Cullinan Therapeutics, Inc. · NASDAQ:CGEM
Cullinan Therapeutics — Investor Presentation (April 2024)
37 slides from Cullinan Therapeutics's investor presentation, Apr 16, 2024
Slide 1: Corporate Overview April 2024
CORPORATE OVERVIEW April 2024
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
Slide 3: Our Mission
Our Mission To create new standards of care for patients Pursuing modality-agnostic targeted therapeutics: Discovering and identifying high-impact targets Then applying the best approach to address each target Rigorously and rapidly advancing only highly differentiated molecules Yielding a diversifi
Slide 4: Our Approach
Our Approach We seek to achieve our mission through our rigorous and differentiated approach to drug development Innovate without borders Remain open to finding the best solutions in-house or through licensing Run early “thriller or killer” experiments Rapidly advance only potential first-in-class a
Slide 5: Cash runway and near-term value-creation opportunities
Cash of $468M* + gross proceeds of $280M from Q2 2024 equity raise to support progress into 2028 *As of December 31, 2023. Includes cash, cash equivalents, investments, and interest receivable. Poised for multiple value-creation opportunities in the near-term CLN-619 Anti-MICA/B mAb for solid tumors
Slide 6: CLN-619 MICA/B-directed mAb
CLN-619 MICA/B-directed mAb
Slide 7: MICA/B are compelling and potentially pan-cancer therapeutic targets
MICA/B are compelling and potentially pan-cancer therapeutic targets 1. Data generated via analysis of TCGA database by Monoceros Biosystems. MICA/B are the most highly expressed NKG2D ligands across 32 different tumor types (TCGA)1 Increasing expression Tumor types MICA/B are the most consistently
Slide 8: CLN-619: Prevents MICA/B shedding to facilitate immune cell engagement
CLN-619: Prevents MICA/B shedding to facilitate innate and adaptive immune cell engagement and ADCC/P IMMUNE EVASION RESTORATION OF IMMUNOSURVEILLANCE Prevention of MICA/B shedding 1 2 Antibody-dependent cellular phagocytosis (ADCP) 3 4 ENHANCEMENT BY CHECKPOINT INHIBITION (CPI) CLN-619 Single-Agent
Slide 9: CLN-619: Ongoing global clinical trial designed for rapid signal generation
CLN-619: Ongoing global clinical trial designed for rapid signal generation Dose Escalation (“3 + 3”) 0.1 mg/kg Disease specific expansion cohorts Endometrial 1o objectives: Evaluate safety & preliminary efficacy, select RP2D CLN-619 Monotherapy Eligible patients: any advanced solid tumor Eligible p
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 All Patients (n = 37) by Dose Level All Patients (n=37) Response Evaluable1 at ≥1 mg/kg (n=22) Complete Response (CR) 1 1 Partial Response (PR) 2 2 Stable Disease (SD) 7 7 CR + PR + SD 10 10 Pro
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 Dose Level Tumor Type Prior Therapy Confirmed Response Detail 3 mg/kg Parotid (mucoepidermoid) 2 prior therapies Prior anti-PD1 (best response = PR) CR at C4D1 3 mg/kg Endometrial
Slide 12: CLN-619: Favorable monotherapy safety profile
CLN-619: Favorable monotherapy safety profile Adverse Event Any n (%) Grade 1/2 n (%) Grade 3+ n (%) Infusion Related Reaction 8 (21.6) 8 (21.6) 0 (0) Pyrexia 8 (21.6) 8 (21.6) 0 (0) Abdominal Pain 8 (21.6) 6(16.2) 2 (5.4) Decreased Appetite 6 (16.2) 6 (16.2) 0(0) Diarrhea 5 (13.5) 5 (13.5) 0 (0) Fa
Slide 13: Endometrial cancer: underdeveloped indication that is large and growing
Endometrial cancer Underdeveloped indication that is large and growing Late-stage endometrial cancer has a 5-year survival of 17%1 Often associated with co-morbidities that make current treatments hard to tolerate Chemotherapy (~15% ORR)3 provides limited clinical benefit for patients progressing po
Slide 14: Clear path forward for developing CLN-619 in endometrial cancer
Clear path forward for developing CLN-619 in endometrial cancer Explore monotherapy activity in ongoing expansion study in larger number of r/r EC patients Generate initial safety data and establish preliminary efficacy signal Explore CLN-619 in combination with PD1 therapy Ongoing; initiated
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 Expansion cohort
Slide 16: CLN-978 CD19xCD3 T cell Engager
CLN-978 CD19xCD3 T cell Engager
Slide 17: CD19 CAR-T 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 Muller, F. et al. NEJM 2024. 1) SLE = Systemic Lupus Erythematosus, IIM = idiopathic inflammatory myositis, SSc = systemic sclerosis Treatment
Slide 18: CAR T cell therapy: multiple challenges may limit broad uptake
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 maligna
Slide 19: TCE and CAR-T cells have comparable efficacy in NHL
TCE and CAR-T cells have comparable efficacy in similar NHL patient populations* YESCARTA1 Axi-cel KYMRIAH2 Tisa-cel LUNSUMIO3 Mosunetuzumab Target/Modality CD19 CAR T CD19 CAR T CD20 TCE (IV) Study / pt pop ZUMA-5 Phase 2 R/R FL 3L+ ELARA Phase 3 R/R FL 3L+ GO29781 Phase 2 R/R FL 3L+ ORR / CR (%) 9
Slide 20: 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 potently triggers redirected lysis of CD19-expressing target cells in vitro and in vivo Engineered to achieve very high affinity binding to CD19 to efficiently target B cells expre
Slide 21: 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 i
Slide 22: CLN-978 pre-clinical highlights: subcutaneous dosing and B cell depletion
CLN-978 pre-clinical highlights: Subcutaneous dosing achieved rapid, deep and sustained B cell depletion with attenuated cytokine release in NHPs 0.1 mg/kg (IV) 1 mg/kg (IV) 0.1 mg/kg (SC) 1 mg/kg (SC) Deep, sustained peripheral B cell depletion after a single dose in NHPs Subcutaneous dosing attenu
Slide 23: Deep B cell depletion in bone marrow, spleen and lymphoid tissues
Bone marrow Spleen Lymphoid tissue GALT Axillary Vehicle Mandibular 0.1 mg/kg 1 mg/kg Percent CD20+ cells Percent CD20+ cells SC = subcutaneous administration, GALT = gut associated lymphoid tissue Deep B cell depletion in bone marrow, spleen and lymphoid tissues following SC administration of CLN-9
Slide 24: Clinical observations from B-NHL study
Clinical observations from B-NHL study (as of 5 April 2024) CLN-978 in B-NHL: Clinically active at starting dose with favorable safety Disease Characteristics and Efficacy Observations Treatment Emergent Adverse Events1 ID Diagnosis Prior Lines Duration of CLN-978 Treatment Best Response (Cheson 201
Slide 25: Subject #3 case study: mantle cell lymphoma
Subject #3 case study: 68-year-old patient with mantle cell lymphoma 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 first dose of CLN-978 Repeat PET-CT after 7 d
Slide 26: B cell depletion demonstrated in B-NHL patients following CLN-978 dosing
Rapid, deep and sustained B cell depletion was demonstrated in B-NHL patients following CLN-978 dosing Rapid, deep and sustained B cell depletion was demonstrated in 2 of 2 subjects with measurable B cells at baseline All patients treated at the starting dose level of 30 ug SC weekly Peripheral bloo
Slide 27: CLN-978-SLE-001 planned study design
CLN-978-SLE-001 planned study design Objectives Primary Objective: Safety of CLN-978 for treatment of active SLE Secondary Objectives: PK B cell kinetics Immunogenicity Preliminary efficacy PART A: DOSE ESCALATION PART B: DOSE EXPANSION PLANNED DESIGN FEATURES Step-wise escalation to determine targe
Slide 28: Systemic Lupus Erythematosus: High unmet need and market opportunity
Systemic Lupus Erythematosus (SLE)1: High Unmet Need Creates a Compelling Market Opportunity High Unmet Need Systemic disease characterized by autoantibodies produced by B cells, leading to multiple affected organ systems (renal, CNS, cardiovascular, respiratory, skin) Largely impacts young, women o
Slide 29: Substantial number of addressable autoimmune diseases
Substantial number of addressable autoimmune diseases Opportunity to Address Multiple B Cell Mediated Autoimmune Diseases 500,000+ U.S. Patients 50,000 - 500,000 U.S. Patients <50,000+ U.S. Patients NMOSD SLE Multiple Sclerosis Rheumatoid arthritis Membranous nephropathy Myasthenia gravis Pemphigus
Slide 30: 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 subcutaneous
Slide 31: Zipalertinib (CLN-081/TAS6417) EGFRex20ins inhibitor
ZIPALERTINIB (CLN-081/TAS6417) EGFRex20ins inhibitor
Slide 32: Exon 20 insertions: largest unmet need segment 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 U.S. Lung cancer incidence1: 238,340 NSCLC1: 80%-85% Exon 202-4: 1.5%-2.0% of NSCLC ~2,800-4,000 patients Other 13-20% Ex19 Deletion 44% L858R 31% Ex20 ~5%-12% References 1. A
Slide 33: 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 Distinct chemical scaffold HER2-sparing High selectivity to mutant vs WT EGFR 41% confirmed overall rate of response (16/39) 12-month
Slide 34: 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 (N=23) 100 mg (N=39) 150 mg (N=11) Total (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
Slide 35: REZILIENT program: zipalertinib development across studies and indications
REZILIENT program: zipalertinib development across multiple studies and indications, including 2 pivotal trials, in collaboration with Taiho Oncology REZILIENT33 Clinicaltrials.gov identifiers: 1NCT04036682, 2NCT05967689 and 3NCT05973773; * includes both approved and investigational exon20 therapies
Slide 36: Diversified pipeline leveraging novel technologies and mechanisms
Diversified pipeline leveraging novel technologies and differentiated mechanisms Program Modality/MOA IND- Enabling Phase 1 Phase 2 Phase 3 Status Zipalertinib (CLN-081/TAS6417) EGFRex20ins inhibitor CLN-049 FLT3xCD3 T-cell engager CLN-619 Anti-MICA/B antibody CLN-978 CD19xCD3 T-cell engager CLN-617
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