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spk05: Good day, and thank you for standing by. Welcome to the Nexter Therapeutics Third Quarter 2022 Financial Results Conference Call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1-1 on your telephone. You will then hear an automated message advising you your hand is raised. Please be advised that today's conference is being recorded. I would now like to hand it over to your speaker today, Vivian Wu. Please go ahead.
spk08: Thank you, Crystal, and good afternoon, everyone. Thank you for joining us today. With us on the call are Howard Robin, our President and CEO, Dr. Jonathan Zalewski, our Chief of Research and Development, Jill Thompson, our Chief Financial Officer, and Dr. Brian Codson, our Chief Medical Officer. On today's call, we expect to make forward-looking statements regarding our business, including statements regarding the therapeutic potential of and future development plans for our drug candidates in research programs, the timing of the initiation of clinical studies, and the availability of clinical data for our drug candidates, the timing and plans for future clinical data presentations, the formation, future development plans, or success of our collaboration arrangements. The expectations following are corporate restructuring and reorganization, financial guidance, and certain other statements regarding the future of our business. Because forward-looking statements relate to the future, they're subject to inherent uncertainties and risks that are difficult to predict, many of which are outside of our control. Our actual results may differ materially from these statements. Important risks and uncertainties are set forth in our Form 10-Q that was filed on August 5, 2022, which is available at sec.gov. We undertake no obligation to update any of these forward-looking statements, whether as a result of new information, future development, or otherwise. A webcast of this call will be available on the IR page of our NECDR website at NECDR.com. With that said, I would like to hand the call over to our President and CEO, Howard Robin. Howard?
spk01: Thank you, Vivian. Thank you to everyone for joining us today. During the third quarter, we continued to make meaningful progress toward execution of our new strategic plan, directed to the fields of oncology and immunology, with a sharp focus on three core R&D pillars, Nectar 358, Nectar 255, and our research activities. With Nectar 358 and Nectar 255, our biologic clinical pipeline is poised to generate value-enhancing clinical trial data beginning in 2023 and continuing through 2025. Importantly, our plan provides us with a cash runway through the middle of 2025, and this is exclusive of any potential future cash inflows from new partnering activities. Each program in our pipeline provides us with a distinct and highly promising opportunity to provide patients with novel potential medicines across a range of therapeutic areas, and we're already starting to see encouraging data across our portfolio. This past quarter, we reported positive data for our clinical stage program in immunology, Nectar 358, now known as RegPEG-Aldisleukin, or ResPEG, in the setting of ectopic dermatitis. ResPEG is being developed with our partner, Eli Lilly, in multiple autoimmune diseases, and in addition to ectopic dermatitis, we're also pursuing lupus, and we have plans to go into at least one additional indication, and we look forward to announcing that new indication in the coming months. Our lupus phase two study, which enrolled about 280 patients, is expected to report top-line data in the first half of 2023. And the important Phase Ib data in ectopic dermatitis patients that were presented in Q3 will shape the robust Phase IIb study in this setting, which is planned to start also in the first part of 2023. The design for that study is being finalized now, and Brian will provide further information on the RESPEC program in a moment. Our second significant clinical program is NECTAR-255, our novel, wholly-owned IL-15 agonist being developed in both liquid and solid tumor settings. In large B-cell lymphoma, we're on track to initiate our own sponsored study of NECTAR-255 in combination with approved autologous CD19 CAR-T products. The study is designed to demonstrate the potential of NECTAR-255 to enhance the efficacy benefit of these therapies. This Phase 2-3 trial will be a randomized, double-blind, placebo-controlled study comparing Nectar 255 versus placebo in relapsed or refractory patients being treated with CAR-T cells. It will position us for key comparative data in 2024 for Nectar 255 in second-line and third-line large B-cell lymphoma, which is the labeled indication for these approved CAR-T products. In multiple myeloma, we plan to present the data from the first several patients enrolled in our study of Nectar-255 in combination with Darzalex Faspro at the upcoming ASH meeting in New Orleans. The study is continuing dose escalation and we're encouraged by the early data we see that continue to support the biologic mechanism of Nectar-255. Specifically, we've observed that Nectar-255 can restore blood NK cell levels after Darzalex-mediated NK cell clearance. And finally, the javelin bladder medley phase two comparative study in combination with Avilamab began actively enrolling patients in the third quarter. Our partner Merck KGA is running this study, and we're on track to generate PFS data for this study by the end of 24. In research, we're working on a novel TNF R2 antibody that we believe will be highly differentiated from anything in the field and holds great promise as a next generation selective Treg agent in autoimmune diseases such as multiple sclerosis and inflammatory bowel disease. This will be the first antibody program in our pipeline and we're focused on advancing this important new mechanism to be prepared for IND enabling studies in 2023. In addition, we're continuing to advance our preclinical work in oncology Nectar-288 is a novel PEG conjugate of interferon gamma designed to modify binding of interferon gamma to its receptor and non-receptor substrates and optimize the duration of interferon gamma signaling. Next week at CITSE, we'll present the first set of preclinical data for this program. We ended the third quarter with approximately $546 million in cash, and as I stated earlier, we've implemented a strategic plan which enables us to have a cash runway for through the middle of 2025. We do not anticipate a need to raise capital during this period. We are well-funded with a strong financial position, and we will enable us to drive our key programs forward to value-generating data and milestones. And now I'd like to turn the call over to Brian to provide an update on RESPEG. Brian.
spk06: Thank you, Howard. RESPEG is a unique molecule, and I am truly excited about the work we are doing with our partner, EI Lilly, on this important first-in-class Treg stimulator for the treatment of autoimmune and inflammatory diseases. Our goal with this program is to address the underlying Treg deficiencies and consequent overactivity of effector T cells in these diseases by selectively activating and expanding Tregs. Unlike immunosuppressive drugs, Respeg is designed to bring the immune system back into a normal balance. The data we recently presented in atopic dermatitis continued to reinforce our conviction in this approach. As Howard mentioned, this past September at the EADV Congress, full data from our first initial proof of concept study in moderate to severe atopic dermatitis were presented. The 12-week Phase 1b study conducted by Lilly, tested two doses of RESPEG compared to placebo, and then followed patients for 36 additional weeks after the last dose of therapy. Treatment with RESPEG showed a dose-dependent reduction in eczema area and severity index scores in patients, also known as the EZ score, with approximately a 70% reduction in scores at week 12 at the highest dose tested. We also saw a trend toward a dose-dependent improvement in the investigator global assessment for atopic dermatitis and its responder rates through week 12 of treatment. Consistent with the RESPEG mechanism of action, total Tregs and CD25 bright Tregs increased versus placebo through week 12. The efficacy observed at 12 weeks of treatment with RESPEG is in line with efficacy observed after 16 weeks of treatment with Dupixent. the current standard of care for moderate to severe disease. But clearly, the most fascinating observation from the study was that when we looked at patients 36 weeks after we stopped dosing RESPEG, their skin scores and other measurements of disease remained very low, and this is an effect that is not observed with Dupixent. This has us and Lily very enthusiastic about the potential for long-lasting responses and infrequent maintenance dosing with ResPeg in the setting of atopic dermatitis. When we began this program at Nectar, our hypothesis was that restoring Treg populations in Treg-deficient patients would restore the normal balance in the immune system and potentially provide a disease-modifying therapy. Along with Lilly, we coined the term resolution therapeutic to describe the mechanism of RESPEG. We are excited to see the long duration of sustained response observed in the atopic dermatitis study consistent with this hypothesis. In addition, we are encouraged by RESPEG's safety profile. No serious or severe adverse events were reported from patients treated with RESPEG. These collective data support our plan to initiate a Phase II study in atopic dermatitis together with Lilly. This will be a relatively large placebo-controlled study. We expect the design of the study to be completed near the end of the year and the studies to start in the first part of 2023. Respeg is also being evaluated in a Phase IIb study in patients with continued active lupus despite being on standard background therapies. As a reminder, this Phase II study evaluates three dose levels of RESPEG compared to placebo in approximately 280 patients for a 24-week treatment period. The study is fully enrolled, and we are on track to report data from the study in the first half of 2023. Lastly, Lilly is also planning a third Phase II study in a yet to be announced autoimmune indication, which we hope to unveil in the coming months. We have a number of important milestones for RESPEG in 2023, and the compelling data generated to date reinforce our confidence in this program. We are looking forward to our continued collaboration with Lilly. And with that, I'll hand the call over to Jay Z to discuss Nectar 255 and our preclinical programs. Jay Z?
spk12: Thanks, Brian. Our therapeutic candidate, Nectar 255, is an agent that engages the full biology of the IL-15 pathway to provide functional activation and homeostatic control of IL-15 responses of immune cells, namely natural killer cells, CD8 T cells, and immune memory subsets. As a full agonist of the IL-15 pathway that can signal through both cis and trans presentation of the tribaric IL-15 receptor complex, NECTAR-255 can be combined with multiple mechanisms ranging from targeted agents to cell therapies, including CAR-Ts, and even checkpoint inhibitors to potentially improve the efficacy of these agents. We are pleased to be presenting the first data for NECTAR255 in combination with Darzalex in patients with multiple myeloma at ASH. This combination study of NECTAR255 plus Darzalex is a key biological proof of mechanism study for NECTAR255 because of the unique consequences of the Darzalex mechanism of action. Darzalex is the CD38 targeting antibody that depletes CD38 positive cells through ADCC mechanism. Darzalex is effective for the treatment of multiple myeloma because M cells, which are the pathogenic tumor cells in multiple myeloma, express CD38 on their cell surface and are effectively targeted and depleted by Darzalex. However, NK cells also express CD38 on their cell surface, and these cells are also directly targeted and depleted by Darzalex. And since NK cells are the critical immune effector cells that execute the ADCC mechanism, an emerging hypothesis is that restoring NK cell levels during Darzalex treatment may be beneficial. Consistent with this hypothesis, last summer we published a paper in Blood Advances with our collaborator, Dr. Nikhil Munshi and Dana Farber, that showed NECTAR255, when used in combination with Darzalex, substantially potentiated the efficacy of Darzalex against multiple myeloma cells in a number of in vitro and in vivo preclinical models. As mentioned by Howard, we're very encouraged to see that the early patients in the NECTAR255 plus Darzalex combination demonstrated NK cell recovery in the peripheral blood within days after starting Nectar 255 administration. This proof of mechanism study is continuing to enroll patients, and as we've stated in the past, we will wait to assess the mature data from dose escalation before making a final determination on any investment in future ADCC combination work in this setting. We are also focused on pursuing Nectar 255 as a potentiator in the landscape of cell therapy. Since their first approvals years ago, The usage of autologous CD19 chimeric antigen receptor T cells, or CAR-T therapy, has grown significantly in the B-cell lymphoma treatment landscape. Although these therapies offer great treatment benefits for those patients who fail first or second line treatment, many patients tend to relapse over time post-treatment with CAR-T. And there is a high unmet need to provide both an extended duration of response and to drive a higher frequency of complete response. We have done a large number of preclinical studies using multiple autologous CAR T therapy, demonstrating that addition of NECTAR255 can drive cell proliferation and expansion in the presence and absence of antigens, as well as maintain CAR T cell functionality and sustain their survival by limiting cell death pathways. In multiple mouse preclinical studies, the combination of NECTAR-255 plus CAR-T is far more effective than CAR-T alone in clearing tumors in xenograft models. So consequently, our clinical hypothesis is that the addition of NECTAR-255 to the CAR-T regimen may increase CAR-T cell levels, leading to enhanced efficacy. As Howard said earlier, we are on track to initiate the NECTAR-sponsored study of NECTAR-255 combined with approved CAR-T therapy. Next month at ASH, we will unveil the trial design of this phase two slash three study in patients with relapsed or refractory diffuse large B-cell lymphoma. The goal of this study is to generate comparative data with NXRD255 plus CAR T cells versus placebo plus CAR T cells. Our target is to initiate the first clinical sites in the study by the end of this year. And as Howard stated earlier, We are expecting initial data in the second half of 2024. We already have two studies underway with external collaborators to evaluate NECTRA255 in combination with CAR T therapy. The first study is sponsored by Dr. Crystal McCall, who is the founding director of the Stanford Center for Cancer Cell Therapy and is combining Stanford's proprietary CD19, CD22 bispecific CAR T cell therapy with NECTRA255 in patients with relapsed or refractory acute lymphoblastic leukemia. The second study is being conducted by Dr. Cameron Turtle's lab at Fred Hutchinson Cancer Center. Fred Hutch is combining Nectar 255 with Brianzi in relapsed or refractory large B-cell lymphoma patients. The goal of these two studies is to demonstrate the pharmacodynamics and safety of Nectar 255 plus CAR T therapy in patients. Our objective is to demonstrate that Nectar 255 promotes CAR T cell expansion and duration of persistence with repeated treatment. Additionally, the studies will assess the full safety profile of Nectar 255 when beginning treatment shortly after the start of CAR T cell therapy. We expect to have results from the first several patients in these studies in 2023. Another focused area for our development plan for Nectar 255 is the work being conducted with Merck KGA, who has initiated the Javlin Bladder Method Study. This Phase II randomized open-label study is comparing abelimab combinations with three anti-tumor agents, Nectar 255, Fidelvi, and one of Merck's own anti-TIGIT therapeutic candidates. tested in the setting of maintenance treatment for bladder cancer in patients whose disease did not progress following a platinum regimen. Avellamab is annualizing at about a $500 million revenue run rate in this setting, and the study gives NEXRA 255 a possible path to a future registrational trial in this setting based upon the strength of the data generated in this Phase 2 study. We expect the first potential PFS data from the Phase II study in late 2024. Now, turning our attention to our preclinical research programs, we are cultivating our research pipeline with a near-term focus on biological programs that have applications in oncology and immunology. One of the programs we are working on is NECTAR-288, a PEG conjugate of the protein interferon gamma. Interferon gamma is a cytokine that induces cellular antigen presentation and enhances tumor antigen-specific cytotoxic T cell responses and may have application in a number of therapeutic areas, including oncology, infectious disease, and others. With Nectar288, we have designed a site-specific conjugate of PEG to protein in order to modify binding of interferon gamma both with its native receptors as well as its other binding substrate, heparin. Overall, this design enhances and prolongs the pharmacodynamic duration of interferon gamut signalment. In our preclinical settings, NECTAR-288 upregulated MHC Class I and PD-L1 expression on tumors and enhanced the anti-tumor activity in mouse models when combined with anti-PD-1 or PD-L1 and also worked as a single agent. We look forward to presenting these and additional data for our NECTAR-288 program at CISI next week. We are also continuing our preclinical work on our tumor necrosis factor receptor 2 program, or the TNFR2 program, in collaboration with Biologic Design. The goal of this program is to generate novel antibodies that are selected agonists of TNFR2. TNFR2 is a key receptor that signals exclusively through transmembrane TNF-alpha to suppress inflammation and promote tissue protection and repair. One key role of TNFR2 is to promote Treg stability, homeostasis, and function in diverse anatomical tissues. We have leveraged our understanding of Treg biology, and in particular, their responsiveness to IL-2 signaling versus NF-kappa-B signaling to drive the TNFR2 antibody discovery in collaboration with biologic design. A TNF R2 agonist could have application for a number of autoimmune inflammatory diseases, including multiple sclerosis, inflammatory bowel disease, arthritis, as well as antibody-mediated autoimmune diseases. We look forward to keeping you updated on our progress as this program matures. With that, I will turn the call over to Bill for a review of our financial guidance. Bill?
spk10: Thank you, Jay-Z, and good afternoon, everyone. We ended the third quarter with $546 million in cash and investments and no debt. Our 2022 financial guidance remains unchanged, and we expect to end the year with approximately $450 million in cash and investments. We rapidly executed our restructuring and strategic plan beginning in April, and because of this, our financial position remains strong with a cash runway that extends through the middle of 2025. This will take us through several key value-generating milestones for our pipeline. Our team has worked diligently to execute an efficient operational wind-down of the BEMPEG program, consistent with our obligations to patients and their physicians. In accordance with that plan, all patients on the six NECTAR-run BEMPEG studies have now transitioned to standard of care or other post-trial treatment options. Now I'd like to remind you of our financial guidance. OUR FULL YEAR GAP REVENUE GUIDANCE IS UNCHANGED AND EXPECTED TO BE BETWEEN $85 AND $95 MILLION, WHICH INCLUDES 15 TO 20 MILLION OF PRODUCT SALES AND 70 TO 75 MILLION IN NONCASH ROYALTIES. WE STILL EXPECT TO RECOGNIZE A TOTAL OF APPROXIMATELY $150 TO $160 MILLION IN RESTRUCTURING AND IMPAIRMENT CHARGES RELATED TO THE BEMPEG PROGRAM TERMINATION. Our R&D expense is still expected to be between $240 and $250 million, including $40 to $45 million in non-cash depreciation and stock compensation expense. And our G&A expense is still projected to be between $90 and $95 million, including $25 to $30 million in non-cash depreciation and stock compensation expense. Our non-cash interest expense is expected to be between $25 and $30 million related to the prior monetization of our royalty streams. I'd like to reiterate that we still plan to end the year with approximately $450 million in cash and investments. And with that, we will now open the call to questions. Crystal?
spk05: Thank you. As a reminder, to ask a question, please press star 1-1. You will then hear an automated message advising you that your hand is raised. And in the interest of time, we do ask that you please limit yourself to one question at this time. Please stand by while we compile the Q&A roster. And our first question will come from Jay Olson from OPCO. Your line is open.
spk07: Oh, hi. This is on the line for Jay. Thanks for taking the question, and congrats on the progress. Maybe on the RASPAC, just wondering how are you thinking about this and that need that can be potentially addressed by RASPAC, and if you think the target population could be those who do respond well to the PICC-Cent. And maybe if I can ask two-by-five questions in combination with CAR-T. Wondering what's the expectation you want to see for the additional benefits, whether are planning or hoping to see higher response rates, say, at month six, where patients may remain disease-free for longer time. Thank you.
spk06: So, thank you for the question. You know, in atopic dermatitis, it's important to emphasize that the mechanism of RESPEC is completely different than any of the other therapeutics now being studied. And because of this, you know, it seems very possible that patients who do not respond to standard of care therapies, for example, Depixent or even other IL-13, you know, directed therapies, can respond to a mechanism like RESPEG, which is really extremely different. You know, it's inducing Tregs to suppress the inflammation at the site without increasing immunosuppression. So, RESPEG has this possibility in terms of the unmet need that you're asking about to not to approach people who are not responding, for example, other standards, others, you know, therapy, standard of care therapies like, for example, Dupixent and the IL-13 directed therapies. It's also important to emphasize that in our initial data, we saw this really fascinating observation that once we stopped therapy, we continued to see a suppression of disease. This was really quite remarkable. And it's this durability of response that also differentiates us from, for example, Dupixent. So it's possible that we could deliver this therapy and maintain responses with very infrequent therapy, much less frequent, for example, than Dupixent. and or even without therapy for long periods of time. And I think this is another area that we can differentiate in this space. So thanks again for the question.
spk08: And we'll have Jay-Z answer the 255 question.
spk12: Yeah, thank you. So the question was about the expectation in our study. So I guess I'll start off by reminding you about some of the preclinical studies that we've conducted. Evaluating vector 255 in combination with a range of different therapy. And we'll be seeing both in vitro and in vivo. Is it the addition of nectar 255 causing 2 really strong biological. Effects very prominent effect 1st is it causes a very large expansion. In the maximum number, the peak of car T cells. That proliferate inside of the organism. after the CAR T cells have been transplanted. Remember, these are living drugs, and they proliferate inside of the patient or inside of the test system and say it's a mouse or something. So with 255, we see a large expansion in cells. Second thing that we see is a prolongation of the cell's survival inside of the animal when we treat with 255. So you get both an increased number and you get an increased persistence. And in those preclinical studies, that leads to substantial efficacy. Efficacy relative to CAR T alone in the absence of 255 is quite different. It's a night and day kind of a difference. So then when we turn our attention to some of our expectations, we hope to see similar kinds of effects. We would like to see increases in CAR T cell number when we add 255 to patients receiving one of the approved CAR T cell regimens. We want to increase their peak, and we want to increase their persistence and duration. We also want to increase their memory phenotype, sustain and stabilize that phenotype, and maintain an activated state in those cells. And then clinically, our hope is that this will give rise to at least two kinds of measurements. We'd like to see an increase in the complete response rate and the durability of that complete response rate. As you know, one of the challenges with these therapies is that the effect wanes over time. We want to make that effect last as long as possible. And then ultimately that should translate to additional time to event endpoints as well. Thanks for the question.
spk05: Thank you. One moment for our next question, please. And our next question will come from Chris Shabutani from Goldman Sachs. Your line is open.
spk04: Yes, good afternoon. Thank you. Two questions. One on the sort of run rate for operating expenses. A lot of hard work this year, obviously difficult work to address the restructuring. Should we think about the level of R&D and SG&A spending that you just posted in this most recent quarter? R&D coming in below what we had projected, and I believe consensus as well. Is this a reasonable proxy if we were thinking about on a go-forward basis for the near to intermediate term? And then a second question perhaps for Howard. Obviously during the quarter there were headlines that related to a potential combination with PureTech, which would have prompted some unique sort of potential combinations for you as an entity. I think that that discussion was relatively briefly in discussions, but then terminated, I think, today was technically originally the end of that. Can you talk to sort of the genesis of that and maybe higher thinking strategically? It's clear that you have the Lilly Partnership, the oncology assets, et cetera, but that certainly was sort of ink in the ointment that not many would have anticipated. And if you could share any comments about how that came about and where we move forward from here in terms of how you and the board are thinking, that would be terrific. Thank you.
spk10: Hi, this is Jill. So I'll take the financial question first. So when we, just to reiterate, we're not changing our guidance for 2022. But as we look forward into 2023 and our runway through 2025, when we announced our restructuring plan last spring, we talked about our burn going, our annual burn going into the direction of 150 to 175 million a year on average over that time period. So I think that's the way you can think about the cash burn guidance. um gap could be a little bit different from that as you know it depends a little bit on the timing of the incurred expenses uh but if you want to focus on the gas the cash i would say 150 to 175 is kind of the right way to think about it for now and of course we'll give updated a guidance in our february call for 2023. hi this is howard good good question let me let me give you some background i think look first of all you know as i said in our in april when we
spk01: reintroduced our strategic plan and we've revised our strategic plan, I said that we'd be listening to anybody, any company that has levels of interest in a business combination. And we certainly continue to do that. And I think like any company from time to time, we're going to evaluate proposals from other companies that could benefit our business and make the proverbial one plus one equals three. And the PureTech approached us We had some discussions with them. Normally, those discussions, we have discussions, actually, we're always having discussions with companies. It's something that goes on on a regular basis. And I can tell you, though, that the only reason it became public is because under certain, they're a UK company, and under certain UK rules, it had to be disclosed, even though we were fairly early in discussions. So I wouldn't read too much into that. I would say that, you know, we're always evaluating opportunities. And if there's an opportunity that makes sense for our shareholders, we are highly interested in pursuing it. And with that, other than that, I really can't comment too much more on what we're doing in that regard. I hope that helps.
spk05: Thank you. One moment for our next question, please. Our next question will come from Mara Goldstein from Mizuho. Your line is open.
spk03: Hi. This is support from Mara. Thank you for taking our questions. Another question is on RESPAC. I know that the Phase II strategy is still being worked out with Lilly, but I'm just curious if you have some sort of baseline activity that you hope to see for the Phase II study, studies in atopic dermatitis. And secondarily, when do you anticipate getting to that point of making a decision whether this would proceed to Phase 3 of registration directed study. Thank you.
spk06: As we mentioned, we're in the process of designing the Phase 2b study, which follows our proof of concept study that was presented. You know, in terms of the goal of the next study, the Phase 2b, is really to fully demonstrate the potential efficacy that we will see with RESPEG. You know, it'll be a study which has, you know, pretty standard elements to it. There'll be an induction phase, probably similar to other agents. There'll be a maintenance phase, and we will study different dosing regimens during that maintenance phase. And I think, you know, the key points that we will be looking for is what type of efficacy, what level of efficacy do we see at the end of induction? And that will be in different, you know, patient subgroups. And then how does that compare to other therapies in the space? And then in terms of, especially in maintenance, you know, what types of infrequent dosing can we you know, get to, can we achieve that maintains the benefit that we see after induction? And, of course, we're hoping for best-in-class, you know, type efficacy. So that's our expectation. Thank you. Thank you.
spk05: Thank you. One moment for our next question, please. We'll take our next question from Roger Song from Jeffries. Your line is open.
spk13: Great. Thank you for taking the question and congrats for the progress. I did have a quick one for 255. Understanding the mechanism is proliferating the T cell. It makes sense to combine with the CAR T. But just curious, given the bispecific, particularly they also, you know, kind of a passive T cell therapy. Do you have any sense why or why not 255 can combine with those bispecifics to drive better efficacy? Thank you.
spk12: Yeah. Hey, Roger. Thanks for the question. This is Jay Z. So, certainly there is no scientific or other reason why Nectar 255 could not be combined with, you know, a bispecific, whether it's a CD3 targeting bispecific for T cells, and even an NK cell targeting bispecific, such as a CD16 arm. In fact, both of those are very relevant and reasonable opportunities as well for NK255. In terms of the basic mechanisms that could lead to potential synergy, right, of a bispecific with an agent like Nectar255, it's not that different from CAR-T. CAR-T cells express IL-15 receptors, so they're a direct target of Nectar255 in this case, whereas in the bispecific, you know, you'd be targeting T cells and giving the T cells that are CD3 positive health in a CD3 engager, or you'd be targeting and enhancing NK cells in a CD56 engager. Our intention to focus in the cell therapy space is obviously there are more approved agents here in this space. There's clearly a high unmet need as well, even in these approved on-label indications with these autologous products. And we think it's a great place to show a lot of opportunity. Another key reason why we're really focused on the cell therapy space as well is also because there's quite a lot of data that shows that IL-15 levels both that are reached post-conditioning regimen, as well as that are maintained after CAR-T treatment has begun, they seem to be highly linked with the patient's ultimate ability to mount the best and most durable, strongest response. So there's also a really strong scientific theory for IL-15 and the IL-15 pathway itself in that cell therapy setting. That's why we chose to focus there, but certainly there's No reason why we also couldn't include bispecifics as a component for a combination strategy in the future.
spk05: Thank you. One moment for our next question, please. Our next question will come from Jessica Five from J.P. Morgan. Your line is open.
spk09: Hey, guys. Good evening. Thanks for taking my questions. I'm curious, do you expect you or Lily to disclose the yet named indication for 358 before or after the lupus phase 2 data?
spk06: No, thanks for the question. I think it's, we just don't know right now. We will be announcing that indication or hope to be announcing that within the next few months, in the upcoming months, but I don't know how that will relate to the timing of the readout of the lupus study, which will also occur in early 2023.
spk05: Thank you. One moment for our next question. Our next question will come from Greg Harrison from Bank of America. Your line is open.
spk11: Hey, guys. Good evening, and thanks for taking the question. Assuming that RESPEG continues to look differentiated in atopic derm, how fast could a pivotal trial be executed, and what would it look like in your ideal scenario? Just trying to get a sense of how a larger data catalyst like this would line up with your cash burn guidance.
spk06: So, you know, I think you can look at typical studies. It does depend on the size of the Phase IIb that's in right now as we talked about, we're in the process of finalizing the design, and that will be completed around by the end of the year. And we're planning to, as we said, to initiate the study in the first part of 2023. So a typical study, the length of that study, maybe 18 to 24 months. So that's when we might expect the data, you know, from this study.
spk05: Thank you. As a reminder, to ask a question, please press star 1-1. Our next question will come from Andy Shea from William Blair. Your line is open.
spk02: Great. Thanks for taking my questions. I got two. So one, maybe for Brian, as you kind of think about the bladder cancer maintenance landscape, You know, perhaps that could potentially be approved around that setting around mid-year next year. So, I'm just curious if there's any, you know, kind of strategy to potentially get incorporated into that setting as opposed to just the maintenance setting. So, that's question number one. Question number two, maybe for Jay Z. You mentioned about the pivotal study with CAR T, which is very, very interesting. I'm curious if you could remind us about explorations that you've done to get a sense of what is the best sequencing. You kind of mentioned, you know, from previous questions about potentially after the conditioning regimen or shortly after the infusion. Curious about whether that's been worked out, especially in light of, you know, Project Optimus, where the FDA is really, you know, honing in on selecting the right dose. Thanks for taking my questions.
spk12: Yeah. Thanks, Andy. So, I think I could actually answer both of them. So, the first question you asked was about the Avelumab setting, right? So, Avelumab's label right now, is in patients that take a platinum regimen, so a chemo regimen right in the first line, and then patients that don't have a complete response, they're eligible for a Belumab maintenance. And it's quite effective, as you know, at maintaining patients, and it has a nice survival that they've presented, and that's probably the key for their approval in that setting. Now, it's true that there is some potential PAD-SEV plus PEMBRO around the corner, but it's still, you know, a phase three study that needs to complete and conclude. It is possible, we're always looking to see if that changes the first line of landscape. So, for example, does it start to erode or displace, you know, that first line chemo, which is where a Velumab is used. So that's a component that we're looking and paying attention to. And you can imagine that our collaborator, Merck KGA, is paying even closer attention to that. But we're very tuned in onto that as well. And then in terms of long-term, depending on the results that we see in this maintenance setting and what we learn in the bladder, yeah, I think there's an opportunity for additional expansion, additional lines to be evaluated as well. even potentially on that PEMBRO-PADSV regimen if that regimen is approved. So that's kind of like a crystal ball kind of a question. And the next question that you asked was about the CAR-T setting. And I think you asked a really great question. So you got in, you know, a mention of Project Optimus and the selection of dose and the selection of regimen. And this was something that we paid a lot of attention to in our preclinical studies. So we did a number of studies with our collaborator, Cameron Turtle, at Fred Hutch, using the same autologous CD19 CAR-T, where we tested multiple dose ranges and dose levels of Nectar 255, as well as timing of administration of starting Nectar 255 relative to the CAR-T cell administration. So that's something that we really, really put a lot of energy and a lot of resource into. When we unveil kind of the design of that phase two slash three study that we'll be sponsoring, and as I mentioned, we'll be unveiling that at ASH at an event that we host, you'll see a lot more color there on how we're directly addressing your question, paying very close attention to both the dose level and the dose regimen that's critical to be used in the cellular therapy. And the reason why it's particularly important in the cell therapy spaces, I mean, we always have to remember these drugs are basically living medicine, the live medicine, right? The cells proliferate. They're CD19 positive. There are a lot of B cells expressing CD19. There's a lot of antigen, right, for these cells to proliferate with and proliferate, you know, with an antigen-driven response. And so, the application of Nectar-255, prolong and sustain that proliferation as well as that total cell population and its fitness is something that both the regimen and the dose is very important to. So we look forward to sharing our approach for that with you pretty much next month.
spk05: Thank you. And I am showing no further questions from our phone lines. And I'd like to turn the conference back over to Howard Robin for any closing remarks.
spk01: Well, thank you, everyone, for joining us today. And I think we've outlined our continued progress in successfully executing on our strategy. And our pipeline and partner programs continue to advance and have the potential to address the needs of significant patient populations and provide the opportunity to create significant value for our shareholders. So I'd like to thank all of our employees for their efforts and hard work. And I want to thank our shareholders for continued support. with an update on our progress. So stay tuned. Thank you very much.
spk05: Thank you. This concludes today's conference call. Thank you for your participation. You may now disconnect. Everyone, have a wonderful day.
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