Calidi Biotherapeutics, Inc. · AMEX:CLDI
Calidi Biotherapeutics — Investor Presentation (October 2025)
22 slides from Calidi Biotherapeutics's investor presentation, Oct 24, 2025
Slide 1: Engineering the Future of Genetic Medicine
Engineering the Future of Genetic Medicine From cancer to other complex diseases, Calidi’s RedTail platform can precisely deliver genetic medicine to distal sites of disease October 2025 NYSE American: CLDI Calidibio.com CALIiDi
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,” “
Slide 3: Calidi Advantages
Calidi Advantages * The RedTail platform is the next leap forward in delivering oncolytic viruses + Systemic delivery reaches distal disease sites + Ability to express proteins to tumors +. Designed to avoid immune clearance and home to metastatic tumor sites, induce tumor lysis and immune priming,
Slide 4: The Systemic Delivery of Oncolytic Viruses
The Systemic Delivery of Oncolytic Viruses Our RedTail Technology Building the Optimal Viral Platform CLD-401: Our Lead Program Leadership and Milestones CALIDi
Slide 5: Proven Efficacy with Intra-Tumoral Oncolytic Viruses
Proven Efficacy with Intra-Tumoral Oncolytic Viruses “ Multiple examples of efficacy with local administration of an oncolytic virus + Amgen: T-Vec approved in 2015 for unresectable lesions in melanoma post surgery * “CG Oncology: BLA submission for cretostimogene in BCG-unresponsive NMIBC. * Candel
Slide 6: Can Oncolytic Viruses Be Used as Systemic Therapy?
Can Oncolytic Viruses Be Used as Systemic Therapy? ~ * Efficacy in r/r solid tumor Ph I studies with IV admin of Newcastle disease virus + 1CR, 3 PRs, and 2 minor responses in 18 pts; ~1/3 pts w/ Gr4 AEs; (10! - 10"! pfu/dose)! + 1 GRand 6 PRs in 20 pts with alpha-Gal-NDV (2025 Cell paper); (10!° -
Slide 7: Building the Optimal Viral Platform, Step by Step
Building the Optimal Viral Platform, Step by Step * Vaccinia virus chosen as basis for Calidi’s RedTail scaffold + Large DNA poxvirus that only replicates in the cytoplasm = No potential for host DNA integration = Large capacity for payload insertion ¢_ Naturally tropic for tumor cells * Rapid and p
Slide 8: Building the RedTail Scaffold: Tumor Tropism and Replication Selectivity
Building the RedTail Scaffold: Step 1 Tumor Tropism and Replication Selectivity * Vaccinia virus has inherent tropism for tumor cells! * Vaccinia virus cell entry is not receptor dependent? * Virus genetically engineered to replicate only in tumor cells *_ Triple knockout version of vaccinia virus c
Slide 9: Building the RedTail Scaffold: Genetic Medicine Payload
Building the RedTail Scaffold: Step 2 Genetic Medicine Payload * Vaccinia has a large genome with high capacity for insertion(s)! = ~200kbp with >200 ORFs; up to 25kbp capacity for insertion ‘ * Calidi has identified proprietary sites in RedTail for gene(s) insertion “+ Vaccinia follows a cascade te
Slide 10: Building the RedTail Scaffold: Enveloped Form of Vaccinia Virus
Building the RedTail Scaffold: Step 3 Enveloped Form of Vaccinia Virus * Vaccinia virus produces two forms of infectious particles! - 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 membrane (
Slide 11: Building the RedTail Scaffold: CD55 Overexpression
Building the RedTail Scaffold: Step 4 CD55 Overexpression * Complement is pivotal for immune clearance for Vaccinia!? = Complement is the major form of Vaccinia clearance? + CD55 expression inhibits complement activation* — RedTail scaffold genetically engineered to express CD55 at high levels = CD5
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 (ae 120 IMV (non-enveloped form) Rss) 100 2 o EEV (enveloped form) 40 % virus survival o 3 20 EEV with CD55 expression Tt T Cell Cell Cell Cell = IMV line line line line #1 #2 M+ H+ 055 _cD55 /) O
Slide 13: The RedTail Platform
The RedTail Platform * Systemic administration «> 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 coverage of platform technology a] CALIDi
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 caoaox infec clearance (EEV/CD55) other tumor calls aip.aot me ~* Targeted tumor cell lysis and immune priming “+ IL-15 superagonist production at the tumor Tumor cell death an
Slide 15: IL-15 Superagonist: Proven Activator of Immunity
IL-15 Superagonist: Proven Activator of Immunity * IL-15 is a powerful growth factor for NK cells (innate) and CD8+ T-cells (adaptive) * Unlike IL-2, IL-15 does not expand Tregs or induce activation-induced T-cell death + IL-15 superagonist is a fusion of IL-15 (N72D) and the Sushi domain IL-15 alph
Slide 16: CLD-401 Delivers High Levels of IL-15 SA Only in the Tumor
CLD-401 Delivers High Levels of IL-15 SA Only in the Tumor Serum concentration in syngeneic murine models is negligible Tumor concentration is much higher than achievable with systemic delivery IL-15 Superagonist Levels in Tumor vs Serum (pM) Day6 Day 10 70000, Cup 60000 iss RedTail gene therapy del
Slide 17: 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
Slide 18: CLD-401 Timeline to Clinic
CLD-401 Timeline to Clinic | 2025 | 2026 | 2027 Preclinical, CMC & Regulatory. Phase 1 CLD-401 € We > IND “> Phase | study to be conducted in a basket of solid tumors (NSCLC, TNBC, Melanoma, etc.) * Rapid dose escalation study with limited # of doses to be tested * Early demonstration of systemic de
Slide 19: Evolving the RedTail Platform
Evolving the RedTail Platform Lead: CLD-401 Next-Generations Oncology Precision Oncology and Other Diseases * Tumor tropism and replication restricted to tumor * Envelope engineering for “programmable” targeting cells — Targeting proteins (scFvs, VHHs, etc.) expressed = a am in envelope * Envelope a
Slide 20: Capitalization Table
Capitalization Table Securities Outstanding {as of September 30, 2025) Common Stock Equivalents Common stock outstanding 7,056,312 Warrants (WAEP $34.97) 5,026,613 Options (WAEP $59.56) 251,036 Forward Purchase Agreements 5,501. Fully Diluted 12,339,462 Cash position: * $5.3M in cash as of June 30,
Slide 21: New Leadership Driving Strategic Progress
New Leadership Driving Strategic Progress “* New management v¥ New CEO, CMO and Chairman with team industry experience to drive value “* Improving the balance —- V Debt reduced from >$8M to $1.4M (2Q25); sheet projected to be $0.6M by end of 2025 “* Reducing operating v G&A expenses reduced by 25% 1
Slide 22: Near-term Milestones
Near-term Milestones CLD-401: SITC presentation — . P Demonstration of IL-15 SA CLD-401: IND-enabling production in tumors versus serum; benefit in animal models inducing complete responses pharmacology and toxicology studies completed RedTail Platform: CLD-401: Open IND Preclinical data for r/r sol
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