Calidi Biotherapeutics, Inc. · AMEX:CLDI

Calidi Biotherapeutics — Investor Presentation (February 2026)

23 slides from Calidi Biotherapeutics's investor presentation, February 2026

  1. Slide 1: Engineering the Future of Genetic Medicine

    Immune Genetic Protection Medicine(s) Engineering the Future of Genetic Medicine Targeting From cancer to other complex diseases, Calidi’s RedTail platform can precisely deliver genetic medicine to distal sites of disease Self-amplifying February 2026 selective vector Platform NYSE American: CLDI Ca

  2. Slide 2: Safe Harbor Statement

    Safe Harbor Statement 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,” “expect,” “intends,” “may,” “

  3. Slide 3: New Technology / New Leadership

    New Technology / New Leadership  RedTail platform and CLD-401 recently  First data presented on RedTail and CLD-401 in presented 2025  New management team with focus on  New CEO, CMO and Chairman with the industry execution experience to drive value  Revamped Scientific Advisory Board to  Mace

  4. Slide 4: Proven Efficacy with Intra-Tumoral Oncolytic Viruses

    Proven Efficacy with Intra-Tumoral Oncolytic Viruses  Multiple examples of efficacy with local administration • Amgen: T-Vec approved in 2015 for melanoma • CG Oncology: BLA submission for bladder cancer • Candel: BLA filing expected in localized prostate cancer • Replimune: BLA submitted for melan

  5. Slide 5: Can Oncolytic Viruses Be Used as Systemic Therapy?

    Can Oncolytic Viruses Be Used as Systemic Therapy?  Immune system quickly clears virus injected systemically into the bloodstream  Some limited success with systemic delivery of viruses1,2,3,4 • Strategy is based largely on dosing very high levels of virus to overcome immune clearance  Calidi has

  6. Slide 6: Building the Optimal Viral Platform, Step by Step

    Building the Optimal Viral Platform, Step by Step  Calidi has created a new strategy for systemic delivery based on eliminating immune recognition of virus • Allows for higher doses of effective virus with lower levels of innate immune stimulation; i.e., better therapeutic window  Vaccinia virus c

  7. Slide 7: Building the RedTail Scaffold: Step 1

    Building the RedTail Scaffold: Step 1 Tumor Tropism and Replication Selectivity • Vaccinia virus has inherent tropism for tumor cells1 • Vaccinia virus cell entry is not receptor dependent2  Virus genetically engineered to replicate only in tumor cells • Triple knockout version of vaccinia virus cr

  8. Slide 8: Building the RedTail Scaffold: Step 2

    Building the RedTail Scaffold: Step 2 Genetic Medicine(s) Genetic Medicine Payload • Vaccinia has a large genome with high capacity for insertion(s)1 – ~200kbp with >200 ORFs; up to 25kbp capacity for insertion • Calidi has identified proprietary sites in RedTail for gene(s) insertion  Vaccinia fol

  9. Slide 9: Building the RedTail Scaffold: Step 3

    Building the RedTail Scaffold: Step 3 Envelope Enveloped Form of Vaccinia Virus • Vaccinia virus produces two forms of infectious particles1 – During infection, >99% of virus is Intracellular Mature Virus (IMV) – <1% of virus is the Extracellular Enveloped Virus (EEV) form that takes on the cell mem

  10. Slide 10: Building the RedTail Scaffold: Step 4

    Building the RedTail Scaffold: Step 4 CD55  CD55 Overexpression • Complement is pivotal for immune clearance for Vaccinia1,2 – Complement is the major mechanism for clearance of Vaccinia3 • CD55 expression inhibits complement activation4 – RedTail scaffold genetically engineered to express CD55 at

  11. Slide 11: CD55 as a Protector Against Complement

    CD55 as a Protector Against Complement CD55  CD55 expression and erythrocytes (red blood cells, RBCs) • RBCs are normally protected from clearance by complement1 • Paroxysmal Nocturnal Hemoglobinuria (PNH) – Mutation in CD55; RBCs are cleared by complement system1 • Parasite induces a loss of CD55

  12. Slide 12: EEV with CD55 Expression Is Highly Resistant to Clearance

    EEV with CD55 Expression Is Highly Resistant to Clearance Virus survival in the presence of Human serum IMV (non-enveloped form) EEV (enveloped form) 6- High therapeutic potential with a multimodal MOA. EEV with CD55 expression Cell Cell Cell Cell IMV line line line line #1 #2 #1 + #2 + CD55 CD55 Ov

  13. Slide 13: The RedTail Platform

    The RedTail Platform Immune Genetic Protection  Systemic administration Medicine(s)  Protected from immune clearance (EEV form / CD55 expression)  Targeted tumor cell lysis and immune priming  Genetic medicine payload(s) expression in the TME  COGS similar to monoclonal antibody  Broad IP cove

  14. Slide 14: CLD-401: The First Lead From the RedTail Platform

    CLD-401: The First Lead From the RedTail Platform  Systemic administration Systemic Administration  Protected from immune CLD-401 infects clearance (EEV/CD55) other tumor cells CLD-401  Targeted tumor cell lysis and immune priming CLD- 401  IL-15 superagonist production at the tumor Tumor cell d

  15. Slide 15: IL-15SA: Proven Activity At High Doses and With an Immune Primer

    IL-15SA: Proven Activity At High Doses and With an Immune Primer  IL-15 is a powerful growth factor for NK cells (innate) and CD8+ T-cell (adaptive) – Unlike IL-2, IL-15 does not expand Tregs or induce T-cell death  A major mechanism of resistance to PD-1 therapy is B2M mutation / HLA loss – B2M/H

  16. Slide 16: IL-15SA: Proven Activity At High Doses and With an Immune Primer

    IL-15SA: Proven Activity At High Doses and With an Immune Primer  Anktiva (IL-15 SA) is approved in bladder cancer for local delivery: – Extraordinary levels of IL-15 SA in the TME (~80K pM) – Given with BCG as an immune priming mechanism – Low systemic IL-15 SA exposure (<20pM)  Anktiva is being

  17. Slide 17: CLD-401: Tumor-specific IL-15SA expression

    CLD-401: Tumor-specific IL-15SA expression • IL-15 SA concentrations in the tumor are similar to Anktiva in bladder cancer – Expression in serum or other tissues is >1,000 times lower – Virus is acting as an immune primer in the tumor IL-15 SA concentrations (pM) in tumor and organs at multiple time

  18. Slide 18: CLD-401: Tumor-specific viral replication

    CLD-401: Tumor-specific viral replication • Viral expression detected only in tumor tissue – Replication in other tissues is ~1,000 times lower or non-detectable – Tumor-specific replication allows for systemic delivery CLD-401 showed high tumor presence with minimal detection in other organs: Tumor

  19. Slide 19: Enhanced Therapeutic Activity With In Situ IL-15 SA Expression

    Enhanced Therapeutic Activity With In Situ IL-15 SA Expression RedTail virus with IL-15 SA payload (CLD-401) dramatically improves treatment efficacy Tumor regression in syngeneic EMT6 model after a single administration of 5e6 PFU viral particles Untreated RedTail Virus (no payload) CLD-401 (IL-15

  20. Slide 20: CLD-401 Timeline to Clinic

    CLD-401 Timeline to Clinic 2025 2026 2027 Preclinical, CMC & Regulatory Phase 1 CLD-401 IND  Phase I study to be conducted in a basket of solid tumors (NSCLC, TNBC, Melanoma, etc.) • Streamlined dose escalation study with limited # of doses to be tested • Early demonstration of systemic delivery of

  21. Slide 21: RedTail: Potential to Enhance Platform and Expand Outside of Oncology

    RedTail: Potential to Enhance Platform and Expand Outside of Oncology Next-Generations Cancer: • Expand payload options (e.g BiTEs) • Engineer envelope for programmable targeting (e.g. HER2, TROP2, CD38, etc) Outside Oncology: • New payloads for inflammatory & immune diseases (I&I) • Target other ce

  22. Slide 22: Delivering High Concentrations of BiTEs and T-cell Amplifier to the TME

    Delivering High Concentrations of BiTEs and T-cell Amplifier to the TME  BiTEs (Bi-specific T-cell engagers) have been transformative in hematological malignancies but have not shown success in solid tumors • The tumor microenvironment in solid tumors inhibits T-cell infiltration and T-cell effecto

  23. Slide 23: Upcoming Milestones

    Upcoming Milestones 1H26 2H26 1H27 CLD-401: IND / Phase I Preclinical, CMC, & Regulatory IND Phase 1 Data presentations AACR ASCGT ASCO ESMO SITC AACR ASCGT ASCO CLD-401 • Data on TME • Presentation of • Data on repeat • Tox and efficacy • Biodistribution • Combination • Update on non- • Combination

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