained in the tumor Very low concentration of CLN-617 detected Retention is critical to preventing systemic exposure in serum following IT administration Without retention With retention 2h post-treatment 100000 IT 24x 80000 IV pM in Serum 60000 28x Transient tumo

83. Slide 83: CLN-617 single-agent activity in checkpoint refractory tumor models

    CLN-617 demonstrates single-agent activity against a wide variety of checkpoint refractory tumor models with minimal toxicity B16F10 CT26 MC38 Melanoma Model Colorectal Cancer Model Colorectal Cancer Model 10/10 CRs 8/10 CRs mCLN-617 mediates improved survival in anti-PD1 refractory 2/10 CRs tumor m

84. Slide 84: Robust systemic antitumor responses and synergy with anti-PD1

    Preclinical data shows robust systemic antitumor responses in distal tumors and synergy with anti-PD1 therapy Systemic immune response as monotherapy; synergy with anti-PD1 Injected Tumor Uninjected Tumor Dual flank tumor study mCLN-617 Injected Flank Tumor Uninjected Liver Mets Liver metastasis mod

85. Slide 85: CLN-617's positioning relative to alternative cytokine approaches

    CLN-617’s positioning relative to alternative cytokine approaches Tumor targeted Nucleic acid Protease Systemic Therapeutic Feature CLN-617 Not-alpha IL-2 Immuno- cytokine activated cytokines cytokines delivery cytokines Leverage synergy between IL-2 and IL-12       Use of fully human domains,

86. Slide 86: CLN-617 clinical development plan

    CLN-617 clinical development plan PA RT 1 : D O S E E S C A L AT I O N PART 2: DOSE OPTIMIZATION PA RT 3 : D O S E E X PA N S I O N n=3~12 CLN-617-Dose Level 6 Per cohort + Anti-PD1 CLN-617-Dose Level 5 Cohort 1, n=15 + Anti-PD1 Test two dose levels, e.g., Top 2 tolerable dose levels Advanced or met

87. Slide 87: Thank You

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

Cullinan Therapeutics — Investor Presentation (April 2025) on 6ix