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spk00: good afternoon this is the operator today's conference call is scheduled to begin momentarily until that time your lines will be placed and hold thank you for your patience once again today's conference call is scheduled to begin momentarily until that time your lines will be placed and hold thank you for your patience Good day, ladies and gentlemen, and welcome to Tracon Pharmaceuticals' first quarter of 2022 Earnings Conference Call. At this time, all callers 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 today's 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 runaway in our development plans and strategies. 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 31, 2021, and subsequent quarterly reports on Form 10-Q. Your caution not to place undue reliance on the on these forward-looking statements, and we disclaim any obligation to update such statements. Now, I would like to turn the call over to Dr. Charles Tuor, President and CEO of TRACON Pharmaceuticals. Dr. Tuor?
spk07: Good afternoon, and thank you for joining TRACON's first 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 months ended March 31st, 2022. Finally, we will conclude by taking your questions. I'll start with an update on our continued progress with the ENVASARC pivotal trial. Recall that in December 2021, the Independent Data Monitoring Committee recommended doubling the ENVA dose to 600 milligrams after noting that ENVA dosed at 300 milligrams was well tolerated and demonstrated a significantly higher objective response rate in lower-weight patients. This recommendation was incorporated into an amended protocol that was submitted to the FDA in January, approved by the FDA in February, and then approved by internal review boards or ethics committees at each of the 30 NVISARC sites, including 29 sites in the U.S. and one site in the United Kingdom. We believe the short timeframe between amendment submission in January and and amendment approval by April at each of the 30 clinical sites is another demonstration of the value of TRACON's CRO-independent product development platform that permits highly efficient interactions between TRACON and the sites that conduct our trials. We also noted in April that more than 10 patients had initiated treatment at the 600 milligram ENVA dose. ENVASARC enrollment continues to be brisk. And as a result, we expect to report on three key interim data monitoring committee assessments this year. First, we expect to report two safety assessments in mid-2022 at three weeks and 12 weeks following enrollment of the 20th patient. In the second half of this year, we expect to report on the interim efficacy assessment three months following enrollment of the 36th patient to allow for an assessment of the preliminary response rate. At that time, the Data Monitoring Committee will apply a formal futility rule that requires at least one response in 18 patients enrolled into each of the two cohorts at the 600 milligram ENVA dose. As a reminder, the ENVA-SARC trial includes one cohort who receives single-agent ENVA and a second cohort who receive ENVA in combination with Urovoi. 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 a 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 your boy. Furthermore, we plan to approach the FDA to discuss a BLA filing strategy as soon as we determine nine responses in either cohort. Our second clinical stage immune oncology asset is YH001, a potential best-in-class CTLA-4 antibody licensed from Ucare BioPharma in October last year. As a reminder, we received a broad license for YH001 to develop and commercialize in North America in sarcoma, and multiple other indications, including microsatellite-stable colorectal cancer, renal cell carcinoma, and KRAS-positive lung cancer. Though 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, Y001 could be combined with existing standard of care agents, including marketed PD-1 antibodies. Our initial development plan for Y001 is to initiate a clinical trial in sarcoma in combination with ENVA in the second half of this year. Importantly, we can leverage data from two completed Phase I trials of Y001 performed by our partner, Ucure, to inform our dosing strategy. These two trials determine the recommended Phase II dose of Y001 as a single agent and in combination with the PD-1 antibody, toropalimab. We intend to initiate a Phase I-II clinical trial studying a triplet that includes Y001, ENVA, and doxorubicin chemotherapy, as doxorubicin is the current frontline standard of care treatment for sarcoma. Following the Phase I portion of the trial to assess the tolerability of the combination of ENVA and Y001 doublet, as well as the triple therapy that includes doxorubicin, we will assess the response rate of 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. For example, in leiomyosarcoma, we plan to compare the response rate of triple therapy to the historical 15% response rate of single agent doxorubicin. In the case of a rare sarcoma subtype like chondrosarcoma, where chemotherapy is not effective, We plan to study the doublet of Y001 and ENVA to assess the response rate compared to historical response rates of less than 5% with standard of care treatments. One of the purposes of this Phase I-II trial is to determine the subtypes of sarcoma that respond best to the combination of ENVA and Y001. Following the potential accelerated approval of ENVA through the ENVASARP 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 triple combination of doxorubicin with ENVA NY001 with PFS as the endpoint. This trial would be expected to enroll patients with UPS and MFS as well as other sarcoma subtypes shown to be responsive to triple 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 will be of great strategic benefit. It is important to understand the sales potential in sarcoma with ENVA at parity pricing is not just the forecasted $200 million in annual ENVA revenues from the initial indications in refractory UPS and MFS. Our clinical development strategy is designed to create the opportunity for ENVA to broadly benefit patients with sarcoma in the front line, adjuvant, and neoadjuvant settings by seeking supplemental indications. Moreover, we believe TRACON's total sarcoma-driven sales revenue should be further enhanced by marketing Y001 and ENVA together as part of the same treatment combination in sarcoma. While development in sarcoma is straightforward due to the lack of any approved immunotherapies, we also see a path forward for Y001 in other indications where there is clear evidence of activity with dual checkpoint inhibition. For example, the combination of Opdivo and Yervoy is approved for the first-line treatment of intermediate and high-risk patients with advanced renal cell carcinoma. However, our discussions with key opinion leaders indicate that most patients receive front-line treatment with a PD-1 antibody and a VEGF inhibitor rather than with Yervoy. Therefore, we believe the unmet medical need in advanced renal cell carcinoma patients is in the PD-1 refractory setting. Data presented at ASCO indicate that PD-1 refractive patients can be resensitized to immunotherapy, and we expect to evaluate Y8001 in this line of treatment. This strategy of second-line dual-checkpoint inhibition may be relevant for many tumor types where PD-1-directed treatment is given in combination with chemotherapy or a VEGF inhibitor, but without your boy in the frontline setting. In addition to our two checkpoint inhibitors, we are pleased the National Cancer Institute continues to fund development of our DNA damage repair inhibitor, TRC102. In February, the NCI initiated a randomized phase two trial assessing TRC102 in stage three non-squamous, non-small cell lung cancer in combination with chemoradiation. The TUMAR trial will enroll 78 patients to assess the benefit of adding TRC102 to current standard of care treatment of pemetrexed, cisplatin, and radiation therapy, followed by consolidated dervalumab 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%. Enrollment is expected to begin this year, and results are expected in 2024. Our fourth clinical stage asset is the CD73 antibody TJ4309 that TRACON is evaluating in a Phase I study as a single agent and in combination with the 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 their desire to exercise their option to terminate the TJ4309 license following completion of the Phase I trial for a payment to TRACON of $9 million, which is expected later this year. Next. Next. I will provide a legal update on the two disputes which are in arbitration with our corporate partner, IMAP. As a reminder, in February this year, arguments for alleged breaches of both of our license agreements with IMAP were heard before an International Chamber of Commerce Arbitration Tribunal under New York law. As we have noted in the past, in March 2020, IMAP issued a press release announcing a strategic partnership with KG Bio whereby KGBio received what the press release described as a right of first negotiation for exclusive rights to commercialize TJ4309 in multiple Asian, African, and Middle Eastern countries for up to $340 million in potential payments to IMAP. We believe that based on the KGBio license, TRACON was entitled to receive a payment at that time under the TJ4309 agreement, although IMAP has disputed that this payment is due. The other dispute with IMAP regards our bi-civic antibody agreement with them. The disputes in this agreement include issues related to IMAP's two license and collaboration agreements with ABO-Bio in July 2018 that preceded our agreement with IMAP in November 2018. As of today, the GJ4309 agreement and bi-civic antibody agreement disputes remain under post-hearing consideration by the tribunal and we have been guided to expect their binding decision later this year. Pending 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 announce their findings. Given the challenging capital markets, the expectation to secure non-dilutive capital from our corporate partner is important. and may be further supplemented by opportunities for non-dilutive capital enabled through our CRO-independent product development platform that we believe makes us 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 premium to our costs, and TRACON then earns a share in the revenue including sub-licensing fees and or 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 other companies 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 therefore reap the rewards of conducting trials faster, at higher quality, and at lower costs than those trials typically contracted to CROs. At this time, Scott will provide an update on our financials.
spk01: Thank you, Charles, and good afternoon, everyone. TRACON's research and development expenses were $3 million for the first quarter of 2022, compared to $2.3 million for the comparable period of 2021. The increase was primarily related to additional enrollment in the pivotal NVSARP trial. General and administrative expenses were $6.5 million for the first quarter of 2022, compared to $2.7 million for the comparable period of 2021. increase was primarily related to legal expenses in connection with the arbitration with IMAP, and 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 $9.5 million for the first quarter of 2022, compared to $5.1 million for the comparable period of 2021. Turning to the balance sheet, At March 31, 2022, our cash, cash equivalents, and investments totaled $16.6 million compared to $24.1 million at December 31, 2021. We expect our current capital resources to be sufficient to fund our planned operations in 2023. With that, I will turn the call back over to Charles.
spk07: Thank you, Scott. As you have heard, our business strategy is proceeding as planned. Allow me to recap the five key events we expect this year. First, we expect to report three interim assessments at the 600-milligram dose of ENVA in ENVASARC this year, including an interim efficacy assessment in the second half of this year. Second, we are on track to initiate a Phase I-II trial of our potential best-in-class CTLA-4 antibody Y8001 in combination with ENVA in the second half of this year to begin first-line development of the combination of our two checkpoint inhibitors in sarcoma. 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 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 I trial this year, preventing 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 significant legal disputes with IMAP. As Scott indicated, our current cash runway extends into 2023 and past each of the five upcoming key 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: As a reminder, if you have questions, you will need to press star 1 on your telephone keypad. Again, that is star 1 to ask a question. We'll pause for just a moment to compile the Q&A roster. Our first question comes from the line of Maury Raycroft with Jefferies. Please ask your question.
spk08: Hi, Charles and team. Thanks for taking my questions. I was just going to start off with the MVSARC study and with the interim analysis later this year for efficacy. I think you've mentioned that's going to include about 36 patients. Just wanted to see if that's correct. And then I'm wondering if the data is going to be pooled or if you're going to break it out by the mono versus combo.
spk07: Hi, Maury. Thanks for your call, and we're looking forward to seeing you at your conference in June in New York and just a month away. With respect to MVSARC, we will do – if you will, an identical analysis to what we did last year at the lower dose. So at the 600 milligram dose we're using currently in the trial, after the 36 patients enrolled, which would mean 18 patients in each cohort, meaning 18 patients who received single agent ENVA and 18 patients who received ENVA and urovoid, once those 18 patients in each cohort has gone three months and had two scans, then we will assess the preliminary objective response rate and present that to the data monitoring committee knowing there's a futility rule whereby we need one response within each of those 18 patients in each cohort in order to continue enrolling that specific cohort. So depending on the review by the data monitoring committee, we will then reveal results to the street pending their guidance, if you will. So I can't promise exactly what will be revealed in terms of aggregate or individual response rates other than that we will reveal that decisions by the DMC with respect to futility and any further announcements by the DMC with respect to modifications or any potential change in the clinical trial. Our expectation will be that the DMC would continue the trial as planned. You know, I would point out even at the lower dose, we saw significant activity, including activity that satisfied the futility analysis. So we feel the futility analysis will be also fulfilled at the 600 milligram dose. And as I mentioned, I think earlier, we expect to see the the activity that we saw in lighter weight patients generalized to patients independent of weight, which I think would be an exciting prospect for patients.
spk08: Got it. That's helpful clarification. And then also wanted to just check on enrollment. We noticed recently that your target sites hit about 30 on CT.gov. And just wondering if you're planning on going beyond 30, Or do you think 30 is sufficient? And if you can put any more finer points on enrollment expectations at this point in the timeline.
spk07: Sure. Yeah, no, I appreciate that. So, you know, there seems to be a lot of excitement for sites wanting to join the trial. So I think initially we planned about 25 sites, but, you know, it's hard to turn away an experienced sarcoma site that wants to be part of the study. So that's why we increased the number now up to 30, 29 in the U.S., and then one in the United Kingdom as well. And I think that will be probably the total for the entire study going forward. Although, again, if a site really comes to us and wants to be part of the study, it would be hard to turn them down. But assume it will be 30 sites going forward. In terms of accrual, we expect to accrue the study between now and the end of 2023. I think we're being fairly conservative in our accrual estimates. And if we exceed that, that would be fantastic. I am encouraged by the fact that Even during processing the amendment, as I disclosed, we enrolled more than 10 patients just in the first quarter alone. So there's, again, a lot of excitement around the trial, and we do expect continued robust accrual.
spk08: Got it. Okay, that's helpful. And the last quick question for me. for the $9 million termination fee and the completion of the Phase I, I guess, is that going to be more of a third-quarter update or a fourth-quarter update when you complete the Phase I and then when you get the $9 million?
spk07: Yeah, currently our expectation, as we disclosed in the queue, is that we'll complete the study by the end of this quarter. And so thereafter, we would expect our partner to exercise their stated intention to terminate the license and then pay us the $9 million. So hard to say exactly when that is, Maury, but I do expect that will be in the second half of this year. Okay. Okay. Thanks for taking my questions. Thank you, Maury.
spk00: 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 I agree. Thanks, Charles. I have three questions. The first one is just on the timing of the interim looks from the Data Safety Honoring Board. Is the safety, are you going to have two safety reviews prior to the efficacy data being released, or how should we be thinking of that?
spk07: Yeah, I appreciate the question, Ed. Yeah, expect really the timing of or the progression of the interim review is similar to what we saw last year, just now be at the higher dose. So we'll see the first review is after the 20th patient's been on study for three weeks. And then this Another safety review will be after the 20th patient has been on study for 12 weeks. So those are two reviews that will happen in sequence, expect mid this year. And then once the 36th patient has been on trial for three months and had two scans, that will permit the interim efficacy assessment, which we expect toward the end of the second half of this year. So that's the sequence of three that, in a sense, will parallel, if you will, the sequence of three that we had last year at the lower dose.
spk03: Okay, thanks, Charles. The second question I have is on your announcement on the product development platform. I'm just curious if you've had any interest yet, and, you know, is there any timing that we could think of seeing a contract signed?
spk07: Sure. Yeah, I mean, I guess I would say in general, so, you know, when people look at TRACON, especially other companies, and they look at our expenses, you know, the you know, that we can run a pivotal trial like Envisarc for about $20 million. I mean, you know, they want to be able to do that themselves. And so, you know, we've used our platform in many ways. So we've used it as a means of gaining commercial rights. For instance, with embufolumab, we say we'll take on the clinical trial burden, run the trials at our cost, knowing that cost is very low, secure U.S. commercial rights with the intent of commercializing the drug, and then share profits with our partners. but not paying up for a milestone. So that's been our standard business, if you will, operation. But as I noted in the past, we have done the revenue share model, whereby, for instance, with Johnson & Johnson, we will take on an asset, but we'll ask the partner to pay for the trial and pay cost plus. Now, we know even if a partner pays cost plus, it's going to be cheaper than if they pay a CRO. And then we want to be aligned with our partner. We don't want to just act like a CRO and not be aligned to do the trial quickly. So we also want a piece of the revenue, whether it be a piece of the sub-licensing fees or the royalty, so that we are aligned to do the trial quickly, at low cost, and at high quality, knowing we'll still save our partner money versus them working with the CRO. And more importantly, we'll save them time versus them working with the CRO. So that's the revenue share model. And I will say there's significant interest in working with TRACON along those lines. I'd say especially in these days where a lot of companies are capital constrained, and whereas two or three years ago they might have cared about throwing a bunch of money to the CRO, now they're saying, you know what, we need to be very judicious, and if they want to be judicious, working with TRACON makes perfect sense. So there is a lot of interest around the revenue share model that I mentioned, which would be beneficial to TRACON because it would allow us to collect non-diluted capital. The third model is something that's more recently come to the front because people A lot of companies say it's great that you would do the trial for us, and we understand you need to be a revenue-sharing partner, but what we'd really like is the keys to the kingdom. We'd like you to teach us to do what you do. And so that's where we've come up with this idea of the franchise model. It's teach someone to do what TRACON does. Teach them how to do trials much faster, at a third the cost, with probably better quality than a CRO, and teach us that magic, if you will, teach us the special sauce. So that's a more recent idea that we've been approached with respect to thinking about. I think with that idea, we'd really want to work with a very trustworthy partner because we would be really teaching them our special sauce. But that is something that is of interest to certain partners. So in terms of when to execute a deal, our stated corporate objective, Ed, would be to do at least one deal this year. around a model that would allow non-dilute capital coming to TRACON.
spk03: Okay. Thanks, Charles. And then perhaps the last question is for Scott. The R&D expense sequentially was down, you know, ever so slightly, but it was down. As you're expanding your trials, I'm just wondering, was there anything one time in nature that in the fourth quarter that perhaps wasn't seen in the first quarter or something in the first quarter that was pushed out to the second quarter and how we should be thinking of the quarters going forward.
spk01: Yeah, thanks for the question. So going forward, the quarter should be similar to Q1, about $3 million in R&D expense. Q1 was down a little bit because of that amendment. We weren't enrolling too many patients in January, but then we enrolled quite a few in February and March. But that was really why it was down just a little bit from Q4. But, yeah, going forward, I would expect about three a quarter.
spk03: Okay, great. Thanks, Scott. Yeah, no problem.
spk00: Very nice question. Thank you, Ed. Your next question comes from the line of Joel Beattie with Baird. Your line is open.
spk02: Great. Hi, Charles and team, and thanks for taking the question. The first one is on the two safety assessments that are coming up for MSR. What will we learn from those? Are those just kind of go-no-go decisions, or is more detailed info provided, and how will the result of those safety assessments be communicated with the street?
spk07: Hi, Joel. Yeah, thanks for your question. Yeah, the safety assessments are really just to see if there's any significant safety signal that we're seeing with Envifolumab or Envifolumab combined with Yervoy that we didn't expect. I would point out that we had these similar safety assessments at the lower dose of Envifolumab, both as a single agent and combined with Yervoy, and there was no issue raised whatsoever, and we released that general finding as a top line press release to the street, and we intend to do the same thing this year. I would also point out that the increased dose of Envifolimab we're using of 600 milligrams is still a dose that's well within the maximum tolerated dose parameters of the drug, in the sense that in phase one testing, this drug was dosed as high as the equivalent dose of 2,400 milligrams every three weeks, so four times higher than the dose we're using in Envisarc. I would say that we feel it's very unlikely we'll uncover a safety signal we haven't seen. Remember, ENVA has been dosed to over 700 patients as a single agent and in combination with other drugs. But this is a formal way to assess safety, have the DMC review it, and make sure there's nothing untoward that we haven't seen or expected that could potentially impact the patients in the trial. Thank you.
spk02: Yeah, that makes sense. And then another question, thinking back to the 70 patients that were enrolled last year, is there any potential to share data on those to help further understand the impact that increasing the dose here could have?
spk07: You know, the 70 patients that enrolled at the lower dose, Joe, I don't expect we'll release data independent of the final data for the trial, but it's important everyone understands how valuable those patients are with respect to informing on the clinical pharmacology of envifolumab. And I mention that because the FDA has put a great deal of emphasis lately on clinical pharmacology and this Optimist project to make sure you're going to file for approval at the right dose. And those patients dosed at 300 combined with the now 160 patients we expect to be dosed at 600 is going to give us a broad, if you will, exposure, a broad base of patients that have various exposures of envifolumab that I think will be incredibly useful to really, if you will, prove to the FDA that we're using the right dose, which is the 600 milligram dose that we expect to file for approval. So those 70 patients and the PK data from those patients and correlating that PK with the responses we've seen in those patients will be incredibly valuable to support our expected application for approval of 600 milligrams.
spk02: Great. And then one last question. For the franchise model that you've been discussing, can you help with quantifying the value to potential partners, such as the magnitude of the cost savings and any other potential benefits?
spk07: Joe, I really appreciate you asking that question, and maybe I'll put it in perspective this way. So let's say you're running a 30-patient Phase I study. Now, we do studies at about $100,000 a patient. So for us to do a simple 30-patient phase one study costs us $3 million. If you were to go to a CRO in oncology in this day and age, and I have seen numbers of about $300,000 per patient. So in other words, if you run a phase one study with a CRO, it will cost you probably around $9 million. So you can understand that if you were to work with TRACON's model, you would say potentially around $6 million just for a phase one trial. If you're running two simple phase one trials using our model, potentially could save a company $12 million in just, say, two years running two simple phase one studies. And if you do a phase two, phase three, it goes up from there. As I mentioned, we're doing Envisar for about $20 to $25 million. I mean, as you well know, pivotal trials typically cost up to five times as much. So, You start to think about how much money a company would save if they used our model. You know, that's kind of the metrics of what we feel a franchise model would be worth to TRACON for us to teach that to another company.
spk00: Great. Thank you.
spk07: Appreciate the question, Joel. Thank you.
spk00: Your next question comes from the line of Nick Abbott with Wells Fargo. Please ask your question.
spk04: Thank you. Good afternoon, Charles and team. First one, Charles, how much do you think you've spent cumulatively on the IMAP litigation?
spk07: I think overall, Scott, maybe you can better answer that question.
spk01: Yeah, and Nick, our normal G&A spend is about $2.25. You know, that's kind of what I'd say it's historically been. So then, you know, last year we spent about $17.50, and so, you know, $17.50, the difference between that and $8, you know, the majority of that I would say would be the IMAP arbitration, and then this year as well is $6.50, and normal would be about $2.00. So that's over $10 million just last year and this year, and then there were some costs in 2020 as well, but that kind of gives you an idea.
spk04: Perfect. Thanks, Scott. And then a couple of people asked about the franchise model, Charles. How do you think – what does the revenue generation from that look like? Is there that? One time fee, is it a per trial fee? How do you think about revenue?
spk07: No, great question, Dick. I appreciate you asking that. So what we think is that there would be a significant upfront payment to TRACON for us to teach the partner, or if you will, give them the keys to the kingdom. You know, it's also a system that we continue to upgrade on an annual basis. So our thought would be it would be an upfront fee and then it would be annual, if you will, maintenance fees to TRACON, say, over a five-year period of time. Because I think it would take that period of time for someone to feel really comfortable that they don't need to continue to kind of reference us and have us mentor them in terms of small parts of the system that you may not get the first time. Remember, it took us, you know, 10 years to finish. We've been doing this for 10 years, I should say, and I'd say it took us three years to really fully internalize and feel comfortable doing the system ourselves. So that's how we think about it, upfront payment and then annual, if you will, maintenance payments, say, for five years as we continue to be a resource for the company that we teach to use the system.
spk04: Thanks, Charles. And maybe just to follow up on that is that do you think that once you've sign a franchisee, is there a plus option where you help them with headcount in order to pass this sort of teaching phase?
spk07: Yeah, I think that's a great point. I mean, we would really, I mean, we always prize those on being a great partner. So with a franchisee, we would really teach them exactly what we're doing, help them understand exactly what personnel they need in each specific role in the company to be able to mimic what we do, knowing that if you have the right people, you don't need a ton of people. Remember, at Tracon, our total number of employees right now is 20, and we're able to run multinational trials with that team just because the systems are so good and the people are so good. So we would have to help them not only get the systems, but have the right people in the right spots on the bus at that company to run the systems well. But it doesn't take a lot of people to if they're well-trained and very capable, which is the case at TRACON, for example.
spk04: And if there's no risk that you lose your people.
spk07: Yeah, I think we'd make sure we sign the contract indication of non-solicitation.
spk04: And then one thing for me, you know, I like the plan for Y8001, and it would be great if Envifolamab could be it. It's Buddy. What do you think the probability is that you can expand their n-vacfolumab license beyond just sarcoma?
spk07: Yeah, no, it's a great question. It's definitely something we would love to do. Clearly, it's something we need to get concurrence from each of our partners, both AlphaMav and 3D Medicine. So, you know, I can't state that we're able to do that right now, but I can state that it is something we clearly wish we can do in the near future. knowing that I think, to your point, if we had our own dual checkpoint inhibitor franchise of ENVA-White-001, that could be broadly powerful and benefit patients across multiple indications, not just sarcoma.
spk04: Okay, great. Thanks, Charles.
spk07: Thank you, Nick.
spk00: Your next question comes from the line of Bert Haslett with BTIG. Please ask your question.
spk06: Thanks. Just kind of a follow-up to the last one in terms of potential triple combinations. Thank you for taking the question. Just with regard to Y001 and ENVA, just so we can kind of frame it, again, the Phase I, Phase II combination with doxy is, you know, really in front line in multiple sarcoma subtypes. That is to generate data in the combination to ultimately move into phase three trial in the first line in that setting.
spk07: Hi, Greg. Thanks for your question. Yeah, exactly right. It's exactly what we're planning to do. I mean, we've seen, for instance, in lung cancer that dual checkpoint inhibitors can be combined with frontline chemotherapy quite effectively. With respect to sarcoma, doxorubicin is the standard frontline therapy used in the majority of sarcoma patients. So our goal would be to do in sarcoma, if you will, what other companies have done, say in frontline lung cancer, which is combine two checkpoint inhibitors with chemotherapy, in this case doxorubicin. So it would be that triple therapy you referenced.
spk06: Okay. So then the discussion about RCC, relative to kind of the answer you just gave to the prior question, and examining an ENVA Y001 combination in PD-1 refractory RCC patients. That's really maybe down the road, and if things can be adjusted, or I just want to make sure I understand kind of the optionality there.
spk07: No, I appreciate it, Bert. So, yeah, with respect to renal cell carcinoma, we have rights to develop Y001. We do not have rights to develop ENVA in that indication. So, If we're unable to expand our license to secure rights to develop ENVA, for example, in renal cell carcinoma, fortunately we could still develop YS001, which is our plan, but in that case we developed it with a PD-1 inhibitor, presumably one that's already approved in renal cell as the combination.
spk06: Okay. Great. Thank you. And as you think about additional combinations, are there other indications behind that? at this point, or things are still under construction there?
spk07: I mean, the other indications where we have rights for YGZ1, for instance, includes microsatellite-stable cancer, particularly colorectal cancer. That's another indication we think is something we potentially could explore. But I would say after sarcoma, right now, top of our list would be renal cell carcinoma.
spk06: Okay, thank you.
spk07: Thank you, Bert.
spk00: At this time, I'd like to remind everyone, if you have questions, please press star 1. Our next question comes from the line of Sumit Roy with Jones Research. Your line is open.
spk05: Hi, everyone. Congratulations on all the progress. If I may ask this question, maybe I'm a little confused. In December, when you were dosing at 300 milligrams, I thought some of those patients were eligible to transition into this higher 600 milligram trial. Is that what is happening, or you have to enroll such new patients?
spk07: No, hi, Shoman. Yeah, to be clear, so the way the trial works is we are enrolling 80 new patients in each of the two cohorts who will start at 600 milligrams. So 80 patients will start at 600 milligrams as single-agent ENVA, And 80 patients will start at end of the 600 with your void. And those are the two cohorts that are the primary cohorts evaluated for the primary objective of response rate where we have to see nine of 80 responses in either cohort to reach the primary endpoint. So that's the, if you will, the data set that's evaluated for potential approval of those two 80 patient cohorts. But the 70 patients already enrolled at 300 There are patients ongoing at 300 milligrams, and those patients individually can dose escalate to 600 to see if that will also benefit the individual patient, and that will also be very useful data as supportive data, but to be clear, the population evaluated for the primary endpoint is this 80 new patients enrolled into each of what we call cohort C of single-agent NVID 600, and cohort D of ENVA 600 plus Urovoid. That's the key population that's evaluated for the primary endpoint.
spk05: I see.
spk07: So in other words, just to clarify, so we expect the total number of patients enrolled in the trial now will be 230. Seventy patients already enrolled at the lower dose of ENVA, and then 160 patients, of which more than 10 are already enrolled as I speak, that will be enrolled in the two cohorts at the higher dose. Please, your question?
spk05: Nice. That really helps. Can you give us any idea how many of those 70 patients you see are dose escalating into 600 milligrams?
spk07: Multiple patients. I can't give you an exact number, but, you know, multiple patients that were on at 300, whether, you know, as we've disclosed, there was really minimal safety issue at 300 have dose escalated to 600, both as single agent and also with your boy.
spk05: Okay. And is there any possibility you would? present that data separately, cohort A, B, or it would all be packaged into one data set for registration?
spk07: Yeah, our thought is it probably will be packaged in one data set. That 70-patient data will be highly supportive data because it will actually be so valuable to us, given this real emphasis by the FDA on clinical pharmacology and the Optimist project. that data is going to be hugely valuable, and that will be part of the filing package, if you will. So to be clear, the endpoint will be determined at the higher dose, the patient who started at the higher dose of ENVA. But that 70 patients' worth of data will be supportive data and be integrated, for instance, into the population BK analysis and the exposure response assessment analysis. That's a key part of any BLA filing in this day and age. Great.
spk05: Thank you, and congratulations on all the progress again.
spk07: Thank you, Shomit.
spk00: There are no further questions at this time. I will now turn the call over back to Dr. Charles Tuer for closing remarks.
spk07: I'd just like to thank everyone for the careful listening to the script and to the dialogue, the questions. I appreciate your time and wish everyone a great day. Thank you.
spk00: This concludes today's conference call. Thank you again for participating. You may now disconnect.
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