Greetings and welcome to the Synthetic Biologics Fourth Quarter and Full Year 2021 Earnings Conference Call. At this time, all participants are in a listen-only mode. A question-and-answer session will follow the formal presentation. [Operator Instructions] As a reminder, this conference is being recorded.

I would now like to turn this conference over to your host, Mr. Chris Calabrese with LifeSci Advisors. Thank you, sir. You may begin..

Thank you, operator and good afternoon, everyone. Welcome to the Synthetic Biologics 2021 year-end investor conference call. Leading the call today will be Steven Shallcross, Chief Executive and Chief Financial Officer of Synthetic Biologics; Dr. Vince Wacher, Head of Corporate and Product Development of Synthetic Biologics; Dr.

Manel Cascallo, General Director of VCN and European Operations; and Dr. Frank Tufaro, currently Head of Operations of VCN, are also on the call and will be available to answer questions during the Q&A session.

Synthetic Biologics issued a press release this afternoon which provided operational highlights and included the financial results for the quarter and year ending December 31, 2021.

The press release can be found in the Investors section of the company website at www.syntheticbiologics.com, together with the annual report on Form 10-K for the year ended December 31, 2021 which was filed 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 for 90 days. During this call, certain forward-looking statements regarding Synthetic Biologics and VCN Biosciences' current expectations and projections about future events will be made.

Generally, the forward-looking statements can be identified by terminologies 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 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-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?.

the initiation of VCN-01 dosing in an investigator-sponsored study of brain tumors at the University of Leeds, the initiation of VCN-01 dosing in combination with mesothelin-directed CAR-T cells in the investigator-sponsored study of pancreatic and ovarian cancer at the University of Pennsylvania, a data readout from the first cohort of the SYN-004 study in allogeneic HCT patients and top line data from the multiple ascending dose study of SYN-020 in healthy volunteers.

During the second half of 2022, we expect to initiate key clinical trials, including the Phase II study of VCN-01 in PDAC patients and possibly a Phase IIa study of SYN-020. Additionally, we anticipate the initiation of a Phase IIb/IIIa pivotal study of VCN-01 in retinoblastoma either by the end of the year or very early in 2023.

Now, I'd like to turn briefly to our financial results for the year ended December 31, 2021. General and administrative expenses increased to $6.5 million for the year ended December 31, 2021, from $5 million for the year ended December 31, 2020.

This increase is primarily comprised of consulting and legal costs related to the VCN acquisition, higher insurance costs, audit fees and public relations expenses. Research and development expenses increased to $7.8 million for the year ended December 31, 2021, from $5.1 million for the year ended December 31, 2020.

This increase was primarily the result of increased clinical trial expenses as we continue dosing patients in the Phase Ib/IIa clinical trial of SYN-004, the dosing of healthy volunteers in the SAD and MAD Phase I clinical studies for SYN-020 and higher indirect program costs for the year ended December 31, 2021, including an increase in manufacturing costs for SYN-020.

Turning briefly to the balance sheet.

We ended 2021 with over $67 million of cash on hand at December 31, 2021 which we believe will provide a significant runway to build support our existing programs as well as help accelerate the development of VCN clinical pipeline, including VCN-01 and VCN-11 through the end of 2023, during which time we expect to achieve a number of important milestones, as I mentioned earlier.

As previously announced, the VCN transaction was structured to preserve our strong balance sheet and enable the planned advancement of our combined clinical development pipelines. As previously disclosed, we acquired 100% of the outstanding equity of VCN which will now operate as a wholly-owned subsidiary of Synthetic Biologics.

The upfront consideration for the acquisition was $4.7 million in cash plus the assumption of $2.4 million of VCN liabilities. In addition, certain VCN shareholders received 19.99% of the total outstanding shares of Synthetic Biologics common stock as of December 14, 2021.

The balance of the VCN purchase price includes up to $70.25 million in future payments contingent upon the achievement of specific Phase II and Phase III clinical and regulatory approval milestones. There will be no additional royalties or commercial sales milestones to the sellers.

Assuming we meet these milestones, we believe the value created for shareholders will far exceed the payments made to VCN. With an advanced clinical pipeline and a strong cash position, we are more excited than ever about the outlook for the newly combined company.

We believe the VCN acquisition will be truly transformational and we look forward to providing further updates as we continue to advance our combined technologies and products. With that, we're happy to take some questions..

[Operator Instructions] Our first question comes from the line of Jim Molloy with Alliance Global Partners. You may proceed with your question..

Hey guys, good afternoon. Thank you so much for taking my question.

One question on VCN-11, what's the expectation for timing to wrap up of the preclinical and sort of file INDs and start going in Phase Is?.

So right now, we're in the middle of completing some animal work on that asset. And we're also aligning ourselves with the CMOs today we can produce some additional supply and validate those runs for future use in human clinical trials.

The idea is that sometime, hopefully by the middle of 2023, we will be positioned as a result of those activities probably in the second half of 2023 to file an IND..

Excellent.

And then on looking at potential partnerships or licensing or [indiscernible] selling the SYN programs, could you speak a little bit to how the market is looking? And are you able to talk -- give us some color around interested parties for those programs?.

Sure. So the reason going back over the last couple of years that we continue to work diligently to advance the SYN-004 and the SYN-020 program is that in order to attract the right interest at the right value, we needed to generate some additional clinical data. So as it relates to ribaxamase, we're still ongoing in that trial.

We'll have our first cohort reporting out in first half year. We still have two more cohorts to get through. So I think it's a little premature to discuss how much time and who may be interested in that program until we completed and generate the necessary clinical data that will sort of give us a tight package to have a legitimate discussion around.

The SYN-020 program is really interesting that's the intestinal alkaline phosphatase program. We have had continued interest around this program over the, I would say, the last 1.5 years or so.

Again, rather than jumping into a partnership with somebody on that, we needed to generate additional clinical data and complete additional manufacturing work around that asset. We've completed both of those Phase I studies. We'll have the top line data coming out very, very shortly. The CMC work continues.

We've been aggressively scaling up production -- we're quite promised -- it's quite promising what we've been able to observe already. All I'll say is there's continued interest from multiple parties on the SYN-020 asset.

And as we've said in the past, when we have something to talk about further about it, we'll make sure we communicate that effectively to all of our shareholders..

Last question then. You guys are excellent stewards of shareholder capital, ending the year with a good number. Does -- I think -- I believe your guidance was the cash through 2023. Does that include sort of any of the payouts for the VCN milestones that you could hit? And then maybe wrapped up and I think you guys did about $14 million of burn in '21.

Is that the rate we should anticipate you guys staying at with the new VCN programs? Or is that going to go up or down through the next couple of years?.

So right now, we're only prepared to give us -- give the guidance through 2023. For modeling purposes, at this point, you could probably divide it in half. Yes, the guidance through '23 includes the deal payments and the milestones that are scheduled out as we advance the VCN programs. There's going to be a slight increase in our fixed burn.

As you guys know, historically, we've been operating SYN at around $400,000 a month in fixed burn, that will scale up to probably closer to $650,000 to $700,000 a month with the addition of the VCN organization. They're a very lean organization, as we are. There's no duplicity. Both of our teams will complement each other very, very nicely.

And then you can kind of back into what the rest of the burn looks like as it relates to CMC and CRO work -- and as we contract with these organizations, we'll be in a position at a later date to give some more detailed guidance around each of those line items..

Understood. Thank you very much for taking the questions..

Our next question comes from the line of Jason McCarthy with Maxim Group. You may proceed with your question..

Hey Steve, thanks for taking the question. Can you talk a little bit or in a little bit more detail about the PDAC program? I think you said it was going to be first line metastatic PDAC.

And if so, what are some general expectations around what gemcitabine and nab-paclitaxel survival or PFS should be where we start to think about what a benchmark might be per upcoming program? And the second part to that question is related to the multi dosing part, a potential multi-dosing part given that there could be some immunity on a repeat dose of an oncolytic virus which I think is the basis of trying to do the VCN-11 program.

So a bit of a complicated two part question but if you can give us some more color, that would be helpful..

Okay. Thanks. Manel, I'll let you take that question..

Sure.

So just to give you a bit more color around the trial, that's designed to be a controlled trial with two arms, okay? So obviously, the data, the historical data for overall survival for the control arm, so the gemcitabine, nab-paclitaxel arm, it's around normally between 8 and 11 months, okay? That's expected overall survival that has been validated in several studies from the drug approval to right now with different studies, just confirming this number.

So our Phase I data in the reduced group of patients that we have treated with the same dose that we are planning to conduct a Phase II study indicates that these numbers can be larger. And we think that probably we can get closer at least to 15 months or even more. In fact, in our Phase I trial in this reduced population is close to 20 months.

So we are quite optimistic about that but obviously, the trial has to confirm this data. And then that could be really impressing.

In terms of response rate, for instance, we are expecting to be in one year overall response rate around, let's say, 65% probably is the number that we are contemplating for statistical purposes, at least, okay? Coming back to your question about the role of immunity and I assume you referred to neutralizing antibodies against the first administration.

It's a very interesting question. And you are right in the sense that it has been previously demonstrated that clinical administration of adenoviruses, in general, several oncolytic viruses in general, generates a peak of neutralizing antibodies.

We have a lot of data collected from our Phase I program in different trials, where we have monitored quite closely with the kinetics of generation and degradation of neutralizing antibodies in patients.

And we have observed that after the first administration, we see a peak that normally, of course, between 15 and -- day 15 and day 30 but normally by, let's say, 12 weeks, this peak decreased significantly and decreased to a level of neutralizing antibodies that we know that we are able to overcome with the doses of VCN-01 that we inject.

And that's something that we have validated in Phase I trial. That's why in our schema with VCN-01, the repeated administration occurs in three month period. That's quite consistent with has been observed in other applications of adenovirus.

For instance, a very popular administration is, for instance, the COVID vaccine for AstraZeneca that it's also based on adenovirus. And as you probably know, the lag time between the two administration of this vaccine fits also in this three month period which is basically the period when the levels of neutralizing antibodies decrease significant.

So we are quite confident because our data previously generated with VCN-01 by systemic administration, confirms that the second dose can be as effective as the first dose is..

Got it. And just as a brief follow-up to that.

What is the expected timing for an outcome with regulators on the trial and getting things started? And about how long do you think it would take to run that trial?.

So maybe I'll let Frank take that piece of the question..

Yes. So if I understand the question correctly then, this is a standard submission to the FDA which -- of the protocol which was then they have 30 days to respond. We're not really waiting for an approval, just a nonresponse means we can proceed.

And during that period of time, we'd be launching -- initiating the sites and getting ready to enroll patients. We need to enroll the patients in, I think the latest number was between 12 and 18 months and that's for statistical reasons, you have to get the patients in the trial fairly quickly.

However, as Steve mentioned before, this is also open label. So we're going to be able to start seeing the outcome much earlier than the completion of enrollment. So we're pretty excited about the trial design.

And we're going to -- because of the unique nature of the VCN product, we're actually able to measure the effect of the second dose, for example. We can actually take a blood test and show that, that's working. So we think we have -- we're going to be learning a lot during the trial as well but we should be able to enroll within 12 to 18 months.

And Manel, correct me on that timing, is that the enrollment time we have set up currently?.

Yes, yes. That's it. So we are planning to finish enrollment between 12 to 15 months, okay? And we are quite optimistic on that. We are taking quite aggressive strategy, just combining European and U.S.-based sites that allows certain flexibility between both geographic indications.

And our first approach to different sites, it's going -- it's been very, very promising in terms of the sites are very interested in the trial; so we expect to really comply with this time line..

Great. Thank you for taking the questions, guys..

Our next question comes from the line of Vivan [ph] with Oppenheimer. You may proceed with your question..

Hi, good afternoon. Thanks Steve for this update and for taking my question. First question on the PDAC study, Manel [ph], you had mentioned you may opt to include an interim analysis there.

Wondering when we might hear on that decision to potentially do so? And what you may use -- what information may come to inform that decision?.

Manel, do you want to go ahead?.

Yes. The trial does not contain a formal interim analysis because it's an open-label study. So we have access to the data in a like [ph] basis.

okay? So we are expecting to have a significant number of patients for generating significant numbers probably in 12 months after the initiation of the trial where, obviously, it depends on the survival with the patients, the active survival of patients.

But taking into account the data that is historical data for the standard of care for Abraxane, we assume that probably in a period of 12 to 15 months, we are going to have that position, with probably we have some data to show, yes..

Okay. And then my next question with respect to retinoblastoma. Wondering if you could share the end points that will be key for that trial if you have thoughts there or know what that design will look like.

And if you'll be able to take any advantage in terms of the FDA regulatory mechanisms to expedite approval perhaps through accelerated approval from that study..

Go ahead, Manel..

Yes. So we are just finalizing the conceptual of this trial. And it's true that the endpoint of this trial, it has to be definitively agreed with the FDA because there has not been any formal trial in retinoblastoma to date. So that's something that definitely we will have to discuss with FDA and we are planning a discussion with them.

Our idea right now is the reduction of vitreous seeds as a primary endpoint of this trial and maybe the ocular survival as a secondary endpoint but as anticipated. That's not definitive yet because that needs to be agreed with the FDA.

And we are, however, quite confident that, that's going to be accepted because there's no formal approval for any retinoblastoma product at this point. So we anticipate that if we are able to demonstrate a significant reduction in the number of vitreous seeds in these patients that's going to be considered and marketing-enabling endpoint..

Great. That’s very helpful. Thanks for taking the question..

Our next question comes from the line of Michael Okunewitch with Maxim Group. You may proceed with your question..

Hey guys, thanks for taking the question. So, I'd like to start to ask a bit about the program with the mesothelin CAR-T. Who's developing that? Is that coming from Carl June over at UPenn.

And if so, is that similar in design to the Juno, Celgene Bristol CAR-T?.

Go ahead, Manel..

Okay. Yes, you're right. So the product comes from UPenn and it comes from Carl June's lab and that's the mesothelin-directed CAR-T cells. As you probably know, the program from Novartis is basically focused on hematological, the cancer and that's the approval indication for this product.

However, Carl June group is working since the last year in treating solid tumors, okay? And that represents additional limitations for the CAR-T therapy because it's easy to treat to liquid [ph] tumor, so hematological tumors because the accessibility of the CAR-T cells to the tumor cells is immediate.

However, when you are dealing with solid tumors, that can be ovarian or pancreatic, you need to have the CAR-T cells able to reach the tumor and to penetrate the tumor.

And these two limitations are basically the major assets that our product contains because VCN-01, it's a virus that express a tumor degrading enzyme; this can [indiscernible] on the base.

And moreover, we have demonstrated in our Phase I program that the product is able to inflame the tumors when replicating okay? So the inflammation of the tumor by effect of replication, it's powering the homing of CAR-T cells into the solid tumor and the expression of [indiscernible] is going to help CAR-T cells to go into the tumor.

So that's why there's a real, very impressive synergy between the programs of Carl June's lab with our product and that's the focus of the trial..

I'd also like to see if there are any plans for combinations with additional immunotherapies like say checkpoints or therapeutic monoclonals due to the potential to expose tumor antigens and cold tumors..

So I don't know, maybe Frank, that's best suited for you..

Yes. So that's a good question. We are considering other immune therapies. As you know, many oncolytic viruses typically try to combine with checkpoint inhibitors, in particular, we would be interested in doing the same. We've started it internally at least, discuss what that would look like.

The difference though between this program and some of the others is the initial data on PDAC that VCN has already generated has a signal, we believe. So -- and checkpoint doesn't typically work in that indication. So we think that's going to be kind of an additive trial that we could do.

We wouldn't likely add it to the existing trial because we think we're going to see a signal compared to control. But we could do another trial with something like pembrolizumab, for example, or a PD-L1 inhibitor.

And even other immune drugs, the beauty of -- again, I'm a bit biased here but the interesting thing about VCN hyaluronidase is it actually opens up the tumor to allow other things to get in like drugs, like pembrolizumab and chemotherapy.

So it's almost like a radiation sensitizer or something where you're adding something that then allows other drugs to work. So we're -- to answer your question, we're very excited about the opportunity. We know that it can be done and VCN is already doing a different trial with combination therapy with a checkpoint drug..

Very interesting stuff. And then just one last one. I'd like to ask us strategically on deployment of capital. Obviously, you have a lot of cash in your balance sheet.

So how do you view your capital allocation going forward? Is it more focused on advancing the current programs that you have in the book and maintaining that nice cash cushion to 2023? Are you looking more to expand the platform into additional indications and settings for the VCN programs or potentially expansion of your oncology pipeline with further M&A opportunities especially given the current pressure in the biotech market?.

Boy, that's a big question there, Mike. So the guidance that we've given right now is that we have cash on hand to get us through 2023. The focus right now is to complete what we started on the SYN-004 and the SYN-020 programs. And a majority of the deployment of capital is going to be focused on the VCN pipelines.

So right now, I mean, we've got a lot on our plate. We'll work diligently to get the WashU trial over the line. We'll have the data coming out on SYN-020 very shortly.

And I would say 85% of our focus this year is going to be getting the PDAC trial up in the last quarter of this year and work diligently to get agreement with the agency on what a retinoblastoma pivotal trial looks like so we can get that going either by the end of this year or early on '23..

All right. Thank you very much. I really appreciate it. A lot of interesting stuff going on..

Ladies and gentlemen, we have reached the end of today's question-and-answer session. I would like to turn this call back over to Mr. Steven Shallcross for closing remarks..

Thank you, Laura and thank you, everybody, for taking the time to join us today on our call. We're extremely excited about the continued growth of our company. And I hope you share our enthusiasm around the outlook for the business, including the prospects following the VCN transaction.

We look forward to executing, as we stated earlier, on a number of key objectives that we believe will drive significant value for our shareholders in the months and years ahead. I'd like to thank our shareholders for their ongoing support and we look forward to providing additional updates on our progress.

Before we conclude today's call, I'd also like to thank our entire combined SYN and VCN team and to the many people who have been supportive along the way, including our patients, patient volunteers and their families. Thank you again and have a great week..

This concludes today's conference. You may disconnect your lines at this time. Thank you for your participation. Enjoy the rest of your day..