Good morning, ladies and gentlemen. Welcome to the Bio-Path Holdings' Full-Year 2020 Earnings Conference Call. At this time, all participants are in a listen-only mode. Following the formal remarks, we will open the call up 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 2020 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. Thank you for joining us. I'm pleased to be addressing you all today to discuss the significant progress we made in 2020, which saw important advances across our clinical development pipeline.

Despite headwinds from COVID-19 pandemic, the progress we made throughout 2020 formed the foundation for us to advance and expand our clinical portfolio toward key inflection points in 2021 and beyond.

We continue to execute on our clinical development plans across our DNAbilize platform of innovative RNAi nanoparticle therapeutics to treat patients suffering with a variety of life-threatening cancer indications.

Despite some groundbreaking progress with immuno-oncology and combination therapies, there continues to be a large unmet medical need for a great number of cancer patients. I'll begin with our lead product candidate, prexigebersen, where we continue to make meaningful progress.

Last year, we dosed the first patient in Stage 2 of our Phase 2 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 2 clinical development of prexigebersen in AML commenced with Stage 1 of the Phase 2 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 [Technical Difficulty]. As many as you know, there has been an evolving landscape [Technical Difficulty] 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. Feedback from treating physicians pointed to a preference for decitabine.

The approval of frontline therapy, venetoclax, provided an opportunity for adding prexigebersen to the newly approved frontline two-drug combination of venetoclax and decitabine for the treatment of previously untreated AML patients.

The amended Stage 2 of this Phase 2 trial in AML is an open-label Phase 2 two-stage multi-center study of prexigebersen in combination with decitabine and venetoclax in two 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 two-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 or intolerant with the two-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 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 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 safety and efficacy of the treatment.

In the event, these results exceed the primary endpoint in a number of patients that meets or exceeds statistically determined threshold, we plan to seek to convert the trial into a registration trial for accelerated approval.

In February, we announced that the United States Patent and Trademark Office issued a third patent in our family of platform intellectual property that offers expanded defense of our DNAbilize platform technology.

In addition, we were pleased to receive the issuance of a patent related to prexigebersen in combination with either a cytidine analog such as Decitabine or the Bcr-Abl tyrosine kinase inhibitors, Dasatinib and Nilotinib. This addition further strengthens our intellectual property portfolio and complements our already granted patents.

Our growing patent estate continues to be a valuable asset for Bio-Path as it provides protection not only for our core product portfolio and research efforts, but now also offers broad protection in combination with established frontline therapies.

These new patents protect the unique therapy combination and supports our ongoing investment in this program to bring in new treatment option to patients with AML who have limited treatment options.

As I have said before, we will continue our efforts to build a fortress of protection around our technology as it safeguards our platform technology and target-specific technology is a deterrent to would-be competitors and creates value around core competencies.

Next, I would like to turn to our planned Phase 1 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. 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 outcome. And it is our hope that prexigebersen may provide clinical benefit for such patients. Turning now to BP1002, our second therapeutic candidate, which targets Bcl-2. Last year, we filed an IND application for our second pipeline candidate, BP1002.

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 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 to provide an alternative for venetoclax patients who have relapsed including AML patients who previously received venetoclax treatments. Finally, let me briefly review the progress we have made on our third drug candidate BP1003 which targeted the STAT3 protein.

This program has shown promising preclinical data, and we are very excited in 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.

The potential for our STAT3 program is compelling for a number of reasons. Signal transduction and Activator of Transcription-3 or STAT3 though typically inactive in normal cells is aberrantly active in cancer cells, the abilities of tumor cells to proliferate uncontrollably resist apoptosis, or cell death.

Induce vascular formation and invade distance organs are well recognized hallmarks of cancer. STAT3 is a regulator of the genes involved in these cancer processes, more recently, the capability of tumors to evade immune surveillance and avoid destruction by the immune system has also gained significant acceptance in the cancer research field.

STAT3, which is a point of convergence for many oncogenic pathways, has emerged as a critical mediator of tumor immune invasion at multiple levels. We're particularly excited to launch our first inhuman validation of this cutting-edge therapy in an especially challenging cancer indication that has limited treatment options.

We're aiming to file an IND application with 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 2020 financials along with balance sheet highlights, Anthony?.

Thanks, Peter. The company reported a net loss of $10.9 million or $2.83 per share for the year ended December 31 2020 compared to a net loss of $8.6 million or $3.24 per share for the year-ended December 31 2019.

Research and development expense for the year ended December 31 2020 increased to $6.6 million, compared to $4.6 million for the year ended December 31 2019 primarily due to increased enrollment for Phase 2 clinical trial of prexigebersen in AML, startup costs related to Phase 1 clinical trials for BP1002 in lymphoma and prexigebersen A in solid tumors and increased preclinical expenses for BP1003.

General and administrative expense for the year ended December 31 2020 increased to $4.3 million compared to $4.1 million for the year ended December 31 2019 primarily due to increased franchise tax expense. As of December 31 2020, the company had cash of $13.8 million compared to $20.4 million at December 31 2019.

Net cash used in operating activities for the year ended December 31 2020 was $11.0 million compared to $8.4 million for the comparable period in 2019. Net cash provided by financing activities for the year ended December 31 2020 was $4.3 million. With that, I'll now turn it back over to Peter..

Thanks, Anthony. I'd like to leave you today with a few thoughts on the imperative Bio-Path has in bringing DNAbilize products to market. According to the American Cancer Society, more than 600,000 people lose their lives to cancer each year. During the COVID-19 pandemic, cancer patients are among our most vulnerable of populations.

This is why we at Bio-Path continue to be relentless in our pursuit to bring better treatment options to these patients who so desperately need them and for whom there are no treatment options.

I'd like to take this opportunity to express my gratitude to the Bio-Path team and the researchers and physicians supporting our scientific and regulatory advancements. Because without their collaboration and support, we could not have made the progress we have made today and we look forward to advancing together to secure our future success.

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

Okay. [Operator Instructions] Your first question is from the line of Yi Chen with H.C. Wainwright..

Hi, thank you for taking my question. My first question is, could you tell us which arm of the AML trial enrolls patients faster than the others, and whether this arm is likely to report interim data before the end of this year? Thank you..

My expectation is that the third cohort, the one that actually is doing the venetoclax intolerant or resistant patients recall that group is being treated with the two-drug combination, prexigebersen and decitabine. And I also think that’s a lower bar, the null hypothesis is smaller and that's a very attractive option.

It's very similar to what we did previously with the two-drug combination, LDAC, and we exceeded the LDAC null hypothesis very nicely. We just couldn't proceed because the gynecology community went away from LDAC. So, I think that one, I believe, we have over half of the patients we need for that interim readout.

And I think not withstanding any kinds of patient interruptions or whatnot with COVID, hopefully, the vaccine program is going to work, and we are not going to have variance and all that kind of things, but that would be the first.

The other one, we are competing with, like in the newly diagnosed, there is still competition for those patients as they continue to try other things with venetoclax. So, I would say, the two-drug combination is the one that is most likely for 2020..

Got it.

And my second question is, is the Phase 1 trial of prexigebersen-A in solid tumors due on track to start soon?.

Yes. We recall there were just some new studies latest testing with the FDA at least in this division wanted. And so, we had to go formally test the entire batch in a reconstituted material. This was [Technical Difficulty] testing. The stability of the drug as reconstituted in our hospital before administration to a patient.

We’ve completed all of that, and then we have an additional test that we are doing that's a new one, and we think we have just about finalized that. Once that's done, we should have the IND right away.

And I am thinking the second quarter unless there is the second set of testing still needs more refinement, because we not only do the testing, but you have to develop a qualified method and whatnot. So, we think that will be case. We had a good call with the FDA on the additional things we wanted.

And so, we know the last steps, those get completed and we should have our FDA and start treating..

Got it. Thank you..

You are very welcome..

Your next question is from the line of Jonathan Aschoff with ROTH Capital Partners..

Thank you. Good morning, guys. I was wondering a little more on prex-A.

Should we expect prex-A development only in ovarian and endometrial? And also for 1003, only in pancreatic, or do you think those two Phase 1 trials would be very much a mixed solid tumor bag?.

Yes, I think, generally, Jonathan, -A and 1003 will have a similar pattern. The Phase 1, of course, is dose finding, and it can go across several sets of solid tumors.

And once you do that dose escalate, establish a safety, find a dose, then we would proceed, let's say, in -A with Phase 1bs, one of the first ones would be paclitaxel and prex-A in advanced ovarian and endometrial. The second, a target trial, would be in Stage IV metastatic pancreatic with gemcitabine.

And MD Anderson and Bio-Path have also worked on breast cancer in, I believe, the hormone-resistant area of triple-negative. The 1003, again, similar concept, enroll from several of the solid tumor cancers.

Once you – again, we dose up, establish safety, get our dose, then we would go on with two candidates that we've done work on, would be again the metastatic pancreatic and also non-small cell lung cancer. So - and I suspect once we get into it, we would do other things. I think STAT3 is also amenable through AML, but that's the general plan.

Broadly across in the one where you dose escalate, establish safety, and then you go into 1bs in the specific areas with your specific combination treatment drug..

Okay, thank you, Peter. I don't know if you addressed this in the opening comments.

But when do you think we can see the safety results with prex in the double and the triple combination? And how soon, once you get those safety board findings, those affirmations of safety can you start your cohorts?.

Well, we're going to -- I expect to be reporting out on that as early as the end of this first quarter. The testing has been done, but we have to have a safety review, and then we'll write it up and put it out, okay? So, we've completed that step and continue to test. So, it's really just the formal reporting part of it..

Okay.

And if you assume no additional warrant option or ATM use, how long does $25.9 million fund operations?.

Well, we actually -- we had, what was it $13 million at the end of the December, and we actually raised close to approximately $20 million in February, so through a couple of different things, including that registered direct with ROTH.

And so we actually have more than $25 million, but that will probably take us well into 2022, and probably through the end of it. So, it's a good slug of money for us. And we will probably do another strategic raise maybe in the third quarter to anticipate all of those trials reaching through their Phase 1s and being 1bs in the following year..

Okay. Thank you very much, Peter..

Thank you, Jonathan. .

The next question is from the line of Laura Engle with Stonegate Capital Partners..

Good morning. Hope all is well.

My main question has already been asked, but I wondered if maybe you could give us an update if there's any progress or anything new to report with some of the collaborations you have going on, which as within MD Anderson or, I think, Thomas Jefferson University at one point, anything new on that horizon that you could share with us?.

Thomas Jefferson, it doesn't really require our active involvement. We supply and develop the drug. We actually have intellectual property on that being developed. So, I think they continue to work on that, but it doesn't require our active involvement. I think that MD Anderson, we're really more through the clinical programs with those folks.

But they continue to have an interest in our technology.

Of course, they're doing their site for the AML, their -- a site for the 1002, and lymphoma and CLL, there'll be a site when we get going in the venetoclax-relapsed AML, so -- and for solid tumors, they were kind of the lead group that did the original -A solid tumor work, which was done in advanced ovarian, so -- and endometrial.

So, they continue to -- we continue to work along with them. We have some other things that, as we've gained more notoriety, we have other collaborations being discussed there, and so -- which we may these on in the near future..

Okay, great. Well, appreciate the update. Look forward to this year, hoping COVID-19 continues to improve so you all can keep making this progress and move forward with these trials. So, again, I'll get back in the queue, but thanks for the update..

Thank you, Laura..

[Operator Instructions] At this time, there are no further questions..

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

Ladies and gentlemen, this concludes today's conference. Thank you for your participation. Have a wonderful day. You may all disconnect..