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spk00: Good morning and welcome to Oncolitics Biotech's first quarter 2023 conference call. All participants are now in listen-only mode. There will be a question and answer session at the end of this call. Please be advised that this call is being recorded at the company's request. I would now like to turn the call over to John Patton, Director of Investor Relations and Communications. Please go ahead.
spk13: Thank you, Operator, and good morning, everyone. Earlier this morning, Oncodex issued a press release providing recent operational highlights and financial results for the first quarter of 2023. A replay of today's call will be available on the events and presentation section of the Oncodex website approximately two hours after its completion. After remarks from company management, we will open the call for Q&A. As a reminder, various remarks made during this call contain certain forward-looking statements relating to the company's business prospects and the development and commercialization of Pallavi Rep, including statements regarding the company's focus, strategy, and objectives, the company's belief as to the potential and mode of action of Pallavi Rep as a cancer therapeutic, the design, aims, and anticipated benefits of the company's current pending clinical trials, and anticipated timing of the release of additional data, the company's plans and expectations regarding potential registrational studies, the business development plans and strategies, the company's financial runway, and other statements related to anticipated developments in the company's business. These statements are based on management's current expectations and beliefs and are subject to a number of factors which involve known and unknown risk delays, uncertainties, and other factors not under the company's control that may cause the actual results, performance, or achievements of the company to be materially different from the performance or expectations implied by these forward-looking statements. In any forward-looking statement in which Oncologics expresses an expectation or belief as to future results, such expectations or beliefs are expressed in good faith and are believed to a reasonable basis, but there can be no assurance that the statement or expectation or belief will be achieved. These factors include results of current or pending clinical trials, risks associated with inactual property protection, financial projections, actions by regulatory agencies, and those are the factors detailed in the company's filings with CDAR and the SEC. OnClinics does not undertake any obligation to update these forward-looking statements, except as required by applicable laws. Speaking on today's call will be OnClinics Chief Executive Officer, Dr. Matt Coffey, Chief Medical Officer, Dr. Thomas Heinemann, Global Head of Business Development, Andrew DiGuttadaro, and Chief Financial Officer, Kurt Gluck. I will now turn the call over to Matt to begin management's remarks. Please go ahead, Matt.
spk02: Thanks, John. It's my pleasure to provide an overview of our recent highlights and outlooks for the coming months. I'll start with the exciting news that came out just last week when we announced the results from our randomized Bracelet-1 trial in HR-positive HER2-negative metastatic breast cancer will be shared in an oral presentation at the upcoming ASCO annual meeting. ASCO is one of the world's most well-regarded oncology conferences and will provide an excellent venue to discuss our results with potential partners and the broader breast cancer community. With Bracelet's ASCO Abstract set to be published later this month, we are weeks away from a crucial milestone for Pella-Briorep, or Pella, as I'll often refer to it. As I've mentioned on previous calls, Bracelet 1 represents Pella's last major step on the path to a pivotal study in HR-positive HER2-negative metastatic breast cancer. Key goals for the trial are to inform and design a subsequent licensure-enabling study and to validate prior randomized Phase II data that showed Pella driving as statistically significant, near doubling of median overall survival when combined with Paclitaxel in this indication. Given Bracelet's importance to Pella's value proposition, setting the stage for its upcoming readout will be the primary focus of today's call. As we look ahead to Bracelet's one upcoming readout and beyond, we believe we are well positioned for growth with a pipeline that includes two core pillars. namely our HR-positive HER2-negative breast cancer and pancreatic cancer programs. Both of these programs represent meaningful registration opportunities supported by compelling proof-of-concept clinical data and FDA fast-track designations. We expect to have additional guidance on the optimal registration enabling pathways for these programs later this year, highlighting just how excited these times are for Oncolytics. With that, I will now pass the call off to Tom.
spk07: Thanks, Matt. Before previewing Bracelet's upcoming readout, let me first briefly recap our HR-positive HER2-negative breast cancer program's current clinical dataset to provide context for the trial's goals. I'll start with an overview of IND213, which was a randomized phase two trial that evaluated Pella combined with Paclitaxel versus Paclitaxel alone. As Matt mentioned, the trial produced statistically significant data that showed a near doubling of median overall survival in HR-positive HER2-negative metastatic breast cancer patients in the combination therapy group. These results supported a subsequent fast track designation from the FDA, as well as a special protocol assessment agreement indicating that IND213 is a sufficient foundation to allow advancement to a pivotal licensure enabling study. Additional data supporting our HR-positive, HER2-negative breast cancer program include Phase I results demonstrating PELLA's single-agent activity in this indication, as well as results of AWARE-1, a window of opportunity study that evaluated PELLA-based treatment combinations in early-stage breast cancer patients. AWARE-1 successfully met its primary endpoint. In addition, AWARE-1 demonstrated PELLA's immunologic mechanism of action, including its ability to remodel the tumor microenvironment in ways that are associated with improved patient prognosis, such as increased infiltration of T cells into the tumor and improvement in the risk of recurrence score. With these prior results providing a robust foundational data set for our HR-positive HER2-negative breast cancer program, the goals of BRACEL1 are to substantiate the positive results of IMD213 and inform the design of a licensure-enabling study. To accomplish these goals, We and our collaborators at Pfizer and Merck KGA designed Bracelet to enroll 48 patients randomized across three cohorts, a control arm consisting of standard of care paclitaxel monotherapy, an arm evaluating paclitaxel combined with Pella, and a third arm in which the checkpoint inhibitor of Valumab was added to paclitaxel plus Pella. The first two arms mirror the IND213 study groups, while the third arm was included to evaluate whether the addition of Avalumab to Paclitaxel plus Pella provides additional benefit. Note that Avalumab is an anti-PD-L1 antibody that was co-owned by Pfizer and Merck KGA when we designed the study. However, today it is solely owned by Merck KGA. Note that Bracelet 1 is not powered to demonstrate statistically significant differences between the treatment groups. Therefore, a successful Bracelet 1 result would be a demonstration that one or both of the Pella-containing arms numerically outperformed the Paclitaxel monotherapy group. The key endpoints that we are monitoring the trial include overall response rate and progression-free survival. Another key endpoint is overall survival. However, these survival results need more time to mature before they come into focus. Next, I'd like to lay out the sequence of events that will take place around the Bracelet 1 announcement all of which will be guided by ASCO's embargo policy. On May 25th at 5 p.m. Eastern Time, the Bracelet One abstract will be published on the ASCO website, which will allow us to put out a press release detailing the contents of the abstract. So please keep a lookout for that press release with the most up-to-date information. On Saturday, June 3rd, Bracelet One's oral presentation will be delivered by Dr. Amy Clark, during one of ASCO's clinical science symposia. Following this presentation, we plan to host the key opinion leader webinar on Monday, June 5th at 8 a.m. Eastern time to provide expert perspective on the results and what they mean for our HR-positive, HER2-negative breast cancer program's next steps. Those who have joined can find the webinar's registration link on the events and presentations section of our website. In addition to the oral presentation on bracelet, the ASCO conference will include a poster on preclinical studies evaluating Pellis potential labeling technology for CAR T-cell therapy in solid tumors. These studies were conducted in collaboration with Dr. Richard Viles' group at the Mayo Clinic and followed the publication of a paper on this topic in Science Translational Medicine last year. As a reminder, data from the Science Translational Medicine paper showed Pella synergistically enhancing the efficacy of CAR T cells leading to cures in marine solid tumor models. This was an exciting finding. To date, CAR T cells have been unable to effectively treat solid tumors despite the fact that they have revolutionized the treatment of blood-based cancers where long-term patient cures have been achieved. Mechanistic analyses link the promising results reported in science translational medicine to Pella's ability to overcome the three key challenges that limit the activity of CAR-T cells against solid tumors, namely poor cell perseverance, immunosuppressive tumor microenvironments, and antigen escape. With solid tumors representing the vast majority of new cancers, these data suggest Pella may have the potential to substantially expand the addressable population for CAR-T cell therapies. Collaborative studies to build on these results are ongoing, and we look forward to sharing additional data at ASCO in the coming weeks. Lastly, before handing it off to Andrew, I'll speak briefly about our Phase I-II Goblet Trial. This trial evaluates treatment combinations, including Pella plus Roche's atezolizumab in gastrointestinal cancers. We continue to make encouraging progress in Goblet with updates from its advanced anal and metastatic colorectal cancer cohorts expected in the second half of the year. In addition, we continue to advance towards key milestones in the trial's pancreatic cancer cohort, which forms the foundation of our pipeline's second core pillar. Updated data from this cohort, as well as guidance on the program's path towards registration, are also expected in the second half of the year. With that, Andrew will now speak about our business development efforts. Andrew?
spk11: Thanks, Tom. Let me start by reiterating our enthusiasm for Pella's core licensing value proposition, which stems from our two substantially de-risked registration opportunities in breast and pancreatic cancer. By 2028, the addressable markets for drug-treatable HR-positive HER2-negative breast and first-line pancreatic cancer are expected to reach approximately 300,000 and 135,000 patients, respectively, across the U.S., major European countries, and Japan. Moreover, data from the IND213 and GOBLET trials provide clinical proof of concept and demonstrate Pella's potential to substantially improve the treatment paradigm in these indications. With clinical data de-risking our efforts in large markets with clear unmet needs for improved treatments, We have been garnering healthy interest in our pursuit of a single licensing deal for our breast and pancreatic cancer programs. While I can't speak to the specifics of ongoing BD conversations at this time, there are a couple of points that I can make now. First, feedback from our ongoing conversations have indicated that Brace at One's readout in a few weeks will hopefully kick off a new phase in our BD process. Given the potential for Brace at One to provide a second randomized data set, demonstrating the ability of a pellet-paclitaxel combination to outperform paclitaxel alone, this feedback isn't surprising. Second, I'll note that even in the event of a successful bracelet one outcome, we don't expect to hastily finalize or announce any deal. If successful, we'd have a breast cancer program supported by two randomized data sets, a special protocol assessment agreement indicating one of two necessary pivotal studies is complete, and a fast-track designation. This would put us in an enviable position in any negotiation, particularly when paired with a pancreatic cancer program. Given all this, we plan to continue advancing our BD activities with a disciplined, methodical approach that seeks to drive competition among multiple parties. Our ongoing past collaborative trials have allowed us to establish formal relationships with many of the leading players in the space, including Pfizer, Roche, Merck Serrano, Bristol Myers Squibb, and Insight, which we believe leaves us well-positioned as we seek the best deal possible for our shareholders. To conclude my section of the call, I'll speak briefly about our preclinical CAR-T program, building off Tom's earlier remarks. Having been heartened by the positive data from the work we've done with Dr. Vial and the Mayo Clinic, we are advancing research collaborations with biotech companies interested in validating or recapitulating the results from the Science Translational Medicine publication. One of these companies has already produced results with Pella in combination with their own CAR-T constructs that are in line with what was seen previously in Dr. Bile's work. That company is now repeating those results to ensure their accuracy, and we look forward to reviewing them with our research partner in the second half of the year. Recapitulating the science-translational medicine results is an important step for our collaborator because, unlike other agents, a class effect cannot be assumed with CAR-T cells since they behave according to their specific genetic makeup. We look forward to providing more information on our CAR-T work with Mayo at the upcoming ASCO meeting. With that, I'll pass the call off to Kirk for a review of our quarterly financials.
spk10: Kirk? Thanks, Andrew. I'm pleased to report that OnClinics remains well-financed through Bracelet 1's readout this quarter, as well as past the important regulatory updates from our breast and pancreatic cancer programs expected in the second half. As of March 31, 2023, we had $29.7 million in cash, cash equivalents, and marketable securities, providing us with an anticipated runway into 2024. This compares to $32.1 million as of December 31, 2022. Our general and administrative expenses for the first quarter of 2023 were $3.2 million compared to $2.6 million for the same period last year. Now, this increase was primarily due to increased investor relations activities, partly offset by lower share-based compensation expenses. Research and development expenses for the first quarter of 2023 were $3.5 million compared to $3.7 million for the same period last year. This decrease was primarily due to lower bracelet one study costs and share-based compensation expenses, partly offset by increased manufacturing expenses associated with a process development production run and higher personnel-related expenses. The net loss for the first quarter of 23 was $6.4 million compared to $6.8 million in the first quarter of 2022. This equated to a net loss of 10 cents per share for the first quarter of 23 and 12 cents per share for the first quarter of 2022. So this completes my financial review and brings us to Matt's closing remarks. Matt?
spk02: Thanks, Kirk. Before moving on to the Q&A session, I'd like to close with a brief recap of all the exciting milestones we expect to achieve between now and the end of the year. The first of these milestones will become later this month when we announce randomized Phase II data from Bracelet 1 in an oral presentation at ASCO, which again is a randomized trial that represents Pella's last major step on the path to a registrational study in HR-positive HER2-negative breast cancers. Also at ASCO, we anticipate reporting additional preclinical data on the combination of Pella and CAR-T cells in solid tumors. In the second half of the year, we expect to provide update data from our first-line pancreatic cancer program and additional guidance on the registrational pathways for this and our other core program in HR-positive HER2-negative breast cancer. As a reminder, our special protocol assessment agreement indicates that we've already completed one of two pivotal studies needed for approval in HR-positive HER2-negative breast cancer. While in pancreatic cancer, we envision a randomized phase 2B3 trial with an adaptive design that would allow us to move seamlessly from a phase 2B interim analysis to a larger phase 3 portion that could support a regulatory filing. Both of these programs are supported by FDA fast-track designations, which should aid in our regulatory interactions as we work to confirm the optimal design for our next trials. Solidifying these designs will further de-risk our programs and expedite our entry into a registration environment with shots on goal and two indications, with large commercial opportunities and long-standing unmet needs. Beyond our core programs, we will continue to follow the blueprints I laid out on our last earnings call to take full advantage of Pella's platform potential. While maintaining focus on our efforts in breast and pancreatic cancer, this blueprint has leveraged collaboration with leading players in industry and academia to advance Pella in additional high-value indications, such as anal and colorectal cancer, and as an enabling technology for CAR-T cell therapy in solid tumors. By sticking to this blueprint, we've been able to maintain a capital-efficient approach while further enhancing Pella's value proposition. Finally, we expect to provide updates on Goblet's cohorts evaluating Pella and Atiz-Elizabeth combinations in anal, and metastatic colorectal cancer in the second half of the year. As we work towards our upcoming milestones, we are fortunate to have the support of world-class collaborators, talented employees, dedicated investigators, and of course, all of our investors. Each of these individuals, as well as our clinical trial participants, have been instrumental to Pellet's development and the progress we have made towards our mission of improving the lives of patients with cancer. I would like to express my gratitude for all their contributions And we'll now open up the call for questions. Operator?
spk00: Thank you, sir. Ladies and gentlemen, if you would like to ask a question, please press star followed by one on your touchtone phone. You will then hear a three-tone prompt acknowledging your request. And if you would like to withdraw from the question queue, please press star followed by two. And if you're using a speakerphone, we do ask that you please lift the handset before pressing any keys. Please go ahead and press star one now if you have any questions. And your first question will be from John Newman at Canaccord. Please go ahead.
spk14: Hi, guys. Good morning. Thank you for taking my question. I'm just curious if you could give us any color on the potential pivotal design for a pelvic rep in breast cancer. I know that there's been some... Studies run in the past with checkpoint inhibitors with various results, but just kind of curious as to how you may or may not work in a checkpoint in a potential pivotal study. Thanks.
spk03: Great question, John. Thanks. And to throw another wrinkle in the works, I'm not sure if you read the news that Pfizer turned back Avelumab to Merck KGA. So Avelumab is no longer of much interest to Pfizer at this point. I'll get Andrew to touch on the economics, but, you know, if we consider IND 213... Hello?
spk08: We've lost you, Matt. Hello?
spk10: We lost you there for a second. Sorry.
spk03: So IND 213 was, you know, we showed an overall doubling of survival and HR positive, HER2 negative. in a very, very heavily appreciated patient population who'd all had previous exposure to taxanes. Bracelet has apaclitaxel versus apaclitaxel-pelaline, and we're in a much earlier patient population who are taxane-naive, so we're hoping to see differences in PFS, ORR, and keep that huge sort of delta that we had seen with overall survival. We would like to see improvement with velumab But the reality of it is if we've doubled overall survival, the increased benefit that the additional $200,000 at a value map would cause really has to be taken into consideration. We're going to have to see quite a dramatic improvement beyond that one-year overall survival to rationalize another $200,000. Andrew, do you want to talk a little bit about what payers have to say, where checkpoint inhibitor might come into lifecycle managements, And then, Tom, I'll get you to talk about what we think is a most probable trial design. So, Andrew, do you want to kick us off?
spk12: Sure. Absolutely. So we actually did some research with European payers to see what they would need to see in terms of a survival benefit to cover the product. And we chose the Europeans because, as you know, they're much more stringent with coverage decisions than the U.S. So it's kind of a harder task master. And the feedback from them was, look, a three-and-a-half to four-month OS improvement over Paclitaxel would probably garner their interest and allow us to discuss contracting and the rest of the coverage process with them. That was propeller re-rep plus Paclitaxel as the value proposition. So if you add a value map and you add another – You know, we haven't decided where we're going to price ours, but let's say for argument's sake that we'll price around what a CDK4-6 would price by then, which with historic price increases would be over $200,000 per year by time of launch. And looking at the price increases for checkpoints, let's assume it's the same as Matt was kind of alluding to. For a Valumab, you're talking about $400,000 charge per patient to treat. you're going to, you know, I haven't spoken to affairs, but having been a reimbursement consultant, I can tell you, they're going to tell us you're probably going to have to find the patients that have a doubling of overall survival. So that's a, you know, the cost of the additional really is a rate limiting factor that has to be considered. If we think we can do well clinically and therefore commercially with just Pella rear rep plus paclitaxel. So that's really one of the challenges that we have to think about. You know, we always think about lifecycle management. We could always do a separate or smaller trial if we choose to not include the checkpoint. I'm not saying we aren't, but one thing that could be done is look at that in the lifecycle management to try and find maybe the patients who would have that kind of a response and therefore be able to tell, say, look, for these patients with this profile, Um, we think they'll respond and talk to the payers that way. Um, Matt, anything else from your perspective there?
spk03: No, I think, I think that's fantastic. I really think, um, it becomes a very important figure in life cycle management. I'm not sure it's as important, uh, for what the phase three looks like. Cause we really do want to capitalize, um, on the two 13 results and then expand those hopefully with bracelet into a phase three, um, Tom, did you want to talk a little bit about what a study would likely look like?
spk07: Yes, sure, Matt. So with the comments of Matt and Andrew in mind, I think the study design will be comparatively straightforward. We would envision a two-arm study with a Paclitaxel control arm and then a Paclitaxel plus Pella rear rep with or without a Valumab investigational arm, and we would then obviously power it appropriately for an overall survival endpoint and perhaps a PFS endpoint depending on how things play out.
spk01: But I think the overall design would be pretty straightforward two-arm study. Thank you, Tom. Okay, great. Thank you.
spk00: Thank you. Next question will be from Louise Chen at the Cantor Fitzgerald. Please go ahead.
spk05: Hi. Congratulations on all the progress this quarter and thanks for taking my questions. So I wanted to make sure I heard you right when you said that bracelet one was not power for stat-sig, and if not, what do you want to see to consider this a successful trial, or what do you expect to see? And then secondly, can you elaborate more on the CAR-T opportunity and what that means for you? And last question I had for you is on your cash runway, what positive inflection points does that bring you through? Thank you.
spk03: Thanks, Louise. Tom, do you want to take the first question, Andrew the second, and Kirk the third?
spk01: Sure. The first question was, I'm sorry, say that again, please.
spk05: Yeah. So did I hear you right in that you did not power a bracelet?
spk07: For the power, yes. Yeah. So the bracelet study is a randomized study. So the patrons are randomized between the arms. However, it was not powered to allow a formal statistical comparison. So what we will look for in that study as criteria for success are numerical differences between the groups in the key, in the primary endpoint, which is objective response rate, as well as any other efficacy endpoints. As we mentioned, we will be reporting the progression-free survival results, but the overall survival results are not mature enough to report at this time. So we will be looking for numerical differences, and then obviously we can, one can conclude based on the magnitude of those differences. But keep in mind also that this study is not a standalone study in that it is the first two arms of this study, which are the paclitaxel versus the paclitaxel plus pelarirap, are basically recapitulating the former IND study in which we saw the strong survival benefit So this is, from an efficacy perspective, will largely be a confirmatory study to provide additional confidence and to de-risk the program further.
spk03: Andrew, there's an opportunity in CAR T. Andrew, you want to talk a little bit about how we would look at sales and royalty in that particular environment and how this could potentially work across platforms?
spk12: Yeah, absolutely. So if you remember from Science Translational Medicine article, each of the mice that had these dramatic responses utilized two doses of Pella Rear Rep, one that was basically conjugated with the CAR T and administered to the mouse, and then a boost dose afterwards. Um, the goal is to open up solid tumors for CAR T's because they have struggled to show any efficacy there and, you know, solid tumors are 85% of the market. So it's, it's right now running fallow. Um, but it's about selling CAR T's and the solid tumors. Two doses of Pella Rear Ep are, you know, a drop in the bucket for us compared to the potential in breast or pancreatic cancer. So it's not about selling Pella, it's about selling the $400,000 CAR T and say a liver patient that, but for the Pella would not be able to be treated with the CAR T. So the way we see this working is that there would be some kind of an upfront that would be determined by the number of CAR T's involved, the number of tumor targets involved. Then there might be some development regulatory milestones along the way, but the big revenue would be some sort of double digit royalty that on the sale of that CAR T in every patient where Pella Rear Rep is added for the treatment. So it could potentially turn into a nice revenue stream for us that could be applied to any number of our needs, but it is not our core focus. We would advise and provide Pella Rear Rep to the CAR T developing and then commercializing the combination, but we don't have any immediate term to get in the car key business ourselves.
spk10: Yeah, then with respect to our cash and cash runway, we reported just under $30 million at the end of the quarter. We anticipate that that provides a runway of at least 12 months. In terms of catalysts and milestones, The cash on hand gets us through more clearly the ASCO bracelet presentation. We have CAR T updated ASCO as well. In addition, the goblet study, we are targeting to provide efficacy updates on the pancreatic cancer cohort. We're targeting ESMO. But that's to be determined. And the other cohorts, the colorectal and the anal cancer cohort, we do expect to provide interim updates on those other cohorts in the second half of the year. And our runway takes us through those events.
spk00: Thank you. Thank you. Next question will be from Patrick Trujillo at HC Wainwright. Please go ahead.
spk09: Thanks. Good morning. Just one clarification as it relates to bracelet one and the registration path for HR-positive HER2-negative metastatic breast cancer. It sounds like you would need just the one pivotal study to submit for potential approval, though maybe you could elaborate more on that point specifically and potential for the accelerated approval pathway and how this upcoming ASCO data specifically could facilitate this pathway. And secondly, Can you give us an update on the GOBLET program, including the expected next data release in the second half, the timing of this data, and what you'd be looking for here to give confidence to advance the program to a registrational study? Thank you.
spk03: Absolutely. So to start with the GOBLET, we've spoken with AIO and our principal investigator, Dirk Arnold. We are starting to see maturity in the pancreatic data. So we'll be able to present PFS and we likely believe evolving or somewhat mature OS by ESMO GI, which is in Barcelona in October. So that's really the timeframe that we're working to. We're also hoping to provide updates on the other three cohorts, likely again within that timeframe of ESMO GI, just because it is such a great showcase for GI therapies and we'd have the right audiences like KOL. So we think that would be very inopportune timing The PEG data we've discussed with stakeholders, the signal was so strong we could have expanded that to an additional 30 patients. But with a 69% objective response rate, really we felt that we had demonstrated a very, very strong signal. And what we wanted to do is move it into a more stringent environment. So what we're talking with corporate partners with is randomized phase two in the 60 patient range. We're also speaking with cooperative groups that would actually be capable of running a Phase 2B3 program, so an adaptive design where we would enroll, I think it's 60 to 80 patients in that first 2B program, and if we're seeing the signal that we want to see, we would just seamlessly move into the Phase 3. This is very attractive because the cooperative groups provide a lot of expertise and cost deferral, but more importantly, they're expeditious. They have pre-approved protocols with the FDA, so If we can get through their selection process, it's just a plug and play to get into the phase three environment. Sorry, Patrick, I'm drawing a blank. What was the first part of your question?
spk09: Yeah, just on the registrational pathway for HR positive, HER2 negative with Pella and with this bracelet one data, just want to clarify that you would only need the one pivotal study you know, going forward for potential submission for, you know, regulatory submission for approval. I just want to, you know, make sure that that is what is possible. And to the extent that it depends on the ASCO data, how does the, you know, just how does that facilitate this accelerated pathway?
spk03: Well, absolutely. That's also another great question. IMD 213 showed a doubling of overall survival. We took that to the agency. And what they told us is this will provide you with a special protocol assessment for anyone who's listening. What that means is we've agreed to a protocol with the agency and they've already, because they have granted that, the 213 de facto is one of the two required randomized studies. So we are only one randomized study away. Now people ask, they're like, why would you then go and do bracelet? And really the question for that was, 2013, we were working under the assumption that this was largely lytic. The results very strongly indicated that lysis was probably occurring, but the mechanism driving this was really a T cell mediated response. So the agency said, listen, you can start that phase three, but you're doing so at some tremendous risk if you don't fully understand mechanisms of action. And if you don't have at least some biomarker plan that measures a T cell response that would tell you whether or not those patients are responding. So Pfizer was looking at the end of these two minutes and the SPA, and they agreed. They said, listen, one of the things that we can actually look at that we're quite excited about, 213 was a very heavily pretreated patient population. Just to remind everyone, we saw about a three-week increment in median PFS. But in that patient population, everyone had already been exposed to or had failed a taxing. Where bracelet's a little bit different is it recapitulates what we saw in 213 but it does it in the group of women who are taxing naive. So our hypothesis was, um, if patients have a less, um, damaged or a less challenged immune system, let's keep in mind standards. Chemotherapies like taxing really are detrimental to an immune response. Um, especially multiple rounds of it. Our thinking was if we moved to an earlier setting, we could actually potentially look at wins in areas like ORR and PFS where we were seeing a hint of a signal, in a pre-treated group. So we thought in a pre-treated group that would expand that opportunity. Now, if that's actually the case, it's potentially very important in terms of our registration path because a PFS win would get us to a registration program much, much earlier than OS would because obviously you have to wait for that OS to mature. So what we're hoping is if we see a positive signal in PFS, we can move to dual endpoints for the registration program that would give us a win that could potentially be as much as 18 months earlier.
spk08: Perfect.
spk09: Thank you so much.
spk08: Thanks, Patrick.
spk00: Thank you. As a reminder, ladies and gentlemen, if you do have a question, please press star followed by one on your touchtone phone. And your next question will be from Douglas Meehan at RBC Capital Markets. Please go ahead.
spk04: Yeah. Good morning. First question. If you were to take the OS data from the IND213 and apply it to the currently ongoing trial, when would you expect to start to see maturity of OS data in Bracelet 1?
spk03: Well, I'll let Tom speak to the expectations. But the last patient put on study was June 2022. So for PFS, the expectation on the control arm is about a six-month medium PFS. So we've got all patients out now 12 months beyond that. So I would say that that's reasonably, well, we'll have mature PFS for ASCO. OS, we're starting to see the events now. As I said, the study started 2020. So we've got patients who are on study now for three or more years. Last patient was more than a year ago. You would anticipate survival here to be about a year or so. We're anticipating we should have a pretty good idea by San Antonio. What we're looking for, though, Doug, is 80% of the event, so it might be an early 2024 event.
spk04: Perfect. And then just remind me, if you're allowed to, were the 48 patients equally divided between the three arms, so 16 in each?
spk03: No, it was 15 on the paclitaxel, 15 on paclitella, because we'd already had that. The agency wanted to see a three-patient safety run-in, so the Pac Pella Valumab had a three-patient run-in plus 15, so they have 18. Perfect. Okay.
spk01: Thank you.
spk03: You're welcome.
spk00: Thank you. And at this time, gentlemen, it appears we have no further questions. Please proceed.
spk03: Thank you, operator, and we wanted to thank everybody who participated this morning. We're just a few weeks away from being able to disclose what happened on bracelets. We're obviously very excited, and we would encourage anyone who can't participate in our KOL call the morning of June 5th. With that, I'll say thanks again, and have a lovely morning, everyone.
spk00: Thank you, sir. Ladies and gentlemen, this does indeed conclude your conference call for today. Once again, thank you for attending. At this time, we ask that you please disconnect your lines. Have yourselves a good weekend.
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