Ladies and gentlemen, thank you for standing by and welcome to the Next PEO R and D Update Conference Call and Webcast. At this time, all participant lines are in a listen only mode. After the speakers' introduction, NextGear will host a question and answer Please be advised that today's conference is being recorded. I would now like to hand the conference over to Mr. Timothy Mayer.
You may now begin.
Thank you, operator. Good evening. My name is Timothy Mayer, Chief Operating Officer. Welcome to NextGear's virtual research and development update conference call and webcast. You can also join this conference call on NextGear's website at nextcure.com.
We are using slides to accompany our remarks today, which can also be accessed from the Investor Relations section of our website. A replay of the conference call will also be available on our website following today's presentation. I'd like to introduce Nexgure's President and Chief Executive Officer, Michael Richmond and our recently appointed Chief Medical Officer, Doctor. Han Miyan, who will also provide remarks today. Michael Hanh, Steve Coborn, our Chief Financial Officer, and I will be available to answer questions as needed.
Before I turn the call over to Michael, I'll remind you of the following Safe Harbor statement. The matters we are discussing today include projections or other forward looking statements about the future clinical, preclinical and operating results, research and development goals and future financial performance of NexCare. These statements are estimates based on management's current expectations and involve risks and uncertainties that could cause them to differ materially from actual results. We refer you to the risk factors discussed in our filings with the SEC, including our annual report filed on Form 10 ks for the year ended December 31, 2020, and in NxQ's other financial filings. These filings identify important risk factors that could cause actual results to differ materially from those in our projections or forward looking statements.
We undertake no obligation to provide any updates to these forward looking statements even if our expectations change. Now I'll turn the call over to Nexgear's President CEO, Michael Richmond. Michael?
Thanks, Tim, and good evening to everyone. We're thrilled that you have joined us on today's call. We thought it was an opportune time to host a call to provide an update on our 2 clinical programs, NC-three 18 and NC-four 10. In addition to these clinical development updates, we have continued to push forward on the R and D side, and we are pleased to introduce NT-seven 62, a new program today. NT-seven 62 is based on strong science and aligned with our focus on developing next generation immunomedicine to treat cancer and other immune related diseases by restoring normal immune function.
In terms of the agenda, Slide 3, I'm going to provide a brief introduction and then I'll introduce you to Doctor. Han Miint, who recently joined Nexgear as our new Chief Medical Officer. Han will provide some additional remarks and then discuss recent updates on our 2 lead programs, NT318 and NT410. Tim will then introduce our new program, NT762, and finalize the presentation with an update on our Find. Io platform.
But before jumping in, I also wanted to note that we announced 4th quarter and full year 2020 financial results in our press release today. Thank you, Steve. We aren't going to review the financials in detail, but I did want to highlight that our current cash and equivalents are expected to fund the company into the second half of 20 23. And as you will hear in today's call, we expect multiple pipeline milestones to occur between now and 2023. On Slide 4, on Next Pure highlights, I'd like to emphasize our 5th anniversary.
Since initiating operations 5 years ago, we have 1, filed 3 investigational new drug applications for novel immune medicines with unique mechanisms of action 2, taken 2 molecules into the clinic, and you'll hear about the 3rd today, NC-seven 62 3, build a GMP manufacturing facility and have produced clinical material to support all of our ongoing clinical work and 4, develop a discovery platform to identify novel proteins that modulate immune activity. We are incredibly proud of this productivity. In Slide 5, let me quickly walk you through the pipeline. This slide shows the breadth of our current pipeline. By the end of next year, we expect to file an IND for a 4th program.
Given the continued productivity of our discovery efforts, we also anticipate filing another IND in 20 23. We look forward to disclosing these programs when appropriate. In order to keep today's call somewhat brief, I'm going to let our other speakers provide additional detail. But first, I do want to highlight that we have maintained the worldwide rights to all of our programs. In Slide 6, let me introduce you to Han.
I'm very excited to introduce Doctor. Han Mient. We conducted a thorough search and we believe the depth of his expertise in oncology product development will provide instrumental will prove instrumental in the advancement of our pipeline. Han has a strong industry track record highlighted by its contribution to several regulatory approvals, both in the U. S.
And globally. Many of you on the line probably know Han, but as a reminder, he comes to us with over 20 years of biopharma and academic experience, including holding senior roles at both Celgene and Neximmune. In his academic years, he worked at prestigious institutions, including King's College London, Rush University Medical Center and the University of Chicago sorry, University of Colorado in Denver. While Han has been with us for less than 2 months, he has hit the ground running and is already having a substantial impact on our clinical plans. I thought it would be beneficial to have Han provide some brief comments today.
Welcome, Han.
Thank you, Michael. I'm incredibly thrilled to have joined NextEacure. As I was looking at the opportunity back then, I came to realize that it's important impact that both NC318410 could have bring the opportunities for the treatment of cancer. And also look at the pipeline that you have in preclinical program and those are very exciting for us. As Michael alluded to earlier on, and I'm a newbie at nixcure, less than 2 months old, but with the help of the team here getting fully up to speed in that short tenure.
And even with this introduction by the team here, I'm more and more optimistic about the potential of the pipeline and the platform. I'm looking forward to speaking with you all in the greater detail in the coming months. So let's start with the NC-three 18 update. I would like to echo Michael's earlier comments about the significant progress that we have made and our enthusiasm going forward. Just a reminder, NC-three 18 targets cGX-fifteen.
In short, we call it S-fifteen. You can see from the cartoon that it blocks this S15 induced immune suppression. Ciclative15 is expressed on the tumor cells as well as M2 macrophages and that led to potently suppressed the T cell function and us, NC-three 18, reversed that effect. On the Slide 8, I'm going to talk to you about the update of our clinical program and I'm going to highlight 2 main updates. Top, you can see our current Phase 2 monotherapy continue to accrue And I'll show you some clinical responses in the next couple of slides.
And also we're developing the assay for selecting the patient with cyclic15 positive tumors. The next is the Yale collaboration. It is a very important collaboration for us because we're looking at NC-three 18 as monotherapy as well as a combination with pembrolizumab, which I will again explain to you more in the next couple of slides. So this is the update for the Phase II program. You may recall, during the Phase 1, we have 1 CR patient and 1 PR patient.
I am glad to report that the CR patient remains on treatment until 118 weeks ongoing and the PR patient remains on treatment over 92 weeks. Now let's draw the attention to Phase 2 part of the program. We give you the update back in December of 2020. And we mentioned the patient with squamous cell carcinoma of head and neck who has partial response. And now we have a confirm to the negative patient that who responded.
And again, I'll give you more detail in the next slide. But I think the exciting thing to note here is that the patient with head and neck patient is now lasted for 40 weeks, but now the patient is discontinued. The triple negative risk patient is still ongoing at 21 weeks. And as I mentioned, because of those responses, we are now moving forward to this second portion of the SIMON 2 stage trial. And we're also very pleased to announce to you about the clear validation of the Sigler-fifteen staining.
And we will be getting the final results by the end of Q1. And therefore, in the Q2 of this year, we're going to revise our protocol to select sigma15 positive patient to enroll in our new amended protocol. Hopefully, we can provide additional clinical results from the CET31 program to you in the Q4 of this year. As I alluded to earlier on the Slide 10, I can show you that I can show you the 2 row if you like to look at. The top row is a patient with head and neck cancer.
And 53 year row with the multiple lesions and the patient at that time had a PD L1 standing was less than 50% And patient was given different therapies in the past, chemotherapy, 3 rounds of radiation. And patient was also given nivo and pembro in a different timeframe, but within the 3 months timeframe patient progress. And you can see from the x-ray from the left to the right baseline with the right ring around with the red color and the week 24 target lesion has decreased in 37% and that is why patient is recorded as partial response. Next is the 2nd row, the next row after that is a patient with triple negative breast cancer. This is an unusual case.
It's a 7 year old with a triple negative breast cancer, very low PD L1 staining less than 1% and patient had previously been treated with 3 cycles of chemotherapy, 1 cycle of radiation and patient was given pembrolizumab and the best response of stable disease, but then patient had a progression. This patient, as I mentioned, had a skin lesion and you can see on the left hand side and compared to the 8 weeks later on the right hand side, it dropped from 18 millimeter drawn to 14 millimeter, which is target lesion decreased by 82 percent. And this lesion remains to be on treatment. The next 1, I'm very, very excited to tell you about this because you may recall we dropped non small lung cancer in the past, but the world authority, Doctor. Roy Hertz and Scott Cattinger from Yale are very excited about our science and they liaise with Merck and brought pembrolizumab into their study design.
So what they're trying to do is 3 arm, there's non randomized 3 arm study. And in the monotherapy arm, they're going to select patient who are CICL15 positive and PD-one failure PD-one, PD L1 access treatment failure In the combo arm, what they're going to do is 2 arms. 1 arm is PD-onePD L1 access naive vision and the other arm is going to be those with failed PD L1PD L1 failed population. And they're going to start accruing in Q2 of this year. And depending on the results, we may be able to add more patient into this study and additional results will be available early part of next year.
So now let's switch attention to very exciting layer science. So just reminder, I want to go through step by step from the left to right so that you can follow me very well. Layer 1 is a membrane bound receptor expressed on the T cells and dendritic cells and it binds to either collagen or C1q on the tumor that expressed this. And then when this happened, it has an inhibitory effect on the immune function. Layer 2 is a natural occurring decoy molecule of Layer 1.
It differs in 2 aspects. 1, it is a soluble protein and 2, it has a higher affinity to the collagen and C1 ligands. So competitively binds to those, so that those 2 collagens and C1q cannot bind to the layer 1 and you can follow the cartoon to the right, you can see that layer 2 modulates the layer 1 mediated immune inhibition. Therefore, activated T cells can do the job of tumor killing. On the Slide number 13 is the what is MC410.
MC410 is a human fusion protein of layer 2 and is a decoy for the layer 1. And what it does is promote the T cell function and dendritic cell activation, as I mentioned earlier. And I show you with the data in the next slide. This was presented by Linji Tian at SITC and there are 3 points I want to make in the 3 rows that you can see. The most important part of 410 is the extracellular matrix remodeling, which is very significant about this particular molecule that we're very excited about it.
And you can see from the middle pictures that you can see, Crenzyme B mediated collagen fragmentation, MMB2 mediated collagen fragmentation, you can see that when this is given week 4, you can see that there's a level on the graph. The next step, it promotes anti tumor immunity. It's not only it does that locally and systemically, and you can see from the picture again in the figure again that using gamma interferon and granzyme B local and in the tumor itself. So what does it do? It enhance the T cell infiltration and tumor killing.
And more importantly, it brings back the normalization of the immune function. And that's the most important part of 410. The other effect of this is the combination potential. And this was presented by Doctor. Lucas Haun at SITC and I want to give you left and right.
On the left, you can see with the PD L1, on the right is the Bintrafuspater combination. PD L1, you can see whether it's alone or 410 alone or anti PD L1 alone. When you compare to combination tumor volume, you can see from the graph very clearly that combination is better than either of 1. I think more importantly, the most exciting thing is the right hand side figure that you can see. And beetroot use, if you try to remember, it is a bifunctional fusion protein.
Is a extracellular domain of human TGF beta2 trap to a flexible linker to the heavy chain of IgG1 of the antibody to PD L1. So you can see the combination on the red color at the bottom, you can see that the tumor secured in this model that they did. And then next is I want to tell you where we are with the clinical program on the Slide number 16. So this is a classic Phase 1 to Phase onetwo study. The Phase 1 at the moment we're in Phase 1 and we're doing classic 3 +3 dose escalation and we're looking at safety and tolerability of this 410.
And what we are looking at tumor types wise, advanced metastatic solid tumors such as non small cell lung cancer, ovarian and pancreas. And we're on track and accruing quite well and we hope to give you the results of the clinical data from the Phase 1 portion of this study towards the end of second half of 20 21. With that, I'd like to call over to Tim. Tim? Thanks, Han.
I'm pleased to introduce NC762, our new program we are disclosing today. NC762 is
a humanized monoclonal antibody that targets B7 H4. B7 H4 has low expression in normal tissue, but is upregulated in multiple solid tumor types, including non small cell lung cancer, ovarian cancer, breast cancer and several others. B7 H4 has been reported to inhibit the proliferation of T cell, suppress antigen presenting cells, stimulate proliferation of T regulatory cells and promote tumor growth. Multiple publications have demonstrated that B7 H4 expression in tumors correlates with poor clinical outcomes. Expression of B7H4 has also been shown to not overlap with PD L1 expression in non small cell lung cancer.
While other B7H4 monoclonal antibodies are in clinical development, we believe NC762 has unique anti tumor properties. Preclinical data demonstrate that binding of NC762 to tumors expressing B7 H4 results in inhibition of tumor growth in vivo. Natural killer cells contributed to the enhanced high assay tumor activity mediated by MC762. However, NC762's inventory effect on tumor growth was not dependent on T cells. On Slide 18, we provide the in vivo data for NC-seven 62.
In these preclinical studies, NC-seven 62 was shown to inhibit melanoma tumor growth alone, but was enhanced by the addition of human immune cells. The figure on the left shows tumor inhibition versus control. The study also included other versions of FC762 that was designed to restrict ADCC activity. And as you can see from the results, tumor inhibition was independent of ADCC activity. The figure in the center shows that for a parent of NC-seven 60 2, tumor inhibition was enhanced with the addition of the natural killer cell.
Finally, the figure on the right demonstrates that purified T cells alone were not required for activity. We believe this profile is incredibly encouraging with a mechanism of action that clearly differentiated from other B7 H4 targeted programs in development. We have filed an IND with the FDA and expect to initiate a Phase 1 clinical trial in the Q2 of this year to assess safety and tolerability in patients with solid or metastatic tumors. We expect to provide initial Phase 1 clinical data in the Q2 of 2022. Finally, I'll highlight our powerful discovery engine we call FIND IO for functional integrated next year discovery in immuno oncology.
The platform integrates multiple components to assess immune function resulting from cellular interactions. The system entails individually transfecting each gene from our library of over 9, 000 genes into a host cell, which will then express the protein on the surface of the cell. We combine the transfected cell expressing the single gene with an immune cell. Finally, and most importantly, we have our functional readouts we observed through our discovery screens, which provide important insight into identifying genes that modulate immune cell activity. We view the immune system holistically and rather than target 1 specific immune cell type, we focus on understanding biological pathways, the interactions of cells and the roles each interaction plays in an immune response.
Our future pipeline will continue to focus on how the immune system interacts within its microenvironment and shapes disease. Given the versatility and flexibility of the Find IO platform, cells and functional readouts can be altered and the platform can be applied to identifying targets in other therapeutic areas. We are currently investigating what we call FIND AI for autoimmune and inflammation targets. Alternatively, the system can be applied to microglial cells and astrocytes to identify novel CNS targets for neuro inflammatory diseases. Moving forward, our anticipated near term milestones include NC-three 18 and providing Phase 2 monotherapy data in the Q4 of 2021 and Yale starting the Phase 2 non small cell lung cancer combination trial in the Q2 of 21 with anticipated initial data in the first half of 20 22.
Reporting MC410 initial Phase 1 data in the second half of 20 21 and initiating the NC762 Phase 1 trial in the second quarter of 2021 and reporting initial data in mid-twenty 22. So in summary, we're excited to have Doctor. Mann as part of the team and draw upon his vast experience in developing oncology products. We continue to make progress on NC-three 18 with the continued advancement of the Phase 2 monotherapy study and the return to non small cell lung cancer with Doctor. Erfsten Yale.
MC410 continues to advance in the clinic and we look forward to sharing data later this year. We look forward to starting MC762, the 3rd candidate we have advanced to the clinic in 5 years and using the unique antitumor properties of the antibody and inhibiting tumor growth. We would like to thank everyone for joining the call this evening. And with that, we'll now open the call up for Q and A.
Operator there? Sorry for the technical difficulties.
Your first question comes from the line of Ted Tenthoff from Piper Sandler. Your line is now open.
Great. Thank you. Good evening, everybody, and thanks so much for the time. And it's a pleasure to get to meet you on. I'm trying to get a sense with respect to N318, sort of what we could be expecting in the 4th quarter?
Which different cancers are we looking at that? And then sort of same question with respect to combination with anti PD-one, what indications are you looking at presently? Thanks. Thanks, Ted. Todd, would you like to take that call?
Yes. So I think the part from the Yale study is quite easy to answer because Yale is only concentrating on the non small lung cancer only. So they will do both monotherapy, as I alluded to earlier on, and the combo with the pembro in the PD-one, PD L1 axis naive as well as failed population that are 3 arms, as I mentioned. So the program is ready to kick off at the end of this month, early next month. So we were expecting to see some of the results as very quickly.
That's why I think we're hoping to see the results by the end of this year, early next year. As far as the company sponsored study, we're still ongoing enrolling patients with head and neck cancer, triple negative breast and that's where we are right now. But as mentioned, once we have the best 15 clear validation stay in these complete by the end of the month, In Q2, we will be looking at revising the protocol and we can update you at that time.
Great. Thank you guys for
the update. I'm excited to hear about the new candidate.
Great. Thanks, Ted.
Your next question comes from the line of Bert Hazlett from BTIG. Your line is now open.
Yes. My congratulations as well. Maybe you just touched on it, but could you discuss a little bit more about the assay development with regard to sigle15? What remains and where would you intend to employ it in the future? And will the Yale investigators be employing something in their study as well?
And then I have 1 or 2 more.
Yes. Thanks, Bert, and good to be speaking with you. That's a great question. So as most of you know, we've been very focused on developing a validated IHC test that we could use on biopsies taken from patients to determine whether or not a given subject is S15 positive. This test has been developed.
It's been in validation over the last few months and will be available to use in our ongoing Phase II trial that Han walked you through. So moving forward, from next year's perspective, we will be applying the CLIA validated NC-three 18 test to select for S15 positive patients. With respect to our ongoing relationship with Yale, there's a number of arms to that study. And over time, we will be integrating the use of that test as it relates to the monotherapy components. And as we move forward and start generating more data, we'll also be ultimately integrating that into the cabo study.
That's terrific. You just touched on the a little bit more of the Yale structure. Could you give us anything with regard to size and endpoints with regard to the Yale study? Again, you touched on it a little bit there, but any more detail would be terrific.
Yes. Maybe Hans can give you a general overview, but Bert, I'd also kind of just reference clinicaltrials dotgov, which kind of clearly delineates the trial in much more detail. But, Anh, did you want to add any color commentary other than you're looking forward to going to New Haven, Connecticut?
Thank you. I don't think no. I think that would be enough, yes.
Bert, it's kind of a really interesting point because as most of you know, even though we're here in Beauxville, Maryland, next year's founding institution is at Yale. And Pat LaRusso participated as 1 of our lead investigators in the Phase I clinical trial for NC-three 18. She participated in the Phase II trial. And through this and through our founder, Liping Chandu, actually discovered PD L1, we got to know Roy Herbst and Scott Gettinger quite well. As most of you know, Roy is kind of the luminary in lung cancer on planet Earth these days.
So we're very fortunate to have both of them obviously working very closely and collaboratively with us on this trial in returning to a non small cell lung cancer. And I should also add that Merck obviously has choices on how they provide KEYTRUDA to looking into evaluating combo trials. So to have the opportunity to work with our collaborators at Yale and also with Merck to provide KEYTRUDA, we think provides the enthusiasm that we all share for looking at this approach.
Can't wait to see the data and remember when you're in New Haven, Sally's Pizza is the best.
We will remember that. Thank you. Thank you.
You will.
Your next question comes from the line of Jeff Hong from Morgan Stanley. Your line is now open.
Thanks for taking the questions and for the R and D update. Maybe if I can just ask a little bit further. In recent months, it looks like your strategy for the 3 18 combo study shifted from chemo combo to anti PD-one combo. So I realize that the combo study is an investigator initiated trial, but can you talk about what went into that decision and what gives you greater confidence in an anti PD-one combo versus a chemo combo? And then I have a follow-up.
Yes. So you may recall the Nature Medicine paper 2 years now, right? We are in 2021, so 2 years ago. And that is a I mean, the figure that I can easily refer to you, I think, figure 6 and the figure 10j in the supplementary, There's beautiful preclinical work done by Yiping and others. I mean, a number of people from our next year was involved too, like Saul and Lindner and Dallas in that paper.
And what they showed is that if you combine the 2 together, tumor growth is definitely a lot lower than what you see like which responses are much better with a combo compared to either of PD-one that is nivo or NT-three 18. And that's the major driver. And as you all know that initially as you know the PD-one and CDL-fifteen expressions are like exclusive to each other. But as you treat, then patient then start to stop responding to PD-one. That's where I think CDL-fifteen CDL-fifteen comes in and help the function again and re drive the function of the sort of pembro or nivo to do the job.
So I think that preclinical data has shown very nicely. I think that's why I think the world authority in lung, people like Roy and Scott are very excited to do that study. Anything to add?
No, that's great. Thanks for that question, Jeff.
Thanks. And if I can follow-up, in the interim Phase II results, you saw the S15 expression in 13% of the valuable biopsies, but there was also some evidence that S15 status can change over time. So I was just wondering if you could clarify how you're taking those pieces into consideration with the revised protocol selecting SigV-fifteen positive patients and what kind of requirements will you have for duration of SigV-fifteen positive status? Thanks.
Yes, that's a great question. And obviously, through our studies, we continue to learn a lot. What we have confirmed is the non overlapping expression between CYCGM15 and PD L1. With respect to this dynamic change, obviously, we're going to continue to monitor that, but we no longer believe that a PD L1 low selection will enrich for F15 positivity. And that's the rationale for developing the IHC test that we talked about earlier.
What we do believe is, especially in the case of lung, we still believe 20% to 25% of lung cancer patients are H15 positive. And if we could target those particular individuals using our test, hopefully, we'll be able to move in the direction of many more responses. On the other comments, Mary?
I think you've done it very nicely.
Okay. Thanks.
Thank you.
Thanks, Jeff.
Your next question comes from the line of Alex Trehanahan from Bank of America. Your line is now open.
Hey, guys. Thanks for taking our questions and thanks for the update. That's good to hear from you.
So first, I've got a couple
of questions on the investigator led study and you've covered a bit of this, but I was hoping to dig a little bit more into the discussions you have you've had with the investigators and sort of the rationale of restarting in non small cell lung cancer.
Is it that
the lung cancer cohort was maybe excluded prematurely from the original study? And if so, which data would you point to supporting this? And I guess along those lines, do you imagine that both S-fifteen and PD L1 selection will be included for enrollment in the combo arm of the study? And then I've got a follow-up.
Yes, great question. So a little history for the audience. So you may recall in the Phase I trial, we had looked at 49 patients, 15 different tumor types and about a fourth of those patients were non small cell lung cancer. And as Tom reported earlier, that's where we reported the CR and the PR, both of those individuals that remain on drug today. We also reported a number of stable disease.
So that gave us a fair amount of confidence moving into the Phase II trial and in particular the non small cell lung cancer cohort. Obviously, we were very disappointed and surprised when we started looking at the data and didn't see any responses in the Phase 2 that would have justified moving into Stage 2 of that SIMON2 stage study. When we went back and we looked at the biopsies regarding the ones that were available, we just did not see that many S15 positive individuals. So I think through the experimental data, that made us kind of go back and rethink our strategy. We weren't writing off non small cell lung cancer, but we did need to use the last 6 months or so to learn a lot more.
So moving forward, we will continue to look at PD L1 status. That's an easy test to do. And many of the individuals that will be coming onto the trial in non small cell lung cancer will be refractory or would have failed prior treatment with KEYTRUDA or nivo or another PD-one or PD L1 therapy. So we will be selecting FREDS-fifteen positive patients. Now more specifically, your question, on the monotherapy arm, we will be selecting 15 patients.
In the combo, we may be ramping into that over time. So ultimately, we'll be moving in that direction. The Yale folks are eager to start, but our test will be available shortly. And once available, we'll be moving in the direction of selecting for those individuals. Am, anything else to add?
No, I think you've covered everything. Yes.
Okay, great. Thanks. And 1 more, if I may, actually on your new asset, MC-seven 62. Should we assume that the Phase I will be structured similarly to studies for your other assets? And do you have a sense based on the literature or your preclinical observations, which tumors might be the most amenable, to targeting a B7 H4?
And I guess, looking longer term, is the plan to limit investigation to oncology? Or do you also expand studies that say autoimmunity or inflammation?
Yes. That's a great question or several questions. So with respect to B7 H4, and 1 thing we have learned in next year is that moving forward, developing the tools for patient selection and developing the assays for biomarker analysis will be integrated into all of our programs. So that speaks to where we are now backtracking with NC-three eighteen's lung, but we'll be applying an NC410 in layer and then to your point, NC762. So many gynecological cancers are heavily overexpressing B7 H4.
So we see this in ovarian cancer, breast cancer, fallopian tube cancer and many other types of cancers. The Phase I with respect to looking at kind of rapid enrollment and looking at safety and tolerability will be kind of enriching for those patients that are naturally B7, H4 positive. But as we segue into the Phase Ib and Phase II, we also have a test that will be CLIA validated midyear that we'll be able to apply for selecting patients. We're also building an extensive toolkit on the biomarker side to give us much more insight to what NT-seven 62 will be doing immunologically and clinically as we dose patients. Is that correct, guys?
Yes. All right, good. Keep me real.
Yes. Good answer.
Yes. Thanks, Alex.
Thanks, guys.
Your next question comes from the line of Ashtika Goonewardene from Churit Securities. Your line is now open.
Hi, guys. Thanks for taking my questions. And hi there. And Pat, good to meet you. So let's start off with I want to jump in on another question on the Yale study, particularly with the PD-one failures.
I'm wondering if the recruitment target here in PD-one failures with the Yale side, will recruiting enough patients delineate between primary progresses and subsequent failures? And I'm just wondering if there's any sort of updated thinking on that interplay between PD L1 and S50 in this particular group? And then I got a few follow ups as well.
Currently the way they were looking at is the patient who had seen either nivo or femoral or any of those PD-one, PD-one therapies and here being the big lung center, as you know, they have about 2 to 4 patient type per month that they will see. So that's what they were looking at to come onto the study. We haven't stratified as far as I recall in the primine numbers that you catch from very beginning or the 1 that already failed. I think that's why I think we had the arm call naive population, but currently they have other studies ongoing that these are going to wrap up. Once those studies wrap up and there are you can predict, right, from some of the based on especially with the pembro, with the MSI high and what you.
And they could have easily predict those and that in future will be used in their naive population. But right now, I think they are considering on the failure population first.
Got it. Okay. And then in terms of the B7 H4, I know there have been maybe some other attempts on that as well. But maybe can you talk to us a bit about what makes MC762 2 unique? Is that particular epitope that you're going after, etcetera?
Yes, that's a great question. So I think how we differentiate this is when we look at product development, we look at targets, we look at candidates and then we look at patient population. So we've always felt B7H4 is a really important target. And I think in an earlier question, people were someone was asking about autoimmunity, and it potentially does have application in looking at autoimmune diseases. But in with respect to the differentiation, our molecule does recognize a different epitope.
We have done comparative studies to determine that. It's got a different affinity. And I think most importantly, as Tim walked through earlier, it has a different functionality. And when we talk about function or mechanism of action, SC-seven 62 is clearly different. And we've spent a lot of time doing a lot of in vitro and in vivo work to not only study the mechanism of action to really but also ascertain how best to position this for when Han would join us and to move this into the clinic.
Tim, anything else you'd like to add?
No, that's exactly the answer.
Great. And then lastly on NC410, are you able to give us any update on where you are on the dosing, dose escalation and or if you complete or how far you're from completing recruitment?
Yes. So where we are right now, we're in the Phase I part of dose escalation. We're kind of working our way towards, I guess, the middle of the various cohorts. And as Tom mentioned, we'll be reporting an update on that trial later this year.
Great. Thank you, guys.
Yes. Thank you very much.
Your next question comes from the line of Tony Butler from Roth Capital.
Just a very simple a couple of very simple questions, I think. When you put in the Siglut 15 inhibitor, it doesn't matter the tumor. You actually peripherally get an increase in T cells. And if you get an increase in T cells, do you have any data that would be, of course, in vitro that they are directed against a particular tumor? That's question 1.
And then in question 2, again going back to the Yale study, is the assumption that non small cell lung cancer naive patients might actually be SIGLIT-fifteen negative versus, of course, those that have failed PD-one because the majority of them will have been on a PD-one regimen at some point and clearly may have become PD L1 negative and thus perhaps Siglut 15 positive. Just curious your thoughts there. Thanks.
So I guess the first question is looking at T cells and all of our in vitro work and data we've generated has demonstrated that we can enhance T cell proliferation and interferon gamma. With respect to the immunophenotyping that we've done on samples from patients, we have seen T cells with respect to an overall proliferation. It's difficult to quantify, I think, that data at this time. Your other question is a little more complex to answer with respect to, I guess, non small cell lung cancer and looking at kind of naive patients that maybe have not been exposed to PD-one or PD L1 therapy and what impact that might have on X15 expression. But what we can say outside of non small cell lung cancer is we have treated or analyzed other patient samples that have not received PD-one where it may not be approved, And we do see some sort of S15 expression in those samples.
In the case of non small cell lung cancer, any thoughts on the naive versus the refractory population and the impact that might have on S15 expression? I'm not sure we know that.
No, I don't think we know that. I mean, that's where we are today, I think. Especially with the Bembro, I'm sure being the center like Yale, they will be doing a lot of other markets, right? MSI is 1 and then there's many other markets that they'll be looking at. They're looking at RNAi stake and so on.
There's so many ways that they've been determining. So I think we will learn a lot from them. That's why I think we're very excited for them to look at the naive population as well. And to answer that question directly to your the way you frame it, I don't think we know the answer.
Yes. So as we talked about today, in the case of Yale, we've got that again the mono arm, the combo arm and in the part of the combo, we've got the naive and refractory patients. So we'll be learning a lot, and we'll be looking at both S-fifteen expression and PD L1 expression.
I agree. I think it's a great trial. So look forward to that data set. Appreciate it. Thank you.
Thank you.
Your next question comes from the line of Ren Benjamin from JMP Securities. Your line is now open.
Hey, good afternoon, guys. Thanks for taking the questions. I have a couple on the head and neck and triple negative and then a follow-up. I guess for the head and neck, very nice results. How many patients overall have been treated in both the head and neck trial and the triple negative study?
And how many do you plan on enrolling after the protocol enroll amendments? And have you I know you mentioned the PD L1 staining at least for the head and neck patient, but any color you can give us regarding the CYCGM15 expression or staining from these patients that are responding?
Yes. So with respect to the Sigmund-fifteen expression, we don't have any of that information at this point. Obviously, we've collected biopsies from these patients and we'll be looking at that. And I'm sorry, the other question?
Just how many patients total have been enrolled in the hep and neck and the triple negative? And how many do you plan on enrolling in the after the protocol amendment has taken place for this?
Right. So it's Simon yes, thank you. Sorry. It's a Simon 2 stage study. We haven't disclosed actually how many patients we've enrolled, but we have reported even in today's press release that we've advanced both the head and neck and the triple negative breast cohorts to Stage 2 of that SIRMIR 2 state study.
Got you. And Michael, how many patients should we think about in terms of the Phase 2 portion or that hasn't been disclosed either?
We've said in the past that our Phase I and Phase II trials will look at about 100 or I'm sorry, our Phase 2 trial will look at about 100 patients in total? Correct.
Got it.
Okay. Thank you for that reminder. And just switching gears to MC410. It seems like a big component, and I think you mentioned it before, is of course biomarker development. Can you give us a kind of sense as to how you might be looking at biomarker development for the NC410 asset?
Yes. Boy, how much time do you have? I love talking about NC410 biomarker. Yes, so as Anh walked you through, so MC410 is a fusion protein of LAYER II, which works through a decoy mechanism to basically stimulate T cells and dendritic cells to restore immune function. But layer 1 and layer 2 by 2 key ligands, collagen, and this is monomeric collagen expressed on the tumor that impacts the extracellular matrix and the architecture of the tumor in the TME.
It also binds C1Q, which is also an important part of the complement system and impacts the immune system. So what we've done is, wow, we've thought the team has been, I think, going a little overboard on developing the tool from a biomarker perspective. So we can look at layer 1, we can look at layer 2, we're looking at collagen and collagen degradation products, we're looking at C1Q. So this becomes a little bit of a bioinformatics puzzle where we're generating all of this data, not only in the patients, but also looking at these various markers in different patient populations and healthy individuals to give us the ability to do some comparative analysis. So independent of the traditional PK and PD analyses that we would do in looking at immunophenotyping, looking at cytokines and chemokines, nanostring.
So many of the biomarkers that most people are familiar with in immuno oncology, we've added on to that with respect to layer 1, layer 2, collagen and C1Q. And I'm sure by tomorrow, there may be a few more. So thanks.
Got it. And maybe just 1 Tim. The 762 asset was came out of the Find IO platform. Is that correct? Or did you guys find it in another way?
No. The MC762 asset is, we said, targets B7H4, and that did not come out of FIND IO. Now historically, Doctor. Chen has worked on the B7H4 program and that would have been before the advent of the precursor of bind IO. So it's a homegrown product candidate.
Got it.
Thank you guys very much for taking the questions.
Thank you.
Your next question comes from the line of Alden Husainov from Benchmark. Your line is now open.
Hi, good afternoon. Congrats on the progress and thank you for taking my questions. The first question I have is about the Phase 2 MONO study. So initially, you planned lung, head and neck, TNBC and ovarian. So lung, you essentially stopped.
Head and neck, you got 1 response TNBC 1 response. But did you see any responses in ovarian cancer?
Yes. So we did not see any responses in ovarian cancer. We also didn't generate the number of biopsies that we had hoped to. So there is a possibility of going back to ovarian cancer, but under such an arrangement, we would request biopsies and select for SVT gene positivity again.
Okay. Understood. And for non small cell lung cancer for the 2 responses that you had, did you measure the S15 expression at any point, especially lately or at any point of the treatment?
Unfortunately, we do not have biopsies in those patients. Both of those individuals, the original CRPR were in our Phase 1 dose escalation study where biopsies weren't collected at that time. So that's most unfortunate. But unfortunately, both patients are still around today.
Right. Yes. And for B7H4, do you see for NC 7 63 asset, do you see any potential synergies with PD L1 or any targeted therapies in the future?
That's a great question. Yes. So our research folks are doing in vivo comparative studies. I mean, there's some things that come to mind, maybe PD-one or PD L1, but there may be some other molecules like PARP inhibitors that are already approved and being used in gynecological cancer applications. So that work is still in research, but like all of our programs, we're going to be open to investigating combos with a clear focus on patient selection and looking at biomarkers.
Anything else on
No, I think you covered it.
Okay. And the last question I have is a general question. It's about your business development plans, if you have any in 2021. I think in the past, you mentioned that you have active business development team. I'm just curious about any plans that you may have in 2021.
Yes. So we haven't provided any guidance with respect to any specific partnerships that might be consummated. But you are correct that we have a very proactive business development team that Tim leads and we're constantly and consistently engaged in multiple discussions on multiple fronts. So we remain opportunistic, but no defined guidance this time.
All right. Thank you very much.
Thank you.
We have a follow-up question from the line of Mr. Tony Butler from Roth Capital.
Sorry for the follow-up, but this is brief. The dosing of the Siguil 15 and Siguil 15 is every other week, if I recall correctly, from, I guess, the deck. But importantly, how do you do the trial or how do you think about doing the trial in conjunction with PD-one given or at least pembro given its dosing, which is clearly different? Thanks again and appreciate the time.
Thank
you. Currently, I think the pembroke is being dosed at every 3 weeks and the our drug is being given every 2 weeks. That's the current design. But as we talked about earlier, this is a moving target, right? We can think about how they could modify the study as we go along.
But right now, that's how they design
it. And there are no questions on queue. Speakers, you may now continue.
Great. Well, thank you very much, everybody. We appreciate you taking the time for the update, and I look forward to continuing our discussion. Have a nice evening.
Thank you very much.
This concludes today's conference call. You may now disconnect.