TRACON Pharmaceuticals, Inc.
Q1 2022 Earnings Call Transcript

Published: 11 May 2022

[Operator:]

Good day, ladies and gentlemen, and welcome to TRACON Pharmaceuticals First Quarter 2022 Earnings Conference Call. At this time, all callers are in a listen-only mode. After the speakers' 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 runway and our development plans and strategy. 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. You are cautioned to not place undue reliance on these forward-looking statements, and we disclaim any obligation to update such statements. Now, I will like to turn the call over to Dr. Charles Theuer, President and CEO of TRACON Pharmaceuticals. Dr. Theuer?

[Charles Theuer:]

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 31, 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 dose 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 ENVASARC 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 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 enrolment 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 follow enrolment of the 20th patient. In the second half of this year, we expect to report on the interim efficacy assessment, three months falling enrolment of the 36-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 ENVASARC trial includes one cohort who receives 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 9 out of 80 objective responses by central review or an 11.25% objective response rate defines level of response that satisfies the primary objective of the study, which is to statistically exceed the 4% objective response rate of Votrient. The only approved treatment for patients with refractory UPS and MFS. Notably Votrient 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 Votrient. 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. Our second clinical stage immune oncology asset is YH001, a potential best-in-class CTLA4 antibody licensed from Eucure 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. With respect to our license, we can substitute any one of those indications for bladder cancer and endometrial cancer or melanoma at our election. In these non-sarcoma indications, YH001 could be combined with existing standard of care agents included marketed PD1 antibodies. Our initial development plan for YH001 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 1 trials of YH001 performed by our partner, Eucure, to inform our dosing strategy. These two trials determine the recommended Phase 2 dose of YH001 as a single agent and in combination with a PD-1 antibody, toripalimab. We intend to initiate a Phase 1/2 clinical trial studying a triplet that includes YH001, ENVA and doxorubicin chemotherapy, as doxorubicin is the current frontline standard of care treatment for sarcoma. Following the Phase 1 portion of the trial to assess the tolerability of the combination of ENVA and YH001 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 double of YH001 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 1/2 trial is to determine the sub types of sarcoma that respond best to the combination of ENVA and YH001. Following the potential accelerated approval of ENVA through the ENVASARC trial, the FDA will require a randomized trial to demonstrate a survival benefit. We expect this Phase 3 post approval trial will compare single agent doxorubicin to the triple combination of doxorubicin with ENVA and YH001 with PFS as the endpoint. This trial would be expected to enrol patients with UPS and MFS, as well as other sarcoma subtypes shown to be responsive to triple therapy based on data from the Phase 1/2 trial that I described earlier. The ability for TRACON to commercialize two unlicensed 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 forecast of $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 frontline, adjuvant and neoadjuvant settings by seeking supplemental indications. Moreover, we believe TRACON's total sarcoma-driven sales revenue should be further enhanced by marketing YH001 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 YH001 in other indications where there is clear evidence of activity with dual checkpoint inhibition. For example, the combination of (0

[Scott Brown:]

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 ENVASARC 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. The increase was primarily related to legal expenses in connection with the arbitration with I-Mab 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 totalled $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.

[Charles Theuer:]

Thank you, Scott. As you have heard, our business strategy is proceeding is 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 1/2 trial of our potential best-in-class YH001 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. 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 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 this year preventing I-Mab a the opportunity to exercise their stated desire to terminate the agreement for a payment to $9 million. Fifth, we expect to report the arbitration panel's binding decision, including potentialdamage awards regarding our significant legal disputes with I-Mab, As Scott indicated, our current cash runway extends into 2023 and passed each of the five upcoming key milestones, including expected non-diluted capital from an existing partnership. Thank you for your time and attention and we are now available to answer your questions.

[Operator:]

Our first question comes from the line of Maury Raycroft with Jefferies. Please ask your question.

[Maury Raycroft:]

Hi, Charles and team. Thanks for taking my questions. I was just going to start off with 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's going to be pooled or if you're going to break it out by the mono versus combo?

[Charles Theuer:]

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 (0

[Maury Raycroft:]

Got it. Its helpful clarification. And then also wanted to just check on enrollment, we noticed recently that you – 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?

[Charles Theuer:]

Sure. Maury and I appreciate that. So there continues to be a lot of excitement for sites wanting to join the trial. So I think initially we planned about 25 sites, but it's hard to turn away an experience (0

[Maury Raycroft:]

Got it. Okay. That's helpful. And last quick question for me for the $9 million termination fee and the completion of the Phase 1. I guess is that going to be more of a third quarter update or a fourth quarter update when you complete the phase 1 and then when you get the $9 million?

[Charles Theuer:]

Yes. Currently our expectation as we disclose in the queue is that we'll complete this study by the end of this quarter and so thereafter we would expect our partner to exercise or state his 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.

[Maury Raycroft:]

Okay. Okay. Thanks for taking my questions.

[Charles Theuer:]

Thank you, Maury.

[Operator:]

Our next question comes from the line of Ed White with H.C. Wainwright. Your line is open.

[Ed White:]

Good afternoon. Thanks for taking my questions.

[Charles Theuer:]

Hi, Ed. Good morning.

[Ed White:]

Hi, Charles. I have three questions. The first one is just on the timing of the interim looks from the data safety monitoring 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?

[Charles Theuer:]

Yes, I appreciate the question, Ed. Yes, really the timing of or the progression of the interim review is similar to what we saw last year just now will be at the higher dose. So we'll see the first review is after the 20th patient has been on study for three weeks. And then another stage review will be after the 20th patient has been on study for 12 weeks. So those are two reviews that will happen in sequence you 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, that the sequence of three that we had last year at the lower dose.

[Ed White:]

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 is there any timing that we could think of seeing a contract signed?

[Charles Theuer:]

Sure. I mean, I guess I would say in general, so when people look at TRACON, especially other companies and they look at our expenses that we can run a pivotal trial again for about $20 million. I mean they want to be able to do that themselves. And so, we've used our platform in many ways, so we've used it as a means of gaining commercial rights. For instance, envafolimab we say, we'll take on the clinical, trial burden run the trials at our cost and that cost is very low, secure U.S. commercial rights with the intent of commercializing the drug and then share profits with our partner, but not paying up front or milestones. 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, Johnson & Johnson, we will take on an asset, but we'll ask the partner to pay for the trial and pay costs 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 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 the trial quickly at low cost and a 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, three years ago the amount they 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-dilutive capital. The third model is something that's more recently come to the front, because a lot of companies say it's great that you would do the trial for us, and we understand your 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. Yes, 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 would be to do at least one deal this year around a model that would allow non-dilutive capital come into TRACON.

[Ed White:]

Okay, thanks Charles.

[Charles Theuer:]

Sure.

[Ed White:]

And then perhaps the last question is for Scott the R&D expense sequentially was down, ever so slightly, but it was down as you are expanding your trials. I'm just wondering, was there anything, one time in nature 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?

[Scott Brown:]

Yes, 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 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 yes, going forward, I would expect about three a quarter.

[Ed White:]

Okay, great. Thanks Scott.

[Scott Brown:]

Yes, no problem.

[Charles Theuer:]

Thank you.

[Operator:]

Your next question comes from the line of Joel Beatty with Baird. Your line is open.

[Joel Beatty:]

Great. Hi, Charles, and team. And thanks for taking the question. The first one is on the two safety assessments that are coming up 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?

[Charles Theuer:]

Hi, Joel. Yes, thanks for your question. Yes the safety assessments are really just to see if there is any significant safety signal that we're seeing with envafolimab or envafolimab combined with Yervoy that we didn't expect. I would point out that we had these similar safety assessments at the lower dose of envafolimab, both as a single agent and combined with Yervoy and there was no issue raise whatsoever. And we released that general finding as a top line press release to the Street. And we would intend to do the same thing this year. I would also point out that the increased dose of envafolimab 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 1, testing this drug was dose as high as the equivalent dose of 2,400 milligrams every three weeks. So four times higher than the dose we're using in ENVASARC. So I would say that we feel very unlikely we’ll uncover a safety signal we haven't seen. Remember ENVA has been dosed 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 is nothing untoward that we haven't seen or expected that could potentially impact the patients in the trial.

[Joel Beatty:]

Yes, 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 that the impact that increasing their dose here could have?

[Charles Theuer:]

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 envafolimab. And I mentioned that because the FDA has put a great deal of emphasis lately on clinical pharmacology and this 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 envafolimab 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 at 600 milligrams.

[Joel Beatty:]

Great. And then one last question for the franchise model that you've been discussing, can you help with maybe quantifying the value to potential partners such as the magnitude of the cost savings and any other potential benefits?

[Charles Theuer:]

Joe, I really appreciate you asking that question. And maybe I'll put in perspective this way. So let's say you're running a 30-patient Phase 1 study. Now we do studies at about a $100,000 a patient. So for us to do a simple 30-patient Phase 1 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 1 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 1 trial. If you are running two simple Phase 1 trials using our model potentially could save a company $12 million in just say, two years running two simple Phase 1 studies. And if you do a Phase 2, Phase 3, it goes up from there. As I mentioned, we're doing ENVASARC for about $20 million to $25 million. I mean, as you well know, pivotal trials typically cost up to five times as much. So you start thinking about how much money a company would save if they used our model. 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.

[Joel Beatty:]

Great. Thank you.

[Charles Theuer:]

Appreciate the question, Joel. Thank you.

[Operator:]

Your next question comes from the line of Nick Abbott with Wells Fargo. Please ask her question.

[Nick Abbott:]

Great. Thank you. Good afternoon, Charles, and team. First one, Charles, how much do you think you've spent cumulatively on the I-Mab litigation?

[Charles Theuer:]

I think overall – Scott, maybe you can better answer that question.

[Scott Brown:]

Yes. And it gets our normal G&A spend is about two a quarter. That's kind of what let's say it's historically been. So then last year we spent about $17.5 million, and – $17.5 million, the difference between that and $8 million the majority of that I would say would be the I-Mab arbitration. And then this year as well is $6.5 million and normal would be about two. 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.

[Nick Abbott:]

Terrific. Thanks, Scott. And then a couple people asked about that franchise model Charles. How do you think, what is the revenue generation from that look like? Is it a one-time fee, is it a per trial fee, how do you think about revenue?

[Scott Brown:]

No. Great question Nick. 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. But it's also a system that we continue to upgrade on an annual basis. So our thought would be, it'd be an upfront fee, and then it'd be annual if you will, maintenance fees to TRACON say over a five-year period of time, because I think it'll 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 10 years to fully internalize. 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 upfront payment and then annual, if you will maintenance payment say for five years as we continue to be a resource for the company that we teach to use the system.

[Nick Abbott:]

Thanks, Charles. And maybe just to follow-up on that, is that, do you think that once you sign a franchisee, is there a plus option where you help them with headcount in order to pass this sort of teaching phase?

[Scott Brown:]

Yes, I think that's a great point. I mean, we would really – I mean, we always 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 help them, not only get the systems, but have sort of 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 if they are well trained and very capable, which is the case of TRACON for example.

[Nick Abbott:]

And if there's no risk that you lose your people.

[Scott Brown:]

Yes, I think, we make sure we sign the contract indication of .

[Nick Abbott:]

And then last one for me, I like the plan for YH001 and it would be great if ENVASARC could be it's – sorry toripalimab could be it's buddy. What do you think the probability is that you can expand their ENVA toripalimab license beyond just sarcoma?

[Charles Theuer:]

Yes, 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 Alphamab and 3D Medicines. So, 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 YH001 that could be broadly powerful and benefit patients across multiple indications, not just sarcoma.

[Nick Abbott:]

Okay, great. Thanks Charles.

[Charles Theuer:]

Thank you, Nick.

[Operator:]

Your next question comes from the line of Bert Hazlett with BTIG. Please ask your question.

[Bert Hazlett:]

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 YH001 and ENVA just so we can kind of frame it. Again the Phase 1 Phase 2 combination with doxy is, really in frontline, in multiple sarcoma subtypes that is to generate data in the combination to ultimately move into Phase 3 trial in the first line, in that setting.

[Charles Theuer:]

Hi Bert great. Thanks for your question. Yes, 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. And 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 and 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.

[Bert Hazlett:]

Okay. So then the about RCC relative to kind of the answer you just gave to the prior question, and examining an ENVA YH001 combination in PD1 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.

[Charles Theuer:]

No, I appreciate it Bert. So yes, with respect to renal cell carcinoma, we have rights to develop YH001. 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 YH001, which is our plan, but in that case, we develop it with a PD1 inhibitor, presumably one that's already approved in renal cell as the combination.

[Bert Hazlett:]

Okay, great. Thank you.

[Charles Theuer:]

Thank you, Bert.

[Bert Hazlett:]

And as you think about additional combinations, are, are there other indications behind that at this point or things are still under construction there?

[Charles Theuer:]

Yes, I mean, the other indications where we have rights for YH001 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.

[Bert Hazlett:]

Okay. Thank you.

[Charles Theuer:]

Thank you, Bert.

[Operator:]

Our next question comes from the line of some Soumit Roy with Jones Research, your line is open.

[Soumit Roy:]

Hi everyone. Congratulations on all the progress. If I may ask this question, maybe I'm a little confused. Prior, in December, when you were dosing at 300 milligram, 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 fresh new patients?

[Scott Brown:]

Hi Soumit. Yes, 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 ENVA600 with Yervoy. 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 eight responses in either cohort to reach the primary endpoint So, that's if you will, the data set that's evaluated for potential approval, those two 80-patient cohorts. But the 70 patients already enrolled at 300, they 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 ENVA600 and cohort D of ENVA600 plus Yervoy. That's the key population that's evaluated for the primary endpoint.

[Soumit Roy:]

I see.

[Scott Brown:]

So in other words, Soumit just to clarify, so we expect the total number of patients enrolled in the trial now will be 230, 70 patients already enrolled at the lower dose of ENVA and then the 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.

[Soumit Roy:]

I see. That really helps. Can you give us any idea how many of those Alimta patients you see are doses escalating into 600 milligram?

[Scott Brown:]

Multiple patients, I can't give you an exact number, but multiple patients that were on a 300 milligram, as we've disclosed, there was really minimal safety issue at 300 milligram have dose escalated to 600 milligram, both a single agent also with Yervoy.

[Soumit Roy:]

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 approval for registration?

[Scott Brown:]

Yes, our thought is that 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 Optimus 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 patients start 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 PK analysis and the exposure response assessment analysis that's a key part of any BLA filing in this day and age.

[Soumit Roy:]

Great. Thank you. And congratulations for all the progress again.

[Scott Brown:]

Thank you Soumit.

[Operator:]

There are no further questions at this time. I will now turn the call over back to Dr. Charles Theuer for closing remarks.

[Charles Theuer:]

I'd just like to thank everyone for the listening to the script and to the dialogue, the questions. I appreciate your time and wish everyone a great day. Thank you.

[Operator:]

This concludes today's conference call. Thank you again for participating. You may now disconnect.