Theriva Biologics, Inc. · AMEX:TOVX
Theriva Biologics — Technical Presentation (October 2025)
33 slides from Theriva Biologics's technical presentation, Oct 8, 2025
Slide 1: Virotherapy with armed OAd
Virotherapy with armed OAd © Theriva BIOLOGICS Y IDIB ELLS a Institut Catala d'Oncologia CELLULAR MEDIC
Slide 2: Declaration of Interest
Declaration of Interest: Honoraria, shares and funding from Theriva Biologics.
Slide 3: VIRAGE randomized phase 2 trial for metastatic pancreatic cancer
Nab-placlitaxel+gemcitabine weekly until progression RECIST VCN-01 (1E13vp iv) Transient and mild AEs: fever, nausea, transaminitis VCN01+CTx vs CTx VIRAGE randomized phase 2 trial for metastatic pancreatic cancer
Slide 4: VIRAGE phase 2B clinical trial: PFS and overall survival
VIRAGE phase 2B clinical trial Progression –free survival: 7.0 vs 4.6 mo (p=0.01; HR 0.55) Overall survival: 10.8 vs 8.6 mo (p=0.05; HR 0.57)
Slide 5: VIRAGE phase 2B clinical trial: duration of response
VIRAGE phase 2B clinical trial Duration of response: 11.2 vs 5.4 mo (p=0.003; HR 0.22) PFS if VCN-01 x 2: 11.2 vs 7.4 mo (p=0.01; HR 0.48)
Slide 6: Pore formation is the hallmark of pyroptosis / immunogenic cell death
Pore formation is the hallmark of PYROPTOSIS / immunogenic cell death From Bertheloot et al. Cell Mol Immunol 18, 1106–1121 (2021)
Slide 7: Rationale for pore-forming toxin parasporin-2 (PS2)
• Strong cytocidal activity against a broad range of human cancer cell lines • Minimal cytotoxicity toward normal hepatocytes and A549 cells • Inactive 37-kDa protoxin is processed to a 30-kDa active form by proteinase K • Exposure to the toxin causes striking morphological changes in susceptible ce
Slide 8: Parasporin pore formation requires several unknown receptors
Parasporin 2 pore formation requires several unknown receptors Created with BioRender.com
Slide 9: PS2 may kill non-infected bystander cells and reduce viral immunodominance
PS2 may kill non-infected bystander cells and reduce viral immunodominance Created with BioRender.com
Slide 10: Parasporin2 (PS2) with furin-mediated activation
Parasporin2 (PS2) with furin-mediated activation Furin-sensitive linkers C-term Inhibitory domain N-term Inhibitory domain CT26 “Fritolysis” Furin cut Furin cut
Slide 11: Slide 11
Slide 12: Furin-cleavable linkers enhance cytotoxicity
Furin-cleavable linkers enhance cytotoxicity CT26 cells , MTS assay % Metabolic activity
Slide 13: PS2 induces membrane calreticulin (marker of ICD)
A549 CT26 PS2 induces membrane calreticulin (marker of ICD)
Slide 14: PS2 induces ATP release (marker of ICD)
CT26 (mouse colorectal adenocarcinoma) PS2 induces ATP release (marker of ICD) HepG2 (human hepatocellular carcinoma) A549 (human lung adenocarcinoma) RealTime-Glo extracellular ATP assay with SNs diluted ½ :
Slide 15: PS2 induces HMGB1 release (marker of ICD)
PS2 induces HMGB1 release (marker of ICD) CT26 (mouse colorectal adenocarcinoma) HepG2 (human hepatocellular carcinoma) A549 (human lung adenocarcinoma) Lumit HMGB1 immunoassay with SNs :
Slide 16: PS2 induces fritolysis in multiple mouse tumor cell lines
PS2 induces “fritolysis” in multiple mouse tumor cell lines CMT64-RG6 (mouse lung adenocarcinoma) CT26 (mouse colorectal adenocarcinoma) MC38 (mouse colorectal adenocarcinoma) TRAMPC2 (mouse prostate adenocarcinoma) B16-CAR (mouse melanoma) Sensitive Resistant KPC (mouse pancreatic ductal adenocarci
Slide 17: PS2 induces cytotoxicity in multiple mouse tumor cell lines
CT26 (mouse colorectal adenocarcinoma) MC38 (mouse colorectal adenocarcinoma) CMT64-RG6 (mouse lung adenocarcinoma) TRAMPC2 (mouse prostate adenocarcinoma) B16-CAR (mouse melanoma) Sensitive Resistant KPC (mouse pancreatic ductal adenocarcinoma) PS2 induces cytotoxicity in multiple mouse tumor cell
Slide 18: PS2 induces bystander fritolysis
CT26 mixed with 293GL CT26 mixed with 293GL-PS2 A549 mixed with 293GL-PS2 PS2 induces bystander “fritolysis”
Slide 19: SNs containing PS2 have antitumor activity
d0 1e+06 CMT64.6 d12 (~50-70 mm3) C57BL/6J 3 IT injections PS2FuT/Control SN d16 d19 Tumor volume (mm 3 ) SNs containig PS2 have antitumor activity
Slide 20: PS2 confers ICD-mediated antitumor immunity
PS2 confers ICD-mediated antitumor immunity Antitumor immune responses were detected in a PS2FuT-treated mouse Created with BioRender.com
Slide 21: ICOVIR-15K-SA-PS2
ICOVIR-15K-SA-PS2 SA pA Fiber RGDK E1a ∆24 MLP L1 L2 L3 L4 L5 E2F boxes PS2FuT N-term Inhibitory domain C-term Inhibitory domain Furin cut Furin cut
Slide 22: PS2-armed OAd intratumoral replication and gene expression upon iv administration
Created with BioRender.com PS2-armed OAd intratumoral replication and gene expression upon iv admin
Slide 23: ICOVIR15K-PS2 vs ICOVIR15K body weight toxicity
*vs. PBS ICOVIR15K-PS2 vs ICOVIR15K body weight toxicity
Slide 24: ICOVIR15K-PS2 vs ICOVIR15K antitumor efficacy
****vs. PBS *vs. PBS #vs. ICO15K ICOVIR15K-PS2 vs ICOVIR15 antitumor efficacy
Slide 25: VCN-12: Next Generation OV Based on VCN-01
VCN-12: Next Generation OV Based on VCN-01 LITR E2F boxes E1A- ∆24 MLP RITR L1 L2 L3 L4 L5 Fiber RGDK VCN-01: PH20 IIIaSA LITR RITR E2F boxes E1A- ∆24 MLP L1 L2 L3 L4 L5 Fiber RGDK ∆E1B/19K ∆E3/19K VCN-12: Bee Hyal Parasporin2 IIIaSA T2A VCN-12 modifications vs VCN-01: • Replace PH20 with Bee hyalur
Slide 26: PS2 and hyaluronidase activity from VCN-12-infected cells
PS2 activity in SN (CT26 cells): CT26 HepG2 Hyaluronidase and PS2 secreted from VCN-12-infected cells Hyaluronidase activity in SN (turbidometry)
Slide 27: Increased cytotoxicity of VCN-12 vs VCN01 in tumor cell lines
2x Increased cytotoxicity of VCN-12 vs VCN01 in a panel of tumor cell lines SK-mel28 8x 3.4x 10x HT29 SW1116 3.5x SK-CO1 13.7x A549 HP1 6x CMT64-RG6-hCAR 6x HKT-1097 Human Hamster Mouse
Slide 28: VCN-12 shows a similar toxicity profile to VCN-01
VCN-12 shows a similar toxicity profile to VCN-01 No differences between VCN-12 and VCN-01 in: • Biochemical, hematological and coagulation parameters • Liver pathology analysis Liver transaminases VCN-12 VCN-12 Body weight loss
Slide 29: VCN-12 shows more antitumor activity than VCN-01 in hamster model
*p-value<0.05 (IIIa-BH-PS2 vs PBS) *p-value<0.05 (VCN-12 vs PBS) ºp-value<0.05 (VCN-01 vs PBS) #p-value<0.05 (VCN-12 vs VCN-01) # Syrian hamster Hamster sc. Tumors HP-1 (pancreatic) Day -11 Day 1 Day 4 Virus administration (IT) Right tumor 2.5E10vp/animal Inoculation Right flank Inoculation Left fla
Slide 30: VCN-12 improves survival and induces complete responses in hamsters
# * *p-value<0.05 (VCN-12 vs PBS) #p-value<0.05 (VCN-12 vs VCN-01) Survival Rejections Syrian hamster Hamster sc. Tumors HP-1 (pancreatic) Day -11 Day 1 Day 4 Virus administration (IT) Right tumor 2.5E10vp/animal Inoculation Right flank Inoculation Left flank Monitor tumor growth Same 2 animals erad
Slide 31: VCN-12 induces long-lasting antitumor immune responses in responders
VCN-12 induces long-lasting antitumor immune responses in responders * * Historical control Tumor rechallenge 2 cured hamsters Day 1 Rechallenge with HP-1 tumor cells Monitor tumor growth Day -43 Tumor disappearance
Slide 32: Summary
Summary Parasporin 2 pore-forming toxin activated by furin linkers and secreted from plasmid-transfected or oncolytic adenovirus infected cells has cytotoxic and immunogenic cell death properties. Bee Hyaluronidase and PS2-armed VCN-12 is superior to VCN-01 in tumor cytotoxicity and immunogenicity
Slide 33: Acknowledgements and collaborators
Laura Moya Mar Tarinas Stan Peters Rafael Moreno Marcel Costa Silvia Torres Pau Fiol Josep M. Piulats Luís Rojas Ana Mato Victoria Maliandi Paz Moreno Carlos López Sheila Connelly Manel Cascalló Collaborators: Cristina Fillat Javier García Castro Manuel Ramírez Orellana Judith Perisé Barrios Juan Fu
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