Cullinan Therapeutics, Inc. · NASDAQ:CGEM
Cullinan Therapeutics — Investor Presentation (October 2024)
55 slides from Cullinan Therapeutics's investor presentation, Oct 16, 2024
Slide 1: Corporate Overview October 2024
CORPORATE OVERVIEW October 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 express or implied statements regardin
Slide 3: Cullinan Therapeutics: Our Mission
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 clinic
Slide 4: Poised for multiple value-creation opportunities in the near-term
*As of June 30, 2024 (unaudited), includes cash equivalents, investments, and interest receivable Poised for multiple value-creation opportunities in the near-term Next milestone/ status Zipalertinib EGFR inhibitor for EGFR ex20ins NSCLC Best-in-class potential Attractive economics incl. $130m miles
Slide 5: CLN-978 CD19xCD3 T cell Engager
CLN-978 CD19xCD3 T cell Engager
Slide 6: 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 Deep scientific expertise to identify high-impact targets Applying best modality to address the optimal target Accelerated development of only the most promising the
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 Multiple Sclerosis ANCA+ Vasculitis Sjogren’s Systemic Sclerosis Myasthenia Gravis NMOSD Pemphigus Vulgaris CURRENT DEVELOPMENT FOCUS OPPORTUNITY FOR OTHER B CE
Slide 8: What role do B cells play in autoimmune diseases?
What role do B cells play in autoimmune diseases? What does research tell us is the best way to regulate B cells? Accelerated development of only the most promising therapies to create new standards of care for patients How do we design the optimal molecule for patients? Applying Cullinan’s research
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 BONE MARROW SECONDARY LYMPHOID ORGANS AND CIRCULATION Adaptive immunological memory resides in subsets of B cells Autoreactive B cells Autoreactive B cells are key drivers of patho
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 B cells develop into plasma blasts and plasma cells that release autoantibodies, which are pathogenic in certain autoimmune diseases like lupus or r
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 Restoring adaptive immunological memory and function of the normal immune system is key to imm
Slide 12: What role do B cells play in autoimmune diseases?
What role do B cells play in autoimmune diseases? What does research tell us is the best way to regulate B cells? Accelerated development of only the most promising therapies to create new standards of care for patients How do we design the optimal molecule for these patients? Applying Cullinan’s re
Slide 13: 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 1 Tedder, T. F. & Engel, P. CD20: a regulator of cell-cycle progression of B lymphocytes. Immunol. Today 15, 450–454 (1994). 2 Reynolds et al. Blood Advances 2023 CD1
Slide 14: B cell depletion therapies resulted in sustained drug free remissions
Therapies achieving B cell depletion resulted in sustained drug free remissions for B cell malignancies ANTI-CD19 T CELL ENGAGERS ESTABLISHED PROOF-OF-CONCEPT FOR DISEASE-MODIFYING T CELL REDIRECTING THERAPIES 1997 2001 NHL RA 2024 2017 2014 ALL ALL Convergence of decades of scientific progress cont
Slide 15: T cell engagers: redirecting 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 X X Any T cell Target cell T cell receptor complex (TCR) Target antigen Bispecific antibody Invariant CD3e subunit CD8 CD4 Gamma/delta NKT Treg Do
Slide 16: T cell redirecting therapies offer deep B cell depletion
Emerging data suggests T cell redirecting therapies offer deep B cell depletion, potential to meaningfully improve upon SOC across certain autoimmune diseases SELECT ANTI-CD19 CAR T IN SLE DATA BCMA-DIRECTED TCE IN SLE SLE = Systemic Lupus Erythematosus; IIM = Idiopathic Inflammatory Myositis; SSc =
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 ADVANTAGES Off-the-shelf Favorable safety profile DISADVANTAGES Limited tissue penetration Lower efficacy CAR T ADVANTAGES High efficacy Potentially di
Slide 18: What role do B cells play in autoimmune diseases?
What role do B cells play in autoimmune diseases? What does research tell us is the best way to regulate B cells? Accelerated development of only the most promising therapies to create new standards of care for patients How do we design the optimal molecule for these patients? Applying Cullinan’s re
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 Therapeutic modality Predictable PK/PD properties, engaging all subsets of T cells to lyse target cells with variable CD19 expression levels. Dosing flexibility and ability to r
Slide 20: Preclinical subcutaneous dosing achieved deep sustained B cell depletion
In preclinical studies, subcutaneous dosing of CLN-978 achieved rapid, deep and sustained B cell depletion with attenuated cytokine release Deep, sustained peripheral B cell depletion after single dose in NHPs SubQ dosing attenuated cytokine release in NHPs Deep B cell depletion in bone marrow, sple
Slide 21: CLN-978 in B-NHL patients: sustained B cell depletion
In a study of B-NHL patients, CLN-978 achieved sustained B cell depletion with promising clinical results CLINICALLY ACTIVE AT 30μg SC WEEKLY STARTING DOSE FOR NHL PATIENTS 2 of 3 patients demonstrated objective clinical benefit, including a complete response Class toxicity: max Gr 1 CRS, no ICANS S
Slide 22: CLN-978 is well differentiated relative to other CD19 TCEs
αCD3 scFv αCD19 scFV αCD3 Fab αCD19 Fab PIT565 RO7507062 CLN-978 is well differentiated relative to other CD19 TCEs in development* IgG-like Blinatumomab CLN-978 αCD3 scFv αCD19 scFV αHSA VHH I IgG-like αCD3 Fab αCD19 Fab CD2 Ligand (CD58) BiTE Half-Life Extended Bispecific TCE POTENTIAL ADVANTAGES
Slide 23: What role do B cells play in autoimmune diseases?
What role do B cells play in autoimmune diseases? What does research tell us is the best way to regulate B cells? Accelerated development of only the most promising therapies to create new standards of care for patients How do we design the optimal molecule for these patients? Applying Cullinan’s re
Slide 24: CLN-978-SLE-001 global study design
CLN-978-SLE-001 global 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 Starting dose of 10 micrograms Step-wise
Slide 25: Systemic Lupus Erythematosus: High unmet need
Systemic Lupus Erythematosus (SLE): High unmet need in complex disease with few approved therapies, limited efficacy and chronic immunosuppression HIGH UNMET NEED Systemic disease characterized by autoantibodies produced by B cells, leading to multiple affected organ systems (renal, CNS, cardiovascu
Slide 26: Rheumatoid Arthritis second indication for CLN-978
Rheumatoid Arthritis (RA) second indication for CLN-978 Methotrexate TNF Inhibitors IL-6 Receptor Antagonist JAK1 inhibitors Refractory Cycling through therapies Current therapies result in chronic immune suppression, increasing infection risk, especially in elderly patients No transformational ther
Slide 27: Rheumatoid arthritis: large pool of highly refractory patients
Rheumatoid arthritis (RA) is a chronic inflammatory disease that mainly affects the joints with pathogenesis associated with autoantibodies ~77% of RA patients present with moderate or severe disease activity Large poly-refractory population with no available treatments Current therapies result in c
Slide 28: 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 Rapidly executing global clinical development strategy in autoimmune diseases driven by expansion of immunology expertise, external collaborations Development in autoimmune d
Slide 29: CLN-619 MICA/B-directed mAb
CLN-619 MICA/B-directed mAb
Slide 30: CLN-619: Engages both innate and adaptive immune cells
CLN-619: Engages both innate and adaptive immune cells 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 MoA CLN-619 Plus CPI MoA CLN-619 Multiple Mode
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 NCT05117476 Corticosteroid, antihistamine, and antipyretic premedications for IRR prophylaxis were required 30–60 minutes before Cycle 1 Day 1 Patients in extension cohorts were required to prov
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 (n=22) CLN-619 monotherapy (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 (
Slide 33: Pembrolizumab combination: objective responses in CPI-unresponsive tumors
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/kg Tumor type Gastric
Slide 34: Pembrolizumab combination: objective responses in CPI-unresponsive tumors
Pembrolizumab combination: Objective responses in patients with tumor types typically unresponsive to CPI therapy Tumor type No. of prior lines of therapy Prior CPI CPI Responsive Tumor Best response DoR, wks NSCLC, ALKr 2 No No PR 12.7 Gastric, HER2+ 3 No No PR 8.9+ (ongoing) NSCLC, EGFRm exon 18/2
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 (n=22) CLN-619 monotherapy (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 (
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 Total treated: N=42 Dose ≥1 mg/kg and RECIST evaluable: N=29 CBR = 41.4% (1 CR, 2 PR, 9 SD ≥18 weeks) Endometrial Adenoid Cystic Carc Breast Ovarian Pancreatic Parotid Gland M
Slide 37: 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 Durable objective response observed in patients with disease progression after prior CPI Durable stable disease observed in a more extensive group of tumors, including gynecologic malignancies (cervical,
Slide 38: NSCLC with oncogenic mutations experienced clinical benefit
Patients with NSCLC harboring oncogenic mutations experienced clinical benefit with both monotherapy and combination therapy Mutation, histology EGFRm, Adeno None, Adeno ALKr, Adeno TP53, Squamous EGFRm, Adeno ALKr, Adeno STK11 APC, Adeno BRAF V600E, Adeno Time on treatment and clinical activity in
Slide 39: Durable partial response in EGFRm NSCLC with liver metastasis
Durable partial response in EGFRm NSCLC with liver metastasis BASELINE 32mm Cycle 4 Day 1 14mm Cycle 7 Day 1 8mm Cycle 10 Day1 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, gefitinib
Slide 40: CLN-619 well tolerated as monotherapy and in combination
CLN-619 was well tolerated as a monotherapy and in combination with pembrolizumab Treatment-related AEs reported in ≥10% of patients were fatigue (combination: 18.2%; monotherapy: 9.5%) and infusion related reactions (IRRs combination: 18.2%; monotherapy: 28.6%) Most IRRs were grade 1 or 2, occurred
Slide 41: 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 durab
Slide 42: CLN-619 + Chemotherapy
CLN-619 + Chemotherapy Platinums and taxanes upregulate MICA/B expression in vitro Chemotherapy leads to increased infiltration/ activation of immune cells including CD8 T/NK cells in preclinical models Several chemotherapeutic agents are known inducers of immunogenic cell death Hypothesis Chemother
Slide 43: CLN-619 current development plan in solid and hematologic tumors
CERVICAL CANCER Monotherapy (10 mg/kg) ENDOMETRIAL CANCER Monotherapy (3 mg/kg, 10 mg/kg) NSCLC Adenocarcinoma priority EGFR or ALK Combination with Checkpoint Inhibitor (3 mg/kg, 10 mg/kg) Monotherapy (10 mg/kg) Combination with Checkpoint Inhibitor (10 mg/kg) R/R MULTIPLE MYELOMA Monotherapy (Phas
Slide 44: Zipalertinib (CLN-081/TAS6417) EGFRex20ins inhibitor
ZIPALERTINIB (CLN-081/TAS6417) EGFRex20ins inhibitor
Slide 45: 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 U.S. Lung cancer incidence2: 234,580 NSCLC1: 80%-85% Exon 203-5: 1.5%-2.0% of NSCLC ~2,800-4,000 patients Other 9% Ex19 Deletion 47% L858R 32% Ex20 12% References 1. Riess JW
Slide 46: 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 ~40% Confirmed ORR in Ph 1/2a and pivotal Ph 2b cohort p
Slide 47: Zipalertinib: superior safety and efficacy at RP2D 100 mg BID
Zipalertinib: Superior safety and efficacy observed at RP2D 100 mg BID dose level in REZILIENT1 Phase 1/2a <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 R
Slide 48: Update on initial patients in prior chemo + amivantamab cohort
Update on initial patients treated in the prior chemo + amivantamab cohort of REZILIENT1 REZILIENT33 Clinicaltrials.gov identifiers: 1NCT04036682, 2NCT05967689 and 3NCT05973773; * includes both approved and investigational exon20 therapies ** following 6-12 patient safety lead in. PACC = P-loop and
Slide 49: Enrolled patients heavily pre-treated, nearly 50% with brain metastases
Enrolled patients were heavily pre-treated, and nearly 50% had history of brain metastases Characteristics, n (%) Ami onlya (n=28) Ami + other ex20insb (n=17) Total (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
Slide 50: Zipalertinib after prior amivantamab shows similar efficacy
Zipalertinib treatment after prior amivantamab shows similar efficacy to Phase 1/2a results Data cut-off 12 January 2024 *Efficacy population includes all treated patients with measurable disease at baseline who have received at least one dose of CLN-081 and one of the following: 1) at least two on-
Slide 51: Best Percentage Change from Baseline of Target Lesions
Best Percentage Change from Baseline of Target Lesions Radiographic tumor regression in all but 2 patients who died prior to 1st on study imaging Zipalertinib was clinically active in patients who had received both amivantamab and other exon20ins drugs Two patients died. ex20ins NS: ex20ins mutation
Slide 52: No new safety signals in post amivantamab population
No new safety signals observed in the post amivantamab population Grade 3 TRAE AE Any Grade No new safety signal identified There were no grade 4 or grade 5 treatment-related adverse events TRAE ≥10%, n (%) Ami only (n=28) Ami + other ex20ins (n=17) Total (N=45) Rash 12 (43) 5 (29) 17 (38) Paronychi
Slide 53: REZILIENT program: zipalertinib development across studies
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 54: 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 demonstrat
Slide 55: Thank You!
Cullinan Therapeutics — Investor Presentation (October 2024) on 6ix