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spk06: Ladies and gentlemen, good morning and welcome to the Tergiva Biologics, Inc. 2023 Second Quarter Earnings Conference Call. At this time, all participants are in a listen-only mode. A brief question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star and zero on your telephone keypad. As a reminder, this conference is being recorded. It is now my pleasure to introduce your host, Chris Calabrese from Lifesave Advisors. Please go ahead.
spk03: Thank you, Operator, and good morning, everyone. Welcome to Theriva Biologics' second quarter of 2023 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, and Dr. Vince Wacher, Head of Corporate and Product Development of Cereva Biologics, are also on the call and will be available to answer questions during the Q&A session. Cereva Biologics issued a press release this morning, which provided operational highlights and included the financial results for the second quarter ending June 30, 2023. The press release can be found in the Investors section of the company website at www.cerevabio.com. together with the quarterly report on Form 10-Q for the quarter ended June 30, 2023, which we plan to file today with the Securities and Exchange Commission, or SEC. In addition to the phone line, this call is being streamed live via webcast, which will be archived on the company website, www.therivabio.com, for 90 days. During this call, certain forward-looking statements regarding Theriva Biologics and VCN 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 upon current beliefs, expectations, and assumptions and are subject to a number of risks and uncertainties, including those set forth in Theriva Biologics 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 is provided only as of the date of this call, and Cereva Biologics undertakes no obligation to update any forward-looking statements contained 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.
spk04: Steve? Thanks, Chris. Good morning, and I appreciate everyone taking the time to join us today. We're making tremendous progress with advancing our organization and addressing unmet needs for difficult-to-treat cancers, and in the second quarter of 2023, we continue to drive forward our oncology-focused portfolio. With our extended cash runway into the fourth quarter of 2024, we believe we're well-positioned to execute on our corporate objectives and remain on track to reach multiple value-enhancing milestones. Our primary efforts and resources are focused on pursuing multiple therapeutic opportunities for our lead clinical candidate, BCN01. As a reminder, BCN01 is a systemically administered oncolytic adenovirus designed to selectively replicate within the tumor, degrade the tumor matrix, and increase tumor immunogenicity. We believe these multiple modes of action position VCN01 for optimized tumor killing across several indications and in combination with different types of therapies. Our confidence in VCN01 is built on a strong clinical foundation as VCN01 has been administered to more than 90 patients so far in diverse indications that include pancreatic ductal adenocarcinoma, or PDAC, head and neck squamous cell carcinoma, colorectal cancer, ovarian cancer, and retinoblastoma. BCN01 has been awarded orphan drug designation in the U.S. and Europe for the treatment of pancreatic cancer and in the U.S. for retinoblastoma, providing additional opportunities for regulatory engagement and, if approved, market exclusivity. The potential use of VCN01 to enable and enhance the use of chemotherapy and immune checkpoint inhibitors in otherwise refractory solid tumors is a strategic focus for Tereva that may provide multiple opportunities in areas of high therapeutic need. I'm pleased today to report recent highlights from our ongoing programs evaluating VCN01 in different indications in combination with chemotherapy, immune checkpoint inhibitors, and CAR T-cells. First, enrollment is accelerating in VIRAGE, our multinational Phase IIb clinical trial evaluating intravenous VCN01 in combination with standard-of-care chemotherapy, gencitabine, napaxitaxel, as a first-line therapy for patients with PDAC. The first patients at study sites in Spain have received their second doses of VCN01, and U.S. sites have dosed their first patients in the trial. Repeated dosing of VCN01, if effective, is expected to enable dosing in more standardized treatment cycles and potentially improve treatment outcomes. Second, survival data for patients treated with VCN01 in combination with the immune checkpoint inhibitor Dervalumab in patients with recurrent metastatic head and neck cancer will be presented at the ESMO conference in October. Biochemical and mechanistic data presented last year demonstrated that VCN01 improved tumor immunogenicity in previous immunotherapy refractory patients, and the upcoming presentation will discuss and highlight some of the first clinical outcomes data evaluating the feasibility of a VCN01 checkpoint inhibitor combination. And third, the University of Pennsylvania continues to enroll and treat patients in their investigator-sponsored trial administering VCN01 with Hugh Carty mesocells in ovarian and pancreatic cancer patients. Initial data from this trial were presented at the Silicon Valley conference in June, highlighting the feasibility of administering VCN01 with Hugh Carty mesocells to treat solid tumors. CAR-T cell therapies have had limited efficacy against solid tumors to date, and we look forward to further data from the study to determine if VCN01 can improve patient outcomes with these powerful immunotherapies. Looking ahead, we intend to meet with the FDA in the second half of 2023 to discuss the development pathway for VCN01 as an adjunct to chemotherapy in pediatric patients with advanced retinoblastoma. Further, As we continue to explore the potentially broad synergistic clinical benefit of ECN01, we remain committed to pursuing new oncolytic virus candidates to leverage our novel of human shield technology, which is designed to protect systemically administered oncolytic viruses from the host immune system and may facilitate repeated administration of oncolytic virus therapies. This may enable our pipeline of programs to be used in standardized treatment cycles that are well-established in cancer chemotherapy and immunotherapy. Additionally, as part of our oncology-focused portfolio, in addition to exploring the potential clinical benefits of VCN01 and different solid tumor indications, we continue to screen and enroll patients in the second cohort, of the Phase 1b two-way clinical trial of SYN4, which we expect to complete in the first quarter of 2024. As a reminder, SYN4 is designed to prevent potentially fatal adverse outcomes in patients who undergo L-genetic hematopoietic cell transplant, or HCT, to treat hematological cancers. I will now provide further detail on how these programs continue to position Theriva at the forefront of oncolytic virus development, starting with our lead program, BCN01. With a five-year survival rate of only 3%, metastatic PDAC has one of the lowest survival rates among all cancers and is an indication that it's ripe for innovation. It is well established that the PDAC tumor matrix is one of the key reasons for the overall poor therapeutic outcomes for these patients. We believe ECN01 has the potential to address the urgent need for new treatment options for patients with PDAC by degrading the tumor matrix and increasing tumor access by standard of care chemotherapy. The initiation of dosing at U.S. sites in the VARAGE trial and the completion of the second VCN01 doses for the first patients in Spain are important accomplishments that add to the strong momentum for VCN01 development. We are extremely encouraged by the reported safety profile following the second VCN dose, which was consistent with the safety profile observed for single doses of VCN01 administered with standard of care chemotherapy in this and previous clinical trials. More broadly, the VARAGE trial will enable us to determine the feasibility of repeated dosing of ECN01, which could shift the paradigm to standardized treatment cycles that are well-established in cancer chemotherapy and immunotherapy and may lead to improved clinical outcomes for patients with PDAC and other solid tumors. The VARAGE trial is expected to enroll 92 patients and currently has four sites open in the U.S. and eight sites open in Spain. As a reminder, in both the control arm and treatment arm of our Phase IIb trial, patients will receive gencitabine and napaxitaxel standard of care chemotherapy in 28-day cycles. In the treatment arm only, patients will also receive systemically administered VCN01 seven days prior to the first and fourth cycles of gencitabine and napaxitaxel treatments. Primary endpoints for the trial include overall survival and VCN safety and tolerability. Additional endpoints include progression-free survival, objective response rate, and measures of biodistribution, VCN-01 replication, and immune response. Since this is an open-label trial, progress will be monitored very closely, and steps to accelerate the clinical program may be implemented if supported by emerging data. In addition to advancing the VARAGE PDEC trial, we continue to work closely with key opinion leaders to refine our clinical strategy in retinoblastoma. We look forward to scheduling conversations with regulatory agencies to discuss the development pathway for VCN01 as an adjunct to chemotherapy in pediatric patients with advanced retinoblastoma. We believe intravitreal VCN01 has the potential to treat vitreous seeds in children with retinoblastoma and we look forward to leveraging our orphan drug designation in this indication to facilitate protocol discussions with the FDA and other regulatory agencies. Since current clinical practice varies and there is no regulatory guidance specific to retinoblosoma drug development, we are working with our key opinion leaders in the U.S., Europe, and Central and South America to develop potential treatment options for this difficult-to-treat cancer. In parallel with company-sponsored studies, the potential utility of BCN01 is being explored in a number of investigator-sponsored studies that are underway at leading oncology research institutions around the world. As previously noted, enrollment and treatment are ongoing at an investigator-sponsored study at the University of Pennsylvania administering BCN01 with UPenn's Heukarty mesocells. In this study, VCN01 is administered 14 days prior to the dose of Heukarty measles cells, and the patients are carefully followed for safety and clinical outcomes. At the recent Silicon Valley conference in June, the University of Pennsylvania investigators presented initial data from two ovarian cancer patients and one pancreatic cancer patient who had received the scheduled doses of VCN01 and Heukarty measles cells. The investigators noted that the combination was generally well-tolerated, which highlights the feasibility of administering VCN01 with UCRT measles cells and supports the continued evaluation of VCN01 in combination with immunotherapy products to treat solid tumors. In a separate investigator-standard study, we are exploring the therapeutic potential of VCN01 in combination with Dervilumab for patients with recurrent metastatic head and neck cancer. We are encouraged by the data generated to date, highlighted by the acceptable safety profile seen with the sequential dosing of VCN01 and Duralumab, as well as the biological activity observed in head and neck cancer patients who failed multiple previous lines of therapy, including treatment with NIPD1 and PD-L1 agents. At the upcoming ESMO Congress in Madrid, Spain, from October 20 through the 24th this year, investigators will present survival data from the ongoing Phase I study, which will provide the first clinical insights into the feasibility of combining BCN01 with an immune checkpoint inhibitor. Furthermore, in collaboration with the University of Leeds, we are evaluating intravenous VCN01 in patients with high-grade brain tumors who are scheduled for surgical resection. This Phase I trial is designed to evaluate the ability of VCN01 to enter brain tumors following systemic administration. The leaky vasculature of many brain tumors may provide an excellent opportunity for systemically administered VCN01 to enter the tumor where it may replicate and initiate tumor cell killing, destroy tumor stroma, and stimulate an anti-tumor immune response. Successful systemic delivery of ECN01 to brain tumors could provide a less invasive intervention and potentially transform the way these cancers are treated. The Leeds investigators have initiated dosing and are exploring protocol refinements that may help expand enrollment. Additionally, enrollment in the Phase I clinical study in collaboration with Hospital San Jean de Deo in Barcelona, Spain, has extended to additional patients. The study is designed to evaluate the safety and tolerability of VCN01 in patients with interocular retinoblastoma refractory to systemic interarterial or intravitreal chemotherapy or radiotherapy. We look forward to using these data in future discussions with regulatory agencies to refine the development pathway for BCN01 and retlobosoma. Turning to our ongoing phase 1b2a clinical trial of SYN4 or ribaximase to prevent acute graft-versus-host disease, or AGVHD, in patients undergoing L-genic ACT treatment for hematological cancers. SYN4 is intended to address key limitations of broad-spectrum antibiotics or IV beta-lactam antibiotics and potentially improve treatment outcomes with this important and widely used class of therapeutics. The Phase 1b-2a study is designed to assess the feasibility of using SYN4 in the 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. As a reminder, the study consists of three sequential cohorts designed to compare different IV beta-lactam antibiotics to treat fever following conditioning therapy. In each cohort, eight patients will receive SYN4 and four will receive placebo. While the data remain blinded, an IRM analysis suggests that SYN4 is well-tolerated and was not observed in the blood samples of a majority of the available patients. Our second cohort is underway and is designed to evaluate SYN4 in combination with piperacillin and tezobactam. This cohort will provide important additional safety information, in particular, whether oral SYN4 has the potential to alter IV antibiotic levels in this patient population. With our collaborators at Washington University, we continue to explore the potential of SYN4 to reduce potentially fatal adverse events related to IV antibiotic use in alginate HCT recipients, including AGVHD, and overgrowth and infection by pathological organisms such as C. difficile and vancomycin-resistant tera-coxime. We are pleased with the progress of our clinical programs. As we continue to build on the growing data that underscores VCN01's differentiated mechanisms of action, A key priority will be to identify new candidates to leverage the novel albumin shield technology and exciting additional technologies from our OB platform, which have tremendous potential for our pipeline. To this end, in May 2023, we appointed Dr. Ramon Albany, Ph.D., the Senior Vice President of Discovery. Ramon is an internationally recognized expert in oncolytic adenoviruses, and as co-founder of VCN Biosciences, is uniquely suited to oversee Theriva's discovery and development pipeline. Ramon will continue to serve as chair of the Scientific Advisory Board and is head of the Immunotherapy and Virotherapy Group at the ProCure Program at the Catalan Institute of Oncology, or ICO, and the Oncobel Program of the Biomedical Research Institute of Belvedere or ITABELM. We look forward to its guidance and strategic leadership in its new role. Additionally, we are grateful for the opportunity to strengthen our relationship with ICO and ITABELM, the leading research institutions, and long-term collaborators where our current OV technologies and products were invented and incubated. Overall, I'm confident that the company's strong cash position and upcoming catalyst provide a solid foundation for execution and value creation. We remain focused on driving our clinical programs forward and exploring opportunities to expand our pipeline through our OV discovery platform. We remain on track to complete enrollment for the VERAGE program by the first quarter of 2024. meet with the FDA to discuss the clinical development and potential registration pathway for BCN01 as an adjunct to chemotherapy in pediatric patients with advanced retinoblastoma before the end of the year, and complete the second cohort of our phase 1b2a clinical study of SYN4 for the prevention of acute graft-versus-host disease in bone marrow transplants in patients in the first quarter of 2024. Now, I'd like to briefly turn to the financial results for the second quarter of June 30, 2023. General administrative expenses increased to $2.7 million for the three months ended June 30, 2023 from $1.5 million for the three months ended June 30, 2022. This increase of 80% is primarily comprised of increased expense related to the fair value of continued consideration adjustment of $0.9 million along with higher audit fees, consultative fees, travel, and VCN administrative expenses not included in the prior year, offset by a decrease in legal costs related to the VCN acquisition. The charge related to stock-based compensation expense was $106,000 for the three months ended June 30, 2023, compared to $86,000 for the three months ended June 30, 2022. Research and development expenses decreased to $3.1 million for the three months end of June 30, 2023, from approximately $3.5 million for the three months end of June 30, 2022. This decrease of 10% is primarily the result of lower expenses related to our Phase 1b2a clinical trial of SIN4 and L-genetic HCT recipients, Phase 1a clinical trial of SIN20, and decreased manufacturing expenses related to our Phase 1A clinical trial, SN20, offset by increased clinical trial expenses related to VCN01. We anticipate research and development expenses to increase as we continue enrollment in our barrage Phase 2 clinical trial of VCN01 and PDAC in our ongoing Phase 1 trial in retinoblastoma, 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 $40,000 for the three months ended June 30, 2023, compared to $27,000 for the three months ended June 30, 2022. Other income was $377,000 for the three months ended June 30, 2023, compared to other expense of $17,000 for the three months ended June 30, 2022. Other income for the three months ended June 30, 2023 is primarily comprised of interest income of $381,000 and an exchange loss of $4,000. Other income for the three months ended June 30, 2022 is primarily comprised of interest income of $26,000 and offset by an exchange loss of $9,000. Cash and cash equivalents total $34.2 million as of June 30, 2023, compared to $41.8 million as of December 31, 2020, 2022. We remain deeply committed to improving patient outcomes for these very, very hard-to-treat cancers. And before we conclude today's call, I want to extend my sincere appreciation to and gratitude for the foundational work that has brought us closer to delivering on our mission. I'd also like to thank the entire three of the team, our investors, and the many people who have been supportive along the way, including our patients and their families. With that, we're happy to take some questions.
spk06: Ladies and gentlemen, we will now be conducting a question and answer session If you would like to ask a question, please press star and 1 on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star and 2 if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. Ladies and gentlemen, we will wait for a moment while the question queue assembles. Our first question comes from the line of James Malloy with Alliance Global Partners. Please go ahead.
spk02: Hi, good morning. Thank you for taking my question. I had a question on the ISTs that are running. We've got the Tancre Addict, the Brain Tour University of Leeds. When should we anticipate going down through the three, so the Brain Tour Phase 1, the the combo with CAR T for ovarian and pancreatic, and the phase one with Infinzi for head and neck. When should we anticipate, I guess, interim looks for these? Essentially, I know it's hard to judge for an IST. Wouldn't it be reasonable to think you might be looking at top-line data on these trials?
spk04: Okay. Thanks, Jim. Let me take the first stab at that. So going down the line, The UPenn study, which we're incredibly excited about, is ongoing, and they have not given us a deadline on how long that trial will continue. We know they continue to enroll patients. As I mentioned, the Silicon Valley Conference, they presented some data. We believe that there are some additional conferences that are coming up this fall that further data will be presented at. Again, it's a function of how quickly they can attract the right patients to enroll in their study and ultimately the data that's presented. But so far, we're very encouraged by what we're seeing in terms of the results that have been generated today with UPenn. The retinoblastoma study, we've kept that open in Spain. And that's important to continue to gather as much data as possible ahead of our meeting with regulatory authorities, including the FDA. I think it's the possibility of closing that trial perhaps as soon as the end of this year, early next year. That's probably the timeline. And once that trial's concluded, we'll update everybody, you know, on the additional data that's been generated. The LEAD study, that one, again, we don't have a firm deadline. We continue to have discussions with the investigators, and we continue to look at ways to make enrollment easier for patients to participate. As you may or may not have heard, the UK health system has been feeling a little bit of pressure from budgetary issues and staffing so the investigators continue to address that and again when we have an update on the timing you know certainly you know bring everybody up to speed with that and then finally we're really excited about the head and neck cancer trial as we said in the in the presentation here today The survival and efficacy data is going to be presented at the ESMO conference in Madrid in October. It's the 20th through the 24th. We don't have a meeting date yet on when the data is going to be presented. But that's going to be, I think, a real opportunity to highlight how VCN01 can be used in combination with checkpoint inhibitors, particularly in patients that have failed previous rounds with checkpoint inhibitors. It became refractory to those treatments. So that's sort of all I have right now. And again, we'll continue to update everybody, you know, as we have more firm, you know, deadlines. Is that helpful for you?
spk02: It is indeed. Yeah, and I had heard that, yeah, the UK is, they're cutting funding and sort of shutting down programs where they feel like they can't get them completed in a reasonable amount of time. Is the University of Leeds IST and brain tumor one of these that's potentially looking at that?
spk04: The study itself is funded. It's the staffing issues at the hospitals where I think they're feeling some pressure. But again, we're in communication with the investigator and we continue to look for ways to enhance the opportunity for patients to be enrolled in that trial.
spk02: Okay, maybe on VARAGE then, just to clarify, enrollment completing first quarter, 24, which is excellent, on track with expectations. Is there an interim look anticipated on that in the current year? And then I think I've got fourth quarter, 23, but maybe I made that up. And then when would you anticipate potentially top-line data for the VARAGE trial instead of wrapping that trial up and taking next steps?
spk04: So first and foremost, the primary endpoint of that trial is overall survival. And assuming that the trial is completely enrolled by the first quarter of next year, you know, arguably, you know, that data will start presenting itself sometime probably in 25. Now, having said that, we have multiple secondary endpoints that will help us evaluate before then whether or not the drug is as expected, and maybe as soon as the end of this year going into next year, we could possibly have a good indication of overall response. How we convey that information to the market is yet to be determined, because depending on what those data say, we may be well-positioned first have a discussion with regulatory authorities before we make that data public. So although it could be an opportunity for us to have such a communication, more importantly, I think the fact that we could have an opportunity to go in front of regulatory authorities to figure out how we can expedite the clinical development of the asset, you know, would be you know, equally important. So stay tuned, I guess, is the answer. Yeah.
spk02: And as an open-label trial, obviously, you have the opportunity to release data as you deem it worthy of release, correct?
spk04: Again, I would not suggest that we plan to release that data before we had a chance to analyze it in person have a discussion with regulatory authorities. I think that wouldn't be fair to the trial, the participants, and our ability to chart the path forward from a clinical development point of view.
spk02: Last couple of questions. I apologize if I missed it on the call. On VCN 11, is the IND on track for third quarter this year?
spk04: talk about VCN11 and our other development initiatives?
spk01: Yeah, I can do that perfectly. So we are working right now with basically the manufacturing part of VCN11. We don't have a formal deadline for this year for this product yet. In fact, our research and development team is working very actively with VCN11 and also with different candidates right now. You know, we have announced at the incorporation of Ramon Alemany during this year, and that has been a real boost for all our discovery activities. So for BCN11, yes, we are advancing, but we are not yet in the phase of applying for IMPD formally. We are working on that, but we need still some work to do before that. And we are also developing a new candidate that can be really, really promising. So I think that probably in the next month we are going to have some additional things to show you. But that's still a bit early.
spk02: Got it. Understood. Thank you. I may have just made up the idea there on my end. And then maybe last question. On the SIN 04 and 021, I know that you've long discussed potentially partnering these companies. these programs, how realistic is the opportunity to partner them? I know that you're still looking at some data from them to perhaps make the product look better. What is a realistic expectation as an outsider we should have thinking about a potential partnership for either the 020 or 004?
spk04: I think it's realistic to certainly expect a potential partnership with either one of those assets. And, you know, as I've said on previous calls, although there's, you know, there's folks that we've had discussions with, we continue to have discussions with, until we have something, you know, committed and over the line, you know, we're not going to talk any further about that.
spk05: Thank you very much for taking the questions. Thank you. Ladies and gentlemen, if you wish to ask a question, please press star and 1.
spk06: As there are no further questions, I will now hand the conference over to Stephen Shellcross for closing comments.
spk04: Thank you, Ryan. Thanks again to everyone for taking the time to join us today. We remain focused on driving our key programs as we've talked about today. and will continue to evaluate strategic opportunities that could, in fact, further drive shareholder value and long-term success. Once again, thanks again for joining us today, and we look forward to keeping you updated on our progress.
spk06: The conference of Teriva Biologics, Inc. has now concluded. Thank you for your participation. You may now disconnect your lines.
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