Good morning, ladies and gentlemen, and welcome to the Bio-Path Holdings Third Quarter 2021 Earnings Conference Call. [Operator Instructions]. I would now like to turn the call over to Will O'Connor of Stern Investor Relations. Please proceed..

Thank you, operator. Welcome to the Bio-Path Holdings conference call and webcast to review the company's third quarter 2021 financial results and to provide an update on recent pipeline and corporate developments. Earlier, we issued a press release, which outlined the topics that we plan to discuss on today's call.

The release is available at biopathholdings.com. With me today from Bio-Path are President and CEO, Peter Nielsen; and Senior Vice President of Finance, Accounting and Administration, Anthony Price. Before we begin the call, I'd like to remind you that today's discussion will contain forward-looking statements that involve risks and uncertainties.

These risks and uncertainties are outlined in today's press release and in the company's recent filings with the Securities and Exchange Commission, which we urge you to read. Our actual results may differ materially from what is discussed on today's call. With that, I'll now turn the call over to Bio-Path's, CEO, Peter Nielsen..

Thanks, Will. Good morning, everyone, and thank you for joining us. This third quarter was marked by significant progress across the board and was highlighted by investigational new drug application clearances for 2 key clinical programs in our DNAbilize development pipeline.

These regulatory clearances allow us to advance these important clinical trials in a variety of oncology indications for which there are limited treatment options and patients are facing life-limiting prognosis.

Let me turn now to a more detailed description of these clinical programs and the progress we are making advancing them through the clinical and regulatory pathway. I'll begin with our lead product candidate, prexigebersen, where we continue to make solid progress.

We continue to make significant progress advancing Stage 2 of our Phase II clinical trial of prexigebersen for the treatment of acute myeloid leukemia, or AML, in combination with frontline therapy, decitabine and venetoclax.

As we have previously reported, Phase II clinical development of prexigebersen in AML commenced with Stage 1 of the Phase II clinical trial, which was open-label and treated de novo AML patients with a combination of prexigebersen and low-dose cytarabine or LDAC.

The combination of prexigebersen and LDAC was shown to be safe and more efficacious to treat this class of patients than with LDAC alone. As many of you know, there has been an evolving landscape for standard care of AML. Despite these new therapies, there are still patients who are refractory or resistant, and those are the patients we aim to help.

As standard of care evolved, we have adapted our trial design to reflect these changes. The amended Stage 2 of this Phase II trial in AML is an open-label Phase II 2-stage multi-center study of prexigebersen in combination with decitabine and venetoclax in 2 cohorts of patients with previously untreated AML and relapsed/resistant AML.

A third cohort includes treating relapsed/resistant AML patients who are venetoclax resistant or intolerant with the 2-drug combination of prexigebersen and decitabine.

The full trial design plans have approximately 54 evaluable patients for the cohort treating relapsed/refractory AML patients and the triple combination treatment of prexigebersen, decitabine and venetoclax and the cohort treating AML patients who are venetoclax resistant or intolerant with the 2-drug combination of prexigebersen and decitabine with a review of both cohorts performed after 19 evaluable patients.

The full trial design plans have approximately 98 evaluable patients for the cohort treating untreated AML patients with the triple combination treatment of prexigebersen, decitabine and venetoclax, with a preliminary review of the cohort performed after 19 evaluable patients and a formal interim analysis after 38 evaluable patients.

The higher number of patients in the full trial design for the untreated AML patient cohort is due to the higher baseline response of the frontline therapy with previously untreated AML patients.

The primary endpoint for this study will be the number of patients who achieved complete remission, which includes complete remission with incomplete hematologic recovery and complete remission with partial hematology recovery. An interim analysis will be performed on each cohort to assess the safety and efficacy of the treatment.

Earlier this year, we were excited to announce the successful completion of the safety run-in of the Stage 2 of the Phase II, and we look forward to advancing this study as we believe its unique design provides us with several definable registration pathways. In December, Dr.

Maro Ohanian, Associate Professor of the Department of Leukemia at the University of Texas, MD Anderson Cancer Center, will present the safety and preliminary efficacy data from the ongoing Phase II trial of prexigebersen before an audience of world-leading oncologists at the 63rd Annual American Society of Hematology, or ASH, Annual Meeting.

Next, I'd like to turn to our planned Phase I clinical trial of prexigebersen-A in patients with advanced solid tumors, including ovarian, uterine, pancreatic and hormone-refractory breast cancer.

Prexigebersen-A, a fourth Bio-Path drug candidate, is a modified product from prexigebersen sharing the same drug substance with enhanced nanoparticle properties.

In October, we were delighted to announce that the FDA has reviewed and cleared our investigational new drug, or IND, application to initiate a Phase I/Ib clinical trial of prexigebersen-A in patients with solid tumors, including ovarian, endometrial, pancreatic and triple-negative breast cancer.

This trial will be conducted at several leading cancer centers and is planned initially to evaluate the safety of prexigebersen in solid tumor patients. Patients diagnosed with recurrent ovarian and endometrial cancer often have poor outcomes, and it is our hope that prexigebersen-A may provide clinical benefit for such patients.

Turning now to BP1002, our second therapeutic candidate, which targets Bcl-2. As you know, Bcl-2 is responsible for driving cell survival in up to 60% of all cancers. High expression of Bcl-2 has been correlated with poor prognosis for patients diagnosed with AML.

Venetoclax has also shown activity against the antiapoptotic protein Bcl-2 and works by neutralizing the protein's BH3 domain. It is an improved treatment for chronic lymphocytic leukemia, or CLL, patients and untreated AML patients.

However, with the exception of some patients treated with allogeneic hematopoietic cell transplantation, disease relapse invariably occurs often times due to BH3 domain mutation over time. BP1002 also targets the Bcl-2 protein. However, BP1002 activity is based on blocking the Bcl-2 messenger RNA and not the BH3 domain.

As a result, we believe that BP1002 could provide an alternative for venetoclax patients who have relapsed, including AML patients who previously received venetoclax treatments.

In August, we announced that the FDA had reviewed and cleared the IND application for BP1002 for an initial Phase I/Ib clinical trial that will evaluate the ability of BP1002 to treat refractory/relapsed AML patients.

We expect this clinical trial to be conducted at several leading cancer centers in the United States, including the Weill Medical College of Cornell University, the University of Texas, MD Anderson Cancer Center and the Georgia Cancer Center.

Initially, a total of 6 evaluable patients are scheduled to be treated with BP1002 monotherapy in a standard 3+3 design with a starting dose of 20-milligram per square meter. The improved treatment cycle is 2 doses per week over 4 weeks, resulting in 8 doses administered over 28 days.

The Phase 1b portion of the study will commence after completion of BP1002 monotherapy cohorts and will assess the safety and efficacy of BP1002 in combination with decitabine in refractory/relapsed AML patients. Finally, let me briefly review the prognosis we've made with our third drug candidate, BP1003, which targets the STAT3 protein.

This program has shown promising preclinical data, and we are very excited for the future of this program. We are studying BP1003 for the treatment of pancreatic cancer in a patient-derived tumor model. Previous models have shown the drug to successfully penetrate pancreatic tumors and enhance the efficacy of standard frontline treatments.

We are particularly excited to launch our first-in-human validation of this cutting-edge therapy in an especially challenging cancer indication that has limited treatment options. We are aiming to file an IND application with this very promising product candidate in 2022.

With that, I'll now turn the program over to Anthony Price for a brief review of our third quarter 2021 financials, along with balance sheet highlights.

Anthony?.

Thanks, Peter. The company reported a net loss of $2.1 million or $0.29 per share for the 3 months ended September 30, 2021, compared to a net loss of $3.0 million or $0.80 per share for the 3 months ended September 30, 2020.

Research and development expense for the 3 months ended September 30, 2021, decreased to $1.0 million compared to $2.0 million for the 3 months ended September 30, 2020, primarily due to timing of activities related to our clinical trial for prexigebersen in AML and timing of drug material manufacturing and shipping activities.

General and administrative expense for the 3 months ended September 30, 2021, increased to $1.1 million compared to $1.0 million for the 3 months ended September 30, 2020, primarily due to increased stock-based compensation expense. As of September 30, 2021, the company had cash of $26.6 million compared to $13.8 million at December 31, 2020.

Net cash used in operating activities for the 9 months ended September 30, 2021, was $7.1 million compared to $8.4 million for the comparable period in 2020. Net cash provided by financing activities for the 9 months ended September 30, 2021, was $20.0 million. With that, I'll now turn the call back over to Peter..

Thanks, Anthony. In the coming weeks, we are looking forward to the data to be presented at ASH as they further support our enthusiasm for the potential of prexigebersen to treat AML and believe they will drive clinical interest from oncologists and hematologists who treat these very sick patients.

The progress we are making is bringing us one step closer to our goal to bring new medicines to patients in need, and I could not be more excited about the opportunities ahead for Bio-Path as we strive to make our vision for the DNAbilize technology a reality for patients battling a variety of cancers.

With that, operator, we are ready to open the call for questions..

[Operator Instructions] Our first question comes from Laura Engel with Stonegate Capital..

Good morning.

How are you?.

I am fine. Thank you. .

So good news on the IND for the prexigebersen-A.

Just one related to that trial, when you get to the point of enrollment, since it is towards solid tumors, can you explain to me being the nonscientist, how it works with the various cancers as far as which patients are available to enroll, say, ovarian, endometrial, pancreatic? Does it end up being focused on which patients come? Or do you take enrollment based on requirements for the various cancer types? I mean does the trial -- let's say, several ovarian patients show up for enrollment, do you balance it out? Or does it end up -- can you be end up focused on one tumor? Or do you wait and see how the results come in based on the varying types of cancer? Does that make sense?.

Yes, that's a good question. And the way it's set up is that the Phase 1 portion of this trial is -- it's open to several tumor categories. We basically want to get the patients in to do the monotherapy and demonstrate the safety in the solid tumors.

The Phase 1b component is when you start focusing into the specific cancer areas or tumor areas of interest, and those will be combination therapy. Most of the early clinical work -- preclinical work was in advanced ovarian and endometrial.

The second one, of course, is pancreatic, but we're going to start with the advanced ovarian endometrial, and that will be with its combination therapy treatment. And then following that and not in a linear fashion, I would expect that we've got some simultaneous activity going on.

We would then probably proceed into the pancreatic area, and that would be Stage IV metastatic people with its combination treatment, gemcitabine, I think it is. And then the third area to come would be I think getting into one of the triple-negative breast areas, I think it's the hormone one. So that's the strategy.

Open in those areas to speed it up, cross section is really safety and then you go into the specifics for treatments in combination therapy..

Got it. So you -- it would be likely that it would be more effective against one type of cancer versus another in solid tumors, then you could potentially later focus on that type of cancer? Just looking forward for this....

Yes. I think -- I know the advanced ovarian and endometrial had good results. They had AACR papers. The pancreatic, I think, was also AACR, and that would be a good one also.

The -- some of the interest in that pancreatic, for example, is that in this kind of unique model that was referenced in my comments, it's basically they take human tumors -- pancreatic tumors and graft them into mice.

And what happens a stroma forms around it, so you really emulate a human pancreatic tumor, and it showed that we could penetrate that. And so there was some interest in that. So at this point, I can't hypothesize which would be more effective. We would hope that we'd be able to benefit some patients in both areas..

Okay, great. Well, thanks for clarifying that for me, and hope you have a great weekend. Appreciate all the detail for us on today's call..

You're very welcome..

Our next question comes from Jonathan Aschoff with ROTH Capital Partners..

Thank you. Good morning Peter. I was wondering if you could update us on when enrollment for 1002 in RR AML might begin.

And how many monotherapy cohorts do you expect for the Phase 1 portion to then be able to go into Phase II based on what you understand of the molecule?.

I think that on 1002 in the AML, starts at 20, then it'll go 40, 60, 90. So that would be your number of cohorts in the mono [indiscernible] from there. You would then look on -- going forward, I think the -- what the company [indiscernible] going forward in Phase II.

So that would be -- and it's hard to say that the timing of it would be in the first quarter. It's always the mundane stuff, getting the documents through the specific sites, going up to their IRBs and all of that content.

And so -- but we're in that process, trying to push it along, and we should be get going with those patients in the fourth quarter..

Okay. And actually, in my question I misspoke, I meant for when you can start Phase 1b combination therapy, not Phase II.

Is that the same answer that you just gave me?.

Yes. That's the Phase 1 piece of it, the monotherapy, it's three patients. There could be -- we think there could be a real potential mean for this. And you probably, I think, know that the survivability of the patients that fail venetoclax or relapse on is not good. So there could be some real interest in it. But I couldn't imagine we'd be through that.

It'll be the second half of next year before we'd be ready to do the 1b..

Okay.

And at ASH, maybe I missed this, but can you tell us what specific cohorts you'll have data from? I'm assuming it's the more rapidly enrolling venetoclax failure intolerance? And any from the other two?.

Yes. I think the intent is to report on the entire trial. So we'll report on the 3 cohorts. In some respects, I think we -- those are really almost separate trials, but all 3 of them, they're all active and all enrolling. We have our supply chain finally recovering from the problems that have occurred. In fact, we're doubling our supply chain for drugs.

So that will really get us going again. And -- but the intent would be to give specifics on all 3 cohorts..

Okay. Lastly, I was just curious, did you have a solid sense of how many venetoclax failures there are in the U.S.

alone every year?.

I don't know that. There is a report out there that -- and that's something we referenced, MD Anderson did that. And I think that's the one that had indicated that survivability post relapse with 3 months or less. But I do not know what that number is, but it's -- the venetoclax and the treatment population.

And the occurrence, it's the mutation of that BH3, and I think that's a pretty broad occurrence, frankly..

Okay. I was just asking because a lot of companies are targeting that specific slice..

It's a real need..

[Operator Instructions] Our next question comes from Yi Chen with H.C. Wainright..

Thank you for taking my questions.

So with respect to the Phase 1 trial of BP1002 in lymphoma and CLL, could you provide an update on whether the trial is still on track to report data in the first half of next year?.

The -- we're continuing to deal with slow enrollment in that trial, and there's two issues I think I've mentioned before. The low starting dose that we have to do, it's like 20-milligram per square meter. And the second thing is that there are some trials out there competing in CAR-T. What we're doing in that is looking -- we're going to add sites.

And frankly, we're also going to look to use some areas, some groups that their business is generating quality candidates. So I think we have to establish that momentum once for that infrastructure, if you will. And once we do that, then we can give a better read-out to you about the pace of getting those patients going in there.

The treatment is effective. We've had good results in the preclinical and the reporting. So it's just being able to get past -- enough patients, to get past this low dose. Oncologists when there's a competing trials out there, there's a reluctance to put them on when the probability of having a benefit for their patients at 20, it's problematic.

So we're taking actions that we think will alleviate that over the coming quarters, and then we'll get back into a better position..

Got it.

And for the Phase II trial of prexigebersen in AML, the triple combo trial, do you think there is still any chance to complete the interim review before the end of this year? Or it's going to be a 2022 event?.

It's got to be a 2022 event. I've had to spend my time reviving, if you will, the drug supply chain. We've had problems on the front end of the drug substance and have basically doubled that -- we've basically doubled that supply chain, adding new firms that are really good that have slots.

And so we think that will get us going again because people do want to enroll in that. So -- and I might add that you'll be pleased with this. We've had a lot of cajoling to get us back into MDS on that treatment, and we will -- we're working to get that lined out.

We can't do it with prexigebersen or with venetoclax because venetoclax is not approved in MDS, but there's just a feeling that prexigebersen and decitabine alone provide a better benefit than decitabine alone in those patients. So and you can look forward to seeing something on that in the near future..

Got it.

And lastly, just to clarify that both the Phase 1 trial of prexigebersen-A and the Phase 1 trial of BP1002 in AML are going to start patient dosing in 2022?.

Yes, because they've both been approved. Of course, solid tumors was fairly recent. AML was sooner than that. But it's just getting everybody lined up paperwork wise. We've got our PIs -- national PIs and that kind of thing lined up.

And so -- but just getting those protocols approved by IRBs and getting the contract agreements signed and everything, that just seem to take time..

Thank you..

Thank you, Yi. .

And I'm not showing any further questions at this time. I'd like to turn the call back over to Peter for any closing remarks..

Thank you, operator. Thank you again, everyone, for joining us and for your continued support of Bio-Path and have a great day. Bye..

Ladies and gentlemen, this does conclude today's presentation. You may now disconnect, and have a wonderful day..