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spk13: you may press star then one on your touch-tone phone. If you're using a speaker phone, please pick up your handset before pressing the keys. To withdraw from the question queue, please press star then two. We please ask that you limit yourself to one question. If you have additional questions, you may re-enter the question queue. At this time, we will pause momentarily to assemble our roster. And the first question will come from Chris Shiv Yatani with Goldman Sachs. Please go ahead.
spk07: Yes, good afternoon. Thank you very much for the opportunity, and it's good to see progress that's being made across the programs here. If I could put my question to 358, upcoming disclosure of additional data in September. To be clear, Have we had any information about the psoriasis program? I don't believe that that had been top-lined by Lilly. Should we expect in September, in addition to the AD data, that that would be the case? And with 358, as we contemplate the different kind of immune-mediated disease indications, can you help us understand if you feel if that particular compound, this approach, 358, might be advantaged for certain patients types of indications. We've seen some early promising in lupus. There was, I believe, some disappointment in UC. If you could just help us understand how to think about that and the September readout. Thank you.
spk08: Thanks, Chris. We'll have Brian answer that question.
spk09: Thank you for the questions. I think I can take them in order, but you may have to remind me of the third one. The first question was, will we be presenting data related to the psoriasis study? And yes, the answer is yes. There will be two presentations at EADV in September. One will be directed to the psoriasis study, the Phase Ib study in psoriasis. The second one will be a Phase Ib summary of the Phase Ib in atopic dermatitis. And I just want to emphasize that The data, you know, for the presentation in atopic dermatitis will be, since we've already presented some interim data, but we'll be presenting, well, Lily will be presenting the full efficacy and the full efficacy and safety data set. You know, we've only presented interim data so far. And then in addition, I think it's worth emphasizing that we'll also be presenting additional endpoints that are also used in studies of atopic dermatitis. What excites us very much about the presentations is you'll be able to see the level of improvement and And as we've emphasized, the durability that we've seen after the drug treatment, after treatment has been stopped. So I know you asked the second question, but I need to be reminded of that one.
spk07: for 358. There's some challenges here. You know, what makes this likely to work, or what have you learned so far, perhaps uniquely mechanistically from the different indications that we're doing early clinical work on? Thank you.
spk09: Yeah, so it's a great question. I think that, you know, we're unveiling new biology here. So, you know, we're pretty much in the lead as we go to these indications and this mechanism of inducing regulatory T-cells that down-regulate the immune responses that are driving these diseases. It's new biology, and as you emphasized, we've seen some incredibly encouraging data in both lupus and in certain dermatologic skin diseases, you know, atopic dermatitis, You also mentioned the fact that we stopped the study in ulcerative colitis. I think it's important to emphasize that the T cells that drive the disease in these different indications are very different. So the T cell driving force in ulcerative colitis is a very different pathogenic pathway than what we've seen in lupus or what we know is in lupus as well as in atopic dermatitis and psoriasis. So, again, I think that we're looking, new biology is being uncovered. I would say that the fact that we saw less efficacy in the UC study that we didn't see the efficacy that we've seen in the other indications is consistent with what other people have reported that. And, you know, both with this mechanism and with other mechanisms, it just takes either higher doses or it takes other types of therapies to have an impact in ulcerative colitis that is not true in these other indications. So thanks again for the question.
spk13: Thank you. And the next question will be from Jay Olson from Oppenheimer. Please go ahead.
spk14: Oh, hi. This is John on the line for Jay. Thanks for taking our question. I guess first for three-size age, I think you previously indicated that phase two studies start in the atopic dermatitis in third quarter, and now it seems like the trial will be started probably in 23. So just wondering what's cause the delay and what are the gating factors? And separately for 255, just wondering, it seems like you are very excited about the opportunity combining 255 with CAR-T. So what will trigger an active sponsor study in that setting? And yeah, that's all. Thank you.
spk08: Thank you, Chiang. We'll have Brian answer the first part of your question, and then Jay-Z will tackle the second.
spk09: So, the reason that we're continuing to design, so the design of the phase two dose ranging study in atopic dermatitis is complex, okay? And it's basically the delay, it's just taking us longer to figure out what's the perfect and perfectly optimal type of design for the questions. I would say that the landscape in atopic dermatitis is changing. And this has also prompted us to spend more time in the study design. And that's why the study is initiation is planned for 2023 rather than the end of this year.
spk11: Thank you.
spk09: Hey, Tom.
spk11: Hey, Toby.
spk12: This is Jay-Z. So for your second question, yeah, we are definitely very excited about the potential nectar 255 combined with CAR T therapies. And I summarize really a lot of the data that we've presented now over the last, you know, almost three years where we've been studying the combination in kind of more and more complex test systems, right? Starting out with simple in vitro studies, you know, the CAR T cells, for example, have IL-15 receptors, right? You can signal With those receptors, you can make the cells proliferate. You can induce anti-apoptotic markers, you know, very simple studies in vitro, moving to more and more complex in vivo studies and cell models, and ultimately moving into, you know, different levels of patient setting. So, to clarify, you know, you asked the question of what would get us, you know, to trigger a sponsored study. Well, we are, in fact, are indeed doing a sponsored study. So this is the study that I mentioned earlier on the call where we'll be evaluating placebo with standards of care CAR T therapies versus 255 added two to three weeks after CAR T therapy transplant into the patients. So we're actually going to be doing that study. Nectar will be the sponsor. We're very excited to kick that study off, and we expect to start that study around the end of this year. And as I mentioned earlier, we expect to have data from that study in 2024.
spk13: Thank you. And the next question will be from Jessica Tsai from JP Morgan. Please go ahead.
spk11: Hi, this is JL for Jeff. Thank you for taking our questions. So our first question is on the interim analysis of 35A in the Phase II lupus study. So based on the press release, it looks like besides the safety, like efficacy also a part of the interim analysis. So we are wondering, does it mean like futurity analysis has been done based on both efficacy and safety? And if safety is part of the interim analysis, what type of safety, sorry, what type of efficacy data has been considered by the committee? Did they have a look at the primary endpoint or any of those secondary efficacy endpoints? And our second question is on the cash runway. We understand that you guided your cash runway could be into the first half 2025, but is it based solely on 255 and 358, or does it also take into any consideration that you might announce new clinical assets between now and the first half of 2025. Thank you very much.
spk08: Thank you. We'll have Brian answer the 358 question and then Jill answer the financial question.
spk09: In order to preserve study integrity and to retain blinding for the study with patients and investigators, we cannot share the data reviewed by the interim assessment committee for the interim analysis. As you know and as we've said, the study is ongoing and it's really important to maintain the integrity of that study. The interim analysis evaluated both efficacy and safety from approximately 60 percent of the patients who had completed the 24-week treatment period. And again, the study is continuing as planned based upon the pre-specified criteria. Lily, and we do not disclose the pre-specified criteria used in the interim analysis. We can say that there was no futility analysis in the study. However, the interim assessment committee had the latitude to stop the study for inadequate efficacy versus placebo. And, of course, they had the opportunity to stop the study for any important safety concern. I just want to remind you also to remember that it is a placebo-controlled study and it compares three different doses of RESPEG to placebo. So yeah, thanks again for the question.
spk06: Hi, this is Jill. So for the second question, Of course, subject to continued positive data, of course, in the preclinical programs, our plans include the continued development of those preclinical programs that Jay Z shared with you. And additionally, as Jay Z mentioned, we will evaluate a collaboration for Nectar 288, you know, and other opportunities as they present themselves.
spk13: Thank you. The next question is from Greg Harrison with Bank of America. Please go ahead.
spk10: Hi there. This is Mary Kate on for Greg. Thanks for taking our question. Maybe how are you looking to position Metro 358 in a topic term? Perhaps maybe what stands out in terms of the mechanism of action or responses seen that could be differentiating here?
spk08: Thank you, Mary Kate. We're going to have Brian answer that question.
spk09: So I think that's part of the ongoing discussion at the moment, how we're going to position 358. especially related to the current changing landscape that I mentioned before. Let me emphasize, first of all, that 358 is a completely different mechanism of action compared to the other drugs that are in the atopic dermatitis space. So, for example, the standard of care is Dupixent, which blocks the IL-4, IL-13 pathway. And some of the other drugs now introduced are basically blocking the same pathway, the IL-13 pathway, so very closely related. And the other major drugs that have been approved or in treatment, you know, in studies for atopic dermatitis are the JAK inhibitors. And there's a whole story behind the JAK inhibitors. But the important thing to emphasize right now is that Nectar 358 is a completely different mechanism. So we're looking at basically we're looking at the endpoints that are very similar in these studies, and we realize that there will be patient subsets that will respond to our mechanism that won't respond to others and vice versa, and that's how we're going to differentiate this drug.
spk13: Thank you. And the next question will come from Mara Goldstein with Mizzou Hub. Please go ahead.
spk03: Hi, this is Jerry Gong, Gong from Mara Goldstein. Thanks for taking our questions. The first is on potential business development opportunities. I know you've spoken to that on the front beforehand. Have you identified opportunities for other candidates, such as NECA 255 or other earlier candidates as well? And is there a type of deal that you may be most interested in, such as front-loaded or back-loaded milestones?
spk08: Thank you, Jerry. We're going to have Howard answer that question.
spk01: Yeah, that good question. Look, we have significant business development efforts centered around Nectar 255, although I don't think at this stage we're looking at licensing it out at all. A lot of collaborations, for sure. We've already been working with a number of companies who have been including Nectar 255 in their programs, and we're seeing some very interesting results, and they're seeing very interesting results. So I do think you will see some collaborations around Nectar 255, but I think they will be kind of diverse because in the area of cell therapy, there are a number of different opportunities. It's actually becoming quite broad, and I would like to see Nectar 255, as I said earlier, become the potentiator of choice in a number of different cell therapies, not just one. So because of that, I see a lot of collaboration potential. I do think Nectar will keep Nectar 255 as a wholly owned asset for now.
spk13: Thank you. And the next question is from Andy Tsai with William Blair. Please go ahead.
spk02: Great. Thanks for taking my question. So, you know, regarding the CAR-T combination, Jay-Z, You know, obviously, there's a lot of behind-the-scenes logistical things that you have to also figure out, the cost of the therapy, you know, hospital fees. I'm just curious if a buy-in from a partner, from a cost perspective, is required for you to go ahead and conduct this trial?
spk08: Thank you, Andy. We're going to have Jay Z answer that question.
spk12: Yeah, hey, Andy, thanks for the question. Certainly, you know, you are correct, right? These are expensive therapies. And also, as you know, when a patient takes the CAR-T, they have to remain geographically very, very close, right, to the hospital as well, right, because the patients have to be monitored so closely. So they're either in the hospital or, you know, literally across the street, if you know what I mean. So all of those things, you know, we weighed in and took into consideration when thinking about how to operationalize and execute the study. And we basically are able to conduct this study on our own. We don't need to partner with another company to execute the study. And that includes the fact that the accessibility to the cell therapy itself, remember, in many cases, it's even covered by insurance reimbursement because this is used in the on-label setting. But either way, you know, we want to make this study as accessible to investigators and as accessible to patients as well. So we took into account logistical considerations, timing considerations, even as you know, Andy, supply chain for some of these, you know, autologous products has even been challenging in some cases. We've even taken those things into account. We're very confident that we can execute this study. We're working with some of the best centers in the United States, in particular centers that have a lot of beds that treat many, many CAR T patients with these approved on-label products. So we feel pretty confident that we can execute the study. And as I mentioned, we expect to kick it off around the end of the year. Thanks for your question, Andy.
spk13: And the next question will come from Roger Song from Jefferies. Please go ahead.
spk15: Great, thank you for taking the question. Maybe just so once on the, so for the, since you're designing the phase two for atopic dermatitis and you're reporting the phase 1B in September, the full data, would you consider the results from the phase 1B as you design the study and or you will have some go-no-go decisions due to be decide as you, if you will, kind of move forward with the Phase II.
spk08: Thank you, Roger. We're going to have Brian answer that question.
spk09: No, we know the results from the Phase Ib study, and we're going forward with the design of the dose-ranging Phase IIb. We have demonstrated proof of concept in this disease indication, and we're moving forward.
spk13: Thank you. And the next question will be from Ben Burnett from Stiefel. Please go ahead.
spk05: Hi, this is Kelly Breezon for Ben Burnett. Thanks for taking our question. We just have one question regarding Nectar 255. We were just wondering if using Nectar 255 alongside CAR-T gives you any room to lower or completely omit lymphodepletion? Thank you.
spk12: Thanks, Vivian. And hello, Kelly. Thanks for the question. It's a very provocative question. Certainly, as you know right now, the most standard approach is to use Biflux, right? And that carries a lot of issues with it, both from the patient standpoint as well as availability of some of those components, as you know, if you follow this field closely. Now the thing is, we've always had this suspicion that with 255, you may have the opportunity to indeed approach sort of thinking of a conditioning regimen in a completely different way. Either it doesn't have to be as much of a, just for lack of a better term, a sledgehammer, you know, on the patient's immune system. There may be different regimens that you could use and you might even be able to omit it all on its own. That would fall into definitely much more exploratory kind of work. Definitely the investigators that we work with are very, very interested in this question, and many of them have proposed and shared some of their scientific thoughts about it. One of those that's central to all of this is that we do know that one of the most important roles of lymphodepletion is actually to create a cytokine environment in the patient that's really highly associated with an effective transplant of lymphocytes. It's basically a very supportive lymphocyte environment. And that happens by basically, you know, depleting lymphocytes and causing the body to want to adaptively replete the immune system. And so that's how you want to transplant into that kind of a kind of systemic milieu. And obviously with a mechanism like 255 and IL-15 pathway agonism, since that's such a critical cytokine, maybe it changed that a And our investigators are interested. But all that said, you know, this would fall more into the exploratory work. I think it's a future opportunity. You know, we'll be starting with using the kind of on-label approach to the CAR-T products in our clinical study. So they'll be, you know, used in the typical way. But that's one of the long-term potential opportunities for 255 is to indeed change potentially the conditioning regimen. Great question. Thank you.
spk13: And thank you. And our final question will come from Dana Gravonk with SVB Learing. Please go ahead.
spk04: Hi. Thanks for the question. A lot of good ones asked already. So I'm going to go to two for NECTAR255 that are related in some of your solid tumor combinations. So the first one in the avelumab maintenance for bladder cancer. I think that's a really interesting study. And the biomarkers you talked about are also interesting that the patients with this higher affinity NK cells seem to do better with that. And I wonder specifically, does, you know, does Nectar 255, have you done work showing that patients with lower affinity CD16 NK cells can be potentiated by Nectar 255? Will you help those patients? Or do you think you'll help the patients with the higher affinity NK cells do better? And then my second question is for the MD Anderson study post-CRT combined with drivalumab. Can you confirm that the single-arm study, and I know that indication is one where outcomes really vary widely from site to site, and how with a single-arm study you think that you could get a good sense of how the outcomes compare to historical without a randomized arm? Thanks.
spk08: Thank you, Dana. We'll have Daisy answer that.
spk12: Yeah, thanks, Dana, for the question. So your first question was around the Afelumab maintenance and the NK compartment. So Merck actually published a really cool paper in the Javelin 100, the registrational study there. And what they showed in the four spots and some of the additional analyses, right, is that patients that had the highest levels of NK cell baseline when they were randomized onto the maintenance really did the best. And so if you parsed out the outcomes, they were really kind of like the highest efficacy, you know, kind of quartile of what they observed. And so it really crystallized, you know, the idea that having an NK-rich environment was very much beneficial. Now, they didn't necessarily, like, do a lot of, well, the comprehensiveness of the phenotyping. I'm not aware of in that study. But to your specific question, you know, in this case, mechanistically, the CD16-positive NK cells right, would be the most critical. Because we do know, you know, there's 56 bright, 16 dim, 56, you know, dim, 16 bright, right? And the 16 bright ones are the ones that participate in ADCC reactions. They have a C gamma R3A that they express in high levels. What we've seen in our, you know, multiple first in human studies, both in solid tumors as well as in liquid tumors, is that we elevate CD16 positive NK cells. And that was very important for us to demonstrate as a very early biomarker of Nectar 255 biology. Because as we advance into ADCC combinations, even in the heme setting, like as in our studies with daratumumab and rituximab, we want to be certain that we're elevating CD16 positive in case health. So all of that looks really, really promising. Merck also thought all of that was very, very promising, you know, and that's why, you know, together we're very, very excited about having 255 as an arm in the javelin bladder medley. It really tests a composite mechanism to add on to Bivencio. And as I mentioned, Bivencio is really unique because it is really the only PD-L1 in IPG1-FC, and it really gives it the opportunity to kind of have potentially two mechanisms at once. with the addition of 255. So your next question around the investigator-sponsored study, so that is indeed a single-arm study, and it is a single-site study at MD Anderson. One of the things that's important here is Dr. Steven Lin is a very experienced thoracic oncologist, and he has a lot of experience working with DERVA in this setting. One of the things that this study is also measuring Your point is very important about kind of differences in regional effects. This study is specifically studying the lymphodepleted population of patients that have lymphodepletion following chemoradiation, right? So it's really looking at the most severe subset of patients. And Dr. Lin has shown in his laboratory that addition of IL-15 in that setting in his preclinical models actually rescues lymphodepletion and actually restores sensitivity to PD-L1 blockade. And so the scientific hypothesis that we're testing here is that you have an opportunity to overcome and correct the lymphodepleted effect that's seen in these subset of patients, and then we should be able to potentiate efficacy with the combination of 255 plus DERVA in these lymphodepleted patients. The other good thing is that MD Anderson does indeed treat a lot of patients. And so they also have a lot of historical experience that they can bring to bear and help in the interpretation of the study, just even within their own institution. So we're really looking forward to that study. I think it's really well designed as a signal-seeking study. And if the data from that look promising, then we would move it to proper, much, much larger studies that are randomized with appropriate comparators. Thanks for your questions.
spk13: And thank you. Ladies and gentlemen, this concludes our question and answer session. I would like to turn the conference back over to President and CEO Howard Robin for any closing remarks.
spk01: Well, thank you everyone for joining us today. Lots of really good questions. You know, today I think we've outlined our continued progress across our pipeline and partnered programs as part of our strategic reorganization. And we believe these programs have the potential to address the needs of significant patient populations and provide the opportunity to create significant value for our shareholders. We look forward to continuing to execute on these key programs and building upon our core research capabilities and unique competencies. I'd like to thank all of our employees for their efforts and their hard work, and I want to thank our shareholders for their continued support. And we look forward to providing you with updates on our progress, so stay tuned. Thanks for joining us.
spk13: And thank you, sir. The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.
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