TOVX Theriva Biologics Inc

 

 

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

 

FORM 8-K

 

CURRENT REPORT

 

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

 

Date of Report (Date of earliest event reported): September 23, 2024

 

THERIVA BIOLOGICS, INC.

(Exact name of registrant as specified in its charter)

 

Nevada		001-12584		13-3808303
(State or other jurisdiction of incorporation)		(Commission File No.)		(IRS Employer Identification No.)

 

9605 Medical Center Drive, Suite 270

Rockville, Maryland 20850

(Address of principal executive offices and zip code)

 

(301) 417-4364

Registrant’s telephone number, including area code

 

N/A

(Former name or former address, if changed since last report)

 

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):

 

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Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

 

¨

Soliciting material pursuant to Rule 14a-12(b) under the Exchange Act (17 CFR 240.14a-12)

 

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Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

 

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Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

 

Securities registered pursuant to Section 12(b) of the Act:

 

Title of each class	Trading Symbol(s)	Name of each exchange on which registered
Common stock, par value $0.001 per share	TOVX	NYSE American

 

Indicate by check mark whether the registrant is an emerging growth company as defined in in Rule 405 of the Securities Act of 1933 (17 CFR §230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (17 CFR §240.12b-2 of this chapter).

 

Emerging growth company ¨

 

If an emerging growth company, indicate by checkmark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ¨

 

 

Item 7.01. Regulation FD Disclosure.

 

Theriva Biologics, Inc. (the “Company”) will be making several presentations to investors over the next several weeks. In connection with the presentations, the Company intends to discuss the Company presentation, which is furnished as Exhibit 99.1 to this Current Report on Form 8-K.

 

The information in this Item 7.01 and in the Company presentation furnished as Exhibit 99.1 to this Current Report on Form 8-K shall not be deemed to be “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or otherwise subject to the liabilities of that section or Sections 11 and 12(a)(2) of the Securities Act of 1933, as amended, and shall not be incorporated by reference into any filing with the U.S. Securities and Exchange Commission made by the Company, whether made before or after the date hereof, regardless of any general incorporation language in such filing.

 

The Company’s Company presentation furnished as Exhibit 99.1 to this Current Report on Form 8-K includes “safe harbor” language pursuant to the Private Securities Litigation Reform Act of 1995, as amended, indicating that certain statements contained therein are “forward-looking” rather than historical.

  

Item 8.01. Other Events. 

 

On September 23, 2024, the Company issued a press release announcing that it has achieved its target patient enrollment of 92 evaluable patients in the VIRAGE Phase 2b clinical trial evaluating the Company’s lead product candidate VCN-01 plus standard-of-care (“SoC”) chemotherapy (gemcitabine/nab-paclitaxel) as a first line therapy for patients with metastatic pancreatic ductal adenocarcinoma (“PDAC”). VCN-01 is a systemically-administered, tumor selective, stroma-degrading oncolytic adenovirus that has been granted Orphan Drug Designation and Fast Track Designation by the U.S. Food and Drug Administration (“FDA”) for the treatment of PDAC. Patients in the VCN-01 treatment arm of the VIRAGE trial are treated with two separate IV VCN-01 doses (1x10¹³ vp/patient) administered approximately 3 months apart: the first VCN-01 dose is administered 7-days prior to initiation of the 1st gemcitabine/nab-paclitaxel SoC chemotherapy cycle; the second VCN-01 dose is administered 7-days prior to initiation of the 4th gemcitabine/nab-paclitaxel SoC chemotherapy cycle. The VCN-01 dose used in the VIRAGE trial was determined in a previously reported Phase 1 dose-escalation study where patients administered a single dose of VCN-01 (1x10¹³ vp/patient) 7-days prior to initiation of gemcitabine/nab-paclitaxel SoC chemotherapy cycles (n=6) showed an overall response rate of 83%, with a median progression free survival of 6.3 months and median overall of 20.8 months. A total of 26 patients were administered different doses of VCN-01 in the Phase 1 study, and the most common treatment-related adverse events were dose-dependent and reversible pyrexia, flu-like symptoms, and increases in liver transaminases.

 

At the time of this filing, a total of 142 patients have been administered at least one dose of VCN-01 across all indications.

 

A copy of the press release is attached as Exhibit 99.2 to this Report on Form 8-K, which is furnished as Exhibit 99.2 to this Current Report on Form 8-K.

 

The press release attached as Exhibit 99.2 to this Current Report on Form 8-K shall not be deemed to be “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or otherwise subject to the liabilities of that section or Sections 11 and 12(a)(2) of the Securities Act of 1933, as amended. The press release attached as Exhibit 99.2 to this Current Report on Form 8-K shall not be incorporated by reference into any filing with the U.S. Securities and Exchange Commission made by the Company, whether made before or after the date hereof, regardless of any general incorporation language in such filing.

 

Item 9.01. Financial Statements and Exhibits.

 

(d)

Exhibits.

 

Exhibit Number		Description
99.1		Presentation of Theriva Biologics, Inc., dated September 2024
99.2		Press Release issued by Theriva Biologics, Inc., dated September 23, 2024
104		Cover Page Interactive Data File (embedded within the XBRL document)

 

 

SIGNATURES

 

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

 

Dated: September 23, 2024	THERIVA BIOLOGICS, INC.
	By:	/s/ Steven A. Shallcross
		Name:	Steven A. Shallcross
		Title:	Chief Executive Officer and Chief Financial Officer

 

 

Exhibit 99.1

 

Corporate Overview September 2024

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," "anticipates ," "intends," "plans," "believes," "estimates," and similar expressions, and include statements regarding oncolytic viruses (OVs) being promising cancer therape uti cs; the potential of VCN - 01 and Theriva OVs and their ability to overcome key OV challenges; clinical advancement of VCN - 01 (including completion of enro llment into the pancreatic ductal adenocarcinoma (PDAC) Phase 2 clinical trial in Q3 2024); potential expansion of VCN - 01 use in different lines of PDAC treatment; potential synergistic antitumor effects of VCN - 01 with topoisomerase inhibitors; the potential of VCN - 01 to enable immuno - oncolo gy therapies in refractory tumors; the potential to obtain expedited status from the FDA; and the potential of the albumin shield to enhance OV systemic de livery. These forward - looking statements are based on management's expectations and assumptions as of the date of this press release and are subjec t t o a number of risks and uncertainties, many of which are difficult to predict that could cause actual results to differ materially from current e xpe ctations and assumptions from those set forth or implied by any forward - looking statements. Important factors that could cause actual results to differ materi ally from current expectations include, among others, Theriva Biologics’ product candidates demonstrating safety and effectiveness, as well as results that are consistent with prior results, the ability to initiate and complete clinical trials on time and achieve the desired results and benefits, continuin g c linical trial enrollment as expected, the ability to obtain regulatory approval for commercialization of product candidates or to comply with ongoing reg ula tory requirements, regulatory limitations relating to Theriva Biologics’ ability to promote or commercialize their product candidates for the sp eci fic indications, acceptance of product candidates in the marketplace and the successful development, marketing or sale of Theriva Biologics’ products, devel opm ents by competitors that render such products obsolete or non - competitive, Theriva Biologics’ ability to maintain license agreements, the continued maintenance and growth of Theriva Biologics’ patent estate, the ability to continue to remain well financed, and other factors described in Theriva Bio log ics' Annual Report on Form 10 - K for the year ended December 31, 2023 and its other filings with the SEC, including subsequent periodic reports on Forms 10 - Q and 8 - K. The information in this presentation is provided only as of the date of this release, and Theriva Biologics undertakes no obligat ion to update any forward - looking statements contained in this release on account of new information, future events, or otherwise, except as required b y l aw.

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 indications (retinoblastoma, HNSCC, CRC) and combinations (immunotherapies) • Albumin Shield platform and innovative VCN - X oncolytic virus discovery engine enable development of a distinct product pipeline OVERVIEW Financial Snapshot NYSE American Exchange TOVX Ticker $16.6M Cash (06/30/2024) Q2 2025 Projected cash runway 715,000 Average Daily Volume (3M Ave) Rockville, MD Barcelona, Spain Locations CRC colorectal cancer. HNSCC head and neck squamous cell carcinoma. SoC standard of care. Immunotherapies include immune chec kpo int inhibitors and CAR - T cells.

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 intravenous. IVit intravitreal. Status* Collaborators Phase 3 Phase 2 Phase 1 Pre - IND Target Candidate Phase 2b Study On - going Orphan Drug Designation US, EU Fast Track Designation US Pancreatic Cancer (IV) with gemcitabine/nab - paclitaxel VCN - 01 Selective, Stroma Degrading OV Phase 1 Complete, CSR in preparation Orphan Drug Designation US Rare Pediatric Disease Designation US Retinoblastoma (IVit) Phase 1 Complete, CSR in preparation HNSCC (IV) + durvalumab Phase 1 Studies On - going Solid Tumors – Brain, Ovarian, PDAC (IV) Preclinical Studies On - going Solid tumors (IV) VCN - X and Albumin Shield OVs Phase 1b/2a On - going Prevention of aGVHD in allo - HCT SYN - 004 [1,2] Oral β - lactamase Phase 1 Studies Complete Potential indications include NAFLD/NASH, celiac, radiation enteritis SYN - 020 Oral IAP

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 is under control of the virus major la te promoter (MLP). Systemic Selective Stroma Degrading Self Reporting E2F binding +++ E1a - Δ24 MLP PH20 -- RGDK Access primary and metastatic lesions High dose, highly replicating Expresses PH20 (hyaluronidase) after viral replication cycle Replicates only in tumor cells Liver detargeted PH20 in blood is a potential biomarker for virus replication in tumors

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 directly without harming healthy tissues 2

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” tumors “hot” and elicit an anti - tumor immune response VCN - 01 nab - paclitaxel gemcitabine T - Cells Tumor Stroma Degraded

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 Product Herpes Simplex Reovirus Vaccinia Adenovirus 5 Adenovirus 5 Virus DNA (enveloped) RNA DNA (enveloped) DNA DNA Type Low tumor IFN ICP34.5 deletion Low tumor IFN Ras activation Low tumor IFN TK deletion Selective replication (Rb - E2F dysfunction) Selective replication (Rb - E2F dysfunction) Tumor selectivity mechanism GM - CSF, GALV - GP R( - ), anti - CTLA - 4 .. .. GM - CSF PH20 Therapeutic Transgene Melanoma (3) Pancreatic, GI (2b) Ovarian (3) Bladder (3) Pancreatic (2b) Lead Indication (Ph) IT IV IP IVESIC IV Route 1x10 7 pfu/mL 4.5x10 10 TCID 50 3x10 9 pfu 1x10 12 vp 1x10 13 vp ² Dose No No No No Yes Stroma Degrading .. .. β - GAL, β - GLU, GFP .. PH20 Biomarker ¹At 18Sep2024. ² Approximately 7x10 11 TCID 50 . References describing the different OV product candidates are provided in the appendix; information is also available on each company’s website and clinicaltrials.gov

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 ® (8) PANCREATIC, OVARIAN - IV + huCART - meso cells (9)* BRAIN TUMORS – IV (1)* HEAD & NECK – IV alone (1) *On - going study. Abraxane® - nab - paclitaxel. Durvalumab (IMFINZI ® , AstraZeneca) is an anti - PD - L1 mAb immune checkpoint inhibitor. huCART - meso are autologous T cells engineered to express an extracellular single chain variable fragment (scFv) with mesothelin specificity. IT - intratumoral. IV - intravenous. IVit - intravitreal. Rb - retinoblastoma. See Appendix for study registry numbers and publications. Rb – IVit alone (9) (Number of VCN - 01 Patients Treated in Parentheses)

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 stroma is associated with reduced treatment efficacy and poor prognosis 4 • VCN - 01 designed to degrade hyaluronic acid • Incidence is growing worldwide • Est. treatment market ~$2.5B (2022) ~$7.0B (2030) 5 ¹ Michael (2019) BMC Palliat Care 18:13, Bengtsson (2020) Sci Rep 10:16425, Carioli (2021) Ann Oncol 32:478, ASCO Pancreatic Cancer Statistics . ² SEER Cancer Stat Facts: Pancreatic Cancer website . ³ American Cancer Society. Cancer Facts & Figures 2024. Atlanta: American Cancer Society; 2024. ⁴ Tahkola (2021) Sci Rep 11:12216, Placencio - Hickok (2022) Pancreatology 22:92. ⁵Data Bridge Market Research website . Pancreatic adenocarcinoma resected from the pancreas body and tail

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) administered at least 4 hours after VCN - 01. ⁴Gemcitabine (30 min infusion) administ ered immediately after Abraxane® infusion. ⁵VCN - 01 doses 3.3x10¹² vp (8) 1x10¹³ vp (6). Garcia - Carbonero (2022) J Immunother Cancer 10:e003255. x Single IV doses of VCN - 01 alone or with standard - of - care ( SoC ) chemotherapy gemcitabine/nab - paclitaxel (Abraxane®) x Evaluate safety and tolerability, recommended Phase 2 dose

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) administered at least 4 hours after VCN - 01. ⁴Gemcitabine (30 min infusion) administ ered immediately after Abraxane® infusion. ⁵VCN - 01 doses 3.3x10¹² vp (8) 1x10¹³ vp (6). Garcia - Carbonero (2022) J Immunother Cancer 10:e003255. SoC ALONE² VCN - 01 DOSE, virus particles (n)¹ OUTCOME Phase 3 (431) Combined (12) 1.0x10¹³ (6) 3.3x10¹² (6) Sequential Regimen 22.9% 50.0% 83.3% 16.7% Responders, % 8.5 13.5 20.8 13.1 Median OS, months 5.5 6.7 6.3 9.9 Median PFS, months 35% 67% . . Survival ≥12 months KOLs advise that Hazard Ratio <0.7 is a significant patient outcome CTCAE SEVERITY RELATED AEs IN ≥1 PATIENT¹ Grade ≥3 Grade 1 - 2 VCN - 01 Combined, Sequential Regimen - 12 (85.7%) Pyrexia/Influenza - like Illness - 3 (21.4%) Nausea - 3 (21.4%) Vomiting - 3 (21.4%) Asthenia/Fatigue 2 (14.3%) 2 (14.3%) Transaminase increases (ALT, AST) - 2 (14.3%) Thrombocytopenia

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 Spain and the USA • Randomized 1:1 to receive gemcitabine/nab - paclitaxel SoC or up to two doses of VCN - 01 plus SoC • Primary endpoints overall survival , VCN - 01 safety and tolerability • Secondary endpoints include response rates , progression free survival, landmark survival Study is intentionally based on the design of prior Phase 3 PDAC clinical trials to enable potential expansion. SoC standard of care

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 and Use of Funds • Achieved target enrollment into the VIRAGE Study Q3 2024 • Initiate commercial scale manufacturing process development² Q4 2024 • Regulatory feedback on Phase 3 from FDA, AEMPS (Spain) and EMA Q1 2025 • Conversion to Phase 3 trial (subject to regulatory agreement)² Q2 2025 VCN - 01 STRATEGY AND PRIMARY CATALYSTS ¹ I nterim analysis to be conducted to support Phase 3 trial design (subject to regulatory agreement), but data will not be relea sed if agreement to proceed to Phase 3 to avoid biasing the study. ²Primary use of funds VCN - 01 manufacturing scale - up and clinical trial activities

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 clinical candidate using the Albumin Binding Domain technology). ISS investigator sponsored Phase 1 study. AEMPS Agencia Española de Medicamentos y Productos Sanitarios. ASGCT American Society of Gene and Cell Therapy. EMA European Medicines Agency. ODD Orphan Drug Designation. RP D D rare pediatric disease designation. SIOP International Society of Paediatric Oncology Q1 2025 • VCN - 01 PDAC • Conversion to Phase 3 trial ( if regulatory agreement )¹ • Establish feasibility of commercial scale VCN - 01 manufacture • VCN - 01 PDAC • EMA Scientific Advice (potential pivotal trial design) • VCN - 01 PDAC • Meeting with FDA (potential pivotal trial design) • Initiate commercial scale manufacturing process development • VCN - 01 PDAC • Ph2 enrollment achieved x • Spanish Government Public - Private Loan - Grant x • Meeting with AEMPS (potential pivotal trial design) • VCN - 01 RETINOBLASTOMA • Finalize Phase 2 study design¹ • VCN - 01 RETINOBLASTOMA • ODD from EMA • VCN - 01 RETINOBLASTOMA • RPDD granted x • THERICEL • Commercial availability of proprietary suspension cell line for manufacturing viral products • VCN OV DISCOVERY • VCN - 12 candidate selection² • VCN - 01 + CAR - T • U. Penn ASGCT poster • SYN - 004 aGVHD • Cohort 2 DSMC Outcomes

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 Plans 287,831 287,831 Total Reserved Common Shares 12,358,307 Remaining Master Common Stock Reserve 14,000,000 Total Common Shares Authorized 28,809 Treasury Shares Note: Numbers are post - split values, rounded for fractional shares

APPENDIX

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 serves as an independent expert for the European Medicines Agencies (EMA) Steven Shallcross Chief Executive Officer, Chief Financial Officer Served as the Company’s CEO since 2018 and CFO since joining the Company in 2015 Deep operational, financial and international biotech industry experience and proven track record of leading the financial development and strategy in the public sector Vince Wacher PhD Head Corporate Development Nearly 30 years leading corporate strategy, partnering, research, clinical development, and intellectual property programs for start - ups, small companies, and new business units within large companies Development experience across oncology, infection, GI, metabolic diseases, transplantation, and drug delivery

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 Composition of Matter (exp 2031 - 5) Methods of Use and Novel Formulations (exp 2035 - 6) SYN - 020 Manufacturing Know - how (Trade Secret) Methods of Use and Novel Formulations (applications filed) Option to additional IP from MGH Hyaluronidase OV Albumin Shield Oral β - Lactamase Oral IAP INTELLECTUAL PROPERTY ODD Orphan Drug Designation provides 7 years market exclusivity in US and 10 years in the EU. OV oncolytic virus. PDAC pancre ati c ductal adenocarcinoma. Rb retinoblastoma.

VCN - 01 IN PANCREATIC CANCER

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 ( streptococcal protein G)¹ Ad5 Adenovirus type 5 E1a - Δ24 deletion of 24 base pairs within the E1a promoter; further modified by insertion of 8 extra E2F binding sites and one Sp1 - binding site at nucleotide site 415 ( 415p ) MLP major late promoter² PH20 soluble human testicular hyaluronidase³ KKTK Lys - Lys - Thr - Lys putative HSPG binding domain on fiber shaft RGDK Arg - Gly - Asp - Lys inserted in place of KKTK on fiber shaft VCN - 12 VCN - 11 armed with additional therapeutic transgene Degrades tumor stroma | Binds host albumin to protect against neutralizing antibodies Amplified replication in tumor cells (high levels of E2F) | L5 L3 E1a - Δ 24 415p SA pA K PH20 LITR RITR L1 L2 L4 MLP L5 L3 E1a LITR RITR L1 L2 L4 MLP L5 L3 E1a - Δ 24 415p SA pA K PH20 LITR RITR L1 L2 L4 MLP Fiber Shaft RGDK ¹Since this is a transgene, progeny virus will also be albumin coated. ²MLP control means transgenes will only be expressed a fte r replication, which occurs selectively in tumor cells. Transgene expression (PH20 in blood) can be a biomarker for viral replication in the tumor. ³PH20 ca ssette inserted downstream of the fiber gene contains a splice acceptor (SA), a kozak sequence (K) and a polyadenylation stop sequence ( pA ) VCN - 01 VCN - 11

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 chain variable fragment (scFv) with mesothelin specificity. HNSCC head and neck squamous cell carcinoma. IV intravenous. IT intratumoral. IVit intravitreal. Registry Status Rout e Co - therapy Indication Phas e Location NCT02045602 Complete¹ IV Part I: None Parts II,III: Gemcitabine + nab - Paclitaxel Part I: Solid tumor Part II, III: PDAC 1 Multicenter (ESP) NCT02045589 Complete² IT Gemcitabine + nab - Paclitaxel PDAC 1 Multicenter (ESP) NCT03284268 Complete; CSR in prep IVit None Retinoblastoma 1 Hospital Sant Joan de Déu, Barcelona NCT03799744 Complete; CSR in prep IV Durvalumab HNSCC 1 Institut Català d'Oncologia (ICO) ISRCTN 517624869 Ongoing IV None Adult brain tumors 1 U. Leeds NCT05057715 Ongoing IV huCART - meso³ PDAC, Ovarian 1 U. Pennsylvania

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 assay. Garcia - Carbonero (2022) J Immunother Cancer 10:e003255 [NCT02045602]. PH20 in serum (pg/ml) CD8 + lymphocytes IDO upregulation PD - L1 upregulation VCN - 01 1.0x10 ¹³ vp (Arms I, II, III) Pre - dose Day 8 Potential biomarker: PH20 levels in patient sera indicate sustained VCN - 01 activity in tumors Immune markers upregulated in biopsies of hepatic metastases

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/Neutrophil count decreased - 2 (14.3%) 4 (33.3%) 3 (25.0%) 1 ( 6.3%) 1 ( 6.3%) Thrombocytopenia/Platelet count decreased 1 (7.1%) - - 1 ( 8.3%) - 3 (18.8%) Diarrhea - 3 (21.4%) - 3 (25.0%) - 2 (12.5%) Nausea - 3 (21.4%) - 2 (16.7%) - 3 (18.8%) Vomiting - 3 (21.4%) 1 ( 8.3%) 5 (41.7%) - 2 (12.5%) Asthenia/Fatigue - 12 (85.7%) - 8 (66.7%) 1 ( 6.3%) 12 (75.0%) Pyrexia/Influenza - like Illness 2 (14.3%) 2 (14.3%) 1 ( 8.3%) 1 ( 8.3%) 3 (18.8%) 2 (12.5%) Transaminase increases (ALT, AST) - - - - 3 (18.8%) 1 ( 6.3%) Pancreatic enzyme increase (lipase, amylase) - - - 3 (25.0%) - 3 (18.8%) Decreased appetite - - - - - 2 (12.5%) Arthralgia - - - 4 (33.3%) - 3 (18.8%) Musculoskeletal pain - - - 1 ( 8.3%) - 1 ( 6.3%) Dizziness - 1 (7.1%) - 1 ( 8.3%) - 1 ( 6.3%) Headache - - - - - 2 (12.5%) Dyspnea - - - 1 ( 8.3%) - 2 (12.5%) Hypotension *Part II: one patient at the highest dose (1x10¹³ vp) died from a combination of thrombocytopenia (Grade 4) and enterocolitis (G rade 5) ¹Garcia - Carbonero (2022) J Immunother Cancer 10:e003255. ²Concomitant IV VCN - 01 3.3x10¹² or 1.0x10¹³ vp/patient administered sam e day as first dose of SoC IV gemcitabine/nab - paclitaxel. ³Sequential IV VCN - 01 3.3x10¹² or 1.0x10¹³ vp/patient administered 7 - days prior to first d ose of SoC.

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 Designation to facilitate regulatory interactions and provide market exclusivity x Fast Track Designation for more frequent communication with FDA and eligibility for Accelerated Approval and Priority Review V IR AGE PHASE 2 CLINICAL TRIAL DIFFERENTIATORS ¹Orphan Drug Designation has been obtained in the USA and Europe

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 - line chemotherapy. ³Eastern Cooperative Oncology Group Performance Status. Abbreviations: CPI checkpoint inhibitor. (m)FOLFIRINOX (modified) leucovorin+5 - FU+irinotecan+oxaliplatin. nab - Paclitaxel nanoparticle albumin - bound paclitaxel. *NALIRIFOX leucovorin+ 5 - FU+liposomal irinotecan+oxaliplatin regimen sNDA accepted by FDA June 2023 for first line metastatic PDAC. Adapted from Tempero (2021) J Natl Compr Canc Netw 19: 439. Resectable Borderline Resectable Metastatic / Recurrent (unresectable) Locally Advanced (unresectable) FOLFIRINOX* Gemcitabine + nab - Paclitaxel 5 - FU + Leucovorin + liposomal i rinotecan Radiotherapy if increases resection margins¹ Neoadjuvant² Gemcitabine ± erlotinib , single agent capecitabine or 5 - FU; ± CPI Stage I Stage II Stage III Stage IV Progression or Recurrence after 1 st Line First - Line Treatments Additional treatment s are available for small subsets of patients with gene mutations such as KRAS, microsatellite instability VCN - 01 Phase 1, 2 VCN - 01 Expansion Opportunities Status Staging Topoisomerase inhibitor combinations*

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 Gemcitabine + Nab Paclitaxel Gemcitabine + Nab Paclitaxel Gemcitabine + Nab Paclitaxel Chemotherapy 383 171 387 431 6 12 (6/dose) No. Patients 41.8% [36.8, 46.9] 31.6% [24.7, 39.1] 36.2% [31.4, 41.2] 29% [25%, 34%] 83% [36, 99.6] 50% [21, 79] Response Rate, % 7.4 [6.0, 7.7] 6.4 [5.5, 7.2] 5.6 [5.3, 5.8] 5.5 [4.5, 5.9] 6.3 [5.7, NE] 6.7 [4.5, 11.7] Progression Free Survival, mos 45.6% 48.4% 39.5% 35% 83.3% 66.7% 12 - Mo. Survival, % 11.1 [10.0, 12.1] 11.1 [9.0, 13.1] 9.2 [8.3, 10.6] 8.5 [7.9, 9.5] 20.8 [12.2, NE] 13.5 [7.1, 29.0] Overall Survival, mos Wainberg Lancet 402:1272 Conroy NEJM 364:1817 Wainberg Lancet 402:1272 Von Hoff NEJM 369:1691 Garcia - Carbonero JITC 10:e003255 Garcia - Carbonero JITC 10:e003255 *Approximately 2.2x10 11 TCID 50 and 7x10 11 TCID 50 respectively.

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 tumor access by co - administered therapies • Multiple potential value opportunities for VCN - 01 • Encouraging clinical data in PDAC, HNSCC, and retinoblastoma support VCN - 01 MOA and safety profile • Phase 1 clinical data suggest potential to improve/enable use of immune CPIs in refractory patients • Phase 1 clinical data support the feasibility of combining VCN - 01 with CAR - T cells in solid tumor patients • Regulatory status expected to facilitate VCN - 01 development • PDAC: Orphan Drug Designation (FDA, EMA), Fast Track designation (FDA) • Retinoblastoma: Orphan Drug Designation (FDA); Rare Pediatric Disease Designation (FDA: access to priority review voucher) • Leading OV discovery engine advancing diverse new product candidates • Potent tumor killing with potential single agent efficacy CPI immune checkpoint inhibitor. PDAC pancreatic ductal adenocarcinoma. R/M HNSCC refractory/metastatic head and neck squamou s c ell carcinoma. SoC standard of care (gemcitabine + nab - paclitaxel in PDAC). Alternate indications include retinoblastoma and brain tumors; phas e 1 data support additional evaluation in colorectal cancer. Topoisomerase inhibitors include topotecan and irinotecan.

VCN - 01 IN HEAD & NECK CANCER

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 doses of VCN - 01 combined with anti - PD - L1 x Patients with metastatic squamous cell carcinoma of the head & neck previously REFRACTORY to anti - PD(L)1 treatment (R/M HNSCC) x Evaluate safety and tolerability, recommended Phase 2 dose | 44 | 29 | 22 | 15 | 8 | 1 Cycle 1 Day ARM I CONCOMITANT HNSCC (6) ARM II SEQUENTIAL HNSCC (14) VCN - 01 3.3x10¹² vp (6) VCN - 01 3.3x10¹² vp (6), 1x10¹³ vp (8) Durvalumab¹ Durvalumab¹ Durvalumab 28 - day cycles starting Day 29 Durvalumab 28 - day cycles starting Day 44 BIOPSY D8 BIOPSY D8 BIOPSY SCR BIOPSY SCR BIOPSY D28 BIOPSY D28

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 with PD - L1 upregulation after VCN - 01 treatment ESMO Congress 2023 P oster 937 P: Survival Outcomes in Phase I Trial Combining VCN - 01 and Durvalumab (MEDI4736) in Subjects with Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma Refractory to Previous Immunotherapy Treatment. Jové M (2023) Ann Oncol 34:S589 Median OS (95% CI), mos Regimen 1.0x10¹³ vp 3.3x10¹² vp .. 10.4 (8.9 - NE) Concomitant 17.3 (11.3 - NE) 15.5 (15.1 - NE) Sequential Overall Survival vs CPS in Biopsies at Day 8 Spearman r = 0.7676 P (2 - tailed) = 0.0050

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 Median OS post - 1st ICI 1/2 3/5 10.4 (8.9 - NE) 1.7 (1.6 - NE) 0/6 21.6 (19.2 - NE) Concomitant Low (3.3E12vp) 1/6 3/6 15.5 (15.1 - NE) 3.7 (2.2 - NE) 1/6 23.9 (16.6 - NE) Sequential Low (3.3E12vp) 1/4 2*/5 17.3 (11.3 - NE) 2.1 (1.4 - NE) 0 /6 21.8 (12.9 - NE) Sequential High (1E13vp) *Complete Responses

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 Grade ≥3 Grade 1 - 2 CTCAE Grade - 3 (50%) - 5 (62,5%) - 2 (33,0%) Pyrexia - 2 (33,3%) 2(25%) 3 (37,5%) - 3 (50,0%) Influenza like illness - 4 (66,6%) 1 (12,5%) 2 (25%) - 2 (33.0%) Asthenia /Fatigue 2 (33,3%) - - 2 (25%) 1 (16,6%) 4 (66,7%) AST increased 2 (33,3%) - - 1 (12,5%) 1 (16,6%) 3 (50,0%) ALT increased - 2 (33,3%) - 3(37,5%) - 1 (16,6%) Decreased Apetite - - 3 (37,5%) - - 1 (16,6%) Lymphocyte count decreased - 1 (16,6%) - 3(37,5%) - - Myalgia - 1 (16,6%) - 2 (25%) - - Hypotension - 1 (16,6%) - 1(12,5%) - 1 (16,6%) Chills - 1 (16,6%) - 1(12,5%) - 1 (16,6%) Vomiting - 1 (16,6%) - 1(12,5%) - 2 (33,0%) Anemia - 1 (16,6%) - 1(12,5%) - - Nausea - 1 (16,6%) - 1(12,5%) - - Headache - - - 1(12,5%) - 1 (16,6%) Erythema - - 1 (12,5%) - 1 (16,6%) - Guillain - Barre Syndrome - - 1 (12,5%) - - - Hepatic enzymes increased 1 (12,5%) - - - - - GGT Increased

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 Analysis) 1 analysis D8 vs Pre - treat. analysis D28 vs Pre - treat. Pre - treatment Post - D8 Post - D28 Sustained differential gene expression profiles associated with downregulation of matrix - related pathways Jové M et al. (2022) Poster 1231P: European Society for Molecular Oncology conference ESMO2022, 12 September 2022

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 downregulation of tumor matrix genes and increased levels of immune markers in tumor biopsies (CD8, PD - L1 , IDO) • VCN - 01 - treated patients showed increased response to subsequent chemotherapy treatment lines after progressing on this trial ESMO Congress 2022 P oster 1231P: Phase I Study to Evaluate the Safety, Tolerability, and Efficacy of VCN - 01 in Combination With Durvalumab (MEDI4736) in Subjects With Recurrent/ Metastatic Squamous Cell Carcinoma of the Head and Neck (R/M HNSCC). Jove M (2022) Ann On col 33:S1112. IDO Indoleamine - 2,3 - dioxygenase.

VCN - 01 IN RETINOBLASTOMA

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 potentially improve outcomes • VCN - 01 could be used as a rescue therapy for patients who fail standard therapy RETINOBLASTOMA, A RARE PEDIATRIC MALIGNANCY ¹https://www.cancer.org/cancer/retinoblastoma/about/key - statistics.html. ²Stacey (2021) Ophthalmology 128:1369. ³One Retinoblast oma World Map https://map.1rbw.org/. ⁴For additional details and references see Appendix. IMAGE: Courtesy of Hospital Sant Joan de Déu, Bar cel ona

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 2.0x10 10 vp per eye (n=8) on days 1 and 15 • Promising antitumor activity and appropriate adverse event profile and tolerability at RP2D • Reduction of vitreous seeds in 4 patients of 9 evaluable patients • Enucleation avoided in 3 patients; low VCN - 01 dose and/or damage from prior chemotherapy meant the eye could not be saved in 6 patients • Earlier VCN - 01 intervention anticipated to have better outcomes VCN - 01 IN RETINOBLASTOMA ¹NCT03284268. ²Pascual Pasto (2019) Sci Transl Med 11:eaat9321. ³Data presented at International Oncolytic Virus Conference IOVC2021, 07 November 2021, Sedona, AZ. Link to IOVC2021 slide deck provided in Appendix. RP2D recommended phase 2 dose. vp virus particles. Pt 2 2 Pt 3 Reduced number and size of tumor vitreous seeds following VCN - 01 administration² Complete tumor regression³ D14 D28 D0 D64 M8 D0 Promising Results in Patients Treated with High Dose 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 Pasto (2019) Sci Transl Med 11:eaat9321. Data presented at International Oncolytic Virus Conference IOVC2021, 07 November 2021, Sedona, AZ. Grade ≥3 All Grades Pts Adverse Reaction % n % n N CTCAE grade 33% 2 33% 2 6 Uveitis 0% 0 17% 1 6 Eye oedema 0% 0 17% 1 6 Conjunctival hyperemia 0% 0 17% 1 6 Eye inflammation • VCN - 01 was reasonably well tolerated after intravitreal administration², although some turbidity and vitritis associated with intravitreal inflammation was observed • Intravitreal inflammation was managed with local and systemic administration of anti - inflammatory drugs • VCN - 01 did not appear to change retinal function (electroretinographic signaling) • VCN - 01 does not replicate in healthy retinal tissue of patients with either somatic or germline Rb mutation³ Stable Electroretinographic Signals

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 (no defined SoC) • PI Dr. Guillermo Chantada, MD PhD ¹ • Status • US Orphan Drug Designation (EU application in process) • Pre - IND meeting with FDA completed Q4 2023 • Rare Pediatric Disease Designation (potential eligibility for Priority Review Voucher) VCN - 01 DEVELOPMENT IN RETINOBLASTOMA ¹Principal Researcher, Associate Physician, Hospital Sant Joan de Déu, Barcelona, Spain; Scientific Director, Pediatric Hemato - Oncology Service of the Hospital Universitario Austral, Argentina

VCN - X NEXT GENERATION OV DISCOVERY PLATFORM

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 • Albumin Shield may enable multiple IV administrations for hard - to - treat patients • Albumin Shield first candidate VCN - 11 is being prepared for a potential Phase 1 clinical trial ALBUMIN SHIELD to ENHANCE OV SYSTEMIC DELIVERY ¹Rojas (2016) J Control Rel 237:78; ABD binds mouse and human serum albumin, but not bovine; ²Mato - Berciano (2021) J Control Rel 332:517. Albumin binding domain ( ABD ) expressed on the virus surface ( hexon ) Y ABD binds serum albumin to form a coating that protects against neutralizing antibodies Y Parent oncolytic virus (OV) susceptible to neutralizing antibodies OV - ABD OV

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 DISCOVERY AND DEVELOPMENT Common Features Product Specific Features VCN - 11 Hyaluronidase alone VCN - 12 Hyaluronidase + Toxins VCN - 13 Fusion Hyaluronidase + scPD - L1 VCN - XX Hyaluronidase + other payloads Advancing founders’ decade of world leading OV innovation

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 and exerts antitumor effects. J ImmunoTher Cancer 9:e00 3254. Garcia - Carbonero R et al. (2019) Poster 5185: Systemic administration of the hyaluronidase - expressing oncolytic adenovirus VCN - 01 in patients with advanced or metastatic pancreatic cancer: first - in - human clinical trial. European Society for Molecular Oncology conference ESMO, 29 Septemb er 2019. Garcia - Carbonero R et al. (2022) A phase I, multicenter, open - label study of intravenous VCN - 01 oncolytic adenovirus with or without nab - paclitaxel plus gemcita bine in patients with advanced solid tumors J ImmunoTher Cancer 10:e003255 Guedan S et al. (2010) Hyaluronidase expression by an oncolytic adenovirus enhances its intratumoral spread and suppresses tumor gro wt h. Mol Ther 18:1275 – 1283 Hidalgo M et al. (2019) Poster 5465: Proof of concept clinical study by EUS - guided intratumor injection of VCN - 01, an oncolytic adenovirus expressing hyaluronidase i n patients with pancreatic cancer. European Society for Molecular Oncology conference ESMO, 28 September 2019. Jove M et al. (2022) Poster 1231P: Phase I study to evaluate the safety, tolerability, and efficacy of VCN - 01 in combination wit h durvalumab (MEDI4736) in subjects with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M HNSCC) Ann Oncol. 33:S1112. European Society for Mol ecular Oncology conference ESMO 2022, 10 September 2022 Kiyokawa M et al. (2021) Modification of extracellular matrix enhances oncolytic adenovirus Immunotherapy in glioblastoma . Clin Cancer Res 27:889 - 902 Martínez - Vélez N et al. (2019) The oncolytic adenovirus VCN - 01 as therapeutic approach against pediatric osteosarcoma. Clin Canc er Res 22:2217 - 25 Mato - Berciano A et al. (2021) Oncolytic adenovirus with hyaluronidase activity that evades neutralizing antibodies: VCN - 11. J C ontrol Rel 332:517 - 528 Pascual Pasto G et al. (2019) Therapeutic targeting of the RB1 pathway in retinoblastoma with the oncolytic adenovirus VCN - 01. S ci Transl Med 11:eaat9321 Pascual - Pasto G et al. (2021) Presentation: VCN - 01 is an encouraging therapy against retinoblastoma. International Oncolytic Virus Conference IOVC2021, 07 November 2021, Sedona, AZ. Rodríguez - García A et al. (2015) Safety and efficacy of VCN - 01, an oncolytic adenovirus combining fiber HSG - binding domain repla cement with RGD and hyaluronidase expression. Clin Cancer Res 21:1406 - 18 Rojas J et al. (2012) Improved systemic antitumor therapy with oncolytic adenoviruses by replacing the fiber shaft HSG - binding d omain with RGD. Gene Ther 19:453 – 457 Rojas J et al. (2010) Minimal RB - responsive E1A promoter modification to attain potency, selectivity, and transgene - arming capac ity in oncolytic adenoviruses. 2010) Mol Ther 18:1960 – 1971 Rojas L et al. (2016) Albumin - binding adenoviruses circumvent pre - existing neutralizing antibodies upon systemic delivery. J Con trol Rel 237:78 – 88 THERIVA ONCOLYTIC VIRUSES KEY PUBLICATIONS

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 ductal adenocarcinoma: a br igh t future. Lancet Oncol 21:e135 - e145 Orth M et al. (2019) Pancreatic ductal adenocarcinoma: biological hallmarks, current status, and future perspectives of combi ned modality treatment approaches. Radiation Oncol 14:141 Placencio - Hickok VR et al. (2022) Hyaluronan heterogeneity in pancreatic ductal adenocarcinoma: primary tumors compared to sites of met as tasis. Pancreatology 22:92 - 97 Sarantis P et al. (2020) Pancreatic ductal adenocarcinoma: treatment hurdles, tumor microenvironment and immunotherapy. World J Gastrointest Oncol 12:173 - 181 Tahkola K et al. (2021) Stromal hyaluronan accumulation is associated with low immune response and poor prognosis in pancreat ic cancer. Sci Rep 11:12216 Yu J et al. (2015) Time to progression of pancreatic ductal adenocarcinoma from low - to - high tumour stages. Gut 64:1783 - 9 INCIDENCE Bengtsson A et al. (2020) The actual 5 - year survivors of pancreatic ductal adenocarcinoma based on real - world data. Sci Rep 10:1 6425. Carioli G et al. (2021) European cancer mortality predictions for the year 2021 with focus on pancreatic and female lung cancer. Ann Oncol 32:478. da Costa WL et al. (2020) Trends in the incidence of pancreatic adenocarcinoma in all 50 United States examined through an ag e - p eriod - cohort analysis. JNCI Cancer Spectrum 4:pkaa033 GLOBOCAN International 2020 survey of persons 0 - 74 years. https://gco.iarc.fr/today/data/factsheets/cancers/13 - Pancreas - fact - sheet.pdf Michael N et al. (2019) Timing of palliative care referral and aggressive cancer care toward the end - of - life in pancreatic cance r: a retrospective, single - center observational study. BMC Palliat Care 18 :1 3. Sung H et al. (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 18 5 Countries. CA Cancer J Clin 71:209 – 249 Ushio J et al. (2021) Pancreatic ductal adenocarcinoma: epidemiology and risk factors. Diagnostics 11:562 TREATMENT Conroy T et al. (2011) FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic Cancer. N Engl J Med 364:1817 - 25. Elsayed M et al. (2021) The latest advancement in pancreatic ductal adenocarcinoma therapy: a review article for the latest guideline s and novel therapies. Biomedicines 9:389 Tempero MA et al. (2021) NCCN Clinical Practice Guidelines in Oncology. Pancreatic Adenocarcinoma, V2.2021. J Natl Compr Canc Netw 19:439 - 457 Toesca DAS et al. (2018) Management of borderline resectable pancreatic cancer. Int J Radiation Oncol Biol Phys 100:1155 - 74 Vogel A et al. (2016) Efficacy and safety profile of nab - paclitaxel plus gemcitabine in patients with metastatic pancreatic canc er treated to disease progression: a subanalysis from a phase 3 trial (MPACT). BMC Cancer (2016) 16:817 Von Hoff DD et al. (2013) Increased survival in pancreatic cancer with nab - paclitaxel plus gemcitabine. N Engl J Med 369:1691 - 703 PANCREATIC CANCER REFERENCES

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) Survival of retinoblastoma in less - developed countries impact of socioeconomic and health - related indicators. B r J Ophthalmol 94:1432 - 6 Fabian ID et al. (2018) Classification and staging of retinoblastoma. Community Eye Health 31:11 - 13 Fabian ID et al. (2020) Global retinoblastoma presentation and analysis by national income level. JAMA Oncol 6:685 Tomar AS et al. (2020) Multicenter, international collaborative study for American Joint Committee on Cancer Staging of Retinoblast om a/ Part I: metastasis - associated mortality. Ophthalmology 127:1719 - 32 INCIDENCE One Retinoblastoma World Map. https://map.1rbw.org/ (accessed April - November 2021) Stacey AW et al. (2021) Incidence of retinoblastoma has increased: results from 40 European countries. Ophthalmology 128:1369 - 71 TREATMENT Abramson DH et al. (2015) Advanced unilateral retinoblastoma: the impact of ophthalmic artery chemosurgery on enucleation rat e a nd patient survival at MSKCC. PLoS ONE 10:e0145436 Ancona - Lezama D et al. (2020) Modern treatment of retinoblastoma: a 2020 review. Indian J Ophthalmol 68:2356 - 65 Tomar AS et al. (2021) Global retinoblastoma treatment outcomes. Association with national income level. 128:740 - 53 RETINOBLASTOMA (Rb) REFERENCES 46

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. (2024) PIVOT - 006: A Phase 3, Randomized Study of cretostimogene grenadenorepvec versus Observation for the Treatment of Intermediate Risk NMIBC Following TURBT. Abstract TPS715. Presentation at ASCO Genitourinary Symposium 2024. J Clin Oncol 42: TPS 715 Tyson M et al. (2023) First Results from BOND - 003: Phase 3 study of cretostimogene grenadenorepvec Monotherapy for Patients with BCG Unresponsive High - Risk NMIBC with CIS +/ - Papillary (Ta/T1) Tumors. Presentation at Society of Urologic Oncology Annual Meeting S UO 2023. Uchio EM et al. A phase 3, single - arm study of CG0070 in subjects with non - muscle invasive bladder cancer (NMIBC) unresponsive to Bac illus Calmette - Guerin (BCG). J Clin Oncol 40:TPS598 Genelux Corporation Olvi - Vec (GL - ONC1, GLV - 1h68, olvimulogene nanivacirepvec ) https://genelux.com Clinicaltrials.gov NCT05281471: Efficacy & s afety of Olvi - Vec and platinum - doublet + bevacizumab c ompared to pl atinum - doublet + bevacizumab in platinum - resistant/​refractory o varian c ancer ( OnPrime , GOG - 3076) Holloway RW et al. (2023) Clinical activity of olvimulogene nanivacirepvec – primed immunochemotherapy in heavily pretreated Patients With Platinum - Resistant or Platinum - Refractory Ovarian Cancer. The Nonrandomized Phase 2 VIRO - 15 Clinical Trial. JAMA Oncol. 9:903 Lin D et al. (2023) Oncolytic virotherapy: basic principles, recent advances and future directions. Signal Transduct Target Ther. 8:156 Mell LK et al. (2017) Phase I trial of Intravenous oncolytic vaccinia virus (GL - ONC1) with cisplatin and radiotherapy in patient s with locoregionally advanced head and neck carcinoma. Clin Cancer Res 23:5696 Zhang Q et al. (2007) Eradication of solid h uman b reast t umors in nude m ice with an intravenously i njected l ight - emitting o ncolytic v accinia v irus. Cancer Res 67:10038 OV COMPANY REFERENCES 47

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 presentation at the European Society for Molecular Oncology Annual Congr ess ESMO 2023. Clements D et al. (2014) Reovirus in cancer therapy: an evidence - based review. Oncolytic Virother 3:69 Lin D et al. (2023) Oncolytic virotherapy: basic principles, recent advances and future directions. Signal Transduct Target Ther. 8:156 Philips MB et al. (2018) Current understanding of reovirus oncolysis mechanisms Oncolytic Virother 7:53 Xie R et al. (2023) Effectiveness and safety of pelareorep plus chemotherapy versus chemotherapy alone for advanced solid tumors: a meta - analysis. Front Pharmacol 14:1228225 Replimune : RP1,RP2 ( vusolimogene oderparepvec ) https://replimune.com Chmielowski et al. (2023) Initial efficacy and safety of RP1 + nivolumab in patients with anti – PD1 – failed melanoma from the ongo ing phase 1/2 IGNYTE study. Abstract 9609. Poster presentation American Society of Clinical Oncologists Annual Meeting ASCO 2023. J Clin Oncol 41: 950 9 Sacco JJ et al. (2023) Preliminary safety and efficacy results from an open - label, multicenter, phase 1 study of RP2 as a single agent and in combination with nivolumab in a cohort of patients with uveal melanoma. Presentation at the International Congress of the Society for Mel ano ma Research SMR 2023. Thomas S et al. (2019) Development of a new fusion - enhanced oncolytic immunotherapy platform based on herpes simplex virus type 1. J ImmunoTher Cancer 7:214 OV COMPANY REFERENCES 48

 

Exhibit 99.2

 

 

 

Theriva™ Biologics Achieves Target Patient Enrollment in the VIRAGE Phase 2b Trial of VCN-01 with Gemcitabine/nab-Paclitaxel for the Treatment of Metastatic Pancreatic Cancer

 

- Target of 92 evaluable patients (46 in each of the control and VCN-01 treatment arms)
enrolled across 15 sites in Spain and the USA within 21 months –

 

Rockville, MD, September 23, 2024 – Theriva™ Biologics, Inc. (NYSE American: TOVX), (“Theriva” or the “Company”), a diversified clinical-stage company developing therapeutics designed to treat cancer and related diseases in areas of high unmet need, today announced that it has achieved their target patient enrollment in the VIRAGE Phase 2b clinical trial evaluating the Company’s lead product candidate VCN-01 plus standard-of-care (SoC) chemotherapy (gemcitabine/nab-paclitaxel) as a first line therapy for patients with metastatic pancreatic ductal adenocarcinoma (PDAC). VCN-01 is a systemically-administered, tumor selective, stroma-degrading oncolytic adenovirus that has been granted Orphan Drug Designation and Fast Track Designation by the U.S. Food and Drug Administration (FDA) for the treatment of PDAC.

 

“We are delighted to have achieved target enrollment for our VIRAGE Phase 2b trial in metastatic PDAC,” said Steven A. Shallcross, Chief Executive Officer of Theriva Biologics. “Rapid progress in the VIRAGE trial is a testament to physician interest in VCN-01 and the significant unmet need for an effective treatment for this deadly disease. We are currently planning regulatory engagements to discuss next steps in VCN-01 clinical development, including the potential for an interim data analysis.”

 

About Pancreatic Ductal Adenocarcinoma

 

Cancer of the pancreas consists of two main histological types: cancer that arises from the ductal (exocrine) cells of the pancreas or, much less often, cancers may arise from the endocrine compartment of the pancreas. Pancreatic ductal adenocarcinoma (“PDAC”) accounts for more than 90% of all pancreatic tumors. It can be located either in the head of the pancreas or in the body/tail. Pancreatic cancer usually metastasizes to the liver and peritoneum. Other less common metastatic sites are the lungs, brain, kidney and bone. In its early stages, pancreatic cancer does not typically result in any characteristic symptoms, so in most cases it is diagnosed in its late stages (locally advanced non-metastatic or metastatic disease) when surgical resection and possibly curative treatment is not possible. It is generally assumed that only 10% of cases are resectable at presentation, whereas 30-40% of patients are diagnosed at local advanced/unresectable stage and 50-60% present with distant metastases.

 

About VCN-01

 

VCN-01 is a systemically administered oncolytic adenovirus designed to selectively and aggressively replicate within tumor cells and degrade the tumor stroma that serves as a significant physical and immunosuppressive barrier to cancer treatment. This unique mode-of-action enables VCN-01 to exert multiple antitumor effects by (i) selectively infecting and lysing tumor cells; (ii) enhancing the access and perfusion of co-administered chemotherapy products; and (iii) increasing tumor immunogenicity and exposing the tumor to the patient’s immune system and co-administered immunotherapy products. Systemic administration enables VCN-01 to exert its actions on both the primary tumor and metastases. In addition to the VIRAGE Phase 2b trial, VCN-01 has been administered to over 80 patients in Phase 1 and investigator-sponsored clinical studies of different cancers, including PDAC (in combination with chemotherapy), head and neck squamous cell carcinoma (with an immune checkpoint inhibitor), ovarian cancer (with CAR-T cell therapy), colorectal cancer, and retinoblastoma (by intravitreal injection). More information on these clinical trials is available at Clinicaltrials.gov.

 

About VIRAGE

 

VIRAGE is a two-arm Phase 2b open-label, randomized, controlled, multicenter clinical trial in patients with histologically confirmed, newly-diagnosed metastatic PDAC. The study is being conducted at 16 sites across the US and Europe with a target enrollment of 92 evaluable patients; 46 in each of the control and treatment arms. In both the control and treatment arms, patients are treated with gemcitabine/nab-paclitaxel standard of care chemotherapy in 28-day cycles. In the treatment arm only, patients also receive single doses of intravenous VCN-01 administered seven-days prior to the first and fourth cycles of gemcitabine/nab-paclitaxel treatment. Primary endpoints for the trial are overall survival and VCN-01 safety/tolerability. Additional endpoints include progression free survival, objective response rate, and measures of biodistribution, VCN-01 replication, and immune response. More information about the trial is available on Clinicaltrials.gov (NCT05673811), through the Spanish Clinical Trials Registry and European Union Drug Regulating Authorities Clinical Trials Database (EudraCT Number: 2022-000897-24).

 

 

About Theriva™ Biologics, Inc.

 

Theriva™ Biologics (NYSE American: TOVX), is a diversified clinical-stage company developing therapeutics designed to treat cancer and related diseases in areas of high unmet need. The Company is advancing a new oncolytic adenovirus platform designed for intravenous (IV), intravitreal and antitumoral delivery to trigger tumor cell death, improve access of co-administered cancer therapies to the tumor, and promote a robust and sustained anti-tumor response by the patient’s immune system. The Company’s lead candidates are: (1) VCN-01, an oncolytic adenovirus designed to replicate selectively and aggressively within tumor cells, and to degrade the tumor stroma barrier that serves as a significant physical and immunosuppressive barrier to cancer treatment; (2) SYN-004 (ribaxamase) which is designed to degrade certain commonly used IV beta-lactam antibiotics within the gastrointestinal (GI) tract to prevent microbiome damage, thereby limiting overgrowth of pathogenic organisms such as VRE (vancomycin resistant Enterococci) and reducing the incidence and severity of acute graft-versus-host-disease (aGVHD) in allogeneic hematopoietic cell transplant (HCT) recipients; and (3) SYN-020, a recombinant oral formulation of the enzyme intestinal alkaline phosphatase (IAP) produced under cGMP conditions and intended to treat both local GI and systemic diseases. For more information, please visit Theriva Biologics’ website at www.therivabio.com.

 

Forward-Looking Statement

 

This release contains 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,” “anticipates,” “intends,” “plans,” “believes,” “estimates,” and similar expressions, and include statements regarding planning regulatory engagements to discuss next steps in VCN-01 clinical development, including the potential for an interim data analysis. These forward-looking statements are based on management’s expectations and assumptions as of the date of this press release and are subject to a number of risks and uncertainties, many of which are difficult to predict that could cause actual results to differ materially from current expectations and assumptions from those set forth or implied by any forward-looking statements. Important factors that could cause actual results to differ materially from current expectations include, among others, the ability to generate clinical data that establishes VCN-01 may lead to improved clinical outcomes for patients with PDAC and other solid cancers; the Company’s and VCN’s product candidates demonstrating safety and effectiveness, as well as results that are consistent with prior results; the ability to complete clinical trials on time and achieve the desired results and benefits; the ability to obtain regulatory approval for commercialization of product candidates or to comply with ongoing regulatory requirements, regulatory limitations relating to the Company’s and VCN’s ability to promote or commercialize their product candidates for the specific indications, acceptance of product candidates in the marketplace and the successful development, marketing or sale of the Company’s and VCN’s products, developments by competitors that render such products obsolete or non-competitive, the Company’s and VCN’s ability to maintain license agreements, the continued maintenance and growth of the Company’s and VCN’s patent estate, the ability to continue to remain well financed and other factors described in the Company’s Annual Report on Form 10-K for the year ended December 31, 2023 and its other filings with the SEC, including subsequent periodic reports on Forms 10-Q and current reports on Form 8-K. The information in this release is provided only as of the date of this release, and Theriva Biologics undertakes no obligation to update any forward-looking statements contained in this release on account of new information, future events, or otherwise, except as required by law.

 

For further information, please contact:
Investor Relations:

 

Chris Calabrese
LifeSci Advisors, LLC
ccalabrese@lifesciadvisors.com
917-680-5608

 

Source: Theriva Biologics, Inc. 

 

 

 

v3.24.3

Cover	Sep. 23, 2024
Cover [Abstract]
Document Type	8-K
Amendment Flag	false
Document Period End Date	Sep. 23, 2024
Entity File Number	001-12584
Entity Registrant Name	THERIVA BIOLOGICS, INC.
Entity Central Index Key	0000894158
Entity Tax Identification Number	13-3808303
Entity Incorporation, State or Country Code	NV
Entity Address, Address Line One	9605 Medical Center Drive
Entity Address, Address Line Two	Suite 270
Entity Address, City or Town	Rockville
Entity Address, State or Province	MD
Entity Address, Postal Zip Code	20850
City Area Code	301
Local Phone Number	417-4364
Written Communications	false
Soliciting Material	false
Pre-commencement Tender Offer	false
Pre-commencement Issuer Tender Offer	false
Title of 12(b) Security	Common stock, par value $0.001 per share
Trading Symbol	TOVX
Security Exchange Name	NYSEAMER
Entity Emerging Growth Company	false

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