Welcome to the Morgan Stanley website at www.morganstanley.com/researchdisclosures. If you have any questions, please reach out to your Morgan Stanley sales representative. For this session, we have Michael Richmond, CEO of NextGear. Welcome, Michael.
Thank you, Jeff.
For those who may not be familiar with Nexgear, can you provide an introduction?
Sure. Yes, I'd be happy to. And first, I'd like to thank you, Jeff and Morgan Stanley for the invitation for next year to present today. Hopefully, you have a copy of your slides that people can that are attached to people can walk through. First and foremost, the next year was started about 5.5 years ago with a focus on developing next generation immunomedicines.
Our next slide is just our forward looking statements. I'd like to kind of walk you through what we call the 3 P's at NextGear, our pipeline, our product and our people. Our pipeline, I'll walk you through briefly today is focused on our first leading product, NC-three 18. This is a humanized monoclonal antibody targeting CEGLIC-fifteen currently in Phase 2 trials. Next, we have our NC410 trial.
This is currently in Phase 1 and focuses on the LAYER pathway to restore immune function. And then finally, most recently, we announced the initiation of our NC762 trial, which focuses on B7 H4. With respect to our platform, our product strategy actually has been somewhat of a triangulation, including patient selection, looking at product strategy, we also have what we call our Find IO Discovery platform, which really sets the stage for building the pipeline and building value in the company in the future. And finally, the 3rd P has to do with people and the through our own GMP manufacturing. We have an experienced leadership team that supports these 3 clinical programs as well as the platform.
And the company was founded by Liping Chen at Yale University who discovered PD L1 many years ago and that's been instrumental in the IO field. The next slide focuses on our product development pipeline. Again quickly, I just mentioned NC318 targeting CYCIGLX-fifteen. We'll be providing a data update towards the end of this year. We're developing this in monotherapy, quite aligned with that strategy.
We're also working with Scott Gittinger and Roy Herbst at Yale University that are conducting a combination study of NC-three 18 with pembro. Our NC-four 10 study will also be providing an update later this year on the Phase 1 clinical trial and then NC762 is just starting with respect to the Phase 1 study. I should note that we have worldwide rights to all of these programs. Slide 5, let me get into NC318. As I mentioned, this is a humanized monoclonal antibody targeting siglec-fifteen.
S-fifteen is uniquely expressed both on tumors and myeloid cells, in particular M2 macrophages. And S15 and NC318 promotes T cell function through activation and interferon production strategy that we've developed with respect to testing and selecting patients, with respect to biomarker evaluations and with respect to combination therapies moving forward. The next slide talks about the Phase 1 study that we've reported on in the past. This involved 49 patients, 15 different tumor types. We saw CR and PR in lung cancer, both of those subjects remain on therapy today.
The Phase 2 study that's ongoing will now has been shifting in the direction of now selecting for S15. We recently announced the resumption and enrollment of non small cell lung cancer patients into that therapy. And we've increased the dose from the 400 mg dose every 2 weeks to now looking at 800 mgs weekly to enhance drug exposure. And in the Phase 2 that we reported on in the past and we'll provide an update on were 2 confirmed PRs, 1 head and neck and 1 in triple negative breast cancer. As I mentioned, we're also conducting a study in collaboration with our colleagues at Yale University looking at a 3 arm approach with respect to looking at S-fifteen positive patients in monotherapy.
And we're also looking at 2 arms in combination therapy with pembro, 1 with respect to PD-one refractory patients and the other with respect to PD-one naive. As I mentioned earlier, we've taken this triangulation approach with respect to selecting patients, developing a significant repertoire biomarkers And then thirdly, looking at combination approaches. This is just an example of the 3 tumor types that we're looking at with respect to siglec-fifteen and where we're now requesting tissue biopsies as part of the consent process. We're testing those biopsies for CYCDS15 positivity to enrich for those patients that we think will be most responsive to NC318. Let me transition into our 2nd program, NC410.
This works through a novel decore mechanism and through a layer 2 fusion quickly because I think layer 1 really sets the stage for a major direction that science is moving in, in understanding the extracellular matrix with respect to tumors and the tumor microenvironment. So NC410 works through the LAYER pathway and LAYER is involved in enhancing T cell activation and ultimately tumor killing. As we saw with NC-three 18 regarding some of the highlights, we're developing IHC assay that we'll use for patient selection in Phase 2. We have an extensive repertoire of biomarkers, which will provide insight into the mechanistic and clinical correlations that we hope to see with NC410. We've seen significant synergies in CONVERT earlier this year with respect to our ASCO poster on the trial and in a recent eLife publication.
This next slide shows really the important progression and advancement in understanding the impact of collagen and the extracellular matrix. And what we call the ECM with respect to the extracellular matrix, we know that it's associated with immune suppression. We also know that the extracellular matrix is predominantly made up of collagen, 1 of the key ligands that layer 1 and layer 2 bind to. And it's this increase in collagen that correlates with PD-one and PD L1 resistance. And we believe that by overcoming this collagen within the extracellular matrix, we can help alleviate immune suppression to restore immune function.
In this next slide, let me walk you through briefly the extracellular matrix and the role of LARE-one. So LARE-one is a co inhibitory molecule and it uniquely binds 1 of 2 ligands, 1 is collagen and the 2 is looking at C1q. In this next slide, you can see the impact of a second gene and protein called LARE 2. So like LARE1, where they share significant homology and binds collagen and C1q, LARE2 differs in 2 respects. 1 is it has greater affinity for collagen and 2, it's soluble.
So LARE 2 acts as a competing decoy to prevent the negative signaling through layer 1 to restore immune function. This next slide shows the molecule that we've created and what we call NC410. This is a dimeric fusion protein representing LARE 2. And as mentioned earlier, it uniquely binds collagen in C1q to change the architecture of the extracellular matrix and to restore immune function. Slide 14 is just some of the recent data that we could fix in combinations.
Slide 15 just kind of outlines at a high level the NC410 Phase 1 study. We're currently midstream through our dose escalation cohorts where this is a 3 by 3 design looking at safety and tolerability. We're looking at a number of collagenous tumor types including lung ovarian and pancreatic. And as I mentioned, we'll be providing an update on this trial later this year. Our 3rd program, NT762, works through a unique mechanism of action in binding B7 H4 overexpressed on many tumor types, including gynecological cancers.
We've initiated the Phase 1 trial and like our other 2 programs, we're developing an immunohistochemistry based test to select for those patients that we think will be most responsive. Slide 17 just kind of briefly walks you through the trial design. Again, it's a 3 by 3 dose escalation study looking at multiple tumor types and our goal is to we've initiated the Phase 1 and we'll be reporting an update on this trial sometime during the middle of next year. Slide 18 just highlights our GMP manufacturing. We doubled our capacity last year, which really sets the stage for supplying clinical material for all 3 of our trials moving forward.
Slide 19 just talks about independent of the pipeline, we have a platform that is uniquely established to select for novel 1st in class proprietary immune modulators that are really setting the stage for the sustainability and continued growth of the organization moving forward. Slide 20 is just some of our near term milestones. I mentioned NC318 and NC410 We'll be providing an update on the Phase 2 and Phase 1 study respectively. And as we enter 2022, we'll continue to update individuals on these various programs. So finally, next year is a fully integrated organization with a very focused approach in leveraging its platform and moving its pipeline moving forward.
So thanks, Jeff. I'll pass it back to you.
Great, great. Thank you. So in the past, you've indicated that Siglyt-fifteen and PD L1 might have limited overlap, but you've also seen signs that S15 and PD L1 may be dynamic. So can you talk about your latest thinking on Siglut 15 and how does that play into your decision to select for S15 positive patients through screening biopsies?
Yes, it's a great question. So from the beginning, we always thought looking at S15 expression as a means to select for those patients that we think would be most responsive to NC-three 18 made sense. When we first started the trial, we did, as you point out, notice there was this non overlapping expression of PD L1 and SIDH15. So the thought process was that if we based on this inverse relationship, if we selected for PD L1 low, we would enrich for patients that were S15 high. We continue to believe that the lapping expression.
Unfortunately, what we saw in the Phase 2 when we selected patients for PD L1 low, we looked at archival historic biopsies. And when we looked at the first biopsies later, we noticed that PD L1 expression, as you mentioned, was dynamic. So it was changing. So many of the individuals that we thought would be enriched for S15 positivity were in fact PD L1 high that had changed over time. So that made our thinking evolve from the standpoint of now developing this clear validated immunohistochemistry test, where we now take consent from patients, we retrieve biopsies and we send those biopsies to our CRO, we're using the test, we can now screen for those patients who are S15 positive either in the tumor or looking at immune cells in the stroma.
And then based on that positivity, we can then continue to treat those patients and hopefully they'll be most responsive.
And for your Phase 2, maybe can you talk a little bit about how you think about the different tumor types? So you mentioned how there were 2 responders in lung. Maybe you can just talk about the different tumor types that you're looking at and the rationale behind those?
Yes. So we've always been driven by the datasets of expression with respect to looking at various tumor types. And this goes back to looking at the TCGA nucleic acid expression where we see S15 expressed on a number of different tumor types, including the 3 that we're pursuing in lung, breast and head and neck. We then complement that data with respect to the immunohistochemistry data where we've looked at tumor microarrays in collaboration with David, Rem and Gail and also on our own working through our CRO. So there we can look at many different tumor types and look at S15 expression either in the tumor, chroma and try to define what those cutoffs might look like as we advance the program moving forward.
So now based on that combined data set, we can now select patients that we think will be most responsive. So now when we couple in the Phase 1 data, as you point out, where we saw, I think we looked at 13 patients out of 49 patients with non small cell lung cancer. That's where we saw PR and CR. Those patients remain on therapy today and we saw multiple stable disease. That kind of set the stage for advancing into the Phase 2 with lung.
And then we also originally included ovarian, breast and head and neck also.
And as you talked about in your introduction, you guys have started enrolling lung cancer patients again. Can you discuss what led to that decision?
Yes. So we never really gave up on lung. We did pause last year when we were doing the SIMON-two stage Phase 2 study and unfortunately did not see any clinical responses based on the lung cancer patients that we have treated. So putting a pause on that with respect to taking the time to develop the test, During that period, we entered into the relationship with Yale to conduct the combo study. As I mentioned, it's a 3 arm study looking at NC318 in monotherapy and then also looking at NC318 in combination with pembro with respect to PD-one refractory patients and PD-one naive patients.
So that then when we started moving forward and we started looking at the statistical data and looking at stable disease and looking at various different patient populations, we concluded that really lung cancer made a lot of sense based on the instance-fifteen expression profile data, both from nucleic acid and the immunohistochemistry perspective that coupled with the data that we had seen from the Phase 1. So we added that back into the cohorts that we were going to investigate further.
Another recent change that you guys have made that you talked about was increasing the drug exposure. Can you talk about what led to this decision and then what you hope to see with that change?
Yes, it's a great question. So we've been doing a lot of biomarker and biostatistical analysis with respect to the impact of markers that validate change based on different dosing, based on different tumor types. And based on this analysis, in particular, we've been looking at soluble versions of different immune modulators. And in this case, we've looked at soluble S15 and the change that has that occurs during the dosing process. And we concluded that if we put much greater drug exposure upfront in treating patients that we're much more likely to see some sort of clinical benefit.
You may recall that we do look at an 800 mg dose in the Phase 1 dose escalation study, although that was every 2 weeks. So we believe the change to 800 mgs weekly hopefully will give enough drug on board to bind S-fifteen and to hopefully see some sort of clinical impact.
Great. And for the update that we're expecting in the Q4, what should we look for in that update? And what does what doses might we see data for?
Yes. So with respect to the doses, obviously, we're going to update people on the original Phase 2, which was 400 mgs every 2 weeks. We'll be doing a full analysis of that Phase 2 data in the context of the Phase 1 data with respect to biomarkers and statistical analysis. Moving forward, now where we're screening for patients with a clear validated test and at the 800 bps weekly to the extent we have patients enrolled in this trial, we'll also provide an update on those patients there.
Okay. For NC410, what should we look for that from that Phase 1 data later this year?
Yes. So NC410, this is a traditional 3x3 Phase 1 safety and tolerability study. We're looking at 8 dose escalation cohorts. We're midstream through those cohorts. So by year end, when we provide an update, we won't be completely through the trial.
We're pretty much close to the end. Independent of looking at reporting traditional safety and tolerability, Obviously, any clinical observations we make, we'll put it on. And then I think quite interestingly will be the biomarker data from the Phase 1 readout. So unlike a lot of trials where we traditionally look at immunophenotyping, we look at cytokines, we look at chemokines, NanoString. In the case of Lair, because of the unique biology, we can actually measure soluble layer 1, soluble layer 2.
We can measure both of the ligands C1Q and also what we call CDPs. These are the collagen degradation products. So as I quickly went through earlier, NC410 is binding collagen and changing the architecture of the extracellular matrix. And by decreasing the density of collagen, which we'll be able to measure in the biomarker context, we think this will open up the ability for combination therapies to work more effectively, where instead of your molecules being blocked by the ECM, this loosening of the matrix itself may create an opportunity to mechanistically and functionally impact treatment.
And how do you think about which tumors to target in the Phase 2 portion or how will you make that decision?
Yes, it's a great question. So like we mentioned in CIGLX-fifteen, we look at layer 1 expression and we look at nucleic acid expression as kind of the first get go to give us kind of a reference frame of those tumor types that are expressing layer 1. We then couple that with the immunohistochemistry Phase 2 looking at LARE 1 expression. So those 2 things will give us some insight into which tumors are expressing LARE 1. We then now couple it based on the understanding of the mechanism of action that we walk through in collagen, many of these tumors are purely collagenous.
1 can look at pancreatic cancer and other tumor types that have a significant amount of collagen that we believe if disrupted may have the opportunity to have some sort of therapeutic benefit through NC410 or potentially combinations moving forward. So we're looking at obviously all comers in the Phase 1. But as we've reported on, we think lung, ovarian and perhaps others may benefit from NC410 treatment. Okay.
And you talked about your 3rd asset, NC762 earlier. Can you talk about what you saw in the initial in vivo data at AACR?
Yes. So NC762 is a humanized monoclonal antibody binding B7 H4. This is a target that's overexpressed in many different tumor types, particular gynecological tumors. So you see it overexpressed in fallopian tube, ovarian and breast. And what we when we were developing an antibody, obviously, we were screening for a lot of different antibodies with unique functionality.
We've always felt that next year that we have to get 3 things right. The target, which we know is expressed on the tumor, the candidate, which is having the right antibody and the engineered molecule and then 3, going into the right patient population. And that's where these screening tests become important. So with respect to the mechanism of action, and that we know others have worked in the B7 H4 space, It's an antibody that has a unique functionality. It seems to have a direct tumor killing effect.
It could be potentially through an ADCC mechanism. However, we believe that based on our preclinical data to date, this works independent of T cells. We also know that NK cells play a very important role in perhaps augmenting this effect. So based on the various immune cells that are being impacted through our in vitro studies looking at B784, we believe that this unique antibody will have monotherapy effect ultimately may ultimately develop it through combinations in the future too.
Okay, great. Maybe in the last couple of minutes, I know that when you guys went public, Find. Io was a fairly important part of the story. Maybe you can talk about that and any updates on Find. Io?
Sure, thanks. Yes, so FIND. Io is really our platform. It's an acronym for functionally integrated next year discovery. And what we're doing with FIND IO is basically we're walking through the entire human proteome using significant assays and screening tools to look at any given protein that may have some functional immune response, whether it's stimulatory or inhibitory.
We've identified and continue to identify novel targets. A number of them are working through the validation and early stages of the pipeline. And I think in the years to come, you'll hear more about some of these novel targets and perhaps not only in cancer, but they may even have some of these targets may have applicability in the neuroscience area or even in the autoimmune space.
Great. Looks like we'll have to leave it there. Thanks so much for your time, Michael.
Yes. Thank you, Jeff. Great speaking with you. Great.