Cullinan Therapeutics, Inc. · NASDAQ:CGEM
Cullinan Therapeutics — Investor Presentation (September 2025)
53 slides from Cullinan Therapeutics's investor presentation, Sep 4, 2025
Slide 1: Corporate Overview September 2025
CORPORATE OVERVIEW September 2025
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, 2025 (unaudited), includes cash equivalents, investments, and interest receivable Poised for multiple value-creation opportunities in the near-term Cash of $511M* supports operations into 2028 First-in-class potential in autoimmune diseases Proven modality (TCE) & differentiated prof
Slide 5: T Cell Engagers in Autoimmune Diseases
T Cell Engagers in Autoimmune Diseases
Slide 6: Combined ~41.6M patients globally
Combined ~41.6M patients globally Source: SLE: Tian J, Zhang D, Yao X, Huang Y, Lu Q. Global epidemiology of systemic lupus erythematosus: a comprehensive systematic analysis and modelling study. Ann Rheum Dis. Published online October 14, 2022. RA: Rheumatoid arthritis: Key Facts. WHO. Published on
Slide 7: Targeting CD19 or BCMA may be central to disease modification
© CULLINAN THERAPEUTICS, INC. ALL RIGHTS RESERVED. Targeting CD19 or BCMA may be central to the disease modification of certain autoimmune diseases BCMA B cell dysfunction is central to the pathogenesis of many autoimmune diseases, and broadly and deeply depleting these cells by targeting CD19 appea
Slide 8: 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 SLE = Systemic Lupus Erythematosus; IIM = Idiopathic Inflammatory Myositis; SSc = Systemic Sclerosis; RA = Rheumatoid Arthritis. BLINATUMOMAB: CD19-DIRECTED TCE IN RA AND SSc B cell d
Slide 9: mAbs vs TCEs vs CAR T
mAbs TCEs CAR T Lower efficacy; limited tissue penetration High efficacy; B cell depletion in tissue High efficacy; B cell depletion in tissue Symptomatic relief Potentially disease modifying Potentially disease modifying Immune modulating Potential for immune reset Potential for immune reset Off-th
Slide 10: CLN-978 CD19xCD3 bispecific T cell engager
CLN-978 CD19xCD3 bispecific T cell engager
Slide 11: CLN-978: highly differentiated CD19xCD3 bispecific T cell engager
CLN-978: a highly differentiated and potentially best-in-class CD19xCD3 bispecific T cell engager HSA = human serum albumin binding domain Therapeutic modality Predictable PK/PD properties, engaging all subsets of T cells to lyse target cells with variable CD19 expression levels. Dosing flexibility
Slide 12: 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 Deep, sustained peripheral B cell depletion after single dose in NHPs SubQ dosing attenuated cytokine release in NHPs Deep B cell depletion
Slide 13: 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 14: 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 IgG-like αCD3 Fab αCD19 Fab CD2 Ligand (CD58) BiTE POTENTIAL ADVANTAGES OF CLN-978 1 2 3 4 Broader B cell lineage depletion due to very high affin
Slide 15: CLN-978-SLE-101 global study design
CLN-978-SLE-101 global study design Objectives Primary Objective: Safety and tolerability of CLN-978 for treatment of active SLE Secondary Objectives: PK B cell kinetics Immunogenicity Clinical activity PART A: DOSE ESCALATION PART B: DOSE EXPANSION Cohort 1 (n=3) Day 1: 10 micrograms Schedule 1 (n=
Slide 16: 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 17: 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 18: CLN-978-RA-101 initial Phase 1 design
CLN-978-RA-101 initial Phase 1 design Objectives Primary Objective: Safety and tolerability of CLN-978 for treatment of active RA Secondary Objectives: PK B cell kinetics in peripheral blood and tissue biopsies Immunogenicity Clinical activity Cohort 1 (n=1) Day 1: 10 micrograms Study Population RA
Slide 19: 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 20: Third indication: Sjögren's disease overlaps with SLE and RA
Third indication for CLN-978: Sjögren’s disease (SjD) has significant overlap with SLE, RA and other connective tissue diseases About half of the time SjD occurs alone, and the other half it occurs in the presence of another connective tissue disease. Signs and symptoms of SjD frequently overlap wit
Slide 21: CLN-978-SjD-101 study design
CLN-978-SjD-101 study design Objectives Primary Objective: Safety and tolerability of CLN-978 for treatment of patients with active SjD Secondary Objectives: PK B cell kinetics in peripheral blood and salivary biopsies Immunogenicity Clinical activity PART A: DOSE ESCALATION PART B: DOSE EXPANSION C
Slide 22: Sjögren's Disease: complex and debilitating disease
Sjögren's Disease (SjD): Complex and debilitating disease occurring in isolation or in association with other systemic conditions HIGH UNMET NEED SjD is a chronic autoimmune disease characterized by lymphocytic infiltration of the salivary and lacrimal glands Autoantibodies play crucial roles in bot
Slide 23: Velinotamig BCMAxCD3 bispecific T cell engager
Velinotamig BCMAxCD3 bispecific T cell engager
Slide 24: Velinotamig: highly selective, differentiated molecule
VELINOTAMIG A HIGHLY SELECTIVE, DIFFERENTIATED MOLECULE Binds to the BCMA and CD3 antigens, redirecting cytotoxic T cells to target BCMA-expressing cells High affinity for BCMA and lower affinity for CD3: affinity for BCMA is two orders of magnitude higher than for CD3, promoting recruitment and act
Slide 25: Velinotamig clinical development status in China
Velinotamig current clinical development status in China GR1803-001: A (follow-up) completed Phase 1 study in patients with relapsed/refractory multiple myeloma GR1803-002: A Phase 2 pivotal study in patients with relapsed/refractory multiple myeloma GR1803-003: A Phase 2 pivotal study in patients w
Slide 26: Velinotamig efficacy in relapsed/refractory multiple myeloma
Velinotamig has demonstrated meaningful efficacy in late-line patients with relapsed/refractory multiple myeloma: Phase 1 results at RP2D target dose Approved moleculesb (in U.S. and or EU) Velinotamiga (n=48) Elranatamab1,2 (n=97) Teclistamab3,4,5 (n=110) Linvoseltamab6 (n=117) ORR (sCR + CR + VGPR
Slide 27: Overview of velinotamig safety data
Overview of velinotamig safety data at RP2D target dose Any grade ≥Grade3 Velinotamig (n=48)* Cytokine release syndrome 89.6% 6.3% Infection 81.3% 50.0% ICANS 0% 0% Neutrophil count decreased 89.6% 64.6% Platelet count decreased 79.2% 39.6% White blood cell count decreased 89.6% 35.4% Lymphocyte cou
Slide 28: Zipalertinib (CLN-081/TAS6417) EGFRex20ins inhibitor
ZIPALERTINIB (CLN-081/TAS6417) EGFRex20ins inhibitor
Slide 29: Exon 20 insertions: largest unmet need segment in EGFR lung cancer
Patients with insertions at exon 20 make up the largest unmet need segment of the lung cancer population with EGFR mutations References 1. Riess JW et al. J Thorac Oncol 2018. 2. American Lung Association (2025) 3. Riess JW et al. J Thorac Oncol 2018. 4. Zhang YL et al. Oncotarget 2016. 5. Burnett H
Slide 30: Zipalertinib: selective EGFR inhibitor for exon20 NSCLC
MAY 2022 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 Zipalertinib is designed as a next generation,
Slide 31: ASCO 2025 data update: REZILIENT1 Phase 2b results
ASCO 2025 data update: REZILIENT1 Phase 2b trial results Pivotal Phase 2b (met primary endpoint) REZILIENT11 NCT04036682 Primary endpoint: ORR + DOR Clinicaltrials.gov identifiers: 1NCT04036682, 2NCT05967689 and 3NCT05973773; * includes both approved and investigational exon20 therapies ** following
Slide 32: REZILIENT1: heavily pre-treated patient population
REZILIENT1: heavily pre-treated patient population, many with brain metastases, relapsed after chemotherapy +/- amivantamab aIncludes first/second generation EGFR tyrosine kinase inhibitors, ALK inhibitors, CDK4/6 inhibitors, NTRK/ROS1 inhibitors, angiokinase inhibitors. ALK, anaplastic lymphoma kin
Slide 33: REZILIENT1: meaningful efficacy including post-amivantamab
REZILIENT1: Zipalertinib demonstrated meaningful clinical efficacy, including in patients previously treated with amivantamab Outcome Primary efficacy population (N=176) Platinum-based chemotherapy without ex20ins-targeted therapy (n=125) Prior amivantamab ± other ex20ins-target therapy (n=51)a BOR,
Slide 34: REZILIENT1: durable benefit after prior amivantamab
REZILIENT1: Durable clinical benefit observed in patients relapsing after prior treatment with amivantamab Despite the approval of amivantamab for EGFR ex20ins NSCLC, patients can still face poor outcomes after exhausting a range of prior therapies Outcome Prior amivantamab without other ex20ins-tar
Slide 35: REZILIENT1: efficacy in patients with brain metastases
REZILIENT1: Efficacy per ICR in patients with brain metastases Outcome Primary efficacy population (N=176) Patients with brain metastasesa (n=68) BOR, No. (%)b CR 1 (1) 1 (2) PR 61 (35) 20 (29) Unconfirmed PRc 7 (4) 2 (3) SD 88 (50) 37 (54) PD 11 (6) 5 (7) Not evaluabled 8 (5) 3 (4) Confirmed ORR, N
Slide 36: REZILIENT1: confirmed ORR of 35.2%
REZILIENT1: Confirmed ORR of 35.2% in the primary efficacy population; best change from baseline of target lesions Platinum-based chemotherapy without ex20ins-targeted therapy (n=125) Platinum-based chemotherapy with amivantamab ± other ex20ins-target therapy (n=51) 120 100 80 60 40 20 0 Best change
Slide 37: REZILIENT1: median PFS of 9.4 months per ICR
REZILIENT1: Zipalertinib shows median progression-free survival (PFS) of 9.4 months per ICR in primary efficacy population 176 125 51 144 103 41 95 71 24 57 42 15 22 15 7 15 10 5 7 7 0 6 6 0 6 6 0 6 6 0 6 6 0 4 4 0 4 4 0 3 3 0 3 3 0 3 3 0 3 3 0 1 1 0 0 0 0 Total Platinum-based chemotherapy only Prio
Slide 38: REZILIENT1: most common treatment-related adverse events
REZILIENT1: Most common treatment-related adverse events Any-grade TRAEs reported in ≥10% of patients, No. (%) Any grade Grade 3 Paronychia 94 (38.5) 0 Rash 74 (30.3) 6 (2.5) Dermatitis acneiform 60 (24.6) 1 (0.4) Dry skin 60 (24.6) 0 Diarrhea 53 (21.7) 5 (2.0) Stomatitis 49 (20.1) 4 (1.6) Anemia 48
Slide 39: REZILIENT1: Phase 2b met primary endpoint of ORR and DOR
REZILIENT1: Pivotal Phase 2b study in 2L+ met the primary endpoint of ORR and DOR, demonstrated a manageable safety profile for zipalertinib Pivotal Phase 2b (met primary endpoint) REZILIENT11 Primary endpoint: ORR and DOR Clinicaltrials.gov identifiers: 1NCT04036682, 2NCT05967689 and 3NCT05973773;
Slide 40: REZILIENT program: broad development of zipalertinib
REZILIENT program: broad development of zipalertinib across multiple studies and indications in collaboration with Taiho Oncology 40 Pivotal Phase 2b (met primary endpoint) REZILIENT11 Primary endpoint: ORR + DOR Clinicaltrials.gov identifiers: 1NCT04036682, 2NCT05967689 and 3NCT05973773; * includes
Slide 41: Potential best-in-class profile of zipalertinib
Potential best-in-class profile of zipalertinib creates opportunity to address large unmet need left by currently approved therapies KEY DATA https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/RYBREVANT-pi.pdf Park K, Haura EB, Leighl NB, et al. Amivantamab in EGF
Slide 42: Taiho zipalertinib collaboration benefits
Taiho zipalertinib collaboration provides Cullinan with financial and strategic benefits 1. Excludes rights to Japan, which were already held by Taiho, and rights to Greater China, which were previously licensed to Zai Labs Upfront Payment $275 million to Cullinan received in 2022 in exchange for pr
Slide 43: REZILIENT program: upcoming milestones and next steps
REZILIENT program: upcoming milestones and next steps Initial results from REZILIENT2 Cohort C to be shared at ESMO Congress 2025 in October 2025 Initial results from Cohort C of REZILIENT2, which is exploring zipalertinib monotherapy in patients with active brain metastases who may or may not have
Slide 44: CLN-049 FLT3xCD3 bispecific T cell Engager
CLN-049 FLT3xCD3 bispecific T cell Engager
Slide 45: Significant unmet need in adult AML
Significant unmet need in adult AML References 1. American Cancer Society (2025) 2. DeWolf and Tallman. Blood 2020. The only curative therapy is intensive chemotherapy +/- stem cell transplantation Curative therapy remains out of reach for most AML patients: 85% patients >60 years old are ineligible
Slide 46: FLT3: an optimal target for AML immunotherapy
FLT3: An optimal target for AML immunotherapy 1 2 3 4 Promising therapeutic potential: FLT3 is expressed on leukemic stem cells as well as blast cells, which may increase response durability. Since FLT3 is an oncogenic driver, target loss is unlikely Validation: FLT3 plays a key role in promoting le
Slide 47: Most AML patients express FLT3 on blast cell surface
Most AML patients express FLT3 on blast cell surface1 Limited expression of FLT3 mRNA in normal tissues1 Compelling biological rationale for FLT3 targeted therapeutic approach in AML Florescence Activated Cell Sorting (FACS) Analysis RNA 1 27 53 79 105 131 157 183 209 235 261 287 313 >10 MFI ratio F
Slide 48: CLN-049: novel bispecific T cell engager targeting FLT3
CLN-049: A novel bispecific T cell engager targeting FLT3 in Phase 1 for r/r AML or MDS and in Phase 1 for MRD in AML Statements based on preclinical data CLN-049 DESIGN CLN-049’S POTENTIAL DIFFERENTIATION Wide therapeutic window Two FLT3-binding Fab arms allow for higher avidity binding to AML cell
Slide 49: CLN-049 mechanism allows broad FLT3-dependent AML blast killing
CLN-049 mechanism potentially allows for broad FLT3 dependent AML blast killing 1 2 3 Statements based on preclinical data Redirects lysis of AML cells expressing mutant or wildtype FLT3 Two FLT3 binding domains drives potent elimination of AML blasts even at low FLT3 expression levels Functionally
Slide 50: CLN-049 preclinical data
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 wildtype or mutant FLT3 No T cell activation by CLN-049 in the absence of target cells Potent elimination of pa
Slide 51: CLN-049 Phase 1 multiple ascending dose design in r/r AML or MDS
CLN-049 Phase 1 multiple ascending dose design in r/r AML or MDS Intravenous dosing module ongoing Accelerated Titration Standard Titration RELAPSED/REFRACTORY AML AND HYPOMETHYLATING AGENT (HMA)-R/R MDS Dose Level X* N = 3–6 pts Max Dose Level tbd N = 3–6 patients Dose Level X + 1 N = 3–6 patients
Slide 52: CLN-049 Phase 1 study design in MRD in AML
CLN-049 Phase 1 study design in measurable minimal residual disease in AML Accelerated Titration Standard Titrations Dose Escalation DL at which grade ≥2 AE occurs* (n=3 to 6 patients/cohort) DL 1 (n=1) Key inclusion Criteria: Patients ≥18 years with AML in complete morphologic remission with persis
Slide 53: Thank You
THANK YOU! ‘© CULLINAN THERAPEUTICS, INC. ALL RIGHTS RESERVED,
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