−Removed: We are a diversified clinical-stage company developing therapeutics in areas of high unmet need.
−Removed: As a result of the acquisition of VCN Biosciences, S.L., now known as Theriva Biologics, S.L.
−Removed: (“VCN”), described in more detail below, we began transitioning our strategic focus to oncology through the development of VCN’s oncolytic adenovirus platform designed for intravenous and intravitreal delivery to trigger tumor cell death, improve access of co-administered cancer therapies to the tumor, and promote a robust and sustained anti-tumor response by the patient’s immune system.
−Removed: Prior to the Acquisition, our focus was on developing therapeutics designed to treat gastrointestinal (GI) diseases which included.
−Removed: our clinical development candidates:
−Removed: (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 (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.
−Removed: As part of our strategic transformation into an oncology focused company, we are exploring value creation options around our SYN-020 and SYN-004 assets.
−Removed: SYN-004 and SYN-020 both have significant potential opportunity in non-oncology related indications.
−Removed: Advancement of these products may be better achieved by out-licensing or partnering and we will explore opportunities for both SYN-004 and SYN-020 moving forward.
−Removed: Acquisition of VCN Biosciences, S.L.
−Removed: (now known as Theriva Biologics, S.L.)
−Removed: On March 10, 2022, we completed our acquisition (the “VCN Acquisition”) of all the outstanding shares of VCN (the “VCN Shares”) from the shareholders of VCN pursuant to the terms of the Share Purchase Agreement (“Purchase Agreement”) that we entered into with VCN and the shareholders of VCN Biosciences, S.L.
−Removed: (the “Sellers”) on December 14, 2021.
−Removed: Upon consummation of the Acquisition, VCN became our wholly owned subsidiary.
−Removed: As consideration for the purchase of the VCN Shares of capital stock, we paid $4,700,000 (the “Closing Cash Consideration”) to Grifols Innovation and New Technologies Limited (“Grifols”), the owner of approximately 86% of the equity of VCN, and issued to the remaining Sellers 2,639,530 shares of our common stock, $0.001 par value (the “Closing Shares”), representing 19.99% of the outstanding shares of our common stock on December 14, 2021, the date of the Purchase Agreement.
−Removed: As additional consideration for the purchase of the VCN Shares held by Grifols, we also agreed to make the following milestone payments to Grifols:
−Removed: Milestone Payments
−Removed: US$3MM upon VCN-01 US IND Safe to Proceed pancreatic ductal adenocarcinoma (“PDAC”, or other first indication), which payment was made in Q4 2022 upon attaining the milestone
−Removed: US$2.75MM upon VCN-01 US IND Safe to Proceed – retinoblastoma (“RB”, or other second indication)
−Removed: US$3.25MM upon VCN-01 US first patient dosed– PDAC (or other first indication) after receipt of VCN-01 US IND Safe to Proceed for PDAC being informed
−Removed: US$3.25MM upon VCN-01 US first patient dosed – RB (or other second indication) after receipt of VCN-01 US IND Safe to Proceed for RB being informed
−Removed: 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)
−Removed: US$8MM upon VCN-01 Pivotal Trial meeting the primary endpoint or upon BLA Submission – RB (or other second indication)
−Removed: US$12MM upon VCN-01 US Phase 3 trial meeting the primary endpoint or upon BLA Submission – PDAC (or other first indication)
−Removed: US$16MM upon VCN-01 BLA Approval – PDAC (or other first indication)
−Removed: US$16MM upon VCN-01 BLA Approval – RB (or other second indication)
−Removed: Pursuant to the Purchase Agreement, at the Closing we assumed $2,400,000 of liabilities of VCN, which includes certain loans from the Spanish Government and the Catalan Government Agency.
−Removed: The Purchase Agreement contains customary representations, warranties and covenants of the Sellers and us.
−Removed: Subject to certain customary limitations, the Sellers have agreed to indemnify us and our officers and directors against certain losses related to, among other things, breaches of their representations and warranties, certain specified liabilities and the failure to perform covenants or obligations under the Purchase Agreement.
−Removed: Effective November 15, 2022, as part of our corporate rebranding, VCN changed its name to Theriva Biologics S.L.
−Removed: without other changes to its corporate structure.
−Removed: Theriva is a clinical-stage biopharmaceutical company developing new oncolytic adenoviruses for the treatment of cancer.
−Removed: 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.
−Removed: 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.
−Removed: 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.
−Removed: 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.
−Removed: Importantly, degrading the stroma exposes tumor antigens, turning “cold” tumors “hot” and enabling a sustained anti-tumor immune response.
−Removed: 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.
−Removed: Recent Developments
−Removed: Effective October 12, 2022, we changed our name to Theriva Biologics, Inc.
−Removed: by filing a Certificate of Amendment to its Articles of Incorporation (the “Certificate of Amendment”) with the Secretary of State of the State of Nevada on October 11, 2022.
−Removed: In addition, effective October 12, 2022, the Company amended and restated its Amended and Restated Bylaws (the “Bylaws”) to reflect the Name
−Removed: Change (the “Amended and Restated Bylaws”).
−Removed: The Amended and Restated Bylaws contain no other changes.
−Removed: In connection with the Name Change, the Company’s Common Stock began trading on the NYSE American LLC under the new ticker symbol “TOVX” effective as of the opening of trading hours on October 13, 2022.
−Removed: Stock Repurchase
−Removed: On December 22, 2022, we repurchased an aggregate of 720,000 shares of our common stock from Manel Maria Cascallo Piqueras, Ramon Alemany and Gabriel Maria Capella Munar (the “Selling Stockholders”), three founders of our subsidiary Theriva Biologics, S.L.
−Removed: (formerly known as VCN Biosciences, S.L.) in a privately negotiated transaction pursuant to the terms of a Share Repurchase Agreement (the “Share Repurchase Agreement”) entered into on December 20, 2022 with each of the Selling Stockholders.
−Removed: The price per share was $0.4001, which was the closing price of the Common Stock on the day prior to the closing for an aggregate purchase price was $288,072.
−Removed: The closing was subject to fulfillment of certain conditions, including delivery of certain closing documents.
−Removed: The Share Repurchase Agreement contains customary representations, warranties and covenants of the parties.
−Removed: The repurchase was funded from the Company’s cash on hand and the shares that were repurchased will be held as treasury stock by the Company.
−Removed: The Selling Stockholders acquired the shares of the Company’s Common Stock as consideration for the sale of their shares of the subsidiary to the Company in March 2022.
−Removed: Recent Clinical Developments
−Removed: On November 3, 2022, we issued a press release announcing the first patient has been dosed in Cohort 2 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 (aGVHD).
−Removed: On January 9, 2023, we issued a press release announcing that the first patient has been dosed in the Phase 1 investigator sponsored clinical trial of intravenous VCN-01 in patients with high-grade brain tumors who are scheduled for surgical resection.
−Removed: On January 17, 2023, we issued a press release announcing the first patient has been dosed 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 (PDAC) (NCT05673811).
+Added: We are a diversified clinical-stage company developing therapeutics designed ot treat cancer and related diseases in areas of high unmet need.
+Added: As a result of the acquisition in March 2022 of Theriva Biologics, S.L.
+Added: (“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.
+Added: 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.
+Added: Prior to the Acquisition, our focus was on developing therapeutics designed to treat gastrointestinal (GI) diseases which included our clinical development candidates:
+Added: (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.
+Added: 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.
Our Current Product Pipeline
*Based on management’s current beliefs and expectations
−Removed: aGVHD acute graft-vs-host disease;
allo-HCT allogeneic hematopoietic cell transplant.
−Removed: IAP recombinant bovine intestinal alkaline phosphatase II.
CPI immune checkpoint inhibitor.
−Removed: Gem/nab-P Gemcitabine + Abraxane® (nab-paclitaxel).
−Removed: HNSCC head and neck
−Removed: squamous cell carcinoma.
+Added: HNSCC head and neck squamous cell carcinoma.
IV intravenous.
IVit intravitreal.
−Removed: MAD multiple ascending dose.
ODD Orphan Drug Designation.
−Removed: OV oncolytic virus.
+Added: 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.
²Depending on funding/partnership.
−Removed: SYN-004 may enter an FDA-agreed Phase 3 clinical trial for the prevention of Clostridioides difficile infection.
+Added: 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.
+Added: 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.
Our Current Oncology-Focused Pipeline
4 unchanged sentences
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.
−Removed: This infection by OVs also alerts the immune system, which can then attack the virus infected cells and the tumor cells to help destroy the tumor in some instances.
−Removed: Our OV candidates products are engineered to efficiently infect and selectively replicate to a high extent in tumor cells versus normal host cells, which enables intravenous delivery.
+Added: This infection and tumor cell killing by OVs also alerts the immune system, which can then attack the virus infected tumor cells to help destroy the tumor in some instances.
+Added: Our OV product candidates are engineered to efficiently infect and selectively replicate to a high extent in tumor cells versus normal host cells, which enables intravenous delivery.
By contrast, many other oncolytic viruses in clinical development today are administered by direct injection into the tumor.
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.
−Removed: Our first product candidate, VCN-01, is a clinical stage oncolytic human adenovirus that is modified to express an enzyme, hyaluronidase, that degrades hyaluronan in the tumor stroma, which helps the virus and other molecules to penetrate and spread throughout the tumor.
+Added: 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.
VCN-01 can be used alone or in combination with other cancer therapies, such as chemotherapy and immunotherapy, for difficult to treat cancers.
−Removed: An expanding intellectual property portfolio supports our oncology programs, and because our products are characterized as biologics, they will be further protected by data and/or market exclusivity in major markets.
+Added: 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.
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
1 unchanged sentence
These modifications have been shown in preclinical and clinical studies to confer tumor selective replication and antitumor activity.
−Removed: VCN-01 was engineered to replicate in and kill virtually all types of cancer cells, to expose tumor neoantigens of lysed tumors, to reduce liver tropism, and to express PH20 hyaluronidase to enhance the penetration of virus, chemotherapy and immune cells into the tumor.
+Added: VCN-01 was engineered to replicate in and kill virtually all types of solid tumor cells, to expose tumor neoantigens of lysed tumors, to reduce liver tropism, and to express PH20 hyaluronidase to enhance the penetration of virus, chemotherapy, immuno-oncology therapy, and immune cells into the tumor.
Malignant tumors are made up of tumor cells as well as significant supporting tissue known as tumor stroma.
The tumor stroma supports the formation and growth of tumors and contains cells and other components that are required for robust tumor growth and metastasis.
−Removed: The stroma also forms an effective barrier to the entry of therapeutic agents such as chemotherapy and antibodies.
−Removed: VCN-01 is designed to overcome the stroma barrier problem by expressing the well-characterized stroma degrading enzyme PH20 hyaluronidase after it infects tumor cells.
−Removed: Expression of PH20 by VCN-01 degrades the hyaluronic acid within the tumor stroma and improves virus spread.
+Added: The stroma also forms an effective barrier to the entry of therapeutic agents such as chemotherapy and immuno-oncology products .
+Added: A key structural component of the tumor stroma is hyaluronic acid, and tumor levels of hyaluronic acid have been clinically associated with reduced survival in metastatic pancreatic cancer patients.
+Added: VCN-01 is designed to overcome the stroma barrier problem by expressing the hyaluronan degrading enzyme PH20 hyaluronidase after it infects tumor cells.
+Added: 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.
2 unchanged sentences
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.
−Removed: VCN-01 has been administered to 82 patients across four Phase 1 clinical trials, including patients with pancreatic cancer, head and neck squamous cell carcinoma, ovarian carcinoma, colorectal cancer, and retinoblastoma.
+Added: 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.
Pancreatic Ductal Adenocarcinoma
2 unchanged sentences
Pancreatic ductal adenocarcinoma (“PDAC”) accounts for more than 90% of all pancreatic tumors.
−Removed: It can be located either in the head of the gland or in the body-tail.
−Removed: Pancreatic cancer usually gives metastases to liver and peritoneum.
−Removed: Other less common sites are the lungs, brain, kidney and bone.
+Added: It can be located either in the head of the pancreas or in the body-tail.
+Added: Pancreatic cancer usually metastasizess to the liver and peritoneum.
+Added: Other less common metastatic sites are the lungs, brain, kidney and bone.
In its early stages, pancreatic cancer does not typically result in any characteristic symptoms.
In many instances, progressive abdominal pain is the first symptom.
−Removed: Therefore, for most cases, pancreatic cancer is diagnosed in its late stages (locally advanced non-metastatic or metastatic stage of the disease) when the radical resection and possibly curative treatment is not possible.
−Removed: It’s 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.
+Added: 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.
+Added: 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.
PDAC Clinical Unmet Need and Market Opportunity
6 unchanged sentences
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.
+Added: 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.
However, the results are still very poor and new therapeutic interventions are needed.
2 unchanged sentences
In May 2011, the Committee for Orphan Medicinal Products (“COMP”) from the European Medicines Agency (“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.
+Added: In June 2023, the FDA granted Orphan Drug designation to VCN-01 for the treatment of pancreatic cancer.
Phase 1a/Proof of Concept Trial of VCN-01 by intratumoral administration in PDAC
18 unchanged sentences
doi:10.1136/jitc-2021-003255).
−Removed: Data from the recent publication had previously been presented, in part, in a poster at the ESMO 2019 annual meeting.
+Added: Data from the publication had previously been presented, in part, in a poster at the ESMO 2019 annual meeting.
The published study was a multicenter, open-label, dose-escalation phase I clinical trial of a single dose of intravenous VCN-01 alone (Part I, 16 patients with advanced refractory solid tumors) or in combination with nab-paclitaxel plus gemcitabine (Part II and III;
22 unchanged sentences
The second VCN-01 dose is administered 7 days before the 4th cycle of chemotherapy (approximately 90 days after the first VCN-01 dose), followed by additional cycles of gemcitabine/nab-paclitaxel chemotherapy.
−Removed: The first patients were dosed in the study in January 2023.
+Added: Patient dosing was initiated in the U.S.
+Added: 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.
+Added: 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).
+Added: According to the IDMC's comprehensive assessment of clinical data from patients enrolled across 6 sites open in the U.S.
+Added: and 9 sites open in Spain, the ongoing Phase 2b trial will continue without any changes to the protocol.
+Added: No safety concerns were raised based on the evaluation of data presented at the IDMC meeting.
+Added: Intravenous VCN-01 has been well tolerated and demonstrated a safety profile consistent with prior clinical trials.
+Added: 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.
+Added: VIRAGE remains on track to complete enrollment in the first half of 2024.
Retinoblastoma
22 unchanged sentences
The investigator has reported that one patient treated with VCN-01 has had a complete regression lasting more than 30 months.
−Removed: Six (6) patients have been treated with VCN-01 to date.
−Removed: This study is ongoing and the enrollment period has been extended to include additional patients.
−Removed: We anticipate meeting with the FDA during 2023 to discuss the path forward for VCN-01 as an adjunct to chemotherapy in pediatric patients with advanced retinoblastoma.
−Removed: On September 30, 2022, we issued a press release announcing an oral presentation entitled “Topotecan enhances oncolytic adenovirus infection, replication and antitumor activity in retinoblastoma,” featuring Dr.
−Removed: Angel Montero-Carcaboso, Researcher at Fundació Sant Joan de Déu at the SIOP 2022 Congress of the International Society of Pediatric Oncology, being held in Barcelona, Spain from September 28-October 1, 2022.
+Added: This Phase 1 trial with VCN-01 has now completed enrollment and a total of nine (9) patients been treated.
+Added: This study is expected to complete patient follow-up in Q1 2024.
+Added: 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.
+Added: 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.
+Added: 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.
8 unchanged sentences
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.
−Removed: 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.
+Added: 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.
Phase 1 Trial of intravenous VCN-01 in Combination with Durvalumab in Subjects with Recurrent/ Metastatic SCCHN
19 unchanged sentences
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.
−Removed: We expect to report additional results from this study in H2 2023 as data become available.
+Added: 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.
+Added: Key data and conclusions featured in the ESMO presentation include:
+Added: ● 20 patients were enrolled with a median of 4 prior lines of therapy, from which six in the concomitant (CS) (single dose of VCN-01 in combination with durvalumab on day 1) and 12 in the sequential (SS) (single dose of VCN-01 on day -14 and durvalumab on day 1) were evaluable for response.
+Added: ● In the CS cohort at the 3.3×10 12 viral particles (vp) dose, overall survival (OS) was 10.4 months.
+Added: ● In the SS cohort at the 3.3×10 12 vp dose OS was 15.5 months, whereas in the SS cohort at the 1×10 13 vp dose OS was 17.3 months.
+Added: ● 11 patients (61.1%) were alive >12 months (2 in CS;
+Added: 5 in SS at 3.3×10 12 vp, 4 in SS at 1×10 13 vp).
+Added: ● In spite of the advanced stage of the disease, and a global objective response rate for the trial of 5.5%, most of the patients appeared to benefit from subsequent treatment, with 2 patients showing complete responses to palliative chemotherapy and at least one patient still alive 4 years after entering the study.
+Added: ● Biological activity:
+Added: Patients showed VCN-01 replication and increased serum hyaluronidase levels were maintained for over six weeks.
+Added: ● Observed an increase in CD8 T cells, a marker of tumor inflammation and an upregulation of PD-L1 in tumors.
+Added: ● Increase of PDL1-CPS (16/21;
+Added: p=0.013) and CD8 T-cells (12/21;
+Added: p=0.007) from baseline were found in tumor biopsies.
+Added: ● There was a statistical 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
8 unchanged sentences
The study is on-going.
+Added: 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 03, 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.
+Added: VCN-01 persistence was suggestive of tumor infection and active replication.
+Added: 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.
+Added: The study will test higher doses of VCN-01 and will interrogate tumor biopsies to gain further insights.
+Added: The results will inform and guide optimization of the combination of CAR T cells with oncolytic virus.
Phase 1 Trial evaluating the intravenous administration of VCN-01 in patients prior to surgical resection of high-grade brain tumors
80 unchanged sentences
Data generated under this contract are consistent with SYN-004’s (ribaxamase) mode of action of preserving the normal gut flora by degrading ceftriaxone in the upper GI tract of study participants treated with SYN-004 (ribaxamase).
−Removed: The data further demonstrated that SYN-004 (ribaxamase) significantly reduced the loss of microbial diversity, reduced overgrowth of opportunistically pathogenic species, and reduced the emergence of antimicrobial resistance (AMR) genes (such as VRE) caused by ceftriaxone treatment in SYN-004 (ribaxamase) treated patients compared to placebo.
−Removed: Future Planning and Potential Regulatory Strategy for Prevention of Primary CDI
+Added: The data further demonstrated that SYN-004 (ribaxamase) significantly reduced the loss of microbial diversity, reduced overgrowth of opportunistically pathogenic species(such as VRE), and reduced the emergence of antimicrobial resistance (AMR) genes caused by ceftriaxone treatment in SYN-004 (ribaxamase) treated patients compared to placebo.
+Added: Future Potential Regulatory Strategy for Prevention of Primary CDI
On November 21, 2018, we announced results from our End-of-Phase 2 meeting with the FDA during which key elements of a Phase 3 clinical program were confirmed.
13 unchanged sentences
aGVHD occurs in 30-60% of allogeneic HCT recipients and is recognized as a primary contributor to morbidity and mortality in this patient population.
−Removed: In 2018, there were approximately 9,000 reported allogeneic HCT procedures in the USA, an estimated 19,800 procedures in Europe, 9,600 in China, and 3,500 in Japan.
+Added: The most recent available data indicate approximately 8,000 reported allogeneic HCT procedures each year in the USA, 19,800 procedures in Europe, 12,700 in China, and 3,500 in Japan.
First-line treatments for aGVHD fail in more than 50% of patients and 2-year survival in patients with steroid refractory aGVHD is only 20%.
9 unchanged sentences
Schroeder, Associate Professor of Medicine, Division of Oncology, Bone Marrow Transplantation and Leukemia.
−Removed: On January 7, 2020, we announced the receipt of official meeting minutes from the FDA following a Type-C meeting held on December 2, 2019, at our request to discuss the development of SYN-004 (ribaxamase) for treatment of allogeneic HCT recipients who are administered IV beta-lactam antibiotics in response to fever.
−Removed: Based on the final meeting minutes, 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.
+Added: 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 goal of this study is to evaluate the safety, tolerability and potential absorption into the systemic circulation (if any) of oral SYN-004 (ribaxamase;
4 unchanged sentences
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.
−Removed: On July 30, 2020, we received written notification from the FDA informing us that they determined the Phase 1b/2a clinical program in adult allogeneic HCT recipients may proceed per the submitted clinical study protocol.
−Removed: On December 22, 2020, we announced that we received approval from the Institutional Review Board (IRB) at Washington University to commence the Phase 1b/2a clinical trial of SYN-004.
−Removed: During the first quarter of 2021, Washington University began screening patients for enrollment of the first of three antibiotic cohorts in the Phase 1b/2a clinical trial of SYN-004 in allogeneic HCT recipients.
−Removed: On April 14, 2021, we announced that the first patient had been dosed in our Phase 1b/2a clinical trial of SYN-004 (ribaxamase) in allogeneic hematopoietic cell transplant (HCT) recipients for the prevention of acute graft-versus-host-disease (aGVHD.
−Removed: 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 of the Company’s Phase 1b/2a randomized, double-blinded, placebo-controlled clinical trial of SYN-004 (ribaxamase) in allogeneic hematopoietic cell transplant (HCT) recipients for the prevention of acute graft-versus-host-disease (aGVHD).
−Removed: To date, we have completed Cohort 1, which enrolled 19 patients who received at least 1 dose of study drug (SYN-004 or Placebo randomized 2:1).
−Removed: Sixteen patients received at least one dose of intravenous (IV) meropenem and 12 of these patients completed sufficient
−Removed: doses of IV meropenem to be evaluable towards the study endpoints.
−Removed: The study is on-going and remains blinded;
−Removed: however, key findings from blinded data for Cohort 1 are included below:
−Removed: ● Adverse events (AEs) and serious adverse events (SAEs) observed in Cohort 1 were typical of those observed in allo-HCT patients and no AEs or SAEs were determined to be related to study drug treatment by the investigators.
−Removed: o A total of 13 SAEs were reported among 10 patients, with the most common SAE being infections and infestations including sepsis.
−Removed: o One patient died 14 days after the last dose of study drug (within the 30-day reporting period) due to sepsis that was not related to study drug.
−Removed: ● Consistent with previous studies of SYN-004 in healthy volunteers, SYN-004 was not observed in blood samples from the majority of the evaluable patients.
−Removed: o A total of 3 plasma samples (~2% of all analyzed samples) had low but quantifiable levels of SYN-004 using a sensitive ECL assay.
−Removed: o None of the 3 ECL positive plasma samples were found to contain active SYN-004 using a functional enzyme activity assay.
−Removed: ● Meropenem pharmacokinetics were as expected for this patient population.
−Removed: Based on a review of the safety and pharmacokinetic data, the DSMC recommended that the study may proceed to enroll Cohort 2 in which study drug (SYN-004 or Placebo) will be administered in combination with the IV beta-lactam antibiotic piperacillin/tazobactam.
−Removed: 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.
−Removed: On November 3, 2022 we announced the first patient has been dosed in Cohort 2 of its Phase 1b/2a randomized, double-blinded, placebo-controlled clinical trial of SYN-004 (ribaxamase) in allogeneic hematopoietic cell transplant (HCT) recipients for the prevention of acute graft-versus-host-disease (aGVHD, NCT04692181 ).
+Added: 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).
+Added: 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.
+Added: 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.
+Added: On November 3, 2022 we announced the first patient had been dosed in Cohort 2.
+Added: 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.
+Added: 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:
+Added: Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR and at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) respectively.
SYN-020 — Oral Intestinal Alkaline Phosphatase (IAP)
SYN 020 is a quality-controlled, recombinant version of bovine Intestinal Alkaline Phosphatase (IAP) produced under cGMP conditions and formulated for oral delivery.
−Removed: The published literature indicates that IAP functions to diminish GI and systemic inflammation, tighten the gut barrier to diminish “leaky gut,” and promote a healthy microbiome.
+Added: The published literature indicates that IAP functions to diminish GI and systemic inflammation, tighten the gut barrier to diminish “leaky gut,” diminish fat absorption, and promote a healthy microbiome.
Despite its broad therapeutic potential, a key hurdle to commercialization has been the high cost of IAP manufacture which is commercially available for as much as $10,000 per gram.
−Removed: We believe we have developed technologies to traverse this hurdle and now have the ability to produce more than 3 grams per liter of SYN-020 for roughly a few hundred dollars per gram at commercial scale.
+Added: We believe we have developed technologies to traverse this hurdle and now have the ability to produce more than 3 grams per liter of SYN-020 and anticipate a cost of roughly a few hundred dollars per gram at commercial scale.
Based on the known mechanisms as well as our own supporting animal model data, we intended to initially develop SYN-020 to mitigate the intestinal damage caused by radiation therapy that is routinely used to treat pelvic cancers.
1 unchanged sentence
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”).
−Removed: Across the six major markets, the total prevalent cases of celiac disease are expected to increase from 5.8 million cases in 2013 to an expected 8.1 million cases in 2023, representing an annual growth rate of approximately 4%.
−Removed: During the same period, prevalent cases in the U.S.
−Removed: are expected to increase from 2.8 million in 2013 to an expected 4.3 million in 2023, representing a significant market opportunity.
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.
2 unchanged sentences
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.
−Removed: The SAD study enrolled 6 healthy adult volunteers into each of four
−Removed: cohorts with SYN-020 given orally as single doses ranging from 5 mg to 150 mg.
−Removed: Analyses of preliminary data demonstrated that SYN-020 maintained a favorable safety profile, was well tolerated at all dose levels, and no adverse events were attributed to the study drug.
+Added: The SAD study enrolled 6 healthy adult volunteers into each of four cohorts with SYN-020 given orally as single doses ranging from 5 mg to 150 mg.
+Added: The data demonstrated that SYN-020 maintained a favorable safety profile, was well tolerated at all dose levels, and no adverse events were attributed to the study drug.
No serious adverse events were reported.
During the third quarter of 2021 we initiated a Phase 1 clinical study evaluating multiple ascending doses (“MAD”) of SYN-020 ( NCT05045833) .
−Removed: On October 21, 2021 we announced that patient enrollment, dosing and observation commenced in the Phase 1 MAD of SYN-020.
+Added: 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.
14 unchanged sentences
With our transition to an oncology focused Company, we are exploring strategic opportunities to enable advancement of this potentially valuable asset.
+Added: Future Potential Regulatory Strategy for Prevention of Primary CDI
+Added: 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
12 unchanged sentences
2021 Apr 10;332:517-528), showing that VCN-11 induced 450 times more cytotoxicity in tumor cells than in normal cells.
−Removed: 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
−Removed: infected tumors in vivo.
−Removed: VCN-11 evaded NAbs from different sources and tumor level were demonstrated in the presence of high levels of NAbs in vivo, whereas the control virus without ABD was neutralized.
+Added: 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.
+Added: 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.
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).
5 unchanged sentences
Our internal discovery programs are currently evaluating new oncolytic viruses derived from VCN-11 that may expand the potential efficacy of Albumin Shield viruses.
−Removed: SYN-006, SYN-007
−Removed: To date, our research programs have been primarily directed to the development of GI acting products that have generated preclinical proof-of-concept with two pipeline products (SYN-006 and SYN-007) that expand the potential utility of our beta-lactamase strategy.
+Added: SYN-006, SYN-007, other oncolytic virus
+Added: 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).
−Removed: Our research programs may be expanded to include development of new oncolytic virus products and/or explore oncology applications of our existing products such as SYN-006 and SYN-007.
+Added: 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.
Intellectual Property
7 unchanged sentences
The SYN-004 (ribaxamase) program is supported by IP that is assigned to Theriva Biologics, namely U.S.
−Removed: patents and foreign patents (in most major markets, e.g.
+Added: and foreign patents (in most major markets, e.g.
Europe (including Germany, Great Britain and France), Japan, China and Canada, among others) and U.S.
7 unchanged sentences
The SYN-020 (oral intestinal alkaline phosphatase (IAP)) program is supported by IP that is assigned to Theriva Biologics, namely U.S.
−Removed: and foreign patent applications (in many major markets, e.g.
+Added: and foreign patents and patent applications (in many major markets, e.g.
Europe, China, Japan, Korea, Canada, and Australia).
−Removed: These patent applications, which cover various formulations, medical uses and manufacture of SYN-020, are expected to expire in 2038-2040, if granted, and without taking potential patent term extensions or patent term adjustment into account.
−Removed: The VCN-01 and VCN-11 programs are supported by patents and patent applications that are assigned to VCN or exclusively licensed from Fundacio Privada Institut d’Investigacio Biomedica de Bellvitge (IDIBELL), Institut Catala d’Oncologia (ICO), and Hospital Sant Joan de Déu in Barcelona.
+Added: 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.
+Added: The VCN-01 and VCN-11 programs are supported by U.S.
+Added: 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.
The patents and patent applications include U.S.
9 unchanged sentences
We seek, where appropriate, the broadest intellectual property protection for product candidates, proprietary information, and proprietary technology through a combination of contractual arrangements and patents.
+Added: Acquisition of VCN Biosciences, S.L.
+Added: (now known as Theriva Biologics, S.L.)
+Added: On March 10, 2022, we completed our acquisition (the “VCN Acquisition”) of all the outstanding shares of VCN (the “VCN Shares”) from the shareholders of VCN pursuant to the terms of the Share Purchase Agreement (“Purchase Agreement”) that we entered into with VCN and the shareholders of VCN Biosciences, S.L.
+Added: (the “Sellers”) on December 14, 2021.
+Added: Upon consummation of the Acquisition, VCN became our wholly owned subsidiary.
+Added: As consideration for the purchase of the VCN Shares of capital stock, we paid $4,700,000 (the “Closing Cash Consideration”) to Grifols Innovation and New Technologies Limited (“Grifols”), the owner of approximately 86% of the equity of VCN, and issued to the remaining Sellers 2,639,530 shares of our common stock, $0.001 par value (the “Closing Shares”), representing 19.99% of the outstanding shares of our common stock on December 14, 2021, the date of the Purchase Agreement.
+Added: As additional consideration for the purchase of the VCN Shares held by Grifols, we also agreed to make the following milestone payments to Grifols:
+Added: Milestone Payments
+Added: US$3MM upon VCN-01 US IND Safe to Proceed pancreatic ductal adenocarcinoma (“PDAC”, or other first indication), which payment was made in Q4 2022 upon attaining the milestone
+Added: US$2.75MM upon VCN-01 US IND Safe to Proceed – retinoblastoma (“RB”, or other second indication)
+Added: US$3.25MM upon VCN-01 US first patient dosed– PDAC (or other first indication) after receipt of VCN-01 US IND Safe to Proceed for PDAC being informed, which payment was made in Q4 2023 upon attaining the milestone
+Added: US$3.25MM upon VCN-01 US first patient dosed – RB (or other second indication) after receipt of VCN-01 US IND Safe to Proceed for RB being informed
+Added: 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)
+Added: US$8MM upon VCN-01 Pivotal Trial meeting the primary endpoint or upon BLA Submission – RB (or other second indication)
+Added: US$12MM upon VCN-01 US Phase 3 trial meeting the primary endpoint or upon BLA Submission – PDAC (or other first indication)
+Added: US$16MM upon VCN-01 BLA Approval – PDAC (or other first indication)
+Added: US$16MM upon VCN-01 BLA Approval – RB (or other second indication)
+Added: Pursuant to the Purchase Agreement, at the Closing we assumed $2,400,000 of liabilities of VCN, which includes certain loans from the Spanish Government and the Catalan Government Agency.
+Added: The Purchase Agreement contains customary representations, warranties and covenants of the Sellers and us.
+Added: Subject to certain customary limitations, the Sellers have agreed to indemnify us and our officers and directors against certain losses related to, among other things, breaches of their representations and warranties, certain specified liabilities and the failure to perform covenants or obligations under the Purchase Agreement.
+Added: Effective November 15, 2022, as part of our corporate rebranding, VCN changed its name to Theriva Biologics S.L.
+Added: without other changes to its corporate structure.
+Added: Theriva is a clinical-stage biopharmaceutical company developing new oncolytic adenoviruses for the treatment of cancer.
+Added: 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.
+Added: 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.
+Added: 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.
+Added: 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.
+Added: Importantly, degrading the stroma exposes tumor antigens, turning “cold” tumors “hot” and enabling a sustained anti-tumor immune response.
+Added: 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
7 unchanged sentences
The validity period of the license granted is unlimited with the only applicable limit being the patent’s own validity.
−Removed: The ICO License Agreement provides that the ICO is entitled to a royalty of low double digit percentage of the net value of the income from the concession of the identified sublicense and low double digit precentage on other lump sums received thereunder.
−Removed: VCN and its sublicensees have an obligation to o use all diligent and commercially reasonable efforts for the exploitation of the patent, otherwise, ICO may proceed to recover the license.
+Added: The ICO License Agreement provides that the ICO is entitled to a royalty of low double digit percentage of the net value of the income from the concession of the identified sublicense and low double digit percentage on other lump sums received thereunder.
+Added: VCN and its sublicensees have an obligation to use all diligent and commercially reasonable efforts for the exploitation of the patent, otherwise, ICO may proceed to recover the license.
The ICO License terminates upon the expiration of the patent rights and is subject to early termination by either party in the event of a breach by the other party of its obligations thereunder.
IDIBELL/ICO License Agreement
−Removed: On March 4, 2016, VCN entered into a License Agreement (the “IDIBELL/ICO License Agreement”) with IDIBELL and the ICO, for the exclusive license of the right to use a family of patents whose priority application is European patent application EP 14 38 2162.7 titled “Adenovirus comprising an albumin-binding molety”.
+Added: On March 4, 2016, VCN entered into a License Agreement (the “IDIBELL/ICO License Agreement”) with IDIBELL and the ICO, for the exclusive license of the right to use a family of patents whose priority application is European patent application EP 14 38 2162.7 titled “Adenovirus comprising an albumin-binding moiety”.
The License Agreement provides that IDIBELL and ICO, as licensors, are entitled to share a low single digit percentage royalty on the annual Net Sales (as defined in the IDIBELL/ICO License Agreement)collected by VCN from the utilization of products derived from the licensed technology and a royalty on sublicensing income received from the licensed technology at a rate of:
14 unchanged sentences
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.
+Added: 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.
+Added: 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.
+Added: Combination of VCN-01 with a topoisomerase I inhibitor is expected to provide a synergistic antitumor effect wherein a chemotherapy-mediated increase in tumor VCN-01 levels may enable greater degradation of the tumor stroma, significantly increasing chemotherapy access and tumor destruction.
Washington University School of Medicine in St.
29 unchanged sentences
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.
−Removed: The Sponsored Research Agreement was amended on October 22, 2015 to extend its termination date to January 15, 2017:
−Removed: on September 2, 2016 to extend the agreement until January 15, 2018;
−Removed: on August 22, 2017 to extend the agreement until January 17, 2019;on August 24, 2018 to extend the agreement until January 21, 2021;
−Removed: and again on August 18, 2020 which extended the agreement until January 17, 2023;
−Removed: provided, however, the Sponsored Research Agreement is subject to early termination upon the written agreement of the parties, a default in the material obligations under the Sponsored Research Agreement which remain uncured for 60 days after receipt of notice, automatically upon our bankruptcy or insolvency and by us in our sole discretion at any time after the one year anniversary of the date of execution thereof upon no less than 90 days’ notice.
−Removed: Upon a termination or due to a breach by the University, we will 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.
+Added: The termination date of the Sponsored Research Agreement n was amended multiple times and Sponsored Research Agreement expired on January 17, 2023.
+Added: 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.
12 unchanged sentences
We plan to rely on third parties to manufacture commercial quantities of products that we successfully develop through regulatory approval.
−Removed: We have contracted with two CDMOs to provide what it believes are adequate clinical supplies for our planned clinical trials.
+Added: We have contracted with GenIbet and ThermoFisher 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.
9 unchanged sentences
Commercial quantities of any drugs we seek to develop will have to be manufactured in facilities and by processes that comply with the FDA and other regulations, and we plan to rely on third parties to manufacture commercial quantities of products we successfully develop through FDA approval.
−Removed: We believe we have sufficient quantities of SYN-004 to complete our planned Phase 1b/2a clinical trial of SYN-004, and are working with qualified third-party vendors for the potential manufacture of additional quantities of SYN-004 and SYN-020 for potential future preclinical studies and clinical trials.
Research and Development
25 unchanged sentences
The testing and approval process requires substantial time, effort, and financial resources, and we cannot be certain that any approval will be granted on a timely basis, if at all.
−Removed: OVs such as VCN-01 are genetically modified organisms and their import and use are subject to additional review and approval by dedicated agencies in some countries where we propose to run clinical trials, including Spain and Germany.
+Added: OVs such as VCN-01 are genetically modified organisms and their import and use are subject to additional review and approval by dedicated agencies in some countries where we propose to run clinical trials, including Spain and other European countries.
Preclinical tests include laboratory evaluation of the product candidate, its chemistry, formulation and stability, and animal studies to assess potential safety and efficacy.
26 unchanged sentences
The FDA has substantial discretion in the approval process and may disagree with our interpretation of the data submitted or identify new concerns.
−Removed: The process may be significantly
−Removed: extended by requests for new information or clarification of information already submitted.
+Added: The process may be significantly extended by requests for new information or clarification of information already submitted.
As part of this review, the FDA may refer the application to an advisory committee, typically a panel of clinicians.
31 unchanged sentences
The requirements, costs and timing for obtaining and maintaining EMA Orphan Drug Designation differ from the FDA.
−Removed: 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.
+Added: 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.
+Added: In June 2023, the FDA granted Orphan Drug Designation to VCN-01 for the treatment of pancreatic cancer.
Other Healthcare Laws and Compliance Requirements
40 unchanged sentences
In addition, many of these competitors may be able to obtain patent protection, obtain FDA and other regulatory approvals and begin commercial sales of their products before us.
−Removed: Companies that currently sell or are developing proprietary products for the prevention and treatment of C.
−Removed: difficile infection include:
−Removed: Actelion Pharmaceutical Ltd., Artugen Therapeutics, Inc., AzurRx, Inc., Deinove, Pfizer Inc., Merck & Co.
−Removed: Inc., Merus B.V., Pfizer Inc., Rebiotix, Inc., Seres Therapeutics, Inc., Summit Therapeutics plc.
−Removed: and Vedanata Biosciences Inc.
−Removed: Companies that sell or are developing products for the treatment or prevention of acute graft-versus-host-disease (aGVHD) include:
−Removed: Amgen, Inc., Astellas Pharma, Janssen Biotech, Inc., Mallinckrodt plc, Mesoblast, Inc., Novartis International AG, Pfizer, Inc.
−Removed: Roche AG and Takeda Pharmaceutical Company Ltd.
+Added: 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.
2 unchanged sentences
More than 60 companies have publicly identified that they are pursuing clinical development of different forms of OV products.
−Removed: Adenoviruses are the most commonly used viruses in these programs, with modified adenoviruses under development by companies including AdCure Bio LLC, Candel Therapeutics, Inc., CG Oncology, Inc., DNAtrix, Inc., EpicentRx, Inc., GeneMedicine, Co Ltd., IconOVir Bio, Inc., Lokon Pharma AB, Multivir, Inc., NewGenPharm Incorporation, Oncolys BioPharma, Inc., Orca Therapeutics B.V., PsiOxus Therapeutics Ltd, Shanghai Sunway Biotech Co., Ltd , Targovax Oy|Targovax ASA, Tessa Therapeutics, TILT Biotherapeutics, Ltd., and Valo Therapeutics Oy.
+Added: 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.
OV products have been or are being developed using other virus backbones, including:
−Removed: Coxsackie virus (Viralytics Ltd., Oncorus Inc.);
−Removed: herpes simplex virus (Amgen, Inc., Candel Therapeutics, Inc., Daiichi Sankyo Company Ltd., Oncorus, Inc., Replimune, Inc., Takara Bio, Inc., Wuhan Binhui Biotechnology Co., Ltd.);
+Added: arenavirus (Hookipa Pharma, Inc.), Coxsackie virus (Viralytics Ltd., Oncorus Inc.);
+Added: herpes simplex virus (Amgen, Inc., Candel Therapeutics, Inc., Daiichi Sankyo Company Ltd.,ImmVira Co.
+Added: Ltd, Replimune, Inc., Takara Bio, Inc., Treovir LLC, Virogin Biotech, Inc.
+Added: Wuhan Binhui Biotechnology Co., Ltd.);
Maraba virus (Turnstone Biologics, Inc.);
−Removed: measles virus (Vyriad, Inc.);
+Added: measles virus (Themis Biosciences GmbH, Vyriad, Inc.);
myxoma virus (OncoMyx Therapeutics, Inc.);
1 unchanged sentence
KG), reovirus (Oncolytics Biotech, Inc.);
−Removed: Seneca Valley virus
−Removed: (Seneca Therapeutics Inc., Oncorus Inc.);
−Removed: vesicular stomatitis virus (Vyriad, Inc.);
−Removed: and vaccinia viruses (Genelux Corporation, KaliVir Immunotherapeutics LLC, SillaJen, Inc., Transgene SA, Turnstone Biologics, Corp.).
−Removed: OV companies that have identified pancreatic cancer or PDAC as a proposed clinical indication include Candel Therapeutics, Inc., GeneMedicine, Co Ltd., Lokon Pharma AB, NewGenPharm Incorporation, Oncolytics Biotech, Oryx GmbH & Co.
−Removed: KG, V2ACT Therapeutics™ LLC (a Genelux Corporation joint venture), and Wuhan Binhui Biotechnology Co., Ltd.
+Added: poliovirus (Istari Oncology, Inc.);Seneca Valley virus (Seneca Therapeutics Inc., Oncorus Inc.);
+Added: vesicular stomatitis virus (Boehringer Ingelheim, Cytonus Therapeutics, Inc., Vyriad, Inc.);
+Added: and vaccinia viruses (Genelux Corporation, Imugene Ltd, Joint Biosciences Ltd, KaliVir Immunotherapeutics LLC, SillaJen, Inc., Transgene SA, Turnstone Biologics, Corp.).
+Added: OV companies that have identified pancreatic cancer or PDAC as a proposed clinical indication include Akamis Bio Ltd, Boehringer Ingelheim GmbH, Candel Therapeutics, Inc., GeneMedicine, Co Ltd., Lokon Pharma AB, Memgen, Inc., NewGenPharm Incorporation, Oncolytics Biotech, Oryx GmbH & Co.
+Added: KG, Takara Bio, Inc., TILT Biotherapeutics Ltd), V2ACT Therapeutics™ LLC (a Genelux Corporation joint venture), Virogin Biotech, Inc.,and Wuhan Binhui Biotechnology Co., Ltd.
OV companies that have identified retinoblastoma as a potential target indication include Seneca Therapeutics Inc.
3 unchanged sentences
have reduced liver tropism compared to wild type adenovirus type 5;
−Removed: and express an enzyme (PH20) that degrades the tumor stroma barrier.
−Removed: If confirmed in Phase 2 and later clinical trials, we believe these features significantly differentiate Theriva Biologics’ products from competing OVs and will enable our products to be co-administered with other therapeutic modalities such as chemotherapy and immune therapy to improve cancer treatment outcomes.
+Added: and express an enzyme (PH20 hyaluronidase) that degrades the tumor stroma barrier.
+Added: If confirmed in Phase 2 and later clinical trials, we believe these features significantly differentiate Theriva Biologics’ products from competing OVs and will enable our products to be co-administered with other therapeutic modalities such as chemotherapy and immuno - oncology products to improve cancer treatment outcomes.
+Added: Companies that currently sell or are developing proprietary products for the prevention and treatment of C.
+Added: difficile infection include:
+Added: Actelion Pharmaceutical Ltd., Artugen Therapeutics, Inc., AzurRx, Inc., Deinove, Pfizer Inc., Merck & Co.
+Added: Inc., Merus B.V., Pfizer Inc., Rebiotix, Inc., Seres Therapeutics, Inc., Summit Therapeutics plc.
+Added: and Vedanta Biosciences Inc.
+Added: Companies that sell or are developing products for the treatment or prevention of acute graft - versus - host - disease (aGVHD) include:
+Added: Amgen, Inc., Astellas Pharma, Janssen Biotech, Inc., Mallinckrodt plc, Mesoblast, Inc., Novartis International AG, Pfizer, Inc.
+Added: Roche AG and Takeda Pharmaceutical Company Ltd.
+Added: 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.
Corporate History
8 unchanged sentences
We believe that our success depends upon our ability to attract, develop and retain key personnel.
−Removed: Prior to the VCN Acquisition, we employed 9 individuals, all of whom were full-time employees, of which 5 were part of our research and clinical development team and clinical development team and 4 were part of our financial reporting and accounting team.
−Removed: As of March 30, 2023, we employed 21 individuals, all 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, 1 is 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.
+Added: 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.
A significant number of our management and professional employees have had prior experience with pharmaceutical, biotechnology or medical product companies.
18 unchanged sentences
● initiating regular communication regarding impacts of the COVID-19 pandemic, including health and safety protocols and procedures.
−Removed: Our principal executive offices are located at 9605 Medical Center Drive, Suite 270, Rockville, Maryland 20850.
−Removed: VCN personnel will continue to operate from laboratories and office space leased from Grifols at Torrent de Can Ninou, naus 5-6, 08150 – Parets del Vallès, Barcelona, Spain.
Available Information
9 unchanged sentences
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.