This conference call transcript was computer generated and almost certianly contains errors. This transcript is provided for information purposes only.EarningsCall, LLC makes no representation about the accuracy of the aforementioned transcript, and you are cautioned not to place undue reliance on the information provided by the transcript.
spk04: Good morning, and welcome to the Presagen second quarter and first half 2023 financial results and business update call. Please note, this event is being recorded. I would like to turn the conference over to Steve Harrison, Vice President of Investor Relations.
spk09: Thank you, Operator, and thank you for joining us today. With me are Dr. Helen Sabzavari, President and CEO of Presagen, and Harry Tomasi, our CFO. Hello. Helen will provide details on today's releases and an update on our portfolio, after which Harry will review our second quarter and first half 2023 financial results. Following our prepared remarks, we'll open the call to Q&A. Before we begin, let me briefly review our forward-looking statement. During today's call, we will make various forward-looking statements. Investors are cautioned that our forward-looking statements are based on current expectations. and are subject to risks and uncertainties that could cause actual results or outcomes to differ materially from those indicated by our forward-looking statements. Please read the safe harbor statement contained in this presentation, as well as risk factors contained in Presagen's most recent SEC filings for a more complete discussion of these risks and uncertainties. I will now turn the call over to Dr. Sabzavary. Helen?
spk00: Helen Sabzavary Thank you, Steve, and thanks to all of you for joining us today. Today is a very exciting day for Precision, and I'd like to provide you with the significant progress that we have made in the first half of this year. I will discuss two major topics today. One is the positive regulatory developments, which we announced this morning for our lead program, PRGN 2012, in an orphan rare disease setting in RRP. And secondly, the portfolio prioritization to focus our efforts to accelerate the development of PRG in 2012 toward commercialization while we continue advancement of our other key programs and extend our cash runways to 2025. With that in mind, let's go to slide number four. We have been, as you know, active in discussions with the FDA to align on a rapid regulatory path for PRGM 2012, given the high unmet need in RRP patients. But there is no approved drugs, and the only treatment options remains is recurring surgeries that are a major burden for these patients, both physically, health-wise, economically. We are pleased to announce that the FDA has confirmed that the ongoing single-arm phase 1-2 study will serve as the pivotal study to support BLA submission for an accelerated approval. At the same time, there is no additional randomized control study will be required to support accelerated approval. And we have agreement with the FDA on endpoints from the ongoing Phase 1-2 study to support the BLA submission, which includes the complete response rate, which is the percentage of patients with no surgical intervention required during the 12 months following the treatment, and an immunological surrogate marker for HPV-specific T cell responses which, by the way, has been already implemented both in phase one and phase two. Precision also has reached an agreement with FDA that a single-arm confirmatory study needs to be initiated, but not completed, and that's very important, prior to the submission of the BLA. At the same token, we are very thankful to the FDA, and they have even encouraged us to add and evaluate the inclusion of exploratory arms to the confirmatory study for a repeat dosing for the non-complete responders to potentially expand the label. And we are very excited about that. The ability of the ongoing Phase I-II to serve as a pivotal for accelerated approval can significantly reduce the developmental time to licensure. And you can imagine what does that mean for our patients, because now the randomized phase 3s are not required here, and we can move much faster, especially as I will go through the path for the licensure for us. To further expedite the development of PRGEN 2012, we are preparing Precision's in-house gene therapy manufacturing facility to produce drug substance for commercial launch. Why are we doing that? Simply, this allows us to maintain control of manufacturing in-house, we leverage our internal expertise, and we reduce the cost and timelines due to reduced reliance on a contract manufacturer. If we look at what has happened under take a moment to recognize the current status of the ongoing single-arm Phase I-II study. As you have seen and we have reported the data, the Phase I has been completed and the enrollment and dosing in the Phase II portion of this study is also completed. Phase II patients follow up, data collection, and the completion is anticipated by the second quarter of 2024. The phase one data that we presented in January has shown 50% of our patients that they were treated at the dose level two have a complete response. And that means they needed no further surgery in the follow up of 12 months. And today, we are pleased to report that all complete responders from the phase one, they remain surgery-free with a minimum follow-up of 18 months, and the responses are still ongoing. We are very pleased and excited about the promise of the PRGN 2012 for RRP patients who received numerous surgical treatments procedures in absence of therapeutic in their lifetime that can be very harmful, financially burdensome to the patients and overall the healthcare system. Getting this therapy as quickly as possible to the patients who need the relief is our highest priority obviously. I'd like to acknowledge at this point the tremendous effort of Precision Team and our investigators and collaborators. to move the PRG in 2012 from discovery phase to a recognition as a pivotal trial on a path for an accelerated approval in about three years, including the pandemic years. With that in mind, if we look at this slide number five, what I would like to highlight is what differentiates PRG in 2012 and the adenovirus platform from the rest. And we have seeked the market and the KOL research, and we have listened to what our KOLs have been telling us, that what is unique and differentiated about this molecule and this platform. As you can see in this slide, one thing that really stands out is the mechanism of action That has been seen as very promising. The physicians described the PRGN 2012 mechanism of action as promising, and particularly they are impressed with this molecule to generate a T cell response that specifically targets HPV6 and HPV11 viral Phytox. which is the root cause of RRP. And this is what is important about this therapy because it goes to the root of the problem, which is the infection in the patients that allows this recurrence of the papillomas in a very, very dangerous regions on vocal cords and trachea and even in the lungs. Secondly, There is a very favorable safety data. We have shown some of the safety data from phase one. And as you can see, and it was mentioned, the safety is grade one and grade two, it's flu-like vaccination. And this is extremely favorable, obviously, for the patients. And the physicians, they appreciate that tremendously. And especially... that some of the patients in the future will be pediatrics, and this clearly is an important factor. And finally, the reduction in the number of surgeries. I think we have heard from our patients continuously that even reduction in one less surgery, it's fundamental to them. And now having complete responders that over 12 months, and ongoing, they do not require any surgery. And by the way, we have been in the most severe patient population, which they require more than three surgeries per year, and being able to accomplish that. So this is quite exciting, and we are really happy for the patients. And finally, this is a platform with a very attractive route of administration. What does that mean? these vaccines have been given subcutaneously to the patients. You can imagine now the patients that they have to go continuously under surgery, now they can go to their physician, basically office, and receive a sub-Q injection very similar to a flu injection. And this is quite an accomplishment and a differentiation. So with that in mind, if we look at the slide number six, And on top of these slides, what you see is the scenario that we are describing in regard to the patient. You are looking at the normal, basically, vocal cord throat of a normal individual. And then on the right-hand side, you are looking at what the RRP patient suffers from. And these patients are dependent on the surgery only continuously. to remove these benign tumors, just to be able to talk or just to be able to breathe. Can you imagine having a child that you have to do this continuously on a monthly basis, take them for this kind of surgery? Obviously, there are no approved therapeutics for the RRP, and this is the importance of the decision of FDA that allowing us to go for accelerated approval, which I'm thankful to the FDA in general for recognizing the need of the patients and also the innovative studies that can be addressing that need. As we have said, the current standard of care is repeated surgeries. And this does not affect the underlying root of this. indication of this disease. Due to the chronic nature of the disease, RRP patients can undergo hundreds of surgeries during their lifetime. And these repeated surgeries, as I mentioned before, can worsen the condition of RRP as it can increase the spread of HPV virus and can result in a significant comorbidity, including loss of vocal functions. There is a significant economic and a quality of life burden of this disease throughout the lifetime of RRP patients. And as you can see on the slide, there are, and these are approximate numbers, that in the U.S. there are 10,000 at least cases of adult and 6,000 of juvenile. And in ex-U.S. there is a much larger population, upwards of 68. And we really don't know the exact number of juveniles, and these are part of the research studies that we will be doing as part of the projected market for the U.S. and ex-U.S. So with the potential now to accelerate towards becoming a commercial estate company and considering the challenging capital markets at this time, We believe that we should be laser focused on expediting the 2012 path to commercialization. By doing this, we believe that we can best position precedent for near-term success in this current environment. On slide number seven, we are highlighting some of the actions that we are taking to realign our resources and pipelines. to realize a substantial savings, especially with respect to external CRO spending and the SG&A costs, compared to the original budget estimates. HARI will further expand on the cost-saving measures we are taking over the past years and the current years. But just to mention, what we are now focused is not only to accelerate the path for PRG in 2012 without damaging the very important other programs that we have, but also extending our cash runway, which allows us to get to the readouts specifically and beyond by various means. So let's go through some of these actions. We are, first of all, reducing the cost of the clinical CROs for outside, reducing the number of the sites that will be involved in various programs as I will go through them. And definitely, we have been reducing our SG&A costs and continue to do so and Harry will highlight that. At the same token, We are redirecting our R&D team to focus on CMC and translational clinical research activities. We have a highly productive and cross-trained team, which currently, as we speak, are involved in shifting focus in order to address the CMC and translational clinical translational work required to support PRGEN 2012 PAD 2 approval. What does this do for us? First of all, there is no reduction in our R&D force. Secondly, this allows us to hold on to our talent without any, again, I stress that, headcount reduction. Furthermore, we will save time and money in trying to adjust the path. And this is very, very important for the very agile timelines that we have for the submission of the BLA. In regard to our PRGN 3006 Ultracar T program, this remains of a high priority for us. As you know, we have shown a positive data at ASH, almost 30% objective response rate in AML patients that they have no other therapy in front of them. And we have received a fast track designation from FDA. With that in view, This is extremely important program. We plan to maintain our two very productive and active sites, Moffitt and Mayo, for the ongoing phase one study for now. We plan still to present the interim phase 1b data in 2024. There will be new initiation of new sites in the remaining part of the 2023. and we provide further updates in upcoming quarterly calls. We also have a plan to give additional clarity on a site expansion in 2024. In regard to PRGN 3005, similarly, we continue our Phase 1B study enrollment at Fred Hutch, and as part of the cost-saving measures, we plan to activate a second site under our CRADA with NCI to continue the advancement of the program without major clinical or CRO costs to us. And that's very, very important for our patients as well as for this program, which is very unique. And with regard to PRGN-3007, obviously that program is investigator-initiated phase one at Moffitt, which is ongoing and continues to move. Now, in regard to what we mentioned for PRGN-2009, especially in a cervical cancer, which is, by the way, on the same platform, adenovirus platform, as PRGN-2012, We are excited to announce that the plan is to activate the NCI site first, and we leverage our CRADA for the phase two study to reduce the clinical cost for this year, and we will be giving update in early 2024 in regard to the other sites. And also, and very important. We have been in discussions with number of parties for non-dilutive funding opportunities, which can even further extend our runway from 2025. We have begun, first of all, the process of a divesting exemplar, and that is important. And I know that Harry will speak to, as we divested, the trans-OVA, and that has allowed us to completely pay off our conversable notes. We are also in discussion, and very exciting discussion, in regard to our AG019 for T1D program with a number of parties, and we are planning to give our investors an update in the upcoming quarterlies. Furthermore, there are ongoing discussions on our Ultra Car T programs for partnerships, and we will be addressing that. And all of this are the means of non-diluted funding opportunities that we have, along with the cash runway that currently we have up to 2025. And we believe that these non-diluted fundings can extend that cash runway much further. So with that exciting update, I'm going to now turn the call over to our CFO, Harry, to discuss the financial update and our strategy.
spk02: Howard. Thank you, Helen, and also thank you to those participating on the call today. I'm going to speak from the notes or the information on slide eight just to focus those on the call. This is a momentous day for Presagen, as Helen has said earlier. Combined with the announced regulatory path for PRGN 2012, we've positioned our balance sheet to provide us the cash runway to successfully transition toward a commercial stage company. As you will see in our financial statements included in our 10Q, which was filed with the SEC earlier this morning, we now retired all of our convertible notes. The retirement of these notes will save us $7 million per year in cash interest costs going forward. In addition, through the efficient early retirement of a significant portion of our convertible notes, we were able to save approximately $8.4 million in cash over the past 10 months. Turning now to discussion around SG&A, since I started with Precision in October of 2021, we've been laser-focused on rightsizing our SG&A costs for the company we are today. And I'm pleased to announce that on a year-to-date basis, compared to the first six months of 2022, our SG&A costs have decreased $5.4 million, or 21%. Just looking at the second quarter of 2023 compared to the same period last year, SG&A costs have decreased $3.4 million, or 27%, showing a positive trend over the first quarter. A portion of these savings were due to past headcount reductions which are now being realized. We finished the quarter with $95.6 million in cash, cash equivalents, and short and long-term investments, providing a basis for a strong, forward-looking cash runway. Taking into account the reprioritization of our pipeline, as Helen has laid out, the elimination of our convertible notes, and continued focus on reducing SG&A expenses, we are now providing guidance on our cash runway into 2025, as Helen has previously mentioned. This extended cash runway is important for our shareholders as it gives us a runway well beyond the pivotal phase two data readout of PRGN 2012 and 2024, and provides us with substantial amount of time to obtain additional funding via non-dilutive methods. I will now turn the call over to the operator for Q&A. Keith?
spk04: Yes, thank you. At this time, we will begin the question and answer session. To ask a question, you may press star, then one on your touchstone phone. If you're using a speakerphone, please pick up your handset first before pressing the keys. To withdraw your question, please press star, then two. At this time, we will pause momentarily to assemble the roster. And the first question comes from Jason Butler with JMP Securities.
spk03: Hi. Thanks for taking the question, and congrats on the progress. A couple on PRGN 2012. Was there any discussion with FDA about the magnitude of benefit and the complete response rate you would need to show in the Phase II portion to support accelerated approval? And then can you just remind us what the patient population was baseline characteristics in the Phase 2 portion look like versus Phase 1, and then I have a follow-up. Thank you.
spk00: Sure. Thank you. Thank you, Jason. So, in regard, obviously, we have had discussions in regard with the complete responses, and we are happy that the FDA has agreed with our endpoints, as I mentioned, as far as the complete responders with the follow-up of 12 months. and the current design of a combination of a phase one, a phase two data for being considered as pivotal for accelerated approval. One of the things that we are very, very thankful and grateful to the FDA leadership is the fact that recognition that our phase two is the exact same design as of our phase one in the same patient population, which are basically minimum of three surgery and above, and both of phase one and two have enrolled patients with the same characteristics. We have the same endpoints. And this is part of the reason that the FDA also has confirmed that we can combine the results from our dose level two of phase one and the phase two, which is all dose level two together. Also, what is also very exciting and in part of the discussions that we have had with the FDA, the possibility to have additional arms done, those are not necessarily part of the confirmatory. It can be additional. That we can expand the label by going to, first of all, patients that they have less than three surgeries, obviously, and as little as one surgery even per year. And also for repeat dosing, one thing that we clearly showed in our data presentation in January, we have the overall 83% response rate in this patient population. 50% of our patients had the complete responses and 33% of our patients reduced their number of surgeries. And FDA definitely recognizes the mechanism of action here and the value of the immunological enhancement of the T cell against the HPV, and has actually encouraged us to have another arm added that we can address those partial responders by repeat dosing, which we are very thankful for that, and I think it's excellent for the future expansion of the label of this drug product. So yes, we have had discussion, and yes, we have agreements And by the way, as I mentioned, and I will mention again, the endpoints for the phase one and phase two and what we have confirmed with the FDA are the same endpoints.
spk03: Great. Thanks, Helen. And then how should we think about repeat dosing in terms of how, you know, the timing after the first dose? Would you wait as long as 12 months or could you actually give a second dose earlier, given that in some of your complete responses, at least, you were seeing it within the six to 12 week timeframe?
spk00: Yeah, excellent question. Definitely, this is something that currently we are discussing with our investigators for this. As you can imagine, the ones that they are, depending on the number of the surgeries, if patients are not complete responders, obviously, they might after finishing the course, which by the way, the course of the treatment here is for vaccination, for treatment. And once that is finished, you can imagine If the patient requires a surgery two months later or so, then this is something that we can obviously, it's not a complete responder, and it will be, at this point, it's considered partial responder or non-responder. And with that, we can design various aspects. And then we can also look at the number of different patient populations. This is all in discussions with our investigators, and obviously as we design those arms, we will be going back to the FDA and also seek further guidance through our breakthrough designation, which is extremely valuable and important to us because it allows us to have a continuous dialogue in a very rapid fashion with the FDA on a number of things, and this would be part of it. So we are looking forward to that. But then again, I want to stress, this is not part of the confirmatory. This is optional for us, and it's actually encouraging that the FDA sees the positive result of this that would like us to and encourages us to even go for the extended repeat dosing.
spk03: Thank you, and congrats again.
spk04: Thank you. Thank you. And the next question comes from Jennifer Kim with Cantor Fitzgerald.
spk01: Hey, good morning. Hi, Jennifer. Thanks for taking my and congrats on a lot of good progress this quarter, especially with 2012. Maybe to start off on 2012, is there a way we should think about the timeline between the positive phase or if there's positive phase two data in the second quarter, starting the confirmatory study and then BLA submission? And I know you just said that the exploratory arms aren't required for BLA submission, but would you want to submit something on that point in conjunction with the submission? Or, you know, what is your thinking currently? And I have a few more after. Thanks.
spk00: Yeah. Obviously, we are laser focused first on getting all of the docs in a row and moving toward the BLA submission. As you know, and we have mentioned, and that's why it's one of the exciting parts, the Phase 1-2, their single arm is an open label. It's not randomized. And as the data comes in, we have the data, and clearly we can start the preparation. We also have a plan through our breakthrough designation to move and ask for a rolling BLA, and this is part of our strategy, so for the rapid. And finally, the last is, as we mentioned, our phase two follow-up will be done by the second quarter of 2024, so we have all the intention to be prepared and move as fast as we can for the submission of our PLA. In regard to the confirmatory trial, clearly our confirmatory trial and part of the agreement is going to be, again, a single-arm trial, very similar to what we have done. And that has to be just initiated, and we are already in the process of that. As you can imagine, there is really not that much discussion around the design of this or what needs to be done. As far as the for the extension of the label and inclusion of the patients with the lower burden of the disease or for the repeat dosing. This is something that currently we are discussing and of the design. Clearly, we will see how that can be done. But the first priority for us is to put the confirmatory in initiate that as we submit the BLA because it's every inch of intention for us to submit the BLA as soon as possible as we know that these patients have no other options and we are looking forward to get this to the commercial path as soon as possible.
spk01: Okay, wonderful. And as you look at the 18-month follow-up data and those complete responders, and you're considering the ability for redosing, how does all of that play into your current thinking about pricing?
spk00: So, yes, we are receiving the data, and we see the data as it goes. Number one, since they are still complete responders and they are in response, they have not required any redosing. So, obviously, that's very exciting, and we are very, very happy for the patients. In regard to the... patients that are partial responders, and we are designing the arm to address the repeat dosing. This is something that we will be addressing, and we will report on what the design would be in the upcoming months, and we will further discuss about the market and pricing at that point, I think.
spk01: Okay, great. And my last question, just on your discussions with parties for non-dilutive opportunities, I think two that you, or two focuses that you mentioned were AG019 and then the UltraCardT platform. I guess when you're talking about this discussion, what type of framework are you working under? Is this more like a research and development collaboration, or is it something where the you know, just trying to understand what the upfront in terms might be to you guys. Thanks.
spk00: Absolutely. So, in regards to the AG019, as you know, we have had the Phase 2 data, positive Phase 2 data, and our group has also prepared for the Phase 3 and manufacturing, commercial manufacturing. However, we had refrain from entering to the phase three because of the prioritization of the program and the cash requirement that the program had. In the past year and a half, it has become very clear in the field that, especially with the approval of some of the antibodies for the antibody for type 1D, and actually in conjunction with the data that we have shown, both as a monotherapy and in combination, that it's actually superior into that treatment. The AG019 has become a center of attention. We are in discussion with a number of parties, and this discussion is not about the research development, I would say, on the level of the AG019 for sure, and it's talking about partnerships. In regard to the Ultracar-T, similarly in view of some of the data, especially on the AML that we have shown and the potential in solid tumors, we are in discussion with a number of parties that it's taken into consideration various type of collaboration or partnership that addresses research and clinical. And we will be reporting, hopefully, in the near future on those. And finally, I think maybe I can add this, even though you didn't ask it, Jennifer. We are also very excited about now we have started the progress on divestiture of our subsidiary exemplar. And I think this will be also very important in providing a non-dilutive solution cash to extend our runway from 2025 to further. So those are all the means that by now extending our cash runway to 2025, not only we get our data readouts, but also it allows the flourishing of these discussions that we have with various partners to come to hopefully reality, and that will even further extend
spk01: Okay, very helpful. Thanks again, guys.
spk04: Thank you. And the next question comes from Arthur He with H.C. Renright.
spk05: Hey, good morning. Thanks for taking my question. There's a technical difficulty. I apologize if the question had been asked before. So... So regarding the 2012 program, I'm just curious from your perspective regarding the efficacy data endpoint. What is the kind of efficacy you think is the approval threshold, and what is the kind of data you think is more commercially favorable?
spk00: I think from a perspective of commercially favorable, as you can see, there is nothing there. There is no other therapeutic that currently exists for this patient except number of surgeries over and over and over again in the lifetime of this. And if you can imagine that if you have this disease from a childhood, it means a lifetime of surgeries and challenges with So, in that regard, we hope to be the first therapeutic on the market for this disease and patient population. In regard to the efficacy, as we have said, we have currently shown what, as far as 50% of our patients from phase one, they are complete responders. One thing that we have discussed with the FDA, and it's very clear, that surgeries alone doesn't lead to the regression of these patients. Because if it was, then all the years that these patients had the surgeries, they should have been cured by now, which unfortunately that is not the case. And therefore, we have the automatic regression It's not there, but even if you consider that it's going to be about 10%, you will be benefiting this patient population, but we are currently standing at 50% response rate. So we are very excited, and by the way, this is a very deep response. Not only we have completed our 12 months of a response, but as I mentioned, from a phase one, our patients' responses, the complete responses are ongoing and none of them have required any CERC.
spk05: Yeah, thank you for the answer. And just to go a little bit deeper regarding the study, during your conversation with the FDA, did they put any color for the pre-existing level of the antibody to the vector? as a screening requirement for the patient? And also, did they make a requirement for monitoring the antibody raised in the body upon their treatment?
spk00: We already had, actually, in our design, we already had immunological readouts, which included both neutralizing antibodies as well as HPV-specific T cells. And actually, FDA very much appreciated that and recognized the importance of these readouts in conjunction with the mechanism of action that we are showing. And one thing I should remind everyone in regard to the Adenoverse platform, again, that as we have shown in previous data, both in regard to PRGEN 2012, but PRGEN 2009, and even in healthy volunteers, there is no prior or very little pre-immunity to the gorilla adenoviruses. And this is the uniqueness of this One other thing that in the data with PRGN 2012 we showed in January is that upon repeat dosing, you would not see increases in a neutralizing antibody, or if there is a slight increase, then it comes down. And therefore, you will not have the issues that you are having with ADD5 and other viruses, which basically limits you to giving this. only once or at best that you can give twice. And we have shown now that data extensively for various drug products that has used the Adenoverse platform both PRGEN 2012 and 2009. And similarly, I will remind everyone that we have shown HPV specific T cells from our phase one PRGEN 2012 as well as phase one in PRGN 2009, which in those settings, the patients that they had HPV cancers, for instance, upon repeat dosing on a monthly basis, we have shown that you can keep enhancing the T cell responses over the years, for instance, that the patients have been on treatment. And again, this is part of the differentiation. of the mechanism of action of this platform versus all the other at-fives, retroviruses, and other platforms that exist there.
spk05: Oh, that's great, Helen. And if I may, I can, if I may, squeeze last question. So regarding the market outside the U.S., what's your current strategy for that? Thanks.
spk00: As we just have confirmed with the FDA, we are moving rapidly with the discussions with the EMA at the same token with the UK and also with Japan currently to basically position PRT in 2012 as a drug product and also on a path for licensure there.
spk05: Thank you. Thanks for taking my question and congrats on the progress.
spk04: Thank you. Thank you. And the next question comes from Ben Burnett with Stateful.
spk06: Hey, thank you very much. And I will throw in my congrats on the progress this quarter.
spk09: Thank you, Ben.
spk06: I want to ask, sticking with PureGN 2012, in the past you've provided efficacy on a number of different endpoints in addition to the 12-month CR rates. I guess, what is kind of the totality of the data that the FDA is going to look at? Are they... are they focused on those other endpoints that you've shown? And I guess maybe how focused are they on durability versus response rate?
spk00: I think, very good question. First of all, part of the endpoints that we put forward, which was very meaningful, was we didn't go for a reduction in the number of surgeries. What we went for upfront and we provided was no surgeries required, and we made that for 12 months, which is quite a long period of time. It was not for three months or six months. And one other thing that we did, which I believe it was seen as a very positive point, was we went to a very severe patient population, which they require three surgeries and higher. So all those elements together, it not only shows the durability of the immune response, especially now that we continue, obviously, following all of our patients, and especially with our responders, we are showing they are well past 12 months, and they continue to be in full response. So that speaks to the durability of that response, that 12-month follow-up and beyond now. On the other hand, the fact that we showed a mechanism of action associated with this. And I think this is, again, was appreciated by the FDA leadership because clearly we have clinical data from the patients that are in full response. that they have generated a specific HPV 6 and 11 responses and that obviously this is due to the treatment as this patient did not have these responses prior to entering to the trial. So I think that has become very, very important. And the fact that the mechanism of action, it relates to the ability to redose with the Adenoverse platform. Again, that's a huge differentiation and difference between us and others because with this, you allow now to give number of, in this case, it's a course of four over 85 days. And by the way, it's subcutaneously given. And it allows, obviously, without having increase neutralizing antibodies or tremendously increase neutralizing antibodies which will hinder usually the T cells and we don't see that at all opposite. It allowed all of that to be considered as the uniqueness of this drug product and also the FDA confirmation for accepting the endpoints that we had plus the immunological markers that we have currently have put in the trials and we are following.
spk06: Okay, excellent. That's very helpful. And I would also like to ask a question around this repeat dosing, which I think is really interesting. I guess, do you have a sense at this point, like how many patients would kind of constitute a relevant database to adjudicate efficacy of repeat dosing and And I'm assuming, would a repeat dosing just be the four-dose course, or would you maybe modify that course in patients that you're redosing?
spk00: Yeah. I think that's a discussion that we have with our investigators. Clearly, you can think of various scenarios for repeat dosing that patients, for instance, after a period of when, if they require surgery and becomes obvious that they are not full responders, then they can receive another course or you can imagine also a situation that this patient received single doses throughout because Again, because of uniqueness of this platform and the fact that you can give it in a repeated fashion as we have done for PRGEN 2009 on a monthly base and we have had patients on the trial that they received this over two years and we had complete responders that similarly they went to very deep responses for over a year after receiving the vaccination with PRGEN 2009. This also can become another scenario that you can be doing on a monthly basis or every three months, and this is the discussions that we have based on the immunological readouts, and we will be designing appropriate arms to address exactly that factor for repeat dosing to address the full population. And you can imagine also this is PRGEN 2012. Clearly, it's extremely important in this RRP. And for us, it's very, very important to address the whole patient population if we can. And we will do that as we also will go into the pediatric population.
spk06: Okay, fantastic. And if I could just maybe squeeze one more just clarification question on the... the updated cash runway, which, by the way, great to hear about the cash runway, and obviously congrats on now fully retiring that remaining debt. Does the updated cash runway include costs associated with this expansion repeat dosing cohort and the confirmatory study, or is that separate?
spk02: It does include, Ben, it does include some of that. Not to the specificity as Helen had said, You know, we're still needing to design that, but there is contemplation of those costs.
spk00: Yeah. Then I can also say that it does include the confirmatory because, again, our confirmatory is a single arm. I want to remind everyone it's not a randomized control phase three. It will be a single arm with a similar exact design as we have done with the phase one or phase two. The extended arms is something that we will be discussed, but that does not have to be initiated prior to BLA, and we can initiate those arms at a later point after the design. So for the purposes of the cost and our runway, we have considered part of our manufacturing. As you can see that we are switching our own manufacturing by reprioritizing our own manufacturing facility to address some of the costs. And it does take to account the initiation of the confirmatory trials.
spk06: Wonderful. Thank you so much.
spk00: Sure. Thanks.
spk04: Thank you. And the next question comes from Brian Chang with JPMorgan.
spk08: Hi, Tim. Thanks for taking my question this morning. From your discussion with the FDA, Have they talked about how long of a safety follow-up do you need in the ongoing study before filing? And then on the preparation work for filing, can you talk about, you know, whether there are any additional preclinical work that you need to tee up between now and filing that you have to work on? And then I have a couple follow-up. Thank you.
spk00: Sure. So in regard to the safety profile, it's similar to the endpoints that we have for efficacy, one-year safety follow-ups, of course, and we will be following these patients regardless as they move on. So those are part of the endpoints, and as we have mentioned, and I will repeat, this product, drug product, has a very favorable effect. safety profile in all of the patients that we have treated. Very, very similar and very favorable. As far as in regard to the preclinical discussions, obviously the preclinical work has been already taken place prior to us going to a phase one, phase two. But obviously as part of any BLA submission, we have to meet all the criteria that the FDA is asking for. This is part of typical of submission for the BLA, which includes, obviously, the Phase II data has to be similar to what we have seen up to this point. It has to meet the clinical endpoints. We also are in discussion with the FDA for manufacturing comparability and using our commercial material in our manufacturing in the confirmatory trial. So those discussions are ongoing. And when we submit our BLA, of course, it has to have all those components in place. for the rapid review and approval, which we are hoping that we will moving towards that very rapid.
spk08: Okay. And then on the manufacturing front, can you elaborate on your commercial readiness? You know, what's needed specifically to prepare on the CMC side? And, you know, at the time of your anticipated launch, what is the capacity that we should anticipate?
spk00: So we have evaluated our own manufacturing facility, which, by the way, provided all of the GMP material that was used in these trials, even during the pandemic time, as you can imagine, because we started the trial of PRGN 2012 in April, I believe, of 2021. So you can imagine our manufacturing had prepared that during the ongoing pandemic, which was very important because at that point, all of the external manufacturing, they were shut down and no one could prepare anything. So that's one of the importance, as I mentioned, why we have decided to move the commercial manufacturing to our own facility and make our facility commercially basically ready for this path and for the licensure path. We will be moving, and our material for the commercial material, as we speak, our teams are working on various aspects of comparability and also production. Since we have produced our GMP material ourselves and the processes are minimally switched We hope that we have a very good comparability profile for manufacturing, which will be obviously presented to the FDA. And we anticipate that we will be ready to launch from our commercial facility here after the approval of our BLA. I should mention that especially within the patient population that is in U.S., we believe our commercial facility has the capability to produce enough doses for that. And also, obviously, after the approval and during this process, we are also looking at further expansions. So with that, we believe that we can be, our facility will be sufficient for production of the doses that is needed into it.
spk08: Great. If I can squeeze in the last one, that would be great. You know, just one on, you know, your overall thinking around the entire R&D portfolio. As you mentioned that there are multiple potential partnerships and divesting opportunities that you currently have on a table. And given that you have a cash runway out to 2025, can you talk about how should we think of how the R&D portfolio will evolve over the next 12 months? And what are the factors that you will take when you think about what to prioritize and what to partner off And thank you.
spk00: Sure, thanks. So very clear, I think, as far as immediate partnership, it's very clear that, and we had announced this previously on AG019, because we believe that this is something that is very exciting. However, Precision does not have the cash requirements to go to extended phase 3s. with this asset, and this is why we have the very active discussions with a number of parties around AG019. In regards to our ultra cars, as I mentioned, especially the PRGN3005, because it's more advanced and from the objective responses, it has the fast track and path to perhaps a rapid regulatory strategy for the AML patients there. We anticipate that the two sites, the Moffitt and Mayo Clinic, have done an excellent job in recruiting, and they will continue to do that, especially in this half of the year. So we will be having the data for Phase 1B in minimum interim data for 2024. Again, this position is not only from a regulatory path and the decisions that have to be made for perhaps a rapid move in that direction, but also in our discussions with groups that right now are interested in the program and in of the program towards the commercialization. The priority of the portfolio, I want to stress this, and I know Harry has stressed, we have now really minimized the costs of SG&A. We have minimized to the limit the extraneous CRO costs. By not opening some of the sites, as we all know in drug development, one of the heaviest costs is your sites that you are initiating, as it requires large cash. By not doing that in an immediate fashion, we are saving to get to the readouts of our PRG in 2012, which is, as I mentioned, Decision of the FDA, why it's so important to us is because it eliminated requirement of a phase three, which you can imagine and appreciate. It would have taken another three or four years just to get to the point of data. And right now, we are basically, first of all, we are seeing our data from phase two as we speak because it's an open trial. And secondly, we will finish the complete follow-up, which is the end point of 12 months that FDA has agreed with, by the second quarter of 2024. So our cash runway is well beyond that, and it allows us to have our readouts and move with our BLA submission. From a non-dilutive fashion, definitely the discussions that we have is very productive and ongoing. And our hope is that will extend our cash runway beyond 2025. One other thing that I have to say, and I'm grateful to the team at Precision for dedication that they have shown. And what we have done, which is not typical to a lot of other companies, is are R&D because of their knowledge, and especially on a side of assay development, immunology, and clinical. They have pivoted, that they have taken a lot of their responsibilities on that side, which we do not need to now hire a tremendous force, retrain, boost time, in order to move rapidly toward the commercialization. And I think that's another strength that Precision has and obviously we are utilizing.
spk08: Thanks, Helen. Thank you.
spk00: Sure. Thank you.
spk04: Thank you. And this concludes the question and answer session. I would like to turn it forward to Dr. Saldivari for any questions and comments.
spk00: Thank you. First of all, I would like to thank you for joining us today. I want to extend our thanks to the patients for participating in clinical trials, our investigators for their dedication and commitment working on studying new therapies for our unmet needs, and to the team at Presagen who have worked so hard over the last several years. As we have discussed today, we believe the PRGN 2012 has a paradigm-changing potential. And with today's announcement of FDA alignment, On a path to an accelerated approval request for our ongoing Phase I-II study, this is an important milestone that brings us a step closer in our transition to a commercial stage company and in realizing our vision of bringing life-changing therapies to patients with unmet medical needs. Given that the Phase I-II is fully enrolled and serves as pivotal, this sets us up for potentially to bring a life-changing first therapeutic option for RRP patients who have been waiting for decades for such an option. Thank you again, and now I return it to operator.
spk04: Yes, thank you. The conference has now concluded. Thank you for attending today's presentation. May now disconnect your lines.
Disclaimer