Theriva™ Biologics Announces Publication of the Results from the VIRAGE Phase 2b Clinical Trial of VCN-01 in Metastatic Pancreatic Cancer Published in Nature Medicine

VIRAGE2 is testing more frequent VCN-01 dosing, with initial biological activity and safety/tolerability data anticipated by Q3 2027.

Rhea-AI Summary

Theriva Biologics (TOVX) announced publication in Nature Medicine of its VIRAGE Phase 2b trial results for VCN-01 in metastatic pancreatic cancer. The randomized, open-label trial enrolled 112 patients. VCN-01 plus gemcitabine/nab-paclitaxel chemotherapy improved overall survival, progression-free survival and duration of response versus chemotherapy alone. Greater improvements occurred in patients receiving two VCN-01 doses three months apart.

The first patient in VIRAGE2, testing more frequent repeated dosing, was treated in August 2026. Theriva expects enrollment completion in the second half of 2026 and initial data on biological activity and safety/tolerability by Q3 2027. The six-evaluable-patient study is not formally powered to evaluate clinical efficacy; results will inform dosing for a potential Phase 3 trial. Theriva is also engaging with the FDA on a potential Phase 2/3 retinoblastoma study.

10 points · 1 major

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Rhea-AI gives every point it takes from this document a weight. Minor counts 1, Moderate 3 and Major 9, so one Major point outweighs several Minor ones. The bar adds up the weights on each side, and when neither side holds more than 65% of the total the balance reads Mixed.

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0 major · 3 points

Hollow bars mark forward-looking points. How the balance works

Positive

• Major pointOverall survival improved with VCN-01 plus gemcitabine/nab-paclitaxel versus chemotherapy alone in VIRAGE.
• Minor pointProgression-free survival improved with VCN-01 plus gemcitabine/nab-paclitaxel versus chemotherapy alone in VIRAGE.
• Minor pointDuration of response improved with VCN-01 plus gemcitabine/nab-paclitaxel versus chemotherapy alone in VIRAGE.
• Minor pointTwo VCN-01 doses three months apart were associated with greater improvements in the reported efficacy measures.
• Minor pointVCN-01 pharmacokinetics, its behavior in the body, did not differ between doses despite neutralizing antibodies.

5 minor points

• Minor pointNature Medicine publication makes the peer-reviewed VIRAGE results available to the scientific community.
• Minor pointVIRAGE2 began treatment in August 2026 to evaluate more frequent repeated VCN-01 dosing.
• Minor point. Forward-looking: it has not happened yet and may not happen.VIRAGE2 enrollment completion is expected in the second half of 2026; initial data are anticipated by Q3 2027.
• Minor pointFDA engagement is underway to finalize a potential Phase 2/3 study in children with treatment-resistant retinoblastoma.
• Minor pointRare Pediatric Disease designation has been received for VCN-01 in retinoblastoma.

Negative

• Moderate pointVIRAGE2 is not formally powered for clinical efficacy; it is a single-arm, open-label study in six evaluable patients.
• Minor point. Forward-looking: it has not happened yet and may not happen.Future pivotal Phase 3 dosing depends on results from VIRAGE2.
• Minor point. Forward-looking: it has not happened yet and may not happen.Priority Review Voucher eligibility is potential and requires VCN-01 approval for retinoblastoma by September 30, 2029.

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Details

Market move: TOVX +7.90% vs previous close. Phase 2b clinical data

$0.21 – $0.23 Day Range

$10.40M Market Cap

On Sep 30, the day this news came out, the latest delayed price for TOVX is 7.90% above the previous close. Our momentum scanner has recorded 2 alerts for this stock so far that day. The latest delayed price is $0.23. Relative volume is very high at 3.4x the average.

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Key Figures

VIRAGE enrollment: 112 patients Prior VCN-01 regimen: 2 doses, 3 months apart VIRAGE2 evaluable patients: 6 patients +3 more

VIRAGE enrollment

112 patients

Phase 2b trial

Prior VCN-01 regimen

2 doses, 3 months apart

VIRAGE Phase 2b; greater improvements in survival parameters were observed with this regimen

VIRAGE2 evaluable patients

6 patients

Phase 2a study

VIRAGE2 planned dosing

At least 3 doses, 2 months between doses

VCN-01 with standard-of-care chemotherapy

Expected enrollment completion

Second half of 2026

VIRAGE2

Anticipated initial data

Q3 2027

VIRAGE2 pharmacodynamic and safety/tolerability data

Previous Clinical trial Reports

1 past event · Latest: Aug 06

Same Type 1 event

1. Aug 06

   VIRAGE2 first dosing

   24h Move

   -0.1%

   First patient dosed in the same VCN-01 repeat-dosing study.

24h Move is the share-price change in the day after each event; other market factors may also have contributed.

Key Terms

kaplan-meier, pharmacokinetics, objective response rate, orphan drug designation, +1 more

5 terms

kaplan-meier technical

"the Kaplan-Meier survival analysis and the timing of responses"

A Kaplan-Meier estimate is a statistical curve that shows how long it takes for a particular event—such as recovery, relapse, or death—to occur in a group over time, with the curve stepping down as events happen. Investors use these curves to assess the duration and timing of a treatment's or risk's effects—like watching how many light bulbs remain working week by week—because the timing and likelihood of outcomes influence clinical decisions, regulatory approval, and revenue prospects.

pharmacokinetics medical

"the pharmacokinetics of VCN-01 were not different between the 2 doses"

Pharmacokinetics is the study of how a substance, such as a drug or chemical, moves through and is processed by the body over time. It tracks how it is absorbed, distributed, broken down, and eventually eliminated. For investors, understanding pharmacokinetics helps gauge the effectiveness, safety, and potential risks of new medications or treatments, which can influence a company’s success and valuation in the healthcare industry.

objective response rate medical

"Secondary endpoints include objective response rate"

The objective response rate (ORR) is the percentage of patients in a clinical trial whose tumors measurably shrink or disappear according to preset rules. Investors use it as a quick, objective signal of a drug’s ability to produce a clear treatment effect—like counting how many plants visibly respond after applying a new fertilizer—and higher ORR can improve odds of regulatory approval, commercial success, and company valuation.

orphan drug designation regulatory

"VCN-01 has been granted Orphan Drug designation"

Orphan drug designation is a special status given to medicines developed to treat rare diseases affecting only a small number of people. This status often provides benefits like faster approval processes and financial incentives, making it more attractive for companies to develop these drugs. For investors, it signals potential for exclusive market rights and reduced competition, which can impact the drug’s profitability.

priority review voucher regulatory

"may be eligible to receive a Priority Review Voucher"

A priority review voucher is a transferable regulatory incentive that lets a company move a future drug or device application to the front of the review line, shortening the review period by several months. For investors it matters because the voucher can speed up market access for a high-value product or be sold to other companies for significant cash, acting like a tradable fast-pass that can accelerate revenue or create immediate financial upside.

AI-generated analysis. How Rhea-AI works. Not financial advice.

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- Publication in this premier journal after rigorous peer review validates the VIRAGE study and supports the continued evaluation of VCN-01 in the treatment of metastatic pancreatic cancer -

- Data are consistent with an immune mediated mechanism of action for VCN-01 that may enhance the antitumor effects of a range of coadministered pancreatic cancer therapies -

- The feasibility of administering more frequent repeated VCN-01 doses to potentially improve clinical outcomes in metastatic pancreatic cancer patients is currently being evaluated in the VIRAGE2 Phase 2a clinical trial -

ROCKVILLE, Md., Sept. 30, 2026 (GLOBE NEWSWIRE) -- Theriva™ Biologics (NYSE American: TOVX), a diversified clinical-stage company developing therapeutics designed to treat cancer and related diseases in areas of high unmet need, today announced that detailed analysis of results from the VIRAGE Phase 2b clinical trial of VCN-01 (zabilugene almadenorepvec) in metastatic pancreatic cancer patients were published in Nature Medicine. The article, entitled “Intravenous hyaluronidase-expressing oncolytic adenovirus with chemotherapy in metastatic pancreatic cancer: a randomised phase 2b trial”, can be read here.

“We are proud to see the peer-reviewed results from the VIRAGE trial published in Nature Medicine and made available to the entire scientific community,” said Manel Cascalló, PhD, General Director of Theriva Biologics S.L. and co-author of the article. “As elaborated in the publication, improved overall survival, progression free survival, and duration of response were observed in metastatic pancreatic cancer patients treated with VCN-01 combined with standard-of-care (SoC) gemcitabine/nab-paclitaxel chemotherapy compared to patients receiving SoC chemotherapy alone. Moreover, the Kaplan-Meier survival analysis and the timing of responses in VCN-01 treated patients suggest an immune mediated mechanism of action for VCN-01 in addition to its stroma degrading effects. We are excited about the potential for VCN-01 in different cancer therapy combinations, and we are extremely grateful to the patients who participated in VIRAGE, their families, our clinical investigators and their teams, and our co-authors for their commitment, dedication and diligence.”

As previously reported, greater improvements in patient survival during the VIRAGE study were observed in metastatic pancreatic cancer patients receiving 2 doses of VCN-01 administered 3 months apart, Following End-of-Phase 2 feedback from both the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA), Theriva has recently initiated VIRAGE2; a small Phase 2a study designed to evaluate the feasibility of more frequent, repeated dosing of VCN-01 in combination with SoC chemotherapy. The first patient in VIRAGE2 was treated in August 2026, and the study is expected to complete enrollment during the second half of 2026. Initial pharmacodynamic and safety/tolerability data are anticipated by Q3 2027. Results from VIRAGE2 will inform the VCN-01 dosing regimen for potential evaluation in a future pivotal Phase 3 clinical trial. For more details see About VIRAGE2 below.

In parallel with VIRAGE2, Theriva is engaging with the FDA to finalize the design of a potential Phase 2/3 study evaluating VCN-01 in children with retinoblastoma with vitreous seeds that are refractory/resistant to the use of current intravitreal chemotherapy. VCN-01 has received Rare Pediatric Disease designation for the treatment of retinoblastoma and may be eligible to receive a Priority Review Voucher if VCN-01 is approved in this indication by September 30, 2029.

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 is intended to enable 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 Company- and investigator-sponsored clinical trials in 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). VCN-01 has also been made available for compassionate use in retinoblastoma patients, and 2 patients have been treated in this program. VCN-01 has been granted Orphan Drug designation for the treatment of metastatic PDAC and retinoblastoma in Europe and the USA, as well as FDA Fast Track designation for the treatment of metastatic PDAC and Rare Pediatric Disease designation for the treatment of retinoblastoma. More information on VCN-01 clinical trials is available at Clinicaltrials.gov.

About VIRAGE

VIRAGE (EUCT 2024-511290-30-00; NCT05673811) was a two-arm, Phase 2b open-label, randomized, controlled, multicenter clinical trial in patients with histologically confirmed, newly-diagnosed metastatic PDAC. A total of 112 patients were enrolled at 5 sites in the U.S. and 9 sites in Spain. In both the control and VCN-01 (zabilugene almadenorepvec) treatment arms, patients received gemcitabine/nab-paclitaxel standard-of-care (SoC) chemotherapy in repeated 28-day cycles until disease progression. In the VCN-01 treatment arm only, patients were also administered intravenous VCN-01 seven-days prior to starting the first and fourth cycles of gemcitabine/nab-paclitaxel treatment (study days 1 and ~92 respectively). As previously reported and presented, PDAC patients in the VCN-01 plus gemcitabine/nab-paclitaxel SoC treatment arm demonstrated increased overall survival, progression free survival, and duration of response compared to patients in the control arm treated with gemcitabine/nab-paclitaxel SoC alone. Greater improvements in these parameters were observed in patients who received 2 doses of VCN-01 administered 3 months apart, and the pharmacokinetics of VCN-01 were not different between the 2 doses despite the presence of neutralizing antibodies.

About VIRAGE2

VIRAGE2 (EUCT: 2026-525566-21-00; NCT07701486) is a Phase 2a, single-arm, open-label, clinical trial in 6 evaluable patients with histologically confirmed, newly diagnosed metastatic PDAC enrolled at a single site in Spain. Patients are intended to receive at least three “macrocycles” of VCN-01 (zabilugene almadenorepvec) and gemcitabine/nab-paclitaxel SoC chemotherapy, followed by SoC gemcitabine/nab-paclitaxel cycles until disease progression. In each VCN-01 macrocycle, intravenous VCN-01 is administered on day 1 followed by gemcitabine/nab-paclitaxel SoC chemotherapy on days 8, 15, 22, 36, 43, and 50. Macrocycles are repeated on days 57 and 113. The primary objective of the VIRAGE2 trial is to evaluate whether administration of at least 3 doses of VCN-01, with 2 months between doses, is well tolerated by patients without adversely impacting VCN-01 pharmacodynamics. Primary endpoints for the trial are the adverse event profile and levels of VCN-01 viral genomes in blood. Secondary endpoints include objective response rate, duration of response, progression free survival, overall survival, and circulating levels of anti-VCN-01 neutralizing antibodies. Exploratory endpoints include estimates of potential VCN-01 shedding by measuring VCN-01 viral genomes in sputum and stool. The study is not formally powered for evaluation of clinical efficacy endpoints and is intended to support evaluation of the potential efficacy of the more frequent repeated dosing regimen in subsequent clinical trials.

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 candidate 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 remains open 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. Enrollment is paused and completion of this trial is pending receipt of grant funding or funding through a partnership or other collaboration. 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 publication in Nature Medicine validating the VIRAGE study and supporting the continued evaluation of VCN-01 in the treatment of metastatic pancreatic cancer; more frequent, repeated VCN-01 potentially improving clinical outcomes in metastatic pancreatic cancer patients; the potential for VCN-01 in different cancer therapy combinations, the VIRAGE2 study expecting to complete enrollment during the second half of 2026; initial pharmacodynamic and safety/tolerability data from VIRAGE2 being anticipated by Q3 2027; results from the VIRAGE2 study informing the VCN-01 dosing regimen for potential evaluation in a future pivotal Phase 3 clinical trial; administering at least 3 doses of VCN-01 in the VIRAGE2 trial given approximately 2 months apart in combination with standard-of-care chemotherapy; finalizing with the FDA the design of a potential Phase 2/3 study evaluating VCN-01 in children with retinoblastoma with vitreous seeds that are refractory/resistant to the use of current intravitreal chemotherapy; and receiving a Priority Review Voucher if VCN-01 is approved for the treatment of retinoblastoma by September 30, 2029. Important factors that could cause actual results to differ materially from current expectations include, among others, the Company’s ability to finalize protocols for future clinical trials evaluating VCN-01; results of future trials supporting further clinical development of VCN-01 and supporting the benefits of more frequent repeated dosing of VCN-01; the Company’s ability to obtain development funding and/or partnerships; the Company’s commencement of planned clinical trials, which remains subject to sufficient financing; the Company’s ability to raise capital and/or enter into one or more strategic alternatives, that may include a business combination, merger or reverse merger; 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 cancer 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 cancer patients; regulatory limitations relating to the Company’s ability to promote or commercialize its 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:
Kevin Gardner
LifeSci Advisors, LLC
kgardner@lifesciadvisors.com

Source: Theriva Biologics, Inc.

FAQ

AI-generated questions and answers. How Rhea-AI works. Not financial advice.

What did Theriva's VIRAGE Phase 2b trial show for VCN-01 in pancreatic cancer?

VCN-01 plus gemcitabine/nab-paclitaxel improved overall survival, progression-free survival and duration of response compared with chemotherapy alone. The randomized, open-label trial enrolled 112 patients with newly diagnosed metastatic pancreatic ductal adenocarcinoma. Greater improvements were observed among patients receiving two VCN-01 doses three months apart.

What dosing schedule and endpoints is Theriva testing in VIRAGE2?

VIRAGE2 evaluates whether at least three VCN-01 doses, two months apart, are well tolerated without adversely affecting the drug's biological activity. Its primary endpoints are the adverse event profile and VCN-01 viral genome levels in blood. Patients are intended to receive at least three treatment blocks combining VCN-01 with gemcitabine/nab-paclitaxel, followed by chemotherapy until disease progression.

Which patients would Theriva's potential VCN-01 retinoblastoma study evaluate?

The potential Phase 2/3 study would evaluate children with retinoblastoma with vitreous seeds refractory or resistant to current intravitreal chemotherapy. Theriva is engaging with the FDA to finalize the study design.

When could Theriva's VCN-01 qualify for a Priority Review Voucher?

VCN-01 may be eligible for a Priority Review Voucher if approved for retinoblastoma by September 30, 2029. It has received Rare Pediatric Disease designation for that indication; voucher eligibility remains conditional.