Theriva Biologics, Inc. · AMEX:TOVX
Theriva Biologics — Investor Presentation (January 2024)
41 slides from Theriva Biologics's investor presentation, Jan 8, 2024
Slide 1: Corporate Overview January 2024
Corporate Overview 08 January 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
4 THERIVA PIPELINE *Based on Management’s current beliefs and expectations. aGVHD acute graft - vs - host disease; allo - HCT allogeneic hematopoietic ce ll transplant. IAP recombinant bovine intestinal alkaline phosphatase. HNSCC head and neck squamous cell carcinoma. IV intravenous. IVit intravi t
Slide 5: VCN-01 Is a Uniquely Engineered Human Adenovirus
5 VCN - 01 IS A UNIQUELY ENGINEERED HUMAN ADENOVIRUS 5 Stroma Cancer Associated Fibroblast 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 6: Designed to Have Multiple Anti-Tumor Actions
6 VCN - 01 DESIGNED TO HAVE MULTIPLE ANTI - TUMOR ACTIONS PH20 PH20 PH20 PH20 PH20 PH20 PH20 PH20 nab - paclitaxel gemcitabine T - Cells Stroma Cancer Associated Fibroblast Neoantigen STROMA degradation by PH20 facilitates tumor access and destruction by coadministered cancer therapies 3 4 IMMUNOGEN
Slide 7: Clinical Data Support Mode of Action
7 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 a
Slide 8: Extensive Phase 1 Program
8 VCN - 01 EXTENSIVE PHASE 1 PROGRAM 87 patients treated in multiple indications and combinations HEAD & NECK – IV (+ Durvalumab)* PANCREATIC - IV (+ Gemcitabine / Abraxane ® ) COLORECTAL – IV (alone) PANCREATIC - IT (+ Gemcitabine Abraxane ® ) PANCREATIC, OVARIAN - IV (+ huCART - meso cells)* BRAIN
Slide 9: Lead Indication Pancreatic Cancer
9 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 disease¹ • USA est. 62,210 new cases and 49,830 deaths in 2022² , ³ • Hyaluronic acid in str
Slide 10: Favorable Outcomes in Phase 1 Trial
10 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) a
Slide 11: Favorable Outcomes in Phase 1 Trial: Results
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) a
Slide 12: VIRAGE Phase 2b Clinical Trial in PDAC
12 V IR AGE PHASE 2B CLINICAL TRIAL in PDAC Multicenter, open - label, randomized, controlled trial (NCT05673811) • Study on - going in patients with first - line metastatic pancreatic ductal adenocarcinoma (PDAC) • Up to 92 patients to be enrolled at sites in Spain and the USA • Randomized 1:1 to r
Slide 13: Development in Pancreatic Cancer
13 • Project complete enrollment into the VIRAGE Study H1 2024 • First DMC safety review Q1 2024 • Potential interim data analysis H2 2024 • Opportunity to discuss pivotal study design and potential expedited status with FDA and EMA • Evaluating potential expansion opportunities in pancreatic cancer
Slide 14: Theriva OV Portfolio Highlights
14 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 15: Achievements and Projected Milestones
15 H2 2024 ACHIEVEMENTS AND PROJECTED MILESTONES Q4 2023 H1 2024 x VCN - 01 PDAC Increased enrollment rate in the VIRAGE Phase 2b study x VCN - 01 RETINOBLASTOMA 3 additional patients enrolled ISS Completed FDA pre - IND meeting x VCN - 01 HNSCC VCN - 01 mediated increase in tumor PD - L1 levels cor
Slide 16: Financial and Investment Goals
16 • Immediate Goals • Augment share register with additional sophisticated institutional investors • Establish a realistic share price/valuation to facilitate financial options • External validation through a funded discovery or development partnership • Mid - to Longer - Term Goals • Institutional
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 (Rb) VCN - 11, Discovery Composition of Matter (exp 2034) Methods of Use and Novel Formulations (examination) SYN - 004, - 006, - 007 Composition of Ma
Slide 20: VCN-01 in Pancreatic Cancer
VCN - 01 IN PANCREATIC CANCER
Slide 21: VCN-01 Is a Uniquely Engineered Human Adenovirus
21 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 22: Extensive Phase 1 Clinical Experience
22 EXTENSIVE VCN - 01 PHASE 1 CLINICAL EXPERIENCE 87 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: Most Common IV Related AEs
23 MOST COMMON IV VCN - 01 RELATED AEs [NCT02045602] ADVERSE EVENTS¹ Part I (Alone, n=16) Part II (Concomitant, 12)² Part III (Sequential, 14)³ Grade 1 - 2 Grade ≥3 Grade 1 - 2 Grade ≥3* Grade 1 - 2 Grade ≥3 Febrile neutropenia - - - 2 (16.7%) - - Neutropenia/Neutrophil count decreased 2 (12.5%) - 1
Slide 24: VIRAGE Phase 2 Clinical Trial Differentiators
24 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 25: Expansion Opportunities for VCN-01 in PDAC
25 (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 26: VCN-01 in Head & Neck Cancer
VCN - 01 IN HEAD & NECK CANCER
Slide 27: VCN-01 IV + Anti-PD-L1 Phase 1 Trial in HNSCC
27 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 28: Extended Survival with VCN-01 + Durvalumab
28 • Higher than expected survival (OS) despite previous anti - PD(L)1 failure • No correlation of survival with baseline tumor PD - L1 expression (CPS) • Significant correlation of survival with CPS 8 - days after VCN - 01 treatment EXTENDED SURVIVAL with VCN - 01+DURVALUMAB Survival correlated wit
Slide 29: May Sensitize Patients to Subsequent Therapy
29 VCN - 01 MAY SENSITIZE PATIENTS TO SUBSEQUENT THERAPY Patients responded to subsequent chemotherapy after progressing with VCN - 01 + durvalumab ARM ICI Treatment Progression (Pre - trial) Current Trial 1st Line after Current Trial 2nd Line after Current Trial Median OS post - 1st ICI ORR Median
Slide 30: AE Profile for VCN-01 and Durvalumab Combination
30 AE PROFILE FOR THE COMBINATION OF VCN - 01 AND DURVALUMAB Most common AEs related to IV VCN - 01 [ NCT03799744] Adverse Reactions Arm I - Concomitant (Dose 3,3E12 , n=6)² Arm II - Sequential (Dose 3,3E12 , n=6)³ Arm II - Sequential (Dose 1E13 , n=8)³ CTCAE Grade Grade 1 - 2 Grade ≥3 Grade 1 - 2 G
Slide 31: Findings in R/M HNSCC
31 VCN - 01 FINDINGS in R/M HNSCC Data support VCN - 01 MOA and immune enhancing effects • VCN - 01 has an acceptable safety profile when administered prior to durvalumab (Imfinzi ® ) • VCN - 01 reaches tumors, has sustained replication and PH20 expression • VCN - 01 treatment led to downregulation
Slide 32: VCN-01 in Retinoblastoma
VCN - 01 IN RETINOBLASTOMA
Slide 33: Retinoblastoma, a Rare Pediatric Malignancy
33 • 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 34: VCN-01 in Retinoblastoma
34 • On - going 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=
Slide 35: Interim Safety Data for Intravitreal VCN-01
35 INTERIM SAFETEY 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 Pasto (
Slide 36: Development in Retinoblastoma
36 • Phase 1 ISS to Complete in H1 2024 • Study to complete H1 2024 • Initial data demonstrate acceptable safety 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 wi
Slide 37: Next Generation OV Discovery Platform
NEXT GENERATION OV DISCOVERY PLATFORM
Slide 38: Albumin Shield to Enhance OV Systemic Delivery
38 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 39: Theriva OV Pipeline Discovery and Development
39 Clinically - tested Adenovirus Expressing PH20 Hyaluronidase to Degrade Stroma + Albumin Shield Ť 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 PIPELI
Slide 40: References
40 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 41: References: Description, Classification, Staging, Stroma
41 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
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