Good morning, ladies and gentlemen, and welcome to the Bio-Path Holdings 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. This 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 Key Opinion Leader conference call to discuss prexigebersen and advances in the treatment landscape for acute myeloid leukemia. 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 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 me today from Bio-Path are President and CEO, Peter Nielsen, and Senior Vice President of Research, Development, and Clinical Design, Dr. Ana Tari Ashizawa. Following the prepared remarks, we'll open up the event to questions. We invite the audience to press star one on their touch-tone telephone to ask a question or to submit via email to me at will@sternir.com.
With that, I'll now turn the call over to Bio-Path CEO, Peter Nielsen.
Good morning, everyone. I am Peter Nielsen, President and Chief Executive Officer of Bio-Path. On behalf of Bio-Path team, I thank you for joining us for what we believe will be an engaging and dynamic discussion on the groundbreaking work being done to deliver targeted cancer treatments that offer effective therapy without harsh side effects, so that even the most fragile patients can have tolerable treatment options. Our program today will feature presentations and discussions with two leading opinion leaders in targeted cancer treatments. Dr. Jorge Cortes, Director, Georgia Cancer Center, Augusta University, has been an oncologist in leukemia, having unique insights into the evolving treatment landscape of acute myeloid leukemia, or AML. Dr.
Maro Ohanian, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, has been the principal investigator for the Bio-Path Phase 2 AML clinical trial at MD Anderson Cancer Center for several years. I would also like to note that Dr. Cortes is chairman of Bio-Path's Scientific Advisory Board. Further, any opinions expressed by Dr. Cortes and Dr. Ohanian are their own and do not necessarily reflect the opinions of the company. I also note that Dr. Ana Tari Ashizawa, Bio-Path's Senior Vice President of Research and Development and Clinical Design, will be on the call. Ana was a member of the scientific team at MD Anderson Cancer Center that developed the liposome delivery technology for antisense.
At Bio-Path, we are focused on delivering a better path for cancer patients by advancing our DNAbilize technology platform to deliver antisense DNA therapeutics directly to the cancer cells. This innovative platform improves upon drawbacks of traditional approaches, which are limited by the toxicity induced by either the DNA backbone or the lipid delivery, and are dose-limiting. Due to instability in plasma and hepatic clearance, antisense DNA without lipid delivery does not reach therapeutically effective levels in blood and serum. DNAbilize overcomes these challenges by combining a neutral charged P-ethoxy DNA backbone with a neutral charged liposome. The result is a high payload liposome with DNA safely delivered inside non-toxic cell membrane-like molecules.
Our antisense DNA can be delivered in high doses to target cells through the blood and lymphatic system, with no evidence of toxicity in patients in clinical trials to date, in contrast to other lipid delivery technologies with dose-limiting toxicities. This technology is different from other lipid-based delivery technologies, which use positively charged lipids to form complexes between the lipids and the molecules of interest. Our neutral lipids form structures similar to cellular membrane, allowing the antisense drug to incorporate within the hydrophobic bilayer and be delivered to the disease cells efficiently. While many companies have focused research on either the DNA stabilization problem or the lipid delivery problem, DNAbilize is the first technology to contemporaneously address both. With this gentler approach to tough diseases, we initially launched our efforts in acute myeloid leukemia and lymphomas...
concerns where the need is very great, given the poor prognoses of these fragile patients. Our goal is to meet the need that exists for non-toxic therapies for vulnerable cancer patients who are ineligible for high-dose chemotherapy. AML is characterized, excuse me, by the rapid accumulation of immature myeloid cells in the blood, resulting in a drop of the other cell types, such as red blood cells and platelets. AML incidence increases with age, with a majority of patients aged 60 or older. AML is the most common acute leukemia in adults. The National Cancer Institute estimates that approximately 20,000 new cases occur each year. There is a critically unmet need for non-toxic therapies for older, fragile AML patients who are unfit or ineligible for high-dose chemotherapy or a stem cell transplant.
The cure rate is merely between 5% to 15% in older adults, and those who cannot receive standard course of chemotherapy have an average survival rate of only five to 10 months. Given this great unmet medical need, you can imagine how excited we were to announce positive results from the interim analysis of the Phase 2 clinical trial of our lead product candidate, prexigebersen, in the treatment of AML, which demonstrated significant clinical improvement and a tolerable safety profile in these high-risk patients. Our featured speakers will discuss these data and highlight the potential role prexigebersen could play in changing the treatment landscape and hopefully the prognosis for those sickest patients. So with that brief overview, let me turn the call over to our physician experts, who will discuss the groundbreaking data. We will open the call up after the presentation to questions for Dr.
Cortes and Ohanian regarding the data and relating to their clinical experience with these difficult-to-treat AML and lymphoma patients. With that, let me introduce our event's featured speakers. It is my pleasure to have Dr. Jorge Cortes with us today. Dr. Cortes is the Director of the Georgia Cancer Center and the Cecil F. Whitaker Jr., GRA Eminent Scholar Chair in Cancer at Augusta University. Prior to joining Augusta University, Dr. Cortes was at The University of Texas MD Anderson Cancer Center, where he held numerous roles, including Deputy Department Chair of the Leukemia Department, Chair of AML and CML Sections, and Deputy Division Chair for MD Anderson Cancer Center, Cancer Network . His clinical interest focuses on new drug development and the management of patients with MDS, acute and chronic leukemias, and MPNs, and he has authored more than 1,000 peer-reviewed original research manuscripts.
Dr. Cortes has over 230 grants and contracts, where he was principal investigator, and he has led the approval of four drugs currently available for patients with leukemia. In addition, we have the privilege of having Dr. Maro Ohanian with us today. Dr. Ohanian is Associate Professor, Clinical Faculty in the Department of Leukemia at MD Anderson Cancer Center, where her focus is clinical care and clinical research for patients with acute and chronic forms of leukemia. Dr. Ohanian conducts clinical trials with the goal of improving survival outcomes of patients, reducing toxicity and complications during treatment, and with consideration for cost-effective treatments that are accessible for patients from all walks of life. As principal investigator for several clinical trials focused on targeting a variety of molecular pathways, she is committed to personalized approaches to leukemia treatment and improving supportive care strategies for leukemia patients. Dr.
Ohanian has strong collaborations with world leaders in cancer prevention and research. She is the recipient of the American Journal of Hematology Young Investigator Award for her innovative research that defined the basis of understanding metals as a therapeutic target for cancer prevention. Dr. Ohanian is board-certified in internal medicine, medical oncology, and hematology. As you can see, both Doctors Cortes and Ohanian are true luminaries in their field, and we are delighted to have them with us today to review our clinical program in AML-... and to discuss the great and urgent need for safe and effective new medicines for these high-risk patients. Dr. Cortes and Ohanian's collective experience give them a wealth of knowledge of clinical and drug development that I am sure will make today's discussion engaging and dynamic. With that, let me turn the program over to Dr. Maro Ohanian. Maro?
Thank you so much, Peter. I'm pleased to be with you all this morning to review the positive interim results of Bio-Path's Phase 2 clinical trial of prexigebersen for the treatment of AML in combination with other frontline therapies, decitabine and venetoclax. Bio-Path's Phase 2 AML trial is an open label, multicenter study of prexigebersen in combination with decitabine and venetoclax in two cohorts of patients, including previously untreated AML and relapsed refractory AML. There's also a third cohort being studied, focused on relapsed refractory AML patients who are venetoclax resistant or intolerant. And in that cohort, patients received two drugs with prexigebersen and decitabine alone. The primary endpoint of the study is the number of patients who achieve either a complete remission, complete remission with incomplete hematologic recovery, complete remission with partial hematologic recovery.
First, we're going to look at cohort I of this study, which includes 14 evaluable patients who are considered frontline for their AML diagnosis. These patients include high-risk, newly diagnosed AML, as well as patients who are technically newly diagnosed with AML. However, they had a prior history of another cancer, and they received chemotherapy for that cancer, and they developed AML secondary to that prior chemotherapy. This cohort also includes some patients who are technically newly diagnosed for AML, but they evolved from a previous bone marrow disease, and some of those patients actually had failed treatment for that previous bone marrow disease. So this is collectively a very high-risk group of AML patients who are early in their diagnosis of AML, but have a variety of very poor risk features.
In terms of risk status, most of these patients are the highest risk category according to the ELN risk stratification. Twelve of the 14 patients in this cohort achieved a complete remission. That's 86%, and two of them achieved a partial remission. So overall, for this cohort of patients with very high-risk features, 100% of them had some type of therapeutic response to the combination treatment. And when considering how this compares to what we would typically see with therapies that are available now, this is higher than what we would expect. For instance, currently, you would expect about a 62% remission rate with decitabine and venetoclax alone. And as I mentioned, the complete remission rate was 86% for this cohort. I've already mentioned why these patients are overall so high risk.
And I think considering that all of them had very high-risk features, this response rate is much better than what we would have expected with, currently available treatments. Now, turning to cohort two, that is the cohort of relapsed refractory AML patients. The response rates were also encouraging. All of these patients in this cohort were very high risk as well, and on top of that, they had failed a number of lines of prior therapies. So they were overall a high-risk, elderly population of people who had failed many lines of prior therapy for their AML and, were generally considered resistant to prior treatments. 57% of them had a remission, and 14% of them had a partial remission. In total, 93% of those evaluable for response had some sort of response to treatment.
This is better than what we would typically expect with currently available treatments. For instance, 21% is a commonly reported remission rate in association with decitabine and venetoclax. So altogether, this is encouraging, particularly considering that this is a nontoxic drug. In our clinical experience, BP1001 does not add toxicity to these treatments, and in the Phase 1 study, when we studied BP1001 up to a very high dose level, we really didn't see any toxicities that were directly attributed to the drug. Altogether, this is encouraging, and it appears that these response rates are much better than what we would typically expect. And I would just like to mention that we have seen responses in patients who had high-risk features that are the worst of the worst.
For instance, we're seeing responses in people who have very bad mutations, such as p53 mutations. And this is really hypothesis-generating and is gonna lead to all sorts of new analyses that could allow us to understand how this drug could impact the worst of the worst types of AML. DNAbilize liposome structure similar to the cellular membrane, and P-ethoxy DNA does not induce hepatotoxicity or thrombocytopenia. And this is noteworthy, considering that we've observed that this drug is well tolerated. And the adverse events that we've seen, for instance, in the frontline patients is typical of what we would typically see with those drugs anyway. As well as in the relapse refractory patients. Overall, the adverse event profiles that we're seeing are typical of what we would see with decitabine and venetoclax.
As a physician who treats patients with all types of drugs, on clinical trials or commercially available, I do believe that there's a lot of potential for this drug to enhance the quality of life of AML patients without adding extra toxicity. That is an unmet need because currently we don't have any drugs available that we can combine with existing chemotherapies that don't add some type of additive toxicity to the regimen. For a population of patients who really do have limited options, this drug has a lot to offer our patients. There are a lot of exciting developments in the near future with the clinical trials. There will be a chance to look more and more into a whole variety of molecular biomarkers that could be responsive to the treatments.
And, certainly we look forward to looking at the potential for this drug to improve clinical outcomes in patients with p53 mutations. That's, a space where many other drugs have already failed to improve outcomes in that population. And, these responses that we've seen in patients, despite having p53 mutations, is very encouraging. Another possibility is exploring this in the childhood cancer space. The incidence of childhood AML, for instance, has been steadily rising over the past many decades, and there is a desperate need for drugs for childhood AML. And there's a desperate need for drugs that don't, add toxicity. Children are particularly sensitive to the toxic effects of drugs, and, there's a real need for that. Now, I'd like to, basically, turn to my colleague .
Dr. Cortes, who is a world expert in AML and has pioneered all the drugs that we're currently using, clinically. And he is a master of this field. Jorge?
Thank you very much, Maro, for your kind words, and thank you, everybody, for having me and for being here to discuss what I see, what others in the call see as a potential for this drug. Let me start by sharing some of my perspectives on the treatment landscape for AML, which has been historically one of the most difficult cancers in... Just to put it back into some perspective, it's been about 50 years since that regimen three plus seven, which is now considered the standard of care, was introduced into the clinical scenario, and that is still the standard today, for better or for worse. It's not a good regimen, but it's what we have.
It took from the 1970s until 2017 until the first new drug was approved for AML. And since then, there has been a number of developments which have been beneficial, but by no means have gotten us anywhere close to where we want to be in the management of acute myeloid leukemia in really turning the corner. The good news is that we are starting to see new developments, and I think we're discussing one of them that I think are getting us much closer to that really significant change in the outcome of patients with AML....
If you look at the number of new cases, per year, there's over about 20,000 that are diagnosed every year, and there's about half of them, if not more, are going to die within the first year or two. Even with the advances that we have today, still, the majority of patients are gonna die of their disease in a relatively short period of time. It is the most common of all the adult leukemias. The survival has been just stable at around 30%, and we could make an argument that the biggest advance for the improvement in survival for many years has been stem cell transplant and the introduction of better supportive care, antimicrobials, growth factors, and so on.
It has been very frustrating. Patients who relapse after frontline therapy, the life expectancy is shorter than six months. Clearly we need much better treatments. The better understanding of the biology of the disease has led us to look for these targeted agents that have a better potential for efficacy and, very importantly, safety. We can incorporate both in the newly diagnosed setting and in the relapsed setting for patients with AML. I think that what you heard today with these drugs, with the results that Mauro presented, are very, very encouraging. First of all, Dr. Ohanian already explained that these patients have been very heavily pretreated, with those treated in the salvage setting.
These patients have very poor, very few treatment options. Even in the frontline setting, we need better therapies. We have heard how the introduction of venetoclax essentially has, you know, people use the word revolutionized the outcome of patients with AML. And indeed, it has been a great advance. Many patients who were not even offered treatment are now being offered treatment with venetoclax in combination with a hypomethylating agent. And this has improved the overall response rate dramatically. But let us not forget that the median survival of these patients is still only about 15 months. That is, relatively, it, it's still very short.
This is just a little over one year, and these patients, for the most part, in the studies that have been published, are in their 1960s, or in their early 1970s. So they're not clearly getting anywhere close to their normal life expectancy. So although the introduction of venetoclax provides, a nice advance and, and a foundation for further development of drugs, we clearly need, to work on how are we going to improve on that foundation. Now, venetoclax combinations are, relatively safe, but that is mostly in terms of the non-hematologic toxicity. We all know that azacitidine plus venetoclax is highly myelosuppressive. So, if we're gonna look at, different combinations with the agents, including venetoclax, we want to, look at drugs that are gonna have very little potential for, additional toxicity.
One, because we want to make it accessible to patients that are unfit for chemotherapy, which is a significant percentage of the patients with AML. And two, because we don't want to escalate the potential of risks induced by the myelosuppression that a venetoclax-based combination could add. Another important factor is that although we are very committed to these targeted agents, and they have been incredibly valuable in many settings, agents such as the FLT3 inhibitors for patients with FLT3 mutations, the IDH inhibitors for patients with IDH1 or IDH2 mutations. Now we're looking at the menin inhibitors for patients with NPM1 or MLL1 mutations or rearrangements. Those are very, very valuable drugs.
The problem with these drugs that are very specifically focused in these mutations is that we see the development of additional mechanisms of resistance with alternative mutations, with the development of new clones that are not inhibited by these very targeted agents, and so on. So there is a value on drugs that are that they have a target which makes them deviate from the toxicity of chemotherapy cytarabine anthracyclines, and so on.... But on the other hand, are not that limited to that one mutation that they can inhibit and that allows the development easier of these other alternative mechanisms of resistance. And this is where an agent such as this has a potential value because it is agnostic for specific mutations.
It is targeted enough that it doesn't target indiscriminately all the cells in the body, and therefore it is safe. And that's one thing that we've seen throughout the development of this drug, that it's been very safe. But it is more inclusive of all the clones that could potentially develop. So it is a very good approach to try to combine, and you can combine it with agents such as FLT3 inhibitors. Or, of course, this, this is you know, the, the hypothetical development.
But I see how this could be another element of the foundation of these approaches, where you could even include these very highly targeted agents in combination with this drug, so that you can minimize the risk of development of these additional mutations. So I see these, and you know, one thing that I think is also very important, that I've always been very excited about this drug, is that the delivery. Oligonucleotides have always been an important target, an important focus of the drug development and a way to counteract specific transcripts that are present in cancer in general.
But the delivery of oligonucleotides has always been a problem, and that is one of the exciting elements of this drug that we know that the delivery works. And we see not only the clinical responses, but the biologic manifestations of the response that let us see that the delivery really is working well. So, you know, all of these elements put together has historically made me very excited about the developing this drug. And I see a potential not only with the combinations that we are exploring now, which are already looking very exciting with the results that you just heard through Dr.
Ohanian, but also for the potential that it has to continue growing, as we continue the development of this drug. So, I'm gonna stop here. We will have, I think, the opportunity to ask any questions. So I'm gonna turn it back, and then we'll open it up for questions. Thank you very much for your attention.
Thank you.
We will now-
Go ahead.
We will now begin the question and answer session. To ask a question, you may press star, then one on your telephone keypad. If you are using a speakerphone, please pick up your handset before pressing the keys. To withdraw your question, please press star, then two. At this time, we will pause momentarily to assemble the roster. Our first question will come from Jonathan Aschoff of Roth MKM. Please go ahead.
Thank you. Thank you, Peter, and the KOLs for doing this. So just, this is a broad question. You know, I have the diverse coverage of companies, and, you know, about 25% of them have AML programs, and it's not even an oncology-centric coverage list. So there are clearly many more companies also in addition, with AML programs. And so what I'm wondering is, you know, where are you seeing the most value added among current clinical AML programs? Or, you know, at least what are you looking for in terms of what you really need to add to existing therapy?
Jorge, could you just, you know, opine on that?
Sure. Well, you know, there, there's many. You are correct. There, there's tons of clinical trials that and drugs that are being developed now for acute myeloid leukemia with many approaches. Some of them specifically targeted, like the ones that I mentioned during my remarks. Some of them are a little bit broader in their scope. The way I see it is that you really need the integration of different approaches. You know, I published a review article in The Lancet two or three years ago, and you know, at the end we had a schematic of how I see the eradication of CML, which is the integration of different elements of that.
I think that the value of one of the things that you see is that there is a lot of redundancy in some of these drug development. You know, there's a lot of many inhibitors being developed. There is a lot of antibody drug conjugates, and there's a lot of, you know, drugs that are- they're looking for the same approach and just trying to be the best in class. The value of this particular approach is that it's very unique. This is, it's an oligonucleotide. There's very little of that being developed. It is specific to a target. Yeah, let's not forget that GRB2 is a client of many of these other kinases and pathways, for example, for FLT3 and many of the others.
So, I think that this is very complementary to all of the, or yeah, many or probably most of the programs that you're seeing in other companies. And again, being so unique, I think it gives it a unique position in the development of drugs. Of course, we always want to see the data, but so far what we have is very positive, and that uniqueness, I think, gives it particular value.
I mean, are you seeing more, as time goes on, of there being incremental efficacy with very little added tox, such that you could imagine combo therapy in the future containing more agents on average than combo therapy contains now? Does that make sense to you?
Yeah, I think that indeed, you are going to see... And again, that's one of the potential values of this drug, that it has so much possibility to be combination. AML is a combination strategy, no question to... Of course, initially you need to develop drugs as single agents, but to really have an impact in AML, you need combinations of therapy. I mean, look at venetoclax. Venetoclax had minimal activity as a single agent. In combination, it made a big change.
So you do need to have a combination strategy, and again, because this is very unique, because it has so little toxicity, I think it lends itself to combine with a lot of these drugs, whether it's an antibody, whether it's a specifically targeted drug, whether it's an immunotherapy, you know, and so on. Of course, again, we need to see the data, but at least the potential is there, and the little toxicity is an important asset when you're trying to combine with other drugs.
Right. And certainly if combo therapy did in the future contain, on average, more agents than it does now, you would surmise, you know, estimate that price expectations would have to sort of come down in line with that. Would that be something you would agree with?
Yeah, certainly. You know, of course, of course, those, those are important considerations that we always have to, have to keep in mind. They, they start becoming particularly relevant once you, once you see benefit. But, but absolutely, you know, increasingly we are becoming more cognizant of these, of the, of the importance of the cost issues and things like that.
Thank you very much, Dr. Cortes.
Thank you.
We have one question that was emailed in. Given the success of some new immunotherapies and checkpoint inhibitors, why do we think those do not provide better responses in AML patients?
Maro?
So you're asking about checkpoint inhibitors in AML and why they didn't make it so far in AML, correct?
Yeah, that's the, that's the question that was emailed in. Yep.
Okay, and then you're wondering, wanting to know how we would consider that, when looking at this drug?
I guess just sort of broadly, why, why hasn't there been?
So why did the immunotherapies not make it in AML?
Yep.
So, the immunotherapies have been studied in AML and, basically I've used them off label in a whole variety of scenarios also. And I think that there's probably multiple reasons for why the drug development stopped in AML, and I'm not, I'm not sure that, that they categorically weren't helpful. I do believe there were multiple reasons for why, why they haven't had more momentum in AML. And, I do think that this drug is completely different, so I don't think that we need to... I don't think that we need to have that type of expectation, for this drug. I believe this drug is totally different from the immune checkpoint inhibitors.
I don't think that we can, you know, base our expectations on what has not been moving forward for AML with respect to the immune checkpoint inhibitors. Dr. Cortes, do you want to add something to that about the multiple reasons, the multifactorial reasons for why the immune checkpoint inhibitors haven't been further developed in AML?
... Yeah, I think that, you know, there's a number of factors that play a role. Number one is, you know, this is a very different tumor. This is, you know, in many of the solid tumors where these checkpoints have worked, is number one, it depends on how many lymphocytes are infiltrating the tumor. That's been a predictive factor in many of the instances. Number two, they usually have a more intact immune system. So it's not just so much the whether the cancer is using the checkpoints to inhibit the attack of an otherwise healthy immune system. You know, in AML, the immune system is part of the problem. It's, you know, keep in mind that, you know, all of this is developed in the bone marrow.
All of the cells that are part of the immune system are produced in the bone marrow, which is unhealthy already. So, it probably would need a different approach. I think that it's just been a complex setting where we haven't learned how to use them. So I think that some of that is the scenario, and some of that is that we... I remember when we started the conversations and even Jim Allison was in the room when we were starting these conversations, when we started these initial trials, the question was, should we start from the beginning, or should we start later when the patient is in remission and the immune system is a little healthier, and do i t then?
I don't know that we've just done enough to figure out the way to develop them, or they really don't work. My guess is that there would be a subset of patients where it would work. We just haven't figured it out. I think that it's part of that is that it takes a little bit more work to see how we're gonna make them do what we want them to do.
Thank you, Dr. Cortes. That's basically, you know, kind of how I felt as well. I mean, the drug development hasn't continued, and there was a loss of momentum, but I don't really feel that we know that they were not helpful. I don't feel that we were able to continue exploring them in the way that we needed to. And there were a bunch of other drugs that were approved around that same time period. I still am optimistic about the possibilities of that type of therapy for AML. But moreover, it's really not relevant when we're considering prexigebersen.
Yeah.
Prexigebersen is a completely different drug, a completely different target, and a very different mechanism and totally different in terms of side effect profile. The immune checkpoint inhibitors do have a lot of toxicities associated with them, and they're not benign drugs, and they can have permanent disabling effects in the patients. And this drug has been, the Bio-Path drug, has been studied in many, many patients without any signals of toxicity. So I think that's a really positive thing for prexigebersen. Additionally, it's the only antisense AML drug currently in clinical development, and there really are no other drugs like it, which is exciting.
This concludes our question and answer session. I would like to turn the conference back over to Peter Nielsen for any closing remarks.
Well, thank you all for joining us today. I trust you found the session to be informative. I'd like to thank Dr. Ohanian and Dr. Cortes for their time and valuable insights. You were both superstars, and we really appreciate it. We appreciate your continued support of Bio-Path. Have a great day. Thank you.
Thank you all.
The conference is now concluded. Thank you for attending today's presentation, and you may now disconnect.