# EDGAR Filing Document

**Accession Number:** 0000894158
**File Stem:** 0001104659-25-098882
**Filing Date:** 2025-10
**Character Count:** 26643
**Document Hash:** 61fa757fa8c2cac2f775aa78bd2fae64
**Contains OCR:** False
**Source Format:** 

## Filing Content

## Filing Summary
**0001104659-25-098882.hdr.sgml**: 20251014

**ACCESSION NUMBER**: 0001104659-25-098882

**CONFORMED SUBMISSION TYPE**: 8-K

**PUBLIC DOCUMENT COUNT**: 15

**CONFORMED PERIOD OF REPORT**: 20251013

**ITEM INFORMATION**: Regulation FD Disclosure

**ITEM INFORMATION**: Other Events

**ITEM INFORMATION**: Financial Statements and Exhibits

**FILED AS OF DATE**: 20251014

**DATE AS OF CHANGE**: 20251014

**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:** 251389258

**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): October 13, 2025**

**THERIVA BIOLOGICS, INC.**

(Exact name of registrant as specified in its charter)

---

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

---

| |
|:---|
| 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)) |

---

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

---

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

On October 13, 2025, Theriva Biologics, Inc. (the "Company") issued a press release announcing the presentation on October 20, 2025 of expanded metastatic pancreatic ductal adenocarcinoma (mPDAC) data from the VIRAGE Phase 2b trial (NCT05673811) at the European Society for Medical Oncology (ESMO 2025) Annual Congress. The press release also announced a separate poster presentation on the same day describing previously reported data for SYN-004 (ribaxamase) in allogeneic hematopoietic transplant recipients at Infectious Diseases Week (IDWeek) 2025 Annual Meeting.

Results from the VIRAGE Phase 2b trial included in the abstract are set forth below:

112 patients were randomized. Patients in the modified intent to treat (mITT) population received at least 1 dose of gemcitabine/nab-paclitaxel (GA) standard of care chemotherapy (GA, Arm I) or VCN-01 (Arm II). Patients in the full analysis set (FAS) population received at least 1 dose of gemcitabine/nab-paclitaxel standard of care chemotherapy (GA; Arm I) or VCN-01 followed by at least 1 dose of GA (Arm II).

---

| | | | | | | |
|:---|:---|:---|:---|:---|:---|:---|
| | mITT | mITT | mITT | FAS | FAS | FAS |
| | Arm I (48) | Arm II (53) | HR (95% CI) | Arm I (48) | Arm II (48) | HR (95% CI) |
| OS<br>mo. | <br> 8.6 | <br> 10.6 | 0.69 (0.42-1.12)<br>*P*=0.196 | <br> 8.6 | <br> 10.8 | 0.57 (0.34-0.96)<br>*P*=0.055 |
| PS<br>mo. | <br> 4.6 | <br> 5.6 | 0.63 (0.4-1.0)<br>*P*=0.047 | <br> 4.6 | <br> 7.0 | 0.55 (0.34-0.88)<br>*P*=0.011 |
| DoR<br>mo. | <br> 5.4 | <br> 11.2 | 0.22 (0.08-0.62)<br>*P*=0.004 | <br> 5.4 | <br> 11.2 | 0.22 (0.08-0.62)<br>*P*=0.004 |
| ORR | 31.3% | 35.8% |  | 31.3% | 39.6% |  |
| Definitions - mo. (Months). OS (overall survival). PS or PFS (progression free survival). DoR (duration of response). ORR (objective response rate). HR (hazard ratio). CI (confidence interval). | Definitions - mo. (Months). OS (overall survival). PS or PFS (progression free survival). DoR (duration of response). ORR (objective response rate). HR (hazard ratio). CI (confidence interval). | Definitions - mo. (Months). OS (overall survival). PS or PFS (progression free survival). DoR (duration of response). ORR (objective response rate). HR (hazard ratio). CI (confidence interval). | Definitions - mo. (Months). OS (overall survival). PS or PFS (progression free survival). DoR (duration of response). ORR (objective response rate). HR (hazard ratio). CI (confidence interval). | Definitions - mo. (Months). OS (overall survival). PS or PFS (progression free survival). DoR (duration of response). ORR (objective response rate). HR (hazard ratio). CI (confidence interval). | Definitions - mo. (Months). OS (overall survival). PS or PFS (progression free survival). DoR (duration of response). ORR (objective response rate). HR (hazard ratio). CI (confidence interval). | Definitions - mo. (Months). OS (overall survival). PS or PFS (progression free survival). DoR (duration of response). ORR (objective response rate). HR (hazard ratio). CI (confidence interval). |

---

Compared to patients who started GA cycle 4 alone (Arm I), patients who received 2 VCN-01 doses and started GA cycle 4 (Arm II) showed greater improvement in OS (14.8 vs 11.6 months; HR 0.44; 95% CI 0.21 - 0.92; *P*=0.046) and PFS (11.2 vs 7.4 months; HR 0.48; 95% CI 0.25 - 0.91; *P*=0.017). VCN-01 administration was well tolerated. All VCN- 01-related serious adverse events (n=13) were resolved, the most common being flu-like symptoms (13,2%), transaminase increase (5.7%) and drug-induced liver injury (3.8%). Viral genome analysis confirmed the bioactivity of the second VCN-01 dose.

This study met its primary endpoints. Patients receiving VCN-01 + GA had improved OS, PFS and DoR compared to GA standard of care.

The full abstract for the presentation has been released by ESMO. A copy of the abstract titled "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)" is filed as an exhibit to this Current Report on Form 8-K.

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. 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 October 13, 2025, the Company issued a press release announcing the presentation on October 20, 2025 of expanded metastatic pancreatic ductal adenocarcinoma (mPDAC) data from the VIRAGE Phase 2b trial (NCT05673811) at ESMO 2025.

Results from the abstract for the VIRAGE Phase 2b trial are set forth below.

112 patients were randomized. Patients in the modified intent to treat (mITT) population received at least 1 dose of GA (Arm I) or VCN-01 (Arm II). Patients in the full analysis set (FAS) population received at least 1 dose of gemcitabine/nab-paclitaxel standard of care chemotherapy (GA; Arm I) or VCN-01 followed by at least 1 dose of GA (Arm II).

---

| | | | | | | |
|:---|:---|:---|:---|:---|:---|:---|
| | mITT | mITT | mITT | FAS | FAS | FAS |
| | Arm I (48) | Arm II (53) | HR (95% CI) | Arm I (48) | Arm II (48) | HR (95% CI) |
| OS<br>mo. | <br> 8.6 | <br> 10.6 | 0.69 (0.42-1.12)<br>*P*=0.196 | <br> 8.6 | <br> 10.8 | 0.57 (0.34-0.96)<br>*P*=0.055 |
| PS<br>mo. | <br> 4.6 | <br> 5.6 | 0.63 (0.4-1.0)<br>*P*=0.047 | <br> 4.6 | <br> 7.0 | 0.55 (0.34-0.88)<br>*P*=0.011 |
| DoR<br>mo. | <br> 5.4 | <br> 11.2 | 0.22 (0.08-0.62)<br>*P*=0.004 | <br> 5.4 | <br> 11.2 | 0.22 (0.08-0.62)<br>*P*=0.004 |
| ORR | 31.3% | 35.8% |  | 31.3% | 39.6% |  |
| Definitions: mo.(months). OS (overall survival). PS or PFS (progression free survival). DoR (duration of response). ORR (objective response rate). HR (hazard ratio). CI (confidence interval) | Definitions: mo.(months). OS (overall survival). PS or PFS (progression free survival). DoR (duration of response). ORR (objective response rate). HR (hazard ratio). CI (confidence interval) | Definitions: mo.(months). OS (overall survival). PS or PFS (progression free survival). DoR (duration of response). ORR (objective response rate). HR (hazard ratio). CI (confidence interval) | Definitions: mo.(months). OS (overall survival). PS or PFS (progression free survival). DoR (duration of response). ORR (objective response rate). HR (hazard ratio). CI (confidence interval) | Definitions: mo.(months). OS (overall survival). PS or PFS (progression free survival). DoR (duration of response). ORR (objective response rate). HR (hazard ratio). CI (confidence interval) | Definitions: mo.(months). OS (overall survival). PS or PFS (progression free survival). DoR (duration of response). ORR (objective response rate). HR (hazard ratio). CI (confidence interval) | Definitions: mo.(months). OS (overall survival). PS or PFS (progression free survival). DoR (duration of response). ORR (objective response rate). HR (hazard ratio). CI (confidence interval) |

---

Compared to patients who started GA cycle 4 alone (Arm I), patients who received 2 VCN-01 doses and started GA cycle 4 (Arm II) showed greater improvement in OS (14.8 vs 11.6 months; HR 0.44; 95% CI 0.21 - 0.92; *P*=0.046) and PFS (11.2 vs 7.4 months; HR 0.48; 95% CI 0.25 - 0.91; *P*=0.017). VCN-01 administration was well tolerated. All VCN- 01-related serious adverse events (n=13) were resolved, the most common being flu-like symptoms (13,2%), transaminase increase (5.7%) and drug-induced liver injury (3.8%). Viral genome analysis confirmed the bioactivity of the second VCN-01 dose.

The study met its primary endpoints. Patients receiving VCN-01 + GA had improved OS, PFS and DoR compared to GA standard of care.

The full abstract for the presentation has been released by ESMO. A copy of the abstract titled "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)." is filed as an exhibit to this Current Report on Form 8-K. and is incorporated herein by reference.

The expanded data will be presented at ESMO 2025 on October 20, 2025.

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

(d) Exhibits.

---

| | |
|:---|:---|
| **Exhibit<br> Number** | **Description** |
| [99.1](tm2528558d1_ex99-1.htm) | [Press Release issued by Theriva Biologics, Inc., dated October 13, 2025](tm2528558d1_ex99-1.htm) |
| [99.2](tm2528558d1_ex99-2.htm) | [Abstract: "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)"](tm2528558d1_ex99-2.htm) |
| 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: October 14, 2025 | **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 |

---

## Exhibit 99.1

**Exhibit 99.1**

![](tm2528558d1_ex99-1img001.jpg)

**Theriva™ Biologics Announces Upcoming Presentations at Medical Meetings**

*- VCN-01 expanded mPDAC data from VIRAGE Phase 2b trial to be presented at ESMO 2025 -*

*- SYN-004 Interim blinded safety and pharmacokinetic data to be presented at IDWeek 2025 -*

**Rockville, MD, October 13, 2025 –** 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 upcoming presentations at the European Society for Medical Oncology (ESMO 2025) Annual Congress and at Infectious Diseases Week (IDWeek) 2025 Annual Meeting.

**VCN-01 upcoming mini-oral presentation at ESMO 2025**

Expanded data from the VIRAGE trial investigating VCN-01 (zabilugene almadenorepvec) are to be presented at a mini oral session at the ESMO 2025 Congress:

&nbsp;&nbsp;&nbsp;&nbsp;· Presenting author: Dr. Rocío Garcia-Carbonero, Hospital 12 de Octubre,
Madrid, Spain

&nbsp;&nbsp;&nbsp;&nbsp;· Title: 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)

&nbsp;&nbsp;&nbsp;&nbsp;· Abstract #: 2216MO

&nbsp;&nbsp;&nbsp;&nbsp;· Date and time: Monday, October 20, 2025, 09:28 a.m. CEST

&nbsp;&nbsp;&nbsp;&nbsp;· Session: Mini oral session 2, GI Tumors Upper digestive

&nbsp;&nbsp;&nbsp;&nbsp;· Location: Bonn Auditorium - Hall 7.1c, Messe Berlin, Berlin, Germany

**SYN-004 upcoming poster presentation at IDWeek 2025**

Previously disclosed blinded safety and pharmacokinetic (PK) data from the ongoing Phase 1b/2a randomized, double-blinded, placebo-controlled clinical trial of SYN-004 (ribaxamase) in allogeneic hematopoietic cell transplant (HCT) recipients for the prevention of acute graft-versus-host-disease (aGVHD). These data will be presented at ID Week 2025:

&nbsp;&nbsp;&nbsp;&nbsp;· Presenting Author: Erik R. Dubberke, MD, Professor of Medicine, Clinical
Director, Transplant Infectious Diseases, Washington University School of Medicine in St. Louis

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;· Title: Safety and tolerability of SYN-004 in allogeneic haematopoietic cell transplant (HCT) recipients
receiving meropenem (MER) or piperacillin/tazobactam (P/T)

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;· Abstract #: P-104

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;· Date and time: Monday, October 20, 2025 from 12:15 to 1:30 p.m US EDT

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;· Location: Poster Hall B4-5, Georgia World Congress Center, Atlanta, Georgia

**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 SYN-004 (ribaxamase)**

SYN-004 (ribaxamase) is an oral prophylactic therapy designed to degrade certain IV beta-lactam antibiotics within the GI tract and maintain the natural balance of the gut microbiome for the prevention of Clostridioides difficile infection (CDI), overgrowth of pathogenic organisms, the emergence of antimicrobial resistance (AMR) and acute graft-versus-host-disease (aGVHD) in allogeneic hematopoietic cell transplant (HCT) recipients. Allogeneic HCT recipients routinely receive long courses of IV beta-lactam antibiotics to treat infection following conditioning therapy. Antibiotic-mediated damage of the gut microbiome in allogeneic HCT recipients may lead to adverse outcomes including CDI, VRE colonization and potentially fatal bacteremia and aGVHD. A previously completed placebo-controlled Phase 2b clinical trial of 412 patients demonstrated SYN-004 protected the gut microbiome from antibiotic-mediated dysbiosis. Patients who received SYN-004 also demonstrated significantly better maintenance and recovery of the gut microbiome as well as lower incidences of new colonization by opportunistic and potentially pathogenic microorganisms such as VRE.

**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 are: (1) 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; (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 <u>www.therivabio.com</u>.

**For further information, please contact:**

Investor Relations:<br> Kevin Gardner<br> LifeSci Advisors, LLC<br> kgardner@lifesciadvisors.com

## Exhibit 99.2

**Exhibit 99.2**

Abstract 5555

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)

Type: Abstract Category: Pancreatic cancer

---

| | |
|:---|:---|
| Authors: | <u>R. Garcia-Carbonero</u><sup>1</sup>, R. Pazo Cid<sup>2</sup>, T. Macarulla Mercade<sup>3</sup>, B. Laquente<sup>4</sup>, A. Nguyen<sup>5</sup>, C. Guillen Ponce<sup>6</sup>, A. Munoz Martin<sup>7</sup>, E. Kim <sup>8</sup>, M. Cazorla<sup>9</sup>, T. Seery<sup>10</sup>, M. Lobo de Mena<sup>11</sup>, C. Nevala-plagemann<sup>12</sup>, V. Sharma<sup>13</sup>, E. Martinez de Castro<sup>14</sup>, C. Le<sup>15</sup>, M. Kaleko<sup>16</sup>, M.A. Shallcross<sup>17</sup>, C. Blasco<sup>18</sup>, M. Cascallo Piqueras<sup>19</sup>, M. Hidalgo<sup>20</sup>; <sup>1</sup>Medical Oncology Department, Hospital Universitario 12 de Octubre Imas12, UCM, Madrid, Spain, <sup>2</sup>Medical Oncology Department, HospItal Universitario Miguel Servet, Zaragoza, Spain, <sup>3</sup>Medical Oncology Dept., VHIO - Vall d'Hebron Institute of Oncology, Barcelona, Spain, <sup>4</sup>Medical Oncology Department, ICO - Institut Català d'Oncologia l'Hospitalet (Hospital Duran i Reynals), L'Hospitalet De Llobregat, Spain, <sup>5</sup>Internal Medicine, Weill Cornell Medicine - Gastrointestinal (GI) Oncology, New York, United States of America, <sup>6</sup>Medical Oncology Department, Hospital Universitario Ramon y Cajal, Madrid, Spain, <sup>7</sup>Medical Oncology, Hospital General Universitario Gregorio Maranon, Madrid, Spain, <sup>8</sup>UC Davis School of Medicine, UC Davis Comprehensive Cancer Center, Sacramento, United States of America, <sup>9</sup>Medical Oncology, HUVV - Hospital Universitario Virgen de la Victoria, Malaga, Spain, <sup>10</sup>Medical Oncology Department, Hospital Universitario 12 de Octubre Imas12, UCM, Newport Beach, Ca, AL, United States of America, <sup>11</sup>Medical Oncology Department, CHGUV - Consorcio Hospital General Universitario de Valencia, Valencia, Spain, <sup>12</sup>Oncology, University of Utah Health - Huntsman Cancer Institute, Salt Lake City, United States of America, <sup>13</sup>Medicine, University of Louisville, Louisville, United States of America, <sup>14</sup>Oncologist, HUMV - Hospital Universitario Marques de Valdecilla, Santander, Spain, <sup>15</sup>Departments of Biometrics, Theriva Biologics, Inc., Rockville, United States of America, <sup>16</sup>Research and Development Dept., Theriva Biologics, Inc., Rockville, United States of America, <sup>17</sup>Clinical Operations, Theriva Biologics, Inc., Rockville, United States of America, <sup>18</sup>Clinical Operations, Theriva Biologics SL, Parets Del Valles (Barcelona)Barcelona, Spain, <sup>19</sup>Management, Theriva Biologics SL, Parets Del Valles (Barcelona), Spain, <sup>20</sup>Hematology Oncology Department, NewYork-Presbyterian Hospital/ Weill Cornell Medical Center, New York, United States of America |

---

**Background**

VCN-01 (zabilugene almadenorepvec) is an oncolytic adenovirus expressing hyaluronidase to degrade tumor stroma, facilitate chemotherapy and enhance the antitumor immune response. Building on an acceptable safety profile and encouraging activity when combined with standard of care (SoC) gemcitabine/nab-paclitaxel (GA), we conducted an open-label, controlled, randomized phase IIb trial to evaluate the efficacy and safety of two doses of VCN-01 with GA in mPDAC

**Methods**

Chemonaïve mPDAC patients were randomized 1:1 to receive SoC doses of GA on days 1, 8 and 15 of repeated 28-day cycles (Arm I) or 2 separate IV doses of VCN-01 (1x10<sup>13</sup> vp/dose) 1 week prior to each of cycle 1 & 4 of GA (Arm II). Primary endpoints were overall survival (OS) and safety. The trial was designed with 80% power to detect OS differences with 2-sided alpha 0.1 in mITT or FAS populations. Secondary objectives included PFS, response rates, duration of response (DoR) and biomarker Ca19.9.

**Results**

112 patients were randomized. Patients in the mITT population received at least 1 dose of GA (Arm I) or VCN-01 (Arm II). Patients in the FAS population received at least 1 dose of GA (Arm I) or VCN-01 followed by at least 1 dose of GA (Arm II).

---

| | | | | | | |
|:---|:---|:---|:---|:---|:---|:---|
| | mITT | mITT | mITT | FAS | FAS | FAS |
| | Arm I (48) | Arm II (53) | HR (95% CI) | Arm I (48) | Arm II (48) | HR (95% CI) |
| &nbsp;&nbsp;OS<br>mo. | <br> 8.6 | <br> 10.6 | 0.69 (0.42-1.12)<br>*P*=0.196 | <br> 8.6 | <br> 10.8 | 0.57 (0.34-0.96)<br>*P*=0.055 |
| &nbsp;&nbsp;PS<br>mo. | <br> 4.6 | <br> 5.6 | 0.63 (0.4-1.0)<br>*P*=0.047 | <br> 4.6 | <br> 7.0 | 0.55 (0.34-0.88)<br>*P*=0.011 |
| DoR<br>mo. | <br> 5.4 | <br> 11.2 | 0.22 (0.08-0.62)<br>*P*=0.004 | <br> 5.4 | <br> 11.2 | 0.22 (0.08-0.62)<br>*P*=0.004 |
| ORR | 31.3% | 35.8% |  | 31.3% | 39.6% |  |
| mo. months | mo. months | mo. months | mo. months | mo. months | mo. months | mo. months |

---

Compared to patients who started GA cycle 4 alone (Arm I), patients who received 2 VCN-01 doses and started GA cycle 4 (Arm II) showed greater improvement in OS (14.8 vs 11.6 months; HR 0.44; 95% CI 0.21 - 0.92; *P*=0.046) and PFS (11.2 vs 7.4 months; HR 0.48; 95% CI 0.25 - 0.91; *P*=0.017). VCN-01 administration was well tolerated. All VCN-01-related serious adverse events (n=13) were resolved, the most common being flu-like symptoms (13,2%), transaminase increase (5.7%) and drug-induced liver injury (3.8%). Viral genome analysis confirmed the bioactivity of the second VCN-01 dose.

**Conclusions**

This study met its primary endpoints. Patients receiving VCN-01 + GA had improved OS, PFS and DoR compared to GA SoC.

**Clinical trial identification**

NCT05673811

**Editorial acknowledgement**