Good afternoon, everyone. My name is Kelly Xu, 1 of the biotech equity analysts at Jefferies. Thank you for attending our virtual healthcare conference. We are very pleased to have Mr. Paul Hastings, President and the CEO from Npata Therapeutics joined us today.
He also brings his big team Kenya, Ralph, Nadia, James and Greg. And to start off, Hal, could you introduce your team and also the company for those who less familiar with that Encarta story?
Yes. Thank you, Kelly, for inviting us and we're thrilled to be here. The beauty of Zoom is you have the whole team, so you can ask whatever questions you'd like, Kelly, and we will be happy to give you multiple points of view on that 1 question you asked. So the team here, you have James, our CSO, Chief Scientific Officer Kanya Majangam is our Chief Medical Officer Nader Mahmoud is our Chief Financial and Business Officer and Ralph Brandenburger is our Senior VP of Tech Ops running all of manufacturing process development. As everybody knows, product and cell therapy.
And Greg Mann, who is our VP of Corporate Communications and Investor Relations and myself, CEO, Paul Hastings. So we're happy to be here. So did you want me to introduce the company too, Kelly? Is that what you asked or just the people?
Yes. At a high level, for the audience who joined us for the first time and not familiar with your story.
Absolutely. Greg, why don't you go to Slide 3. So let me just say at the outset that we're laser focused on engineering CAR NK cell therapy for cancer. So the beauty of the NK cell is as part of the innate immune system, they're short lived cells, they tend to go in, they tend to attack the tumor and they tend to leave. So like an antibody or chemotherapeutic agent, these are cells that you can give multiple times and they don't have the long acting activity of the adaptive immune system, which is still a good activity to have, but the NK cell is a short lived cell.
So it has the benefit of being able to be dosed like an antibody. All of our programs from our NKG2D targeted NK cell to our CD19 targeted NK cell CD70 are designed to be allogeneic for off the shelf use. And they have the broadest possible access ultimately where you can cryopreserve these cells, put them in vials, freeze them, thaw them, give them at the patient's therapeutic side, could be in an infusion center, could be in a hospital setting, could be in a community based setting. And that potential for outpatient administration is something that is very unique and very exclusive to the NK cell. So much easy cell type to give in an outpatient administration in the community oncology center.
So we're starting with donor derived cells. There's a lot of talk out there about platforms. And I have to tell you, if someone asked me as a patient, do I want to start with a real NK cell that gets expanded as a real NK cell in large numbers with a relatively modest cost of manufacturing so that you have the flexibility to multiple dose and to have real NK cells that haven't been altered, that's the way I would go. So a healthy donor derived platform and a next generation healthy donor derived platform being an allogeneic off the shelf cryopreserved in the vial product is 1 that we really want to focus on and that's where we start. We design ourselves with donor derived cells.
We use a proprietary expansion technology that our founder, our companion came up with K562 cell line and we achieved a very attractive cost of manufacturing around $2, 000 dose for cryopreserved product in a vial at peak and that's a conservative estimate between 50700 doses per healthy donor. We also have the potential to have a universal donor as time goes on. So we've got a lot of the advantages of any other platform, the ability to gene engineer. We recently did a deal with CRISPR, so we can do that as well and do everything that any other platform can do, but with a natural killer cell to start with. We have 2 co lead programs, 101, which is our NKG2D based NKCAR NK cell therapeutic.
NKG2D is the natural receptor on the NK cell. So actually turbocharging the NK cell with additional NKG2D ought to take what's in the literature with unengineered NK cells in the disease like KML and really help to get that kind of effect, that kind of CRA longer term in a more controlled setting. So we expect to have data in a handful of patients by the end of this year for the NK G2D program in AML and MDS. Our NKX-nineteen program, the IID was recently cleared and we expect to be dosing patients in the second half of this year and we expect to have data in 2022 and we'll give more guidance on that as soon as we get closer to FPI or first patient in for the 19 program. So 2 co lead programs that will ultimately read out in the early part of 2023.
So both together and the capital we raised in our IPO will take us into the second half of 'twenty 3. So proof of concept for 2 co lead programs in the timeframe of our capital raise and where that will take us. Our platform is strongly differentiated. We start and finish with real natural killer cells. I cannot emphasize that enough.
We're not differentiating from stem cells. We're starting with natural killer cells. Donor source is important and we start with a high volume of cells. The manufacturing is rapid. We're not putting cells through rounds and rounds of manipulation that can add complexity costs and genetic variability.
We're starting with the real NK cell, we're expanding over 14 days, not 45 and we're coming up with a very attractive cost of manufacturing. We have an integrated platform with all the company components in place, expansion, proprietary stimulatory cells, engineering for persistence with a proprietary membrane bound IL-fifteen, proprietary targeting like our CD19 as well as cryopreservation. As you know, these cells don't like to be frozen, they don't like to be thawed. We've been able to do that, freeze them, thaw them, put them in a vial, ship them, thaw them, give them to patients in an outpatient based setting. So all of that is integrated into our platform and we just recently added the deal with CRISPR, so we can now add genomic engineering with CRISPR to our already very robust platform.
So at the end of the day, while much is made of the cell source in the NK field, it's the final product that drives efficacy. When there's clinical data, that's what's going to matter and not the starting material. A lot of questions we hear about platform differentiation will be settled by clinical data and we're well on our way to showing that both with 101 as well as 19. So that's an introduction to the company, Kelly.
Great. It's very informative. And clearly, 2021 is a big year for Encarta. And before we dive into pipeline and for details, maybe I have 1 high level questions for you to share your insight for the cell therapy space. So what do you think about CAR NK versus CAR T?
What's the advantage and disadvantage? And also in terms of the stage of development for NK cell space or CAR NK, Could you actually share some comments on that relative to the stage of CAR T? And what kind of new development innovation going to come in next 3 to 5 years in N case space?
There's a lot to unpack there, but Greg, why don't you go to the slide that James can talk about the differences between NK versus T. James, you want to take grab that 1?
Sure. And I'll comment first that we're big fans of T cells and CAR T cells as well as CAR NKs and we have a program that we'll be collaborating with CRISPR on that combines the 2 modalities together. Ultimately, I think the cell types have different strengths. From a manufacturing point of view, it's much easier, I believe, to expand very large numbers of NK cells as well as to engineer them. They are somewhat safer in their application.
They should be because they don't have that sort of wild expansion that T cells exhibit. And they're naturally suited to allogeneic use without editing, because they don't cause GVHD, you don't need to worry about their targeting of the T cell receptor. And we see advantages to combining the 2 modalities. They support 1 another. They're complementary to 1 another.
In terms of indications, I'm sure we'll see that there's spaces where NK cells are naturally better suited than other spaces where T cells are. Was this the slide you wanted me to speak to Paul?
No, I think I wanted you to go to the T cell versus NK cell.
Yes. Because I guess the only other point I would make about them, we know that NK cells on a cell per cell basis are highly cytotoxic and they recognize many different determinants that are over expressed on tumor cells. So what we've observed is that even on against cell types that are expressing very low levels of the target ligand, say very low levels of CD19, NK cells retain their cytotoxic capability in settings where T cells will tend to lose their potency because they can no longer see their target antigen. And again, even without our engineering, NK cells will recognize and kill target tumor cells in solid tumor settings, that's likely to be a really important factor. So I'm not sure this is a slide that illustrates that, but it's we had data speaking to that point and I think it's generally understood of NK cells as well.
And since you're on this slide, maybe I can add on another question regarding. So it is well known that another company actually working on iPSC derived NK cells and then you're working on donor derived NK cells. And I think 1 difference standing out is the variation of the NK cell population. So my question here is for the manufacturing process, you actually expand NK cells from individual donor. Alternatively, you actually put cells from different donors and so to gain better homogeneity and which way you think is better?
And I mean, first, what is your manufacturing process? And secondly, maybe make a comparison between these 2 approaches?
All right.
So James is going to answer that with this slide. Thank you, James. And I have to apologize, the slide I was referring to is no longer in this deck. So James did a great job answering the question without the slide. We've kind of moved on between the comparison with NKs and Ts, but I think this question is a really important 1.
So James, why don't you go through this slide and the differences and then Ralph can talk about our 14 day expansion and our manufacturing process after you do that, if that's okay?
Yes. So again, I mean, I think this is illustrating differences between cell sources and you were asking specifically about variability in the final product. And I think it's important to bear in mind with cell products in general, a lot of that variability will be driven by your process. So we found that the our expansion and engineering process tends to focus the phenotypes of the cells to a great extent. So that's from donor to donor final product sales exhibit more similarity than difference.
That's partly because it's a very rapid process. We're not keeping them in culture for an extended period of time. We're driving the expansion, the activation very strongly and very consistently in every donor. We have a very, I would say, for this field, a very simple and straightforward process. By contrast with iPSCs for instance, it's typically over 6, 7 week process with multiple steps of differentiation.
It's hard to maintain complete control of a cell product over that period of time and hard to keep costs under control. Final point, I guess, I would make is you asked about deriving the cells from a single donor rather than a pool. We use single donors and at this point that's supported by all the regulatory guidelines as well, where pooling of donors is really kind of a high bar and it's discouraged by the regulatory agencies.
So let me just add a little bit to that, Kelly. When anybody refers to 1st generation and 2nd generation platforms, 1st generation human derived platform is generally referring to the autologous T cell platform. We are not that 1st generation. We're a next generation platform with allogeneic off the shelf current case. So Ralph, with that, do you want to answer Kelly's question about our manufacturing process and walk people through that?
Sure. I'd be happy to do that. Just to remind everybody, right, is that all our product candidates are being designed as off the shelf therapies, right, and that our eventual manufacturing process at commercial scale is going to deliver hundreds of doses from a single healthy donor. And our starting material are, as we've already discussed, are bona fide NK cells from adult healthy donors. So we start with real NK cells at the beginning of the process.
And the 2 critical components of our expansion technology are proprietary to stimulatory cell line as well as the transduction with a membrane bound IL-fifteen, both of which are required and activate the AK cells induce them to grow and are important for the persistence of the cells. Another key component of the manufacturing platform is of course cryopreservation. We have been able to come up with a cryopreservation process that results in functional cells straight at the vial. So at the clinical side, there is no further processing or culture of the cells required other than that basically saw and value the cells for administration. And we can show both in vitro and vivo experiment that the cells out of cryopreservation maintain their potency and are really straight up in the vial.
If you
go to the next slide, I think I want to talk a little bit about the potential for expansion. As you can see in our roughly 2 week manufacturing process, we can get several fold several thousand fold of expansion of the NK cells. And if you take that together with the high number that the several 100, 000, 000 NK cells we get from a single donation that enables this manufacturing platform where we think we can get greater than or at the 500 plus doses from a single manufacturing run at a 1, 000, 000, 000 cells per dose. That's another advantage, for example, of a core blood cells, right, the starting material from core blood is about a 100 fold less NK cells compared to adult healthy donors. And this large potential this potential for large expansion that also drives down the cost of manufacturing.
So we believe you can get to about $2, 000 per dose from a cost of manufacturing perspective.
And Rob, you could go longer than the 14 days as well and expand further, right? And so this is a relatively conservative approach, but 1 that we're really comfortable with at the moment.
Yes, that is correct. We can continue to expand these cells beyond that time.
And also from 1 donor per run, you actually can generate enough doses for 1 Phase III trials. I mean, is cell therapy actually a pivotal trial, such not Phase III?
Thank you for saying that, Kelly. Yes, it's a very, very accurate and timely manufacturing process from the healthy donor.
I see. I can see the advantage. And I think we went through the good information regarding your technology and the manufacturing process. Now we should switch the topic to your lead assets in the pipeline. Maybe start with 101.
Could you talk more about the rationale to select the MTG2D? And also why prioritize hem malignancies, AML and MDS as the first 2 indications given that NKG2D actually has very broad expression across tumor types including solid tumors.
Right. That's very good point. Why don't you go to the pipeline slide, Greg, that way Kelly can ask more questions on the pipeline. And Tanya, if you'd like to kind of walk through a little bit the rationale behind AML MDS first and then solid tumors because that's both of those are in the pipeline?
Yes, happy to, Paul. So 1 of the biggest rationale for us with looking at NKX-one hundred and 1 in relapsedrefractory AML as our first in human indication comes from clinical literature using non engineered NK cells in these patients. So I believe we have a slide on that as well. So what we did is when you and that's relevant to NKX101 because NKG2D is the main activating receptor on a natural unengineered NK cell or naked NK cell. And we've always done or I shouldn't say all.
What we've done is taken it, added it to a CAR along with a membrane bound IL-fifty. So this table on the right directly answers the question of why we chose relapsed refractory AML. So when you look at the clinical experience of non engineered NK cells, when folks across variety of small single center academic trials, they have noticed a response of between 20% to 50% of complete remissions with varying decrease of hematologic recovery in patients with these malignancies. So that's the main rationale that drove us to evaluating ENKX101 in AML as our first trial. But as you rightly pointed out, these ligands are regulated across a variety of different tumor types as shown on the table on the left here.
So it is our intention as clinical data supports it to expand our development program into other indications as well.
So Kelly, just to be clear, so NKG2D has the potential in multiple indications, both heme and solid tumor in its current form. So we're really excited about this, the small molecule and NK GGD being the natural receptor in the NK cell makes absolute good sense to use this as the first program of the 2 COLI programs going forward along with our CD19 program.
Very interesting. And clearly also introduced us regarding the Phase I trial design and where you're at? And what would be the next data readout?
Kanya?
Yes. So our Phase 1 trial design is summarized on the slide. There's a lot of information, so I'll walk you through quickly from the top to the bottom. So it's a multicenter Phase I study with a primary goal of finding safety DLTs and also looking at efficacy, of course. So we think of our study treatment as multi dose in a cycle, and there's an option to give multiple cycles as well.
So in NKX101. We are evaluating 2 regiments in parallel of NKX101, 1 given on day 714, another on day 7. And the rationale for both of these regimens is driven by, again, from dose that when you use a regimen like this with cyan flu based lymphodepletion, there's a 2 to 3 week window where the host immune system is suppressed. These being allogeneic cells, we want them to be given during that window and they can go in and hopefully achieve deep tumor control, hence the multiple doses. There is an efficacy assessment on day 28.
And based on protocol pre specified criteria, there is an there is the option to continue to get additional cycles to try and deepen the
upfront and 2 doses versus them spread out over 3 doses to see if there might be a different impact. We've seen in the literature, we've heard that by giving a loading dose of these NK cells, it may have an impact on the efficacy of the product. So we're going to see that now with this new amendment.
Great. Makes sense. And so even though you call it a multi dosing cycle, it's actually only composed of 2 approaches, 1, 2 doses, 1 for 3 doses. And I'm just curious if you see the disease progression, are you going to actually offer additional doses beyond the 3rd dose?
Yes. So we think of this as 1 cycle. So depending on any response on day 28, there is the ability to give another identical cycle lymphodepletion and multiple doses as well. We assessment of is there blast reduction in the case of AML or lymphoma regression in the case of OVA9 as well as safety criteria being met to get additional cycles.
Okay. So the decision point is actually after you see disease progression probably, not actually before.
No, I want to clarify, right? So it is to get a second cycle, it's to deepen a response. So those patients who already have some evidence of activity, a partial reduction, for example, or some decrease in blast, they can get an additional cycle to deepen the response.
Okay. Got it. Thank you. This is very helpful. And so switch to 2nd Vida asset, 19, it targets very well known CD19.
So my question here is, given there are already 3 CD19 CAR T in a commercial place, what's the rationale actually to work on this target?
Yes. Let me just start with, if you can create an allogeneic off the shelf CAR NK cell cryopreserved in the vial that can be given multiple times with proprietary bits on the technology like our CD19, like our membrane bound IL-fifteen. We believe there are advantages of the CAR NK cell as in terms of other CAR NK cells, but also in terms of T cells. It just provides another option of giving a shorter live cell multiple times without having that longer term expansion of the T cells. So we think that the space is right for CAR T CD19 programs as well as CAR NK CD19 programs.
So I think though when you look at the CAR NK landscape, is there room for more than 1 player with a CD19? Absolutely. There's more than 1 big pharma company interested in CD19. There's more than 1 autologous CD19 company interested in allogeneic off the shelf CD19 cells. So there's a lot of opportunities for the CD19 program and it's a target that everybody knows, has proof of concept both clinically and from a manufacturing point of view.
So we've got a great program with some great proprietary technology around it in a cryopreserved vial ready for shipment, ready for thaw and ready for injecting new patients. Anything anyone wants to add to that?
Tim, the 1 additional piece to add to that is, while I think we've seen tremendous progress in the allogeneic CAR T space, I think as we think about moving from the specialized centers that currently administer autologous T cells and try and move more into the community outpatient setting. I think there's a spectrum of sort of opportunities there. And we might still be with the allogeneic CAR Ts kind of moving from specialized center inpatient to outpatient, but maybe not quite to community settings. The safety profile and benefits of an NK cell platform, I think are going to move the paradigm dramatically towards that true community setting. And I think the patient access that that enables with the safety, the manufacturing costs and the ability to multiple dose, you're starting to think more like you're dosing an antibody rather than a cell therapy.
And I think it's that paradigm shift that the NK cell enables.
Makes a lot of sense. The NK cell has the flexibility. And so the very last question is for the next 6 to 12 months, what will be the key milestones and the different events for investors to pay attention? And also what are the key learnings since the company was established in MK space?
Great.
Why don't you go to that slide, Greg. So as you can see, we've guided to a handful of patients in the AKX101 trial. So the AML, MDS trial will have a handful of patients and data by the end of this year. That's what we've guided to. The protocol amendment that Kanya just went through with the regimen B will only enhance our ability to get there by the end of this year.
We haven't said where we might present the data. It could be at a medical meeting. It might just be a presentation. But we're we have the patients and we have a couple of cohorts and maybe a dose response, we're going to talk about those data. So that's 1 key milestone coming up.
The IND for CD19 was cleared recently and first patient will be in the second half of this year. And we'll have, as Nadir, I think mentioned earlier, data in the 2022 timeframe interim data. Then final data on both programs will happen in the first half of 20 23 for proof of concept for both of our programs and the proceeds from our IPO right now we guided will take us in the second half of 20 23. So proof of concept data from the 2 co lead programs. Additionally, we'll file an IND amendment for a solid tumor indication for NKX-one MKX101.
That's hepatocellular carcinoma, cholangiocarcinoma and colorectal carcinoma isolated from the liver with a local regional approach. So you get as many cells as possible into the solid tumor for proof of concept and then we'll bridge into a systemic type of administration. So that's another milestone that's coming up real soon. The CD70 program is coming up as well and that's attached to a very major milestone that we recently did, which was an awesome deal with CRISPR Therapeutics, which Nadir just did. And this is a multi gene editing genome engineering deal that we did with CRISPR where we're taking the benefits of our technology together with the benefits of their technology in a very equal partnership contributing equal to the cost as well as the profits of the CD70 program and the NK plus T program and another third program to be determined later.
And so that is part of our pipeline now and that collaboration with CRISPR where we're using their experience with their CD70 CAR T cell and their clinical experience with our CD70 CAR NK cell as well as their T cell component along with our NK cell component in the NK plus T program. So we're really, really excited about that. I wish we had another 10 minutes for Nadeer to take you through that deal because it's really exciting for the next time. And then finally, the manufacturing. We put that on the pipeline side because it's important you own your own manufacturing.
The process is the product. We've completed a roughly 3, 000 square foot clinical GMP facility that's making our 019 clinical supplies and will make our 101 clinical supplies. And now we're planning on a commercial facility, which is here on the bottom of this chart, which will enable the launch of our products where we will own our process and own our manufacture. So those are the milestones. What have we learned from the beginning of the company?
Own your own manufacturing is 1 of the most important things, particularly in light of what we went through with COVID. The best thing to do is have control of your manufacturing, have your own people who are responsible for the process development implementation of your process, be involved in the manufacture of your process, have it nearby. That's our intention for our commercial facility. That's 1 big thing. The other is to pick indications for your lead molecules and to have a balance of that sort of novel target on a novel platform with a well known target that has clinical proof of concept on a novel platform to use natural killer cells as the starting material to expand natural killer cells into more natural killer cells, so that what you're giving patients is a natural killer cell engineered for targeting and persistence and cryopreserved in a vial so you can deliver that product to a patient in the community as well as a hospital based study.
Great. A lot ongoing and it's very exciting moment. And we are running overtime and we have to wrap up our session here. And thanks again from Encana team joining us today. And we are looking forward to the next milestone.
And thanks everyone online for attending our session. Thank you.
Thanks, Kelly.