Theriva Biologics, Inc.

Good day and welcome to the TerraEV Biologics Formally Synthetic Biologics 2022 Third Quarter Operational Highlights and Financial Results. Today's conference is being recorded. At this time, I would like to turn the conference over to Mr. Chris Calabresi, LifeSci Advisors Relationship Manager. Please go ahead, sir.

Thank you, Operator, and good morning, everyone. Welcome to the Theriva Biologics 2022 Third Quarter Investor Conference Call. Leading the call today will be Stephen Shawcross, Chief Executive and Chief Financial Officer of Theriva Biologics. Dr. Manel Cascaio, General Director of Theriva Biologics European Subsidiary, Dr. Frank Tafaro, Chief Operating Officer, and Dr. Vince Wacher, Head of Corporate and Product Development of Theriva Biologics are also on the call and will be available to answer questions during the Q&A session. Cereva Biologics issued a press release last evening which provided operational highlights and included the financial results for the third quarter ending September 30, 2022. The press release can be found in the investor section of the company website at www.cerevabio.com, together with the quarterly report on Form 10-Q for the quarter ended September 30, 2022. which we filed last night with the Securities and Exchange Commission. In addition to the phone line, this call is being streamed live via webcast, which will be archived on the company website, www.CerevaBio.com, for 90 days. During this call, certain forward-looking statements regarding Cereva Biologics and DCN Biosciences, current expectations and projections about future events will be made. Generally, the forward-looking statements can be identified by terminology such as may, should, expects, anticipates, intends, plans, believes, estimates, and similar expressions. These statements are based on current beliefs, expectations, and assumptions. subject to a number of risks and uncertainties, including those set forth in Cereva Biologic filings with the SEC, many of which are difficult to predict. No forward-looking statements can be guaranteed, and actual results may differ materially from such statements. The information on this call was provided only as of the date of this call, and Cereva Biologics undertakes no obligation to update any forward-looking statements on this conference call on account of new information, future events, or otherwise except as required by law. With that, I'd like to turn the call over to Steve. Steve?

Thanks, Chris. Good morning, everyone, and I appreciate you taking the time to join us on our call today. We are very pleased to be speaking with you today as Theriva Biologics, a unifying new brand for the company, that reflects our rapidly increasing momentum as a leading multinational developer of innovative, differentiated therapies for cancer and related diseases. Along with a new name, logo, and corporate website, the company began trading on the NYSE under the ticker TOVX on October 13th. Today, I'll present an update on our progress and well-defined path forward, which we believe will drive shareholder value and long-term success. In the third quarter of 2022, we accelerated the clinical advancement of Theriva's oncology-focused portfolio, dedicating our primary resources to our lead clinical candidate, BCN01, a systemically administered oncolytic adenovirus designed to selectively replicate within the tumor, remodel the tumor matrix, and increase tumor immunogenicity. We also reported positive clinical data and have now initiated the second cohort of a Phase 1b2a clinical trial of SYN4, our product designed to prevent potentially fatal adverse outcomes in patients who undergo alginic hematopoietic cell transplant, or HCT, to treat hematologic cancers. Preclinical pipeline expansion activities during the third quarter concentrated on optimizing VCN11 and exploring related oncolytic virus candidates, incorporating our novel albumin shield technology, which is designed to protect systemically administered oncolytic viruses from the host immune system. We believe the albumin shield technology may facilitate repeated administration of oncolytic virus therapies, increasing their efficacy, and potentially allowing our pipeline programs to be used in standard treatment cycles that are well established in cancer chemotherapy. Overall, we're extremely pleased with our progress that positions Theriva at the forefront of oncolytic virus development. With a focused portfolio and an expected financial runway into the first quarter of 2024, we are well positioned to deliver on a number of value-enhancing milestones. I'm now excited to share with you the details of our pipeline progress, starting with our lead program, VCN01. Building on the positive results of our Phase I studies, we've designed VARAGE, a multinational Phase II clinical study evaluating intravenous VCN01 in newly diagnosed metastatic pancreatic cancer patients treated with first-line standard of chemotherapy, namely genocidabine and napaxitaxel. The RIVAGE clinical trial is a randomized, controlled, multi-center, open-label Phase II study that's expected to enroll up to 92 adults at sites across the U.S., Spain, and Germany. In one treatment arm, patients will receive genocidabine and napaxitaxel standard of care chemotherapy, and in the second, treatment arm, patients will receive VCN01 administered seven days prior to gencitabine and napaxitaxel. Two doses of VCN01 will be administered approximately three months apart. In the third quarter, Virage received regulatory clearance from both the FDA and the Spanish Competent Authority to proceed. We've also received clarification queries from regulators in Germany, and we plan to respond to these very shortly. We've also commenced site initiation visits in Spain, and we remain on track to dose the first patient in the fourth quarter of 2022. Primary endpoints for the study include overall survival and safety and tolerability. Additional endpoints include progression-free survival, objective response rates, and measures of biodistribution, virus replication, and immune response. Since this is anticipated to be a two-arm, open-label study, we plan to monitor the study's progress very, very closely and try to accelerate the clinical program if supported by the emerging data. In addition to initiating the VIRAGE pancreatic cancer trial, we've continued to refine our proposed clinical trial in retinoblastoma. Since there is no regulatory guidance for the development of retinoblastoma medicines, we have worked closely with key opinion leaders from well-known treatment centers across the U.S., Europe, Central, and South America to confirm the optimal patient population and treatment line for intravitreal BCN01 to treat vitreous seeds and children with retinoblastoma. We look forward to leveraging the orphan drug designation for BCN01 in this indication to facilitate protocol discussions with the FDA and other regulatory agencies. In addition to the planned company-sponsored studies, there are several investigator-sponsored studies underway at world-leading oncology research institutions. At this year's ESMO Congress, we presented initial data from a Phase I investigator-sponsored study evaluating VCN01 in combination with drivalumab for patients with recurrent metastatic squamous cell carcinoma of the head and neck. We are encouraged by the acceptable safety profile seen in the sequential arm of this study, as well as the biological activity observed in these head and neck cancer patients previously treated with anti-PD-L1 agents. These data speak to the promise of VCN01 as a potential means of enhancing the efficacy of immunotherapeutic agents in patients whose cancers have been unresponsive to these powerful cancer therapies. Our investigator-sponsored study with Universita leads to evaluate VCN01 in patients with high-grade brain tumors. It's currently recruiting patients with dosing of the first patient expected in the fourth quarter of 2022. This study is designed to determine whether systemically administered VCN01 can reach tumors in the brain. Treatment of these tumors typically requires surgery and or direct injection. Therefore, successful delivery of VCN01 to the brain after systemic administration could potentially transform the way these cancers are treated. In parallel to our clinical studies with VCN01, we are keenly advancing our albumin shield technology platform. Our albumin shield oncolytic viruses incorporate a proprietary albumin binding domain in the virus's outer shell. This is designed to improve systemic delivery by enabling the virus to coat itself with host serum albumin to prevent inactivation by antiviral neutralizing antibodies. IND-enabling studies are being planned, and we expect to begin these studies following the completion of ongoing preclinical and CMC activities. We look forward to building upon our foundation of compelling proof-of-mechanism data and continuing to advance our VCN11 program through clinical development. Finally, I'm turning to SYN4, or ribaximase. Washington University has dosed the first patient in Cohort 2 of our Phase 1b-2a study of CIN4 to prevent acute graft-versus-host disease in patients undergoing allogeneic HCT to treat hematologic cancers. In the Phase 1b-2a study, it's designed to assess the feasibility of using CIN4 in a specific patient population and to provide key information requested by the FDA regarding the safety and tolerability of SYN4 in patients with impaired intestinal barrier function. The study targets completion of eight participants who received SYN4 and four who received placebo in each of three sequential cohorts designed to compare different IV beta-lactam antibiotics to treat fever following conditioning therapy. As we reported in September, Progress to cohort two was permitted by an independent safety monitoring committee after a detailed review of safety and pharmacokinetic data from the first antibiotic cohort administering meropenem. The second antibiotic cohort will evaluate combination of SYN4 with pripracillin and tezobactam. We are very pleased with the continued advancement of SYN4 as part of our oncology portfolio, and we are grateful for the tremendous support from Dr. DeBerkey and his team at Washington University. Together, we will continue to work towards reducing potentially fatal adverse outcomes such as KGVHD and L-genetic HCT recipients. In summary, we've made steady progress throughout the third quarter of 2022. With a cash runway into the first quarter of 2024, we are well positioned to reach potentially transformational inflection points across our oncology-focused pipeline. Near and long-term clinical milestones include the dosing of the first patient in barrage, our Phase II study in patients with metastatic PDAC in the fourth quarter of 2022, the dosing of BCN01 in the first patient with high-grade brain tumors at the University of Leeds in the fourth quarter of 2022, holding a pre-IND meeting with the FDA for our planned clinical study in retinal blastoma in early 2023, ahead of the anticipated study initiation in the second half of 2023, and completing the second cohort of our Phase 1b2a clinical study of SYN4 for the prevention of acute graft-free cystosis disease in bone marrow transplant patients in the first quarter of 2024. As you can see, we've positioned our company to deliver on a number of key value creating milestones over the next six to 12 months. By prioritizing our core clinical programs, we have the ability to efficiently utilize our current cash position, which carries us into the first quarter of 2024 to deliver on important clinical data and related milestones. Now I'd like to turn briefly to our financial results for the three months ended September 30, 2022. General administrative expenses increased $2.4 million for the three months ended September 30, 2022 from $1.3 million for the three months ended September 30, 2021. This increase of 88% was primarily comprised of increased consulting and legal costs related to the VCN acquisition, an increase in the fair value of contingent consideration, higher insurance cost audit fees and public relation expenses, and VCN administrative expenses not included in the prior year. The charge related to SOC-based compensation expense was $93,000 for the three months ended September 30, 2022 compared to $83,000 for the three months ended September 30, 2021. Research and development expenses increased to $2.6 million for the three months ended September 30, 2022 from $2 million for the three months ended September 30, 2021. This increase of 30% is primarily the result of VCN research expense related to VCN01 not incurred in the prior year and, to a lesser extent, higher manufacturing expenses related to our Phase I clinical trial of CIN20. We anticipate research and development expense to increase as we plan for and initiate enrollment for our VARAGE Phase II clinical trial for VCN01 in PDAC and our proposed clinical trial retinobistoma, expand GMP manufacturing activities for VCN01 and continue supporting our VCN 11 and other preclinical and discovery initiatives. The charge related to stock-based compensation expense was $28,000 for the three months ended September 30, 2022, compared to $19,000 related to stock-based compensation expense for the three months ended September 30, 2021. Other income was $161,000 for the three months ended September 30, 2022, compared to other income of $2,000 for the three months ended September 30, 2021. Other income for the three months ended September 30, 2022 is primarily comprised of interest income of $170,000 offset by an exchange loss of $9,000. Other income for the three months ended September 30, 2021 was primarily comprised of interest income. Cash and cash equivalents totaled $50.5 million as of September 30, 2022, compared to $67.3 million as of December 31, 2021. In summary, we've had yet another quarter of great progress, and we're very excited about Toreba's renewed corporate strategy and path towards strategic growth. We believe our OV programs could represent a generational leap forward for patients in need of better treatment options And we look forward to advancing VCN01 and VCN11 through clinical development. In parallel, we will continue to evaluate strategic opportunities that unlock value for our company. And with that, we're happy to take questions.