Full Year 2020 Synthetic Biologics Inc Earnings Call

Yes.

Good afternoon, and welcome to the synthetic biologics 2020, your and Investor Conference call all participants will be in listen only mode.

Should you need assistance. Please signal of the conference specialist by pressing the star key followed by zero.

After today's presentation there'll be an opportunity to ask questions to ask the question you May Press Star then one on your telephone keypad to withdraw your question. Please press Star then two please note. This event is being recorded at this time I would like to turn the call over to Vincent Perrone director of corporate Communications.

Synthetic biologics. Please go ahead.

Thanks, Gary and good afternoon, everyone welcome to synthetic biologics 2020 year, and Investor Conference call today, I'm joined remotely by Steven Shallcross, Chief Executive and financial Officer, Dr. Michael Calico, Senior Vice President Research and development and Dr. Vince Wager head of product and corporate development.

Synthetic biologics issued a press release this afternoon, which provided operational highlights and reported our financial results for the year ending December 31, 2020. The release can be found on the Investor Relations section of our website.

During our call today, we will provide an operational update on our Gi and microbiome focused clinical programs and summarize our financial results. We'll take questions. After our prepared remarks, and addition to the phone line this call, which will be streamed live via webcast and will be archived on our website at www dot synthetic biologic stock com for 90 days during this.

Call, we will be making forward looking statements regarding synthetic biologics current expectations and projections about future events 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.

Upon current beliefs expectations and assumptions and are subject to a number of risks and uncertainties, including those set forth and 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.

Thanks, Vince and good day.

Afternoon, everyone and thank you for joining our 2020, Nir and Investor Conference call I.

And I hope everyone is staying safe and healthy as we continue to navigate the global health crisis sparked by the COVID-19 pandemic.

It was a busy year and the start of the new year for the same team.

And I'm very excited to be with you. This afternoon, the share or operational highlights and financial results.

I'd like to start our call by saying that we are more encouraged than ever by the outlook for our business.

We've made important progress this year by advancing and demonstrating the significant value of our pipeline of Gi and microbiome focused clinical programs and as we look ahead into 2021 and 2022.

There are more reasons than ever to be excited about our company's future prospects.

Before I give you an update on our two lead clinical programs and I'd like to provide a brief recap of several of our operational milestones, which have unquestionably allowed us to strengthen our balance sheet and position our company for what I believe will be significant long term growth as well as the delivery.

And of multiple short and long term clinical milestones.

Starting in January and the favorable market conditions triggered the exercise of the cash exercise of approximately 65% of the warrants associated with our 2018 public financing and allowed us to efficiently utilize our at the market facility.

In addition, the conversion of all of our outstanding shares of series, a and series B convertible preferred stock into common stock have not only further help streamline our capital structure and balance sheet, but allowed us to position the company to meet the conditions to fully regained NYSE.

Listing compliance.

As a result of these activities were pleased to announce that our current cash balance is approximately $72 $6 million, the strongest cash position and the company's history.

Our strength and financial position now provides us with the runway to continue our operations well into 2020 three.

Importantly, we now have the financial foundation to fully fund our phase <unk> clinical trial of Syn <unk> and planned phase one and phase two clinical studies of <unk> 'twenty.

In addition, we are now positioned to evaluate and potentially acquire new technologies and our assets intended to enhance our development pipeline, which we believe may benefit from our incredibly experienced team.

As we anticipate clinical trials returning to normal our recently strengthened financial position will allow us to conduct multiple clinical studies. During the next several years advancing our portfolio of Gi focused clinical programs through proof of concept.

As we think about the remainder of 2021 and moving into 2022, we are excited about several potential catalysts and clinical milestones that can create additional significant value for our shareholders specifically.

Specifically for 10 and for our therapy and development to prevent acute graft versus host disease or a gvhd.

We are excited to announce that Washington University has begun screening patients for enrollment of the first cohort and the phase <unk> clinical trial and the Elgin are committed periodic cell transplant or <unk> recipients.

We expect to begin dosing patients in this cohort before the end of the month and if the enrollment proceeds as planned we will be positioned to announce up to three interim data readouts. During the next 12 to 18 months with the first one anticipated before the end of the year pandemic conditions from.

<unk>.

<unk> and 'twenty are intestinal elfa and phosphatase program. The phase one single ascending dose study or sad study is expected to begin during the second quarter of <unk>.

Top line readout for this clinical trial is expected during the third quarter of 2021, and our second phase one multiple ascending dose study or Mad study of Syn <unk> 'twenty is expected to begin in Q3 with top line data expected in Q1 of next year.

Both phase one trials are designed to support the development of <unk> and 'twenty in multiple clinical indications.

Following what we believe will be of successful phase. One program. We were we are preparing a phase II clinical study and celiac patients as well as clinical programs for other potential indications that could begin as soon as.

Early 2022.

We believe syn <unk> and development of Brent Adv, HD, and <unk> and 'twenty of recombinant intestinal alkaline phosphatase program addressed very sizable and underserved markets and have the potential to be foundational long term drivers of value for our company.

And our shareholders.

With that backdrop.

To provide and update on our clinical development activities, beginning with our syn <unk> or <unk> program.

<unk> is our first in class therapeutic intervention designed to protect the gut microbiome from antibiotic mediated <unk>.

We believe protection of the gut microbiome may play a pivotal role and improving health outcomes for patients administered long courses of intravenous beta lactam antibiotics as part of their treatment plan for bone marrow and solid organ transplantations.

L generic HCP recipients REIT to routinely receive long courses of IV beta lactam antibiotics to treat neutropenia fever, which occurs and $80 to 90% of the patients.

Microbiome damage from IV beta lactam antibiotics is associated with Eva of Gvhd, vre colonization, bacteremia and C difficile infection.

<unk> occurs in the 30% to 60% of allogeneic <unk> recipients and is a leading cause of graft failure and mortality.

Prevention of Gvhd is absolutely critical in this patient population since first line <unk> stared, the steroid therapies fail and more than 50% of the patients, resulting in a two year survival rates of around 20%.

The use of <unk> 'twenty I'm, sorry of the use of <unk> four and <unk>. Each thet patients is well supported by our existing clinical data.

And <unk> potential to preserve the intestinal microbiome and allogeneic <unk> recipients could provide remarkable benefits to patients providers and payers.

Estimates of in hospital cost for Allogeneic, <unk> recipients and the U S range from $180000 to more than $300000.

Cause inpatient and outpatient costs are estimated to be greater than $600000 per patient when measured up to 12 months after hospital admission.

And at least one U S study found that allogeneic <unk> recipients, who developed <unk> HD had a three times higher in hospital mortality rate and almost twofold increase and higher median hospital cost and patients who did not develop a gvhd.

If <unk> could reduce <unk> incidence by 30% it may provide significant improvements and patient outcomes, including prevention of an average of 11 deaths and a reduction of $4 $3 million and hospital treatment cost per 1000 patients.

In 2018, there were approximately 29000 allogeneic <unk> procedures conducted in the us and Europe and an additional 13000 procedures conducted in Japan and China.

While these are comparatively small patient numbers the substantial potential benefits and four may provide and this patient population could allow for premium pricing and significant market value.

Conservatively, our modeling suggests a revenue opportunity and the U S and European markets of more than $800 million and the first five years of sales when considering pricing of $1000 of day for 14 days of treatment.

If we were able to expand the opportunity for syn <unk> for use in solid organ transplant recipients the market opportunity could be four times larger.

It is worth noting that developing syn for for use in the specific patient.

And the specific patient population may also provide an opportunity to seek orphan drug designation, which may further facilitate phase III clinical development.

Last year, we outlined our plan and the move this program forward and collaboration with our clinical development partner of the Washington University School of Medicine, and St. Louis and the form of the phase <unk> clinical trial of Syn <unk> and allogeneic <unk> recipients.

And the goal of the study is to evaluate the safety Tolerability and pharmacokinetics of Syn <unk> administered to as many as 36 adult allogeneic <unk> recipients, who receive and it.

Who receive of beta lactam antibiotic to treat fever.

Participants will be enrolled and three sequential cohorts that will be administered of different IV beta lactam antibiotic.

<unk> participants eight.

The eight participants in each cohort will receive syn <unk> and four will receive placebo.

Patients enrolled and the first antibiotic cohort will receive the antibiotic mayor of pin them, which is not the graded by <unk> four and order to determine whether <unk> four is systemically absorbed in this patient population.

The pharmacokinetic data from our previously completed phase one and phase II clinical trials provided support evidence supporting evidence that syn <unk> should not affect the IV antibiotic in the bloodstream.

If we see Thats and four is not systemically absorbed in this first cohort we will consider applying for orphan drug designation and begin to prepare for our phase III program as the remainder of this clinical trial completes.

At this time and Washington University is currently screening patients for enrollment in this first cohort and dosing of the first patient is expected to take place this month.

If enrollment proceeds as planned a topline data readout for the first cohort may be available before the end of the year.

Next I'd like to turn the call over to my colleague Dr. Michael Calico, who will provide an update on our syn <unk> intestinal alkaline phosphatase or IAP program, which is currently being developed as the treatment for celiac disease as well as other potential Gi and systemic inflammatory.

And age related disorders.

Mike.

Thanks, Steve.

Welcome this opportunity to discuss this in 'twenty program and to outline the anticipated clinical program and our selected indications sort of.

Boucher reached an important milestone with the first clinical trials scheduled to begin next month.

Since <unk> is the high specific activity form of intestinal alkaline phosphatase, which I'll refer to as IAP.

Produced recombinant Lee and show sales and.

Delivered orally.

Formulated to be protected and the stomach and released and the upper small intestine.

And then 'twenty is resistant to the digestion and is anticipated to remain in the Gi tract and eventually emerge and the stool inactive form.

IAP is an endogenous enzyme produced by the sales the line the small intestine and.

And it has multiple functions.

Tequila.

First it removes the phosphate from inflammatory mediators, such as and the toxin to diminish local inflammation and the Gi tract.

And second my AEP acts directly on the sales line, the Gi tract to improve barrier function and diminished so called leaky gut.

And third IAP serves to maintain and healthy microbiome.

The combination of these three functions suggest that.

Addition to withdrawal and diminished and Gi inflammation.

And it also diminished the low grades systemic inflammation and that has been associated with metabolic diseases and with aging.

The therapeutic potential of IAP supplementation, and it's been verified and many animal studies.

Oral administration of the IH Pete Erodes, the has been efficacious and virtually every model of colitis, and as well as models of metabolic syndrome and liver disease.

Interestingly a recent publication from our collaborator Dr. Richard Houghton at Massachusetts General Hospital show, the long term supplementation of IAP and monies diminish the inflammatory and metabolic changes that occur with normal aging and.

And prolonged the mouse lifespan.

Why then average other companies developed oral IAP products.

The answer would seem to be that is remarkably difficult to manufacturer.

Most of the studies and the literature had been performed with IEP the ROI.

<unk> from Caf and test.

Half of intestinal IAP cost up to $10000 per Gram, which is prohibitive who are on oral therapeutic.

And published reports with various recombinant platforms and of described very poor yields again is sufficient for an oral therapeutic.

And that is synthetic biologics we've overcome this hurdle.

Our unique advantage is the we've been able to generate a high yield production cell line that had commercial scale is anticipated to enable cost effective manufacturing.

We've shown that our recombinant the IAP and that is.

Lindsay is biologically equivalent the caf derived IAP and it was well tolerated and mouse and dog toxicology studies, the doses up to 50 fold of both the anticipated clinical dose.

And last June we filed an IND application and received a study may proceed approval from the FDA for our first in human phase one single ascending dose clinical study to evaluate since 2000 and safety Tolerability and bio distribution and healthy.

And the tears.

Really excited to say the first clinical study is scheduled to begin next month.

And four cohorts will be run sequentially and top line data are anticipated in the third quarter of this year.

The single ascending dose study will be followed by a multiple ascending dose study again to assess safety tolerability and bio distribution, but in this case with twice daily dosing for 10 days.

We're aiming to initiate the study and the third quarter of this year with top line data anticipated in the first quarter of next year.

Importantly, both of these phase one studies are designed to provide support for the subsequent clinical trials in multiple indications.

We've previously discussed three potential indications for early since 'twenty evaluation.

Radiation, enteropathy, Luton enteropathy, or celiac disease, and non alcoholic fatty liver disease.

We've now prioritize these indications and devised the clinical development plan for the ensuing two to three years.

Our initial indication for Syn <unk> clinical development will be celiac disease.

Auto immune disease triggered and genetically predisposed individuals by the ingestion of gluten proteins from wheat as well as other grades.

Celiac disease prevalence is approximately one percentage of the U S population and income.

<unk> children and adults the.

Clinical manifestations include both gastrointestinal and systemic symptoms.

All of the disease presentation and of course vary from patient to patient the underlying causes of the same.

Pacifically gluten derived peptides open the gut barrier leak into the intestinal.

Stimulator and inflammatory response, and then of course and auto immune reactions of human proteins, most notably the <unk> transplant candidates.

The disease is unique among autoimmune disorders and the trigger that is gluten is known and withdraw can and most cases mitigate the symptoms.

The only act disease has a very significant unmet medical need and there are no pharmaceutical treatments.

And so condemned to of lifelong highly restrictive gluten free diet and even in some patients fail to respond to of the time.

The disease can be very severe and rare cases can lead to early debt from lymphoma.

From a mechanistic perspective, we believe in 'twenty is well suited to improve clinical outcomes when combined with the right.

First on bolstering the gut barrier and <unk>.

And when he May block the initial step of gluten and entry into the intestinal wall.

Second through its anti inflammatory activities.

On Wednesday may serve to attenuate the immune response to the gluten peptides.

And finally patients with active celiac disease have been shown to have reduced levels of their own endogenous or the AP.

Presumably because of the disease, how much is the intestinal villi with normally produce.

The.

So in 'twenty, and celiac patients with potentially supplement and correct their low endogenous IAP levels.

The first proposed clinical evaluations and 'twenty and celiac patients will be a six week sales.

And one b to a gluten challenge study and patients who are well controlled on a gluten free diet.

The anticipated that the phase <unk> study will be followed by a 12 week phase II B study and patients who are poorly controlled on a gluten free diet.

Clinical endpoints for both studies will include patient reported outcomes laboratory data and endoscopic biopsies with.

Assuming successful completion of the phase one studies in healthy volunteers to phase <unk> study and celiac patients is tentatively scheduled to commence and the second half next year.

The anticipated that these two studies will provide the information with safety and potential efficacy and therapeutic dose and supports subsequent pivotal studies.

I'm also very pleased to announce the we have engaged a consultant Dr. Alessio for Sano of Harvard University, and Massachusetts General Hospital.

Nokia for Sarnia was the division chief of pediatric Gastroenterology, and nutrition and the director of the center for Celiac research and treatment.

Of the point, Dr. Fasano, who is the world's leading key opinion leader and the field of Celiac disease, who can guide us through the clinical analysis.

Finally, I would like to finish by re emphasizing the since 20 has the potential to treat both gastrointestinal and systemic diseases.

Warningly. We're currently drafting of clinical plan to evaluate <unk> and 'twenty the the treatment of non alcoholic fatty liver disease.

The utility of the since 2000 and for this indications well supported by the efficacy studies in multiple animal models of metabolic and liver disease.

We anticipate clinical entry as the phase <unk> placebo controlled double blind study and patients with modest elevations of serum liver enzymes the.

The study will address safety and Tolerability and follow the liver enzymes as well as relevant metabolic parameters.

To assist with the clinical design.

I'm very pleased to announce that we've engaged as the consultant Dr. Rohit Limbaugh and UC, San Diego Lockyer of lumbar as the director of the N. A S. L D. Non alcoholic fatty liver disease Research Center and.

On a world, leading kols and the field of non alcoholic fatty liver disease.

I'll provide more on this indication has the plan materializes.

Sure we were excited to see the scent and 'twenty program advanced into the clinic.

Thanks for your attention and I'll turn it back to Steve.

Thanks, Mike.

Our since 2000 and platform technology has a remarkable opportunity to help address a considerable unmet need for innovative new therapies targeting Gi disorders stemming from the immune and inflammatory responses, including celiac disease.

Currently there are no FDA approved therapies to treat celiac disease and disease management predominantly relies on lifestyle modifications and adherence to our strict gluten free diet.

Across the six major markets. The total prevalent cases of Silly Act disease are expected to increase from $5 8 million cases, and 2013, two and expected $8 1 million cases in 2023, representing an annual growth rate of approximately 4%.

During the same period prevalent cases, and the U S are expected to increase from $2 8 million in 2013 to and expected $4 3.002 million 23, representing a significant market opportunity.

Non alcoholic fatty liver disease is also an indication with high unmet need is.

It is estimated that the worldwide prevalence of non alcoholic fatty liver disease is anywhere from 6% to 33% and.

And the U S. Non alcoholic fatty liver disease is highly prevalent with an estimated prevalence of approximately 30% and the general population.

Non alcoholic fatty liver diseases also strongly associated with metabolic syndrome, and like celiac disease. No approved pharmaceutical therapies are available to treat this illness and disease management is dependent on lifestyle modification.

I hope we have conveyed our excitement for this first of all program and its potential to become a platform therapeutic for our company.

We believe <unk> will play a major role and delivering long term value to our shareholders, while targeting large underserved markets, including celiac disease.

With that backdrop I'll review, our financial results for the year ended December 31 2020.

Throughout 2020, we operated very efficiently.

We remain focused on prudent cash management and continued to identify areas to further reduce nonessential operating expenses.

And we ended the year with approximately $6 million and cash and cash equivalents, however, due to favorable market conditions, which triggered the cash exercise of approximately 65% of the warrants associated with our 2018 public financing and the efficient utilization of our at the market facility.

Our current cash position is approximately $72 $6 million.

Now I'll turn to the year and financial results.

General and administrative expenses increased to $5 million for the year ended December 31, 2020 from $4 6 million for the year ended December 31 2019.

This increase of eight 7% is due to increased legal costs related to business development patent execution employee contract matters vacation expense insurance costs and registration fees.

The charge related to stock based compensation expense was $300000 for the year ended December 31, 2020 compared to $300000 for the year ended December 31 2019.

Research and development expenses decreased to $5 $1 million for the year ended December 31, 2020 from $11 1 million for the year ended December 31 2019 the.

The decrease of 54, 1% is primarily due to a reduction and preclinical and manufacturing activity of the sin 2000, and IAP program and the result of the response to the global COVID-19 pandemic by our clinical development partners, which led to the postponement of the phase one b two way <unk>.

Trial of <unk> four in allogeneic <unk> recipients, the Syn 10 clinical trial and to a lesser extent the discontinuation of the phase two the investigator sponsored clinical trial of Syn 10.

Research and development expense also included a charge related to noncash stock based compensation expense of $66000 for the year ended December 31, 2020 compared to $75000 for the year ended December 31 2019.

Total other income was $44000 for the year on December 31, 2020, compared to other income of $283000 for the year and December 31 2019.

Total other income for the year ended December 31, 2020, and 2019 is primarily comprised of interest income from investments.

I hope we've conveyed in our remarks the.

The.

Embarking on a transformative and exciting direction that were taking our company.

We believe our newly found financial strength and long term outlook will allow us to unlock and further showcase the value of our clinical assets and generate long term and value for our shareholders.

Looking ahead to the remainder of 2021 and into 2022 upcoming significant major announcements and potential catalysts include for <unk> for our program and.

And the development to prevent.

Acute graft versus host disease and we.

We anticipate dosing the first patient and the phase <unk> clinical trial of this month and if enrollment proceeds as planned at top line data readout for this first cohort is expected before the end of the year.

For <unk> 'twenty, our therapeutic intended to treat celiac disease. Our first phase one single ascending dose study is expected to commence next month and a top line data readout is expected during Q3 of this year.

Our second phase one multiple ascending dose study is expected to start.

In Q3, and the topline data readout from this clinical study is expected during the first quarter of 2022.

Following the completion of our phase one studies were preparing for our phase II proof of concept of clinical studies and celiac patients. While also planning for clinical studies to evaluate <unk> and 'twenty for use and other potential indications that could also begin as soon as early 2022.

We look forward to continuing to update you on our progress and the weeks and months ahead.

So now I'll turn it back the call back over the Vincent.

Thanks, Steve Gary we'd like to open the phone line of questions can you. Please describe the procedure to ask questions for our listeners.

To ask the question you May Press Star then one on your telephone keypad. If you are using a speakerphone. Please pick up your handset before pressing the keys to withdraw your question. Please press Star then two.

At this time, we will pause momentarily to assemble our roster.

Our first question is from Jim Molloy with Alliance Global Partners. Please go ahead.

Okay.

Hey, guys. Good afternoon, and thank you for taking my questions and certainly a lot going on and a nice change from previous calls and as if we could cash and in and it looks like and exciting 2021, and setting up here and let it go through.

Some of the.

The.

The and Naphthyl and get rid of the and.

Youre talking about the phase ones for the novel.

And the.

And I was wondering on the phase one does the the.

One of your current currently running for celiac will that sort of cover the now because we're on a separate.

Phase one for that and what's kind of the timing on.

Net.

Okay. Thanks for the questions Jim.

Im going to let Mike take that question and walk you through the phase <unk>.

<unk> programs and as you'll see from his discussion.

The data that we gather from the phase one studies will allow us to advance the program and multiple indications of for phase two but I'll, let Mike walk you through that again.

Okay. Thanks.

So the.

Initial phase one studies will be of single ascending dose study and the multiple ascending dose study notes of both the single ascending dose study will be completed this year. The multiple ascending dose study will start this year and be completed early next year. Both of those are in normal healthy.

Volunteers Theyre designed to demonstrate safety Tolerability and bio distribution, we would like to show the same 20 days and the Gi tract.

And.

And not moving into the systemic circulation.

Once those safety studies are completed and then we go into a phase one the <unk> study and celiac disease.

It's the that's the challenge study and that should start in the middle of NEC.

The next year and that will be followed by a phase <unk> study in.

And celiac patients.

Shortly thereafter.

Now as a separate indication, there's non alcoholic fatty liver disease.

Okay that'll start as a phase one b study.

And and patients with mild elevations of <unk>.

Liver enzymes and we expect the during that study or we hope to see the liver enzymes diminish and we will also be following other metabolic parameters for target validation in those patients now those too.

Patient studies celiac.

And non alcoholic fatty liver disease are independent they.

And they are both supported by the phase one sad and Mad studies and normal healthy volunteers.

But the patient studies on our independent <unk>.

At the moment, we plan to start the Celiac study very shortly after the net the Mad study and normal healthy volunteers is finished.

And then somewhere along the way, we would move into non alcoholic fatty liver disease and the timing for that is not yet determined.

But it can potentially be run in parallel the silly back it is not dependent upon celiac.

Yes.

Does that clarify things.

That does very much clarify thanks, Thank you very much and get a lot of trials and sort of <unk>.

Starting up here and thank you for land and that helped yeah, it's pretty cool.

Yes.

On.

What should we anticipate for <unk>.

And for 2020 one of these various trials and about burnt through about 10, $10, one and $2 million and 2020.

On from obviously again.

And from 56 of two.

2019, do we get back to the 15 levels.

With the cash on hand, and trials ramping up would we stay sort of somewhere between 10 and 15 any guidance on that.

I would expect our fixed burn the stay in the 4% to 500000 of months that might start to increase a little bit more next year the.

The.

The phase one.

Study that will be conducted starting this next month.

And the Sad study.

Probably around $1 million study the.

The second one the Mad study you could probably think about it in terms of about $1 million and $5.

The on.

Ongoing.

Trial that is about to get on the trial is about to get underway with wash U as we previously disclosed that's about a $3 $6 million trial.

About 700000 has already been spent on that so there is just under $3 million or so.

That would be spread over the next 12 months to 18 months.

The phase II programs, we haven't.

Analyzing our cost on that yet.

So when we have a little bit more clarity on that and we'll share the does that help you out.

Very helpful. Thank you and then just my last question and you have a couple of other couple of programs, obviously didn't work out.

And it's the nature of drug development of <unk>.

<unk> and sort of the thoughts on the C Diff program.

Should we anticipate you guys might do with these compounds and something that has any interest from potential partners or are these just pretty much can be sort of shelves for the.

The future.

So the Syn 10 program, we've discontinued our license with Cedars Sinai was the mutual termination. So we are not spending any more money on that program and we've moved on from it.

I'll, let vince wage or talk about.

Our long term strategy as it relates to syn <unk> or write backs of mace and where we're beginning and ultimately how we could get to a broader C. Diff indication and Vince you want to take that.

Thanks, David Jimmy.

The the <unk> compounds and the bone marrow transplant and the allo HSH and compound on one and the same exactly the same product.

And are pursuing the bone marrow indication because it enables us to advance the prana.

And more effectively and four and a smaller number of patients and smaller clinical trials and ideally with a greater number of endpoints that we can evaluate to help move that program forward.

And the mechanism is exactly the same for both indications the bone marrow transplant and the safety of and in fact, preventing status is and anticipated outcome in bone marrow transplant patients and addition to reducing gvhd.

So this is one of the ways to think about the overall development plan is that we start with the bone marrow transplant patients looking at Gvhd and looking at vre colonization and and also looking at C difficile and all of the opportunistic infections and.

And that data can be leveraged to move into broader populations as David referenced the solid organ transplant population, we know that they have issues with opportunistic infections and those immunosuppressed patients and so that's an indication of where if we expand it would be more focused on the opportunistic infections and <unk>.

And then ultimately.

Using the data that's accumulate and as we move through these increasing indications to get back to the broader use and say this.

As we've explained before required of massive phase III trial that was that was beyond us at the time and so we're pursuing this more focused approach to get to get the product forward and generate that data.

Excellent. Thank you for taking the questions.

The next question is from Jason Mccarthy with Maxim Group. Please go ahead.

And it is the Michael accumulates on the line for Jason.

For taking my question and congratulation on the progress of it seems like things are really moving forward now.

Thanks.

Okay.

I'd like to ask regarding the the trial design.

Our sinful if you give a bit more on that like the overall timeline for the study and which antibiotics from the three cohorts and of which of the cohorts of the one you are expecting to read out by year end.

But once you go ahead, Vince and take that one as well.

No problem.

The three cohort study and the.

The use each cohort uses of different antibiotic and the way that the stage is to minimize risk to the patients based on the <unk> and potential effects of a full so to quickly recap some of our pointed grades penicillin and cephalosporin antibiotics debt not cobre, Panama and antibiotics.

So what we want to do is start where the cobre, Panama antibiotic and our first cohort and measure the.

Potential for absorption of four and what would be considered the cohort of the lowest risk. If there was any absorption because our product of thousand degree.

The type of Panama, even if it got it and that we don't believe it will even if anybody and it's known or likely to affect the antibiotic because its a top of Panama.

And with that.

The cohort.

Just to give us the results that we need if we have the successful completion of that cohort. That's the one that will initially read out and the data we will get from that will be safety and tolerability data of <unk>.

And the target population, who will also get a read on whether or not <unk> is absorbed into the circulation of patients with impaired barrier function and those are two key questions that the FDA had some of the program in general so with that data in hand.

And we will be able to proceed to the next cohort, which will be the pursuant times of that Tam.

Which is a cohort where the.

Pursuing compete the graded by us.

And so it was present and the circulation, but ties of back Sam stops it from doing that so these patients have.

Have a mindset of.

But he got there.

The antibiotic that would if our product and absorbed it would prevent it from degrading. So that's the next.

The risk level.

Again, a cohort that would read out subsequent to the first one and give us another set of PK data and other set of antibiotic data and safety data and the final cohort is set of pain that is.

The cephalosporin antibiotics and that antibiotic is expires and that has no. It's the great. It could be the greater buy a product and.

And it has also got nothing to protect and so it is a.

Product.

And that's the final cohort that we would run because that's the one where <unk> got into the circulation and it would be the Haas from skeptic righting the antibiotics.

Alright, Thank you and then.

I'd actually touch on the.

M&A M&A side of things you mentioned that business development is the potential and wouldn't be surprising given you a fairly stable cash balance at this point, so what sort of compounds would you be looking for it seems like you guys have expertise and Gi and microbiome health as well as Gi delivery of drug.

So could you help narrow down which disease areas or which type of drugs you might target.

So.

I think it's best that we kind of hold our cards a little tight at the moment I can tell you. This we've been evaluating.

Many opportunities.

And some are a little bit further along than others and diligence and.

And.

I'll, just say that when we're ready to talk about.

Those details will we'll get that out and disseminated accordingly, but we just prefer to keep our.

Our cards close at this point.

Alright.

And then on one more on just like the touch real quick on.

On some of the existing safety data out there for IP I mean, obviously, you don't have anything for <unk> and 'twenty quite yet.

Hi.

Has been out there.

So you know of patients with the radiation enteropathy and severe celiac, maybe willing to take on some safety risks with some adverse events, but diseases like well controlled celiac and naphtha, which is largely asymptomatic and maybe less willing to take the.

And take those risks so how the out of the safety look like or IAP and general.

Mike and I'll take that.

Okay.

And I E P AAP as I say it is an endogenous.

Enzyme and senior intestines, all the time, although we are using the bovine version of it because it's kind of higher specific activity.

The safety profile for IAP is.

And is very good or the wood.

And it would be even more of a few says the.

I think that's necessary at this point.

And our for our Syn <unk> 'twenty.

We saw virtually no.

And.

Adverse events and canine and mouse studies.

And we're six weeks long.

And this is up.

254 of the anticipated clinical dose.

The other companies of developed.

The bovine and human IAP products.

Most notably though.

Sure.

Intravenous use.

And in the safety studies again, it was pretty much a fairly remarkable profile and I really don't want to speak completely from other companies because I'm not privy to their data.

The the most part of intravenous delivery of <unk>.

And then.

IAP and in patients.

Doses that increase the interest the alkaline phosphatase level sales I believe of about 500 fold.

The background was well tolerated.

And there was there's been one oral study with bovine.

The IAP again, very well tolerated and that was and ulcerative colitis colitis patients and.

And let's see.

I think that's.

And that's probably about it.

And you could consider the safety profile that we anticipate to be.

And quite good we anticipate a very reasonable risk benefit ratio even for diseases that are.

Net.

Total.

And.

And I should also finally and debt celiac disease, yes, there are patients who are well controlled on the gluten free diet, but that's the really unpleasant diet and there are a large percentage of patients who are not well controlled on it.

And some of them have refractory disease. So I don't think we will have trouble finding the right.

Dissipates and won't have trouble finding of patient.

<unk>.

The two because as the.

Home tour.

And I think you know debt among patients with non alcoholic fatty liver disease.

Maybe 20% of them will go on to get Nash, which is the associated with fibrosis cirrhosis and occasionally of kind of cellular carcinoma.

And then I don't think we will find.

We'll find the.

The difficulty finding of patient population or St.

And does that answer your question.

Yeah, Yeah, great answer thank you very much.

This concludes our question and answer session I would like to turn the conference back over to Steve Shallcross for any closing remarks.

Thanks, Andrew.

So before we end the call.

Like the make a few final comments about our company.

First.

Incredibly proud of our talented team who have just worked countless hours to get us where we're at today the effort take and to advance our programs.

And could not of happen without their dedication and persistent drive to help a patient population and that just continues to be underserved.

Second we're we're in the strongest financial position and the company's history and and because of this.

We're now very very well positioned to.

Not only.

Fund our clinical programs for the next two years, but of the.

The liver on multiple clinical milestones over the next 12 months to 24 months.

So the value of these programs that we have under development can be further supported and potentially the value potentially fully realized by the markets.

And we also have this great great opportunity finally to go out and acquire or license new technologies to further expand our product portfolio and and.

Add additional shareholder value.

So on closing.

I'd like to thank our long term shareholders for their ongoing support and also just welcome any new shareholders that of discovered us and are equally excited to be of part of our great company.

I promise you that 2021 will be and exciting year and we look forward to just keeping you informed and updated on our progress.

Have a good weekend and we look forward to talking to you next time. Thank you.

The conference has now concluded. Thank you for attending today's presentation you may now disconnect.

[music].

Yes.

[music].

And.

[music].

Okay.

[music].