Calidi Biotherapeutics, Inc. · AMEX:CLDI
Calidi Biotherapeutics — Investor Presentation (March 2025)
27 slides from Calidi Biotherapeutics's investor presentation, Mar 10, 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 moa CALIDi BIOTHERAPEUTICS
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 és) CALiD IOTHERAPEUTICS 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 mult
Slide 4: RTNova Program (CLD-400), a Systemic Virotherapy Solution
RTNova Program (CLD-400), a Systemic Virotherapy Solution v New treatment option for advanced metastatic disease or lung cancer v Simple |V administration avoiding the need for image-guided delivery. ¥ Able to survive in circulation Y Designed to home and self-amplify in tumor sites CALIDi © 2025 Ca
Slide 5: Multimodal Mechanism of Action of Enveloped RT Virotherapy
Multimodal Mechanism of Action of Enveloped RT Virotherapy 1 Delivery of transient Protected enveloped virotherapies gene therapy (payload) 2a _—— Selective viral |——+ survive bloodstream and target tumor sites amplification and spread With envelope technology vector can target all tumor sites ‘Asa
Slide 6: RT Vaccinia Virus: An Extracellular Enveloped Vaccinia (EEV) Strain
RT Vaccinia Virus: An Extracellular Enveloped Vaccinia(EEV) Strain 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 » Targeting/
Slide 7: Novel methodology to manufacture extracellular enveloped vaccinia viruses (EEVs)
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 (DAF) in viral envelop - + Standard Media Human Serum 12.4% Survival 79.3% Survival and pe
Slide 8: Targeting and Tumor-Selective Amplification of RT - Triple Knockout (3KO) virus
Targeting and Tumor-Selective Amplifica 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) 3,000.0 SC aopen RT 3KO virus targets preferentially the jay iy
Slide 9: RT-3KO Induces Direct Killing of Multiple Tumors Cell Types
RT-3KO Induces Direct Killing of MultipleTumors Cell Types Analysis of tumor cytotoxicity for RT-3KO across over 60 tumor cell lines using the NCI-60 panel. Mot 0.01 0.4 100 Leukemia => RT3KO demonstrated notable and direct cytotoxic effects after 72 hours post-treatment at a low multiplicity of inf
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 and express selected payload (i.e imaging protein TurboFP635) Untreated envRT-
Slide 11: RT Virotherapy Leads to Significant Modulation of All Tumor Microenvironment
RT Virotherapy Leads to Significant Modulation of All Tumor Microenvironment Supporting an Anti-Tumor Immune.Re Leukocytes cDS+ T cells 608+ cells Tregs sy tt yt Biv + 4 ¢ : z . 3 3 3 3 i i . tis ' 3” g So. a gy ° H Seo z i z a}: a i g pe z oe i ge 4 3 2 ad 3 2 2 Fz 2 3 £ a 3 S ott ° o- Bo °. 3 Cont
Slide 12: Maximizing Therapeutic Efficacy Through Delivery of Gene Immunotherapy Payload
r Maximizing Therapeutic Efficacy ThroughDelivery 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. D> The adminis
Slide 13: Pipeline And Early Partnership Opportunities
Pipeline And Early Partnership Opportunities EnvRT-01s Lead generation EnvRT-02s Combo with Immune cell therapy EnvRT-03s Novel Payload Tumor killing TME reprogramming, Payload undisclosed Tumor killing, Prime solid tumors to prepared for combo Tx Improved TME reprograming and killing. Payload undis
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 CALIDi BIOTHERAPEUTICS.
Slide 16: Maximizing Therapeutic Responses with Directed Localized Administration
Maximizing Therapeutic Responses with Directed Localized Administration Directed — Localized Administration j CLD-101 (Neuronova) Completed Phase 1 Y High therapeutic index of treated lesion/areas Y Low toxicity v Strong activation of local and systemic antitumor immunity CLD-201 (Supernova) . ae Ph
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 e New allogeneic program developed to reach Strong initial signals of efficacy wider cancer population
Slide 19: Upcoming Planned Milestones (2025-2026)
Upcoming Planned Milestones (2025-2026) a ee ee CLD-101 Clinical trial anten dosed ca tte i WE asian dosed wo ae a a newly diagnosed HGG) Clinical trial Update Clinical trial Update CLD-101 (occ US cinta omer s s a ar recurrent HOG) studies update Phase 1, Dose escalation rare Clinical wal Update re
Slide 20: Appendix
Appendix CLD-400 Additional Scientific information NYSE American: CLDI moa CALIDi BIOTHERAPEUTICS.
Slide 21: Vaccinia Virus as a Systemic Antitumor Virotherapy Viral Vector
Vaccinia Virus as a Systemic itumor Virotherapy Viral Ve 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 antitumor syste
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): High production of EEV To be able to be manufactured by » enriching EEV particles 2
Slide 23: Vaccinia Viruses are genetically engineered to express TurboFP635
‘Vaccinia Viruses are genetically engineered to Comet assay of two distinct vaccinia viruses express TurboFP635 (red fluorescence). Vaccinia virus strain CAL2 producing low EEV particle — Redtail (RT) Strain Along “tail” in a comet assay indicates that the virus can produce high levels of EEV leadin
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- Hear Lung: Liver Spleen 5e+007 Kidneys- Ovaries Intestines: Brai
Slide 25: EnvRT Can Eliminate Lung Cancer and Metastasis
of EnvRT Can Eliminate Lung Cancer An Metastasis One (1) dose (5e6 PFU) was able to decrease and eliminate lung cancer and metastatic tumors into the lung. + Control c Bioluminescent Emission xg 210% Metastasized 1.5x109 Lung tumors 110% 5xt08 a 0: Control envRT Total Emission (Photon/s) Tumor signa
Slide 26: Systemic Administration of enveloped RT virus Targets Lung Cancer and Metastatic
Systemic Administration of enveloped RT virus Targets Lung Cancer and Metastatic Tumor signal: Rainbow (Bioluminescence) LL2 lung cancer cells colonize lungs after I.V. administration. - Systemic administration of envRT-01 targets multiple tumor loci. Page 26 CALIDi
Slide 27: Targeting all metastasis: immunohistochemistry data
CALDi Untreated tumor envRT-01 Modulation Targeting all metastasis: Immunohistochemistry data indicates systemic envRT treatment targets metastasis inducing major infiltration of immune cells in all tumor loci ( H&E re te, rimental metastasis lung cancer tumors) Zoom -in and pending Page 27 Biothera
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