Theriva Biologics, Inc. · AMEX:TOVX
Theriva Biologics — Investor Presentation (September 2024)
48 slides from Theriva Biologics's investor presentation, Sep 23, 2024
Slide 1: Corporate Overview September 2024
Corporate Overview September 2024
Slide 2: Forward Looking Statements
2 FORWARD LOOKING STATEMENTS This presentation includes forward - looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 . In some cases forward - looking statements can be identified by terminology such as "may," "should," "potential," "continue," "expects," "
Slide 3: Overview and Financial Snapshot
3 • Theriva Biologics is developing unique oncolytic viruses optimized for systemic administration • VCN - 01 is undergoing a Phase 2b clinical trial in first - line metastatic pancreatic cancer in combination with SoC chemotherapy • VCN - 01 Phase 1 clinical trials support multiple additional indic
Slide 4: Theriva Pipeline
THERIVA PIPELINE *Based on Management’s current beliefs and expectations. aGVHD acute graft - vs - host disease; allo - HCT allogeneic hematopoietic ce ll transplant. CSR clinical study report. IAP recombinant bovine intestinal alkaline phosphatase. HNSCC head and neck squamous cell carcinom a. IV i
Slide 5: VCN-01 is a uniquely engineered human adenovirus
5 VCN - 01 IS A UNIQUELY ENGINEERED HUMAN ADENOVIRUS 5 Replication enhanced by significantly increased E2F binding. E1a - δ24 gene deletion means replication only in cells with a defective Rb - E2F pathway. Fiber shaft RGDK modification. PH20 soluble human testicular hyaluronidase enzyme expression
Slide 6: VCN-01 is a uniquely engineered human adenovirus
6 VCN - 01 IS A UNIQUELY ENGINEERED HUMAN ADENOVIRUS 5 Cancer Associated Fibroblast Stroma Tumor Surrounded by STROMA VCN - 01 1 SYSTEMIC administration enables VCN - 01 access to primary tumor and metastases and detargets the liver SELECTIVE replication at very high levels lyses tumor cells directl
Slide 7: Designed to have multiple anti-tumor actions
7 VCN - 01 DESIGNED TO HAVE MULTIPLE ANTI - TUMOR ACTIONS PH20 PH20 PH20 PH20 PH20 PH20 PH20 PH20 Neoantigen Cancer Associated Fibroblast Stroma STROMA degradation by PH20 facilitates tumor access and destruction by coadministered cancer therapies 3 4 IMMUNOGENIC actions of VCN - 01 turn “cold” tumo
Slide 8: Compared to other oncolytic viruses in development
8 VCN - 01 COMPARED TO OTHER ONCOLYTIC VIRUSES IN DEVELOPMENT REPLIMMUNE ONCOLYTICS BIOTECH GENELUX CG ONCOLOGY THERIVA BIOLOGICS COMPANY NASDAQ: REPL NASDAQ:ONCY NASDAQ: GNLX NASDAQ: CGON NYSE MKT: TOVX Ticker $757M $71M $85M $2.5B $4M Market Cap ¹ RP1, RP2 Pelareorep Olvi - Vec CG0070 VCN - 01 Pro
Slide 9: Extensive clinical program
9 VCN - 01 EXTENSIVE CLINICAL PROGRAM 142 patients treated with VCN - 01 to date in multiple indications and combinations HEAD & NECK – IV + Durvalumab (20) PANCREATIC - IV + Gemcitabine / Abraxane ® Phase 1 (26) and Phase 2b (53)* COLORECTAL – IV Alone (15) PANCREATIC - IT + Gemcitabine / Abraxane
Slide 10: Lead indication pancreatic cancer
10 VCN - 01 LEAD INDICATION PANCREATIC CANCER Highly fatal cancer protected by dense tumor stroma • Orphan disease with the highest mortality of all solid tumors • Median survival 8 - 11 months for metastatic disease 1,2 • USA est. 6 6,440 new cases and 51,750 deaths in 2024 3 • Hyaluronic acid in s
Slide 11: Favorable outcomes in Phase 1 trial
11 VCN - 01 FAVORABLE OUTCOMES IN PHASE 1 TRIAL Multicenter, open - label, dose escalation study (NCT02045602) ¹Single dose of VCN - 01 (1x10¹¹ to 1x10¹³ vp /dose) administered by 10 min IV infusion. ²VCN - 01 doses 3.3x10¹² vp (n=6) and 1x10¹³ vp (6). ³nab - Paclitaxel (Abraxane®; 30 min infusion)
Slide 12: Favorable outcomes in Phase 1 trial
12 VCN - 01 FAVORABLE OUTCOMES IN PHASE 1 TRIAL Multicenter, open - label, dose escalation study (NCT02045602) ¹Single dose of VCN - 01 (1x10¹¹ to 1x10¹³ vp /dose) administered by 10 min IV infusion. ²VCN - 01 doses 3.3x10¹² vp (n=6) and 1x10¹³ vp (6). ³nab - Paclitaxel (Abraxane®; 30 min infusion)
Slide 13: VIRAGE Phase 2b clinical trial in pancreatic cancer
13 V IR AGE PHASE 2B CLINICAL TRIAL in PANCREATIC CANCER Multicenter, open - label, randomized, controlled trial (NCT05673811) • Study on - going in patients with first - line metastatic pancreatic ductal adenocarcinoma ( PDAC ) • Achieved target of 92 patients (46 in each arm) enrolled at sites in
Slide 14: Strategy and primary catalysts
14 • Strategy • Seek regulatory agency agreement to convert the VIRAGE Phase 2b study to a Phase 3 registration trial¹ • Reduce potential Phase 3 size and costs; expected to shorten time to marketing application • Leverage Phase 3 status (if agreed) to engage potential partners • Primary Catalysts a
Slide 15: Achievements and projected milestones
15 H2 2025 ACHIEVEMENTS AND PROJECTED MILESTONES Q3 2024 Q4 2024 ¹ Contingent on Theriva obtaining required funding for a clinical trial and subject to regulatory agreement . ²VCN - 12 is an armed version of VCN - 11 designed to express an additional functional payload ( VCN - 11 is the first clinic
Slide 16: TOVX capitalization table
16 TOVX CAPITALIZATION TABLE 1,382,672 Common Shares Issued at September 6, 2024 (28,809) Less: Treasury Shares 1,353,862 Common Shares Issued and Outstanding at September 6, 2024 12.9% 175,191 Stock Options Issued (2007,2010, 2020 Plans) 8.3% 112,640 Common Shares Available for Future Grants 2020 P
Slide 17: Appendix
APPENDIX
Slide 18: Seasoned leadership team
18 SEASONED LEADERSHIP TEAM Manel Cascall ó PhD General Director, EU Subsidiary Expertise in oncolytic adenovirus clinical development, received several patents for the use of adenovirus as antitumoral agents and authored many peer - reviewed scientific publications Deep regulatory experience and se
Slide 19: Intellectual property
19 VCN - 01, VCN - 11 Composition of Matter (exp 2030) Methods of Use and Novel Formulations (examination) Use in Rb (exp 2036) ODD EU (PDAC) ODD US (PDAC & Rb) VCN - 11, Discovery Composition of Matter (exp 2034) Methods of Use and Novel Formulations (examination) SYN - 004, - 006, - 007 Compositio
Slide 20: VCN-01 in pancreatic cancer
VCN - 01 IN PANCREATIC CANCER
Slide 21: VCN oncolytic virus genetic modifications
21 VCN ONCOLYTIC VIRUS GENETIC MODIFICATIONS Fiber Shaft RGDK Hexon ABD Ad5 wild type | Reduces liver tropism Fiber Shaft KKTK Host albumin | Enables replication in normal cells | Facilitates liver sequestration | Replication restricted to tumor cells (Rb - E2F defective) ABD albumin binding domain
Slide 22: Extensive Phase 1 clinical experience
22 EXTENSIVE VCN - 01 PHASE 1 CLINICAL EXPERIENCE 88 Patients Treated in Diverse Cancer Indications ¹Garcia - Carbonero (2022) J Immunother Cancer 10:e003255. ²Bazan - Peregrino (2021) J Immunother Cancer 9:e003254. ³huCART - meso are autologous T cells engineered to express an extracellular single
Slide 23: Clinical data support mode-of-action
23 CLINICAL DATA SUPPORT VCN - 01 MODE - OF - ACTION Remodels the tumor matrix and turns “cold” tumors “hot” IDO indoleamine 2,3 - dioxygenase, PD - L1 programmed death - ligand 1 and CD8 + lymphocyte infiltration measured by immunohistochemistry. PH20 (hyaluronidase) levels measured using an ELISA
Slide 24: Most common IV related AEs
24 MOST COMMON IV VCN - 01 RELATED AEs [NCT02045602] Part III (Sequential, 14)³ Part II (Concomitant, 12)² Part I (Alone, n=16) ADVERSE EVENTS¹ Grade ≥3 Grade 1 - 2 Grade ≥3* Grade 1 - 2 Grade ≥3 Grade 1 - 2 - - 2 (16.7%) - - - Febrile neutropenia - - 1 ( 8.3%) 1 ( 8.3%) - 2 (12.5%) Neutropenia/Neut
Slide 25: VIRAGE Phase 2 clinical trial differentiators
25 x First - line treatment of metastatic PDAC patients x Direct comparison with standard - of - care chemotherapy in the same trial x Repeated dosing of VCN - 01 may improve treatment outcomes x Open label provides real - time opportunity to review emerging VCN - 01 treatment effects x Orphan Drug
Slide 26: Expansion opportunities for VCN-01 in PDAC
26 (m)FOLFIRINOX (ECOG 0 - 1)* or Gemcitabine + nab - Paclitaxel (ECOG 0 - 2) or s ingle agent gemcitabine, capecitabine, 5 - FU (ECOG 3 - 4)³ EXPANSION OPPORTUNITIES for VCN - 01 in PDAC Alternate treatment lines and new chemotherapy combinations ¹Used in <20% of PDAC cases. ²Identical to first - l
Slide 27: With gemcitabine/nab-paclitaxel potential survival benefit
27 VCN - 01 WITH GEMCITABINE/ NAB PACLITAXEL Potential survival benefit compared to all first - line chemotherapy PDAC FIRST LINE CHEMOTHERAPY THERIVA BIOLOGICS (Phase 1) COMPANY .. .. .. VCN - 01 VCN - 01 Virus .. .. .. .. 1x10 13 vp x 1* 3.3x10 12 vp x1 1x10 13 vp x 1* Dose NALIRIFOX FOLFIRINOX Ge
Slide 28: Theriva OV portfolio highlights
28 THERIVA OV PORTFOLIO HIGHLIGHTS Unique MOA enables multiple indications and combinations • Highly differentiated OV designed to have multiple antitumor effects • Systemic administration, selective tumor replication, stroma degradation • Designed to increases cell lysis, tumor immunogenicity, and
Slide 29: VCN-01 in head & neck cancer
VCN-01 IN HEAD & NECK CANCER |
Slide 30: IV VCN-01 + anti-PD-L1 Phase 1 trial in HNSCC
30 VCN - 01 IV + ANTI - PD - L1 PHASE 1 TRIAL in HNSCC Multicenter, open - label, dose escalation study (NCT03799744) ¹Durvalumab 1500 mg (60 min infusion) administered at least 4 hours after VCN - 01. HNSCC head and neck squamous cell carcinoma. Jové M (2023) Ann Oncol 34:S589 – S590. x Single IV d
Slide 31: Extended survival with VCN-01 + durvalumab
31 • Higher than expected survival (OS) despite previous anti - PD(L)1 failure • No correlation of survival with baseline tumor PD - L1 expression (CPS) BUT significant correlation of survival with CPS 8 - days after VCN - 01 treatment EXTENDED SURVIVAL with VCN - 01+DURVALUMAB Survival correlated w
Slide 32: May sensitize patients to subsequent therapy
32 VCN - 01 MAY SENSITIZE PATIENTS TO SUBSEQUENT THERAPY Patients responded to subsequent chemotherapy after progressing with VCN - 01 + durvalumab 2nd Line after Current Trial 1st Line after Current Trial Current Trial ICI Treatment Progression ( Pre - trial ) ARM ORR ORR Median OS Median PFS ORR M
Slide 33: AE profile for VCN-01 and durvalumab
33 AE PROFILE FOR THE COMBINATION OF VCN - 01 AND DURVALUMAB Most common AEs related to IV VCN - 01 [ NCT03799744] Arm II - Sequential (Dose 1E13 , n=8)³ Arm II - Sequential (Dose 3,3E12 , n=6)³ Arm I - Concomitant (Dose 3,3E12 , n=6)² Adverse Reactions Grade ≥3 Grade 1 - 2 Grade ≥3 Grade 1 - 2 Grad
Slide 34: Induces transcriptomic changes in tumor microenvironment
34 VCN - 01 INDUCES TRANSCRIPTOMIC CHANGES in TUMOR MICROENVIRONMENT RNAseq Analysis in Clinical Samples from HNSCC Patients [NCT03799744] Principal Component Analysis 1 including all the Pre - and Post - treatment samples Most significant Reactome and KEGG pathways in GSEA (Gene Set Enrichment Anal
Slide 35: Findings in R/M HNSCC
35 VCN - 01 FINDINGS in R/M HNSCC Data support VCN - 01 MOA and immune enhancing effects • VCN - 01 has an acceptable adverse event profile when administered prior to durvalumab (Imfinzi ® ) • VCN - 01 reaches tumors, has sustained replication and PH20 expression • VCN - 01 treatment led to downregu
Slide 36: VCN-01 in retinoblastoma
VCN - 01 IN RETINOBLASTOMA
Slide 37: Retinoblastoma, a rare pediatric malignancy
37 • Retinoblastoma (Rb) is an orphan indication that accounts for ~2 - 3% of all childhood cancers¹ • 200 - 300 cases each year in the USA, EU² - ⁴ • VCN - 01 selectivity enables development as an intravitreal treatment for Rb patients • VCN - 01 could be used in combination with chemotherapy to po
Slide 38: VCN-01 in retinoblastoma Phase 1
38 • Single center, open - label, dose escalation study of intravitreal (IVit) VCN - 01¹ - ³ • Children aged 1 - 12 years (n=9) • Retinoblastoma that is recurrent or refractory to chemotherapy and for whom enucleation is the best treatment option • VCN - 01 doses of 2.0x10⁹ vp per eye (n=1) or 2.0x1
Slide 39: Interim adverse event data for intravitreal VCN-01
39 INTERIM ADVERSE EVENT DATA FOR INTRAVITREAL VCN - 01 Two Intravitreal VCN - 01 Doses of 2.0x10⁹ or 2.0x10 10 vp per eye¹ ¹NCT03284268. ²Intravitreal VCN - 01 doses of 2.0x10⁹ virus particles (vp) per eye (Patient 1) or 2.0x10¹º vp per eye (Patients 2 - 4) administered on days 1 and 15. ³Pascual P
Slide 40: Development in retinoblastoma
40 • Phase 1 ISS Completed H1 2024 • Initial data demonstrate acceptable adverse event profile and one durable complete response • Developing a clinical protocol for an open - label, multinational study • Retinoblastoma patients with vitreous seeds • IVit VCN - 01 in combination with chemotherapy (n
Slide 41: VCN-X next generation OV discovery platform
VCN - X NEXT GENERATION OV DISCOVERY PLATFORM
Slide 42: Albumin Shield to enhance OV systemic delivery
42 OV - ABD • Albumin Shield technology protects OVs as they travel to tumors after systemic administration¹ , ² • Albumin Shield modified OVs bind albumin in the patient’s blood to form a protective coating • Albumin Shield genetic modification allows parent and progeny virus to be albumin coated •
Slide 43: Theriva OV pipeline discovery and development
43 Clinically - tested Adenovirus Expressing PH20 Hyaluronidase to Degrade Stroma + Albumin Shield To Prevent Neutralization by anti - viral Antibodies and Facilitate IV Multidosing + Unique Multifunctional Proteins to Turn Cold Tumors Hot and Enhance Anti - tumor Immune Response THERIVA OV PIPELINE
Slide 44: References
44 Bayo - Puxan N et al. (2006) Role of the putative heparan sulfate glycosaminoglycan - binding site of the adenovirus type 5 fiber sh aft on liver detargeting and knob - mediated retargeting. J Gen Virol 87:2487 – 2495 Bazan - Peregrino M et al. (2021) VCN - 01 disrupts pancreatic cancer stroma an
Slide 45: References: description, classification, staging, stroma
45 DESCRIPTION, CLASSIFICATION, STAGING, STROMA Balachandran VP et al. (2019) Broadening the impact of immunotherapy to pancreatic cancer: challenges and opportunities. Gast roe nterology 156:2056 - 72 Christenson ES et al. (2020) Current and emerging therapies for patients with advanced pancreatic
Slide 46: References: retinoblastoma
46 DESCRIPTION, CLASSIFICATION, STAGING American Academy of Ophthalmology. EyeWiki ®. Retinoblastoma. https://eyewiki.org/Retinoblastoma American Cancer Society. Key statistics for retinoblastoma. https://www.cancer.org/cancer/retinoblastoma/about/key - statistics.html Canturk S et al. (2010) Surviv
Slide 47: References: CG Oncology
47 CG Oncology CG0070 ( cretostimogene grenadenorepvec ) https://cgoncology.com Ramesh N et al. (2006) CG0070, a conditionally r eplicating granulocyte macrophage c olony - stimulating factor - armed o ncolytic a denovirus for the treatment of bl adder c ancer. Clin Cancer Res 12:305 Svatek RS et al
Slide 48: References: Oncolytics Biotech
48 Oncolytics Biotech: Pelareorep (formerly Reolysin ®) https://oncolyticsbiotech.com Arnold D et al. Pelareorep (pela) + atezolizumab ( atezo ) and chemotherapy in first - line (1L) advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) patients – Results from the GOBLET study. Poster prese
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