Nov 15, 2023
Good morning, ladies and gentlemen. Welcome to the Bio-Path Holdings Third Quarter 2023 Earnings Conference Call.
At this time, all participants are in a listen-only mode. [Operator Instructions] Following the formal remarks, we will open the call up for your questions.
Please note, the call is being recorded. I would now like to turn the call over to Will O'Connor of Stern Investor Relations.
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 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.
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 in DNA-powered medicine that we believe will give patients a fighting chance to beat these difficult-to-treat cancers.
I'll begin with 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 II 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.
This is meaningful because these patients are at the end of the line of treatment options. Note, 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 II of our Phase II trial in AML.
It is an open-label, 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. The third cohort includes treating relapsed/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 I and treated with at least one cycle of the prexigebersen, decitabine and venetoclax combination therapy.
All patients in this cohort were adverse risked by 2017 European LeukemiaNet or ELN guidelines or secondary AML. Prexigebersen was well tolerated, and adverse events were generally consistent with decitabine and venetoclax treatment and/or for AML.
12 of the 14 evaluable patients or 86% achieved complete remission, and two or 14% achieved partial remissions. In total, 100% of the evaluable patients had a response to treatment.
The complete remission rate of 86% for the evaluable patients in Cohort I is significantly higher than completion rates of 62% for newly-diagnosed patients treated with the frontline combination treatment of decitabine and venetoclax. This result is further highlighted by the high-risk rating of our Cohort I evaluable patients and the inclusion of secondary AML patients, both of which are classes of patients with very difficult-to-treat disease.
14 refractory/relapsed evaluable AML patients in Cohort II were treated with at least one cycle of prexigebersen, decitabine 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 decitabine and venetoclax treatment and/or for AML. Eight 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.
In total, 93% of the evaluable patients had a response to treatment. The complete remission rate of 57% of the evaluable refractory and relapsed patients in Cohort II is significantly higher than complete remission rate of 21% for refractory/relapsed patients treated with combination treatment of decitabine and venetoclax.
As with newly-diagnosed patients in Cohort I, this result is further highlighted by the high-risk rating of Bio-Path Cohort II evaluable patients and the inclusion of secondary AML patients. Efficacy data from the initial interim analysis of Cohort I and Cohort II are compelling and show that prexigebersen-based combination therapy was not only safely administered in Cohort I and Cohort II to high-risk, newly-diagnosed and refractory/relapsed AML patients considered unsuitable for standard chemotherapy but also demonstrated efficacy signals significantly better than current therapies.
This is particularly encouraging as relapsed/refractory patients are a challenging population in which current treatment options are suboptimal. On the strength of these data, we currently plan to pursue US Food and Drug Administration or FDA, expedite 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.
Maro Ohanian, true luminaries in hematologic and oncology space as our guest speakers. The discussion was illuminating and engaging, bolstering our conviction in the prexigebersen clinical development program as both physician experts were deeply encouraged by our interim results and further underscored the great unmet medical need for these relapsed 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 and expert point of view that support Bio-Path's mission was inspiring.
I encourage you all to listen to the archive of this event, which is available on our website. Turning now to our BP1002 program, which targets Bcl-2.
As you know, Bcl-2 is responsible for driving cell survival in 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-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 allogeneic hematopoietic cell transplantation, disease relapse invariably occurs often times due to BH3 domain mutation over time. BP1002 also targets 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 treatment.
A total of six 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 improved 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 will assess the safety and efficacy of BP1002 in combination 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 [BP100-A] (ph) in patients with solid tumors, including ovarian, endometrial, pancreatic and triple-negative breast cancer, some of the most challenging cancers to treat with today's therapeutic toolkit. 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 the safety in solid tumor patients.
Patients diagnosed with recurrent ovarian and endometrial cancer often have poor outcomes, and it's 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, metastasis 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 tumor initiation, migration and taxol resistance.
STAT3 also contributes to 5-FU resistance in colorectal cancer cells. Its role in numerous malignancies makes STAT3 a potential cancer therapy target.
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 nominal strategy for patients with advanced solid tumors. 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.
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 trough 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 noncash 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 cements our conviction and support of the advancement of these important programs.
Despite the gloom in 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 questions.
We will now begin the question-and-answer session. [Operator Instructions] Our first question comes from Jonathan Aschoff with ROTH MKM.
Please go ahead.
Thank you. Good morning.
Peter, I was curious, with the third cohort prex, where there was no data yet available. It was rel/ref AML that was resistant or intolerant to venetoclax.
Is there any update there even if just on enrollment?
Just -- hi, Jonathan, just harder to find patients for them. We actually have had five enrolled, and we have three evaluable patients.
What happens is, oftentimes, when a patient is on a borderline for that, the investigators slip them into Cohort II so they can get the triple combination. But no, and we're treating them right now.
We have patients we continue to treat. The other ones, we've reached our -- exceeded valuable milestone for this interim analysis.
So we're backing off on those. But no, we continue with Cohort III.
It just takes longer to get them and get the patients. And -- but like somewhat too, it's settled.
The bar is pretty low on that. The frontline comparison is decided and alone, and that's a 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 have a note or a sentence in my last note that we expected to see an ASH abstract from you guys, but there is none for prex or prex-A -- prex, I mean, just regular prex.
We're too late. So -- and we rushed to get out.
And -- but 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'll -- we're pulling together to try and meet ASCO.
And that's another good meeting, and we presented there before. And in fact, I think we had a session where we had an oral several years back.
So that's the game plan. It's just time-driven.
Okay. Your last timing indication for prex-A was full enrollment by the end of the year, which I think you just switch to data by early 2024.
So that's fine. But for 1002, the last timing you gave was completion of the first cohort before the end of the year.
Is that still relevant for the Phase I/Ib trial?
Check my notes here, but I think we mentioned that we were enrolling a couple of new sites for the lymphoma 1002, and a couple of good ones. And one of which is Einstein in New York, and we actually have that third patient to close out the cohort next week.
I think it finishes, and we'll be able to do that for safety. So you have that.
That meets it, and I'm pleased with that because we needed to get to a higher dose from our starting of 20 mgs per square meter. The AML in that, we've completed the patients for that first.
We're just doing -- we have to schedule the safety meeting and all that. I mean these things take time.
But do that, and we should have something that I can put it even before the end of the year. And the 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 second.
So we've gone from starting. Now when the drug substance recall is prexigebersen, different formulation so it's treated as a different drug, that had started at 60 mgs per square meter and now is in the second cohort at 90 mgs per square meter, and I think there's real interest in that treatment.
So that's a [step close] (ph).
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 won't go over the issue.
Getting the detection for PK work. We have that.
We actually have two sources. And one is new.
And actually the other is one that we use for drug 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, tongue-in-cheek, demonstrate that, indeed, you had drug substance in our safety studies. And so I think it would be more mid-latter part.
The whole holdup again is being to get the detection of oligo drug substance in patient or in the animal study plasma because it's two points on that. One, just to be able to again demonstrate that you had drug substance in your tox studies.
And then, of course, going forward, the issue is you need that 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 compiling the IND, and 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 INDs are lot of data, as you know. So that's the status on that, but I feel better about that now since we are able to detect that.
Okay. And lastly, did I mishear you?
Were you developing 1002 in AML? Or did I just mishear you say CLL?
No, there's two separate INDs. It's the FDA.
We had the CLL one going, and patients enrolled and wanted to do the AML venetoclax failure patients. So that's a real opportunity for us.
Venetoclax operating on the Bcl-2 protein in the cytoplasm. And as usually happens with TKIs [Technical Difficulty].
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 -- so anyway, we committed on that.
But administratively, the FDA handles those two diseases in different divisions. So we had filed a separate IND for AML relapsed to patients.
It's generally AML relapsed/resistant. Beyond just -- beyond just AML, it's venetoclax-resistant patients.
But yes, and we have two clinical trials and two INDs for that. So both are -- will be announced here shortly to six weeks for moving on to the next dosing cohort.
Thank you those details, Peter.
This concludes 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 the Bio-Path. Have a great day.
The conference has now concluded. Thank you for attending today's presentation.
You may all now disconnect.