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Item 1. Business

2025-03-06 compared with 2024-03-25 · 227 added, 172 removed, 604 unchanged (40% of the section changed)

We are a diversified clinical-stage company developing therapeutics designed ot treat cancer and related diseases in areas of high unmet need.

We are a diversified clinical-stage company developing therapeutics designed to treat cancer and related diseases in areas of high unmet need.

As a result of the acquisition in March 2022 of Theriva Biologics, S.L.

(“VCN”, formerly named VCN Biosciences, S.L.), described in more detail below (the “Acquisition”), we began transitioning our strategic focus to oncology, which is now our primary focus, through the development of VCN’s new oncolytic adenovirus platform designed for intravenous and intravitreal delivery to trigger tumor cell death, to improve access of co-administered cancer therapies to the tumor, and to promote a robust and sustained anti-tumor response by the patient’s immune system.

Our lead product candidate, VCN-01, a clinical stage oncolytic human adenovirus that is modified to express an enzyme, PH20 hyaluronidase, is currently being administered in a Phase 2 clinical study for the treatment of pancreatic cancer, a Phase 1 clinical study for the treatment of retinalblastoma, a Phase 1 clinical study for the treatment of head and neck squamous cell carcinoma and a Phase 1 clinical study for the treatment of solid tumors.

(“VCN”, formerly named VCN Biosciences, S.L.), described in more detail below (the “Acquisition”), we transitioned our strategic focus to oncology through the development of VCN’s new oncolytic adenovirus platform designed for intravenous and intravitreal delivery to trigger tumor cell death, to improve access of co-administered cancer therapies to the tumor, and to promote a robust and sustained anti-tumor response by the patient’s immune system.

Prior to the Acquisition, our focus was on developing therapeutics designed to treat gastrointestinal (GI) diseases which included our clinical development candidates:

(1) SYN-004 (ribaxamase) which is designed to degrade certain commonly used intravenous (IV) beta-lactam antibiotics within the GI tract to prevent microbiome damage, thereby preventing overgrowth and infection by pathogenic organisms such Clostridioides difficile infection (CDI) and vancomycin resistant Enterococci (VRE), and reducing the incidence and severity of acute graft-versus-host-disease (aGVHD) in allogeneic hematopoietic cell transplant (HCT) recipients, and (2) 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.

(1) SYN-004 (ribaxamase) which is designed to degrade certain commonly used intravenous (IV) beta-lactam antibiotics within the GI tract to prevent microbiome damage thereby preventing overgrowth and infection by pathogenic organisms such as Clostridioides difficile infection (CDI), and vancomycin resistant Enterococci (VRE), and reducing the incidence and severity of acute graft-versus-host-disease (aGVHD) in allogeneic hematopoietic cell transplant (HCT) recipients, and (2) 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.

As part of our strategic transformation into an oncology focused company, we are exploring value creation options for our SYN-004 and SYN-020 assets, including out-licensing or partnering.

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allo-HCT allogeneic hematopoietic cell transplant.

CPI immune checkpoint inhibitor.

CSR clinical study report.

HNSCC head and neck squamous cell carcinoma.

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IVit intravitreal.

ODD Orphan Drug Designation.

For other abbreviations see the text.

¹Additional products with preclinical proof-of-concept include SYN-006 (carbapenemase) to prevent aGVHD and infection by carbapenem resistant enterobacteriaceae and SYN-007 (ribaxamase) DR to prevent antibiotic associated diarrhea with oral β-lactam antibiotics.

¹Additional products with preclinical proof-of-concept include SYN-006 (carbapenemase) to prevent aGVHD, CDI, and microbiome damage in patients treated with carbapenem antibiotics and SYN-007 (ribaxamase) DR to prevent antibiotic associated diarrhea with oral β-lactam antibiotics.

²Depending on funding/partnership.

SYN-004 may enter an FDA-agreed Phase 3 clinical trial for the treatment of CDI.

³We have an option-license agreement with Massachusetts General Hospital to develop SYN-020 in several potential indications related to inflammation and gut barrier dysfunction.

4 We have an option agreement with Sant Joan de Déu-Barcelona Children’s Hospital to license their intellectual property rights related to the use of VCN-01 in combination with topoisomerase I inhibitor chemotherapies for the treatment of cancer.

SYN-004 may enter a U.S.

Food and Drug Administration (“FDA”)-agreed Phase 3 clinical trial for the treatment of CDI.

Our Current Oncology-Focused Pipeline

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This novel class of anticancer agents has unique mechanisms of action compared to other cancer drugs.

Oncolytic viruses exploit the fact that cancer cells contain mutations that cause them to lose growth control and form tumors.

Oncolytic viruses (“OV”) exploit the fact that cancer cells contain mutations that cause them to lose growth control and form tumors.

Once inside a tumor cell, oncolytic viruses exploit the tumor cell machinery to generate thousands of additional copies of the virus, which then kill the tumor cell and spread to neighboring cells, causing a chain reaction of cell killing.

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Intravenous delivery has the potential to expand the therapeutic effect of OVs because the virus can infect both the primary tumor and tumor metastases throughout the body.

Our first product candidate, VCN-01, is a clinical stage oncolytic human adenovirus that is modified to express an enzyme,PH20 hyaluronidase, that degrades hyaluronan in the tumor stroma, which helps the virus and other molecules to penetrate and spread throughout the tumor.

Our first product candidate VCN-01, is a clinical stage oncolytic human adenovirus that is modified to express an enzyme, PH20 hyaluronidase, that is designed to degrade hyaluronan in the tumor stroma, which helps the virus and other molecules to penetrate and spread throughout the tumor.

VCN-01 can be used alone or in combination with other cancer therapies, such as chemotherapy and immunotherapy, for difficult to treat cancers.

An expanding intellectual property portfolio supports our oncology programs, and because our products are characterized as biologics with Orphan Drug designation in our target indications, they will be further protected by data and/or market exclusivity in major markets.

An expanding intellectual property portfolio supports our oncology programs, and because our products are characterized as biologics with Orphan Drug designation in our target indications, if approved by the FDA they will be further protected by data and/or market exclusivity.

VCN-01 — An oncolytic human type-5 adenovirus engineered for intravenous administration and to express a tumor matrix degrading enzyme (PH20 hyaluronidase) that facilitates the entry of therapeutics and immune cells into tumors

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VCN-01 is designed to overcome the stroma barrier problem by expressing the hyaluronan degrading enzyme PH20 hyaluronidase after it infects tumor cells.

Expression of PH20 by VCN-01 is designed to degrade the hyaluronic acid within the tumor stroma and improves virus spread throughout the tumor.

Based upon the foregoing, we believe our oncolytic virus platform, exemplified by VCN-01, represents a new and potentially powerful form of therapy that combines tumor cell killing, anti-tumor immunity and stroma destruction after intravenous delivery.

Expression of PH20 by VCN-01 is designed to degrade the hyaluronic acid within the tumor stroma and to improve virus spread throughout the tumor.

Based upon the foregoing, we believe our oncolytic virus platform, exemplified by VCN-01, represents a new and potentially powerful form of therapy to be combined with tumor cell killing, anti-tumor immunity and stroma destruction after intravenous delivery.

The VCN-01 product candidate is provided as a sterile liquid concentrate that is diluted for infusion or injection.

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Our initial indication for clinical development is unresectable metastatic pancreatic cancer, a disease for which there is currently no cure and only limited therapeutic options.

VCN-01 has been administered to 116 patients across multiple Phase 1 clinical trials and Phase 2 VIRAGE trial, including patients with pancreatic cancer, head and neck squamous cell carcinoma, ovarian carcinoma, colorectal cancer, and retinoblastoma.

VCN-01 has been administered to 142 patients across multiple Phase 1 clinical trials and the Phase 2 VIRAGE trial, including patients with pancreatic cancer, head and neck squamous cell carcinoma, ovarian cancer, colorectal cancer, and retinoblastoma.

Pancreatic Ductal Adenocarcinoma

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It can be located either in the head of the pancreas or in the body-tail.

Pancreatic cancer usually metastasizess to the liver and peritoneum.

Pancreatic cancer usually metastasizes to the liver and peritoneum.

Other less common metastatic sites are the lungs, brain, kidney and bone.

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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.

It is generally assumed that only 10% of cases are resectable at presentation, whereas 30-40% of patients are diagnosed at the locally advanced/unresectable stage and 50-60% present with distant metastases.

PDAC Clinical Unmet Need and Market Opportunity

PDAC is one of the most fatal cancers, accounting for the 4 th highest cause of cancer-associated deaths in the US and the European Union.

PDAC is currently the 3 rd leading cause of cancer-related deaths in the United States and the 4 th leading cause of cancer-related deaths in the European Union and it is projected to become the second leading cause of cancer-related deaths in the United States before 2030.

Despite significant research efforts, minimal progress has been achieved to date.

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In recent years, the combination of gemcitabine with albumin-bound paclitaxel (GA), and the combination of folic acid, 5-fluorouracil, irinotecan and oxaliplatin (FOLFIRINOX) have emerged as the standard of care.

More recently, liposomal irinotecan, approved for second line PDAC in combination with fluorouracil and leucovorin, has shown potential as first line therapy when administered along with 5-FU and other chemotherapies.

In 2024, liposomal irinotecan (ONIVYDE®), which was previously approved for second line PDAC in combination with fluorouracil and leucovorin, was approved in the United States and Europe as first line therapy for metastatic PDAC when administered along with oxaliplatin 5-FU and leucovorin (the NALIRIFOX regimen).

However, the results are still very poor and new therapeutic interventions are needed.

The increase is particularly evident in younger people and several studies anticipate that pancreatic cancer is expected to become the second leading cause of cancer-related death in the United States by 2030.

The increase is particularly evident in younger people.

The rising incidence of pancreatic cancer and its current economic burden place increased pressure to improve outcomes for patients.

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In June 2023, the FDA granted Orphan Drug designation to VCN-01 for the treatment of pancreatic cancer.

In May 2024, the FDA granted Fast Track designation to VCN-01 for the treatment of pancreatic cancer.

Phase 1a/Proof of Concept Trial of VCN-01 by intratumoral administration in PDAC

In September 2019, VCN presented a poster at the European Society for Molecular Oncology (“ESMO”) annual meeting describing initial mechanism of action data from a multicenter, Phase 1 dose escalation study of intratumoral (“IT”) VCN-01 administered to pancreatic cancer patients in combination with standard doses/schedules of either gemcitabine or nab-paclitaxel plus gemcitabine (NCT02045589).

The study was conducted at three hospitals in Spain and 8 patients with confirmed histologic diagnosis of unresectable PDAC amenable to endoscopic ultrasound guided (“EUS”) injection were treated with 3 injections (coincident with 1 st day of the chemotherapy cycles) at two different dose levels of VCN-01 (six patients had metastatic disease and two had locally advanced disease).

The study was conducted at three hospitals in Spain and 8 patients with confirmed histologic diagnosis of unresectable PDAC amenable to endoscopic ultrasound guided (“EUS”) injection were treated with 3 injections (coincide with 1 st day of the chemotherapy cycles) at two different dose levels of VCN-01 (six patients had metastatic disease and two had locally advanced disease).

The treatment regimen was generally well-tolerated.

however, one patient died from severe intraabdominal fluid collection that was considered to be related to VCN-01 treatment.

VCN-01-related adverse events were dose-dependent and mainly consisted of asthenia (6 patients), fever (4 patients), and transaminase increases (3 patients).

One patient died from severe intra-abdominal fluid collection that was considered to be related to VCN-01 treatment.

Evaluation of virus pharmacokinetics and PH20 levels in serum were consistent with strong virus replication in the tumors.

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In March 2022, we announced the peer-reviewed publication of a Phase 1, multicenter, open-label, dose-escalation study investigating the safety, tolerability and biodistribution of intravenous VCN-01 oncolytic adenovirus with or without standard-of-care (SoC) chemotherapy (gemcitabine/nab-paclitaxel) in patients with advanced solid tumors (NCT02045602).

The data, published in the Journal for ImmunoTherapy of Cancer, suggests that intravenous treatment with VCN-01 is feasible and has an acceptable safety profile, with encouraging biological and clinical activity.

The data, published in the Journal for ImmunoTherapy of Cancer, suggests that intravenous treatment with VCN-01 is feasible and has been well tolerated, with encouraging biological and clinical activity.

(Journal for Immunotherapy of Cancer 2022;10:e003255.

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In January 2023, we dosed the first patients in VIRAGE, the Phase 2b randomized, open-label, placebo-controlled, multicenter clinical trial of systemically administered VCN-01 in combination with standard-of-care (SoC) chemotherapy (gemcitabine/nab-paclitaxel) as a first line therapy for patients with newly-diagnosed metastatic pancreatic ductal adenocarcinoma.

The study is expected to enroll 92 patients and be conducted at approximately 25 sites in the US and EU.

The study is being conducted at approximately 17 sites in the US and EU.

Two doses of VCN-01 are included in the treatment arm:

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Patient dosing was initiated in the U.S.

in July 2023 and the fourteen patients have received their second doses of intravenous VCN-01, which were well tolerated and demonstrated the expected VCN-01 safety profile.

On February 7, 2024, we announced that the Independent Data Monitoring Committee (IDMC) recommended the continuation of enrollment as planned into VIRAGE, a multinational, Phase 2b, randomized, open-label, controlled clinical trial evaluating VCN-01 in combination with standard-of-care chemotherapy (gemcitabine/nab-paclitaxel) as a first-line therapy for patients with metastatic pancreatic ductal adenocarcinoma (PDAC).

According to the IDMC's comprehensive assessment of clinical data from patients enrolled across 6 sites open in the U.S.

and 9 sites open in Spain, the ongoing Phase 2b trial will continue without any changes to the protocol.

in July 2023 and on September 23, 2024, we announced that we have achieved our target patient enrollment of 92 evaluable patients in the VIRAGE Phase 2b clinical trial.

Thirty-six patients have received their second doses of intravenous VCN-01, which were well tolerated and demonstrated the expected VCN-01 adverse event profile.

Topline data for the VIRAGE Phase 2b clinical trial is anticipated for Q2 2025.

On January 30, 2024, the accumulated clinical data from patients enrolled across 6 sites open in the U.S.

and 9 sites open in Spain were reviewed by an Independent Data Monitoring Committee (IDMC).

According to the IDMC’s assessment, the ongoing Phase 2b trial continued without any changes to the protocol.

No safety concerns were raised based on the evaluation of data presented at the IDMC meeting.

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Importantly, no additional toxicities were observed in patients receiving a second dose of VCN-01, providing the first clinical evidence of the feasibility of repeated systemic dosing.

VIRAGE remains on track to complete enrollment in the first half of 2024.

On May 10, 2024, we presented data demonstrating enhanced anti-tumor effects in human pancreatic cancer xenograft-bearing mice treated with lead product candidate VCN-01 and liposomal irinotecan.

These data support the potential synergy of VCN-01 and first-line pancreatic cancer chemotherapy regimens.

On May 23, 2024, we announced that the FDA granted Fast Track Designation (FTD) to lead clinical candidate VCN-01 in combination with gemcitabine and nab-paclitaxel to improve progression-free survival and overall survival in patients with metastatic pancreatic adenocarcinoma.

On June 1, 2024, we presented the design of VIRAGE trial in a poster at the American Society of Clinical Oncology (ASCO) Annual Meeting 2024 Congress held and in Chicago (Illinois) from May 31- June 4, 2024.

The poster discussed the objectives, endpoints and key inclusion and exclusion criteria included in the trial protocol, together with the treatment schedule for each arm of the study.

On December 5, 2024 we announced the outcomes of a Type D meeting with the FDA to obtain guidance on the design of a Phase 3 clinical study of VCN-01 in combination with standard-of-care chemotherapy for the treatment of PDAC.

FDA advised that the optimal path forward for the VCN-01 PDAC program is to conduct a stand-alone Phase 3 study of VCN-01 with gemcitabine/nab-paclitaxel.

The FDA provided general agreement with our proposed design for a Phase 3 clinical study and indicated that inclusion of additional standard-of-care chemotherapy for PDAC was not necessary as it would complicate the study design and analysis.

The FDA meeting also highlighted the FDA’s preferences regarding certain statistical elements of confirmatory clinical studies, including methods for sample size estimation and the study population(s) used for data analysis

On February 4 th , 2025, we received Scientific Advice from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) on the design of a Phase 3 clinical study of VCN-01 in combination with standard-of-care chemotherapy for the treatment of metastatic PDAC.

Consistent with feedback from the FDA, CHMP advised that a marketing authorization application (MAA) for VCN-01 in metastatic PDAC could be supported by positive results from a randomized, controlled, stand-alone Phase 3 study comparing VCN-01 combined with gemcitabine/nab-paclitaxel to gemcitabine/nab-paclitaxel standard-of-care alone.

The Scientific Advice also included CHMP suggestions regarding the study populations, inclusion/exclusion criteria, randomization and blinding, priority endpoints, and proposed statistical strategies for data analysis.

An additional note from the EMA Committee for Orphan Medicinal Products (COMP) noted that the potential benefit of VCN-01 with gemcitabine/nab-paclitaxel in a Phase 3 trial will be compared with the therapeutic effects of the other approved standard-of-care chemotherapies (FOLFIRINOX, NALIRIFOX) when considering maintenance of the Orphan Medicinal Product status of VCN-01 at the time of an MAA.

Retinoblastoma

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During the third quarter of 2017, VCN entered into a Clinical Trial Agreement with Hospital Sant Joan de Déu (Barcelona, Spain) to conduct an investigator sponsored Phase 1 clinical study evaluating the safety and tolerability of two intravitreal injections of VCN-01 in patients with intraocular retinoblastoma refractory to systemic, intra-arterial or intravitreal chemotherapy, or radiotherapy, in whom enucleation was the only recommended treatment (NCT03284268).

Patients received two doses of VCN-01 injected 14 days apart using a dose escalation regimen.

At this time, the dose-escalation phase of the study has already been completed in 6 patients distributed in two cohorts (2 x 10 9 vp/eye and 2 x 10 10 vp/eye).

VCN-01 was well tolerated to date after intravitreal administration, although some degree of intravitreal inflammation and associated turbidity were observed.

Inflammation has been managed and potential turbidity minimized with local and systemic administration of anti-inflammatory drugs.

Patients received two intravitreal injections of VCN-01, 14 days apart, at a dose of either 2 x 10 9 vp/eye (n=1) or 2 x 10 10 vp/eye (n=8).

The clinical database for the study has now been locked and the clinical study report is being prepared.

On April 23, 2024, we announced positive topline data from this study, with agreement by the study Monitoring Committee that the study had a positive outcome.

VCN-01 was well tolerated after intravitreal administration at the 2 doses and the most frequently reported treatment-related adverse events were Grade 1 or 2.

There were no dose limiting toxicities and no ocular or systemic toxicities equal to or greater than Grade 3 during the evaluation period.

● Some degree of ocular inflammation and associated turbidity was observed after VCN-01 injection.

Inflammation was managed, and vitreous haze improved in some cases, by local and systemic administration of anti-inflammatory drugs.

● VCN-01 does not appear to change the retinal function, and selective VCN-01 replication in retinoblastoma cells has been observed by immunohistochemical analysis.

Replication within retinoblastoma tumors over time was detected and VCN-01 reduced the number of vitreous seeds in 4 out of 5 patients treated at 2 x 10 10 vp/eye (n=5).

The investigator has reported that one patient treated with VCN-01 has had a complete regression lasting more than 30 months.

This Phase 1 trial with VCN-01 has now completed enrollment and a total of nine (9) patients been treated.

This study is expected to complete patient follow-up in Q1 2024.

A pre-IND meeting with the FDA was held on December 19, 2023 to discuss the path forward for VCN-01 as an adjunct to chemotherapy in pediatric patients with advanced retinoblastoma.

● Replication within retinoblastoma tumors over time was detected

● Intravitreal VCN-01 demonstrated promising antitumor activity:

o Four patients presented a response characterized by unequivocal improvement in vitreous seed density.

o Eye enucleation was avoided in 3 patients to date, one of whom has retained their eye after 4 years of follow-up.

Per the terms of the clinical trial agreement, the determination by the study Monitoring Committee that the study had a positive outcome means we received an exclusive, worldwide technology license, and related patents from Hospital Sant Joan de Déu for the treatment of pediatric patients with advanced retinoblastoma and we will pay to Hospital Sant Joan de Déu the amount of three hundred twenty thousand, two hundred and sixty five Euros (€320,265) or approximately $334,000, upon receipt by us of the final clinical study report.

A pre-Investigational New Drug (“IND”) meeting with the FDA was held on December 19, 2023 to discuss the path forward for VCN-01 as an adjunct to chemotherapy in pediatric patients with advanced retinoblastoma.

The FDA provided some guidance on the potential endpoints and patient population for an advanced clinical trial and encouraged submission of a formal protocol under a US IND in order to provide more detailed commentary.

Angel Montero-Carcaboso presented new data from the study for which he is the lead investigator atan oral presentation entitled “Topotecan enhances oncolytic adenovirus infection, replication and antitumor activity in retinoblastoma,” at Fundació Sant Joan de Déu at the SIOP 2022 Congress of the International Society of Pediatric Oncology, that was held in Barcelona, Spain from September 28-October 1, 2022.

The new data from the study for which Dr.

Angel Montero-Carcaboso is the lead investigator further support evaluation of VCN-01, an oncolytic adenovirus expressing hyaluronidase, and topotecan for the treatment of refractory retinoblastoma.

Key data and conclusions showcased in the SIOP presentation include:

● VCN-01 treatment in combination with topotecan, but not with carboplatin or melphalan, significantly increased VCN-01 infection and replication in retinoblastoma cells (p=0.0007) in vitro.

● In athymic mice engrafted with human retinoblastomas, topotecan administered systemically after intratumoral VCN-01 increased viral genome replication and the number of VCN-01 infected cells when compared to administration of VCN-01 alone (p = 0.0002).

● Sequential administration of intratumoral VCN-01 followed by systemic topotecan significantly increased median ocular survival, compared to VCN-01 alone (p =0.0364).

On July 30, 2024, we received notice from the FDA that we had been granted Rare Pediatric Drug Designation (RPDD) for VCN-01 for the treatment of retinoblastoma.

The FDA grants RPDD for rare diseases (fewer than 200,000 affected persons in the United States) that are serious and life-threatening and primarily affect children ages 18 years or younger.

If a Biologics License Application for VCN-01 for the treatment of retinoblastoma is approved by the FDA by September 30, 2026, we may be eligible to receive a Priority Review Voucher.

Previously, the FDA granted orphan drug designation to VCN-01 for treatment of retinoblastoma.

On October 11, 2024, the European Commission adopted the European Medicines Agency (EMA) recommendation to grant Orphan Medicinal Product Designation to VCN-01 for the treatment of retinoblastoma

VCN-01 in combination with Immunomodulatory therapeutics

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Preclinical experiments demonstrated that VCN-01 significantly increased extravasation of an anti-PD-L1 antibody into subcutaneous xenograft tumors compared to non-treated (PBS) tumors and also that PH20 hyaluronidase improves the ingress of T-cells in animal models.

Thus, we hypothesize that the administration of VCN-01 into the tumor will help to overcome the observed resistance to PD-L1 checkpoint inhibitors and to mesothelin-directed CAR-T cells.

We believe that the administration of VCN-01 into the tumor may help to overcome the observed resistance to PD-L1 checkpoint inhibitors and to mesothelin-directed CAR-T cells.

Phase 1 Trial of intravenous VCN-01 in Combination with Durvalumab in Subjects with Recurrent/ Metastatic SCCHN

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and downregulation of matrix-related pathways after VCN-01 administration.

The last patients in this study are currently being followed for overall survival and patent samples are being analyzed to evaluate potential VCN-01 pharmacodynamic effects.

On October 16, 2023, we presented additional data from this study in a poster at the European Society for Medical Oncology (ESMO) 2023 Congress held virtually and in Madrid, Spian from October 20-24, 2023.

The study has been completed and the clinical study report is being prepared.

On October 16, 2023, we presented additional data from this study in a poster at the European Society for Medical Oncology (ESMO) 2023 Congress held virtually and in Madrid, Spain from October 20-24, 2023.

Key data and conclusions featured in the ESMO presentation include:

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● Observed an increase in CD8 T cells, a marker of tumor inflammation and an upregulation of PD-L1 in tumors.

● Increase of PDL1-CPS (16/21;

● Increase of PDL1-combined positive score (CPS;

p=0.013) and CD8 T-cells (12/21;

p=0.007) from baseline were found in tumor biopsies.

● There was a statistical significant correlation between OS observed in patients and CPS on day 8 (p=0.005).

● There was a statistically significant correlation between OS observed in patients and CPS on day 8 (p=0.005).

Phase 1 Trial evaluating the safety and feasibility of huCART-meso cells when given in combination with VCN-01

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On July 8, 2022, we were notified that the first patient to be dosed with VCN-01 had passed the safety evaluation period in this study.

The study is on-going.

On June 22, 2023, at their Cellicon Valley conference, and again at the Society for Immunotherapy of Cancer (SITC) meeting in San Diego, CA on November 3, 2023, and the International Oncolytic Virotherapy Conference (IOVC2023) in Calgary on November 13 2023, University of Pennsylvania investigators presented preliminary clinical safety and pharmacokinetic data from this study highlighting the feasibility of administering VCN-01 in sequence with huCART-meso cells in pancreatic and ovarian cancer patients.

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The peak and duration of huCART-meso T cells in the peripheral blood as well as duration of stable disease in evaluable patients showed encouraging trends.

The study will test higher doses of VCN-01 and will interrogate tumor biopsies to gain further insights.

The results will inform and guide optimization of the combination of CAR T cells with oncolytic virus.

On October 16, 2024, at the 2024 Advancing Gene Therapy and Cell Therapies for Cancer conference by the American Society for Gene and Cell Therapy in Philadelphia, University of Pennsylvania investigators presented results from the Phase 1 trial of huCART-meso cells administered in combination with VCN-01 in patients with pancreatic and serous epithetlial ovarian cancer.

Safety was in line with expectations from monotherapy studies and 3.3x10 12 was defined as the dose for further development.

The C max of huCART-meso cells showed some signs of enhancement in patients previously infused with VCN-01.

66.6% (4 out of 6) patients with measurable disease receiving huCART-meso after VCN-01 showed tumor shrinkage, indicating a promising trend in disease stabilization in patients receiving huCART-meso and VCN-01 compared to either agent alone.

On November 19, 2024 we were notified by the investigators that they would not continue with the present clinical trial, instead preferring to focus on advancement of a next-generation mesothelin-specific CAR-T.

This new CAR-T could potentially be evaluated in combination with VCN-01 in a future clinical trial.

Phase 1 Trial evaluating the intravenous administration of VCN-01 in patients prior to surgical resection of high-grade brain tumors

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When the natural balance or normal function of these microbial species is disrupted, a person’s health can be compromised.

All of our programs are supported by our growing intellectual property portfolio.

We are maintaining and building our patent portfolio through:

filing new patent applications;

prosecuting existing applications;

and licensing and acquiring new patents and patent applications.

All of our programs are supported by our established intellectual property portfolio and prosecution of existing applications.

We are exploring value creation options for our SYN-004 and SYN-020 assets, including out-licensing or partnering.

SYN-004 (ribaxamase) — Prevention of antibiotic-mediated microbiome damage, thereby preventing overgrowth and infection by pathogenic organisms such as Clostridioides difficile infection (CDI) and vancomycin resistant Enterococci (VRE), and reducing the incidence and severity of acute graft-versus-host disease (aGVHD) in allogeneic HCT recipients

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Other risk factors for CDI include hospitalization, prolonged length of stay (estimated at 7 days), underlying illness, and immune-compromising conditions including the administration of chemotherapy and advanced age.

According to a paper published in BMC Infectious Diseases (Desai K et al.

BMC Infect Dis.

303) the economic cost of CDI was approximately $5.4 billion in 2016 ($4.7 billion in healthcare settings;

$725 million in the community) in the U.S., mostly due to hospitalizations.

Limitations of Current Treatments and Market Opportunity

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According to the European Society of Clinical Microbiology and Infections Disease (ECCMID), failure to address AMR could lead to a potential “antibiotic Armageddon”, resulting in 10 million deaths worldwide by 2050 and may cost as much as $100 trillion in worldwide economic output.

According to a paper published in BMC Infectious Diseases,”Epidemiological and economic burden of Clostridium difficile in the United States:

estimates from a modeling approach”.

(Desai et.al., BMC Infect Dis 16:

303), it is estimated that approximately 606,000 patients are infected with C.

difficile annually in the U.S., and it has been reported that approximately 44,500 deaths are attributable to CDI-associated complications each year.

According to IMS Health Incorporated*, in 2016, the potential addressable market for SYN-004 (ribaxamase) included approximately 227 million doses of intravenous Penicillin and Cephalosporin antibiotics which were administered in the United States and which may contribute to the onset of CDI.

Additional data derived from IMS Health Incorporated states that in 2016, the worldwide market for SYN-004 (ribaxamase)-addressable intravenous beta-lactam antibiotics was approximately 7.5 billion doses, which may represent a multi-billion-dollar market opportunity for us.

The Centers for Disease Control estimates the crude overall incidence rate of CDI in the United states to be 121.2 cases per 100,000 persons (approximately 500,000 patients) with a higher rate of community associated compared to healthcare associated infection (CDC Emerging Infections Program Healthcare-Associated Infections–Community Interface Report Clostridioides difficile Infection Surveillance, 2022.

https://www.cdc.gov/healthcare-associated-infections/media/pdfs/2022-CDI-Report-508.pdf) The overall incidence of CDI has declined since 2015 as better infection prevention practices and antimicrobial stewardship have decreased the number of healthcare associated acquired infections (Guh et al.

N Engl J Med.

however, the economic and social burdens of CDI remain high.

CDI infections are estimated to cost $5 billion per annum in the United States, primarily due to increased hospitalization and hospital length of stay, while mortality rates as high as 39% have been reported for patients with multiple episods of recurrent CDI (Feuerstadt et al.

BMC Infect Dis 23:132;

Malone et al.

Antimicrob Steward Healthc Epidemiol 3:e17.).

If approved, SYN-004 (ribaxamase) would be the first therapeutic intervention indicated to prevent the onset of antibiotic-mediated primary CDI.

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Schroeder, Associate Professor of Medicine, Division of Oncology, Bone Marrow Transplantation and Leukemia.

The Phase 1b/2a clinical trial will comprise a single center, randomized, double-blinded, placebo-controlled clinical trial of oral SYN-004 (ribaxamase) in up to 36 evaluable adult allogeneic HCT recipients.

The Phase 1b/2a clinical trial was a single center, randomized, double-blinded, placebo-controlled clinical trial of oral SYN-004 (ribaxamase) in up to 36 evaluable adult allogeneic HCT recipients.

The goal of this study is to evaluate the safety, tolerability and potential absorption into the systemic circulation (if any) of oral SYN-004 (ribaxamase;

150 mg four times daily) administered to allogeneic HCT recipients who receive an IV carbapenem or beta-lactam antibiotic to treat fever.

Study participants will be enrolled into three sequential cohorts administered a different study-assigned IV antibiotic.

Study participants were enrolled into three sequential cohorts administered a different study-assigned IV antibiotic.

Each cohort seeks to complete eight evaluable participants treated with SYN-004 (ribaxamase) and four evaluable participants treated with placebo.

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The study will also evaluate potential protective effects of SYN-004 on the gut microbiome as well as generate preliminary information on potential therapeutic benefits and patient outcomes of SYN-004 in allogeneic HCT recipients.

To date, we have completed the first of 3 cohorts (Cohort 1) in this study, which enrolled 19 patients who received at least 1 dose of study drug (SYN-004 or Placebo randomized 2:1).

Sixteen patients received at least one dose of intravenous (IV) meropenem and 12 of these patients completed sufficient doses of IV meropenem to be evaluable towards the study endpoints.

To date, we have completed 2 of 3 cohorts (Cohorts 1 and 2) in this study.

On September 27, 2022, we issued a press release announcing positive outcomes from the Data and Safety Monitoring Committee (“DSMC”) review of results from the first Cohort and their recommendation that the study may proceed to enroll Cohort 2 in which study drug (SYN-004 or Placebo) is administered in combination with the IV beta-lactam antibiotic piperacillin/tazobactam.

On November 3, 2022 we announced the first patient had been dosed in Cohort 2.

Patient dosing is on-going and if enrollment proceeds on the current schedule, we may be positioned to announce data readouts for the second cohort during the first half of 2024 and the third cohort during the first half of 2025.

On February 16, 2023 and April 13, 2023, we announced the presentation of safety and pharmacokinetic data from Cohort 1 of the Phase 1b/2a Clinical Trial of SYN-004 (ribaxamase) in allogeneic hematopoietic cell transplant recipients at the 2023 Tandem Meetings:

Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR and at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID), respectively.

On October 3, 2024, we announced a positive outcome from the DSMC review of results from the second Cohort of our 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.

Based on a review of the safety and pharmacokinetic data, the DSMC recommended that the study may proceed to enroll Cohort 3 in which study drug (SYN-004 or Placebo) will be administered in combination with the IV beta-lactam antibiotic cefepime.

Based upon our current available funding and our focus on our clinical development of VCN-01 we do not anticipate that enrollment for the third cohort will commence unless we obtain grant funding, or find a licensee or partner for the SYN-004 development program.

SYN-020 — Oral Intestinal Alkaline Phosphatase (IAP)

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While we believe SYN-020 may play a pivotal role in addressing acute and long-term complications associated with radiation exposure to the GI tract, we have also begun planning for potential development of SYN-020 in large market indications with significant unmet medical needs.

Such indications include celiac disease, non-alcoholic fatty liver disease (“NAFLD”), and indications to treat and prevent metabolic and inflammatory disorders associated with aging, which are supported by our collaboration with Massachusetts General Hospital (“MGH”).

Such indications include celiac disease, non-alcoholic fatty liver disease (“NAFLD”), and indications to treat and prevent metabolic and inflammatory disorders associated with aging.

On June 30, 2020, we submitted an IND application to the FDA in support of an initial indication for the treatment of radiation enteropathy secondary to pelvic cancer therapy.

On July 30, 2020, we announced that we received a study-may-proceed letter from the FDA to conduct a Phase 1a single-ascending-dose (“SAD”) study in healthy volunteers designed to evaluate SYN-020 for safety, tolerability and pharmacokinetic parameters (NCT04815993).

On April 1, 2021, we announced that enrollment had commenced in the Phase 1 SAD clinical trial of SYN-020.

On June 29, 2021, we announced that enrollment, patient dosing and observation had been completed in the Phase 1, open-label, SAD study of SYN-020.

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During the third quarter of 2021 we initiated a Phase 1 clinical study evaluating multiple ascending doses (“MAD”) of SYN-020 (NCT05045833).

On October 21, 2021 we announced that patient enrollment, dosing, and observation commenced in the Phase 1 MAD study of SYN-020.

The placebo-controlled, blinded study enrolled 32 healthy adult volunteers into four cohorts with SYN-020 administered orally in doses ranging from 5 mg to 75 mg twice daily for 14 days with a follow-up evaluation at day 35.

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Additionally, fecal SYN-020 analyses verified intestinal bioavailability while plasma levels of SYN-020 were below the limit of quantitation in all samples at all timepoints verifying that SYN-020 was not absorbed into the systemic circulation.

During the second quarter of 2020, we announced that we entered into an agreement with Massachusetts General Hospital (“MGH”) granting us an option for an exclusive license to intellectual property and technology related to the use of IAP to maintain GI and microbiome health, diminish systemic inflammation, and treat age-related diseases.

During the second quarter of 2021, we announced an amendment to our option for an exclusive license agreement with MGH to include intellectual property and technology related to the use of SYN-020 to inhibit liver fibrosis in select diseases, including NAFLD.

Research published by a team of investigators led by Richard Hodin, MD, Chief of the Massachusetts General Hospital Division of General and Gastrointestinal Surgery and Professor of Surgery, Harvard Medical School, evaluated long-term oral supplementation of IAP, including SYN-020, in mice.

Hodin’s research demonstrated that IAP administration, starting at 10 months of age, slowed the microbiome changes, gut-barrier dysfunction, and gastrointestinal and systemic inflammation that normally accompany aging.

Additionally, the IAP administration resulted in improved metabolic profiles in the aged mice, diminished frailty, and extended lifespan.

Under the terms of the agreement, we are granted exclusive rights to negotiate a worldwide license with MGH to commercially develop SYN-020 to treat and prevent metabolic and inflammatory diseases associated with aging.

If executed, we plan to use this license in the advancement of an expanded clinical development program for SYN-020.

The Phase 1 data from our SAD and MAD studies are intended to support the development of SYN-020 in multiple clinical indications including radiation enteritis, NAFLD, celiac disease, and indications supported by our collaboration with Massachusetts General Hospital.

The option expired unexercised on July 1, 2024.

With our transition to an oncology focused Company, we are exploring strategic opportunities to enable advancement of this potentially valuable asset.

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As part of our strategic transformation into an oncology focused company, we are exploring value creation options for our SYN-004 and SYN-020 assets, including out-licensing or partnering.

Research Programs

VCN-11 Albumin Shield™ Technology

VCN-11 is a novel virus that we believe has the potential to extend our OV platform.

VCN-11 has been engineered to contain all of the features of VCN-01 as well as an additional modification to include an albumin binding domain (ABD) in the virus capsid.

VCN-01 + Topoisomerase Inhibitors

On May 10, 2024, we presented non-clinical describing enhanced anti-tumor effects in human pancreatic cancer xenograft-bearing mice treated with lead product candidate VCN-01 and liposomal irinotecan in a poster at the 27 th American Society of Gene and Cell Therapy (ASGCT) 2024 Congress held in Baltimore (Maryland) from May 7-11, 2024.

These data support the potential synergy of VCN-01 and additional first-line pancreatic cancer chemotherapy regimens FOLFIRINOX and NALIRIFOX.

Key finding reported in the poster include:

● The combination of VCN-01 + topoisomerase I (topo1) inhibitors, such as liposomal irinotecan, has a tolerable toxicity profile and may improve efficacy in the treatment of human pancreatic cancer.

● Viral protein expression was increased in human pancreatic cancer cell lines when they were exposed to topo1 inhibiting chemotherapeutics, irinotecan, its active metabolite, SN-38, and topotecan.

● Synergy of VCN-01 plus liposomal irinotecan was observed in animals bearing subcutaneous human pancreatic tumors.

In human pancreatic mouse xenograft models, treatment with VCN-01 at a dose of 4x1010 vp or liposomal irinotecan alone (at both the 10 mg/kg and 5 mg/kg doses) resulted in significant tumor growth inhibition compared to saline.

Combination therapy with VCN-01 + liposomal irinotecan at either dose displayed significantly reduced tumor growth compared to each treatment alone.

qPCR analyses performed on tumors collected at end of study confirmed the presence of viral genomes, indicating ongoing transcriptional activity of VCN-01, which is consistent with viral replication for several days after administration.

VCN-X Next Generation OVs and Albumin Shield™ Technology

In parallel with VCN-01 clinical development, we are developing next-generation oncolytic adenoviruses (termed VCN-X) with novel therapeutic payloads and structural modifications to increase tumor cell killing and improve systemic virus pharmacokinetics.

Preclinical proof-of-concept has been established with VCN-11, which has been engineered to contain all of the features of VCN-01 as well as an additional modification to include an albumin binding domain (ABD) in the virus capsid.

The virus capsid is the target for neutralizing antibodies (NAbs) that are generated by the host immune system to destroy circulating viruses.

The presence of an albumin binding domain, however, blocks the binding of most neutralizing antibodies, which allows the virus to reach the tumor following intravenous administration.

This “Albumin Shield” works because human blood contains a large amount of albumin to coat the VCN-11 virus.

The presence of an ABD, however, blocks the binding of most neutralizing antibodies, which allows the virus to reach the tumor following intravenous administration.

This “Albumin Shield” works because human blood contains a large amount of albumin to coat the ABD-containing virus.

Importantly, this coating of albumin appears to be displaced after the virus reaches tumor cells to infect them.

In pre-clinical mouse studies to test the functionality of the “Albumin Shield”, mice pre-immunized with virus are able to completely neutralize an unmodified OV because they have a large concentration of neutralizing antibodies in their blood.

By contrast, viruses containing the albumin binding domain such as VCN-11 are not neutralized and retain their ability to infect and destroy tumor cells.

We believe these results support the further development of VCN-11 for tumors in which rapid multi-dosing may be beneficial.

In the second quarter of 2020, VCN had several interactions with Spanish regulatory authorities (AEMPS) to agree on the design of the non-clinical GLP toxicology and biodistribution studies that are required to support a first-in-human clinical trial for VCN-11.

By contrast, viruses such as VCN-11 that contain the ABD are not neutralized and retain their ability to infect and destroy tumor cells.

We believe the results with VCN-11 support the application of the Albumin Shield technology in our VCN-X program to advance treatments for tumors in which rapid multi-dosing may be beneficial.

In March 2021, preclinical data obtained with VCN-11 was published (J Control Release.

2021 Apr 10;332:517-528), showing that VCN-11 induced 450 times more cytotoxicity in tumor cells than in normal cells.

VCN confirmed VCN-11 hyaluronidase production by measuring the activity of the PH20 enzyme with a hyaluronic acid-degradation assay, and by measuring PH20 activity in VCN-11 infected tumors in vivo.

VCN-11 evaded NAbs from different sources and tumor levels of VCN-11 were demonstrated in the presence of high levels of NAbs in vivo, whereas the control virus without ABD was neutralized.

2021 Apr 10;332:517-528), showing that the ABD-containing virus induced 450 times more cytotoxicity in tumor cells than in normal cells.

Hyaluronidase production was confirmed by measuring the activity of the PH20 enzyme with a hyaluronic acid-degradation assay, and by measuring PH20 activity in VCN-11 infected tumors in vivo.

The ABD-containing virus evaded NAbs from different sources and tumor levels of virus were demonstrated in the presence of high levels of NAbs in vivo, whereas the control virus without ABD was neutralized.

VCN-11 showed a low toxicity profile in athymic nude mice and Syrian hamsters, allowing treatments with high doses and fractionated administrations without major toxicities (up to 1.2x10 11 vp/mouse and 7.5x10 11 vp/hamster).

VCN-11 increased ALT levels on day 3 within an acceptable range that returned to normal levels by day 9.

Fractionated intravenous administration of VCN-11 (splitting the dose into two portions administered 4 h apart) appeared to improve VCN-11 circulation kinetics and increase tumor levels.

VCN-11 showed antitumor efficacy in the presence of NAbs against Ad5 and itself.

In May 2022, we presented on VCN-11 at the 25th Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT).

The presentation included preclinical results showcasing the potential of VCN-11 to balance safety, with no major toxicities observed, and effectively target tumors after intravenous re-administration, even in the presence of high level NAbs.

Our internal discovery programs are currently evaluating new oncolytic viruses derived from VCN-11 that may expand the potential efficacy of Albumin Shield viruses.

SYN-006, SYN-007, other oncolytic virus

To date, our Research programs that have been directed to the development of GI acting products have generated preclinical proof-of-concept with two potential pipeline products (SYN-006 and SYN-007) designed to expand the utility of our beta-lactamase strategy.

SYN-007 is a specially formulated version of SYN-004 (ribaxamase) designed to be used with orally administered beta-lactam antibiotics to protect the gut microbiome from antibiotic-mediated dysbiosis.

SYN-006 is a carbapenemase designed to degrade intravenous (IV) carbapenem antibiotics within the GI tract to maintain the natural balance of the gut microbiome for the prevention of CDI, overgrowth of pathogenic organisms and the emergence of antimicrobial resistance (AMR).

The scope of our research is expanding to include development of new oncolytic virus products with alternative modes of action, and may include oncology applications of our existing products such as SYN-006 and SYN-007.

ALT levels were increased on day 3 within an acceptable range that returned to normal levels by day 9.

Fractionated intravenous administration of the ABD-containing virus (splitting the dose into two portions administered 4 h apart) appeared to improve virus circulation kinetics and increase tumor levels.

Antitumor efficacy was observed in the presence of NAbs against Ad5 and the ABD-containing virus.

In May 2022, we presented data at the 25th Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT).

The presentation included preclinical results showcasing the potential of the Albumin Shield Technology to effectively target tumors after intravenous re-administration, even in the presence of high level NAbs, with no major toxicities observed.

Our internal VCN-X discovery programs are currently evaluating new oncolytic viruses that contain the Albumin Shield technology and may expand the potential efficacy of Theriva’s oncolytic viruses.

Intellectual Property

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and foreign patents pending.

The SYN-004 (ribaxamase) program is supported by IP that is assigned to Theriva Biologics, namely U.S.

The SYN-004 (ribaxamase) program is supported by intellectual property (“IP”) that is assigned to Theriva Biologics, namely U.S.

and foreign patents (in most major markets, e.g.

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These patents and patent applications, which cover various formulations, medical uses and manufacture of SYN-020, are expected to expire in 2038-2040, without taking potential patent term extensions or patent term adjustment into account.

The VCN-01 and VCN-11 programs are supported by U.S.

The VCN-01 and Albumin Shield programs are supported by U.S.

and foreign patents and patent applications that are assigned to VCN or exclusively licensed from Fundació Privada Institut d’Investigacio Biomedica de Bellvitge (IDIBELL), Institut Catala d’Oncologia (ICO), and Hospital Sant Joan de Déu in Barcelona.

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US$6MM upon VCN-01 US Phase 2 trial meets the primary endpoint or if a Phase 2 trial is not conducted and only a Phase 3 trial is conducted then upon a Phase 3 being initiated – PDAC (or other first indication)

US$8MM upon VCN-01 Pivotal Trial meeting the primary endpoint or upon BLA Submission – RB (or other second indication)

US$8MM upon VCN-01 Pivotal Trial meeting the primary endpoint or upon Submission of a Biologics License Application (‘BLA”)– RB (or other second indication)

US$12MM upon VCN-01 US Phase 3 trial meeting the primary endpoint or upon BLA Submission – PDAC (or other first indication)

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without other changes to its corporate structure.

Theriva is a clinical-stage biopharmaceutical company developing new oncolytic adenoviruses for the treatment of cancer.

Theriva’s lead product candidate, VCN-01, is being studied in clinical trials for pancreatic cancer and retinoblastoma with additional investigator sponsored trials in indications including head and neck squamous cell carcinoma (HNSCC) serous epithelial ovarian cancer and brain tumors.

VCN-01 is designed to be administered systemically, intratumorally or intravitreally, either as a monotherapy or in combination with standard of care, to treat a wide variety of cancer indications.

VCN-01 is 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.

Degrading the tumor stroma has been shown to improve access to the tumor by the virus and additional therapies such as chemo- and immuno-therapies.

Importantly, degrading the stroma exposes tumor antigens, turning “cold” tumors “hot” and enabling a sustained anti-tumor immune response.

Theriva has the exclusive rights to four patent families for proprietary technologies, as well as technologies developed in collaboration with the Virotherapy Group of the Catalan Institute of Oncology (ICO-IDIBELL) and with Hospital Sant Joan de Deu (HSJD), with a number of additional patents pending.

Our Current Collaborations

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In addition, the licensors have the right to revoke the IDIBELL/ICO License Agreement if VCN during a continuous period of two years abandons its research or development activities of the licensed patent or activities aimed at exploitation of the resulting products, VCN has undertaken no marketing whatsoever during the term of the IDIBELL/ICO License Agreement or uses the patent licensed for purposes other those as set forth in the IDIBELL/ICO License Agreement.

Saint Joan De Déu Collaboration and License Agreement

On February 15, 2016, VCN entered into a Collaboration Agreement to Conduct a Clinical Trial and Grant an Operating License (the “Collaboration and License Agreement”) with the Saint Joan De Déu Hospital (the “Hospital”) and the Saint Joan De Déu Foundation (the “Foundation”, and together with the Hospital, the “Institution”) regarding the conduct of a clinical trial to evaluate the safety and activity of VCN-01 in patients with refractory retinoblastoma.

Sant Joan De Déu Collaboration and License Agreement

On February 15, 2016, VCN entered into a Collaboration Agreement to Conduct a Clinical Trial and Grant an Operating License (the “Collaboration and License Agreement”) with the Sant Joan De Déu Hospital (the “Hospital”) and the Sant Joan De Déu Foundation (the “Foundation”, and together with the Hospital, the “Institution”) regarding the conduct of a clinical trial to evaluate the safety and activity of VCN-01 in patients with refractory retinoblastoma.

The Collaboration and License Agreement provides that if the trial results are positive and VCN is interested in continuing with the development of VCN-01 for the treatment of retinoblastoma;

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The Collaboration and License Agreement continues in force and effect until all obligations arising from the trial have been fulfilled, subject to early termination for a material breach by a party of any of their contractual and/or legal obligations, or, in the case of any other type of breach, when the breaching party has been asked in writing to remedy the breach and the breach is not cured within thirty (30) days from the date on which the written request was sent.

Per the terms of the clinical trial agreement, the determination by the study Monitoring Committee that the study had a positive outcome means we will receive an exclusive, worldwide technology license, and related patents from Hospital Sant Joan de Déu for the treatment of pediatric patients with advanced retinoblastoma and we will pay to Hospital Sant Joan de Déu the amount of three hundred twenty thousand Euros (€320,265) or approximately $334,000, upon receipt by us of the final clinical study report

On November 1, 2023, VCN and Sant Joan de Déu-Barcelona Children’s Hospital entered into an agreement for an exclusive worldwide option to negotiate an exclusive license of certain Sant Joan de Deu intellectual property rights related to the use of VCN-01 in combination with topoisomerase I inhibitor chemotherapies for the treatment of cancer.

This option was extended by amendment on November 18, 2024.

The collaboration builds on growing data that suggests coadministration of VCN-01 with topoisomerase I inhibitors such as topotecan can enhance VCN-01 replication and antitumor activity in preclinical cancer models.

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We have the right to terminate the CTA (i) effective immediately if Washington University fails to perform the study in accordance with the terms of the protocol, the CTA or applicable laws or regulations or if Washington University or the principal investigator become debarred or (ii) upon 14 days written notice and Washington University has the right to terminate the CTA upon 14 days notice if the principal investigator becomes unable to perform or complete the Study and the parties have not, prior to the expiration of such fourteen (14) day period, agreed to an alternative principal investigator.

Massachusetts General Hospital Exclusive Option License Agreement

On May 27, 2020, we entered into an agreement with Massachusetts General Hospital (“MGH”) granting us an option for an exclusive license to intellectual property and technology related to the use of intestinal alkaline phosphatase (“IAP”) to maintain gastrointestinal (GI) and microbiome health, diminish systemic inflammation, and treat age-related diseases.

If executed, we plan to use this license in the advancement of an expanded clinical development program for SYN-020, our proprietary recombinant version of bovine IAP currently in pre-clinical development.

To date, we have not exercised the option.

The University of Texas at Austin License Agreement and Sponsored Research Agreement

On December 19, 2012, we entered into a Patent License Agreement (the “Texas License Agreement”) with UT Austin for the exclusive license of the right to use, develop, manufacture, market and commercialize certain research and patents related to pertussis antibodies developed in the lab of Dr.

Maynard, Associate Professor of Chemical Engineering.

In accordance with the terms of the Texas License Agreement we made the following payments to the UT Austin:

a payment of past patent expenses, an annual payment of $50,000 per year commencing on the effective date through December 31, 2014 and a $25,000 payment on December 31, 2015.

The Texas License Agreement also provides that UT Austin is entitled to milestone payments of $50,000 upon commencement of Phase 1 Clinical Trials, $100,000 upon commencement of Phase 3 Clinical Trials, $250,000 upon NDA submission in the United States, $100,000 upon European Medicines Agency approval and $100,000 upon regulatory approval in an Asian country.

In addition, the University is entitled to a running royalty upon Net Product Sales and Net Service Sales (as defined in the Texas License Agreement and currently projected to be 2037 (not accounting for possible extensions)).

The License Agreement terminates upon the expiration of the patent rights (as defined in the Texas License Agreement);

provided, however that the Texas License Agreement is subject to early termination by us in our discretion and by the University for a breach of the Texas License Agreement by us.

In connection with the Texas License Agreement, we also entered into a Sponsored Research Agreement (the “Sponsored Research Agreement”) with the University pursuant to which the University will perform certain research work related to pertussis under the direction of Dr.

Jennifer Maynard.

All inventions conceived during such research shall be subject to the Texas License Agreement and we will obtain certain rights to patents and technology developed during the course of such research.

We paid the University a fixed fee for the first year of $303,287 and the second and third years of $316,438 and $328,758, respectively.

The termination date of the Sponsored Research Agreement n was amended multiple times and Sponsored Research Agreement expired on January 17, 2023.

Upon a termination or due to a breach by the University, we were only be responsible for all reasonable expenses that do not exceed the fixed annual amount and that are incurred by the University prior to the termination date for services performed prior to the termination date.

We have an issued U.S.

patent and patents pending in the U.S.

and internationally ( e.g.

Europe, China, Japan, Australia, and China) on compositions and uses of SYN-005 that are co-owned by UT Austin and ourselves or licensed to us, and we have an issued U.S.

patent and patent applications on other pertussis mAbs licensed from UT Austin.

Manufacturing

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We plan to rely on third parties to manufacture commercial quantities of products that we successfully develop through regulatory approval.

We have contracted with GenIbet and ThermoFisher to provide what we believe are adequate clinical supplies for our planned clinical trials.

We have contracted with CDMOs to provide what we believe are adequate clinical supplies for our planned clinical trials.

Our upstream and downstream processes for producing oncolytic viruses are well understood in the industry and use industry standard cell factories and single use bioreactors for manufacturing.

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We have previously encountered some delays in manufacturing due to the impact of COVID-19 on the supply chain.

The potential impact of similar supply chain issues from a COVID-19 resurgence or other pandemic, if any, on our on-going and future clinical trials is currently unknown.

The potential impact of similar supply chain issues from a future pandemic or other disruption to global trade and supply chains, if any, on our on-going and future clinical trials is currently unknown.

SYN-004 and SYN-020

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These and other entities regulate research and development and the testing, manufacture, quality control, safety, effectiveness, labeling, storage, record keeping, approval, advertising, and promotion of our products.

The drug approval process required by the FDA under the Food, Drug, and Cosmetic Act and Public Health Service Act (for biologics) generally involves:

The drug approval process required by the FDA under the Food, Drug, and Cosmetic Act (the “FDCA”) and Public Health Service Act (the “PHS Act”)(for biologics) generally involves:

● preclinical laboratory and animal tests;

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● adequate and well-controlled human clinical trials to establish safety and efficacy for intended use;

● submission to the FDA of an NDA or BLA;

● submission to the FDA of a new drug application (“NDA”) or BLA;

● FDA review and approval of an NDA or BLA.

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Clinical trials must be supervised by qualified investigators in accordance with current good clinical practice (cGCP) regulations, which include informed consent requirements.

Each study must be approved and monitored by the appropriate Institutional Review Boards (IRBs) or ethics committees (ECs) which are periodically informed of the study’s progress, adverse events and changes in research.

Each study must be approved and monitored by the appropriate Institutional Review Boards (IRBs) or Instituional Ethics Committees (IECs) which are periodically informed of the study’s progress, adverse events and changes in research.

OVs such as VCN-01 are genetically modified organisms and their use is also subject to review and approval by the Institutional Biosafety Committee (IBC) at each clinical trial site.

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We cannot be certain that we will successfully complete Phase 1, Phase 2, or Phase 3 testing of our product candidates within any specific time period, if at all.

Furthermore, the FDA or comparable foreign regulator, an IRB/EC or the IND sponsor may suspend clinical trials at any time on various grounds, including a finding that subjects or patients are exposed to unacceptable health risk.

Furthermore, the FDA or comparable foreign regulator, an IRB/IEC or the IND sponsor may suspend clinical trials at any time on various grounds, including a finding that subjects or patients are exposed to unacceptable health risk.

Under the Pediatric Research Equity Act, we also must prepare, within 60 days of an End of Phase 2 meeting, a pediatric study plan or request for waiver or deferral of pediatric studies in the indication under development.

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Submission of an NDA or BLA with clinical data requires payment of a substantial fee.

In return, the FDA assigns a goal for review and decision on the application, in which the FDA may approve or deny the NDA or BLA, or issue a complete response letter outlining information needed to support approval, including a potential need for additional clinical data.

The FDA assigns a goal for review and decision on the application, in which the FDA may approve the NDA or BLA or issue a complete response letter outlining information needed to support approval, including a potential need for additional clinical data.

Even if these data are submitted, the FDA may ultimately decide the NDA or BLA does not satisfy approval criteria.

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In addition, exclusive marketing rights in the United States may be lost if the FDA later determines that the request for designation was materially defective or if the manufacturer is unable to assure sufficient quantities of the product to meet the needs of patients with the rare disease or condition.

Accelerated Approval

There are a variety of pathways under which applicants may seek expedited approval from FDA, including Fast Track, breakthrough therapy, priority review and accelerated approval.

Fast Track is a process designed to facilitate the development and expedite the review of investigational drugs to treat serious conditions and fill an unmet medical need.

Drugs that receive Fast Track designation may be eligible for more frequent communications and meetings with the FDA to discuss the drug’s development plan, including the design of the proposed clinical trials, use of biomarkers and the extent of data needed to support approval.

Drugs with Fast Track designation may also qualify for accelerated approval and priority review of new drug applications if relevant criteria are met.

However, Fast Track designation may be withdrawn by the FDA if the FDA believes that the designation is no longer supported by data emerging in the clinical trial process.

The FDA accelerated approval program provides for early approval of drugs based on a drug on a clinical trial(s) showing that the drug meets a surrogate or an intermediate clinical endpoint rather than a clinical benefit endpoint.

Accelerated approval is possible for drugs for serious conditions that fill an unmet medical need.

Under priority review, the FDA reviews an application in six months rather than ten months after it is accepted for filing.

A surrogate endpoint used for accelerated approval is a marker, such as a laboratory measurement, that is thought to predict clinical benefit, but is not itself a measure of clinical benefit.

Likewise, an intermediate clinical endpoint is a measure of a therapeutic effect that is considered reasonably likely to predict the clinical benefit of a drug, such as an effect on irreversible morbidity and mortality.

Because it sometimes can take many years for a drug trial to show a clinical benefit, the use of a surrogate endpoint or an intermediate clinical endpoint can significantly shorten the time required to complete clinical trials and obtain FDA approval.

If a drug receives an accelerated approval, the company that sponsored the application must conduct a post-approval trial to confirm the anticipated clinical benefit.

These trials are known as Phase 4 or post-approval confirmatory trials.

If the confirmatory trial shows that the drug actually provides a clinical benefit, then the FDA grants traditional approval for the drug.

Failure to conduct required post-approval studies, or confirm a clinical benefit during post-marketing studies, will allow the FDA to withdraw the drug from the market on an expedited basis.

All promotional materials for drug candidates approved under accelerated regulations are subject to prior review by the FDA.

If the confirmatory trial does not show that the drug provides clinical benefit, FDA has regulatory procedures in place that could lead to removing the drug from the market.

Rare Pediatric Disease Vouchers

The Rare Pediatric Disease Voucher Program is intended to encourage development of new drug and biological products for prevention and treatment of certain rare pediatric diseases.

Although there are existing incentive programs to encourage the development and study of drugs and biologics for rare diseases, pediatric populations, and unmet medical needs, this program provides an additional incentive for the development of drugs and biologics for rare pediatric diseases, which may be used alone or in combination with other incentive programs.

A rare pediatric disease is defined as a disease that is a serious or life-threatening disease in which the serious or life-threatening manifestations primarily affect individuals aged from birth to 18 years, including age groups often called neonates, infants, children, and adolescents;

and is a rare disease or condition as defined in the FDCA, which includes diseases and conditions that affect fewer than 200,000 persons in the United States and diseases and conditions that affect a larger number of persons and for which there is no reasonable expectation that the costs of developing and making available the product in the United States can be recovered from sales of the product in the United States.

The sponsor of an application for a drug product that obtains rare pediatric disease designation may be eligible for a voucher that can be used or sold to obtain a priority review for a subsequent application submitted under section 505(b)(1) of the FDCA or section 351 of the PHS Act.

A rare pediatric disease drug product must meet certain eligibility requirements for a priority voucher at the time the sponsor seeks approval.

The rare pediatric disease priority review voucher program was most recently re-authorized by Congress through December 20, 2024, with the potential for priority review vouchers to be granted through September 30, 2026.

If a BLA for VCN-01 for the treatment of retinoblastoma is approved by the FDA by September 30, 2026, we may be eligible to receive a priority review voucher.

Pediatric Information and Pediatric Exclusivity

Under the Pediatric Research Equity Act (“PREA”), certain NDAs and BLAs and certain supplements to an NDA or BLA must contain data to assess the safety and efficacy of the drug for the claimed indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective.

The FDA may grant deferrals for submission of pediatric data or full or partial waivers.

The Food and Drug Administration Safety and Innovation Act (“FDASIA”), amended the FDCA to require that a sponsor who is planning to submit a marketing application for a drug that includes a new active ingredient, new indication, new dosage form, new dosing regimen or new route of administration submit an initial Pediatric Study Plan (“PSP”) within 60 days of an end-of-Phase 2 meeting or, if there is no such meeting, as early as practicable before the initiation of the Phase 3 or Phase 2/3 study.

The initial PSP must include an outline of the pediatric study or studies that the sponsor plans to conduct, including study objectives and design, age groups, relevant endpoints and statistical approach, or a justification for not including such detailed information, and any request for a deferral of pediatric assessments or a full or partial waiver of the requirement to provide data from pediatric studies along with supporting information.

The FDA and the sponsor must reach an agreement on the PSP.

A sponsor can submit amendments to an agreed-upon initial PSP at any time if changes to the pediatric plan need to be considered based on data collected from preclinical studies, early phase clinical trials and/or other clinical development programs.

The Best Pharmaceuticals for Children Act, or BPCA, provides NDA holders a six-month extension of any exclusivity — patent or non-patent — for a drug if certain conditions are met.

Pediatric exclusivity, if granted, adds six months to existing exclusivity periods and patent terms.

Conditions for exclusivity include the FDA’s determination that information relating to the use of a new drug in the pediatric population may produce health benefits in that population, the FDA’s written request for pediatric studies, and the applicant’s agreeing to perform, and reporting on, the requested studies within the statutory timeframe.

Applications under the BPCA are treated as priority applications, with all of the benefits that designation confers.

Drug Development in the European Union

Orphan Drug Designation is also available in Europe from the European Medicines Agency (EMA) and provides for 10 years of market exclusivity if granted.

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In May 2011, the Committee for Orphan Medicinal Products ("COMP") from the EMA recommended granting Orphan Medicinal Product Designation to VCN-01 for the treatment of pancreatic cancer and in June 2011, the European Commission confirmed the designation under Regulation ("EC") No 141/2000 of the European Parliament and of the Council.

In February 2022, the FDA granted Orphan Drug designation to VCN-01 for the treatment of retinoblastoma.

In June 2023, the FDA granted Orphan Drug Designation to VCN-01 for the treatment of pancreatic cancer.

In October 2024, the European Commission adopted the European Medicines Agency (EMA) recommendation to grant Orphan Medicinal Product Designation to VCN-01 for the treatment of retinoblastoma.

The European Commission confirmed the designation under Regulation ("EC") No 141/2000 of the European Parliament and of the Council.

In the European Union, our future products may also be subject to extensive regulatory requirements.

Similar to the United States, the marketing of medicinal products is subject to the granting of marketing authorizations by regulatory agencies.

Also, as in the United States, the various phases of pre-clinical and clinical research in the European Union are subject to significant regulatory controls.

In the European Union, approval of new medicinal products can be obtained through one of three processes:

the mutual recognition procedure, the centralized procedure and the decentralized procedure.

We intend to determine which process we will follow, if any, in the future.

Mutual Recognition Procedure:

An applicant submits an application in one European Union member state, known as the reference member state.

Once the reference member state has granted the marketing authorization, the applicant may choose to submit applications in other concerned member states, requesting them to mutually recognize the marketing authorizations already granted.

Under this mutual recognition process, authorities in other concerned member states have 55 days to raise objections, which must then be resolved by discussion among the concerned member states, the reference member state and the applicant within 90 days of the commencement of the mutual recognition procedure.

If any disagreement remains, all considerations by authorities in the concerned member states are suspended and the disagreement is resolved through an arbitration process.

The mutual recognition procedure results in separate national marketing authorizations in the reference member state.

Centralized Procedure:

This procedure is currently mandatory for products developed by means of a biotechnological process and optional for new active substances and other “innovative medicinal products with novel characteristics.” Under this procedure, an application is submitted to the European Agency for the Evaluation of Medical Products.

Two European Union member states are appointed to conduct an initial evaluation of each application.

These countries each prepare an assessment report that is then used as the basis of a scientific opinion of the Committee on Proprietary Medical Products.

If this opinion is favorable, it is sent to the European Commission, which drafts a decision.

After consulting with the member states, the European Commission adopts a decision and grants a marketing authorization, which is valid throughout the European Union and confers the same rights and obligations in each of the member states as a marketing authorization granted by that member state.

Decentralized Procedure:

The most recently introduced of the three processes for obtaining approval of new medicinal processes in the European Union, the decentralized procedure is similar to the mutual recognition procedure described above, but with differences in the timing that key documents are provided to concerned member states by the reference member state, the overall timing of the procedure and the possibility of, among other things, “clock stops” during the procedure.

Post-Marketing Requirements

Following approval of a new product, a pharmaceutical company and the approved product are subject to continuing regulation by the FDA and other regulatory authorities, including, among other things, monitoring and recordkeeping activities, reporting to applicable regulatory authorities of adverse experiences with the product, providing the regulatory authorities with updated safety and efficacy information, product sampling and distribution requirements, and complying with promotion and advertising requirements, which include, among others, standards for direct-to-consumer advertising, restrictions on promoting drugs for uses or in patient populations not described in the drug’s approved labeling (known as “off-label use”), and limitations on industry-sponsored scientific and educational activities.

Although physicians may prescribe legally available drugs for off-label uses, drugs may be marketed only for the approved indications and in accordance with the provisions of the approved labeling.

Modifications or enhancements to the products or labeling or changes of site of manufacture are often subject to the approval of the FDA and other regulators, which may or may not be received or may result in a lengthy review process.

The FDA regulations require the products be manufactured in specific approved facilities and in accordance with current good manufacturing practices, and NDA holders must list their products and register their manufacturing establishments with the FDA.

These regulations also impose certain organizational, procedural and documentation requirements with respect to manufacturing and quality assurance activities.

Drug manufacturers and other entities involved in the manufacture and distribution of approved drugs are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with current good manufacturing practice and other laws.

NDA holders using contract manufacturers, laboratories or packagers are responsible for the selection and monitoring of qualified firms.

These firms are subject to inspections by the FDA at any time, and the discovery of violative conditions could result in enforcement actions that interrupt the operation of any such facilities or the ability to distribute products manufactured, processed or tested by them.

Other Healthcare Laws and Compliance Requirements

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The federal Anti-Kickback Statute prohibits any person, including a prescription drug manufacturer (or a party acting on its behalf), from knowingly and willfully soliciting, receiving, offering or providing remuneration, directly or indirectly, to induce or reward either the referral of an individual, or the furnishing, recommending or arranging for a good or service, for which payment may be made under a federal healthcare program such as the Medicare and Medicaid programs.

The federal False Claims Act imposes liability on any person or entity that, among other things, knowingly presents or causes to be presented, a false or fraudulent claim for payment by a federal healthcare program.

The qui tam provisions of the False Claims Act allow a private individual to bring civil actions on behalf of the federal government alleging that the defendant has submitted a false claim to the federal government, and to share in any monetary recovery.

In addition, various states have enacted anti-kickback statues and false claims laws analogous to the False Claims Act.

Also, the Health Insurance Portability and Accountability Act of 1996 (HIPAA) created several federal crimes, including healthcare fraud, and false statements relating to the delivery of or payments for healthcare benefits, items or services.

HIPAA and its implementing regulations also established uniform federal standards for certain “covered entities” (healthcare providers, health plans and healthcare clearinghouses) governing the conduct of certain electronic healthcare transactions and protecting the security and privacy of protected health information.

The federal False Claims Act (“FCA”) imposes liability on any person or entity that, among other things, knowingly presents or causes to be presented, a false or fraudulent claim for payment by a federal healthcare program.

The qui tam provisions of the FCA allow a private individual to bring civil actions on behalf of the federal government alleging that the defendant has submitted a false claim to the federal government, and to share in any monetary recovery.

In addition, various states have enacted anti-kickback statues and false claims laws analogous to the FCA The Federal Physician Payments Sunshine Act within the Affordable Care Act, or the ACA, and its implementing regulations, require that certain manufacturers of drugs, devices, biological and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program (with certain exceptions) to report on an annual basis information related to certain payments or other transfers of value made or distributed to physicians and teaching hospitals, or to entities or individuals at the request of, or designated on behalf of, the physicians and teaching hospitals and certain ownership and investment interests held by physicians and their immediate family members, with the information made publicly available on a searchable website Also, the Health Insurance Portability and Accountability Act of 1996 (HIPAA) ), as amended by the Health Information Technology for Economic and Clinical Health Act (HITECH) and its implementing regulations, imposes certain requirements relating to the privacy, security and transmission of individually identifiable health information.

Among other things, HITECH makes HIPAA’s privacy and security standards directly applicable to “business associates” — independent contractors or agents of covered entities that receive or obtain protected health information in connection with providing a service on behalf of a covered entity.

HITECH also created four new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates and possibly other persons, and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorneys’ fees and costs associated with pursuing federal civil actions.

Because of the breadth of these and other laws and the narrowness of available statutory and regulatory exemptions, it is possible that some of our business activities could be subject to challenge under one or more of such laws.

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personal data to the U.S.

Environmental, Health, and Safety Regulation

We are subject to numerous federal, state and local environmental, health and safety (“EHS”), laws and regulations relating to, among other matters, safe working conditions, product stewardship, environmental protection, and handling or disposition of products, including those governing the generation, storage, handling, use, transportation, release, and disposal of hazardous or potentially hazardous materials, medical waste, and infectious materials that may be handled by our research laboratories.

Some of these laws and regulations also require us to obtain licenses or permits to conduct our operations.

If we fail to comply with such laws or obtain and comply with the applicable permits, we could face substantial fines or possible revocation of our permits or limitations on our ability to conduct our operations.

Certain of our development activities involve use of hazardous materials, and we believe we are in compliance with the applicable environmental laws, regulations, permits, and licenses.

However, we cannot ensure EHS liabilities will not develop in the future.

EHS laws and regulations are complex, change frequently and have tended to become more stringent over time.

Although the costs to comply with applicable laws and regulations, have not been material, we cannot predict the impact on our business of new or amended laws or regulations or any changes in the way existing and future laws and regulations are interpreted or enforced, nor can we ensure we will be able to obtain or maintain any required licenses or permits.

Competitive Environment

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Our oncology product candidates compete with all other oncology products being developed for the indications that we are focusing oncolytic virus (OV) products being developed by third parties.

Only three oncolytic virus (OV) products have been approved in different global markets.

Only three OV products have been approved in different global markets.

Amgen Inc.’s Imlygic® (T-VEC, OncoVEX) for melanoma (USA);

Daiichi Sankyo Company, Limited‘s DELYTACT® for malignant glioma (Japan) and Shanghai Sunway Biotech Co., Ltd Oncorine® for patients with late-stage refractory nasopharyngeal cancer (China).

A BLA filed by Replimune, Inc.

for their OV RP1 (vusolimogene oderparepvec) in combination with nivolumab for patients with advanced melanoma has been accepted by the FDA with a Prescription Drug User Fee Act (PDUFA) action date of July 22, 2025.

In June 2024, CG Oncology, Inc.

announced that their Phase 3 OV cretostimogene grenadenorepvec was available in the U.S.

for patients with BCG-unresponsive non-muscle invasive bladder cancer (“NMIBC”) who meet certain program eligibility criteria.

More than 60 companies have publicly identified that they are pursuing clinical development of different forms of OV products.

Adenoviruses are the most commonly used viruses in these programs, with modified adenoviruses under development by companies including AdCure Bio LLC, Calidi Biotherapeutics, Inc.,Candel Therapeutics, Inc., CG Oncology, Inc., Elicera Therapeutics AB, EpicentRx, Inc., GeneMedicine, Co Ltd., IconOVir Bio, Inc., Lokon Pharma AB, Memgen, Inc., Multivir, Inc., NewGenPharm Incorporation, Oncolys BioPharma, Inc., Orca Therapeutics B.V., Akamis Bio Ltd (formerly PsiOxus Therapeutics Ltd), Shanghai Sunway Biotech Co., Ltd, Circio Holding ASA (formerly Targovax Oy|Targovax ASA), Teolytics Ltd, Tessa Therapeutics, TILT Biotherapeutics, Ltd., and Valo Therapeutics Oy.

Adenoviruses are the most commonly used viruses in these programs, with modified adenoviruses under development by companies including AdCure Bio LLC, Calidi Biotherapeutics, Inc., Candel Therapeutics, Inc., CG Oncology, Inc., Elicera Therapeutics AB, EpicentRx, Inc., GeneMedicine, Co Ltd., IconOVir Bio, Inc., Lokon Pharma AB, Memgen, Inc., Multivir, Inc., NewGenPharm Incorporation, Oncolys BioPharma, Inc., Orca Therapeutics B.V., Akamis Bio Ltd (formerly PsiOxus Therapeutics Ltd), Shanghai Sunway Biotech Co., Ltd, Circio Holding ASA (formerly Targovax Oy|Targovax ASA), Theolytics Ltd, Tessa Therapeutics, TILT Biotherapeutics, Ltd., and Valo Therapeutics Oy.

OV products have been or are being developed using other virus backbones, including:

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Roche AG and Takeda Pharmaceutical Company Ltd.

Not only do our product candidates compete with other product candidates being developed for similar or the same indications, we also compete for employees and for clinical trial sites.

Not only do our product candidates compete with other product candidates being developed for similar or the same indications, we also compete for employees, clinical trial sites, and clinical trial participants.

Corporate History

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On October 12, 2022, we changed our name to Theriva Biologics, Inc.

On August 26, 2024, we effected a one for twenty-five reverse stock split of our authorized, issued and outstanding common stock.

Human Capital

We believe that our success depends upon our ability to attract, develop and retain key personnel.

As of March 25, 2024, we employed 22 individuals, all but one of whom are full-time employees, of which 6 were part of our research and clinical development team in the United States and 9 are part of VCN’s research and clinical development team located in Spain, 2 are part of VCN’s management team located in Spain and 4 are part of our financial reporting and accounting team located in the United States.

As of March 6, 2025, we employed 22 individuals, all but two of whom are full-time employees.

Six (6) were part of our research and clinical development team in the United States and Ten (10) were part of VCN’s research and clinical development team located in Spain, Two (2) are part of VCN’s management team located in Spain and Four (4) (including the CEO) are part of our financial reporting and accounting team located in the United States.

A significant number of our management and professional employees have had prior experience with pharmaceutical, biotechnology or medical product companies.

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We also offer a variety of voluntary benefits that allow employees to select the options that meet their needs, including flexible time-off, telemedicine, and unpaid parental leave.

Health and Safety

The health and safety of our employees is our highest priority, and this is consistent with our operating philosophy.

Accordingly, with the global spread of the ongoing novel coronavirus pandemic, we have implemented plans designed to address and mitigate the impact of the COVID-19 pandemic on the safety of our employees and our business, which include:

● adding work from home flexibility;

● adjusting attendance policies to encourage those who are sick to stay home;

● increasing cleaning protocols across all locations;

● initiating regular communication regarding impacts of the COVID-19 pandemic, including health and safety protocols and procedures.

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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business