Bio Path Holdings Inc (BPTH) 2023 Q3 法說會逐字稿

Good morning, ladies and gentlemen, and welcome to the Bio-Path Holdings third-quarter 2023 earnings conference call. (Operator Instructions) Please note the call is being recorded.

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 2023 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'll plan to discuss on today's call. The release is available at bio-pathholdings.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's 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. We entered the tail end of 2023 in a stronger position than ever. We have exceptionally promising data with prexigebersen in AML and expect to generate even more data in 2024.

Beyond prexigebersen we continue to advance our robust clinical development program across a number of important programs that leverage our innovative DNAbilize platform technology to deliver RNAi nanoparticle therapeutics directly to cancer cells. We are forging a new path and DNA power of medicine that we believe will give patients a fighting chance to beat these difficult-to-treat cancers.

I'll begin with the progress we have made with our lead product candidate, prexigebersen. As you know, we continue to be encouraged by the positive interim results from 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. And this is meaningful because these patients are at the end of the line of treatment options. Note that most have already relapsed or essentially everything of everything in the treatment armamentarium currently available. So a drug like prexigebersen can give hope to these patients.

Recall the study is an amended Stage 2 of our Phase II trial in AML is an open-label two stage multi-center study of prexigebersen in combination with the side of an eventual collapse and two cohorts of patients with previously untreated AML and relapsed resistant AML.

Third cohort includes treating relapse resistant AML patients who are venetoclax resistant or intolerant with the two drug combination of prexigebersen and decitabine. The primary endpoint of 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 hematologic recovery.

As a recap of these very promising results we achieved, there were 14 newly diagnosed patients evaluable in Cohort 1 and treated with at least one cycle of the prexigebersen decitabine then and venetoclax combination therapy. All patients in this cohort were adverse risk by 2017, European leukemia net or ELN guidelines or secondary AML.

Prexigebersen was well tolerated and adverse events were generally consistent with decitabine and venetoclax treatments and or for AML. 12 of the 14 evaluable patients or 86% achieved complete remission and 2% or 14% achieved partial remission. In total, 100% of the evaluable patients had response to treatment. The complete remission rate of 86% for the evaluable patients in Cohort 1 is significantly higher than completion rates of 62% for newly diagnosed patients treated with the frontline combination treatment of venetoclax and decitabine .

This result is further highlighted by the high risk rating of our Cohort 1 evaluable patients and the inclusion of secondary AML patients, both of which are classes of patients with very difficult-to-treat disease. 14 refractory relapse evaluable AML patients in Cohort 2 were treated with at least one cycle of prexigebersen decided and venetoclax combination therapy.

All patients in this cohort were adverse risk by 2017 ELN guidelines or secondary AML. Prexigebersen was well tolerated and AEs were generally consistent with the size of and venetoclax treatments and or for AML. 8 of the 14 evaluable patients or 57% achieved complete remission, two patients or 14% achieved partial remission and three patients or 22% achieved stable disease and total 93% of evaluable patients had a response to treatment.

The complete remission rate of 57% of the evaluable refractory and relapse patients in Cohort 2 is significantly higher than complete remission rate of 21% for refractory relapse patients treated with combination treatment of decitabine and venetoclax.

As with newly diagnosed patients in Cohort 1. This result is further highlighted by the high risk rating of Bio-Path Cohort 2 evaluable patients and the inclusion of secondary AML patients. Efficacy data from the initial interim analysis of Cohort 1 and Cohort 2 are compelling and show that prexigebersen based combination therapy was not only safely administered in Cohort 1 and Cohort 2 the high risk newly diagnosed and refractory relapse AML patients considered unsuitable for standard chemotherapy, but also demonstrated efficacy signals significantly better than current therapies. This is particularly encouraging as relapse refractory patients are a challenging population in which current treatment options are sub optimal.

On the strength of these data, we currently plan to pursue US Food and Drug Administration or FDA expedited programs for fast-track and breakthrough therapy designations. We look forward to keeping you apprised of our progress on the regulatory front.

In October, we hosted a key opinion leader event to discuss the evolving treatment landscape in AML. We were privileged to have Dr. Jorge Cortes and Dr. William Hahne [true luminaries] in the hematologic and oncology space as our guest speakers.

The discussion was illuminating and engage bolstering our conviction in the prexigebersen clinical development programs as both physician experts was deeply encouraged by our interim results and further underscored the great unmet medical need for these relapse patients.

It was heartwarming to have these AML specialists highlight the fact that results of this magnitude are simply not seen in this patient population. Having this independent expert point of view that support Bio-Path mission was inspiring. I encourage you all to listen to the archive of this event, which is available on our web website.

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

Venetoclax has shown activity against anti anti-apoptotic protein Bcl-2 and works by neutralizing the protein's BH3 domain. It is an approved treatment for chronic lymphocytic leukemia or CLL patients and untreated AML patients. However, with the exception of some patients treated with allo genetic 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 could provide an alternative for venetoclax patients who have relapsed, including AML patients who previously received,venetoclax treatments.

Total of 6 evaluable patients will be treated with BP1002 monotherapy in a standard three plus three design for the starting dose of 20 milligrams per square meter. The approved treatment cycle is two doses per week over four weeks, resulting in eight 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 combinations with decitabine in refractory relapsed AML patients. We expect cohort completion and initial data readout from this study in the coming months.

Next, let's turn to our Phase I/Ib study clinical trial of BP1001-A in patients with solid tumors, including ovarian, endometrial, pancreatic and triple-negative breast cancer. Some of the most challenging cancers to prove with today's therapeutic tool kit.

BP1001-A is a modified product from prexigebersen sharing the same drug substance with enhanced nanoparticle properties. The clinical trial is in the second dose cohort. This trial is being conducted at several leading cancer centers and will initially evaluate safety in solid tumor patients. Patients diagnosed with recurrent ovarian and endometrial cancers often have poor outcomes, and it is our hope that we may provide clinical benefit for such patients. We look forward to cohort completion and data readout from this study in early 2024.

Finally, let's review the progress we've made with BP1003 which targets the STAT3 protein. STAT3 is a transcription factor that regulates various tumorigenic processes such as tumor proliferation, metathesis and 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 promotes tumor initiation migration and taxol resistant.

STAT3 also contributes to 5-FU resistance and tolerance of colorectal cancer cells. Its role in numerous malignancies made STAT3 a potential cancer therapeutic target. BP1003 is a novel liposome incorporated STAT3 antisense oligodeoxynucleotide that efficiently reduces STAT3 expression enhances 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 as a novel strategy for patients with advanced solid tumors.

We are particularly excited to launch our first anti-human validation of this cutting-edge therapy in an especially challenging cancer indication that has limited treatment options.

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

Thanks, Peter. The company reported a net loss of $3.2 million or $0.32 per share for the three months ended September 30, 2023, compared to a net loss of $3.5 million or $0.49 per share for the three months ended September 30, 2022.

Research and development expense for the three months ended September 30, 2023 decreased to $2.3 million compared to $2.4 million for the three months ended September 30, 2022, primarily due to decreased manufacturing development expenses, partially offset by an increase in expense related to our clinical trial for prexigebersen in AML due to increased patient enrollment in 2023.

General and administrative expense for the three months ended September 30, 2023 decreased to $1.0 million compared to $1.2 million for the three months ended September 30, 2022, primarily due to decreased legal fees.

Change in fair value of the company's warrant liability for the three months ended September 30, 2023, resulted in non-cash income of $0.1 million. The company did not have the warrant liability in the comparable period for 2022. As of September 30, 2023, the company had cash of $2.4 million compared to $10.4 million as of December 31, 2022.

Net cash used in operating activities for the nine months ended September 30, 2023 was $9.7 million compared to $10.1 million for the comparable period in 2022. Net cash provided by financing activities for the nine months ended September 30, 2023 was $1.7 million.

With that I'll now turn the call back over to Peter.

Thanks, Anthony. It's been another exceptional quarter for Bio-Path, particularly as the data we just discussed, cement our conviction and support of the advancement of these important programs. Despite the gloom and the financial markets, the excitement we see and feel in the clinical markets with progress such as we've made with prexigebersen spurs on to continue the good fight.

As such, we remain committed to our mission to delivering a better path for cancer patients.

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

(Operator Instructions)

Jonathan Aschoff, ROTH MKM

Thank you. Good morning. Peter, I was curious was the third cohort tracks, where there was no data yet available? It was a real risk AML that was resistant or intolerant to the class. Is there any update there even just on enrollment?

Hi Jonathan,just harder to find patients for that. We actually have had five enrolled and we have three evaluable patients. What happens is oftentimes when a patient is on the borderline for that, the investigators, slip amended Cohort 2 so they can get the triple combination. But no, and we're treating them right now. We have patients continuing to treat the other ones. We've reached our three exceeded valuable milestone for this interim analysis. So we're backing off on those.

But no, we continue with Cohort 3. It just takes longer to get them and the patients and the like to propose to the federal. The bar is pretty low on that the on the frontline comparison is decided on a load factor 16% to 20% CR so I think that's a good one for us to pursue. So that's the status on that.

Okay. And just a yes or no on this. I had a note or a sentence on that last note that we expect to see an ASH abstract from you guys, but there there is none for [PRAX] just regular [PRAX] .

We're too late. So we rushed to get out. And but the what we'll probably do, I'm sure we'll end up doing the full blown report interim next year. But for the near term, we're pulling together two trying to meet the Asco, and that's a good meeting. And we we presented there before. And in fact, I think we had a session where we had an oral several years back. So I guess that's the game plan. It's just time driven.

Okay. Your last timing indication for PRAX was full enrollment by the end of the year, which I think you just just switch to data on by early 2024. So that's signed. But for 102 the last timing you gave was completion of the first cohort before the end of the year.

Is that still relevant for on the Phase1/1b trial?

I think we mentioned that we were enrolling a couple of new sites for the lymphoma, 1002, and the a couple of good ones and one of which is Einstein in New York. And we actually have that the third patient that close out the cohort the next week, I think it finishes and we'll be able to do that. It was safe to say you have a that meets it, and I'm pleased with that because we needed to get to a higher dose from our starting of 20 megs per square meter, the well in that the we've completed the patients for that first, we're just doing we have to schedule the safety meeting and all and I mean these things take time, but to do that, and we should have something, but I can put a rig on it even before the end of the year.

And solid tumor. As I noted, we're already in the second quarter. So we've graduated we put a short release out on that, and we're in the spec. And so we've gone from starting selling the drug substance recall is the prexibertion, numerous different formulation. So it's treated as a different drug. But the that's the it started at 60 megs per square meter and now is in the second cohort at the 90 megs per square meter. And I think there's a real hit in that treatment, do that's a step.

That's definitely helpful.Do you still expect an early 2024 filing for the IND. for 1003?

It won't be early. We do I think I will go over the issue of getting the detection for PK work we have that actually have to use two sources and the one's new and actually the other is one that we use for drug The actual nanoparticle characteristics, which we've found they have a division that can do GLP human plasma.

And so we're going to get them online. So I think that we'll finally be able to demonstrate that testing. And of course, you'd like to be able to have tongue-in-cheek demonstrate that indeed, you had drug substance in your in your safety studies. And so I think it would be more mid latter part, the whole hold up again, being to get the detection of Haleko drug substance in, patient or so in the animal study of plasma.

Because, you know, it's two points on that one, just to be able to again demonstrate you had drug substance in years tox studies. And then, of course, going forward the issue is you need to do your pharmacokinetics.

So the answer is no. We won't have all of that submitted and done because once we have this PK detection work done then we just have to quickly do one study, which is a couple of months, and then we'll start the compiling the IND. I'll bring on an outside consultant to help with that writing so we can move it along. So best case would be late summer. I would think those ideas are a lot of data, as you know, so that's the status on that.But I have I feel better about that now since we are able to detect that.

Lastly and did I mishear you developing 1002 in AML or did I just miss you say?

No, there's two separate INDs. It's the FDA. We had the CLL one going and patients enrolled and the and wanted to do the AML of venetoclax failure patients. So that's a real opportunity for us venetoclax operating on beef protein in the in the cytoplasm. And as usually happens with TKIs that capture cycle. So eventually the drugs the patient becomes resistant. We're a natural step in behind that because we don't involve that kind of activity.We just block the expression of the Bcl-2.

So that's a so anyway submitted on that. But the administratively the FDA handles those two diseases in different divisions. So we had that file a separate IND for AML relapsed patients. It's generally AML, relapse resistance or beyond just AML in venetoclax of resistant patients. But yes, and we have two clinical trials and two INDs for that. So both will be announced here shortly to six weeks for moving on to the next dosing cohort.

Thank you for those details Peter.

You're welcome.

This begins our question and answer session. And I would now like to turn the call over to Peter for any closing remarks.

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

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