Calidi Biotherapeutics, Inc. · AMEX:CLDI
Calidi Biotherapeutics — Investor Presentation (March 2025)
27 slides from Calidi Biotherapeutics's investor presentation, March 2025
Slide 1: Targeting and Attacking Tumors with Multimodal Virotherapies
Targeting and Attacking Tumors with Multimodal Virotherapies A New Era of Systemic and Localized Immuno-Oncology Therapies NYSE American: CLDI March 2025
Slide 2: Forward-Looking Statements and Legal Disclaimer
Forward-Looking Statements and Legal Disclaimer This presentation may contain forward-looking statements for purposes of the “safe harbor” provisions under the United States Private Securities Litigation Reform Act of 1995. Terms such as “anticipates,” “believe,” “continue,” “could,” “estimate,” “ex
Slide 3: Executive Summary - Overview
Executive Summary - Overview Cancer is a complex disease, often leading to patient mortality due to metastasis, which underscores the need for innovative solutions. Calidi is transforming immune-oncology treatment by pioneering a new generation of systemic and localized multimodal virotherapies. Cal
Slide 4: RTNova Program (CLD-400), a Systemic Virotherapy Solution
RTNova Program (CLD-400), a Systemic Virotherapy Solution ✓ New treatment option for advanced metastatic disease or lung cancer ✓ Simple IV administration avoiding the need for image-guided delivery. ✓ Able to survive in circulation ✓ Designed to home and self-amplify in tumor sites © 2025 Calidi Bi
Slide 5: Multimodal Mechanism of Action of Enveloped RT Virotherapy
Multimodal Mechanism of Action of Enveloped RT Virotherapy 1 2a 2b Protected enveloped virotherapies Selective viral Delivery of transient survive bloodstream and target tumor sites amplification and spread gene therapy (payload) With envelope technology vector can target all tumor sites Enveloped V
Slide 6: RT Vaccinia Virus: An Extracellular Enveloped Vaccinia (EEV) Strain
RT Vaccinia Virus: An Extracellular Enveloped Vaccinia (EEV) Strain Enveloped: 1- High production of enveloped viruses is genetically encoded in RT virus genome. 2- Virus is manufactured enveloped with a human cell membrane containing human surface receptors offering: Protection/immunomodulation Tar
Slide 7: Protection: Envelope Maximizes Resistance Against Humoral Immunity
Protection: Envelope Maximizes Resistance Against Humoral Immunity We developed a novel methodology to manufacturing extracellular enveloped vaccinia viruses (EEVs) Expression of anti Enveloped Vaccinia virus survives rapid inactivation by human complement receptor CD55 serum making feasible systemi
Slide 8: Targeting and Tumor-Selective Amplification of RT Triple Knockout Virus
Targeting and Tumor-Selective Amplification of RT - Triple Knockout (3KO) - virus Targeting, amplification & biodistribution analysis after single dose administration of RT-3KO virus Lung tumor-bearing mice (copies viral DNA/uG tissue. n=3) 3,000,000 RT 3KO (Day 1) RT 3KO virus targets preferentiall
Slide 9: RT-3KO Induces Direct Killing of Multiple Tumors Cell Types
HT29 Colon G2 HCT-116 HCT-15 RT-3KO Induces Direct Killing of Multiple Tumors Cell Types CNS COLO 205 HCC-2998 SF-268 U251 SF-295 SNB-19 % Cytotoxicity SNB-75 60 SF-539 Analysis of tumor cytotoxicity for RT-3KO across over 60 tumor cell lines using the NCI-60 panel. MALME-3M SK-MEL-2 LOX IMVI SK-MEL
Slide 10: RT Virotherapy Targets and Eliminates Multiple Tumors in Preclinical Models
RT Virotherapy Targets and Eliminates Multiple Tumors in Preclinical Models After one (1) systemic administration, envRT Mouse model bearing 3 different human solid tumor types (enveloped RT) can target all distant tumors Untreated envRT-01 % Tumor Growth inhibition and express selected payload (i.e
Slide 11: RT Virotherapy Modulates Tumor Microenvironment Supporting Anti-Tumor Immune Response
RT Virotherapy Leads to Significant Modulation of All Tumor Microenvironment Supporting an Anti-Tumor Immune Response Leukocytes TILs CD3+ T cells CD8+ cells Tregs ✱✱ Myeloid cells ✱✱ CD8+ T cells (%CD3+ T cells) 60 ✱✱ 100 ✱✱ 3 ✱✱ Myeloid cells (% Leukocytes) 80 80 ✱✱ 100 Leukocytes (% Live cells) T
Slide 12: Delivery of Gene Immunotherapy Payload to All Targeted Tumors
Maximizing Therapeutic Efficacy Through Delivery of Gene Immunotherapy Payload to All Targeted Tumors RT 3KO, serving as a viral vector, has the capacity to genetically introduce the in-situ production of immunomodulators (payload) in tumors, drastically improving treatment efficacy. Local productio
Slide 13: Pipeline And Early Partnership Opportunities
Pipeline And Early Partnership Opportunities Program Mode of Action Target Indication Discovery/Preclinical IND-enabling Phase 1 EnvRT-01s • Tumor killing Metastatic NSCLC Lead generation • TME reprogramming, (Lung Cancer) • Payload undisclosed EnvRT-02s • Tumor killing Advanced solid tumors Combo w
Slide 14: Building the Future of Systemic Virotherapies
Building the Future of Systemic Virotherapies RTNova introduces a significant advancement in true systemic virotherapy by employing enveloped technology to survive bloodstream and target all tumors. RTNova is designed with a multimodal MOA which includes, a) direct killing, b) induction of antitumor
Slide 15: Clinical pipeline
Clinical pipeline Intratumoral and localized cell-based virotherapies NYSE American: CLDI March 2025
Slide 16: Maximizing Therapeutic Responses with Directed Localized Administration
Maximizing Therapeutic Responses with Directed Localized Administration Directed – Localized Administration CLD-101 (Neuronova) ✓ High therapeutic index of treated lesion/areas Completed Phase 1 ✓ Low toxicity ✓ Strong activation of local and systemic antitumor CLD-201 immunity (Supernova) Phase 1 @
Slide 17: CLD-101 (NeuroNova) in High Grade Glioma (HGG)
CLD-101 (NeuroNova) in High Grade Glioma (HGG) Completed: Phase 1 (NWU) Ongoing: Phase 1 (COH) In preparation: Phase 1b/2 (NWU) single dose multiple dose multiple dose in newly diagnosed HGG in recurrent HGG in newly diagnosed HGG • Treatment was well tolerated • Primary Objective: analyze • Primary
Slide 18: CLD-201 (SuperNova) in Advanced Solid Tumors
CLD-201 (SuperNova) in Advanced Solid Tumors Completed: Safety Study In Preparation: Phase 1 (Calidi) Autologous settings - single dose Allogeneic, off-the shelf - multiple dose • Treatment was safe and tolerable. • Strong initial signals of efficacy • New allogeneic program developed to reach docum
Slide 19: Upcoming Planned Milestones (2025-2026)
Upcoming Planned Milestones (2025-2026) 2025 2026 1H 2H 1H 2H CLD-101 Clinical trial (NNV1: multiple doses 1st patient dosed enrollment update newly diagnosed HGG) Clinical trial Update Clinical trial Update CLD-101 (NNV2: Multiple doses Clinical trial & biomarker recurrent HGG) studies update Phase
Slide 20: Appendix
Appendix CLD-400 Additional Scientific information NYSE American: CLDI March 2025
Slide 21: Vaccinia Virus as a Systemic Antitumor Virotherapy and Viral Vector
Vaccinia Virus as a Systemic Antitumor Virotherapy and Viral Vector 1- RT Vaccinia virus is a highly cytolytic virus - tumor agnostic. 2- Genetically stable. 200kB dsDNA virus. 3- Large insertion capacity (25-45Kb), allowing delivery of existing therapeutic proteins into the tumor, potentiating anti
Slide 22: New Vaccinia Backbone Designed for Systemic Delivery
•. New Vaccinia Backbone Designed for Systemic Delivery → Vaccinia virus has 2 main forms: 1- EEV (Extracellular Enveloped Virus) (Protected) Requirements of new backbone selected and engineered by Calidi (RT strain): VACV cycle High production of EEV To be able to be manufactured by enriching EEV p
Slide 23: Redtail (RT): A New Vaccinia Virus Strain Which Produces High Levels of EEV Particles
Redtail (RT): A New Vaccinia Virus Strain Which Produces High Levels of EEV Particles Vaccinia Viruses are genetically engineered to Comet assay of two distinct vaccinia viruses express TurboFP635 (red fluorescence). Vaccinia virus strain CAL2 Redtail Vaccinia virus envRT-01 producing low EEV partic
Slide 24: Generation of a Tumor-Selective RT (Triple Knockout, 3KO) Vaccinia Virus
Generation of a Tumor-Selective RT (Triple Knockout, 3KO) Vaccinia Virus Ex-vivo imaging of major organs after administration of different engineered (KO) RT viruses (expressing TurboFP635) Ex-Vivo Signals (Mean Radiance) 1e+008 Tumor RT viruses with double KO (RT 2KO) or Heart triple KO (RT 3KO) re
Slide 25: Systemic Administration of EnvRT Can Eliminate Lung Cancer And Metastasis
Systemic Administration of EnvRT Can Eliminate Lung Cancer And Metastasis One (1) dose (5e6 PFU) was able to decrease and eliminate lung cancer and metastatic tumors into the lung. Control envRT Bioluminescent Emission C. 2.5×10 9 Total Emission (Photon/s) 2×10 9 1.5×10 9 1×10 9 5×10 8 0 Control env
Slide 26: Systemic Administration of enveloped RT virus Targets Lung Cancer and Metastatic Sites
Systemic Administration of enveloped RT virus Targets Lung Cancer and Metastatic Sites - LL2 lung cancer cells colonize lungs after I.V. administration. - Systemic administration of envRT-01 targets multiple tumor loci. Note: animals were euthanized, and organs imaged 6 days following 1 single admin
Slide 27: envRT Targets All Disseminated Tumor Sites Inducing Major Immune Modulation
envRT Targets All Disseminated Tumor Sites Inducing Major Immune Modulation Targeting all metastasis: Immunohistochemistry data indicates systemic envRT treatment targets metastasis inducing major infiltration of immune cells in all tumor loci (experimental metastasis lung cancer tumors) Untreated t
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