Q4 2024 Nektar Therapeutics Earnings Call
and Andrew Vandervook.
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Speaker Change: Good day and thank you for standing by welcome to the Nektar Therapeutics fourth quarter 2024 financial results Conference call.
At this time all participants are in a listen only mode.
Speaker Change: 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 one on your telephone.
Speaker Change: You will then hear an automated message advising your hand is raised to withdraw your question. Please press star one again.
Speaker Change: Please be advised that today's conference is being recorded.
Speaker Change: I'd now like to hand, the conference over to your Speaker today Vivian Liu Please go ahead.
Speaker Change: Thank you Crystal and good afternoon, everyone. Thank you for joining us today with us on the call are Howard Robin, Our President and Chief Executive Officer, Dr. Jonathan <unk>, Our Chief Research and development Officer, Dr. Brian <unk>, our interim Chief Medical Officer, and Sandra Gardner, our Chief Financial Officer.
Speaker Change: On today's call, we expect to make forward looking statements regarding our business, including statements regarding the therapeutic potential and future development plans for drug candidates and research programs.
Speaker Change: Timing of initiation of clinical studies and availability of clinical data for drug candidates the timing of plans for future clinical data presentations the formation future development plans or success of our collaboration agreements financial guidance and certain other statements regarding feature for business.
Speaker Change: Because forward looking statements relate to the future, they're subject to uncertainties and risks that are difficult to predict many of which are outside of our control.
Speaker Change: Actual results may differ materially from these statements important risks and uncertainties are set forth in our Form 10-Q that was filed on November eight 2024, which is available at SEC Gov.
Speaker Change: We undertake no obligation to update any of these forward looking statements, whether as a result of new information future developments or otherwise.
Speaker Change: A lot of cast of this call will be available on the IR page of doctors website at <unk> Dot com.
With that said I would like to hand, the call over to our President and CEO Howard Robin Howard.
Speaker Change: Thank you Barry and thank you all for joining us today.
Speaker Change: 2024 was a productive year for next year and I'm very proud of our team for executing on important clinical development milestones.
Speaker Change: Our lead autoimmune pipeline program, whereas peg Pal. This weekend also known as Red spot.
Keeping up these clinical development goals prepares us for meaningful data catalysts for restaurant in 2025.
Speaker Change: Earlier this year, we announced the enrollment completion for both our electric sponsored Phase <unk> studies, a 400 patient result, 80 trial in atopic dermatitis opening enrollment in October of 23 and completed enrollment in just 14 months, our 90 patient resolve AA study and that would be shared.
Speaker Change: <unk> opened in March of 2024, and completed enrollment in roughly one year.
Speaker Change: Both studies were completed on schedule in highly competitive clinical trial landscapes for both indications.
Speaker Change: <unk> demonstrates the enthusiasm from patients and physicians for <unk> novel mechanism of action and through the data that has been generated to date.
Speaker Change: Jay Z will discuss in a minute some of the unique operational features of our studies that are designed to minimize clinical operational risk we.
Speaker Change: Look forward to data from both trials in atopic dermatitis alopecia wrong.
Speaker Change: Quarter in fourth quarter of this year respectively.
Speaker Change: Now in the U S alone.
Speaker Change: There are over 16 million people living with moderate to severe atopic dermatitis, and we know that less than 10% of those patients who could do we could receive biologic treatments for this chronic skin disorder are actually receiving treatment new mechanisms are the key to growing this underserved market.
Speaker Change: This belief also extends to alopecia area. According to the National Alopecia Areata Foundation, nearly 7 million people in the U S alone travel will develop this disease and the treatment market that is estimated to reach $5 2 billion in the United States and Europe by 2023.
Speaker Change: These disorders significantly affects the quality of life for patients and the approved JAK inhibitor therapies with their high relapse rates are not durable and can carry significant potential safety risks with respect we hope to offer a more durable treatment option in the form of a novel immuno modulating mechanism.
Speaker Change: Now moving on to type one diabetes, we recently announced the clinical trial agreement with trials in.
Speaker Change: In International clinical trial network at the forefront of diabetes research in which they will conduct and fund a phase III clinical trial to investigate <unk> in <unk>.
Speaker Change: 66 patients with new onset type one diabetes.
Speaker Change: We're proud to support <unk> mission of advancing innovative mechanisms aimed at slowing or stopping the progression of this disease.
Speaker Change: 2 million people in the U S with type one diabetes and the disease incidents continues to rise at a rate of 3% to 5% per year and Brian will talk more about this later in the call.
Speaker Change: Turning to the progress we've made with our preclinical programs over the past year, we expanded the company's preclinical pipeline in immunology and inflammation.
First we continue to advance our novel TNF are two agonist antibody program nectar a $1 six spots.
Speaker Change: I'd, enabling studies are ongoing with the goal of preparing for an IND submission in the second half of 2025.
Speaker Change: Last year, we presented the first preclinical data you are showing that this antibody demonstrated selective enhancement of T. Reg cell function given the importance of TNF receptor agonism, and a number of autoimmune diseases <unk> <unk> six five could potentially be developed in autoimmune diseases, such as multiple sclerosis.
Speaker Change: Ulcerative colitis and bit of lager.
Speaker Change: We're also designing a pipeline a bi specific molecule that pair TNF are two agonism with other antibody targets and we're planning for the first five specific in this program to be ready for IND, enabling studies within the.
Speaker Change: Next quarter.
Speaker Change: We look forward to providing more color on our early pipeline as these programs progressing Jay Z will discuss more on this later.
Speaker Change: Now before I turn to the R&D discussion I want to reintroduce Bryan Carlson, who we announced last month would be returning connector to lead the development of rest bag as interim Chief Medical Officer.
Speaker Change: Brian has over 40 years of expertise in immunology and has extensive development and management experience. He has also been supporting the clinical development of <unk> in various capacities since 2017 and its intimate familiarity with this program has provided a seamless transition and before I hand, the call over to Brian I want too high.
Speaker Change: Light that vector remains in a strong financial position with a cash runway that extends into the fourth quarter of 2026, ending 2024 with $269 million in cash and investments on hand.
Speaker Change: I'm going to ask Brian to share a few comments on his enthusiasm for <unk> and also comment on our recent announcement for the program in type one diabetes before we turn it over to Jay Z to review more details on <unk> ongoing phase <unk> studies in our early pipeline programs Brian.
Speaker Change: Thank you Howard.
Speaker Change: It's great to be back at that time.
Speaker Change: As Howard mentioned I've had the great pleasure to work on <unk> since 2017, even continuing as a strategic advisor since retiring in 2023.
Speaker Change: When Howard and JV called me with the opportunity to work on this program with my colleagues at Nektar again.
Very enthusiastic to help.
Speaker Change: I have a great passion for the potential of boosting regulatory T cells in autoimmune disease and does peg is the most advanced IL two T regs stimulating mechanism in the field.
Speaker Change: Having closely worked for several years and its clinical development I believe it has the potential to truly address unmet needs for safe and durable therapeutic options for patients battling atopic dermatitis alopecia area and now type one diabetes.
Speaker Change: As Howard mentioned, we recently announced a collaboration agreement with trial to evaluate <unk> in a phase II placebo controlled clinical trial in patients with new onset type one diabetes.
Speaker Change: I've had great interest in pursuing those take in this indication since it first and through the clinic and I'm very excited to work with some of my colleagues at trial net on this new clinical study.
Speaker Change: And type one diabetes patients, there's dysregulation of the balance between regulatory T cells, and pathogenic Autoreactive T cells, which leaves the auto reactive T cells to destroy insulin producing beta cells in the pancreas studies.
Speaker Change: Studies of mouse models in early human research of low dose IL, two and other agents have shown that boosting T. Regs can lead to the preservation of insulin producing beta cells. This.
Speaker Change: Operation of endogenous insulin secretion is key to improving long term health outcomes and quality of life for patients with this disease.
This is why I'm. So excited about the work the trial known as recommending for Ret spec.
Speaker Change: The proposal the proposed placebo controlled trial and that study will enroll approximately 66 patients while they still have preserved.
Speaker Change: Partially preserved beta cell function and influence and insulin production, we will start evaluation in adult patients and move to pediatric and adult patients in different phases of the study.
Speaker Change: Trial <unk> goal is to initiate the study later this year.
Speaker Change: Okay.
JV: And with that I'd like to hand, the call to JV.
JV: Thank you, Brian it's exciting to be working with you on a daily basis again.
Speaker Change: As Howard mentioned, we announced in January we completed enrollment in the resolve a phase <unk> trial in patients with atopic dermatitis.
JV: Just under 14 months.
JV: We're grateful to the patients and physicians, who has strong interest in this novel mechanism and proof of concept clinical data lead to enrollment completion of this large phase <unk> study and we look forward to reporting the topline data from the 16 week induction period in June of this year.
JV: In February <unk> was granted fast track designation by the FDA for the treatment of adult and pediatric patients with moderate to severe atopic dermatitis.
JV: This designation allows us to collaborate closely with the agency on the design of the Registrational program for <unk> and we'll be leveraging it as we work on our phase III Registrational strategy and atopic dermatitis.
As a reminder, the resolve study randomized approximately 400 biologic naive patients with moderate to severe atopic dermatitis across three different dosing regimens of <unk> or placebo.
JV: Guided by our scientific advisory board of industry, leading dermatologists. We designed this study to ensure high quality sites were used and implemented criteria with the goal of addressing some pitfalls in operational execution from past trials.
JV: Patients were recruited from approximately 110 sites globally to ensure adequate geographic representation.
JV: Patients were stratified based on geographic region, as well as baseline disease severity <unk>.
JV: 67% of patients were enrolled in Europe across Poland, Bulgaria, Germany, Chechnya, Spain, Croatia in Hungary.
JV: 17% enrolled in the United States and the rest were enrolled in Canada and Australia.
JV: We had a goal to balance use recruitment due to the recent phenomenon in the last several years of a rising placebo effect observed in the U S.
We are very pleased with the 17% Ultimate U S recruitment figure, which aligns more closely with the recent winning atopic dermatitis studies in terms of site distribution.
JV: Other important criteria that were used in the study include requiring most of our sites be board certified dermatologist or an analysis with prior experience.
JV: <unk> participating in other atopic dermatitis studies.
JV: We also required that patients enroll met our strict easy threshold.
JV: It's consistent with both screening and randomization.
JV: Unlike some other trials that have only required easy measurement that screening.
JV: Reconfirming that the patient's disease severity has not changed significantly between screening and baseline time point allows us to reduce the potential for enrolling patients with flaring or episodic disease into the study.
JV: Patients with stable disease or with the significant changes between screening and randomization screened them.
JV: After randomization patients receive either <unk> or 'twenty 400 micrograms per kilogram twice a month.
24 micrograms per kilogram once a month and a team micrograms per kilogram twice, a month or placebo for a 16 week induction treatment periods.
After the induction period patients that meet you see 50 or better efficacy threshold to advance from induction and maintenance are re randomized into one of two maintenance regimen at their original dose level two.
JV: To receive that dose on either a once a month or once every three month regimen.
JV: The maintenance portion of this study is 36 weeks, which will in total provide 52 weeks of treatment duration for patients in the study.
JV: We are following participants for one year. After the conclusion of the 52 week treatment period, enabling us to evaluate <unk> potential for long term limited effects.
JV: As I just mentioned, we anticipate topline data from the 16 week induction period of this phase <unk> study in June.
JV: And we expect data from the 36 week maintenance period of the study in the first quarter of 2026.
JV: Now turning to resolve a steady.
JV: <unk> is a durable disease in which the patient's immune system mistakenly attacks to hair follicle and disrupts the body's normal ability to keep and grow her.
JV: Leading to higher loss.
JV: There is strong rationale for <unk> in this indication based on the role of T regs to either prevent or down regulate the underlying pathology.
JV: Sure.
Last month, we announced enrollment completion for our 90 patient phase <unk> study.
JV: The trial recruited patients across approximately 30 global sites.
JV: <unk> had to present with severe to very severe disease.
JV: Find itself 50 to 100 for at least six months in order to be eligible for inclusion.
JV: 62% of patients were enrolled in Poland, 24% in Canada, and the rest in the U S.
JV: Randomized patients will be treated for a period of 36 weeks and observed for up to 60 weeks in total our primary endpoint for this study is mean percent improvement in salt or the severity of alopecia tool the week 36.
JV: We'll also be looking at a number of other secondary endpoints, including the proportion of patients that was observed to have varying degrees of improvement in salt score, including the regulatory approval endpoint in <unk> 'twenty.
JV: We expect top line data from the 36 week treatment period in the fourth quarter of this year.
JV: Turning to our preclinical programs in the immunology I'll start by talking about our novel TNF IL two agonist antibody program nectar all 165.
JV: TNF are two agonism has been shown to potentiate T Reg function as well as maintenance of T. Reg lineage stability, especially in the non lymphoid tissue compartments.
JV: Genetic studies show that a TNF far too is absent the phenotypic effect does that have an immunity as well as other conditions that resemble a fox P. III lots of functions.
In contrast, its presence and activation of a signaling has been associated with immune regulatory function in tissue protective effects.
JV: The first preclinical data from this program presented last year at <unk> demonstrated that <unk> hundred 65 is a very high specificity for signaling through <unk> on T regs and enhancing immunosuppressive activity.
It also showed that the agonist, we discovered are able to signal through the TNF are two multimarket receptor single arm monovalent antibodies, which is a very novel finding for our TNF agonist antibodies.
JV: We're very excited with Nextera <unk> unique and differentiated profile and we believe it has the potential to become a first in class treatment for various autoimmune diseases, including multiple sclerosis alternative colitis have been alive.
JV: And we are rapidly advancing this program into the clinic with plans to submit an IND in the second half of this year.
JV: Since the TNF IL two agonist antibody specificities, we discovered are active as a single arm antibody. We have leveraged this to design a pipeline TNF are two containing bi specific molecules.
Per TNF are two agonism other specificity.
JV: First of these is known as vector at $1 66.
JV: These assets take advantage of multiple mechanisms to bring about novel molecules to target autoimmune diseases.
JV: We will nominate the first development candidate <unk> six from this pipeline in the second quarter of this year and look forward to providing more color around this in the future.
JV: Overall, we have observed growing interest for our selective <unk> agonist like next year of about six five and as we move forward with our IND, enabling studies and develop the bi specific pipeline, we remain open to opportunities to work with companies interested in these areas strategize and the best path forward.
JV: Before turning the call over to Sandy I will make a few comments on <unk> 255, our IL 15 based oncology program.
JV: Last year, we presented data an extra 255, the highlight its potential to augment the response and patient outcomes in a variety of cancer treatments in both solid and liquid tumors.
Data published in blood to peer reviewed medical journal of the American Society of Hematology from Stanford ISP demonstrated that metric to Wi Fi when combined with Stanford 2019, CD 22 by car T cell therapy double the 12 months relapse free survival rate for patients with B cell acute lymphoblastic leukemia.
JV: PBF at 67% compared to 38% Tan, France historical controls treated with the same car T cell therapy.
JV: At Ash, we shared supporting data showing that <unk> five enhanced complete response rates. Following CD 19, directed car T therapy in patients with relapsed refractory large b cell lymphoma.
JV: 73% of the negative $2 five treatment group achieved a complete response at six months.
JV: <unk> to 50% in the placebo group.
JV: This clinical benefit surpasses the published historical benchmark data from multiple pivotal trials and real world analyses.
JV: Available commercials, CD 19 car T cell therapies.
JV: Finally interim data presented at <unk>.
Speaker Change: Dr. Stephen Lynch Phase II study suggest that <unk> hundred five has the potential to confer a clinical benefit in <unk>.
Patients with locally advanced non small cell lung cancer.
Speaker Change: Results showed that an extra 255 in combination with <unk> demonstrated a statistically significant improvement in the eight week absolute lymphocyte count compared to historical control data.
Speaker Change: These data strengthen our belief in <unk> therapeutic potential as a new application of combination treatment with checkpoint inhibitors.
Speaker Change: The growing body of evidence showcases its broad applicability to be combined with a variety of therapies across cancer indications. Looking ahead, we will continue to collaborate with able data to evaluate <unk> in combination with our tumor infiltrating lymphocyte in patients with advanced non small cell lung cancer, we do not.
Not respond to anti PD one therapy.
Speaker Change: And we continue to work with Merck to evaluate <unk> five in combination with <unk> in their phase III javelin bladder med. This study with the first potential PFS readout expected in the middle of this year.
Speaker Change: As this is an event driven analysis.
Speaker Change: As we continued to generate supportive data in these combination studies, we continue to explore the best areas for continued development of this drug candidate in partnership with collaborators.
Speaker Change: And with that I will turn the call over to Sandeep for a review of our financial guidance.
Sandeep: Thank you Casey and good afternoon, everyone.
Sandeep: We ended 2024 with $269 1 million in cash and investments with no debt on our balance sheet under.
Sandeep: On December 2nd 2024, we completed the sale of our Huntsville manufacturing facility for a consideration of $64 7 million in cash net of transaction costs and approximately 20% equity ownership in the new.
New portfolio company <unk> biochem.
Sandeep: Turning to the income statement, our revenue with $29 2 million for the fourth quarter of 2024, and $98 4 million for the full year 2024.
Sandeep: Our R&D expenses were $28 7 million for the fourth quarter and $129 million for the full year.
Sandeep: Our G&A expenses were $17 1 million for the fourth quarter and $76 8 million for the full year.
Sandeep: In connection with the sale of our Huntsville manufacturing facility, we recognized the gain of $44 million.
Sandeep: Our noncash interest expense for the fourth quarter was $10 2 million and $28 1 million for the full year.
Sandeep: And our net income for the fourth quarter with $77 3 million or three basic and diluted earnings per share for.
Sandeep: For the full year 2024, our net loss was 119 million or <unk> 58.
Sandeep: Basic and diluted loss per share.
Sandeep: I will now review, our 2025 financial guidance.
Sandeep: We remained strong and our financial position and still expect our cash runway to extend into the fourth quarter of 2026.
Sandeep: Plan to end 2025, with approximately $100 million in cash and investments.
Sandeep: Our revenue for the full year of 2025 is expected to be between 40 and $50 million, which primarily includes noncash royalties.
Sandeep: As a result of the sale of our Huntsville manufacturing facility.
We'll no longer have product revenue and cost of goods sold.
Sandeep: We anticipate full year R&D expense will range between 110, 120 million, including approximately $5 million to $10 million of noncash depreciation and stock based compensation expense.
Sandeep: We expect R&D expense to remain consistent with 2024 levels as we continue our phase <unk> study in atopic dermatitis in alopecia Areata.
We expect G&A expense for the full year 2025 to be between 60, and 65 million, including approximately $5 million to $10 million of noncash depreciation and stock based compensation expense.
Sandeep: Our full year non cash interest expense is expected to be between 15 and $20 million.
Sandeep: And as I stated earlier, we expect to end the year with approximately $100 million in cash and investments.
Sandeep: And with that now I'll open the call up for questions operator.
Thank you.
Sandeep: As a reminder to ask a question. Please press star one one on your telephone and wait for your name to be announced to withdraw your question. Please press star one again.
Sandeep: In the interest of time, we do ask that you. Please limit yourself to one question at this time please.
Please standby, we compile the Q&A roster.
And our first question will come from Yasmin Rahimi from Piper Sandler Your line is now open.
Good afternoon, Kim. Thank you so much for all the great updates on I'm very much looking forward to the data across both of the studies for this year.
Sandeep: The first question is you guys have shown in the earlier stage really phenomenal dose responses.
Sandeep: And the easy scores, who would love to understand how you're thinking about dose response across the three dose arm.
Sandeep: And then secondly, if you could just maybe remind us what is the criteria or responders responder analysis define for patients to be eligible to go from the induction phase two the maintenance phase and then I'll jump back in the queue.
Speaker Change: J C. You want to take that call that answered question sure. Yes. Thanks guys.
Speaker Change: The first question about the dose response, so we addressed that with three different cohorts that address both dose level that regimen. So two of our codes dose cohorts evaluated the 24 microgram per kilogram dose one of those evaluated that dose twice a month the other cohort at once a month.
Speaker Change: And we changed the frequency there because that was sort of designed to model. The pharmacodynamic profile of the T. Regs that we measure in the blood.
Speaker Change: That's why we wanted to have the same <unk>, one time different exposures in the once a month versus twice a month.
Speaker Change: So that was the goal there to assess that based on the PK PD knowledge and then we also selected 18 micrograms per 1000 dose twice a month that doses higher than the 12 microgram per kilogram that we've used in the phase <unk> study, we felt that that dose 12 wildly did separate.
Speaker Change: A little bit from placebo.
Speaker Change: A little bit on the lower efficacy side. So we wanted to evaluate a higher dose level and 12 micrograms per kilogram in the phase <unk> and Thats why we chose to 18 micrograms per kilogram halfway between 12 and 24 from the Phase <unk> study so.
Speaker Change: So thats our expectations around the design of the phase <unk> and <unk>.
Speaker Change: Then in terms of the criteria for patients moving from the induction to the maintenance arms of the study.
Speaker Change: At the end of the 16 week induction patients that have an easy 50% or better response are eligible to be re randomized to enter into the maintenance and then in the maintenance. They are re randomized to stay on the same dose level that they were on in the induction portion of the study, but now the regimen is either once.
A month or once every three months. So we use that easy 50 criteria for advancement from induction to make.
Casey: Thank you Casey.
Speaker Change: Okay.
Speaker Change: Thank you.
Our next question will come from Julian Harrison from BTG. Your line is open.
Julian Harrison: Alright. Thank you for taking my questions first on the phase <unk> atopic dermatitis data expected next quarter, but I'm wondering if you could talk about what kind of efficacy bar either on easier Iga, you think it would be commercially viable and worthwhile to advance <unk> into pivotal development.
Julian Harrison: Yes, that's a good question I think we've done a lot of homework in that area, especially recognizing that.
Julian Harrison: Amgen just released its data on ox 40, so I'll, let I'll, let Jason give you a more thorough answer on that.
Speaker Change: Yeah. Thanks, Julien So we definitely see at least two different versions.
Of activity.
Speaker Change: Honestly there is ranges of easy that are active and that are desirable to achieve and also the separation from placebo. Both features are very important.
Speaker Change: We like what we saw in our phase <unk> study right. We showed both the dramatic separation from placebo in terms of placebo adjusted and also an 83% change from baseline. So we're looking to replicate that kind of data in our phase IV will be also acknowledged that as a drug with a novel mechanism.
Speaker Change: And an agent that has already shown a remit of effect as we've shown in the phase IV that even efficacy in the range of two Pixar. The standard of care. Currently would also be a very successful outcome for us.
Speaker Change: Totally aware of the recent results in the field, including Amgen's broker data.
Speaker Change: I think that data is probably considered a little bit underwhelmed by some some some of the folks that have addressed and looked at that data and we think that we're in a great position to replicate the phase <unk> results that we had with <unk>.
Speaker Change: And always remember that.
Speaker Change: This isn't a zero sum game and it really is a quite underserved market with a very serious disease.
Speaker Change: Having a novel mechanism.
Certainly going to be appreciated by patients and physicians I'm sure of that.
Sure.
Got it. Thank you that makes a lot of sense and then one more if I may I'm curious, how you're thinking about your rights to peer listen that in light of the recent letter filler map royalty monetization.
Speaker Change: Are there any differences compared to fill a map that are worth noting.
Jay Z: Jay do you want to comment on that.
Yes.
Speaker Change: <unk> mechanism of action of course, right one is the <unk> inhibitor.
Jay Z: Targeted more of the Plasmacytoid.
Jay Z: Arm.
Jay Z: Of course that drug has shown activity in both systemic lupus and cutaneous lupus and it seems like it has maybe even more potential in the cutaneous form of the disease.
Jay Z: Duffy right as the CD 40 ligand targeting agent right. So it addresses different mechanisms of action.
Jay Z: And then so thats mechanistically both of the drugs have.
Jay Z: Demonstrated I think impressive results in phase III, and obviously <unk> is positive phase III data as well.
Jay Z: Alright excellent. Thank you.
Jay Z: Thank you our.
Jay Olson: Our next question will come from Jay Olson from Oppenheimer. Your line is open.
Speaker Change: Oh, Hey, congrats on all the progress and thank you for providing this update.
Jay Olson: Maybe.
Jay Olson: Another question on the.
Jay Olson: Top line phase two atopic dermatitis results in the second quarter.
Jay Olson: Can you just talk about the scope of data that you are planning to share in that top line release and.
Jay Olson: Maybe some of the secondary endpoints, we should be looking for and then also what do you think the <unk>.
Jay Olson: <unk> would be.
Jay Olson: Help you capture meaningful market share in a first line setting.
Speaker Change: Yes, I think good questions I think we haven't discussed a lot about the exact secondary endpoints at this point.
Jay Olson: I think clearly as it is.
Jay Olson: A novel mechanism in a completely different approach than IL 13.
Jay Olson: We'd like to see I would like to see a drug that's similar in activity to depiction.
Jay Olson: With a very different.
Speaker Change: Biologic profile I'll, let Jason talk a little bit more about that go ahead JJ.
Speaker Change: Yes sure. Thanks Jay.
Speaker Change: So just to reiterate as Howard said, we haven't sort of.
Speaker Change: On the specificity of the top line, obviously is the majority of the data we.
Presented at medical meeting, but.
Speaker Change: But we would intend to focus obviously on the 16 week induction data as we have described.
Speaker Change: And to give at least a minimum directional understanding.
Speaker Change: <unk> of the performance of the drug I think is a bare minimum.
Speaker Change: Cover that more later.
And then in terms of the profile.
Speaker Change: It's pretty obvious that the greatest way to impact the share in the frontline setting is with efficacy.
Speaker Change: Alright, so if we are able to replicate the phase <unk> results that were really quite quite.
Speaker Change: Alright market quite notable.
Speaker Change: It's one of the strongest ways to impact the first line treatment space, but even all that aside we are a completely different mechanism. We're not another IL 13, we're not depleting antibody like roka is.
Speaker Change: We're really providing a completely different mechanism of action and we're providing the data set that has already demonstrated the potential for really durable responses, which could translate into very very low frequency dosing regimen, which would at a minimum the highly convenient to patients. So we think there are really a number of.
Ways.
Speaker Change: We can impact this market and we're very excited that being a novel T. Reg mechanism gives us these additional avenues.
Speaker Change: Yes, I think it's also important to point out that while depicts and certainly an excellent drug no debate on that.
Speaker Change: There is a high percentage of patients failed depicts and therapy over time and as Jay Z, Jeff said, having a novel mechanism that works in a completely different fashion.
Speaker Change: Something thats market desperately need so.
When we when we wind up comparing our results to depicts our results certainly I'd like to see similarities but recognize that youre youre dealing with a completely different way of approaching the treatment of this disease.
Thank you that's super helpful and if I could sneak in a question on 295.
Speaker Change: Can you just talk about any updates on.
Timing or expectations for the interim PFS PFS results from the javelin.
Speaker Change: Bladder medley study and what we should be looking for there. Thank you.
Speaker Change: But we should be seeing we should be seeing results from that middle of this year, Jay Z do you want to comment a little further.
Jay Z: Yes, that's exactly right. It is event driven right. So you need to accumulate the PFS events.
Merck gave us some guidance at the middle of the year.
Summertime is about the kind of time, when we might expect to see that and then in terms of PFS events. Obviously, our goal is to improve right on the PFS and potentially maybe even the OS of.
Jay Z: Single agent <unk> in this setting right in the post chemo setting. So that's obviously the objective of the study and so we'd like to see is with Merck would like to see as well in that type of a study has been designed with <unk> as an active comparator to directly test.
The combination of 295, plus <unk> versus <unk>.
Jay Z: Hello.
Jay Z: Thank you Super helpful. Thanks for taking the questions.
Jay Z: Okay.
Jay Z: Thank you.
Speaker Change: Our next question will come from Roger song from Jefferies. Your line is open.
Jay Z: Sure.
Roger Song: Great. Thanks for that day, and taking all the questions I have a quick one related to the phase Iia type of dermatitis, given taking gold mine.
Roger Song: You have now you have completed year to compare to the <unk>.
Roger Song: Atopic dermatitis trial.
Roger Song: What's your expectation into the patient baseline.
Roger Song: And then how will that impact.
Roger Song: Particularly on the placebo arm.
Roger Song: Expectation thank you.
Roger Song: Yes.
Speaker Change: Jay Z or Brian you want to take that one.
Speaker Change: Sure. Thanks, Roger So so one of the things that we really like to see is the baseline easy to be in the range of late.
Speaker Change: 25% to 25% to 30%.
Speaker Change: Alright, because as we've seen other studies historically.
Speaker Change: Those kind of baseline easy scores for the entire population have generally been linked with.
Speaker Change: Lower overall placebo responses and also better studies is more dynamic range to measure from patients that are having higher easy scores. So thats one of the things that we'd like to see.
Something in that kind of range for baseline and then in terms of setting expectations for placebo.
Speaker Change: We don't know I mean this is.
Blind study, but certainly we would like to see much much lower placebo response rates that have been reported.
Speaker Change: Recently for some of the studies, including the studies that were reported last December such as from Q3 to the placebo rate is very very high one of the things that we did in our study.
That I tried to cover earlier.
Speaker Change: And our call was that we really had a number of prospective features that we built into the study.
Speaker Change: Such as limiting the U S footprint geographically, we only had 17% of our sites in the U S. Focusing on board certified dermatologist and Immunologists that had demonstrated experience working in atopic dermatitis studies as well as measuring the easy score multiple times before.
Speaker Change: <unk> was administered in patients who were randomized and all of those things we did prospectively.
Speaker Change: Sure to protect the study.
Speaker Change: Sure.
Speaker Change: Again, we don't have very very high placebo response rate. So obviously when we present the results of the top line later this year in June we will.
Roger: It will show what that is directly the thanks for the question Roger.
Speaker Change: Thank you.
Speaker Change: Thank you and our next question will come from my Montana from B Riley Securities. Your line is open.
Yes, good afternoon team thanks for taking our questions.
Speaker Change: I'm glad to see the progress here could you touch on just a related question to the last comment Jay Z and any thing you can touch on the screen failure rate you've seen on this.
Speaker Change: Extra stringent criteria, you're using and how that may compare to some.
Speaker Change: Other studies that have been done.
Speaker Change: Now in screening and randomization and then I have a quick follow up.
Speaker Change: Yes that would be the kind of information we would share in the future.
Speaker Change: We presented the results of the study.
Speaker Change: Okay, Okay got it and then the.
Speaker Change: Escape.
Speaker Change: <unk>.
Piece.
Speaker Change: And the political how patients.
On the escape and could you just remind me how thats kind of structured.
Speaker Change: Induction and maintenance and then speed is high level.
Speaker Change: <unk> 2080 data set that has all of the study.
Speaker Change: Any translation Mark because youre looking at would be helpful. Thanks for taking my question.
Speaker Change: Sure Yes.
So and the way. The study is designed which was one of the expert pieces of advice also given to us by the steering committee is that when.
Speaker Change: When patients to reach the end of the 16 week induction.
Speaker Change: If they are not better than easy 50, then they have the option to enter into an escape arm and the escape arm is the 24 microgram per kilogram dose of <unk> given twice a month.
Speaker Change: Particularly good for patients for example, the client is steady but that might have been randomized to placebo arm right. It gives everyone a chance to have access to truck. So that's how that escape arm work and so the primary entry point is that that 16 week time point at the end of induction for patients that fail to meet the easy 50 or better.
Speaker Change: <unk> re randomization criteria to enter and maintenance the other way that patients can enter into the escape.
Speaker Change: During the maintenance if for one reason or another.
Speaker Change: Luiz this activity or this response and they have a second chance to enter into those K Barnes.
Really the way that it works and it's really very standard.
Speaker Change: These kinds of studies that offer an escape arm therapy to patients that are in the study.
Speaker Change: And then in terms of other kind of questions you asked about sort of read through.
We selected alopecia really because it is a key dermatological indication and then as you know with <unk>, we've seen activity in multiple dermatological inflammatory conditions ranging from skin manifestations in lupus psoriasis atopic dermatitis and also they underlie.
And knowledge about the biology of immune privilege and the role the T. Rex play in helping to maintain and sustain that immune privilege state.
Speaker Change: We will be looking at Biomarkers across both studies in and as you saw from our publication in nature Communications in October of last year, a number of Biomarkers that we measure our induction markers because our drug is an agonist and so I expect we'll be able to measure those kind of induced pathways independent of underlying disease.
Speaker Change: Etiology of the patient those will just be based on the signaling of our molecule onto T. Rex for example.
Speaker Change: So those will be some some very important causes biomarkers of OCA collecting in the future and we're looking forward to the readout of both of these studies.
Speaker Change: As we discussed the first one atopic derm is coming in June for that introduction and for alopecia Areata and <unk>.
Speaker Change: Fourth quarter of this year, we expect to be reading out the 36 week treatment data from that study as well.
Speaker Change: Thank you.
Speaker Change: Thank you.
Our next question will come from Arthur <unk> from H C. Wainwright Your line is open.
Arthur: Hey, good afternoon, Howard and team thanks for taking our question.
Speaker Change: So Jamie thanks for the additional color on the dose regimen for the ADP study.
I just wanted to follow up a little bit on the rationale to pick those three regimen arms. So.
Speaker Change: Why not go for a higher dosing regimen, and then 24 microgram per kilo Q2 W.
Speaker Change: Yes.
Speaker Change: Follow up on the trial as well.
Speaker Change: Yes across the clinical program, we have evaluated various doses.
Speaker Change: Both weight based dosing such as what we are using in the study and also flat dosing as opposed to using other studies like the Lupus study and then really when you look at it that gives you a range of different doses that we've established so we've got a well above and well below.
And actually the 24 microgram per kilogram is really an optimal dose level.
Speaker Change: US all of the things that we want to have from a PK PD relationship we engage the target very effectively we get very robust T. Reg expansion and you can dose for a very long time.
Speaker Change: Dose level without seeing any cessation or any hysteresis in any of the pharmacodynamic responses.
Speaker Change: And from the biomarker data that was asked earlier and that will be published you can also see the very robust induction of immune pathways that we see at that dose level. So that's really an optimal dose level, though we're really focused on.
Thanks for that so and the question is also regarding but part of it.
Speaker Change: Both <unk> and the <unk> study could you remind us how is the stratification in both study and base in terms of the disease.
Speaker Change: So we're attitude wise, how that could be.
Decided it.
Speaker Change: Should application.
Speaker Change: Yes, so we haven't shared all of the details of the full stratification study, but I will share I think what's the most relevant and important Arthur so so our study.
Speaker Change: Is enrolling the severe and very severe population.
So severe people have the salt score between 50 and 95.
Speaker Change: Very severe people are 95 to 100 and very severe people are almost like they're like.
Speaker Change: Almost if not in all cases completely halt.
Speaker Change: Alright.
Speaker Change: And so our study has quite a high number.
Speaker Change: In both categories and one of the stratification is to balance that between the treatment arm alright. So thats, one key stratification that severe and very severe patients we want to balance across the treatment arms and there'll be other ones as well that we'll present when we present the topline results from that study in the fourth quarter.
Speaker Change: I think severe very severe and it's probably what you were.
Speaker Change: Wondering about.
Speaker Change: So how about.
Speaker Change: <unk> eight study.
Speaker Change: Yes, again, we haven't we will share all of the full details of that.
Speaker Change: Later, when we present the top line, but just as an example, a flavor of the geographic regions as one of the important things to to stratify and those kinds of studies and Thats one of our criteria.
Speaker Change: I see.
Speaker Change: Thanks for the congrats on the progress.
Speaker Change: Okay. Thank you.
Thank you and as a reminder to ask a question. Please press star one line.
Speaker Change: And our next question will come from Chris <unk> from Goldman Sachs. Your line is open.
Speaker Change: Hey, Good afternoon. This is Eric on for Christy Battani. Thank you so much for taking my question.
Speaker Change: So just wanted to elaborate a little more on the point you made about the biomarker analysis.
Speaker Change: Trial do you have a sense of how translatable. This correlation between Biomarkers and clinical outcomes are in and maybe the larger trial or potentially or across different patient populations and are there plans to incorporating this biomarker and future trial designs.
Speaker Change: Yes, Thanks, Eric that's a really good question. So what we were able to do in the phase <unk> atopic Derm studies, what I call more like descriptive analysis.
Speaker Change: Characterize the dose dependency of Biomarkers analyzed by an MRM model against various covariance.
Speaker Change: We did an analysis and we could see pathways that were statistically changed both as a function of dose and as a function of time.
Speaker Change: Consider it more of like a like a summary, a descriptive analysis is because the study was pretty small.
Speaker Change: Actually in the Phase <unk> study.
Speaker Change: High number of responders was not really the right dataset to do a lot of Korlym of analysis, we did try.
Speaker Change: Currently a analysis.
Speaker Change: It wasn't clear from.
Speaker Change: That particular study given its small size now in our phase <unk> study. So this atopic dermatitis study, we're doing that again, but now the study is designed.
Speaker Change: It's much larger.
Speaker Change: And also we have a lot more understanding about the collection time points that we learned from the phase one b that are more optimized in this phase II and also we're collecting tape strips. So that we can collect what's happening locally in the lesion.
Speaker Change: Against the serum biomarkers using the OLED panels and the size of their analysis by flow cytometry. So one of our objectives translational and this phase two study.
Speaker Change: In addition to all of the other normal kind of.
Speaker Change: Efficacy and safety endpoints as we also wanted to die very deeply into the translational sort of molecular phenotype of the patients and then understand any of these correlate of analysis, whether they can be predictive prognostic and so on so that would be a very exciting dataset, we'll be excited to share in the coming in the future.
Alright, Thank you very much.
Speaker Change: Thank you.
Speaker Change: And that does conclude our question and answer session for today's call I'd now like to turn the conference back over to Howard Robin for any closing remarks.
Howard Robin: Well. Thank you everyone for joining us today, and we look forward to sharing important data from our phase <unk> studies of <unk> later this year.
Howard Robin: We remain focused on advancing our pipeline and efficiently executing each of our unique programs I want to thank all of our employees for their hard work and diligence and of course I want to thank our investors for their continued support. So please stay tuned thank you very much.
Howard Robin: This concludes today's conference call. Thank you for your participation you may now disconnect everyone have a wonderful day.
Howard Robin: Okay.
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Howard Robin: Yeah.
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Howard Robin: So.