Carisma Therapeutics, Inc. · OTC:CARM
Carisma Therapeutics — Investor Presentation (2024)
69 slides from Carisma Therapeutics's investor presentation, 2024
Slide 1: Harnessing the Power of Macrophages
HARNESSING THE POWER OF MACROPHAGES Steven Kelly President & CEO
Slide 2: Cautionary Note Regarding Forward-Looking Statements
Cautionary Note Regarding Forward-Looking Statements Statements in this slide deck about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute “forward-looking statements” within the meaning of The Private Securities
Slide 3: Pioneering engineered macrophages in oncology and beyond
Pioneering engineered macrophages in oncology and beyond
Slide 4: Engineering Myeloid Cells: CAR-M and Beyond
Engineering Myeloid Cells: CAR-M and Beyond Technology Current Status Ex Vivo CAR-M Phase 1 clinical program for HER2+ solid tumors Oncology: First Development Candidate targets GPC3 for the treatment of solid tumors, including HCC** In Vivo CAR-M* Collaboration with Autoimmune disease: Expanded Col
Slide 5: First-in-Class Pipeline
First-in-Class Pipeline Multiple value inflection points across therapeutic areas and modalities PRODUCT INDICATION PLATFORM DISCOVERY PRE-CLINICAL PHASE 1 PHASE 2 PHASE 3 COLLABORATOR CANDIDATE Oncology HER2+ CAR-Monocyte Next milestone: Initial Phase 1 data1 (4Q 2024) CT-0525 solid tumors (Autolog
Slide 6: Targeting HER2: From CAR-Macrophages (CT-0508) to CAR-Monocytes (CT-0525)
Targeting HER2: From CAR-Macrophages (CT-0508) to CAR-Monocytes (CT-0525)
Slide 7: Macrophages are Ideally Suited for Solid Tumor Cell Therapy
Macrophages are Ideally Suited for Solid Tumor Cell Therapy CAR-M: Carisma’s proprietary technology converts myeloid cells into targeted therapies with CARs CAR-Monocytes differentiate into CAR-Macrophages in vivo • Myeloid cells are abundantly recruited to tumors • Carisma’s proprietary platforms e
Slide 8: Key Learnings from CT-0508 Monotherapy Study
CT-0508 Monotherapy Key Learnings from CT-0508 Monotherapy Study* CT-0508 was a well-tolerated and active therapy; strong rationale for further development of anti-HER2 CAR-M Safety and Tolerability • Well-tolerated with no severe CRS, no ICANS, and no dose-limiting toxicities • Successful autologou
Slide 9: ctDNA Reduction Observed in 75% of HER2 3+ Patients
CT-0508 Monotherapy ctDNA Reduction Observed in 75% of HER2 3+ Patients ctDNA reductions are clear evidence of clinical activity ctDNA in 8 evaluable HER2 3+ pts 86% decrease 80% decrease KEY TAKEAWAYS at week 4 at week 4 • 75% (6/8) of HER2 3+ patients exhibited a decrease in ctDNA, indicating anti
Slide 10: CAR-Macrophage Monotherapy: Individual Case Study
CT-0508 Monotherapy CAR-Macrophage Monotherapy: Individual Case Study Activity in patient with HER2 3+ inflammatory breast cancer with skin involvement Prior to treatment Following CT-0508 treatment Cancer Type & Prior History • Stage IV Inflammatory Breast Cancer (IBC) • HER2 3+ • Patient progresse
Slide 11: T cell Exhaustion Was a Limiting Factor to CAR-Macrophage Efficacy
T cell Exhaustion Was a Limiting Factor to CAR-Macrophage Efficacy Study 101 patients with lower baseline CD8 T cell exhaustion (in blood) trended toward Stable Disease KLRG1 LAG3 PD1 TIGIT Based on single-cell RNAseq analysis of CD8 T cells within apheresis material.;SD: Stable Disease; PD: Progres
Slide 12: Key Learnings from CT-0508+Pembrolizumab Combination
CT-0508 + anti-PD1 Key Learnings from CT-0508+Pembrolizumab Combination* Study successfully met its primary endpoint of safety, tolerability and manufacturing feasibility Safety and Tolerability • Well-tolerated with no severe CRS, no ICANs, and no on-target off-target toxicity Feasibility • Success
Slide 13: Synergistic Immune Activation
CT-0508 + anti-PD1 Synergistic Immune Activation Pembrolizumab Potentiates the Ability of CT-0508 to Stimulate the Adaptive Immune System Increased T cell clonality (blood)1 Increased effector memory and activated Increased PDL1 CPS in TME, a CD8 T cells (blood)2 biomarker of CPI response3 Effector
Slide 14: From CAR-Macrophage to CAR-Monocyte
From CAR-Macrophage to CAR-Monocyte: Monocytes are a favorable cell type for solid tumor cell therapy CAR-Monocyte Mechanism of Action: Benefits to the CAR-Monocyte platform: • Increased persistence1 • Increased tumor infiltration1 • Increased anti-tumor activity1 • In vivo differentiation into CAR-
Slide 15: CT-0525: HER2 Targeted CAR-Monocyte (Macrophage Precursor)
CT-0525 CT-0525: HER2 Targeted CAR-Monocyte (Macrophage Precursor) Potential to significantly improve upon the observed biological activity of CT-0508 Highlights CT-0525 CAR COMPONENTS Key Manufacturing Advantages Over CAR-Macrophage Humanized anti-HER2 scFv • Higher cell numbers • Faster manufactur
Slide 16: CT-0525 Directly Addresses the Key Limitations of CT-0508
CT-0525 CT-0525 Directly Addresses the Key Limitations of CT-0508 Pre-clinical models demonstrate increased potency with ~2,000-fold increased exposure over CT-0508 Dose Trafficking Persistence Comparison of Signal in Tumors CT-0508 Cells Produced fromvs. CT-0525 Single Apheresis: Trafficking in sol
Slide 17: CT-0525 Study 102: Phase 1 Clinical Trial Design
CT-0525 CT-0525 Study 102: Phase 1 Clinical Trial Design Assessing safety, tolerability, and manufacturing feasibility of CT-0525; additional analyses on TME impact Cohort 1: Up to 3 billion cells of CT-0525 in bolus dose D1 (n≥3) HER2 2+/3+ solid tumors (n≥6) Enrollment ongoing G-CSF mobilization a
Slide 18: Potential to Enhance Response with Repeat Dosing of CT-0525
CT-0525 Potential to Enhance Response with Repeat Dosing of CT-0525 ctDNA: single dose CT-0508 Improved persistence plus redosing to increase potential response Single Dose CAR-Macrophage Redosing CAR-Monocyte CT-0525 Exposure ctDNA Minimum threshold to maintain pharmacological pressure Conceptual G
Slide 19: CT-0525 Represents the Next Stage of CAR-M Development
CT-0525 CT-0525 Represents the Next Stage of CAR-M Development Initial CT-0508 Study Initial CT-0525 Cohorts CT-0525 Expansion Cohorts* Optimize dosing regimen: Demonstrate initial Demonstrate initial Repeat dosing safety, tolerability, safety, tolerability, feasibility & MOA: feasibility & MOA: CAR
Slide 20: In Vivo CAR-M: Oncology & Autoimmune disease
In Vivo CAR-M: Oncology & Autoimmune disease
Slide 21: In Vivo CAR-M: Collaboration with Moderna
In Vivo CAR-M In Vivo CAR-M Collaboration with Moderna to discover, develop & commercialize in vivo CAR-M in oncology & autoimmune disease Highlights Redirecting endogenous myeloid cells with mRNA for cancer immunotherapy Collaboration Overview • Combines Carisma’s CAR macrophage technology with Mod
Slide 22: In Vivo CAR-M Controls Metastatic Pancreatic Cancer
In Vivo CAR-M In Vivo CAR-M Controls Metastatic Pancreatic Cancer Systemic LNP administration in humanized mouse model of pancreatic cancer Systemic mRNA/LNP Administration 10 9 Dose 2mg/kg, 2x/week, intravenously (Bioluminescence [p/s]) PANC1-hHER2 i.v. Sac Tumor Burden 10 8 CD34+ ***** Humanized 0
Slide 23: Glypican-3 (GPC3): A validated target in HCC
In Vivo CAR-M Glypican-3 (GPC3): A validated target in HCC HCC remains an area of significant unmet medical need HCC overview: • >40,000 new cases in the US in 2024, and the 2nd leading cause of cancer-deaths worldwide1,2 • 22% 5-year survival for all HCC cases; 3.5% 5-year survival for advanced HCC
Slide 24: In Vivo CAR-M: Next Steps
In Vivo CAR-M In Vivo CAR-M: Next Steps Strategic alliance, fully funded by Moderna Rationale PoC achieved Next Steps • Off-the-shelf: In vivo ✓ Robust data: • Lead Program: Advance lead program, a GPC3 CAR-M are • Platform: Pre-clinical targeted in vivo CAR-M, into clinic for HCC LNP/mRNA based and
Slide 25: Developing macrophage cell therapies beyond oncology: Fibrosis
Developing macrophage cell therapies beyond oncology: Fibrosis
Slide 26: Macrophages have Robust Anti-fibrotic and Anti-inflammatory Potential
Fibrosis Macrophages have Robust Anti-fibrotic and Anti-inflammatory Potential Substantial Unmet Need Clinical Evidence of Promising Preclinical Results In Liver Fibrosis Macrophage Cell Therapy from Engineered Macrophages Large (and growing) patient Carisma’s engineered population Non-engineered ma
Slide 27: Carisma's Platform: Engineered Anti-fibrotic Macrophages
Fibrosis Carisma’s Platform: Engineered Anti-fibrotic Macrophages Pre-clinical proof-of-concept with relaxin-IL10 co-expressing macrophages Visualization of the mechanism of action, including existing payloads and a callout to potential future payloads ECM: extracellular matrix 27
Slide 28: A Single Dose of Engineered Macrophages Significantly Reduced Liver Fibrosis
Fibrosis A Single Dose of Engineered Macrophages Significantly Reduced Liver Fibrosis1 CCl4 model of established fibrosis Relaxin-IL10 macrophages significantly reduced established fibrosis Mɸ (I.V.) Healthy Liver Untreated Week: 0 1 2 3 4 5 6 CCl4 Engineered Mɸ significantly -55% reduced hepatic co
Slide 29: Engineered Macrophages Reduced Liver Fibrosis in a High Fat Diet-Induced Model
Fibrosis Engineered Macrophages Reduced Liver Fibrosis in a High Fat Diet-Induced Model1 High fat diet MASH model Relaxin-IL10 macrophages significantly reduced Mɸ (I.V.) fibrosis Healthy Liver Untreated Week: 0 2 11 13 21 23 25 Modified HFD: -25% -45% CCl4: Engineered Mɸ significantly reduced fibro
Slide 30: Liver Fibrosis: Next steps
Fibrosis Liver Fibrosis: Next steps Wholly-owned program Rationale PoC achieved Next Steps • Resolution of liver ✓ Pre-clinical PoC data • Present additional liver fibrosis data at AASLD fibrosis: Engineered shows anti-fibrotic effect November 2024 macrophages enhance with relaxin-IL10 as innate act
Slide 31: Corporate & Financial
Corporate & Financial
Slide 32: Financial Snapshot
Financial Snapshot As of June 30, 2024 41.5M $40.4M Into 3Q 2025 Shares outstanding Cash and cash equivalents Expected cash runway 32
Slide 33: Operating Plan and Corporate Milestones
Operating Plan and Corporate Milestones Capital efficient R&D program designed to reach significant value inflection points INDICATION PRODUCT CANDIDATE PLATFORM RECENT AND ANTICIPATED MILESTONES Oncology 4Q’23 IND cleared ✓ CT-0525 CAR-Monocyte 2Q’24 Treat first patient ✓ HER2+ (Autologous) solid t
Slide 34: Thank You
THANK YOU as % Carisma carismatx.com
Slide 35: Appendix
APPENDIX as % Carisma carismatx.com
Slide 36: Carisma Platform
Carisma Platform
Slide 37: CAR-M Mechanism of Action in Oncology
1st time only CAR-M Mechanism of Action in Oncology Potential to address the challenges of treating solid tumors with cell therapies 1 2 3 TRAFFICKING & PHAGOCYTOSIS IMMUNE ACTIVATION ANTIGEN PRESENTATION MHC: Major Histocompatibility Complex 37
Slide 38: Macrophages: The Ultimate Multitasker
1st time only or for platform Macrophages: Patrol circulation Remove aged cells pitch The Ultimate Multitasker Recycle hemoglobin Remove apoptotic cells liver Kupffer cell Patrol lung Remove surfactant Remove particulate matter Macrophages can: First responders in lung lung Alveolar macrophage • Tra
Slide 39: CARISMA's Broad Myeloid Cell Engineering Platform
CARISMA’s Broad Myeloid Cell Engineering Platform Proprietary technology, world-leading macrophage engineering know-how, and strong IP position ensure leadership position Monocyte & Macrophage Engineering Capabilities: • Proprietary platforms for robust/durable monocyte & macrophage engineering • Es
Slide 40: Strong Patent Position
Strong Patent Position Broad Coverage for Monocyte and Macrophage Targeted Therapies • Worldwide patent coverage with issued and 37 pending applications in major markets • Multiple issued US patents covering CAR-M PAT E N T S G R A N T E D WORLDWIDE* composition of matter • Broad patent portfolio co
Slide 41: Strong Leadership Team and Advisors
Strong Leadership Team and Advisors Deep research, clinical and operational expertise in cell and gene therapy and oncology Management Board of Directors • Sanford Zweifach – Chairperson • Steven Kelly – President and CEO • Briggs Morrison, MD – Independent Director • Michael Torok – Independent Dir
Slide 42: CAR-Monocytes: Differentiated from CAR-T and CAR-NK
CAR-Monocytes: Differentiated from CAR-T and CAR-NK CAR-M has advantages that are potentially key for solid tumor oncology CAR-T CAR-NK CAR-Mono Mechanism of Action Effector Cell CD4/CD8 T cells Natural Killer Cells Monocytes Persistence Months/Years Days/Weeks 45-day half-life* Trafficking Potentia
Slide 43: CAR Monocytes: Numerous Advantages Over CAR Macrophages
CAR Monocytes: Numerous Advantages Over CAR Macrophages CAR Macrophage CAR Monocyte Cell Characteristics Monocyte-derived macrophage Origin CD14+ monocyte from peripheral blood (ex vivo differentiated for 7 days) Natural location Macrophages: Various tissues Monocytes: Blood Cell size 16-20µm 10µm D
Slide 44: Targeting HER2: CT-0525
Targeting HER2: CT-0525
Slide 45: CT-0525 Manufacturing Process
CT-0525 CT-0525 Manufacturing Process One day, automated process yielding up to 5x more cells per apheresis than CT-0508 Highlights CAR Expression: >90%* CAR-Monocyte Rapid Manufacturing Process Viability: >90%* Purity: >95%* Ad5f35 (adenovirus) based process Monocytes are primed to support in situ
Slide 46: Targeting HER2: CT-0508 Monotherapy
Targeting HER2: CT-0508 Monotherapy
Slide 47: CT-0508 Study 101: First in Human Phase 1 Clinical Design
CT-0508 Monotherapy CT-0508 Study 101: First in Human Phase 1 Clinical Design Assessing safety, tolerability, feasibility and TME impact of CT-0508 monotherapy Group 1: CT-0508 fractionated dose D1,3,5 Data (n=9) Reported HER2 2+/3+ solid tumors Demonstrated manufacturing feasibility, safe G-CSF adm
Slide 48: CT-0508 Study 101: Phase 1 Study Patient Demographics
CT-0508 Monotherapy CT-0508 Study 101: Phase 1 Study Patient Demographics Heavily pre-treated patients with Stage IV HER2 2+/3+ solid tumors Characteristics N=14 Tumor Type, n (%) Breast Cancer 8 (57.1) Esophageal Cancer 2 (14.3) Salivary Carcinoma 2 (14.3) Cholangiocarcinoma 1 (7.1) Ovarian Cancer
Slide 49: CT-0508 is Well-Tolerated with No Dose Limiting Toxicities
CT-0508 Monotherapy CT-0508 is Well-Tolerated with No Dose Limiting Toxicities Preliminary data supports a safe and well-tolerated product profile Number of Adverse Events Adverse Event Data by Patient 12 G1: Fractionated G2: Bolus Combined 10 Patients Treated N=9 (%) N=5 (%) N=14 (%) Grade 1 8 Cyto
Slide 50: Clinical Activity Observed in HER2 3+ Patients
CT-0508 Monotherapy Clinical Activity Observed in HER2 3+ Patients Correlation of target expression and clinical activity supports mechanism of action Change in tumor ctDNA at week 4 based on Correlation between HER2 status and HER2 status: Best Overall Response SD: PD: n=4 n=5 PD: n=5 % change in c
Slide 51: Early Efficacy Evaluation
CT-0508 Monotherapy Early Efficacy Evaluation Best Overall Response of Stable Disease Best Overall Change in Tumor Burden RESULTS 100 • Best Overall Response of Stable Disease in 4 Change in Target Lesion from Baseline (%) 80 of the 14 evaluated participants (28.6%)*+ 60 • Largest reduction in targe
Slide 52: CT-0508 remodeled the TME and induced anti-tumor T cell immunity
CT-0508 Monotherapy CT-0508 remodeled the TME and induced anti-tumor T cell immunity Improved TME remodeling and T cell dynamics seen in patients that achieved Stable Disease Expanding T Cell Clones Emergent T Cell Clones Score change (screening to week 4)3 1 Sum frequency Sum frequency 0 -1 Antigen
Slide 53: T cell Exhaustion is a Limiting Factor to CAR-Macrophage Efficacy
CT-0508 Monotherapy T cell Exhaustion is a Limiting Factor to CAR-Macrophage Efficacy Study 101 patients show high baseline T cell exhaustion, and inhibitory pathways are further upregulated T cell exhaustion markers in CT-0508 Changes in exhaustion markers (left) and exhausted CD8 T Correlation of
Slide 54: Targeting HER2: CAR-M + anti-PD1
Targeting HER2: CAR-M + anti-PD1
Slide 55: CAR-M + Anti-PD1: Robust Synergy
CAR-M + Anti-PD1: Robust Synergy Synergy in a solid tumor model that is resistant to anti-PD1 monotherapy Synergistic anti-tumor activity Synergistic TME modulation with combination 100 1 CAR-M + aPD-1 1 ✱ CAR-M probability (%) (%) Anti-PD1 aPD-1 ✱✱✱✱ Survival probability CTRL CTRL 50 CAR-M + anti-P
Slide 56: CAR-M + Anti-PD1: Robust Synergy
CT-0508 + anti-PD1 CAR-M + Anti-PD1: Robust Synergy Synergy in a solid tumor model that is resistant to both CAR-Macrophage and anti-PD1 monotherapy I.V. CAR-M1 + anti-PD1 leads to I.V. CAR-M1 + anti-PD1 leads synergistic tumor control to 100% survival 1500 100 3) 3 (mm ) CTRL (mm 75 (%) CTRL aPD1 1
Slide 57: Targeting HER2: CT-0508 + anti-PD1
Targeting HER2: CT-0508 + anti-PD1
Slide 58: CT-0508 Study 101: CT-0508 + Pembrolizumab Sub-study
CT-0508 + anti-PD1 CT-0508 Study 101: CT-0508 + Pembrolizumab Sub-study Assessing safety, tolerability and TME impact of CT-0508 in combination with anti-PD1 pembrolizumab Group 1: CT-0508 fractionated dose D1,3,5 (n=9) Data Reported Demonstrated manufacturing feasibility, safe administration, cell
Slide 59: CT-0508+Pembrolizumab Combination: Demographics
CT-0508 + anti-PD1 CT-0508+Pembrolizumab Combination: Demographics1 Patient Demographics were consistent with patients enrolled in the monotherapy groups Summary of Participant and Tumor Characteristics Characteristic N=6 Characteristic N=6 Median age (range), years 58 (45, 73) Tumor Type, n (%) Bre
Slide 60: CT-0508+Pembrolizumab Combination: Well-Tolerated, No Dose Limiting Toxicities
CT-0508 + anti-PD1 CT-0508+Pembrolizumab Combination: Well-Tolerated, No Dose Limiting Toxicities Similar safety profile to CT-0508 monotherapy CT-0508 Monotherapy CT-0508 Monotherapy CT-0508 + Pembrolizumab CT-0508 + Pembrolizumab Group 1: Fractionated Group 2: Bolus Dosing Regimen 1 Regimen 2 Dosi
Slide 61: CT-0508+Pembro Combination: Regimen Level 1 and 2 Summary
CT-0508 + anti-PD1 CT-0508+Pembro Combination: Regimen Level 1 and 2 Summary Regimen Best Overall HER2 Patient Disease Additional Treatment Details Level Response Status Stage IV Breast • Treated with dexamethasone due to G2 CRS post CT-0508 Patient 1 RL1 PD HER2 2+ Cancer infusion, prior to pembrol
Slide 62: CT-0508+Pembrolizumab Combination: Individual Case Study
CT-0508 + anti-PD1 CT-0508+Pembrolizumab Combination: Individual Case Study Patient 3: EAC patient with 6 prior lines of therapy and refractory to Enhertu Cancer type: Stage IV Esophageal adenocarcinoma (EAC), HER2 3+ Prior history: 6 Prior lines of therapy; Most recent prior line: achieved BOR* of
Slide 63: CT-0508+Pembrolizumab Combination: Individual Case Study
CT-0508+Pembrolizumab Combination : Individual Case Study Patient 3: 46% reduction in 1 of 2 target lesions Paratracheal LN Target Lesion: 46% reduction by week 13 Dosing Baseline Week 8 Week 13 • Patient received 3.10E+09 cells • Patient missed the 2nd cycle of pembrolizumab Tumor assessments • Par
Slide 64: CT-0508+Pembrolizumab Combination: Individual Case Study
CT-0508 + anti-PD1 CT-0508+Pembrolizumab Combination : Individual Case Study Patient 3: High baseline peripheral CD8 T cell exhaustion and achieved BOR of SD CD8 T-Cells Patient 3 achieved BOR of SD despite high baseline peripheral CD8 T cell exhaustion Monotherapy Response Pembro Response PD Patien
Slide 65: CT-0508+Pembrolizumab Combination: Individual Case Study
CT-0508 + anti-PD1 CT-0508+Pembrolizumab Combination : Individual Case Study Patient 3: Greatest increase in peripheral blood T cell clonality seen to-date across all 17 patients treated with CT-0508 Increased T cell clonality in the peripheral blood Monotherapy Pembrolizumab combo – cohort 1 Pt #3
Slide 66: In Vivo Oncology
In Vivo Oncology
Slide 67: Directly Reprogramming Myeloid Cells In Vivo with mRNA/LNP
In Vivo CAR-M Directly Reprogramming Myeloid Cells In Vivo with mRNA/LNP Direct TAM reprogramming shrinks tumors* Redirecting endogenous myeloid cells with mRNA for cancer immunotherapy Control Anti-HER2 CAR mRNA/LNP mRNA/LNP CAR Distribution in vivo (Mouse Blood) 40 Control mRNA/LNP % of CAR+ Cells
Slide 68: In Vivo CAR-M Suppresses Liver and Lung Metastasis
In Vivo CAR-M Suppresses Liver and Lung Metastasis Systemic LNP administration in humanized model leads to robust disease control Tumor Lesions in Liver (BLI) Tumor Lesions/Liver (IHC) Tumor Lesions in Lung (IHC) Control CAR 0.3 ✱ mRNA/LNP mRNA/LNP % GFP+ cells mRNA/LNP ✱✱ 0.2 mRNA/LNP Control 10000
Slide 69: Drive to 2025
Drive to 2025 Leverage world-leading macrophage engineering platform to deliver three product opportunities Program 2024 Tactical Plan 2025 Objectives CT-05251 Safety Study Cohort 1: 3 Billion Cells HER2 CAR-M CT-05251 Safety Study Cohort 2: 10 Billion Cells Phase II/III Regimen Identified2 In vivo