Cullinan Therapeutics, Inc. · NASDAQ:CGEM

Cullinan Therapeutics — Investor Presentation (May 2024)

38 slides from Cullinan Therapeutics's investor presentation, May 15, 2024

  1. Slide 1: Corporate Overview

    CORPORATE OVERVIEW May 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

    Our Mission • Pursuing modality-agnostic targeted therapeutics: o Discovering and identifying high-impact targets o Then applying the best approach to address each target • Rigorously and rapidly advancing only highly differentiated molecules • Yielding a diversified, robust portfolio of clinical-st

  4. Slide 4: Our Approach

    Our Approach We seek to achieve our mission through our rigorous and differentiated approach to drug development Run early “thriller or killer” Seek clear evidence of Innovate without experiments monotherapy activity borders Rapidly advance only potential first-in- Avoid uncertainty of early-stage R

  5. Slide 5: Poised for multiple value-creation opportunities in the near-term

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

  6. Slide 6: CLN-619

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

  7. Slide 7: MICA/B are compelling and 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

  8. Slide 8: CLN-619: Prevents MICA/B shedding to facilitate immune cell engagement and ADCC/P

    CLN-619: Prevents MICA/B shedding to facilitate innate and adaptive immune cell engagement and ADCC/P 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

  9. Slide 9: CLN-619: Ongoing global clinical trial designed for rapid signal generation

    CLN-619: Ongoing global clinical trial designed for rapid signal generation Parallel dose escalation and expansion for CLN-619 Monotherapy + Pembrolizumab combination Eligible patients: any advanced solid tumor Eligible patients: tumor specific cohorts CLN-619 Dose Level Extension Dose Escalation (“

  10. Slide 10: CLN-619 monotherapy efficacy observed across multiple dose levels

    CLN-619 monotherapy efficacy observed across multiple dose levels Time on Treatment and Clinical Activity AR A R A Response R A All RA Evaluable1 R A Patients at ≥1 mg/kg AR A (n=37) AR A (n=22) R A R A Complete RA 1 1 R A Response (CR) AR A A A Partial Response A A AR 2 2 R A A (PR) A AR A FR R A S

  11. Slide 11: CLN-619: Monotherapy activity in heavily pre-treated patients

    CLN-619: Monotherapy activity achieved in heavily pre-treated patients, including after progression on anti-PD1 therapy Objective Response Detail (Data cutoff March 31, 2023*) Dose Level Tumor Type Prior Therapy Confirmed Response Detail Parotid 2 prior therapies CR at C4D1 (mucoepidermoid) Prior an

  12. Slide 12: CLN-619: Favorable monotherapy safety profile

    CLN-619: Favorable monotherapy safety profile reat ent E ergent A verse Events ( EAE) in ≥ 10% of Patients Any Grade 1/2 Grade 3+ Adverse Event n (%) n (%) n (%) • CLN-619 was well tolerated and most Infusion Related Reaction 8 (21.6) 8 (21.6) 0 (0) TEAEs were Grade 1/2 • No AEs met protocol-defined

  13. Slide 13: Endometrial cancer

    Endometrial cancer Underdeveloped indication that is large and growing U.S. Endometrial cancer market opportunity High unmet need • Late-stage endometrial cancer has a 5-year 66,200 Incidence of endometrial cancer1 (US females >= 18 years of age) survival of 17%1 • Often associated with co-morbiditi

  14. Slide 14: Clear path forward for developing CLN-619 in endometrial cancer

    Clear path forward for developing CLN-619 in endometrial cancer  Generate initial safety data and establish preliminary efficacy signal Ongoing; initiated June 2023  Explore monotherapy activity in ongoing expansion study in larger number of r/r EC patients Planned expansion cohort  Explore CLN-6

  15. Slide 15: CLN-619 status and next steps

    CLN-619 status and next steps • CLN-619 monotherapy was well tolerated • Clinical benefit, including objective responses, observed across multiple tumor types, including after progression on checkpoint inhibitor therapy • Notable monotherapy activity observed in gynecological malignancies ✓ Expansio

  16. Slide 16: CLN-978

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

  17. Slide 17: CD19 CAR-T cell therapy generated immune system reset 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

  18. Slide 18: 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

  19. Slide 19: TCE and CAR-T cells have comparable efficacy in similar NHL patient populations

    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

  20. Slide 20: 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

  21. Slide 21: 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…

  22. Slide 22: 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

  23. Slide 23: 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

  24. Slide 24: 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 80 80 80 80 15 15 15 15 60 60 60 60 cells Percent CD20+ cells Percent CD20+ cells Vehicle Percent CD20

  25. Slide 25: 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

  26. Slide 26: 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

  27. Slide 27: 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

  28. Slide 28: 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 PA R T B : D O S E E X PA N 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 Ob

  29. Slide 29: Systemic Lupus Erythematosus (SLE): High Unmet Need

    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

  30. Slide 30: 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

  31. Slide 31: 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

  32. Slide 32: Zipalertinib

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

  33. Slide 33: Exon 20 insertions make up the largest unmet need segment of 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 U.S. EXON 20 INCIDENCE Other 13-20% U.S. Lung cancer incidence1: Ex20 238,340 ~5%-12% NSCLC1: 80%-85% Ex19 Deletion 44% L858R Exon 202-4: 31% 1.5

  34. Slide 34: 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

  35. Slide 35: Zipalertinib: Safety and efficacy at 100mg BID in Phase 1/2a

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

  36. Slide 36: 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

  37. Slide 37: Diversified pipeline leveraging novel technologies and mechanisms

    Diversified pipeline leveraging novel technologies and differentiated mechanisms Program IND- Geographic Phase 1 Phase 2 Phase 3 Status Modality/MOA Enabling Rights Initial combo data and CLN-619 Pan-cancer monotherapy update in Anti-MICA/B antibody 2Q24; Disease specific or its subsidiary owns worl

  38. Slide 38: Thank You

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

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