Bio Path Holdings Inc (BPTH) 2022 Q2 法說會逐字稿

Good morning, ladies and gentlemen, and welcome to the Bio-Path Holdings Second Quarter 2022 Earnings Conference Call. (Operator Instructions) At this time, I'd like to turn the floor 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 second quarter 2022 financial results and to provide an update on recent pipeline and corporate development. 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, 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. The first half of 2022 was marked by execution across our entire organization, and I am pleased to report the progress we have made to date. Throughout the second quarter and in recent weeks, we have made substantial operational progress as we continue to advance our DNAbilize platform of products along the clinical pathway.

Towards that end, we look forward to initiating our Phase I studies of BP1001-A, a drug product modification of prexigebersen, for the treatment of solid tumors; and BP1002 to treat relapsed refractory acute myeloid leukemia, or AML, including venetoclax-resistant patients in the coming weeks. This progress is highlighted in today's announcement of the pending initiation of our Phase I/Ib studies of these 2 products. I'll describe the importance of these 2 milestones in more detail later in the call.

Moving now to our clinical programs and our lead product candidate, prexigebersen. We continue to make significant progress advancing Stage 2 of our Phase II clinical trial of prexigebersen for the treatment of acute myeloid leukemia in combination with frontline therapy, decitabine and venetoclax. As you know, 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 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 formed on each cohort to assess the safety and efficacy of the treatment.

Next, I'd like to turn to our planned Phase I clinical trial of BP1001-A in patients with advanced solid tumors, including ovarian, uterine, pancreatic and hormone refractory breast cancer. BP1001-A, a fourth Bio-Path drug candidate, is a modified product from prexigebersen sharing the same drug substance with enhanced nanoparticle properties.

You will recall that last year, the FDA cleared our investigational new drug, or IND, application to initiate a Phase I/Ib clinical trial of BP1001-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 may provide clinical benefit for such patients. We look forward to bringing this exciting program into the clinic in the coming weeks.

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 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 allogenetic 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 BP1002 could provide an alternative for venetoclax patients who have relapsed, including AML patients who previously received venetoclax treatments.

As I mentioned earlier, we will initiate in a few weeks a Phase I/Ib study and tend to conduct it at leading cancer centers in the United States, including the Weill Medical College of Cornell Universe, the University of Texas M.D. Anderson Cancer Center, the Georgia Cancer Center and the University of California, Los Angeles Cancer Center. A total of 6 evaluable patients will be treated with BP1002 monotherapy in a standard 3-plus-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 we'll assess the safety and efficacy of BP1002 in combination with decitabine in refractory relapsed AML patients. We hope to be able to provide incremental updates on this program as we establish safety first, followed than by efficacy in these smaller patient cohorts.

Finally, let's review progress we've made with our third drug candidate, BP1003, which targets the STAT3 program. STAT3 is a transcription factor that regulates various tumorigenic processes, such as tumor proliferation, metastasis drug resistance. Its overexpression and aberrant activation characterize many cancers, including breast, lung, ovarian, liver and colon cancer.

Activation of the STAT3 pathway in breast and ovarian cancer cells promotes tumor initiation, migration and taxol resistance. The STAT3 also contributes and promotes 5-FU resistance in colorectal cancer cells. Its role in numerous malignancies and make STAT3 a potential cancer therapeutic agent.

BP1003 is a novel liposome-incorporated STAT3 antisense oligodeoxynucleotide that efficiently reduces STAT3 expression and enhances the sensitivity of breast and ovarian cancer cells to taxol and 5-FU. These results are in line with previous work in which BP1003 plus gemcitabine displayed enhanced antitumor activity in pancreatic ductal adenocarcinoma.

Together, these results strongly suggest that BP1003 combination therapy is a novel strategy for patients with advanced solid tumors. In April, we were delighted to present supportive preclinical data from this program at the 2022 American Association of Cancer Research Annual Meeting before an audience of world-leading cancer researchers and physicians.

Dr. Maria Gagliardi, a research scientist on our team, highlighted preclinical studies of BP1003 in combination with paclitaxel or fluorouracil as a potential treatment against breast and ovarian cancer cells. We are particularly excited to launch our first-in-human validation of this cutting-edge therapy and an especially challenging cancer indication that has limited treatment options. Our goal is to file an IND application for this very promising product candidate late in the fourth quarter or the first quarter of 2023. The timing is determined by finalizing preclinical testing of drug substance presence in the animal species used in testing.

With that, I'll now turn the program over to Anthony Price for a brief review of our second quarter 2022 financials, along with balance sheet highlights. Anthony?

Thanks, Peter. The company reported a net loss of $3.0 million or $0.42 per share for the 3 months ended June 30, 2022, compared to a net loss of $1.8 million or $0.26 per share for the 3 months ended June 30, 2021. Research and development expense for the 3 months ended June 30, 2022, and increased to $1.9 million compared to $0.8 million for the 3 months ended June 30, 2021, primarily due to manufacturing expenses related to drug product releases in the second quarter of 2022 and increased patient enrollment related to our Phase II clinical trial for prexigebersen in AML.

General and administrative expense for the 3 months ended June 30, 2022, was $1.2 million, an increase of $0.1 million compared to the 3 months ended June 30, 2021, primarily due to increased legal fees. As of June 30, 2022, the company had cash of $17.0 million compared to $23.8 million at December 31, 2021. Net cash used in operating activities for the 6 months ended June 30, 2022, was $6.7 million compared to $4.2 million for the comparable period in 2021. With that, I'll now turn the call back over to Peter.

Thanks, Anthony. I trust today's update leaves you as excited as we are for the future as we are making and will continue to make good progress advancing these important clinical trials in cancers where current therapies are woefully inadequate or where life changing new therapies are greatly needed.

Our team remains steadfast in our commitment to advancing our DNAbilize platform technology as we seek to deliver a better path for cancer patients worldwide. With that, operator, we are ready to open the call for questions.

(Operator Instructions) Our first question today comes from Yi Chen from H.C. Wingright.

Could you provide an update on the number of enrollment in broad patients in each 3 cohorts of the Phase II trial BP1001?

Well, as I think I'd mentioned we had -- the trial was slowed down in the last 1.5 years previously from manufacturing issues related to COVID and just the environment. But we have -- across the cohorts now picked up the treating -- enrolling and treating and in fact, we've -- I think had mentioned that we were doubling our supply chain of the key manufacturing plants, our overall manufacturer and then our final drug product manufacturer. And these are all -- that plan is coming to fruition as we are adding more drug supplies and able to treat more patients. That's the principal reason that you saw the R&D expense jump up. I think as we've talked about many times on these calls, as we produce new drug product for treating patients. It accumulates on the balance sheet prepaid. And then when it's done and released to the company for use in the trial, it drops to an expense. Overall, I'd say we're about halfway in the cohorts. Some may be a little bit faster than the others. And -- but we continue to think that we're looking towards being able to start interim results late in the late fourth quarter or more likely in the first quarter of 2023. At that point, we'll assess our efficacy and safety and as appropriate move with the FDA to see if there's any opportunities for expedited programs.

So just to clarify, you think the trial will reach 19 evaluable patients for interim analysis at the end of this year or in the first quarter of '23, right?

Yes. I think that -- or it just depends on how quickly we can treat those and get the evaluable patients. But the end of it, I think, has been going pretty well. So 19, it's safe to say that we'll be in the middle of doing that in the first quarter and evaluating them. So.

Got it. Got it. And during the remainder of 2022, shall we expect to see preliminary data from the Phase I trial of BP1001-A and BP1002?

Well, we I think as we indicated, we've completed the work now of getting that trial -- both of those trials open. And so we've generated I think a lot of interest in the trial. I think there are 6 sites for the -A and 3 real quality sites for the resistant AML. So you can never tell how fast they come in. But I'd like to think we'd hit at least 1 cohort for both of those trials in 2022. So -- and we'll report on that.

And lastly, is there any additional preclinical study for BP1003 that needs to be concluded before the drug came into the clinical trial?

I think, of course, we just did the AACR, and we are working on -- a lot of our focus in preclinical right now is on AML, venetoclax-resistant cells. So we may have something coming out on that. And -- so other than that, I really don't want to reference any of our programs. But our research group stays pretty active in doing preclinical work that's supportive of the products that we're trying to advance.

(Operator Instructions) Our next question comes from Jonathan Aschoff from ROTH.

I just had one question, Peter. The world seen clinical experience with 1001 and you're certainly talking about the difficulty in getting low doses, getting doctors interested in low doses on 1002. Excuse me, I have COVID. My question is 1001-A being kind of similar to 1001, do we expect 1001-A to have that kind of low dose, low enrollment that you're now experiencing and have been for a while with 1002? Or can it piggy back at all on the earlier 1001 experience because it is a highly similar agent?

Yes. The substance is the same, too. It's a good question, and you're right. Because of the body of experience we have with prexigebersen, we're able to start at a higher dose, 60-milligram per square meter. So that's the dose in AML. Do a cohort at that and then go on to 90. So yes, we don't have to go through the low 20-milligram cohorts.

That's helpful to know. Did you disclose that earlier? Or is that the first time you said that you can start at 60 with A?

Well, I think that's -- it's certainly been in our documents. So I don't know if I specifically mentioned that. But if I haven't -- I know (technical difficulty) documents because obviously, as you pointed out, that's a real feature that we can start out at 60.

And ladies and gentlemen, at this time, in showing no additional questions, I would like to turn the conference call back over to Mr. Nielsen for any closing remarks.

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

And ladies and gentlemen, with that, we'll conclude today's conference call and presentation. We do thank you for joining. You may now disconnect your lines.