# EDGAR Filing Document

**Accession Number:** 0000894158
**File Stem:** 0001104659-26-044906
**Filing Date:** 2026-4
**Character Count:** 29436
**Document Hash:** 4e6c80ce8688b867f05f79b576c5266b
**Contains OCR:** False
**Source Format:** 

## Filing Content

## Filing Summary
**0001104659-26-044906.hdr.sgml**: 20260417

**ACCESSION NUMBER**: 0001104659-26-044906

**CONFORMED SUBMISSION TYPE**: 8-K

**PUBLIC DOCUMENT COUNT**: 15

**CONFORMED PERIOD OF REPORT**: 20260417

**ITEM INFORMATION**: Regulation FD Disclosure

**ITEM INFORMATION**: Other Events

**ITEM INFORMATION**: Financial Statements and Exhibits

**FILED AS OF DATE**: 20260417

**DATE AS OF CHANGE**: 20260417

**FILER**: 

**COMPANY DATA:**
- **COMPANY CONFORMED NAME:** Theriva Biologics, Inc.
- **CENTRAL INDEX KEY:** 0000894158
- **STANDARD INDUSTRIAL CLASSIFICATION:** PHARMACEUTICAL PREPARATIONS [2834]
- **ORGANIZATION NAME:** 03 Life Sciences
- **EIN:** 133808303
- **STATE OF INCORPORATION:** NV
- **FISCAL YEAR END:** 1231

**FILING VALUES:**
- **FORM TYPE:** 8-K
- **SEC ACT:** 1934 Act
- **SEC FILE NUMBER:** 001-12584
- **FILM NUMBER:** 26871748

**BUSINESS ADDRESS:**
- **STREET 1:** 9605 MEDICAL CENTER DRIVE
- **STREET 2:** SUITE 270
- **CITY:** ROCKVILLE
- **STATE:** MD
- **ZIP:** 20850
- **BUSINESS PHONE:** (734) 332-7800

**MAIL ADDRESS:**
- **STREET 1:** 9605 MEDICAL CENTER DRIVE
- **STREET 2:** SUITE 270
- **CITY:** ROCKVILLE
- **STATE:** MD
- **ZIP:** 20850

**FORMER COMPANY:**
- **FORMER CONFORMED NAME:** Synthetic Biologics, Inc.
- **DATE OF NAME CHANGE:** 20120305

**FORMER COMPANY:**
- **FORMER CONFORMED NAME:** ADEONA PHARMACEUTICALS, INC.
- **DATE OF NAME CHANGE:** 20081027

**FORMER COMPANY:**
- **FORMER CONFORMED NAME:** PIPEX PHARMACEUTICALS, INC.
- **DATE OF NAME CHANGE:** 20061214

?xml version='1.0' encoding='ASCII'?

**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): April 17, 2026**

**THERIVA BIOLOGICS, INC.**

(Exact name of registrant as specified in its charter)

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| | | |
|:---|:---|:---|
| **Nevada** | **001-12584** | **13-3808303** |
| (State or other jurisdiction of<br> incorporation) | (Commission File No.) | (IRS Employer Identification<br> No.) |

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**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) |
| Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
| Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |

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

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| | | |
|:---|:---|:---|
| &nbsp;&nbsp;**Title of each class** | &nbsp;&nbsp;**Trading Symbol(s)** | &nbsp;&nbsp;**Name of each exchange on which <br> registered** |
| &nbsp;&nbsp;Common stock, par value $0.001 per share | &nbsp;&nbsp;TOVX | &nbsp;&nbsp;NYSE American |

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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.**

On April 17, 2026, Theriva Biologics, Inc. (the "Company") issued a press release announcing an upcoming poster presentation of new data and subgroup analyses from the VIRAGE Phase 2b clinical trial evaluating VCN-01 (zabilugene almadenorepvec) plus gemcitabine/nab-paclitaxel in newly-diagnosed metastatic pancreatic cancer patients at the American Association for Cancer Research (AACR) Annual Meeting to be held in San Diego, CA from 17-22 April 2026.

&nbsp;&nbsp;&nbsp;&nbsp;· Presenting author: Dr. Manuel Hidalgo, NYU Langone Health Perlmutter Cancer Center, New York, NY

&nbsp;&nbsp;&nbsp;&nbsp;· Title: Analysis of tumor and biomarker responses in the VIRAGE Trial, a randomized Phase IIb, open-label,
study of nab-paclitaxel and gemcitabine with/without intravenous VCN-01 in patients with metastatic pancreatic cancer (mPDAC)

&nbsp;&nbsp;&nbsp;&nbsp;· Poster #: CT162

&nbsp;&nbsp;&nbsp;&nbsp;· Date and time: Monday April 20, 2026, 2:00-5:00 PM US PDT

&nbsp;&nbsp;&nbsp;&nbsp;· Session: PO.CT01.05 - Phase II and Phase III Clinical Trials

&nbsp;&nbsp;&nbsp;&nbsp;· Location: San Diego Convention Center, Hall B, Section 52, Board 26.

The information in this Item 7.01 and in the press release 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 press release 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 April 17, 2026, the Company issued a press release announcing an upcoming poster presentation of new data and subgroup analyses from the VIRAGE Phase 2b clinical trial evaluating VCN-01 (zabilugene almadenorepvec) plus gemcitabine/nab-paclitaxel in newly-diagnosed metastatic pancreatic cancer patients at the American Association for Cancer Research (AACR) Annual Meeting to be held in San Diego, CA from 17-22 April 2026.

Details of the poster presentation are below:

&nbsp;&nbsp;&nbsp;&nbsp;· Presenting author: Dr. Manuel Hidalgo, NYU Langone Health Perlmutter Cancer Center, New York, NY

&nbsp;&nbsp;&nbsp;&nbsp;· Title: Analysis of tumor and biomarker responses in the VIRAGE Trial, a randomized Phase IIb, open-label,
study of nab-paclitaxel and gemcitabine with/without intravenous VCN-01 in patients with metastatic pancreatic cancer (mPDAC)

&nbsp;&nbsp;&nbsp;&nbsp;· Poster #: CT162

&nbsp;&nbsp;&nbsp;&nbsp;· Date and time: Monday April 20, 2026, 2:00-5:00 PM US PDT

&nbsp;&nbsp;&nbsp;&nbsp;· Session: PO.CT01.05 - Phase II and Phase III Clinical Trials

&nbsp;&nbsp;&nbsp;&nbsp;· Location: San Diego Convention Center, Hall B, Section 52, Board 26.

Included in the poster presentation are the conclusions set forth below.

&nbsp;&nbsp;&nbsp;&nbsp;· Patients receiving VCN-01 + gemcitabine/nab-paclitaxel ("GnP") had improved overall survival and progressive free survival
compared to GnP alone. The late separation of survival curves may reflect an immune-mediated mechanism of action.

&nbsp;&nbsp;&nbsp;&nbsp;· Treatment with VCN-01 + GnP resulted in later-emerging, higher magnitude, and more durable responses than GnP alone.

&nbsp;&nbsp;&nbsp;&nbsp;· The OS benefit of VCN-01 + GnP was generally maintained across subgroups including liver metastases, despite a post-recruitment imbalance.

&nbsp;&nbsp;&nbsp;&nbsp;· Patients receiving a second administration of VCN-01 revealed a greater benefit in OS and PFS.

The full poster for the presentation has been released by the American Association for Cancer Research. A copy of the poster presentation titled Analysis of tumor and biomarker responses in the VIRAGE Trial, a randomized Phase IIb, open-label, study of nab-paclitaxel and gemcitabine with/without intravenous VCN-01 in patients with metastatic pancreatic cancer (mPDAC)is filed as exhibit 99.2 to this Current Report on Form 8-K. and is incorporated herein by reference.

**Item 9.01. Financial Statements and Exhibits.**

(d) Exhibits. <br>The following exhibit is furnished with this Current Report on Form 8-K.

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| | |
|:---|:---|
| **Exhibit<br> Number** | **Description** |
| [99.1](tm2612012d1_ex99-1.htm) | [Press Release issued by Theriva Biologics, Inc., dated April 17, 2026](tm2612012d1_ex99-1.htm) |
| [99.2](tm2612012d1_ex99-2.htm) | [Poster Presentation titled "Analysis of tumor and biomarker responses in the VIRAGE Trial, a randomized Phase IIb, open-label, study of nab-paclitaxel and gemcitabine with/without intravenous VCN-01 in patients with metastatic pancreatic cancer (mPDAC)"](tm2612012d1_ex99-2.htm) |
| 104 | Cover Page Interactive Data File (embedded within the XBRL document) |

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**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.

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| | | | |
|:---|:---|:---|:---|
| Dated: April 17, 2026 | **THERIVA BIOLOGICS, INC.** | **THERIVA BIOLOGICS, INC.** | **THERIVA BIOLOGICS, INC.** |
|  | By: | /s/ Steven A. Shallcross | /s/ Steven A. Shallcross |
|  |  | Name: | Steven A. Shallcross |
|  |  | Title: | Chief Executive Officer <br> and Chief Financial Officer |

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## Exhibit 99.1

**Exhibit 99.1**

![](tm2612012d1_ex99-1img001.jpg)

**Theriva™ Biologics Announces Upcoming Presentation of Additional Data from the VIRAGE Phase 2b Clinical Trial of VCN-01 in Metastatic Pancreatic Cancer at AACR 2026 Annual Meeting**

*- Tumor reponse, biomarker, and subgroup analyses from the VIRAGE Phase 2b clinical trial support a VCN-01 immune-mediated mode of action and demonstrate improved outcomes in VCN-01 treated patients across multiple subgroups, including patients with liver metastases -*

*- Data to be presented in a poster session at the American Association of Cancer Research (AACR) Annual Meeting in San Diego, California on Monday April 20, 2026-*

**Rockville, MD, April 17, 2026 –** Theriva™ Biologics (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 an upcoming poster presentation of new data and subgroup analyses from the VIRAGE Phase 2b clinical trial evaluating VCN-01 (zabilugene almadenorepvec) plus gemcitabine/nab-paclitaxel in newly-diagnosed metastatic pancreatic cancer patients. Tumor reponse, biomarker data, and subgroup analyses are to be presented at the American Association for Cancer Research (AACR) Annual Meeting to be held in San Diego, CA from 17-22 April 2026.

Details of the poster presentation are below:

&nbsp;&nbsp;&nbsp;&nbsp;· Presenting author: Dr. Manuel Hidalgo, NYU Langone Health Perlmutter Cancer Center, New York, NY

&nbsp;&nbsp;&nbsp;&nbsp;· Title: Analysis of tumor and biomarker responses in the VIRAGE Trial, a randomized Phase IIb, open-label, study of nab-paclitaxel
and gemcitabine with/without intravenous VCN-01 in patients with metastatic pancreatic cancer (mPDAC)

&nbsp;&nbsp;&nbsp;&nbsp;· Poster #: CT162

&nbsp;&nbsp;&nbsp;&nbsp;· Date and time: Monday April 20, 2026, 2:00-5:00 PM US PDT

&nbsp;&nbsp;&nbsp;&nbsp;· Session: PO.CT01.05 - Phase II and Phase III Clinical Trials

&nbsp;&nbsp;&nbsp;&nbsp;· Location: San Diego Convention Center, Hall B, Section 52, Board 26.

"The new data and analyses to be presented at the AACR meeting further reinforce our confidence in the clinical potential of VCN-01 plus gemcitabine/nab-paclitaxel chemotherapy to help metastatic PDAC patients," said Steven A. Shallcross, Chief Executive Officer of Theriva Biologics. "Taken together, the tumor response and biomarker data support an immune-mediated mode of action for VCN-01, which is consistent with the previously reported clinical <u>observations</u>, showing that patients treated with VCN-01 plus gemcitabine/nab-paclitaxel experienced a significantly protracted duration of response concomitant with a later-stage prolongation of survival compared to patients treated with gemcitabine/nab-paclitaxel alone. We have achieved alignment with both the FDA and the EMA on a proposed pivotal Phase 3 clinical trial to evaluate multiple doses of VCN-01 plus gemcitabine/nab-paclitaxel in first-line metastatic PDAC patients, and we are planning a small study to assess whether more frequent and extended VCN-01 dosing could further improve outcomes."

![](tm2612012d1_ex99-1img001.jpg)

**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. In many instances, progressive abdominal pain is the first symptom. Therefore, in most cases, pancreatic cancer is diagnosed in its late stages (locally advanced non-metastatic or metastatic stage of the 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 (zabilugene almadenorepvec) 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. VCN-01 has been administered to 142 patients to date in clinical trials of different cancers, including pancreatic ductal adenocarcinoma (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 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's subsidiary Theriva Biologics, S.L. , has been developing 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 clinical-stage candidates is VCN-01 (zabilugene almadenorepvec), 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. An exploratory clinical trial is also on-going with 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. For more information, please visit Theriva™ Biologics' website at <u>www.therivabio.com</u>.

![](tm2612012d1_ex99-1img001.jpg)

**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 the Company's confidence in the clinical potential of VCN-01 plus gemcitabine/nab-paclitaxel chemotherapy to help metastatic PDAC patients; tumor response and biomarker data supporting an immune-mediated mode of action for VCN-01; alignment with the FDA and EMA on a proposed Phase 3 clinical trial evaluating multiple doses of VCN-01 plus gemcitabine/nab-paclitaxel in first-line metastatic PDAC patients; and planning a small study to assess whether more frequent and extended VCN-01 dosing could further improve outcomes. Important factors that could cause actual results to differ materially from current expectations include, among others, the Company's ability to finalize the proposed pivotal Phase 3 study protocol and file a BLA; the Company's ability to obtain development funding and/or partnerships; the Company's ability to reach clinical milestones when anticipated, including the ability to continue to enroll patients as planned; generating clinical data that establishes VCN-01 may improve patient outcomes in metastatic PDAC patients; the ability to obtain regulatory approval for commercialization of product candidates or to comply with ongoing regulatory requirements, including approval of VCN-01 to treat patients with PDAC; regulatory limitations relating to the Company's ability to promote or commercialize their product candidates for the specific indications; acceptance of the Company's product candidates in the marketplace; the successful development, marketing or sale of the Company's products; developments by competitors that render such products obsolete or non-competitive; the Company's ability to maintain license agreements; the continued maintenance and growth of the Company'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, 2025 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:<br> Kevin Gardner<br> LifeSci Advisors, LLC<br> kgardner@lifesciadvisors.com

## Exhibit 99.2

**Exhibit 99.2**

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| | |
|:---|:---|
| &nbsp;&nbsp;![GRAPHIC](tm2612012d1_ex99-2img001.jpg) | &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;\*Address correspondence to: manuel.hidalgo@nyulangone.org CT162: Analysis of tumor and biomarker responses in the VIRAGE trial, a randomized phase IIb, open-label, study of nab-paclitaxel and gemcitabine with/without intravenous VCN-01 in patients with metastatic pancreatic cancer (mPDAC) Rocio Garcia-Carbonero1 , Roberto Pazo Cid2 , Teresa Macarulla 3 , Berta Laquente 4 , Alana Nguyen 5 , Carmen Guillén 6 , Andrés Muñoz 7 , Edward J Kim8 , Mireya Cazorla 9 , Tara Seery 10 , Miriam Lobo de Mena 11 , Chris Nevala-Plagemann12, Vivek Sharma13, Eva Martínez de Castro 14 , Charles Le 15 , Ana Mato-Berciano 16 , Luis A. Rojas 16 , Carmen Blasco 16 , Manel Cascallo 16 , Manuel Hidalgo18,\* 1Hospital Universitario 12 de Octubre, Imas 12, Madrid, Spain; 2Hospital Universitario Miguel Servet, Zaragoza, Spain; 3Hospital Universitari Vall d'Hebron, Barcelona, Spain; 4Catalan Institut of Oncology, Barcelona, Spain; 5Weill Cornell Medicine/NYP Hospital, New York, NY; 6Hospital Universitario Ramon y Cajal, Madrid, Spain; 7Hospital Universitario Gregorio Marañón, Madrid, Spain; 8UC Davis Comprehensive Cancer Center, Sacramento; 9Hospital Regional Universitario, Málaga, Spain; 10Hoag Memorial Hospital Presbyterian, Newport Beach, CA; 11Consorcio Hospital General Universitario de Valencia, Valencia, Spain; 12Huntsman Cancer Institute at University of Utah, Salt Lake City; 13University of Louisville, Louisville, KY; 14Hospital Universitario Marqués de Valdecilla, Santander, Spain; 15Theriva Biologics Inc., Rockville, MD, USA; 16Theriva Biologics SL., Parets del Vallès, Spain; 18NYU Langone Health Perlmutter Cancer Ctr., NY. VCN-01 is a clinical-stage oncolytic adenovirus engineered to replicate selectively in cancer cells with an aberrant RB1-E2F pathway. The VCN-01 E1A promoter is modified by inclusion of eight E2F1 binding sites and a 24-bp deletion that promotes viral transcription in cells with elevated free E2F1 and renders the virus replication-deficient in RB1-functional, normal cells. Here, human pancreatic cancer cell lines were exposed to topoisomerase I (topo1) inhibiting chemotherapeutics, irinotecan (IRI), its active metabolite, SN-38, and topotecan (topo; see Figure A). Notably, in NP-18 cells, E2F1 mRNA was increased ~3-fold compared to untreated cells, and E1A mRNA was boosted ~5-fold in cells treated with VCN-01 + topo1 inhibitors compared to VCN-01 alone. These data suggest that topo1 inhibitor-mediated elevations in E2F1 increase VCN-01 transcription. Based on these promising in vitro results, the potential synergy of VCN-01 plus the liposomal formulation of IRI (B A C K G R O U N D Zabilugene almadenorepvec (VCN-01) 1 is an oncolytic adenovirus engineered to replicate in cancer cells with a dysfunctional RB1 pathway. VCN-01 expresses PH20 hyaluronidase to improve intratumoral viral dissemination, enhance chemotherapy penetration, and facilitate immune cell infiltration. Previous phase I showed that intravenous administration of VCN-01 is feasible and has an acceptable safety profile2 . VCN-01 reached and replicated in tumors, induced an inflammatory tumor microenvironment, and showed encouraging biological and clinical activity when administered sequentially with GnP to patients with mPDAC. In this phase IIb VIRAGE trial, the primary endpoints of overall survival (OS) and safety were accomplished (previously presented at ESMO 2025) 3 . Figure 1. Mechanisms of action of VCN-01 Chemonaïve mPDAC patients were randomized 1:1 to receive GnP on days 1, 8 and 15 of repeated 28-day cycles (GnP group) or 2 separate IV doses of VCN-01 (1x1013 vp/dose) 1 week prior to cycles 1 and 4 of GnP (VCN-01 + GnP group). • Primary endpoints: • Overall survival (OS) • Safety and tolerability • Secondary objectives: • Progression free survival (PFS) • Objective response rates (ORR) • Disease control rate (DCR) • Duration of response (DoR) • Changes of CA 19-9 over time • Exploratory analyses: • Viral genomes (vg) in blood • Neutralizing antibodies (NAbs) in serum Figure 2. Treatment schedules for the VIRAGE trial D E S I G N & O B J E C T I V E S • Patients receiving VCN-01 + GnP had improved OS and PFS compared to GnP alone. The late separation of survival curves may reflect an immune-mediated mechanism of action. • Treatment with VCN-01 + GnP resulted in later-emerging, higher magnitude, and more durable responses than GnP alone. • The OS benefit of VCN-01 + GnP was generally maintained across subgroups including liver metastases, despite a post-recruitment imbalance. • Patients receiving a second administration of VCN-01 revealed a greater benefit in OS and PFS. C O N C L U S I O N S R E S U LT S Demographics and survival outcomes Figure 3. Survival outcomes. Kaplan-Meier analysis of OS (a) and PFS (b) in the patients receiving VCN-01 + ≥1 full dose of GnP (VCN-01 + GnP) or ≥1 full dose of GnP (GnP). P values by two-sided log-rank test. Quality of response Table 2. OS rates at selected timepoints Analysis of subgroups 1. Rodríguez-García A et al. Safety and efficacy of VCN-01, an oncolytic adenovirus combining fiber HSG-binding domain replacement with RGD and hyaluronidase expression. Clin Cancer Res. 21:1406-18 (2015). 2. Garcia-Carbonero, R. et al. Phase I, multicenter, open-label study of intravenous VCN-01 oncolytic adenovirus with or without nab-paclitaxel plus gemcitabine in patients with advanced solid tumors. J. Immunother. Cancer 10, (2022). 3. García-Carbonero, R. et al. 2216MO VIRAGE trial: Randomized phase IIb, open-label, study of nab-paclitaxel and gemcitabine with/without intravenous VCN-01 in patients with metastatic pancreatic cancer (mPDAC). Ann Oncol. 36:S1146-7 (2025) The authors are grateful to the patients and their families, investigators, co-investigators, and study teams at clinical sites for their participation and dedication. The clinical study was supported by Theriva Biologics S.L. A C K N O W L E D G E M E N T S R E F E R E N C E S Efficacy in patients receiving four cycles of GnP (two doses of VCN-01) Patients with liver metastases Table 3. Secondary efficacy parameters in patients receiving 4 cycles of GnP Figure 6. Efficacy in patients receiving two doses of VCN-01 a, b, Kaplan-Meier analysis of OS (a) and PFS (b) in the subgroup population of patients receiving a 4th cycle of GnP (GnP) or a 4th cycle of GnP plus a 2nd dose of VCN-01 (VCN-01 + GnP). P values by two-sided log-rank test. Viral genomes and neutralizing antibodies Figure 7. Viral genomes in blood (a) and neutralizing antibodies in serum (b). Geometric mean + 95% CI. The dotted line indicates the limit of quantification. VCN-01 administrations are indicated by blue arrows. Figure 5. Analysis of subgroup populations. a, Forest plot of OS in selected subgroups (post-hoc analyses). \* For the GnP group, the equivalent of 2 doses of VCN-01 corresponds to patients who received a 4th cycle of GnP. Hazard ratio P values by Cox Proportional-Hazards model. b, c, Kaplan-Meier analysis of OS (b) and PFS (c) in the subgroup of patients with liver metastases. P values by two-sided log-rank test. Multivariate analysis adjusting for liver metastases confirmed that the survival benefit of the VCN-01 + GnP group was independent of the imbalance in liver metastases between treatment groups (HR = 0.6 (95% CI, 0.36-1.01), P = 0.055). a b a c b d a c b a b a b Table 3. Secondary efficacy parameters in overall population e Figure 4. Quality of response. a, Duration of response (DoR). b, Maximum percentage change in target lesion size from baseline. c, Swimmer's plot showing OS in the GnP group (left) and the VCN-01 + GnP group (right); disease progression, responses, complete responses (CR), VCN-01 doses, and death events are indicated. d, Time to response, defined as the interval from treatment initiation to the first documented clinical response. e, Percentage change from baseline of CA19-9 levels in individual patients at initiation of cycles 3, 6, and 9 of GnP. The red line indicates the median. P values by two-sided log-rank test (a) and two-tailed Mann-Whitney test (d). Table 1. Baseline demographics and clinical characteristics Characteristic GnP (n = 48) VCN-01 + GnP (n = 48) Age (years) Median (range) 68.5 (52-85) 66.0 (41-86) <70 years, n (%) 26 (54.2) 33 (68.8) ≥70 years, n (%) 22 (45.8) 15 (31.2) Gender Male, n (%) 22 (45.8) 23 (47.9) Female, n (%) 26 (54.2) 25 (52.1) Region European Union, n (%) 41 (85.4) 39 (81.3) North America, n (%) 7 (14.6) 9 (18.8) Body Mass Index (kg/m2) Median (range) 25.65 (19.1-37.0) 23.70 (17.9-38.4) ECOG at randomization 0, n (%) 17 (35.4) 19 (39.6) 1, n (%) 31 (64.6) 29 (60.4) Liver metastases at baseline Yes, n (%) 40 (83.3) 31 (64.6) No, n (%) 8 (16.7) 17 (35.4) Number of metastatic sites 1 or 2, n (%) 38 (79.2) 37 (77.1) ≥3, n (%) 10 (20.8) 11 (22.9) Primary tumor location Head, n (%) 20 (41.7) 18 (37.5) Body and tail, n (%) 28 (58.3) 30 (62.5) CA 19-9 at baseline ≤ 37 UI/ml, n (%) 8 (16.7) 9 (18.8) > 37 UI/ml, n (%) 40 (83.3) 39 (81.2) Months GnP (%) VCN-01 + GnP (%) 12 31.9 42.6 15 12.77 35.5 18 8.52 31.1 Parameter GnP (n = 48) VCN-01 + GnP (n = 48) P value CR, n (%) 0 (0) 1 (2.1) - PR, n (%) 15 (31.3) 18 (37.5) - SD, n (%) 19 (39.6) 18 (37.5) - PD, n (%) 14 (29.2) 11 (22.9) - ORR, n (%) 15 (31.3) 19 (39.6) 0.41 DCR, n (%) 34 (70.8) 37 (77.1) 0.59 Parameter GnP (n = 29) VCN-01 + GnP (n = 34) P value CR, n (%) 0 (0) 1 (2.9) - PR, n (%) 14 (48.3) 18 (52.9) - SD, n (%) 15 (51.7) 15 (44.1) - PD, n (%) 0 (0) 0 (0) - ORR, n (%) 14 (48.3) 19 (55.9) 0.62 DCR, n (%) - - - |

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