Theriva Biologics, Inc. is a diversified, clinical-stage biopharmaceutical company dedicated to developing innovative therapeutics designed to treat cancer and other high-unmet need diseases. With a strategic focus on oncology, the company has leveraged its expertise to advance a robust pipeline of product candidates, led by its lead asset VCN-01, a novel oncolytic adenovirus.
Business Overview and History
Theriva Biologics, formerly known as Synthetic Biologics, Inc., has undergone a significant transformation in recent years. The company was originally focused on developing therapeutics for gastrointestinal (GI) diseases, with key clinical development candidates including SYN-004 (ribaxamase) and SYN-020 (intestinal alkaline phosphatase). SYN-004 was designed to degrade certain IV beta-lactam antibiotics within the GI tract to prevent microbiome damage, while SYN-020 was a recombinant oral formulation of the enzyme intestinal alkaline phosphatase intended to treat local GI and systemic diseases.
In March 2022, the company made a strategic shift by acquiring Theriva Biologics, S.L. (formerly VCN Biosciences, S.L.), a clinical-stage oncology company based in Spain. This acquisition marked a pivotal moment in the company's history, transitioning its focus to oncology and bringing VCN-01, an oncolytic adenovirus designed for intravenous and intravitreal delivery to treat cancer, into its pipeline.
Since the acquisition, Theriva Biologics has primarily focused on advancing VCN-01 through clinical development. However, the company has maintained its earlier GI-focused programs, including SYN-004 and SYN-020, although it has faced challenges in advancing these programs due to funding constraints. As a result, Theriva has explored opportunities to out-license or partner the further development of these assets while prioritizing its oncology-focused pipeline.
VCN-01, Theriva's lead product candidate, is a systemically administered, tumor-selective oncolytic adenovirus engineered to express the PH20 hyaluronidase enzyme. This innovative approach is designed to degrade the tumor stroma, improving the penetration and distribution of the virus as well as co-administered cancer therapies. VCN-01 is currently being evaluated in a Phase 2b clinical trial for the treatment of metastatic pancreatic ductal adenocarcinoma (PDAC) in combination with standard-of-care chemotherapy. Additionally, the company is investigating VCN-01 in a Phase 1 trial for the treatment of retinoblastoma, a rare pediatric eye cancer.
Theriva's pipeline also includes several earlier-stage programs focused on next-generation oncolytic viruses and the company's proprietary "Albumin Shield" technology, which is designed to enhance the tumor-targeting capabilities of its oncolytic viruses.
Financials and Liquidity
As of June 30, 2024, Theriva Biologics reported cash and cash equivalents of $16.6 million. The company has not generated any revenue, as its pipeline candidates are still in various stages of clinical development. For the six months ended June 30, 2024, the company reported a net loss of $13.5 million, with research and development expenses of $6.4 million and general and administrative expenses of $3.4 million.
Theriva's financial position and liquidity have been a concern, as the company has experienced significant losses since its inception and has a substantial accumulated deficit of $322.8 million as of June 30, 2024. The company's independent registered public accounting firm has issued a report for the year ended December 31, 2023 that includes an explanatory paragraph referring to the company's recurring losses from operations, anticipated continued losses in the future, and net capital deficiency, which raise substantial doubt about its ability to continue as a going concern without additional capital.
To address its capital needs, Theriva Biologics has been actively pursuing additional equity or debt financing, including through the use of an at-the-market (ATM) offering program. During the six months ended June 30, 2024, the company raised $1.8 million in net proceeds through the ATM program. However, the company's ability to continue as a going concern remains uncertain, and its future funding requirements will depend on the progress and success of its clinical development programs, particularly VCN-01.
For the most recent fiscal year (2023), Theriva Biologics reported a net loss of $18,349,000. In the most recent quarter (Q2 2024), the company reported a net loss of $8,316,000, with an operating cash flow of -$3,452,000 and a free cash flow of -$3,453,000. The net loss for the quarter was primarily due to continued investment in research and development activities, including the ongoing Phase 2 clinical trial of VCN-01 in pancreatic cancer, as well as a goodwill impairment charge of $4.07 million recorded during the quarter.
As of June 30, 2024, Theriva Biologics had a debt-to-equity ratio of 0.006, a current ratio of 2.88, and a quick ratio of 2.88. Management believes that the current cash and cash equivalents of $16.59 million will be sufficient to fund operations into the second quarter of 2025. However, the company will need to raise additional capital in the future to continue the development of its product candidates.
Pipeline and Clinical Development
Theriva Biologics' clinical pipeline is primarily focused on the development of VCN-01, its lead oncolytic adenovirus candidate. The company is currently conducting the following key clinical trials:
1. VIRAGE Phase 2b Trial in Metastatic Pancreatic Cancer - In January 2023, Theriva initiated the VIRAGE Phase 2b randomized, open-label, placebo-controlled, multicenter clinical trial of systemically administered VCN-01 in combination with standard-of-care chemotherapy (gemcitabine and nab-paclitaxel) as a first-line therapy for patients with newly diagnosed metastatic PDAC. - The trial is expected to enroll approximately 92 patients across 17 sites in the U.S. and Europe. - Topline data from the VIRAGE trial is anticipated in the second half of 2025.
2. Phase 1 Trial of Intravitreal VCN-01 in Retinoblastoma - In 2017, Theriva entered into a clinical trial agreement with Hospital Sant Joan de Déu Barcelona, Spain to conduct a Phase 1 investigator-sponsored study evaluating the safety and tolerability of two intravitreal injections of VCN-01 in patients with intraocular retinoblastoma. - In April 2024, Theriva announced positive topline data from this study, with the study's Monitoring Committee determining the trial had a positive outcome. - Based on these results, Theriva will receive an exclusive, worldwide license and related patents from the hospital for the treatment of pediatric patients with advanced retinoblastoma.
In addition to the VCN-01 programs, Theriva's pipeline includes several earlier-stage candidates focused on next-generation oncolytic viruses and the company's proprietary "Albumin Shield" technology, which is designed to enhance the tumor-targeting capabilities of its oncolytic viruses.
The company is also developing next-generation oncolytic adenoviruses called VCN-X, which include modifications to improve tumor cell killing and pharmacokinetics. Preclinical proof-of-concept has been established for VCN-11, which includes an albumin-binding domain to help evade neutralizing antibodies.
Theriva Biologics' GI and microbiome-focused pipeline includes two clinical candidates:
1. SYN-004 (ribaxamase): An oral capsule therapy designed to degrade certain IV beta-lactam antibiotics in the GI tract to prevent disruption of the gut microbiome, which can lead to conditions like Clostridioides difficile infection (CDI) and acute graft-versus-host disease (aGVHD) in allogeneic hematopoietic cell transplant recipients. A Phase 1b/2a clinical trial of SYN-004 is ongoing.
2. SYN-020: A recombinant, orally-delivered form of the enzyme intestinal alkaline phosphatase (IAP) intended to treat GI and systemic inflammatory conditions. Phase 1 clinical trials evaluating the safety and pharmacokinetics of SYN-020 have been completed.
Competitive Landscape and Risks
Theriva Biologics operates in the highly competitive oncology space, with numerous large pharmaceutical and biotechnology companies developing various cancer therapies. The company faces significant competition from both established and emerging players in the oncolytic virus and immuno-oncology fields.
Key risks facing Theriva Biologics include: - Uncertainty around the company's ability to continue as a going concern due to its significant accumulated losses and limited cash resources - Risks associated with the clinical development and regulatory approval of its pipeline candidates, particularly VCN-01 - Intense competition from larger, well-resourced companies in the oncology space - Potential challenges in manufacturing and scaling up production of its virus-based therapies - Reliance on key strategic partnerships and collaborations to advance its programs
Outlook and Conclusion
Theriva Biologics' transition to an oncology-focused company has been a pivotal moment in the company's history, as it seeks to leverage its expertise in oncolytic viruses to address significant unmet medical needs in cancer treatment. The advancement of VCN-01 through clinical trials, particularly the ongoing VIRAGE Phase 2b study in metastatic PDAC, will be a crucial determinant of the company's future success.
However, Theriva Biologics faces substantial financial and operational challenges, including its ability to secure the necessary funding to sustain its clinical development efforts. The company's survival will depend on its ability to effectively navigate the competitive oncology landscape, establish strategic partnerships, and demonstrate the clinical and commercial potential of its innovative therapeutic approach.
As Theriva Biologics continues to evolve, investors will closely monitor the company's progress in advancing its pipeline, particularly VCN-01, as well as its efforts to address its liquidity concerns and long-term viability. The company's ability to overcome these obstacles and capitalize on the promise of its oncolytic virus platform will be key to its future success in the dynamic and highly competitive oncology market.
The company's focus on developing both oncology-focused and GI and microbiome-focused pipelines demonstrates its commitment to addressing multiple areas of unmet medical need. However, the lack of revenue generation and ongoing losses underscore the challenges faced by clinical-stage biopharmaceutical companies. Theriva Biologics will need to carefully manage its resources and potentially secure additional funding to support its ongoing clinical trials and advance its pipeline candidates towards potential commercialization.