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spk00: Good day, ladies and gentlemen, and welcome to the TRACON Pharmaceuticals Second Quarter 2022 Earnings Conference Call. At this time, all calls are in a listen-only mode. After the speaker's prepared remarks, we will conduct a question and answer session, and instructions will be given at that time. During this call, we will be making certain forward-looking statements, including statements regarding expected timing of clinical trials and results, regulatory activities, future expenses, and cash runway. our development plans and strategy, and the timing and results of our arbitration with IMAP. These statements are subject to various risks that are described in our filings made with the Securities and Exchange Commission, including our annual report on Form 10-K for the year ended December 31st, 2021, and subsequent quarterly reports on Form 10-Q. You are cautioned not to place undue reliance on these forward-looking statements, and unless required by applicable law, we disclaim any obligation to update such statements. I'll turn the call over to Dr. Charles Thor, President and CEO of Tracon Pharmaceuticals. Dr. Thor?
spk07: Thank you for joining Tracon's second quarter 2022 financial results and business update call. I will begin with an update on our pipeline and then review our recent activities. Following that, Scott Brown, our Chief Financial Officer, will review our financial results for the three and six months ended June 30, 2022. Finally, we will conclude by taking your questions. I'll start with an update on our continued progress with the NVISARC pivotal trial. We have now enrolled more than 36 patients in NVISARC, which is open for enrollment at 29 sites in the US and one site in the UK. Accrual has been robust and is ahead of our estimates that project full accrual of 160 patients dosed at the 600 milligram dose to be completed by end of 2023. This morning, we announced that the IDMC reviewed three weeks of safety data from more than 20 patients and recommended the trial continuous plan at the 600 milligram and the dose. We expect two additional IDMC reviews this year. The second safety assessment that occurs 12 weeks after enrollment of the 20th patient is expected in October. And the interim efficacy assessment that occurs three months following enrollment of the 36th patient is expected in the fourth quarter. During the interim efficacy assessment, the committee will apply a futility rule that requires at least one response in 18 patients in each of the two cohorts at the 600 milligram NVidose. Note an identical futility threshold was achieved at the interim analysis performed last year in 36 patients who received the 300 milligram NVidose. Recall at that time, a significantly higher response rate was observed in lighter weight patients which prompted the IDMC to recommend increasing the ENVA dose to 600 milligrams. As a reminder, the ENVASARC trial includes one cohort who received single-agent ENVA and a second cohort who received ENVA in combination with Yervoy. The primary endpoint in each cohort is objective response rate by resist, as confirmed by blinded independent central review, with duration of response being a key secondary endpoint. In each cohort, the demonstration of nine out of 80 objective responses by central review, or an 11.25% objective response rate, defines the level of response that satisfies the primary objective of the study, which is to statistically exceed the 4% objective response rate of Votrien, the only approved treatment for patients with refractory UPS and MFS. Notably, Votrien is a drug with a black box warning for fatal liver toxicity. We believe ENVA has the potential to transform the care of refractory sarcoma patients through the demonstration of superior efficacy and safety compared to Votrien. Based on data from trials of other checkpoint inhibitors in refractory UPS and MFS, we are targeting a 15% response rate for single-agent ENVA and up to a 30% response rate for ENVA given with Yervoy. Furthermore, We plan to approach the FDA to discuss a BLA filing strategy as soon as we determine nine responses in either cohort. Finally, based on activity already observed in NVSARC, we've applied for a fast-track designation with the FDA and expect a response from the agency later this year. Our second checkpoint inhibitor, YH001, is a potential best-in-class CTLA-4 antibody we licensed from Utrea BioPharma in October of last year. Earlier this month, we submitted an IND application to the FDA for the initiation of a Phase I-II clinical trial of Y8001 in combination with ENVA and doxorubicin for the treatment of sarcoma patients, including patients who have not received prior therapy. As a reminder, we received a broad license to develop and commercialize Y8001 in North American sarcoma and multiple other indications, including microsatellite-stable colorectal cancer, renal cell carcinoma, and KRAS-positive lung cancer. Note, with respect to our license, we can substitute any one of those indications for bladder cancer, endometrial cancer, or melanoma at our election. In these non-sarcoma indications, Y8001 could be combined with existing standard of care agents, including marketed PD-1 antibodies. Our initial Y8001 trial leverages data from two Phase I trials conducted by our partner, U-Cure. These two trials demonstrated the recommended Phase II dose of Y8001 as a single agent and in combination with the PD-1 antibody, toripalamab. Our sponsored Phase I-II clinical trial will evaluate a triplet that includes Y8001, ENVA, and doxorubicin chemotherapy, as doxorubicin is the current frontline standard of care treatment for sarcoma. Following the phase one portion of the trial to assess the tolerability of the combination of the ENVA and Y001 doublet, as well as the triplet therapy that includes doxorubicin, we will assess the response rate in common and rare sarcoma subtypes to combination treatment, with the intent of demonstrating superior response rates compared to historical data using standard of care agents. In leiomyosarcoma and liposarcoma, we plan to compare the response rate of triplet therapy to the historical 10 to 15% response rate of single agent doxorubicin. In the case of rare sarcoma subtypes, like chondrosarcoma and alveolar soft part sarcoma, where chemotherapy is not highly effective, we intend to study the doublet of Y001 and ENVA to assess the response rate compared to the historical response rates with chemotherapy or single agent checkpoint inhibition. One of the purposes of this Phase I-II trial is to determine the subtypes of sarcoma that best respond to the combination of ENVA, Y001, and doxorubicin. Following the potential accelerated approval of ENVA, assuming positive trial results in the pivotal ENVASARC trial, the FDA will require a randomized trial to demonstrate a survival benefit. We expect this Phase III post-approval trial will compare single-agent doxorubicin to the triplet combination of doxorubicin with ENVA and Y001, with PFS at the endpoint. This trial would be expected to enroll patients with UPS and MFS, as well as other sarcoma subtypes shown to respond to triplet therapy based on data from the Phase I-II trial that I described earlier. The ability for TRACON to commercialize two in-licensed immune oncology therapies together in sarcoma is of great strategic benefit. It is important to understand the sales potential in sarcoma with ENVA at parity pricing is not solely the forecasted $200 million in annual ENVA revenues expected in the initial indications of refractory UPS and MFS, as well as the $100 million in annual revenue in rarer sarcoma subtypes where the activity checkpoint inhibition has been demonstrated. Our clinical development strategy is designed to create the opportunity for ENVA to broadly benefit patients with sarcoma in the frontline, adjuvant and neoadjuvant settings by seeking supplemental indications. Moreover, we believe TRACON's total sarcoma-driven sales revenue would be significantly enhanced by marketing Y0001 and ENVA together as part of a treatment combination in sarcoma. In addition to our two checkpoint inhibitors, we are pleased that the National Cancer Institute continues to fund development of our DNA damage repair inhibitor, TRC102. the National Cancer Institute has initiated a randomized phase two trial assessing TRC-102 in stage three, non-squamous, non-small cell lung cancer in combination with chemoradiation. The two-arm trial will enroll 78 patients to assess the benefit of adding TRC-102 to current standard care treatment of pemetrexed, cisplatin, and radiation therapy, followed by a consolidated drivalumab treatment. The primary endpoint of the trial is PFS, and the trial is designed to detect an improvement in PFS at one year from 56% to 75%. Results are expected in 2024. Our fourth clinical stage asset is the CD73 antibody TJ4309 that TRACON is evaluating in a phase one study as a single agent and in combination with a checkpoint inhibitor, Ticentric. We are working to complete data analysis of the trial which has enrolled the last patient. As a reminder, IMAP has indicated the desire to exercise their option to terminate the TJ4309 license following completion of the Phase I trial for a payment to TRAC of $9 million. While we expected the study would be completed by the end of the second quarter, we are awaiting results of the final clinical sample testing that we now expect will be completed this quarter. This then triggers IMAP's option to reacquire TJ4309 for $9 million. Next, I will provide an update on our legal disputes with IMAP. As a reminder, IMAP commenced arbitration in June 2020 after TRACON invoked contractual dispute resolution provisions asserting that IMAP had breached its contractual obligations concerning both of our agreements entered into in November 2018. We filed counterclaims in the arbitration seeking to recover over $200 million in damages from IMAP based on the alleged breaches. Under the applicable rules of the arbitration, the prevailing party may also be awarded attorney's fees at the tribunal's discretion. In February of this year, arguments for alleged breaches of both of our agreements with IMAP were heard before an International Chamber of Commerce arbitration tribunal under New York law, and the final post-hearing briefs were submitted to the tribunal in late May. On June 2nd, the International Court of Arbitration of the ICC notified us to expect a final decision by September 30th, although the tribunal may ask the ICC for a further extension if warranted. The claims under the arbitration are complex. Accordingly, we cannot predict the outcome of the arbitration, and we are unable to estimate the amount of recovery of damages, if any, that may be awarded by the tribunal. Depending on results of the arbitration, we continue to meet our obligations under the terms of both agreements. We will promptly provide an update when the tribunal panel announced their findings. Given the challenging capital markets, the expectation to secure non-dilutive capital from our corporate partners is important. In the meantime, we recently secured capital through another source. In June, our largest shareholder, Opelai, purchased $4 million in common stock and pre-funded warrants at market price without the issuance of common warrants. Capital from this transaction extends our cash runway into the first half of 2023. Our runway would be further extended by the $9 million payment expected later this year from IMAP related to the stated intent to reacquire TJ4309 following completion of the Phase 1 trial and would be further extended through any arbitration award. As we have noted in the past, we expect to further supplement our CAST position through opportunities for non-dilutive capital enabled through our CRO independent product development platform that we believe positions us as one of the most efficient clinical development organizations. We expect to continue to leverage our platform in two ways that provide for potential non-dilutive capital to TRACON. First, we are evaluating drug candidates whereby TRACON performs clinical trials at a lower cost than a CRO but still at a premium to our costs using a pay-for-performance model that track on further benefits by earning a share of the revenue, including sub-licensing fees and our royalties from commercialization. This is an aligned structure we used in the past, for example, with Johnson & Johnson. Second, we are exploring a franchise model whereby we are paid to share our proprietary capabilities and know-how to enable another company to independently internalize clinical operations and use these new capabilities to avoid contracting with CROs to execute clinical trials. As has been the experience at TRACON, such an investment would be expected to result in substantial time and cost savings for our partner. We believe that over time, our product development platform has earned strong credibility as a compelling solution for companies who wish to become CRO independent and reap the rewards of conducting trials faster, at higher quality, and at lower cost compared to trials typically contracted to CROs. At this time, Scott will provide an update on our financials.
spk02: Thank you, Charles, and good afternoon, everyone. TRACON's research and development expenses were $2.9 million and $5.9 million for the three and six months ended June 30, 2022, respectively, compared to $3.1 million and $5.4 million for the comparable periods of 2021. The increase in the six-month period was primarily related to additional enrollment in the Pivotal and the SARC trial. General and administrative expenses were $3.3 million and $9.8 million for the three and six months ended June 30, 2022, respectively, compared to $6.1 million and $8.8 million for the comparable periods of 2021. The decrease in the three-month period was due to the lawsuit filed in Delaware Court of Chancery by IMAP in 2021, and the increase in the six-month period was primarily related to legal expenses in connection with the arbitration hearing with IMAP in February of this year. We expect G&A expenses to decrease significantly for the remainder of the year as the arbitration hearing is now complete. Our net loss was $6.2 million and $15.7 million for the three and six months ended June 30, 2022, respectively, compared to $8.9 million and $14 million for the comparable periods of 2021. Turning to the balance sheet, at June 30, 2022, our cash and cash equivalents totaled $13.6 million, compared to $24.1 million at December 31, 2021. We expect our current capital resources to be sufficient to fund our planned operations into 2023. With that, I will turn the call back over to Charles.
spk07: Thank you, Scott. As you have heard, our corporate strategy is proceeding as planned. Allow me to recap with five key events we expect this year. First, We expect to report the IDMC interim efficacy assessment for the two ENVASAR cohorts at the 600 milligram dose of ENVA. Second, we expect to dose the first patient in the Phase 1-2 trials of our potential best-in-class CTLA-4 antibody Y8001 in combination with ENVA and doxorubicin as a potential first-line treatment for sarcoma. Third, we expect to further leverage our unique product development platform to provide TRACON non-dilutive capital in exchange for enabling companies tired of being beholden to CROs to potentially benefit from our capabilities and realize for themselves the substantial time and cost savings we enjoy at TRACON. Fourth, we expect to complete the TJ4309 Phase 1 trial, permitting IMAP the opportunity to exercise their stated desire to terminate the agreement for a payment to TRACON of $9 million. Fifth, we expect to report the arbitration panel's binding decision, including potential damage awards regarding our legal disputes with IMAP. As Scott indicated, our current cash run rate extends into the first half of 2023 and past each of the five key upcoming milestones, including expected non-dilutive capital from an existing partnership. Thank you for your time and attention, and we are now available to answer your questions.
spk00: Thank you. To ask a question, you will need to press star 11 on your telephone. Please stand by while we compile the Q&A roster. Our first question comes from Mario Raycroft with Jefferies. Your line is now open.
spk01: Hi, Charles. Thanks for taking my questions and congrats on the progress. First question I was going to ask is just for checking the box on the 70 original patients in MVSARC at the lower dose. Can you say what proportion of those patients have been titrated up to the 600 mg dose? And to clarify, would those data be disclosed along with the final analysis for MVSARC?
spk07: Hi, Maury. Thanks for the questions. As you pointed out, we treated 70 patients with an initial dose of 300 mg of Envifolumab, and then once The amendment to dose at 600 milligrams was approved at each individual site. Those patients that were on study at that time were able to dose escalate to 600 milligrams. You know, I can't give you exact numbers, Maury, but many patients have dose escalated from 300 to 600 milligrams. And so really they're going to be, in terms of the final data, if you will, The primary endpoint, to be clear, is being assessed with respect to the 600 milligram dosing patients, meaning the patients who started the trial at 600 milligrams. There will be 80 patients that received ENVA 600 and 80 that received ENVA plus Urovoi with ENVA 600. And that's the primary data set for the primary outcome. But there will be additional data in 70 patients dosed at 300 milligrams initially and a subset of those that escalated to 600. Those are the three data sets, and all those will be part of the filing for the expected approval of the drug, with the 70 patients, including those that dose escalated to 600, being a supportive data set. But I can't give you exact numbers in terms of the categories within the 70 that dose escalated to 600.
spk01: Got it. Okay, understood, and that's helpful. And I also wanted to ask a question about the Phase 1-2 with ENVA, YH-001, and Dr. Rubison. Do you plan on reporting data after the Phase I portion is completed? And can you remind me if you see potential for an accelerated approval path based on the Phase II? Great questions, Maury.
spk07: With respect to the trial, we do expect to provide data following completion of the Phase I. This is not a registrational trial, so it's different with respect to the design than is the NVISARC trial, which is, as you know, a pivotal study. We will plan to report data at the conclusion of the Phase I portion, and then also each of the four Phase II cohorts may enroll kind of at different paces, if you will. There are two common sarcoma subtypes and two rarer ones, so we'll report the Phase II data kind of as it comes out per cohort. You know, you ask an interesting question. I mean, we are dealing with respect to the Phase II portion of the study with some very underserved subtypes of sarcoma. You know, we're not planning this phasal entry trial as a pivotal study, to be clear. But if there's very promising data, you know, there is a possibility of bringing up discussions with the agency to meet what are incredible unmet needs within these patient populations. But at the outset, this is not planned as a pivotal study. But that said, you know, data will dictate our approach to interacting with the agency around very promising data, if that were to be the case.
spk01: Got it. That makes sense. And for advancing into the frontline phase three, can you talk about some of the gating factors that you're going to be looking for in the phase one, two prior to starting that phase three?
spk07: Sure. I appreciate the question, Maury. So each of the four phase two cohorts, so leiomyosarcoma, dedifferentiated liposarcoma, chondrosarcoma, and alveolar soft part sarcoma, each have a separate, if you will, endpoint, meaning a targeted objective response rate they were looking to hit that would be clearly superior to the objective response rate seen with single agent chemotherapy with doxorubicin. So if all four hit that targeted response rate, which is our goal, then we'd enroll all four of those subtypes in addition to UPS and MFS in that potential phase three trial.
spk01: Got it. And last question and then I'll hop back in the queue. I'm just wondering if you have insight into UCURE data updates for YH-001 that could happen this year or next year, and will one or two of those updates be relevant to TRACON that we should be looking for?
spk07: Yeah, I think the most recent update, you know, UCURE did present data at ASCO with the combination study of Y001 with toripalamab. I thought it was very encouraging data, both from a safety perspective, but also from an efficacy perspective where there were several responses across multiple solid tumor types. We could see some additional data from the single-agent trial. That is also a Phase I study. Remember, there were two Phase I studies they did, the combo with toripalimab and then the single-agent study. So we might see an update on the single-agent data. I think with respect to further updates on the combination trial, I think the ASCO poster actually was fairly complete with respect to the patients that have been enrolled. So we were pleased to see that updated report and encouraged by both the safety and efficacy that was reported at ASCO this year. Got it. Okay.
spk01: Thanks for taking my questions. Thank you, Maury.
spk00: Thank you. Our next question comes from the line of Ed White with HC Wainwright. Your line is open.
spk03: good afternoon thanks for taking my questions so uh charles just want to change gears here a little bit and ask you a little bit about your um cro independent clinical development program and capabilities there um are you how does it work with the franchise model has there been any company that's been interested so far and how long would a process take to get that technology or in know-how over to a separate company?
spk07: Hi, Ed. Thanks for the question. We have generally explored the franchise model in the following manner. There are companies that right now have a significant pipeline. And if they have a significant pipeline, in our view, they're paying an exorbitant amount of their their operational expenses to fund those trials, running them through a CRO using the fee-for-service plus guaranteed monthly payment model that, frankly, is not the best use of capital. We feel those companies were to adopt our franchise model, they could run their trials at half the cost or even potentially lower of what they're paying a CRO. So you can appreciate that the ideal company for this type of model is one that has a pipeline of say more than one product in one trial. But for that company, learning our systems would be transformative in terms of the capital they would save, the time they would save, and frankly we also think the quality would be better. Now in terms of identifying that company, we have identified let's say a handful of companies, just a couple I think is kind of how we look at it. initially focus on one company because it is a major undertaking for both us and the company. It's going to be something, it's something, for instance, Tracon adopted over 10 years. But with respect to that company, we do feel that if they intensely invested in this program, within six months, they would be running their own trials. It could be phase one, it could be phase two, it could be phase three. They would be saving incredible amounts of capital. and they'd be engaged in a process, much like TRACON, where we feel they could save a year per phase of development. So a year on each phase one, phase two, and phase three trial, such that if an overall program goes to market, they potentially could save three years on the process of developing their drug. So that should give you, I think, a general idea of how we're thinking about it, why it appeals to certain companies, and why it takes a special company that we want to, if you will, teach this franchise model initially And once that company learns it, then we would kind of move on to another company. But our goal is to really transform the industry, help more people reap the advantage we have by being CRO independent.
spk03: And from a timing standpoint, do you think you'd be more likely to do a franchise model first or you're paid for a performance model? It sounds like that would be an easier sell.
spk07: I think that's a great point, Ed. I mean, I think the nice thing about the pay-for-performance model is that we've done that. For instance, with Johnson & Johnson, we've executed around that model. And it's a lot easier for the company that collaborates with us through pay-for-performance because they don't have to learn our systems, right? They're saying, please work with us. We'll give you the molecule. You take it through the trial. And then it's still Our partners' molecule, they still have commercial rights. We share in the revenue from that commercialization. But from our partners' point of view, it's not much more work than if they hired a CRO. The advantage is it's cheaper for them, it's faster for them, and we also feel the quality of our work is better. But it doesn't require a big investment of their time to learn systems de novo, which the franchise model does. So to your point, Ed, I think continue to execute around the pay-for-performance model which is something that we've done on more than one occasion, would make the most sense in terms of what would get done in the sooner timeframe.
spk03: Okay. Thanks, Charles. And one last question, if I may. Just on the 4309, what is the definitive last thing that needs to be done in order for IMAD to terminate the license and pay the $9 million?
spk07: Yeah, it really is. Completing the phase one study is really analyzing some clinical samples, which we expect to be able to complete this quarter, and then that would trigger the opt-in.
spk03: Okay, Charles, thanks for taking my questions.
spk07: Thank you, Ed. Much appreciated.
spk00: Thank you. Our next question comes from Sumit Roy with Jones Research. Your line is now open.
spk05: Hi, everyone, and congratulations on all the progress. If I may ask one question on the NVIRSAR trial. So year-end when you're going to present interim data from the 36 patients, what do you expect the duration on drug would be? Are we going to be in a similar situation as last year where most of the patient won't be around 24 weeks where we mostly see the responses happen? So any color on that would be appreciated.
spk07: No, I appreciate the question, Shoman. It is a bit like last year in the sense that with respect to this year at the 600 milligram dose, we were dosing patients by first quarter. So there's a potential for patients to be on drugs as long as say 11 months, if you were to say to go to the very end of the year. In terms of the minimum time on study is three months. So I'd say anywhere between say three and say 10 months or so would be the maximum time a patient would be on therapy. As is the case last year, we're going to report and do the analysis. It's a preliminary response rate, knowing, to your point, not every patient responds on the first or second CT scan. We know that for a fact, especially with combination checkpoint inhibition, that many patients won't respond, to your point, until, say, 24 weeks or thereafter. So our goal is to clearly see activity in both cohorts. We need to see at least one response per the futility analysis. It would be nice to see a double digit response rate, even at this early analysis, knowing that that response rate likely would grow, and it could grow significantly, based on what you pointed out, that many responses in sarcoma to IO therapy take more than just three months to develop.
spk05: So would you say at least half the patients will have six months on drug, or less than that?
spk07: Well, you know, we announced the 36th patient was enrolled as of July. So, you know, those patients, and we did see, I'd say, a nice amount of accrual, you know, in the last three months. So, yeah, I think a lot of patients will have three months on therapy. You know, there will be a segment that will have six months, and then that rare segment will have, say, nine months potentially. Yeah, I would say a lot of patients will have, if you will, just two scans. Maybe the third scan will get done before we actually have the DMC meeting, but it's gonna be in that kind of ballpark showman, if you will.
spk05: Okay, no, that's really helpful, thank you for that. And one last question on the, when you're starting the frontline trial in sarcoma, I was under the impression that it would not be UPS, MFS, and it would focus more on well-differentiated or leiomyosarcoma so that it doesn't compete with your current second-line or relapsed refractory.
spk07: No, you're exactly right, Shoman. No, no, you're exactly right. So, the Phase I-II trials, to be clear, those are enrolling patients with sarcoma that does not include MFS and UPS. So, to your point, we will not cannibalize enrollment into the ENVISARC trial. What is expected to happen is that once the Phase 1-2 trial is done and NVSARC is done, when we start that Phase 3 study, which will be the post-approval commitment study, that that would then enroll UPS and MFS because NVSARC will be fully enrolled and also include other subtypes, including the subtypes that would enroll in the Phase 1-2 trial where we see activity of that triplet therapy.
spk05: Got it. And you are not having any enrollment criteria on the TPS score, or would you... get only greater than 5%.
spk07: Yeah, so for sarcoma, in the Phase 1-2 study, we're enrolling by histology. We will do post-hoc analyses looking at biomarkers, including PD-L1 expression, including, for example, what's called the sarcoma immune class. We'll do post-hoc analyses looking at biomarkers, including PD-L1 expression, including, for example, what's called the sarcoma immune classification. to see if there's a possibility of selecting patients based on a biomarker. That would be a post-hoc analysis based on the Phase 1-2 trial. But if that is highly informative, it's possible that the Phase 2 trial could also include biomarker-enriched enrollment. So all those are to be determined based on the results of the Phase 1-2 trial.
spk05: And thank you so much for taking the questions, and congratulations again on all the progress.
spk07: Thank you, Sherman. Appreciate it.
spk00: Thank you. As a reminder, to ask a question at this time, please press star 1-1 on your touch-tone telephone. Our next question comes from Nick Abbott with Wells Fargo. Your line is now open.
spk06: Good afternoon. Thanks for your questions, and congrats, Charles and the team. First one, Charles, can you just elaborate on the FAST-TRACK application? Is that ENVA, ENVA plus U of OE, ENVA plus YH001? What does that cover?
spk07: Sure. No, I appreciate the question, Nick. Yeah, the FAST-TRACK application is for Envifolumab based on activity we've seen as a single agent. So our expectation is to gain FAST-TRACK status for Envifolumab that would then facilitate the expected NVSARC pivotal trial filing or the filing based on the NVSARC pivotal trial data. And we do expect to receive that designation later this year.
spk06: And is that, presumably that's the activity you've seen outside of cohort C and D? This is from the phase one, I mean, I think you've got orphan drug based on clinical activity. So in, instead of all, I'm not saying it implies that you haven't seen activity for the combination, but what about the combination of it?
spk07: No, good question. You know, with respect to Fast-Track, it's really more pertinent. I'd say the data is more pertinent to single-agent activity just because you can definitively say that's your drug. So, to your point, we saw single-agent activity in sarcoma in phase one in the alveolar soft part sarcoma, which was really important in terms of securing orphan drug designation. And then we saw single-agent activity at 300 milligrams in the Envisarc trial. Again, with that activity significantly more evident in the lighter weight patients. So, Based on the single agent activity we've seen in phase one and also in Envisarc, even at the lower dose, we feel there's clear evidence of single agent activity that we feel will be sufficient to secure fast track designation.
spk06: Okay. And then how does that play with, you know, your prior comments on seeking breakthrough therapy designation?
spk07: Yeah, no, great, great question. So, you know, breakthrough therapy designation is a higher hurdle, and so we would await the results of the interim analysis end of the year as the basis for considering a breakthrough application. Just because that is clearly a higher hurdle, and we don't have enough data at this point until we do the interim analysis end of the year to consider an opportunity like that.
spk06: Okay. And then, I've asked this before, obviously the opportunity to to broaden the Envifolimab license. Where are you on that? And as you think about this franchise model, is there an opportunity to sort of do some horse trading that you might be able to broaden Envifolimab in return for a franchise?
spk07: You know, that's a very perceptive question, Nick. I would say just in general, we remain incredibly interested in expanding the field of use for Envifolimab. And we would definitely entertain, you know, offering our expertise in terms of running clinical trials in order to do that. So still a high priority for our company is to expand the field of use for Envifolimab.
spk06: Okay. And you kind of mentioned right at the very end, you know, the franchisor raising non-polluted capital. And you said from an existing partnership. And I think you sort of outlined, I think it was Ed's question earlier, you know, what what some of this entails, but do you feel confident that you might be able to land either a franchisee this year or secure at least one development opportunity?
spk07: It's definitely one of our goals for the year. Nick, to the earlier question, I think it's probably much more likely that we'd engage in the pay-for-performance model that includes the revenue share just because that's an easier idea to understand for a potential partner and something we've executed multiple times before. But that is an important corporate goal for us this year.
spk06: Okay, thanks. And then just to add to that, I know you've spent some time describing the YHO-1 trial, but can you just outline again the steps in order, you need to get there in order to get to the first-line patients and, you know, what, you know, when we might see data from that stepwise approach. Yeah.
spk07: Sure, sure, Nick. Yeah, so the study is a Phase I-II trial, and we expect to initiate dosing this year in the Phase I portion. You know, I don't think the Phase I portion will take that long because we have the advantage that our partners have already completed two Phase I trials, but We want to just make sure that the dose of Y0 is when we select is not only tolerable with Envifolumab, but also with doxorubicin. But once we establish that dose, the Y0 is one that's tolerable with Enva 600 and standard dose doxorubicin, the phase two portion will dose frontline patients, including frontline patients with Lyme or sarcoma and de-differentiated liposarcoma, which are two of the major classifications of sarcoma. That, I think, is exciting. Those patients right now are getting doxorubicin chemotherapy or maybe a couple chemotherapeutics together with doxorubicin. We will be giving them the opportunity to get dual checkpoint inhibition with dox as frontline therapy, and I think that's going to be really exciting. Investigators are excited because of that prospect, as are we as a company.
spk06: So you take that. That's a realistic objective for next year is to get into phase two.
spk07: Yes. Yeah, exactly right, Nick.
spk06: Last one for me. I think when you did the Y8001 license, you talked about perhaps starting a solid tumor trial later this year, and I think renal cell was high up on your list. Is that still a goal for this year?
spk07: That's still a goal for the program. I don't think we'll start that this year, Nick, but that is a goal for the program. That would be a goal for 2023 is to begin investigation of a non-sarcoma indication once we get the sarcoma study up and running.
spk06: Okay, perfect. Thanks, y'all.
spk07: Appreciate the questions, Nick. Thank you.
spk00: Thank you. Our next question is a follow-up from Mari Raycroft with Jeffries. Do you want to open it?
spk01: Hi, thanks for taking the follow-up question. I just wanted to ask one about the $200 million in damages related to 4309 arbitration. I'm guessing you can't say too much about your specific case, but are there good proxies or analogs as it relates to your case that support, number one, the claim for $200 million in damages, and then number two, I guess, how much was rewarded in those other proxy cases? Hi, Maura.
spk07: I appreciate the question. I can't say a ton about arbitration because it is a confidential proceeding. And yeah, I think that's the other problem with thinking about proxies. A lot of times arbitration is confidential as opposed to, say, a lawsuit in a public court. You know, I would just point out that the arbitration damages that we seek relate not just to TJ4309, but also to the Biospecific Antibody Agreement, which As you recall, you know, it was an agreement whereby TRACON was to be provided five bisectant antibodies over the course of, or we were able to pick five bisectant antibodies over the course of five years and had the option to acquire rights to any or all of those bisectant worldwide outside of Korea and China. And we felt that was a very valuable agreement to us. And that's reflected in some part as well as the TJ409 breach in the award that we talked about. The only thing I could just point out is by pipeline access, again, we feel is very valuable. And I think if you were to evaluate deals done by pharma companies to get that type of access, those are deals that are valuable as indicated in the public announcements. That's maybe a proxy to think about, but I can't go into details regarding the arbitration itself. Got it.
spk01: Understood. That makes sense. Okay. Thank you. Thanks again. Thank you, Maury. Appreciate it.
spk00: Thank you. Our next question comes from the line of Joel Beattie with Baird. Your line is now open.
spk04: Hi, great. Thanks for taking the questions. The first one's on the Fulimab. Can you discuss the confidence now in the 600 milligram dose level? And is it, you know, pretty much based on what was learned, you know, before starting this new cohort? Or are there additional learnings either from this cohort or from the patients that were escalated from 300 to 600 in the previous cohort that, you know, could help add to the confidence?
spk07: Sure, John. I appreciate the question. escalated from 300 to 600 milligrams at the advice of the IDMC when they noted that there was clearly significantly higher activity in lighter weight patients. And because it's a flat dose, if we double the dose, we give every patient the optimal chance to respond irrespective of their body weight. And I think what we've learned going to 600 so far is that the drug has been very safe. And I think that was reflected in today's announcement when the DMC evaluated more than 20 patients' worth of data at the higher dose. And I would point out that that's not surprising. We know from phase one testing that this drug was dosed at even fourfold higher doses than 600 and was shown to be tolerable. So it's nice to confirm that the 600 milligram dose is safe and And that, again, is not an unexpected announcement. You know, in terms of activity, you know, we knew in phase one that patients that responded to sarcoma in phase one had the equivalent of the 600 milligram dose. So that was useful data to understand why that's a logical choice to increase two once we saw the increased activity in the lighter weight patients. You know, in terms of 300 milligrams to 600 milligram dose escalation, I'd point out that that happened based on the decision already to go to 600. So we will have data on those patients. As I mentioned, that'll be part of the supplemental data to support the expected BLA, but those data actually didn't inform our decision to go to 600 because that decision was made before the dose escalation happened in those individual patients. And the dose escalation is really based on the clear activity we saw at that dose level in phase one, the fact that it was expected to be safe, the fact that the 600 milligram dose is higher even than the dose approved in China that showed a very robust response rate in MS by high cancer. And so those were all factors that made the 600 milligram dose logical to move to in Embisark.
spk04: Yeah, yeah, that makes sense. And then a question on expenses. I just think about them over the next couple of quarters as, you know, it seems like clinical trial activity could be increasing while the legal dispute may be winding down.
spk02: Yeah. Thanks, Joel. This is Scott. So, on the G&A side, you know, we do expect expenses to continue to come down. You know, our normal baseline is around $2 million a quarter. So that's what we would expect in the low $2 million range for the second half of this year and even in the first part of next year, assuming no additional legal expenses related to the arbitration. And then on the R&D side, we'd expect similar to the first half of the year in around $3 million a quarter with probably small increases due to additional enrollment and the YH001 trial getting up and running, but nothing too much above, you know, kind of a low to mid $3 million a quarter.
spk04: Great. Thank you. Yep.
spk02: Thank you, Joel.
spk00: Thank you. And I'm currently showing no further questions at this time. I'd like to turn the call back over to Dr. Thurber for closing remarks.
spk07: Well, I just wanted to thank the listeners and thank you especially to the analysts for your questions. We look forward to updating you later this quarter. Have a good day.
spk00: Thank you for participating. You may now disconnect.
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