Nektar Therapeutics (NKTR) Q2 2023 Earnings Report, Transcript and Summary

Good day and thank you for standing by. Welcome to the Nektar Therapeutics Second Quarter 2023 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. [Operator Instructions] Please be advised that today’s conference is being recorded. I would now like to hand the conference over to your speaker today, Vivian Wu. Please go ahead.

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 Zalevsky, our Chief of Research and Development; Dr. Mary Tagliaferri, our Chief Medical Officer; Jennifer Ruddock, our Chief Business Officer; and Sandra Gardiner, our acting Chief Financial 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 drug candidates and research programs. The timing of the initiation of clinical studies and the availability of clinical data for drug candidates, the timing and plans for future clinical data presentations, the formation, future development plans or success of our collaboration agreements, the expectations following our corporate restructuring and reorganization plans, financial guidance and certain other statements regarding the future of our business. Because forward-looking statements relate to the future, they are subject to 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 May 10, 2023, 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 developments or otherwise. A webcast of this call will be available on the IR page of Nektar’s website at nektar.com. Before turning over the call to Howard, I would like to note that Jennifer will be moderating the Q&A session for our team, so we can avoid technical issues during the session. We appreciate your patience. With that said, I would like to hand the call over to our President and CEO, Howard Robin. Howard?

Thank you, Vivian, and thank you for all joining us today. The first half of this year has been a pivotal time for us. In April, we implemented a new strategic plan that focuses on our immunology programs and also extends our cash runway through at least the middle of 2026. Our most advanced program is REZPEG, which a large Phase IIb study is being initiated shortly for patients with atopic dermatitis. I’ll talk more about that in yesterday’s announcement in a moment. We’re also continuing to advance our preclinical programs in immunology, a TNFR2 agonist antibody and a CFS 1 program. Our goal is to file an IND for one of these programs in 2024. Additionally, we’re continuing the two Phase II randomized clinical studies for NKTR-255 in solid and liquid tumors. With our new strategic plan, we believe we’ve created a company that is strongly positioned to get to important value-enhancing Phase II catalysts in 2024 and 2025. And these will come well before our cash runway guidance, which extends us into at least the middle of 2026. So, first and foremost, we’re committed to advancing REZPEG. Our first-in-class regulatory T-cell program, REZPEG is now a wholly owned asset of Nektar’s and preparations are well underway to initiate a randomized Phase IIb study for REZPEG in patients with atopic dermatitis, and we expect to have initial data from this study in the first half of 2025. Yesterday, we announced that clinical efficacy data previously generated by Eli Lilly for REZPEG were incorrectly calculated for both atopic dermatitis and for psoriasis. This discovery was made after all rights to REZPEG were return to Nektar and the raw data files from the REZPEG clinical studies were transferred to Nektar. The internal statistical and clinical teams in charge of these two studies at Lilly were made aware that Nektar discovered the data errors and Lilly confirmed the errors in writing -- in written communications with Nektar. The new and corrected data from the atopic dermatitis study demonstrate that 12 weeks of REZPEG therapy at the highest dose resulted in a mean EASI score improvement of 83% and an EASI 75 response rate of 41%. The corrected data also show REZPEG resulted in a very rapid and steep drop in EASI scores shortly after therapy start much sooner than existing biologic therapies approved today. And one of the most interesting attributes of REZPEG, is that when the 12-week induction treatment period was over and treatment stopped, the mean drop in EASI score continues for patients who are followed in the study. The possibility that REZPEG offer both a differentiated mechanism to the existing field of IL-13 therapies and a remitted effect for patients is clearly a provocative one. The biologic treatment landscape for atopic dermatitis is significantly growing. The approvals of DUPIXENT and other IL-13 based biologics have driven this growth. About 16 million people are living with atopic dermatitis in the U.S. alone, with 75% of these affected by moderate to severe disease. In 2021, biologic sales for atopic dermatitis were close to $5 billion and these sales continue to grow. An agent like REZPEG that eliminates the need for frequent dosing after induction treatment period would be highly disruptive to the multibillion-dollar biologic treatment landscape for atopic dermatitis for the therapies available today and near approval. Continued and frequent dosing is required to maintain benefit. And in many cases, when a therapy is removed, patients see their eczema atopic dermatitis return. And we also know that at least 50% of patients on IL-13 therapies fail to adequately respond to therapy. So, clearly, REZPEG holds great promise for treating patients with atopic dermatitis and these corrected data reinforce Nektar’s strategic plan to invest in a robust Phase IIb study for REZPEG. As we stated in our press release yesterday, we plan on holding an investor meeting and key opinion leader meeting in the coming weeks to discuss these data and share the study design for the Phase IIb trial for REZPEG atopic dermatitis. JZ will discuss more on the corrected REZPEG data in a moment and also discuss our early-stage immunology programs. With respect to our oncology asset, NKTR-255, we’re continuing to evaluate potential strategic partnership options for the program, at the same time, as we’re continuing the Phase II clinical trials. I’ve asked Mary to join us to share more about the ongoing clinical studies for NKTR-255. And with that, I’ll hand the call over to JZ to discuss REZPEG and our preclinical programs in immunology. JZ?

Thank you, Howard. Starting off with our lead immunology program, REZPEG is a unique molecule that aims to address the underlying Treg deficiencies and consequently, over activity of affected T-cells in autoimmune diseases by selectively activating and expanding Tregs. REZPEG provides a completely different mechanism of action compared to the other drugs that are currently approved or under development in the atopic dermatitis space. This program is uniquely positioned as the most advanced IL-2-based Treg mechanism in the clinic. REZPEG has potential in multiple autoimmune diseases, and while right now, our focus is on atopic dermatitis, there are plans to explore REZPEG in other autoimmune indications in the future. As Howard mentioned, we discovered the data previously reported for REZPEG by Eli Lilly was miscalculated. The primary errors were related to miscalculations for the EASI score and the PASI score, as well as the EASI-related and PASI-related clinical efficacy endpoints reported at EADV in September of 2022 in the atopic dermatitis and psoriasis posters that were presented. This discovery was only made after all rights to REZPEG were returned to Nektar and the raw data files from the REZPEG clinical studies were transferred to Nektar. A leading independent statistical firm was then employed to analyze the raw data de novo and the firm confirmed that the original statistical analysis calculated by Lilly were incorrect. For atopic dermatitis, EASI is the validated and widely used standard measurement for atopic dermatitis study that has been used by clinicians and reported in the literature for over 20 years. The EASI measures the severity of atopic dermatitis for patients and scoring ranges from zero with no disease to 72 maximal disease. The corrected and audited interim data analysis for the atopic dermatitis study utilizes the validated 72-point EASI scoring system and includes all the patient data that was available at the time of the EADV 2022 data cut. The data demonstrate that 12 weeks of REZPEG therapy at the highest dose resulted in a mean EASI score improvement of 83% with a p-value of 0.002 as compared to placebo and an EASI 75% response rate of 41%. In addition to the strong efficacy, we observed the 12 weeks of treatment with REZPEG, which is at least in line with or better than efficacy observed after 16 weeks of treatment with dupilumab, which in Phase IIa and Phase IIb studies showed a 74% and 68% improvement, respectively. An important observation in the new and corrected data was that REZPEG also provided a rapid and steep drop in EASI scores immediately after initiation of therapy. Specifically, after only two doses of REZPEG, the mean drop was minus 71% for the highest dose at the week four-time point. The corrected data also reinforces the remitted effect and durability of REZPEG responses in atopic dermatitis patients. As Howard stated, the possibility that REZPEG could provide, for the first time, a therapy that could be dosed less frequently than anything patients have available now and could provide real long-term durability. With the differentiated T-regulatory cell mechanism that we specifically designed, the underlying scientific basis for why this is happening has been hypothesized for some time. The concept is that stimulating the T-regulatory cells could result in the reeducation of the immune system by treating the underlying pathology to not just the symptoms of the disease. These clinical data provide for the first time a novel clinical finding, demonstrating that the Treg mechanism can translate into effectively what looks like memory of the immune system, resulting both in long-term durability and strong efficacy in atopic dermatitis. This is the first clinical observation of a Treg stimulating therapy being efficacious in atopic dermatitis and has the key opinion leaders extremely enthusiastic. The durability of response that we’ve observed is not seen with DUPIXENT or the other agents in the IL-4 and IL-13 class or with JAK inhibitors. And again, this has us and KOL is very enthusiastic about the potential for long-lasting responses and infrequent maintenance dosing with REZPEG in the setting of atopic dermatitis. There were no underlying formulaic or mathematical miscalculations of the other efficacy endpoints presented at EADV last year. However, I’ll point out that with all the patient data included in the new and corrected data, there was also some improvement in the vIGA responder and NRS Itch responder endpoints from what was previously reported at EADV. For the highest dose of REZPEG, the vIGA increased from 24% reported at EADV up to 29%. And for the NRS Itch measurement, the improvement was from 35% reported EADV up to 41%. For psoriasis, endpoints related to the PASI were similarly miscalculated for the validated 72-point PASI scoring system. PASI is also a validated and widely used standard for over 20 years, which is used by clinicians and reported in the literature to measure the severity of psoriasis plaques in patients. The scoring also ranges from zero with no disease to 72 for maximal disease. The corrected and audited final data analysis for the psoriasis study utilizes the validated 72-point PASI scoring system. The corrected data showed a 44% change from baseline PASI and PASI-50 and PASI-75 response rate of 32% and 21%, respectively. The statistical and clinical teams in charge of the two studies at Lilly were made aware that Nektar discovered the data errors. The Lilly team confirmed the errors and written communications with Nektar. We plan to hold an investor meeting with key opinion leaders in the coming weeks to present additional new data from the atopic dermatitis study for the 12-week induction and for the 36-week follow-up period for REZPEG, all of which strengthens the concept of REZPEG providing a remitted effect. We will also share more details about the new study design for the Phase IIb study in biologic-naïve patients with moderate-to-severe atopic dermatitis who have progressed on topical corticosteroids. We expect to initiate the trial in October of this year and we expect data in the first half of 2025. While our near-term focus for REZPEG is on atopic dermatitis, we continue to believe that REZPEG has broad potential in multiple indications. As development of this program progresses, we will continue to evaluate further opportunities and indications for REZPEG. Now turning to our immunology preclinical research programs. We are advancing our research pipeline for two autoimmune disease programs. The first program we are working on is our TNF receptor 2 or TNFR2 agonist antibody being developed in collaboration with biologic design. TNFR2 is highly expressed on Tregs, neuronal cells and endothelial cells, and TNFR2 agonism has been shown to potentiate the suppressive effect and overall functional properties of Tregs. If absent it is associated with autoimmunity and other genetic conditions resembling FOXP3 loss-of-function. In contrast, its presence has been associated with immunoregulatory function and protective effects for multiple cell populations and tissues in the body. Working with our collaborator, we have identified two lead antibodies that have been validated for selective TNFR2 binding, cell type specificity and TNFR2 agonism in primary human cell-based assays. The lead antibodies are currently undergoing manufacturing cell line development. We, along with the immunology community are very excited about the TNFR2 target and our lead TNFR2 agonist antibodies show a desirable biochemical and cellular profile. We are aggressively progressing this program toward IND-enabling studies and believe that a selective TNFR2 agonist holds great promise for the treatment of multiple autoimmune diseases. Our second preclinical program is a conjugate version of the CSF1 protein. This molecule was engineered to optimize the receptor ligand interaction and the exposure to selectively modulate the resolution process of inflammation. So traditionally, CSF1 is a myeloid targeting cytokine that’s involved in monocyte development and monocyte mobilization. In the right cytokine MOU [ph], CSF1 creates the kind of resolution macrophages that are ideal whenever you need to turn off an inflammatory response. With CSF1, we have tuned the ligand receptor binding property to generate a novel signal to the CSF1 receptor. We are characterizing this biology in multiple biologic contexts, including acute and chronic inflammation, as well as fibrosis. We are very excited about these programs and plan to file an IND for at least one of the programs in 2024 and look forward to keeping you updated on our progress as these programs mature. And now I’d like to turn the call over to Mary to provide an update on our oncology program, NKTR-255. Mary?

Thank you, JZ. We have two different development pathways for NKTR-255, one in solid tumors and a second in liquid tumors with cell therapies. So let’s talk about our bladder cancer study first. In our partnered program with Merck KGaA, Merck is conducting a randomized clinical trial comparing avelumab versus avelumab plus NKTR-255 as maintenance therapy for unresectable or metastatic bladder cancer after completion of first-line platinum-based chemotherapy. Our joint scientific hypothesis is that NKTR-255 will synergize with avelumab by generating new cytotoxic and memory T-cells, as well as NK cells to enhance the unique ADCC effect of avelumab. With the ability to capitalize on this dual mechanism of action in the JAVELIN Bladder Medley study, we are excited about the combination of avelumab and NKTR-255. Enrollment in the Merck KGaA study is on track and the first interim data analysis for progression-free survival is scheduled for the second half of 2024. Our second development pathway is in liquid tumors. Enhancing and develop [ph] T-cell function or fitness of CAR-T cells has been a key focus to improve the efficacy of cellular therapies. Several studies have now shown that higher endogenous IL-15 concentration post lymphodepletion are associated with greater CAR-T cell expansion and improved persistence, as well as clinical responses. Because of this foundational data, we are evaluating NKTR-255 in one Nektar sponsored study and two investigator-sponsored trials to enhance the cellular PK of CAR-T cell therapies to improve response rates and clinical outcomes. We believe there is a potential broad application for NKTR-255 to enhance the efficacy of cellular therapies, including autologous and allogeneic CAR-T cells and other cell therapy products from TILs to TCR-based therapies. And with that, I will turn the call over to Sandra for a review of our financial guidance. Sandra?

Thank you, Mary, and good afternoon, everyone. We ended the second quarter with $409.4 million in cash and investments with no debt on our balance sheet and we still expect to end 2023 with at least $315 million in cash and investments. We rapidly executed our restructuring and strategic plan in April, and because of this, our financial position remains strong with a cash runway that extends at least through the middle of 2026. This will take us through several key value-generating milestones for our pipeline. As discussed in May, we reduced our San Francisco-based workforce by approximately 60% and this personnel reduction represents approximately $30 million a year in operating expense reductions. The costs related to the restructuring were substantially paid in the second quarter and we have begun to realize the cost savings in this third quarter and will fully realize the annual savings in 2024. In Q2, we recorded a $13.3 million non-cash impairment charge for leased assets. For the full year 2023, we now expect to recognize restructuring, impairment and cost of terminated programs of approximately $40 million to $45 million, which includes $27 million of non-cash impairment charges recognized in the first half of 2023. I will now review the remainder of our 2023 financial guidance, which remains unchanged. Our GAAP revenue for the full year 2023 is expected to be between $80 million and $90 million, these revenue includes $65 million to $70 million in non-cash royalties and $15 million to $20 million in product sales. We anticipate full year 2023 GAAP R&D operating expenses will range between $105 million and $115 million, which includes approximately $15 million to $20 million of non-cash depreciation and stock compensation expense. We expect G&A operating expense for full year 2023 to be between $75 million and $80 million, which includes approximately $15 million to $20 million of non-cash depreciation and stock compensation expense. Our full year 2023 non-cash interest expense is expected to be between $20 million and $25 million. As I mentioned earlier, we expect to end 2023 with at least $315 million in cash and investments. We will now open the call for questions. Operator?

Thank you. [Operator Instructions] And our first question will come from Jay Olson from Oppenheimer. Your line is open.

Oh! Hey. This is Cha [ph] on the line for Jay. Thanks for taking the question. We kind of have a couple of questions on REZPEG if we may and congrats on the corrected data on the Phase Ib -- ab trial. I guess one thing that’s caught our attention and JZ you alluded to is that, the corrected data now seem to have even stronger, early separation of curves and you can now see like over 70% EASI improvement at week four, week six. So I’m just curious if you think this is like something potentially differentiating from others and how important is the early symptom improvement based on your market research and KOL feedback? And I have a follow-up.

Thank you.

Yeah. Sure.

JZ, go ahead.

Yeah. Certainly. Yeah. So thank you for the question. So -- and you rightly noted and that you saw in the materials that we released with the press release yesterday, that there is a very rapid and steep drop. And that week four-time point is very interesting, because it’s basically after patients have taken two dose administrations of REZPEG, first week zero, the next week two. And you see a pretty strong inflection point and actually a change in the slope in the curve and you reach a minus 70% reduction in EASI score, which is quite fast. Now this is a really important element because, remember, in this disease, patients are used to being treated with topical corticosteroids. And basically, those patients expect pretty fast relief by applying a cream. Now in our patient population, patients have progressed, their disease is no longer under control. by topical corticosteroids and they’re moving on to systemic biologic therapy as they are in our study. So again, having a really rapid response is very good. It’s very good for the patient and it’s very good for the expectations. We do think this is a sign of differentiation for REZPEG and it goes quite well with the depth of the response that we reported at week 12, and of course, the additional very highly differentiated element of that prolonged disease control that we observed for 36 weeks after we stopped dosing. All three of those elements really go together and we think that’s one of the elements that comes from this novel mechanism. So then I think you had a second question.

Got it. Thanks. Yeah. Thanks. Just like with the more robust data now in AD. Just curious how you are thinking about the timing and also interest level in exploring additional opportunity with REZPEG maybe in ultra-immune diseases, also I’m wondering some potential opportunity in, even like newer inflammatory diseases? Thank you.

Yeah. I can answer that. Look, it’s a very good question. I think at this point, given our capital position and our strong financial position, I want -- I would like to focus our company on atopic dermatitis right now. I think REZPEG, if it proves successful in atopic dermatitis, which I think at this point it will based on this very robust data, as you said. I think there’s opportunities in other autoimmune diseases. I still -- while lupus is a much smaller market, of course, than atopic dermatitis, I think it worked fairly well in lupus and there are data corrections there that also we’re analyzing. And I do think there’s other indications, type 1 diabetes, food allergy, there’s a number of places where one could develop REZPEG, if we believe we have a drug that proliferates regulatory T-cells in the proper fashion. But for now, for Nektar, our focus is on getting excellent results in a Phase IIb study, a randomized Phase IIb study in atopic dermatitis and we -- and then from that point on, if that’s successful, we can go from there.

Thank you. And our next question will come from Chris Shibutani from Goldman Sachs. Your line is open.

Hi, everyone. Thank you for taking our questions. This is Charlie [ph] on for Chris, and also, I’ll extend my congrats on the corrected REZPEG data. So just two quick ones from us. First, just wondering if -- did Lilly provide any basis for the exclusion of the three atopic dermatitis patients. Just wondering if there is a specific reason behind that exclusion that they may have provided. And then also with the corrected REZPEG data, just wondering if there was any impact on the safety and tolerability results that were presented last year? Thank you.

Thanks, Charlie. I’m going to ask JZ to comment on both of those questions. Go ahead, JZ.

Yeah. Thank you. Thanks for the question. So really, the -- in terms of the data that was excluded, so that was really a judgment that Lilly made. And it was a judgment on using a criteria around topical medications that were permitted by the protocol. And so in reality this is something that all the patient data should have been included from the very beginning as all of that patient data and the use of all of those components are specified in the protocol. Now the next question you asked for was about safety and tolerability. And so those results are the same as they were in the EADV presentation. So in terms of what we did at Nektar is we reviewed everything. We calculated and recalculated all of the components and for the safety information that was presented at EADV from last year, that is the same. Thanks.

Great. That’s very helpful. Thank you so much.

Thank you. Our next question will come from Mara Goldstein from Mizuho. Your line is open.

Great. Thanks so much. I apologize I signed in late, so if this is repetitive, please excuse me. But two questions for you. And one is, given the reanalysis of data and the prior clinical, do you have to approach FDA with this? I mean, obviously, you’re planning on launching a trial, but is this something that they need to be apprised of number one? And then the second question is on the lawsuit understanding that you can’t comment on, because you’re in active litigation. Maybe you can just tell us procedurally what are the next steps here since you have filed that suit?

Yeah. Mary, could you take the first part about FDA and then I’ll ask Howard to comment on the second.

Sure. Regarding the reporting of data to the FDA, we would do that in a clinical study report. At this time, we have not finalized the clinical study report and we will be providing all of the updated and corrected data into the clinical study report, which will be submitted to the FDA. And then I turn it over to Howard for the next question -- next part of the question.

Sure. Look, in regard to the lawsuit, obviously, as you correctly stated, we’re not going to comment on an active litigation. So suffice it to say that we will move forward on this and we take it -- look, we take this lawsuit very seriously. It’s significant, it’s substantial. If you look at the development of REZPEG, REZPEG could have likely been in a Phase II study in atopic dermatitis a year ago, a year and half ago. So we take this lawsuit very seriously. We went out to a very, very well-known and well-respected outside statistical firm to have them recalculate everything de novo, basically gave them the raw data, gave them the clinical plan and said, what do you come up with? And they came up with the same corrective numbers we did. So we take it seriously. I can’t comment on how it proceeds, but it’s important to us, obviously.

Thank you. And our next question comes from Roger Song from Jefferies. Your line is open.

Hi, team. This is Kambiz on for Roger. Why have you decided to move into Phase IIb in specifically bio naïve patients? Any preclinical and mechanism action related reasons, REZPEG work better in those patients? Thank you.

Yeah. Thanks, Kambiz. JZ, I’ll ask you to address that.

Sure. Thanks, Kambiz. So one of the things that we wanted to do importantly is to build upon the data from the Phase Ib study that we’ve just been speaking about today and for which we released corrected data yesterday. So that study was run in biologic naïve patients. So we wanted to continue the development in the same patient population and the strength of the data that we discussed today, as well as all of the elements of differentiation that REZPEG provides in this patient population, we want to just really continue to build on in the very next focused clinical development step for REZPEG. Now in terms of maybe your broader question, which is, what is the applicability of this mechanism and specifically in atopic dermatitis, one of the things that we think is quite compelling about the Treg component of the mechanism is that it really should have the ability to work in multiple lines. So while we’re starting our focus in the biologic naïve patient population, there’s a very good scientific rationale to also expect there will be efficacy in patients that are post-biologics. So for example, patients that have stopped to respond or never responded to an IL-13 therapy like DUPIXENT or Adbry and even other mechanisms that are in development, you should be able to provide a Treg component in that post-population as well. And so in our future development plans, we’ll be looking as well into the biologic experience population.

Thank you. Our next question will come from Greg Harrison from Bank of America. Your line is open.

Hi. This is Mary [ph] here on for Greg. Thanks for taking my question and going through the programs. I guess looking at the potential with REZPEG and the path forward with atopic derm, are you aware of any precedent for this situation, and if so, what was the path-forward here?

Well, let me try…

Yeah. Go ahead, Howard. Yeah. Okay.

Yeah. I’m not -- when you say are there any precedents for this, I am -- I don’t know of any precedents for companies making this kind of a calculation error. So I can’t comment on that. The path-forward, as you know, is we are -- now that we have what I think is very impressive Phase Ib data in a randomized trial, I believe that we’re certainly very enthusiastic about moving forward into Phase II, where I think we can demonstrate that REZPEG becomes a novel therapeutic mechanism for treating autoimmune disease patient’s atopic dermatitis in this case. The lawsuit that we filed against Lilly, we’ll be working on that, and as I said, it’s very, very important to us. But I don’t know if many precedents for this. It’s a -- it’s in my mind, an egregious error.

Thank you. And our next question will come from Boris Peaker from TD Cowen. Your line is open.

Thank you for taking my question. This is Jane [ph] for Boris. So for the -- for REZPEG, are you still exploring psoriasis as your next indication or are you exploring other indication? And I have a follow-up.

Thanks, Jane. And you have a follow-up as well. JZ, I’ll ask you to take the first part of the question.

Sure. Yeah. Thank you. So one of the things we discussed today, right, was about the PASI score calculation and sort of the underreporting of the data from EADV, which we’re very pleased to have been able to correct yesterday. In terms of those long-term focus of REZPEG development, from a dermatology standpoint, we’re clearly focused on atopic dermatitis where we see a very, very profound activity for REZPEG that we’ve been discussing on this call. In psoriasis, there are other mechanisms of action that are quite well entrenched, such as the IL-17 inhibitors and so we might consider psoriasis as a potential development in the future or maybe even in the life cycle management setting. But right now, near-term, we’re really focusing on atopic dermatitis for our development in the dermatology space.

Thank you. For the next question, just regarding your developing preclinical assets targeting TNFR2 and CSF1. Can you just talk generally regarding the competitive landscape over those two targets and your potential market opportunities there? Thank you.

Thanks.

Sure. That’s…

Yeah.

Okay.

Yeah. Thank you for that question. So they’re early assets, obviously, in the research setting, but I can give you some flavor around the targets and the opportunities. So with TNFR2 that is certainly a very kind of hot target and there are just a couple of companies sort of that are coming up that are studying that target and trying to create agonistic drugs. Some of the companies are focusing on applications for oncology and others are focusing on applications for autoimmune disease. We’re interested in the autoimmune disease applications for the TNFR2 target and our agonistic antibodies. Now it’s a very unique target, because it really controls a lot of tissue protective and tissue regenerative pathways. And it can particularly well act on regulatory T-cells once they move into individual compartments in the body and they undergo different kinds of cytokine pressure. And basically, NF-κB be signaling through the TNF superfamily become much more critical for driving their biological importance. So we can see a lot of application for a TNFR2 agonist antibody in certain kinds of organ and sort of pathology type of inflammatory conditions. So the GI and a family of GI diseases is one, neuronal and neuroinflammatory diseases are another, for example, MS. And so there’s really a range of opportunities for a TNFR2 agonist. In the case of our CSF1 program, that targets a myeloid component of the immune system and it targets it with the goal of creating an immunoregulatory effect. So this is not targeting lymphocytes, not targeting T-cells like the other molecules in our pipeline, but targeting a whole different set of immunoregulating and immunosuppressing cell populations. And we think that could have, again, also a very broad application because the myeloid compartment participates in a large number of diseases from the common rheumatic diseases to even some more rare ones as well. Thanks for the question.

Thank you. [Operator Instructions] And our next question will come from Daina Graybosch from Leerink Partners. Your line is open.

Hi. Thank you. I have two questions. I wonder for the EASI score recalculation, if you could help us by separating out the impact of the two changes, Lilly’s mathematical error and then the inclusion of the additional patients, how much of the additional total benefit and the speed of benefit came from those two changes? And then I’ll have a follow-up after that.

Thanks, Daina. Appreciate it. JZ.

Yeah.

Yeah.

Sorry, Jennifer. Yeah. Hi, Daina. Yeah. Thanks for the question. So, basically, the majority, if not the totality, of the difference in the data that we presented on Monday really comes from the mathematical calculations of the EASI score. So, for example, if you correctly calculate the EASI score and you include all the patient data, the week 12 LS mean results that we presented yesterday were 83% reduction. If you correct the EASI score, but not correct the data that was excluded, then the LS mean results at week 12 are 82%, right? So the two numbers are virtually the same. Really, the majority of the effect and the change, right, in the corrected data that we reported came from the mathematical calculation of the EASI score.

That is very helpful. Thank you. My second one is it seems like they made a mistake and correct me if I’m wrong in setting up their staff. So was the mistake consistent for all patients, meaning a certain column or certain multiplier was consistently left out and does that actually tell us anything about the biology of REZPEG that we got such a big benefit from that consistently being left out?

JZ, do you want to take that as well?

Yeah. Sure.

Yeah.

Yeah. Thank you. Yeah. So, basically, when you calculate the 72-point EASI or PASI score, there are multiple components that make up that -- the mathematics that get you to the 72-point number. So the first set are typically what are kind of known as the severity scores, and so they score components of eczema or components of psoriasis depending on if the EASI or PASI is used, and they score those categorically in four sections of the body. Then the next components of the score really assessed the area and so they assess how much skin in each region is affected by disease. And then they also take into account if you’re scoring the head, that’s less dermis on your body than if you’re scoring lower extremities, which is much more. And so sort of consistently the same error was made across both the EASI and the PASI that didn’t capture all of those severity and area components. And so, consistently, a score was arrived at that was less than the 72-point score and that same mathematical calculation was done for every person and every time point. It was basically like an error kind of like in the code that was used to do the calculation. So a couple of important points to add to that to sort of complete the thought of your question, is that, really for over 20 years, there’s been only one measure used for either atopic derm or psoriasis studies. Not only is it validated, but these are the key endpoints that have been seen in study after study after study, as well as just in use in dermatology clinics. And the only score is a 72-point score, anything other than that is not even an apple-to-apple kind of a comparison. So I hope that answers your question and give some more color around this.

Thank you. And I am showing no further questions from our phone lines. I’d now like to turn the conference back over to Howard Robin for any closing remarks.

Well, thank you, everyone, for joining us today and we remain focused on executing on the development of REZPEG and our immunology-focused research programs. And I’d like to thank, of course, all of our employees for their efforts and their extraordinarily hard work and I want to thank our shareholders for their continued support. So we look forward to providing you with updates on our progress and stay tune. Thanks again for joining us today.

This concludes today’s conference call. Thank you for your participation. You may now disconnect. Everyone have a wonderful day.