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spk01: 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.
spk03: 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?
spk02: 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.
spk01: Thank you, sir. Ladies and gentlemen, if you would like to ask a question, please signal by pressing star 1 on your telephone keypad. If you are using a speakerphone, please make sure your mute function is turned off to allow your signal to reach our equipment. Once again, please press star 1 to ask a question. We will pause for just a moment to allow everyone an opportunity to signal. We'll take our first question today from Jim Malloy of Alliance Global Partners. Please go ahead. Your line is open.
spk05: Good morning, Steve. Thanks for taking my question and excellent update on the quarter. In looking at the broad investigator-sponsored trial pipeline, and obviously these are great ways to be successful, the shepherd capital, but sometimes it can be harder to control the timing. How much influence do you guys have on trying to impress upon the ISTs the need to sort of move as expeditiously as possible while at the same time, obviously, it's their trial?
spk02: Yeah, that's something that we actually have a lot of discussion around on a weekly basis. I think the reality is you know, the balls in their courts when they take these programs forward. But I think the dialogue between the organizations that we're working with, you know, folks at ICO, folks at Leeds, folks at UPenn, you know, I think we have an engagement that is, you know, respected, you know, quite nicely. And that, you know, because of that dialogue, I think both parties understand the importance of continuing to advance these programs. And to be quite honest, you know, it's really a great opportunity for the company because, you know, although we're providing study drug for these, these organizations typically fund, you know, these programs on their own, and they provide their own staff to monitor the progress of the programs. So it's a nice way for us to continue to explore uses for VCN01 while limiting how many resources we need to, you know, commit internally. It's something that, again, we pay a lot of attention to. And as we've seen from the head and neck trial, we've generated some really interesting data that was presented in Paris recently. there's still more data specifically to come of that trial and survivability, and we're looking forward to that data coming out sometime, you know, in the next probably six months or so. Is that helpful for you? It is indeed.
spk05: Thank you. I appreciate that. And then on the combo in pediatric retinoblastoma, the orphan in the U.S., And the Verage for PDAC first line combo with chemo, we have Orphan EU, correct? Do I have the orphans correct on those two?
spk02: That's correct. And we're in the process of applying for orphan indication for PDAC in the U.S. as well. Excellent.
spk05: And then how, is there a way to, obviously you're guiding for fourth quarter 23 to start the retinol trial. Is there a way to advance that? I'm sure there's a lot that goes into it that you can't talk about in advance of that, but is there a way to advance either that or I guess that's the only one. The other one, the University of Leeds is an IST, so that's at their discretion.
spk02: So I'm going to, I'll hand this over to Manil in a second to give you a little bit more color on how we're thinking about the retinoblastoma trial. The reality of that is that there's no approved treatment for retinal blastoma. In the U.S., there's around 200, you know, a little bit more patients a year, the same in the U.U., but the larger patient population is in South America, India, and Asia. And, you know, one of the things that we've learned is that there may be opportunities as we design this trial to take advantage of those much larger patient populations to more quickly gather data. Maybe I'll hand this over to Manel, and he could talk about some of the findings that we've learned as a result of some of the discussions that we have ongoing with key opinion leaders. Manel?
spk07: Yeah, sure. Sure, Steve. Yeah, in fact, we are very actively working in the retinal blastoma program, but we have a lot to learn because obviously the way as retinal blastoma is treated, it's changing and we need a careful monitoring of all the activities that have been on all the treatments that has been proposed more recently. But right now we have a quite good consensus after having to speak with European leaders in Europe and in US, also in Brazil and in India, And we are very clear in what's going to be the target population and also the treatment schedule, which is very important. And, in fact, we have presented quite recently in collaboration with one of our academic collaborations in the hospital. Very nice data showing that BCN01 plus topotecan, that it's a drug that is currently used for treatment in some patients in retinoblastoma, results in really enhanced antitumoral activity. which is very interesting, and it looks quite specific of the combination of topotecan and BCN01. That's data that has been presented in a scientific congress from the International Society of Periodic Oncology last September. So we are learning a lot, but we are in the good pathway. So we are right now just targeting the conversation with FDA. with the agreement of the key opinion leaders around the world, basically, and we are very confident that the trial can be a real success in the field of retinoblastoma because, as indicated by Steve, there's no unapproved treatment for retinoblastoma, and that could really be a major milestone in the field.
spk05: Maybe to follow up on that, if I could, please. You guys recently held, on Monday, I think, was it an excellent KOL call on PDAC, I guess that's written now. But over on the PDAC side for Verage, how would you – what sort of key takeaways you guys heard from the Monday KOL call that – obviously, I'm talking about the challenges in the market that you can apply to the Verage trial?
spk06: Go ahead, Manil.
spk07: So basically, the KOL meeting was really interesting because they highlighted a lot of things in the field of pancreatic cancer. I'm pretty happy with the inputs that we have get in this conversation. In fact, they have highlighted the ability of our product to reach hepatic metastasis, but I think it's one of the key things in this trial. I think that obviously there are challenges related with the recruitment rate, but I think that the fact that we have positioned our product at first line in metastatic pancreatic cancer warrants that we are going to have a good recruitment rate, and that's also the feeling that we have with the BIs that are engaged in our trial, both in US and Europe. I mean, I think that KOL meeting was really, really encouraging for us in order to see that the general perception of our product in terms of safety, in terms of activity, mechanism of administration, et cetera, was really the right pathway. So we are happy with that.
spk05: And maybe final question for Stephen. How would you characterize the market for your partnership opportunities for SIN004? I know you've been obviously, correctly, I think, moving away from SIN-004 and focusing on DCN-01 and the opportunity to partner it out. How is that effort going?
spk02: So, historically, we've had discussion with interested parties on SIN-004, and we've actually had some discussions with folks that have a franchise in the transplant arena. So, I guess the feedback we were given was that it would complement their portfolio of products for transplantation, whether it be blood cancers or solid organ transplants. But the feeling was that, OK, let's overcome this issue on whether or not SYN4 could possibly be systemically absorbed and interfere with the antibiotic used after conditioning in this more fragile patient population as we've described. So the first cohort of that study has been completed. We reported that data out in September and the trial and the outcome of that trial was what we expected. So now we're actually going to the next cohort where the CIN4 enzyme has the ability to degrade PIPTASO. So this will be key. So then, you know, once this trial wraps up, I think we'll have, you know, a very, very strong data package, you know, not only what we generate from this ongoing trial, but what we've previously been able to demonstrate in the original phase two trial for the prevention of C. diff and AMR, to, you know, re-approach potentially interested parties. So it's definitely on the radar. You know, we're really happy with how this trial is performing. And, you know, Dr. DeBerke and his team at WashU have just done a tremendous job in the trial design and how it uses three antibiotics, increasing, you know, in level of the type of activity we expect to see you know, with the use of ribaxamase. I don't know, Vince, do you have any other comments on that perhaps?
spk00: No, I think that that's all a reasonable assessment. We've got to get further data to really consolidate in this indication, but I will say that the interest in prevention in this indication, say compared to other indications, is extremely high and entrenched in the therapeutic rationale for this disease. Unlike other things, other conditions related potentially to infection, in bone marrow transplant, it is well established you must prevent, must prevent AGVHD, must prevent Clostridium difficile, must prevent VRE infections because they can be fatal. There's no question that prevention is key. So it's a much better indication for us as far as taking forward these products. I'll also say that there was an FDA and CDC workshop not too long ago that we participated in, and it was good to see that the FDA and the CDC are making a joint effort to understand how to prevent these hospital-acquired infections, of which clearly Sino4 is in that space. And we were one of the participants. And I think what the great takeaway from that was something that people in industry knew and maybe people at the FDA and CDC didn't, which is the need is tremendous to prevent hospital-acquired conditions, hospital-acquired infections, things related to antibiotic use and such as what we're trying to address with Sino4. But I don't think that the FDA and the CDC understood the challenge of getting clinical trials done in those indications and the cost of moving them forward. So that's a positive outcome that we, on the corporate side, on the company side, were able to impart that, not just Cereva slash Synthetic, but other companies working in the space were able to say, listen, this is an important problem we're addressing. But we need to work out a way to make these studies happen more easily and get to approvals faster.
spk06: Excellent. Thank you. Actually, one last question.
spk05: What does the VARAGE stand for on the PDAC trial? How did you guys come up with that name for the trial?
spk02: Go ahead, Manal.
spk07: So basically, as anticipated by Steve, we have already got the approval from Spanish authorities and the safety proceed from FDA in September. So we are initiating sites in Spain. In fact, there's already sites already initiated and ready to recruit patients. So we expect recruiting patients very soon and definitely before the ending of this year. And we are also... finalizing our answers to the queries raised by German authorities that are basically classical questions associated with the manufacturing of product that we are very familiar with because obviously we have been previously asking the same questions and we are very happy to provide answers to this question. So we expect that Germany is going to be open slightly bit later than probably US and Spain, but very soon also. So, in fact, all the machinery is ready, all the vendors are ready, and the physicians are really excited by this program. In fact, the investigator meetings that we have conducted, we have had an investigator meeting in Paris that has been very successful with the researchers from all the different areas where where trial is trying to be conducted, expressed really excitement about this trial because it generates a unique opportunity because our product combines different mechanisms of action in a single product, and that generated a lot of interest in order to see if we can really have a major impact on the survival of patients with pancreatic cancer, which is obviously really a net need.
spk04: I think also the question, I think it was also the name of the virage also was picked by, it really means to change course, essentially. That's what we're trying to do, change the course of pancreatic cancer. But also it's kind of a global name, and you can think about it as virus, adenovirus, gemcitabine. It's sort of the way we thought about it. So it actually works pretty well.
spk06: Okay, sorry for my misunderstanding. Thank you.
spk01: It appears we have no further questions at this time. I would like to turn the call back over to Mr. Shawcross for any additional or closing remarks.
spk02: Thank you, Elaine. And thank you to everyone for taking the time to join our call today. We remain deeply committed to improving patient outcomes for these really, really hard-to-treat cancers, and we look forward to providing future updates on our progress. Once again, I'd like to thank our shareholders, the entire team, and the many people who have been supportive along the way, including our patients and their families. And finally, on this Veterans Day, we'd like to thank those who have served to protect our great, great country. Once again, thank you for joining us, and we look forward to keeping you updated on our progress. Have a great weekend.
spk01: Thank you. Ladies and gentlemen, that will conclude today's conference call. Thank you for your participation. You may now disconnect.
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