Good morning, ladies and gentlemen. Welcome to the Bio-Path Holdings Full Year 2021 Earnings Conference Call. At this time, all participants are in a listen-only mode. Following the formal remarks we will open the call out for your questions. 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 full year 2021 financial results and to provide an update on recent pipeline and corporate developments. Earlier, we issued a press release, which outlines 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. 2021 was an important year for Bio-Path, and we are well positioned as we enter 2022 to advance our mission of developing meaningful medicines to aid in the fight against cancer.

Before we dive into our programs in detail, I'd like to highlight the progress we've made shoring up our supply chain. We made considerable advancements throughout 2021 improving our clinical scale manufacturing process. Our supply chain capacity has been doubled, providing a significant increase in drug candidate manufacturing capacity.

In addition, we have increased scheduling flexibility for ordering new batches of drug product for our clinical trials. 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 we have highlighted before, there has been an evolving landscape for standard of care in 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 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 with the triple combination treatment of prexigebersen, decitabine and venetoclax, and the cohort treating AML patients who are venetoclax resistant and 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 for the cohort performed after 19 evaluable patients and a formal interim analysis after 38 evaluations.

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 achieve 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. In December, Dr.

Maro Ohanian, Associate Professor of the Department of Leukemia at the University of Texas MD Anderson Cancer Center, presented 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.

The data presented included 6 patients, 4 patients, or 67% with de novo AML and 2 secondary AML patients, or 33%, that were treated with at least 1 cycle of prexigebersen plus decitabine combination therapy.

All patients in this cohort with a median age of 72 years old, were considered high risk due to having either adverse risk status by European Leukemia Net or ELN, or treated secondary AML. Data showed that adverse events, or AEs, were generally consistent with those expected with decitabine and/or AML.

Three of the 6 patients, or 50%, had a response including 2 de novo patients, or 33%, who achieved a complete remission with incomplete blood count recovery, or a CRI, and 1 secondary AML patient, or 17%, who achieved a partial remission. Patients with these conditions generally have less than a 20% CR/CRI response rate.

Six patients were treated with at least 1 cycle of prexigebersen plus decitabine plus venetoclax combination therapy. Of the 6 patients, 2, or 33% had de novo AML and 4, or 67%, were relapsed refractory. All patients in this cohort were adverse risk by ELN or relapsed refractory.

AEs were generally consistent with decitabine and venetoclax treatment and/or for AML. Four patients, or 67% achieved a CR/CRI or morphological leukemia-free state, and 1 patient, 17%, achieved a partial response. Of these 5 patients, 3 were relapsed refractory and 2 were de novo.

This is meaningful, as CR rates for combination treatment with decitabine and venetoclax for relapsed refractory AML patients are 42% to 52% or 0% to 39% for relapsed/refractory secondary AML patients.

These preliminary data are compelling, and show that prexigebersen-based combination therapy was not only safely administered to high-risk and relapsed refractory AML patients considered unsuitable for standard chemotherapy, but also demonstrated encouraging efficacy signals.

This is particularly encouraging as relapsed refractory patients are a challenging population in which current treatment options are suboptimal. 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.

Last year, we were delighted to announce that the FDA had reviewed and cleared our Investigational New Drug, or IND, application to initiate a Phase I-Phase 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 or endometrial cancer often have poor outcomes, and it is our hope that prexigebersen may provide clinical benefit for such patients.

We look forward to bringing this exciting program into the clinic in the second quarter of this year. Turning now to BP1002, our second therapeutic candidate, which targets Bcl-2. As you know, Bcl-2 is responsible for driving cell survival and 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 anti-apoptotic 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 allogenetics and monopolietic cell transplantation, disease relapse invariably occurs oftentimes 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.

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

A total of 6 evaluable patients will be treated with BP1002 monotherapy in a standard 3+3 design, with a starting dose of 20 milligrams per square meter. The approved treatment cycle is 2 doses per week over 4 weeks, resulting in 8 doses administered over 28 days.

The Phase Ib 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's review the progress we've made with our third drug candidate, BP1003, which targets the STAT3 protein.

This program has shown promising pre-clinical 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 look forward to presenting supportive pre-clinical data from this program at the 2022 American Association for Cancer Research Annual Meeting taking place in New Orleans, Louisiana next month. Dr.

Maria Gagliardi, a Research Scientist on our team, will discuss preclinical studies of BP1003 in combination with paclitaxel and fluorouracil as a potential treatment against breast and ovarian cancer.

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 for this very promising product candidate later this year.

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

Anthony?.

Thanks, Peter. . The company reported a net loss of $10.4 million or $1.55 per share for the year ended December 31, 2021, compared to a net loss of $10.9 million or $2.83 per share for the year ended December 31, 2020.

Research and development expense for the year ended December 31, 2021, decreased to $5.9 million compared to $6.6 million for the year ended December 31, 2020, primarily due to timing of activities related to our clinical trial for prexigebersen in AML, partially offset by an increase in manufacturing expenses related to drug product batch releases in the fourth quarter of 2021.

General and administrative expense for the year ended December 31, 2021 increased to $4.5 million compared to $4.3 million for the year ended December 31, 2020, primarily due to increased stock-based compensation expense. As of December 31, 2021, the company had cash of $23.8 million compared to $13.8 million at December 31, 2020.

Net cash used in operating activities for the year ended December 31, 2021 was $9.9 million compared to $11.0 million for the comparable period in 2020. Net cash provided by financing activities for the year ended December 31, 2021, was $20.0 million. With that, I'll now turn the call back over to Peter..

Thanks, Anthony. At Bio-Path, we aim to be innovative and efficient, with patients at the forefront of everything we do. Our robust and growing pipeline continues to advance, and I'm proud of the bolus of clinical data that we've generated in support of our DNAbilize platform.

As we look to the balance of the year, we expect to build on this with a number of value-creating milestones, and I look forward to keeping you apprised of our progress. With that, operator, we are ready to open the call for questions..

[Operator Instructions] We have a question from Yi Chen with HC Wainwright. Your line is open..

Could you update us on the current enrollment status for each of the 3 arms of the Phase II trial of prexigebersen in AML?.

Well, enrollment is over $30 million and -- for the 3 combined. And that was slowed somewhat, I think, as I've mentioned before, by the limitations in drug supply. It's one of the reasons we worked on doubling our supply chain. We had some COVID plant incidents and whatnot. For this year, we think we'll add another 30, plus 30 to that.

I think that we can start hitting some of these interim points towards the end of the fourth quarter, first quarter next year. So we'll be able to get some pretty significant readouts. So the other ones are just really starting up.

The lymphoma one has been slow, but I think we have done some things to -- recruited some additional help resources to find some patients for us. There's a lot of -- a lot of trials going on in that area right now, and as we've talked about before, getting these first patients to get past 20 milligrams per square meter is the milestone.

So we continue to work on that..

And which arm do you think is likely to reach 19 evaluable patients first? Is it the third arm which is the relapsed refractory AML patients who are venetoclax resistant or intolerant?.

It may be the 2, the prexigebersen, decitabine cohort. Second behind that would be the second cohort, which is treating refractory resistant AML patients with the triple combination. But they're all picking up now that as I bring more drug back up, we are experiencing it in all of them. But that would be my assessment..

And the Phase I trial of BP1002 in lymphoma and CLL, is it still on track to report data in the first half of this year?.

We'll have to see how these new resources. What we'd report on would be this 20-milligram per square meter. We already have a patent. We're starting to see -- we had a couple of more patients, one ended up not making it through screening.

We have another one that we think has made it through, so we'll see if these additional patient recruiting programs can help us. Again, we have to find kind of the specialized patient situation to pull them in at this level..

And for BP1003, when do you expect to file an IND for clinical studies?.

Well, we've just reviewed that again yesterday, and the goal is by the end of the year. The issue has been developed the PK study, I think I've mentioned that before. We have that now being tested and we should have read out on that.

Once we have that, then we'll do our final animal tox study, which won't take that long, and we can get that data and be ready to compile the IND in the third quarter. So that's the game plan.

And I think we have the right drug, manufactured drug because we engineer these things with our DNAbilize approach, and you have to get the solubility and hydrophobicity correct on it, the balancing act, and get that done. So that's the game plan. We think we can. We're really excited about the growth. Okay..

And lastly, the operating expenses of the fourth quarter last year.

Is it a good starting point to project numbers for this year as you prepare to start 2 additional clinical trials in the second quarter this year?.

You're talking about updating your models and projecting?.

Yes, operating expenses. Quarterly operating expenses..

Yes. I think we're going to operate at a higher level. I think 12 months from March through Feb '23, looking at $14 million in cash, okay, and that's probably a good measure for you..

Thank you. And there are no further questions in the queue. I'd like to turn the call back to Peter Nielsen for closing remarks..

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

This concludes today's conference call. Thank you for participating. You may now disconnect..