day and thank you for standing by. Welcome to the Agenius Business Update. At this time, all participants are in a listen only mode. After the speakers' presentation, there will be a question and answer session. I would now like to hand the conference over to your speaker today, Divya Vasudevan, Senior Director of Oncology Strategy and Investor Relations.
Please go ahead.
Thank you very much, Catherine, and thank you all for joining us today. Today's call is being webcast and will be available on our website for replay. Before we begin, we would like to remind you that this call will include forward looking statements, including statements regarding our clinical development, regulatory and commercial plans and timelines, as well as timelines for data release and partnership opportunities. These statements are subject to risks and uncertainties, and we refer you to our SEC filings for more details on these risks. As a reminder, this call is also being recorded for audio broadcast.
Joining me this morning are doctor Garo Armen, chairman and chief executive officer and doctor Jennifer Buell, president and chief operating officer. Now I'll turn the call over to Garo. Garo?
Thank you very much, Julia. Today, we announced a strategic decision to withdraw our Biologics License Application, our BLA, for balstilimab for the treatment of patients with second line recurrent or metastatic cervical cancer. This decision to withdraw the BLA does not change the development plans for Bofilimab combinations. Following the full approval of Bofilimab announced four months ahead of BLA's GOLD AID, or I should say following the full approval of pembrolizumab announced four months ahead of FDA's BLA GOLD date, the agency no longer considered it appropriate to review the BLA for accelerated approval and recommended us to withdraw the application. The BLA submission for balsilimab received fast track and priority review designation from the FDA back in June with a target action date of 12/16/2021 for the decision on a BLA.
As part of the BLA review process, we successfully completed three FDA inspections. At the conclusion of these inspections, there were no cited issues, concerns, or form four eighty threes in technical terms. And all of this, of course, is a testament to our commitment, readiness, and quality of our organization. We made this decision despite the fact that balstilimab having met its trial endpoints in the largest single arm trial to date in this population, involving 140 patients. Balsilimab showed responses in both PD L1 positive and PD L1 negative patients, which were twenty percent and eight percent respectively, compared to pembrolizumab responses of fourteen percent and zero percent in a trial of seventy seven patients, which resulted in its accelerated approval for only PDL-one positive patients back in 2018.
Now, course, in single arm trials, it's hard to compare results from one trial versus another. However, we are very heartened by the fact that our response rates were quite robust in a trial, which represented almost double the number of patients in the pembrolizumab trial. Balstilimab has also shown superior killing of PD L1 negative tumors compared to other anti PD-one therapies, including pembrolizumab, suggesting a broader mechanism consistent with molstilimab's clinical activity in both PD L1 positive and negative cervical cancer. From the start, we anticipated the commercial market for balstilimab monotherapy in second line cervical cancer would be small. And it has become smaller today because the market has gotten considerably crowded after the recent approval of pembrolizumab in the first line setting.
And that of course, also affects the potential size of the market. However, given the importance of PD-one blockade in cancer intervention, we had always prioritized balstilimab as a necessary component in our pursuit of highly effective combinations within our portfolio and potentially with partners, including combinations with our next generation CTLA-four, AGEN1181. And of course, these facts, continue to be, the driver for our Bostolimab,
advancement. Our PD-one strategy
is driven by the urgent unmet need for effective and affordable cancer therapies. Hence, the independence from third party PD ones has been key to our strategy and continues to be. At this year's SITC conference, we will present new data on AGEN1181 as monotherapy and in combination with fostamatinib. We will also announce further details on our plans to accelerate the development of AGEN1181 plus fostamatinib in multiple tumor types. Our objective is to pursue trials designed to enable full approval, while pursuing accelerated approval pathways for rapid commercialization and access to patients when appropriate.
In addition to withdrawing our BLA for balstolimab in second line cervical cancer, we will also discontinue our confirmatory trial, RABA. This is expected to reduce r and d expenses by over $100,000,000 spread over at least a couple of years. However, given the clinical benefit demonstrated by balstilimab, we're planning to launch expanded access programs to give patients and doctors access to balstilimab in several countries, including The US of course, pending a regulatory process in each country. So in summary, let me point out several things. One is that austilimab BLA withdrawal was not related to product performance or company performance in being able to bring this to the finish line.
As I indicated, our product performance was very, very satisfactory. It met the standards that were predefined for the accelerated approval process. And also very importantly, we were able to pass three very important, inspections by the agency, including clinical inspection, quality inspection,
and
CMC inspection with no four eighty three sightings, which is something that we are very proud of as a company. Secondly, as I said earlier, balstilimab continues to be a very important cornerstone of our combination strategies, particularly with eleven eighty one. And we expect to disclose some data that we believe will show the efficacy of both eleven eighty one and fostamimab in SITC in early November. And thirdly, we have plenty of cash resources that we will end up the year with. My estimation is that we will end up the year with approximately a quarter of million in cash.
And that will allow us to certainly bridge any process into a major corporate development transaction as well as allow us to take our programs forward. Did I say quarter of a 0, my COO who is sitting right next to me here, pointed out that I said quarter of a million, I meant quarter of a billion. Thank you very much. So with that, I end the, formal comments, and I'm happy to take any, questions, of course.
Thank Our first question comes from Mayank Mamtani with B. Riley Securities. Your line is open.
Good morning. Thanks for taking our questions, and and sorry to hear about this unfortunate development. So, Garo, are are you able to comment you know, two peep two pieces to my question. Is there a regulatory and commercialization path ex US you you're able to talk about? And then accessing an approved checkpoint inhibitor is obviously core to any combinations in in immuno oncology, as you know well.
So how does, you know, your plan to develop one one eight one, obviously, but also, you know, a pipeline that was relying on this foundational asset, how should we think differently about that as a result of today? And then I have a follow-up.
Sure. So for your first question is easy, Mayank. We are definitely exploring those options because as you know, there is a tremendous unmet need, not just in cervical cancer, but some of the other cancers that we have touched with our products so far. And our expanded access program is designed actually, the aim of the expanded access program will be to make patients be able to get our products when appropriate, of course. And if we can submit data to other countries that will allow us to market products, And that will, of course, be also a part of our strategy.
With regard to your second question, if I understand it, correctly, you're asking how would the withdrawal of the BLA for austilimab affect our development pipeline, our plans, our timelines, and so on and so forth. Is that is that fair?
That that's accurate because That's right, Garo.
So as as you know, right now, our strategy you know, when we started on our bowel journey, we never really expected to have a commercial opportunity with bile as a monotherapy. In fact, we were getting a lot of questions about, does the world need a fifth, sixth, seventh, eighth, PD-one, antibody? And the answer is no, you cannot really compete with being the six, seven, eight in the marketplace. But, we pursued cervical cancer, to go through the process of first approval because there was a window available, even though we never thought the commercial opportunity for cervical cancer would justify, really a commercial effort per se, we thought this will be a nice drive on for us. But in essence, the potential of bowel for us is in combinations with the rest of our pipeline.
I mean, that has been, our strategy, when we entered the bowel arena with our own discovery of bowel five, six years ago, and that doesn't change. And so in terms of the vigor with which we will pursue combinations, that doesn't change. One can say, because we're discontinuing the BRAVA trial, which is a confirmatory trial, an expensive trial, now we will have more resources to dedicate, to combinations and perhaps more bandwidth of the organization to do that
Appreciate the color. And then my my follow-up question sort of related, Gato, is, you know, you were thinking of sort of building an OBGYN focused organization to begin with. But how should we you know, are you able to comment on what sort of initial tumor type focus should we expect from you? You know, is it is it really going to solely be focused now where one one eight one goes, for example, colorectal cancer? And then, you know, how should we think about timelines as as you sort of reset?
Because your, you know, your commercial organization was leaning towards maybe that that OBGYN focus initially. So how should we think about that commercialization timeline and and how you might I think you're commenting on on 100,000,000 on that, basically, on the r and d spend from that clinical trial. But what about the, you know, the commercial spend also that that was scaling up?
Yeah. Very good question, Mayang. And, let me address it this way. So as you know, because of what I said earlier, because of the smaller potential market size for, cervical cancer, we didn't invest an enormous amount of effort to build a commercial organization, specifically for gynecological cancers just yet. And but what we're doing is we have a very, very efficient organization that has been put into place, a chief chief commercial officer along with, several, professionals that, we were contemplating on building around very quickly to hire salesmen and some marketing professionals and so on and so forth.
So, but because we decided to do this prudently, now we can divert some of the efforts of this very slim organization to medical education. Medical education is going to be a linchpin of our strategy with, expanded access program. This is not, designed to, generate revenues in any way, it'll be strictly medical education, and allowing patients access to our products when appropriate, when it's deemed appropriate by, physicians, specialists in the field. Now, one thing that I should say is that a lot of companies also initiate expanded access programs with a objective of generating revenues. I will say to you and to the rest of the world that our expanded access program will be comprised of, an ability to provide patients and doctors drug free of charge.
We will incur all expenses associated with it, because typically with open access programs or expanded access programs, there's a mechanism, to get reimbursement for your costs. We're abandoning that. We will not require any reimbursement or expense sharing associated with this program, which is specifically designed to make the program much more patient and doctor friendly, so that, patients who are suffering from advanced cancers don't get wrapped up in, filling a lot of paperwork in order or the company, at the same time, waste a lot of time and effort, filling out papers to justify reimbursement. So that's something that we're committing to. And that's something that I think is the morally right thing to do for patients.
Sorry, Garo. Can can you comment on path to market, for combinate like, what what sort of initial indications you might be thinking? You know, maybe maybe one one eight one focused.
Okay. So I would encourage you all to wait until our SITC presentation when we will disclose our plans both in expanded gynecological tumors, as well as other tumors where we have seen very important signals with eleven eighty one plus belstilimab, and in some cases, eleven eighty one alone. So, I'm sorry that I will not give you additional information on that to comply with the SITC rules. But if you wait for a few weeks, I think you will get a fair amount of disclosure.
Looking forward to that. Thank you, Garo, for taking my question.
Thank you. Thank you very much.
Thank you. Question from Matt Phipps with William Blair. Your line is open.
Hi. Good morning, Gail. You know, you were going through the process several here, appreciate that Vowel opportunity was limited, but, know, did seem to be Val Zou had an opportunity given the increased efficacy. But, you know, you you ran into the problem of trying to get two novel drugs approved and then obviously had to submit VAL first. So is this an issue you're gonna have on the next, you know, first indication for November?
And, you know, any other ways you see of kind of trying to get bowel approved alone to help with those combinations?
So, Matt, are you asking if we will pursue bowel approval alone in any of these combinations? The answer is probably not. Is that the question, though?
Yeah. I mean, that's pretty much the question. Just what other does that I mean, it creates a little bit more complexity in designing a trial, I guess, with with two unapproved agents and depending on the indications, I guess, that you go into.
Hi, Matt. I'm gonna just jump in here for a moment. Thanks for the question. So our trials, and certainly, you'll be hearing more about the development plans for November, as Gaurav just mentioned, in order to support approval, based on the plans that we've developed, we will demonstrate contribution of components and the necessity to have the combinations where they're needed. So there may be cases where eleven eighty one can support as a monotherapy, may support approval, and there may be indications where the combination with bowel will support approval.
But our trials will be designed to demonstrate and differentiate, which will enable us with novel novel combinations to get approval. Our trials will also be designed to support full approval. We will be where it's necessary. We will have a VAL only arm to demonstrate this contribution or an eleven eighty one only arm and the combination. So that's how the development will go, and that won't put us in any compromised or unsettled position with respect to, the combination potential.
So this decision to withdraw VAL won't slow or delay our programs with eleven eighty one because our trials are designed to support approval based on the the differentiation of contributions for each component.
Okay. Thanks, Jim. Thank
you. Our next question comes from Mike King with H. C. Wainwright. Your line is open.
Good morning, guys. Thanks for taking the questions. Garo, did you was there any discussion about, potential for accelerated approval pathway in the PD L1, less than 1%? I mean, I know that the numbers were small. I guess 39 is what I'm looking at from the ESMO, presentation.
But was there any contemplation that that may be a foundation that you could have built off of for bowel?
Very good question, Mike. And of course, it makes sense. And of course, we tried. But because of what you said, numbers in that subset, the agency didn't accept the argument. And our argument was even though, the response rates are lower in PD L1 positive patient, I mean, L1 negative patients, the fact is that these patients, do not have any viable treatments.
And so we were very heartened to see that in PD L1 negative patients, not only did we have responses, but we also had responses that were of long duration. And some of these responses are still going on. But And you get into the argument of numbers, of course, and that did not work. Now, as you and others have concentrated, the bottom line in all of this for us is we know we have a highly active PD-one. That's number one.
We know that our PD-one based on our proprietary assays, preclinical assays has some differentiated attributes that makes it more important in PD L1 negative patients. And we have compared several PD-one molecules to show that differentiation in these proprietary assays. We also know from a very substantial safety database, encompassing over 400 patients, and that our PD-one could be a very, very effective and very good caring agent in combinations. And that safety database that we have, built is going to be very helpful for us in getting approval in combinations going forward. So, and we also know, of course, as I said earlier, that our organization can take these products through with stellar performance.
We know how to, bring a compound from discovery all the way to the finish line of potential, BLA approval and then, access to patients beyond that. So all of these things are positives. And, but unfortunately, we didn't win this getting over the finish line in this particular case because of what we consider to be a technicality. And that's all, really. Yeah.
Understand. Second question excuse me. Second question is if it sounds to me like you're stepping back from ZAL. Am I misreading that? Most of your focus on the CTLA-four side has been on eleven eighty one, which I understand.
But, you know, since ZAL has a large database of safety and efficacy, I thought it was still logical to use that as the lead CTLA-four unless strategy has shifted there.
So another very good question. And of course, this is a subject dear to our hearts. We have, the luxury of having two CTLA-four's, one is the next generation, ZAL is the first generation. But even with the first generation compound, we have shown and it was presented at ESMO that in combination with bowel, our first generation CTLA-four has shown, thirty three percent responses, objective responses in a trial of one hundred and twenty five patients in PD L1 positive patients. So, of course, that is a big, big delta from any other existing compound in terms of response rates, any other treatment in advanced cervical cancer.
Now bear with us in terms of determining what the next steps may be with ZAL. The issue with that trial is that while it's a very large trial, 125 patients, we have two components to treatment, bowel and ZAL. And, because it was a single arm trial, even though we did a separate bowel trial that showed, twenty percent response rates, in a very similar patient population, the FDA will require to show the contribution of the And each so that complicates it a little bit from an approval perspective. But that doesn't mean that we will not pursue it. But we need to clarify the pathway of that approval with the agency before we make a commitment.
Right. Yeah, because I mean, the way I would think about is, okay, so pembro is there in the first line, but it's with chemo and potentially with or without bev. And seems like, you know, a lot going on. There is probably room in the marketplace for an all IO option. So I guess my question is how is is it possible to get there in cervical or is it just a lost cause?
Well, bear with us. We're governed by regulation. And sometimes, even though, we may think regulation is unreasonable at times, as was the case with ostolimab monotherapy in our opinion. Still we have to respect it because that's a governing body that determines, these decisions. And so bear with us until we get some clarification and then we'll come back and inform you of the strategy.
Okay. Thanks for taking the questions.
Thank you, Mike.
Thank you. And there are no other questions in the queue. I'd like turn the call back to the company for any closing remarks.
Thank you very much for your attention this morning. And I think we cover a lot. And if you have any separate questions, we're always available. But be rest assured that the company's strategy, its programs, the impact on value creation has not changed. And of course, this is a little disappointment, but not from a commercial or value creation perspective.
It's a disappointment from accomplishing what we wanted to get to do by crossing the finish line. And we came very close to it. We did everything right, in a stellar fashion. We have an active product. We have a product whose safety is very much in line with this class of compounds.
And we also believe that with our expanded access program, when it is launched, with regulatory approval, and we hope that that will come. This program will help patients that are in need of products as, Mike King mentioned, even with Bowel's Val combination, this is something that should be made available to patients under the expanded Access Program. And we believe that let the doctors and the patients decide what is in the best interest of the patients. And for this reason, we're making the sacrifice of providing product for free. And we will bear the burden of that cost since we're not being burdened by the confirmatory trial costs right now.
Thank you very much for your time again.
This concludes today's conference call. Thank you for participating. You may now disconnect.