Greetings, and welcome to the Theriva Biologics 2023 first quarter operational highlights and financial results. 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 zero on your telephone keypad. As a reminder, this conference is being recorded. It is now my pleasure to introduce your host, Chris Calabrese of LifeSci Advisors. Thank you, Chris. You may begin.
Thank you, operator. Good morning, everyone. Welcome to Theriva Biologics' first quarter 2023 investor conference call. Leading the call today will be Steven A. Shallcross, Chief Executive and Chief Financial Officer of Theriva Biologics. Dr. Manel Cascalló, General Director of Theriva Biologics' European subsidiary, 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. Theriva Biologics issued a press release this morning, which provided operational highlights and included financial results for the first quarter, ending March 31st, 2023.
The press release can be found in the investors section of the company website at www.therivabio.com, together with the quarterly report on Form 10-Q for the quarter ended March 31st, 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 the 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, actual results may differ materially from such statements. The information on this call is provided only as of the date of this call, Theriva 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. Steve?
Thanks, Chris. Good morning. I appreciate everyone taking the time to join us today. I'd like to begin by reiterating our deep commitment to advancing our organization and addressing unmet needs for difficult to treat cancers. In the first few months of 2023, we continue to make steady progress across our oncology folks portfolio and remain on track to reach multiple value-enhancing milestones. With cash runway into the third quarter of 2024, we believe we're well-positioned to execute on our corporate objectives. As a reminder, our lead clinical candidate, VCN-01, is a systemically administered oncolytic adenovirus designed to selectively replicate within the tumor, degrade the tumor matrix and increase tumor immunogenicity. We believe these features position VCN-01 for use in multiple indications in combination with multiple different types of therapies, providing multiple mechanisms of tumor killing.
Building on strong phase I clinical data, we are advancing VIRAGE, our phase IIB trial for patients with newly diagnosed metastatic pancreatic ductal adenocarcinoma, or PDAC. We are pleased with the progress to date. Enrollment and dosing are also underway for the phase I trial of VCN-01 in patients with brain tumors. We're preparing to engage with regulatory agencies to discuss the development and potential registration pathway for VCN-01 as an adjunct to chemotherapy in pediatric patients with advanced retinoblastoma. As part of our oncology focus portfolio, in addition to exploring the potential clinical benefits of VCN-01 in different solid tumor indications, we continue to screen patients and enroll them in the second cohort of the phase IB/phase IIA clinical trial of SYN-004, which we expect to complete in the first quarter of 2024.
As a reminder, SYN-004 is designed to prevent potentially fatal outcomes in patients who undergo allogeneic hematopoietic cell transplant, HCT, to treat hematologic cancers. In parallel, we've taken important steps to identify new candidates through our OV discovery platform, which is designed to protect systemically administered oncolytic viruses from the host immune system and may facilitate repeated administration of oncolytic virus therapies, thus increasing their efficacy and potentially allowing our pipeline programs to be used in standardized treatment cycles that are well established in cancer chemotherapy and immunotherapy. With this brief introduction, I will now provide an update on recent activities and share details on how these programs continue to position Theriva at the forefront of oncolytic virus development, starting with our lead program, VCN-01.
It is well known that PDAC has one of the lowest survival rates among all cancers. Despite the growing incidence, efforts to improve upon the standard of care chemotherapy treatments have largely stalled. We believe VCN-01 has the potential to address the urgent need for new treatment options for patients with PDAC. Enrollment and dosing are underway in VIRAGE, the multinational phase IIB clinical study evaluating intravenous VCN-01 in newly diagnosed PDAC patients treated with first-line standard of care chemotherapy, gemcitabine and nab-paclitaxel. The trial is expected to enroll up to 92 adults at up to 25 sites across the US and Europe. We are encouraged by the enrollment to date, which is a testament to both the engagement of our clinical trial sites and the intense commitment of our experienced clinical team.
In both the control arm and treatment arm, patients will receive gemcitabine and nab-paclitaxel standard of care chemotherapy in 28-day cycles. In the treatment arm only, patients will also receive systemically administered VCN-01 seven days prior to the first and fourth cycles of gemcitabine and nab-paclitaxel treatment. Primary endpoints for the trial include overall survival and VCN-01 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 initiating the VIRAGE PDAC trial, we continue to work closely with key opinion leaders to refine our clinical strategy in retinoblastoma.
We believe intravitreal VCN-01 has the potential to treat vitreous seeds in children with retinoblastoma. We also 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 retinoblastoma drug development, we are working with our key opinion leaders in the U.S., Europe, and Central and South America to develop new potential treatment options for this difficult-to-treat cancer. In parallel with company-sponsored studies, the potential utility of VCN-01 is being explored in a number of investigator-sponsored studies that are underway in leading oncology research institutions around the world. In collaboration with the University of Leeds, we are evaluating intravenous VCN-01 in patients with high-grade brain tumors who are scheduled for surgical resection.
This phase I trial is designed to evaluate the ability of VCN-01 to enter brain tumors following systemic administration. The leaky vasculature of many brain tumors may provide an excellent opportunity for systemically administered VCN-01 to enter the tumor, where it may replicate and initiate tumor cell killing, destroy tumor stroma, and stimulate an antitumor immune response. Successful systemic delivery of VCN-01 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 expand enrollment. Additionally, enrollment in the phase I clinical study in collaboration with SJD Barcelona Children's Hospital Sant Joan de Déu in Barcelona, Spain, has been extended to additional patients. The study is designed to evaluate the safety and tolerability of VCN-01 in patients with intraocular retinoblastoma refractory to systemic intra-arterial or intravitreal chemotherapy or radiotherapy.
We plan to hold a meeting with the FDA in the second half of 2023 to discuss the clinical development and potential registration pathway for VCN-01 as an adjunct to chemotherapy in pediatric patients with advanced retinoblastoma. A separate investigator-sponsored study is exploring the therapeutic potential of VCN-01 in combination with durvalumab for patients with recurrent metastatic squamous cell carcinoma of the head and neck. We are encouraged by the data generated to date, highlighted by the acceptable safety profile seen with sequential dosing of VCN-01 and durvalumab, as well as biological activity observed in head and neck cancer patients who failed multiple previous lines of therapy, including treatment with anti PD-1 and PD-L1 agents.
We are planning to present additional efficacy and survival data from the study in the second half of 2023, and we will continue to explore collaboration and partnering opportunities to advance VCN-01 in this indication. The potential to enable the use of immune checkpoint inhibitors in refractory or in insensitive cancer patients is a particularly compelling goal of VCN-01 that may have valuable utility in a range of cancer indications. Turning to our ongoing phase IB/phase IIA clinical trial SYNFORA or ribaxamase to prevent acute graft-versus-host disease or aGVHD in patients undergoing allogeneic HCT treatment for hematologic cancers. SYNFORA 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 Ib/phase IIB study is designed to assess the feasibility of using SYN-004 in this specific patient population and to provide key information requested by the FDA regarding the safety and tolerability of SYN-004 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 SYN-004 and four will receive placebo. Data from the first cohort were recently presented in April at the 33rd European Congress of Clinical Microbiology & Infectious Diseases. While the data remain blinded, interim analysis suggests that SYN-004 is well-tolerated and was not observed in the blood samples of a majority of the available patients. Building on these results, our second cohort is underway and is designed to evaluate SYN-004 in combination with piperacillin and tazobactam.
This cohort will provide important additional safety information, in particular, whether oral SYN-004 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 SYN-004 to reduce potentially fatal adverse events related to IV antibiotic use in allogeneic HCT recipients, including aGVHD and overgrowth and infection by pathological organisms such as C. difficile and vancomycin-resistant enterococci. We are pleased with the progress of our clinical programs and in parallel, continue to identify new candidates through our OV platform. Our proprietary technologies have tremendous potential for our pipeline, and we look forward to building upon our foundation of compelling proof of mechanism data generated with VCN-01 and VCN-11 to develop new albumin shield candidates incorporating additional therapeutic payloads.
I'm confident that the company's strong cash position and upcoming catalyst will 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 VIRAGE by early 2024, hold a pre-IND meeting with the FDA in the second half of 2023 to discuss the clinical development and potential registration pathway for VCN-01 as an adjunct to chemotherapy in pediatric patients with advanced retinoblastoma, present additional data from the study of VCN-01 in combination with durvalumab in patients with recurrent metastatic squamous cell carcinoma of the head and neck in the second half of 2023, and complete the second cohort of our phase IB/phase IIB clinical study of SYN-004 for the prevention of acute graft-versus-host disease in bone marrow transplant patients in the first quarter of 2024. I'd like to briefly turn to our financial results for the first quarter ended March 31st, 2023.
General and administrative expenses increased to $2.2 million for the three months ended March 31st, 2023, from $1.7 million for the three months ended March 31st, 2022. This increase of 29% is primarily comprised of increased expense related to the fair value of the contingent consideration, additional salary and benefits related to new headcount, audit fees, consulting fees, travel and VCN administrative expenses not included in the prior year, offset by a decrease in consulting and legal costs related to the VCN acquisition. The charge related to stock-based compensation expense was $87,000 for the three months ended March 31st, 2023, compared to $85,000 for the three months ended March 31st, 2022.
Research and development expenses increased to $3 million for the three months ended March 31st, 2023, from approximately $2.6 million for the three months ended March 31st, 2022. This increase of 15% is primarily the result of increased clinical trial expenses related to VCN-01 not incurred in the prior year, offset by lower expenses related to our phase IB/phase IIB clinical trial of SYN-004 in allogeneic HCT recipients, and decreased manufacturing expenses related to our phase IA clinical trial of SYN-020. We anticipate research and development expense to increase as we continue enrollment in our VIRAGE phase II clinical trial of VCN-01 in PDAC and our ongoing phase I clinical trial in retinoblastoma, expand GMP manufacturing activities for VCN-01, and continue supporting our VCN-11 and other preclinical and discovery initiatives.
The charge related to stock-based compensation expense was $39,000 for the three months ended March 31st, 2023, compared to $28,000 for the related to stock-based compensation expense for the three months ended March 31st, 2022. Other income was $370,000 for the three months ended March 31, 2023, compared to other expense of $21,000 for the three months ended March 31st, 2022. Other income for the three months ended March 31st, 2023, is primarily comprised of interest income of $364,000 and an exchange gain of $6,000. Other expense for the three months ended March 31st, 2022, is primarily comprised of an exchange loss of $23,000, offset by interest income of $2,000.
Cash and cash equivalents totaled $36.1 million as of March 31st, 2023, compared to $41.8 million as of December 31st, 2022. We remain deeply committed to improving patient outcomes for these very hard-to-treat cancers. Before we conclude today's call, I want to extend my sincere appreciation and gratitude for the foundational work that has brought us closer to delivering on our mission. I'd also like to thank the entire Theriva team, our investors, and the many people who've been supportive along the way, including our patients and their families. With that, we're happy to take some questions.
Thank you. We will now be conducting a question and answer session. If you would like to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star two 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 star keys. One moment please while we pull for questions. As a reminder, if you'd like to ask a question, please press star one. Our first question comes from the line of James Molloy with Alliance Global Partners. Please proceed with your question.
Hi. Good morning, guys. Thank you very much for taking my question. My apologies. I had it on mute there at first when I hit the star one. On the VIRAGE trial, when do you anticipate? You're looking for interim data here, fourth quarter 2023, I believe. When do you anticipate sort of, this trial concluding and top-line data coming through?
Jim, as we previously disclosed, we plan to complete the enrollment by early 2024, so that's all 92 patients in. Enrollments currently are, you know, on target with our expectations. We expect that sometime by the end of the year, we should have enough patients enrolled that will give us the opportunity to evaluate the data and make some determinations on whether or not, the trial and the patients in the trial are responding as we expect them to respond. At that point in time, that will give us the opportunity to, if we're foreseeing that robust response, to have discussions with the regulatory authorities and look at our options on how we could accelerate the trial.
Since the primary endpoint is overall survival, you know, we expect this trial to go out, you know, beyond 2024 and into 2025 before it is fully completed. Obviously, the longer the better, 'cause obviously that would mean that, you know, patients are living longer. We will have, in our opinion, a real good feel, you know, perhaps as soon as the end of the year, on whether or not we're seeing the response rate that we observed or something close to it, in the phase I trial.
Excellent. Actually, excuse me. How go the UPenn and the Leeds IST trials? Any updates there that? When do you anticipate getting data potentially from those trials? I know they're out of your hands a little bit.
You're correct on that. First, the Leeds trial, we have the first patient dosed. They're in the process of recruiting still. Recently, there were some proposed protocol amendments that would give the sponsor some additional flexibility to improve the enrollment rate, so that's ongoing, and we have no specific timeline on when that study will conclude and at what point we'll actually have the data. That effort is totally in their hands. The UPenn study, similarly, we know that they're dosing patients. We have no specific data on exact numbers and what they're observing in terms of response rate.
We would expect that sometime, in the middle or going into the third quarter this year that we would have a communication. It's also possible that UPenn, which they are, again, controlling the study, may perhaps present some of that data at a public forum.
How often is the communication between you guys and the ISTs? Again, I know ISTs are outside of your hands, but what's the sort of the schedule of these updates? You mentioned potentially second half this 2023. Is there a set board meeting to or panel meeting to coordinate efforts on these trials?
You know, depending on how active the site is, sometimes we'll discuss and have discussions with them on a monthly basis. Sometimes it's quarterly basis. The head and neck trial, for example, we've been in active discussions with them because that data is being prepared to be, you know, released sometime in the third quarter at an upcoming conference. In that case, you know, the discussions with the PI, you know, are pretty active and pretty regular. You know, again, it depends on the trial and how aggressively the enrollments are progressing.
Understood. Then, on SYN-004, I think you've made it clear, I think in the previous calls, you're looking to partner, continue development beyond sort of the phase IB/phase IIB, that you're currently working on. How would you characterize the partnership environment for SYN-004 currently?
There is interest, and we've had inbound interest and, you know, again, you know, these things take time to play out and, you know, once we have something that's more definitive, we certainly will communicate that to everybody.
Would you think it's something that is likely a 2023, or is it just still too early to even put a timeline on it?
I can't put a timeline. I mean, this environment is very tricky nowadays. You know, you get a lot of interest, you have discussions, and, you know, there are a lot of reasons why something, you know, moves at the rate it does. You know, again, we're doing everything we can to actively engage with interested parties across our whole portfolio of products. You know, when we have something, you know, more definitive, we'll obviously again, communicate that.
Outstanding. Thank you very much for taking the questions.
Thank you. Our next question comes from the line of Jason McCarthy with Maxim Group. Please proceed with your question.
Hi, guys. This is Chad on for Jason. Thanks for taking the question. For the retinoblastoma program, I know it's, you know, those meetings with FDA are coming up, but do you anticipate, if you can speak on it, if this could be a registrational trial, if you guys maybe go with phase II-phase III or would you need, do you think an additional study after that?
The bottom line is we won't know until we have a discussion with the FDA.
Right.
Manel, if you wanna give a little bit more color about, some of the discussions we've had with the KOLs.
Yeah.
How we're moving forward.
Yeah, exactly. Yes, as anticipated by Steve, that's something that is going to be very dependent on our interaction with FDA, obviously. We are working very intensively, having some very interesting discussions with key opinion leaders, both here in US and in Europe with the top investigators, but also with some physicians involved in treatment of this disease in low and medium income countries. In that geographical areas, it's where retinoblastoma, it's much more abundant and patients normally are not diagnosed as soon as it could be, for instance, in US. That give us a opportunity to really impact with our treatment in that population that otherwise it's orphan of indications.
We are just getting a double effort with some relevant sites in U.S. and also sites in low and medium income countries, just trying to develop a program that is, it's going to be probably more in the line of a health global health system, let's say, okay? Again, that's something that we should discuss with FDA. We have a very nice ideas, I think, to discuss, and we are getting support for these ideas from the key opinion leaders. Until we have this discussion, it's really hard to know exactly what's going to be the complete development pathway for this program, but eventually it could be.
Great. Thanks for taking the question.
There are no further questions at this time. I'd like to turn the floor back over to Steve for closing comments.
Thanks, Devin. Thanks again to everyone for taking the time to join us today. We remain focused on driving our key programs forward, and we'll continue to evaluate strategic opportunities that we believe will help further drive our shareholder value and long-term success. Once again, thanks for joining us, and we look forward to future updates.
This concludes today's teleconference. You may disconnect your lines at this time. Thank you for your participation, and have a wonderful day.