Synthetic Biologics, Inc.

Good day, ladies and gentlemen. You are currently on hold for today's conference. We are awaiting additional participants and we'll start very shortly. Thank you for your patience and please continue to hold. Thank you. Good day and welcome to the Synthetic Biologics Second Quarter 2022 Earnings Call. Today's conference is being recorded, and at this time I'd like to turn the conference over to Chris Calabrese. Please go ahead, sir.

Thank you, Operator, and good morning, everyone. Welcome to the Synthetic Biologics 2022 Second Quarter Investor Conference Call. Leading the call today will be Steven Chalcross, Chief Executive and Chief Financial Officer of Synthetic Biologics. Dr. Manel Cascaio, General Director of Synthetic Biologics, European Subsidiary. Dr. Frank Tafaro, Chief Operating Officer. And Dr. Vince Wade, Chair, Head of Corporate and Product Development of Synthetic Biologics are also on the call and will be available to answer questions during the Q&A session. Synthetic Biologics issued a press release this morning which provided operational highlights and included the financial results for the second quarter ending June 30th, 2022. The press release can be found in the investor section of the company website at syntheticbiologics.com. Together with the quarterly report on form 10Q for the quarter ended June 30th, 2022. 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.syntheticbiologics.com, for 90 days. During this call, certain forward-looking statements regarding synthetic biologics and BCN Biosciences' current expectations and projections about future events will be made. Generally, the forward-looking statements could be identified by terminology such as may, should, expects, anticipates, intends, plans, beliefs, 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 synthetic 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 Synthetic Biologics undertakes no obligation to update any forward lifting 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?

Thank you, Chris. Good morning, and I appreciate everyone taking the time to join us on this call today. In the second quarter of 2022, we continue to execute on our plan to advance our exciting portfolio of clinical assets and to address a number of structural and administrative items that we believe are critical to our long-term success. Today, I will present an update on our progress as well as outline our priorities and path forward. Our team continues to advance our highly differentiated oncolytic adenovirus programs and we believe we are well positioned to lead the clinical path forward for oncolytic virus therapies. First, our VCN01 product has been administered to 76 patients to date, and we believe that there are very few, if any, competing programs that have dosed as many patients by systemic administration as we have. we've generated promising clinical data that gives us the confidence to advance our products into important planned clinical trials. Thirdly, our programs are led and advised by a world-class team of renowned scientists as evidenced by ongoing clinical collaborations and the formation of our SAB earlier this year to advance our oncology pipeline. Finally, Our strong cash position of approximately $53.5 million is expected to comfortably take us into the first quarter of 2024. This should enable us to deliver on a number of value-enhancing milestones before we need to raise additional capital. I am very proud of how we positioned our company for future growth as we continue to work diligently to advance the development of our pipelines. Our oncolytic adenovirus platform currently comprises our lead clinical stage drug candidate, VCN01, a systemically administered oncolytic adenovirus designed to break down the tumor stroma, and preclinical stage drug candidate, VCN11, the first candidate from the truly novel of human shield technology that is designed to protect systemically administered oncolytic viruses from the host immune system. The differentiating mechanisms of action of these two product candidates are intended to improve the anti-tumor effect of both oncolytic viruses and co-administered chemotherapies and or other immuno-oncology products. Importantly, degrading the stroma can also expose new tumor antigens, turning cold tumors hot and enabling a sustained anti-tumor response by the patient's own immune system. In parallel with VCN01 and VCN11, our CIN4, or ribaximase program, is progressing in a phase 1b2a clinical study of L-genetic hematopoietic cell transplant, or ACT, recipients for the prevention of acute graft-versus-host disease in bone marrow transplant patients. I would now like to provide an overview of our pipeline and walk you through key updates, starting with our lead oncology product. VCN01 is designed for intravenous, intratumoral, and intravitreal delivery. It is engineered to selectively replicate within the tumor and has the potential to remodel the tumor matrix and increase tumor immunogenity. As a reminder, VCN01 was granted orphan drug designation in 2011 by the European Medicines Agency for the treatment of pancreatic ductal adenocarcinoma, or PDAC, and also granted orphan drug designation by the FDA in February this year for the treatment of retinoblastoma. If VCN01 is approved by the FDA, orphan drug designation will provide critical market exclusivity, and we plan to take full advantage of the development benefits to which we could be eligible under the Orphan Drug Act, including tax credits, reduced user fees, and again, market exclusivity. We are highly encouraged by the regulatory support for VCN01, which builds on extensive Phase I data across 76 patients, primarily with PDAC and in children with retinal blastoma. We look forward to leveraging our encouraging findings from our Phase I studies in the planned implementation of a controlled Phase II study of intravenous VCN01 in combination with gencytomine and napaxitaxel, the standard of care chemotherapy as a first-line therapy in newly diagnosed patients with metastatic PDAC. We expect to initiate the Phase II study in the fourth quarter of 2022. During the second quarter of 2022, the protocol for the Phase II PDAC clinical trial was submitted to the FDA, as well as Spanish and German regulatory agencies. The proposed trial is designed as a randomized, controlled, multi-center, open-label Phase II study that is expected to enroll up to 92 adults with PDAC at sites in the U.S., Spain, and Germany. The study will have two treatment arms. In arm one, patients will receive gencitabine and napaxitaxel, the standard of care chemotherapy, and in arm two, Patients will receive VCN01 administered seven days prior to gensidamine and napaxitaxel. We are proposing that two doses of VCN01 be administered approximately three months apart. The primary endpoints for the study may include overall survival and safety and tolerability. Additional endpoints may include progression-free survival, objective response rate, 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 closely and may try to accelerate the clinical program if supported by the emerging data. The study will be led by Dr. Manuel Hidalgo, an internationally renowned oncologist, scientist, academic, and the chief of the Division of Hematology and Medical Oncology at Weill Cornell Medicine, New York Presbyterian Hospital. Now, moving on to the planned study for advanced retinoblastoma. We believe UCN01 holds tremendous promise as an adjunct to intravitreal chemotherapy in patients who fail standard systemic or intra-arterial therapeutic treatments. We are working closely with key opinion leaders from well-known treatment centers in the U.S., Europe, and South America to develop a protocol for a Phase 2-3 study of intravitreal VCN01 to treat vitreous seeds in children with retinoblastoma. There is currently no regulatory guidance for the development of retinoblastoma medicines, so we plan to engage regulatory agencies to determine the appropriate study design and endpoints. We expect to initiate this Phase 2-3 study of VCN01 in the second half of 2023. In addition to the planned company-sponsored studies, there are several investigator-sponsored studies underway exploring the therapeutic potential of VCN01 at world-leading oncology research institutions. In July of 2022, the first patient was dosed and cleared in the safety evaluation period in the University of Pennsylvania's investigator-sponsored open-label, non-randomized Phase I clinical trial evaluating VCN01 in combination with mesothelin-directed lentiviral transduced human chimeric antigen receptor-modified T cells for patients with pancreatic and serious epithelial ovarian cancers. Methothelin is a tumor antigen that is highly expressed in many human cancers, including malignant mesothelioma, pancreatic ovarian, and lung adenocarcinomas. A human chimeric antigen receptor-modified T-cells, or QCART mesome, are autologous T-cells engineered to express an extracellular single-chain variable fragment with methylthelin specificity. The Phase I trial is designed to evaluate the safety and feasibility of this novel combination therapy. We will continue to report on progress of the study as we receive updates. We are also excited about our collaboration with the University of Leeds to evaluate BCN01 in patients with high-grade brain tumors. This study is designed to evaluate whether systemically administered BCN01 could reach tumors in the brain. Treatment of these tumors typically requires surgery and or direct injection. If systemic BCN01 can reach the brain to exert a therapeutic effect, it could potentially transform the way these cancers are treated. The investigator-sponsored study is currently recruiting patients with dosing of the first patient expected in the second half of 2022. In addition to our clinical trials with VCN01, we are keenly advancing our albumin shield technology platform. Albumin shield oncolytic viruses incorporate a preparatory 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 and prevent inactivation by antiviral neutralizing antibodies. Ideally, this may enable multiple administrations of a systemic OB in traditional therapeutic cycles that could improve treatment outcomes. Preclinical proof of concept for the technology has been demonstrated with VCN11, an albumin shield modified version of VCN01, and we are exploring other albumin shield modified oncolytic viruses with different potential therapeutic payloads. IND-enabling studies are being planned, and we expect to begin these following the completion of ongoing preclinical studies 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. As part of our company's transition to an oncolytic or an oncology focus, we are exploring options to unlock value around our SIN20 and SIN4 assets, which have significant potential opportunity in non-oncology indications. We are currently evaluating the best path forward for these assets and whether to advance these programs internally, out-license, or partner them. In the interim, Washington University continues to screen and enroll patients in our Phase 1b2a clinical study of SYN4 or riboxamase and L-genetic HCT recipients for the prevention of acute graft-versus-host disease in bone marrow transplant patients. The Phase 1b28 study is designed to assess the feasibility of using SYN4 in this 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. Last year, we announced that enrollment in patient dosing had commenced in the first of three sequential antibiotic cohorts that will each be administered a different IV beta-lactam antibiotic to treat fever following conditioning therapy. In total, eight participants in each cohort will receive CIN4 and four will receive placebo. To date, we have dosed 19 patients in the first antibiotic cohort, 12 that are currently considered available. This completes the enrollment requirement for the first cohort, and we expect to report top line data from the first cohort in the second half of 2022. Shortly after, we plan to initiate dosing of the second cohort in the fourth quarter of 2022. In summary, we have made steady progress throughout the second 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 impressive pipeline. Near and long-term clinical milestones include the initiation of our Phase 2 study in patients with metastatic PDAC in the fourth quarter of 2022. Top-line data from the first cohort in our Phase 1b2a clinical study of SYN4 and HCT recipients for the prevention of acute graft-versus-host disease in bone marrow transplant patients in the second half of 2022. The data from the VCN01 Phase I investigator-sponsored study in head and neck cancer to be presented at a major medical conference in the third quarter of 2022. Dosing of VCN01 in the first patient with high-grade brain tumors at the University of Leeds in the second half of 2022 The initiation of the second cohort in our Phase 1b2a clinical study of SYN4 for the prevention of acute graft-versus-host disease in bone marrow transplant patients in the fourth quarter of 2022. A planned pre-IND meeting with the FDA for our planned Phase 2-3 study in retinoblastoma by early 2023, and the initiation of our planned Phase 2-3 study in retinoblastoma in the second half of 2023. As you can see, we've positioned our company to deliver on a number of key value-creating milestones over the next 6 to 18 months. By prioritizing our three core clinical programs, VCN01, VCN11, and CIN4, we have the ability to effectively utilize our current cash position, which carries us into the first quarter of 2024, to deliver on important clinical data and related milestones. During the remainder of 2022, we have also planned a number of initiatives to expand our presence with the scientific and investment communities through targeted conferences, outreach, and rebranding activities. We expect to provide more information on our efforts in the months ahead. Before turning to our financial results, I would remind you that the company's common stock began trading on a split-adjusted basis on July 25, 2022. The reverse stock split was affected to ensure we could continue to meet our per share price listing requirements of the NYSE American Stock Exchange. We believe maintaining our listing on the NYSE American is important to the company's performance, corporate visibility, and will provide greater flexibility with respect to future capital market access. On July 29th, With MSD Credit Opportunity Master Fund, we closed the $3 million private placement of 275,000 shares of Series C convertible preferred stock and 100,000 shares of Series D convertible preferred stock. Each share of Series C and Series D preferred stock has a purchase price of $8. Each of these shares are also convertible into shares of the company's common stock at an initial conversion price at $1.22 per share. The proceeds. the SOC offering will further support the advancement of our clinical development programs. The purpose of this financing was twofold. First, the structure of the transaction will aid us administratively during our upcoming shareholder meeting to ensure that we have the necessary quorum for the meeting and the votes needed to help pass key initiatives that we believe are critical to our long-term success and viability. and this is very important, we've added a significant and highly respected institutional investor who is very supportive of the management team, our technologies, and our strategy. Now, I'd like to turn briefly to our financial results for the three months ended June 30, 2022. General administrative expenses increased to $1.5 million for the three months ended June 30, 2022 from $1.3 million for the three months of the June 30, 2021. This increase of 19% primarily comprises of increased consulting and legal costs related to the VCN acquisition, higher insurance costs, audit fees, and public relations expenses, and VCN administrative expenses not included in the prior year. The charge related to stock-based compensation expense was $86,000 to the three months end of June 30, 2022, compared to $83,000 to the three months end of June 30, 2021. Research and development expenses increased to $3.5 million to the three months end of June 30, 2022, from approximately $1.9 million for the three months end of June 30, 2021. This increase of 80% is primarily the result of BCN research expense related to BCN01, not included in the prior year, and to a lesser extent, higher manufacturing expenses for SIN 20, costs incurred related to our Phase 1A clinical trial of SIN 20, and expenses related to our Phase 1B2A clinical trial of SIN 4 and L-genetic HCT recipients. We anticipate research and development expenses to increase as we plan for and initiate enrollment for our Phase 2 clinical trial for BCN01 and PDAC, Phase 2-3 clinical trial in retinoblastoma, expand GMP manufacturing activities for VCN01, and continue with supporting our VCN11 and other preclinical and discovery initiatives. The charge related to stock-based compensation expense was $27,000 for the three months ended June 30, 2022, compared to $19,000 related to stock-based compensation expense for three months ended June 30, 2021. Other income was $17,000 for the three months ended June 30, 2022, compared to other income of $2,000 for the three months end of June 30, 2021. Other income for the three months end of June 30, 2022 is primarily comprised of interest income of $26,000 offset by an exchange loss of $9,000. Other income for the three months end of June 30, 2020 is primarily comprised of interest income. Cash and cash equivalents. totaled $52.3 million as of June 30, 2022, compared to $67.3 million as of December 31, 2021. Our cash and cash equivalents totaled approximately $53.5 million as of August 1, 2022. We believe with an advanced clinical pipeline and strong cash position, we are now well positioned to execute on our priorities despite geopolitical and macroeconomic uncertainty, as well as headwinds in the biotech marketplace. We are more excited than ever about the outlook of the company, and we look forward to providing further updates as we advance our technologies and products. With that, we're happy to take questions.

Ladies and gentlemen, if you would like to ask a question, you can do so now by pressing star one on your telephones. That's star one if you'd like to ask a question. We will now take our first question from Laura Thurl from Allianz Global Partners. Please go ahead.

Hi, this is Laura calling in for Jim Malloy from ADP. Thank you for taking our questions and congratulations on all your progress this quarter. So for the, for VCN 11, so with the current plans for IND enabling studies for this candidate, what is the overall current status on the IND filing? And also a question regarding your SIN 4 and SIN 20 candidates, how are potential partnership discussions going on for them? Thank you.

Okay, so first I'll take the SIN 4 and SIN 20 question, and then I'll have Manel give you an update on our plan as we continue to advance VCN 11. So as I stated last quarter, the SIN 20 program has interest from outside parties. We've had diligence discussions on that asset, and they continue. And as I've previously stated, once we have something that is definitive and more clear-cut, We'll certainly get that information out there. For the SYN4 asset or Abaxamase, there is a nice fit within an oncology platform, and that is a preventative for acute graft-versus-host disease in bone marrow transplant patients. We just completed the first cohort of that study, and we announced we'll have that data released here in the second half. We're very encouraged about that program and we're getting it teed up once we clear the safety data monitoring board at WashU to advance that into the next cohort. I think there'll be a real opportunity and an inflection point for us to make a decision around that asset once we complete this phase one study and demonstrate the safety of this program in this more fragile patient population and the decision point once we complete the study will be whether to partner that or to continue to advance that, you know, on our own. So, you know, that one, I think the decision is a little bit further down the line. The discussions on SIN 20 continue, and we'll have some information on that as we have something that's a little bit more concrete. Manel, why don't you take the status on the BCN11 program?

Okay, perfect, Steve. So with BCN11, we have been conducting several preclinical activities, and we have definitively set what's the candidate definition. We have a very clear idea about the safety, the pharmacokinetic, and the toxicity profile of the product. And also, we have been conducting several activities related to establishing the different mechanism of action of the product and the effectiveness of anti-tumor activity in several preclinical models. And in parallel to all these activities, we have also been working on the final definition of the manufacturing process for BCN11, which is very similar to BCN01, but with some specificities. Not major, but obviously we need to test that. And that's what we are doing right now in our internal CMC department. and we're planning to start manufacturing as soon as we have all these internal activities finished with respect to be not very far in the next months probably. As soon as we have this done and we can translate the manufacturing process to the CMO, we are going to have the material to conduct the IMD enabling studies. So we are progressing quite smoothly with this candidate and we are pretty convinced that in the next months we are going to have major advances with him.

Thank you.

We will now take our next question from Michael Uckenwich from Maxim Group. Please go ahead.

Hey, guys. Thank you for taking the question, and congratulations on the progress over the quarter. I guess my first question, I'd like to ask a bit more just about the rationale for targeting retinoblastoma. Is this largely based on the relatively short path to market, or are there any particular mechanistic rationales that make this indication particularly attractive?

I'll take the first part, and then I'll hand it over to Manel to talk about the scientific rationale. For me, this is really exciting because there's no approved treatment for this serious, serious type of cancer that affects these pediatric patients. And if you would see the outcome opportunities, they're not very pleasant. If present treatments, whether it's cryotherapy or different forms of chemotherapy don't work, these eyes get enucleated to prevent the cancer to spread to the brain and ultimately cause death. So We're very excited not only to be able to utilize our technology, but to hopefully prevent the serious destruction of the eyes of these types of patients and prevent their deaths. With orphan drug designation, I think that gives us a real opportunity, assuming the data that we continue to generate from our Phase I study and ultimately the data we hope to generate from a Phase III study to separate us from anybody else who's tried to advance a serious treatment for these patients. I'll turn it over to Manel and let him talk about the scientific rationale and maybe some of the observations we've had as we've used VCN to treat these patients, VCN-01 to treat these patients.

Okay, thank you, Steve. Yes, there's a list of different scientific reasons for selecting retinoblastoma as a target indication for BCN01. First of all, it's basically the genetic reasons for retinoblastoma. Retinoblastoma is a tumor that is characterized by the mutation of retinoblastoma protein. That's the reason for the name of this tumor. And our bioselectivity is just based on the retinoblastoma pathways. not only is it related to the mutation of retinal blastoma, but any mutation in the retinal blastoma pathway, but also the mutation of retina. So, the mechanism of action is extremely well fitted because we are basically comparing selectivity to BCN01 based on the pathway that is mutated in this specific tumor indication, okay? That's an initial indication. The other very interesting thing for this indication is that one of the major problems with current therapies in retina of the stomach is the toxicity of the chemotherapy that the patients are receiving, the child are receiving for controlling the growth of retinoblastoma tumor cells. Majority of the tumors, majority of therapies that patients are receiving are damaging the retina of the patient, and that makes that this patient maybe can live without tumor, but also without a major view, a major capacity of view, okay, of sight. So that's also one of the reasons because BCN1 has demonstrated in our phase one trial that is extremely selective for retinoblastoma cells. We have collected biopsies from patients, and we can observe the replication capability in tumor cells compared to standard retina, and we know that the virus is not affecting at all the normal retinal patients. So the visual capacity of patients are not impacted at all. And that's a major thing in the field of retinoblastoma because that's really a real need for this type of really selective therapies that maintain not only the viability of the eye, but also the visual accuracy of patients. Okay. So, in addition to that, obviously, there are other reasons. The convenience of administering DGN-01 as the VTL disease, as in the VTL therapy, it's also very convenient in retinoblastoma because they are quite useful to this type of administrations and probably with a single or, let's say, a reduced number of doses of our products. we can allow maintaining the response of patients for long periods. And in fact, we have observed even a complete response in a patient that is still free of disease more than three years and a half after administration of our product. So there's several scientific reasons that make the retinoblastomas a perfect target for BCM01.

Thank you very much. I appreciate the additional color. As a follow-up, I'd like to talk a bit about the Albumin Shield Program and VCN11, and specifically how you're viewing that program strategically. Is this more of a follow-up to VCN01 where it can excel on the same indications, but you have the option for multiple dosing? Or does it open up new indications where a single dose may not be ideal?

So... Let me just take the first part and then I'll hand it off to Manel again. We see this as a strategic asset to build on the data that we're generating on VC-101. And we believe this has a really nice opportunity to treat more difficult cancers out there. And, you know, one of the keys has always been, you know, neutralizing antibodies. And I think the design of this allows us to address that, and as you suggested, to allow us to use multiple dosings with these more difficult-to-treat cancers. Manel, do you want to comment further on the technology?

Yes. Obviously, as said by Steve, that's the first goal of this program is to expand the range of tumors that can be treated with a product like BCN01. However, we are also working very intensively in improving and putting albumin binding technology with other payloads that obviously maintain the other one, because we think that it's critical for the therapeutic effect that we are observing in our patients with this kind of one. But we are exploring to add additional payloads. And eventually, these additional payloads with the albumin shielding technology can bring these products to a new stage. And I think that we can be... That's obviously, that's something that we are still in very clinical early stage, let's say. But that can open additional venues to what we have right now with BCN01. But that's something more speculative at this point. So BCN11, it's probably more direct continuation of BCN01. But eventually, that opens the door to new technologies and new products that can be even more differential.

All right. Thank you very much for the answers.

Thank you. As a reminder, if you'd like to ask a question, please press star one on your telephone. There are no further questions. Pardon me, we do have a question. One moment. Sorry, the caller has stepped away.

There are no further questions. I will turn the call back to your host.

Thank you, Emma. And thank you to everyone for taking the time to join our call today. Looking ahead, we are well positioned to deliver on our focused clinical development strategy, as well as our key objectives that we believe will drive significant value for our shareholders in the months and years ahead. We remain deeply committed to improving patient outcomes for hard-to-treat cancers, and we look forward to providing updates on our progress. Once again, I would 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. Once again, thank you for joining us today, and have a great weekend.

Ladies and gentlemen, that will conclude today's conference. You may now all disconnect.