Q4 2023 Nektar Therapeutics Earnings Call
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Okay.
Operator: Good day, and thank you for standing by. Welcome to the Nektar Therapeutics fourth quarter 2023 financial results conference call. At this time, all participants are in the listen only mode.
Speaker Change: Good day and thank you for standby welcome to the Nektar Therapeutics fourth quarter 2023 financial results Conference call. At this time, all participants are in a listen only mode.
Operator: 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. You will then hear an automated message advising that your hand is raised.
Speaker Change: After the speaker's presentation, there will be a question and answer session.
Speaker Change: 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.
Operator: To withdraw your question, please press star 11 again. 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.
Speaker Change: 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.
Vivian Wu: Thank you, Crystal, and good afternoon, everyone. Thanks 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, Sandra Gardiner, our Chief Financial Officer, and Jennifer Ruddock, our Chief Business 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 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 presentations, the formation, future development plans, or success of our agreement. Additionally, the expectations following are corporate restructuring and reorganization, financial guidance, and certain other statements regarding the future of our business. Because forelooking 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.
Vivian Wu: Thank you Crystal and good afternoon, everyone. Thanks for joining us today with us on the call are Howard Robin, our President and CEO, Dr. Jonathan <unk>, our chief of research and development Dr.
Vivian Wu: Dr. Mary Tagliaferri, our Chief Medical Officer, Andrew Gardiner, Chief Financial Officer, and Jennifer erotic our Chief business Officer.
Vivian Wu: On today's call, we expect to make forward looking statements regarding our business, including statements regarding the therapeutic potential of future development slate of candidates.
Vivian Wu: Candidates.
Vivian Wu: Yeah.
Vivian Wu: The timing of the initiation of clinical studies and the availability of clinical data or drug candidates, the timing and plans for future clinical data presentations the formation future development plans or success of our.
Vivian Wu: The agreement.
Vivian Wu: Expectation is following our corporate restructuring and reorganization financial guidance and certain other statements regarding the future of our business.
Vivian Wu: 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.
Vivian Wu: Our actual results may differ materially from those stated. Important risks and uncertainties are set forth in our Form 10-Q that was filed on November 8, 2023, which is available at SBC.gov. We undertake no obligation to update any of our legislative statements, whether as a result of new information, future developments, or otherwise.
Vivian Wu: Results may differ materially from these statements.
Vivian Wu: Important risks and uncertainties are set forth in our Form 10-Q that was filed on November eight.
Vivian Wu: 'twenty, three which is available at SEC Gov.
Vivian Wu: We undertake no obligation to update any forward.
Vivian Wu: As a result of new information future developments or otherwise well watch as of this call will be available the IR page of doctors website.
Howard W. Robin: A webcast of this call will be available on the IR page of Nektar's website at nektar.com. With that said, I would like to hand the call over to our President and CEO, Robin Howard. Thank you, Vivian, and thank you for all joining us today. 2023 was a pivotal year for Nektar.
Okay.
Vivian Wu: With that said I would like to hand, the call over to our CEO Howard <unk>.
Howard W. Robin: Robin Howard.
Howard W. Robin: Thank you Vivian.
Howard W. Robin: Thank you for all joining us today.
Howard W. Robin: 2023 was a pivotal year for nectar.
Howard W. Robin: We refocused the company's development pipeline on immunology and inflammation, with our primary near-term goal to advance Respeg to meaningful data catalysts in the first half of 2025. Respeg is poised to be highly disruptive in the biologic treatment landscape for atopic dermatitis by offering a novel Agonistic Mechanism. ResPeg is designed to both dampen the inflammatory response and simultaneously restore immune balance by directly expanding functional Treg cells and engaging multiple immunoregulatory pathways in patients with ectopic dermatitis and other autoimmune disorders. Through its unique mechanism, Respec also has the potential to provide patients with superior efficacy as well as more favorable frequency of dosing. There are over 30 million people in the U.S. alone battling this chronic skin condition, and it can greatly impact quality of life and mental health for these patients.
Howard W. Robin: We refocused the company's development pipeline on immunology and inflammation.
Howard W. Robin: With our primary near term goal to advance rest bag to meaningful data catalysts in the first half of 2025.
Howard W. Robin: Roseburg is poised to be highly disruptive and the biologic treatment landscape for atopic dermatitis by offering a novel.
Howard W. Robin: <unk> mechanism.
Howard W. Robin: <unk> is designed to both tap into the inflammatory response and simultaneously restore immune balance by directly expanding functional T reg cells and engaging multiple immuno regulatory pathways in patients with atopic dermatitis and other autoimmune disorders.
Howard W. Robin: So what's unique mechanism respect also has the potential to provide patients with superior efficacy as well as more favorable in frequent dosing.
Howard W. Robin: There are over 30 million people in the U S alone.
Howard W. Robin: The weakness chronic skin condition and it can greatly impact quality of life and mental health for these patients.
Howard W. Robin: We made significant advancements in 2023 with respect to our ResPeg program. Most notably, we regained the full rights to ResPeg from Eli Lilly and now own the program 100% with no encumbrance. We moved to quickly design a phase 2B study in ectopic dermatitis based on the promising results from the phase 1B placebo-controlled randomized study at ResBag, which showed an 83% drop in eczema skin scores after just 12 weeks of treatment. Our phase 2b global study and this indication was launched in October 23, and enrollment is on track for data readout in the first half of 25. In late 2023, we also began work designing a Phase IIb study in alopecia areata, another area of high unmet need. The study is starting this month. There are approximately 7 million patients in the United States and 160 million people worldwide who have alopecia areata.
Howard W. Robin: We made significant advances advancements in 2023 with respect to our <unk> program, most notably we regained full rights to respect from Eli Lilly and now on the program, 100% with no encumbrances.
We moved to quickly design the phase <unk> study in atopic dermatitis based on the promising results from the phase one be placebo controlled randomized study of <unk>, which showed an 83% drop in excellent skin scores. After just 12 weeks of treatment.
Howard W. Robin: Our phase <unk> Global study in this indication was launched in October of 'twenty, three and enrollment is on track for data readout in the first half of 'twenty five.
Howard W. Robin: In late 2023, we also began work designing a phase <unk> study in alopecia areata that another area of high unmet need.
Howard W. Robin: The study is starting this march.
Approximately 7 million patients in the United States, and 160 million people worldwide, who have alopecia areata.
Howard W. Robin: JAK inhibitors are the primary treatment option for patients with alopecia, but they have a significant rebound effect with treatment cessation and several black box warnings. Based on the data we've generated to date on ResVag in the skin-related autoimmune condition of atopic dermatitis, psoriasis, and in patients with cutaneous manifestations of lupus, We believe Respeg has strong scientific rationale in the setting of alopecia and could have the potential to be a highly differentiated treatment option with a similar remittive effect for this unserved patient population. As I stated earlier, we look forward to the Phase 2b data for our ectopic dermatitis study and for our alopecia study in the first half of 2025. These will be highly meaningful data catalysts.
Howard W. Robin: JAK inhibitors are the primary treatment option for patients with alopecia, but have a significant rebound effect with treatment cessation and several black box warnings.
Howard W. Robin: Just on the data we've generated to date on Reds peg in the skin related autoimmune condition of atopic dermatitis psoriasis and in patients with cutaneous manifestations of lupus.
Howard W. Robin: We believe <unk>, a strong scientific rationale and the setting of alopecia and could have the potential to be a highly differentiated treatment option with a similar remit of effect for this unserved patient population.
Howard W. Robin: As I stated earlier, we look forward to the phase <unk> data for our topic dermatitis study and for our Alopecia study in the first half of 2025.
Howard W. Robin: These will be highly meaningful data catalysts for next year.
Howard W. Robin: In addition to RESPEG, we have another important immunology program that we're moving toward the clinic. This is a first-in-class differentiated mechanism in immunology, a TNFR2 agonist antibody, Nektar 165. TNFR2 has been shown to potentiate the suppressive effects and overall functional properties of Tregs, and the program is built on what we've learned through our deep experience with ResPeg and the Treg field and represents a promising mechanism for treatment of autoimmune disease, including multiple sclerosis and ulcerative colitis. We're currently conducting IND-enabling studies with the goal of targeting an IND submission in the first half of next year In line with our objectives to advance our immunology pipeline, today, we announced a $30 million financing that further bolsters Nektar's financial position as we head into transformative data catalyst. Importantly, we're pleased to bring on a new high quality long-term investor, TCG Crossover, who clearly shares our belief in the potential of respite. At a price of $1.20 per share, the transaction represents a premium of over 80% to Nektar's 30-day VWI.
Howard W. Robin: Yeah.
Howard W. Robin: In addition to resume we have another important immunology program that we're moving towards the clinic. This is a first in class differentiated mechanism in immunology.
Howard W. Robin: <unk> two agonist antibody nectar $1 65.
Howard W. Robin: TNF or two has been shown to potentiate, the suppressive effects and overall functional properties of T. Regs and the program is built on what we've learned through our deep experience with Red Peg and the T. Reg field and represents a promising mechanism for treatment of autoimmune diseases, including multiple sclerosis, and ulcerative colitis.
Howard W. Robin: We're currently conducting IND, enabling studies with the goal of targeting an IND submission in the first half of next year.
Howard W. Robin: In line with our objectives to advance our immunology pipeline today, we announced a $30 million financing further bolsters <unk> financial position as we head into transformative data catalysts.
Howard W. Robin: Accordingly, we're pleased to bring on a new high quality long term investor TCG crossover, who clearly shares our belief in the potential of <unk> bank at.
Howard W. Robin: At a price of $1 20 per share the transaction represents a premium of over 80% connectors 30 debut.
Howard W. Robin: This puts us in a strong financial position and extends our cash runway from our previous guidance, which was the middle of 2026, to now well into the third quarter of 2026. And with that, I'll hand the call over to Jay-Z for an R&D discussion. Jay-Z?
Howard W. Robin: This puts us in a strong financial position and extends our cash runway from our previous guidance, which was the middle of 2026 to now well into the third quarter of 2026.
Howard W. Robin: And with that I'll hand, the call over to Jay Z Arent R&D discussion Jay Z.
Jonathan Zalevsky: Thank you, Howard. Let's begin today with ResPeg, which is the most advanced IL-2-based T-reg mechanism in the field. Across the ResPeg studies that have been conducted to date, we have observed a consistent and highly predictable clinical pharmacology profile with respect to target engagement as well as the peak and duration of Treg mobilization. It has demonstrated a well tolerated safety profile and clear clinical efficacy in atopic dermatitis, as well as psoriasis, and in patients with cutaneous manifestations of lupus. Our deep experience with ResPeg to date across the totality of this clinical program gives us conviction in our ongoing phase 2b studies in atopic dermatitis and alopecia areata. Specifically, in atopic dermatitis, there are three important issues that patients with this disease continue to face.
Howard W. Robin: Yeah.
Thank you Howard.
Jay Olson: Let's begin today with Red Tag, which is the most advanced Iot based T Reg mechanism in the field.
Jay Olson: Across the rest peg studies that have been conducted to date, we have observed a consistent and highly predictable clinical pharmacology profile with respect to target engagement as well as the peak and duration of T. Reg mobilization.
Jay Olson: It has demonstrated a well tolerated safety profile and clear clinical efficacy in atopic dermatitis, and also psoriasis and in patients with cutaneous manifestations of lupus.
Jay Olson: Our deep experience with rents pegged to date across the totality of the clinical program gives us conviction in our ongoing phase <unk> studies in atopic dermatitis and alopecia Areata.
Jay Olson: Specifically in atopic dermatitis.
Jay Olson: Our three important issues that patients with this disease continue to face.
Jonathan Zalevsky: First, there is a need for great, specifically a deeper magnitude of response and rapid onset of treatment. Second, patients lack durable responses and therapy-free remission. Once current therapies are discontinued, patients rebound rapidly. And third, treatments with favorable safety profiles are lacking. This is especially important given the chronic nature of the disease and the need for continuous dosing. We believe there are major opportunities in this disease state that the differentiated profile of RASPEC could potentially address. Diving into our Phase 1b data in atopic dermatitis.
First there is a need for great efficacy.
Jay Olson: Specifically, a deeper magnitude of response and rapid onset of treatment.
Jay Olson: Second patient slack durable responses and therapy free remission.
Jay Olson: <unk> current therapies or discontinued patients rebound rapidly.
Jay Olson: And third treatments with favorable safety profiles are lacking.
Jay Olson: Especially important given the chronic nature of the disease and the need for continuous dosing.
Jay Olson: We believe that there are major opportunities in this disease state that the differentiated profile of brad's pad could potentially address.
Jay Olson: Diving into our phase <unk> data in atopic dermatitis through.
Jonathan Zalevsky: Through the 12-week induction period, RAS-Tag demonstrated dose-dependent efficacy across both physician-assessed and patient-reported efficacy measures, reaching statistical significance across many of these measures. At the highest dose level, RAS-PEG demonstrated a very rapid onset of response, with over 40% of patients achieving EC75 by week 3 after only two doses of RAS-PEG. This rapid onset of action rivals that of JAK inhibitors, which have outperformed the pill amount of this parameter. At the end of the induction period of 12 weeks, we observed a profound magnitude of effort.
Jay Olson: Through the 12 week induction period.
<unk> demonstrated dose dependent efficacy across both physician and patient reported efficacy measurements, reaching.
Jay Olson: Reaching statistical significant across many of these measures.
Jay Olson: At the highest dose level <unk> demonstrated a very rapid onset of response with over 40% of patients achieving <unk> 75 by week three after only two doses of breath back.
Jay Olson: This rapid onset of action rivals that of JAK inhibitors, which have outperformed pillar matter does parameter.
Jay Olson: At the end of the induction period of 12 weeks, we observed a profound magnitude of efficacy.
Jonathan Zalevsky: An 83% reduction in percent change from baseline EASY score with the highest dose tested. This is the largest magnitude of change that we've seen for a biologic and outside of one. Importantly, we are encouraged by the extended durability seen for the retina.
Jay Olson: And 83% reduction as a percent change from baseline easy score with the highest dose tested.
Jay Olson: This is the largest magnitude of change that we've seen for a biologic and outside of <unk> JAK inhibitor.
Jay Olson: Importantly, we are encouraged by the extended durability seen curb ratbag long after the completion of the 12 week induction period, many patients maintain durable disease control for an additional 36 weeks after the end of dosing.
Jonathan Zalevsky: Long after the completion of the 12-week induction period, many patients maintained durable disease control for an additional 36 weeks after the end of dosing, and this type of extended disease control after the end of dosing is not observed for tapilumab or for JAK. Durability of the EZ-75 response was observed with approximately 70% of EZ-75 responders maintaining that response for 36 weeks after the end of the 12-week induction period. This is a very exciting result and suggests that RET-PAG has the potential to be the first remitted therapy for atopic dermatitis. For both patient-reported outcomes and physician-assessed endpoints, we observed the same trends, rapid onset of effect, dose dependence, and long durability of control. Additionally, Respeg was well-tolerated, and treatment with Respeg did not induce anti-drug antibodies in patients, which has been reported with some examples of the IL-2 mutine class.
Jay Olson: And this type of extended disease control. After the end of dosing is not observed for <unk> or for JAK inhibitors.
Durability of the EZ 75 response was observed with approximately 70% <unk> 75 responders maintaining that response for 36 weeks. After the end of the 12 week induction period.
Jay Olson: This is a very exciting result, and suggests that <unk> has the potential to be the first rebid of therapy for atopic dermatitis.
Jay Olson: For both patient reported outcomes and physician assessed endpoints, we observed the same trend rapid onset of effect dose dependence and long durability of control.
Jay Olson: Additionally, <unk> was well tolerated and treatment with <unk> did not induce anti drug antibodies in patients, which has been reported that some examples of the IL two new teen class.
Jonathan Zalevsky: These promising data have us and KOLs very enthusiastic about the potential for long-term responses and infrequent maintenance dosing with ResPak in the setting of atopic dermatitis. In October 2023, we initiated the Phase 2b study of ResPEG in biologic-naive atopic dermatitis patients, and enrollment is well underway. Our goal is to enroll roughly 400 patients with three different regimens of Respeg versus placebo, evaluated over a 16-week induction period. After the induction period, patients that meet a threshold to advance from induction to maintenance will be re-randomized into one of two maintenance regimens, at different dosages at either once a month or once every three months dosing. And that schedule will continue for another 28 weeks.
Jay Olson: These promising data have us and kols very enthusiastic about the potential for long lasting responses that infrequent maintenance dosing with <unk> in the setting of atopic dermatitis.
Jay Olson: In October 2023, we initiated the phase <unk> study of <unk> bag, and biologic naive atopic dermatitis patients and enrollment is well underway.
Jay Olson: Our goal is to enroll roughly 400 patients with three different regimens of <unk> with <unk>.
Jay Olson: Tivo.
Jay Olson: Evaluated over a 16 week induction period.
Jay Olson: After the induction period patients that meet that threshold to advance from induction to maintenance will be re randomized into one of two maintenance regimens at different dosages at either once a month or once every three month dosing and that schedule will continue for another 28 weeks.
Jonathan Zalevsky: Our enrollment for this study is on track, and we expect data in the first half of 2025. Moving to alopecia areata, we believe RASPAG has a strong scientific rationale in this indication. Alopecia areata is also a disease of the skin where your immune system starts to attack the hair follicles, thereby weakening the ability of stem cells to grow hair. With prolonged immune attack, this eventually causes the hair follicle to release the hair altogether, leading to patchy hair loss and, as the disease progresses, baldness. Biologically speaking, RESPEG, through its central pathway of Treg rescue, is uniquely poised to address the diversity of immunopathology, providing broad potential for targeting multiple dermal diseases, including alopecia. For example, in alopecia, there are almost no immune cells in normal hair follicles, meaning the hair follicle is an immune-privileged tissue.
Jay Olson: Our enrollment for this study is on track and we expect data in the first half of 2025.
Jay Olson: Moving to alopecia Areata, we believe ratbag had strong scientific rationale in this indication.
Jay Olson: <unk> is also a disease of the skin, where you are in.
Jay Olson: System starts to attack the hair follicles, thereby a weakening the ability of stem cells to grow hair.
Jay Olson: With prolonged immune attack. This eventually causes that hair follicle to release their altogether, leading to Apache hair loss and as the disease progresses to bulk.
Jay Olson: Biologically speaking.
Jay Olson: Through its central pathway of T Reg rescue.
Jay Olson: Is uniquely poised to address the diversity of immuno oncology, providing broad potential for targeting multiple terminal diseases, including alopecia.
Jay Olson: For example in alopecia, there are almost no immune cells.
Jay Olson: Normal hair follicles, meaning the hair follicle is an immune privileged tissue.
Jonathan Zalevsky: Tregs are very important in maintaining that immune privilege, and people with alopecia areata develop a breakdown of that immune privilege state. We think the Treg mechanism of RasPak can restore immune privilege and could provide durable disease control, which we believe would be game-changing in this industry. JAK inhibitors are the only agents approved in alopecia, and they do not provide disease durability after a patient discontinues treatment. With JAK inhibitors, it can take a patient anywhere from 9 to 18 months to grow hair.
Jay Olson: T regs are very important in maintaining that immune privilege and people with alopecia area out to develop a breakdown of that immune privilege state.
Jay Olson: We think the T. Reg mechanism of <unk> can restore immune privilege and could provide durable disease control, which we believe would be game changing in this indication.
Jay Olson: JAK inhibitors are the only agents approved in alopecia and they do not provide disease durability after a patient discontinued treatment.
Jay Olson: With JAK inhibitors, it could take a patient anywhere from nine to 18 months to grow hair.
Jay Olson: And once a patient stops taking a JAK inhibitor, which may happen for a variety of reasons, including toxicity their hairstyles out again rapidly.
Jonathan Zalevsky: And once a patient stops taking a JAK inhibitor, which may happen for a variety of reasons, including toxicity, their hair falls out again rapidly. There is a high unmet need in this patient population for tolerable treatment options that provide durable responses. And we believe that restoration of immune privilege is key to obtain durability. For these reasons, we believe there is an opportunity for ResPeg to become a novel biologic therapy for alopecia areata.
Jay Olson: There is a high unmet need in this patient population for tolerable treatment options that provide durable responses.
Jay Olson: And we believe that restoration of immune privilege key to obtain durability.
Jay Olson: These reasons, we believe there is an opportunity for <unk> to become a novel biologic therapy in alopecia Areata.
We are initiating a phase <unk> study of <unk> in alopecia this month.
Jay Olson: The phase <unk> study to recruit roughly 80 patients with severe to very severe alopecia, who will be randomized to <unk> or placebo.
Jonathan Zalevsky: We are initiating a Phase 2B study of RASPEG and alopecia. The Phase 2B study plans to recruit roughly 80 patients with severe to very severe alopecia who will be randomized to ResPeg or placebo. Patients will be treated for a period of 36 weeks and observed up to 60 weeks in total.
Jay Olson: Patients will be treated for a period of 36 weeks and observed up to 60 weeks in total.
Jay Olson: Our primary endpoint for this study is the mean percent improvement install or the severity of alopecia tool at week 36, which is the validated outcome measure used for regulatory approval.
Jonathan Zalevsky: Our primary endpoint for this study is mean percent improvement in salt, or the severity of the alopecia tool, at week 36, which is the validated outcome measure used for regulatory approval. We will also be looking at a number of other secondary endpoints, including the proportion of patients who saw a reduction. Now turning to Nektar 0165, our TNFR2 agonist antibody. TNFR2 is highly expressed on Tregs, myeloid suppressor cells, regulatory B cells, neuronal cells, and others.
Jay Olson: We will also be looking at a number of other secondary endpoints, including proportion of patients who saw a reduction itself.
Jay Olson: Now turning to Nextera, <unk>, six five or TNF or two agonist antibody.
Jay Olson: TNF are too it's highly expressed on T. Reg myeloid suppressor cells regulatory beat.
Jay Olson: Neuronal cells than others and TNF are two agonism has been shown to potentiate, the depressive effect and overall functional properties of T regs and these other suppressive cell population.
Jay Olson: If TNF or two is absent it is associated with auto immunity and other genetic conditions that resemble Fox P. Three loss of function.
Jonathan Zalevsky: And TNFR2 agonism has been shown to potentiate the suppressive effect in overall functional properties of Tregs and these other suppressive cell populations. If TNFR2 is absent, it is associated with autoimmunity and other genetic conditions that resemble 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. This TNF-R2 agonist program in our pipeline is built upon many years of TREG experience gained from residents. For example, we know that central T cells, such as Thymex, require a substantial JAK-STAT signal that is physiologically provided by the IL-2 receptor pathway.
Jay Olson: In contrast, its presence has been associated with immuno regulatory function and protective effects for multiple cell populations in tissues in the body.
Jay Olson: This TNF are two agonist program and our pipeline is built upon many years of T. Reg experience gained from raspberries for.
Jay Olson: For example, we know that central T regs, such as Diamond T regs require a substantial JAK stat signaling that it physiologically provided by the IL two receptor pathway and this is essential theme and the mechanism of action of <unk>.
Jay Olson: In contrast, T regs that lead the central compartment and infiltrate the distal organs and tissues.
Jay Olson: There are less dependent on the JAK stat pathway and instead shipped their reliance answer Nf Kappa b pathway engagement or their maintenance of suppressor function.
Jay Olson: TNF or two is the most abundant TNF superfamily member expressed on T regs and the key driver of Nf Kappa B signaling in those top <unk>.
Jonathan Zalevsky: And this is a central theme in the mechanism of action of RASP. In contrast, Tregs that leave the central compartment and infiltrate the distal organs and tissues are less dependent on the JAK-STAT pathway and instead shift their reliance onto NF-kappa-B pathway engagement for their maintenance of suppressive function. TNF-R2 is the most abundant TNF super family member expressed on Tregs and the key driver of NF-kappa-V signaling in those cells, and consequently, a bona fide TNFR2 agonist would be an incredibly exciting addition to our pipeline. Examples of indications that could be addressed by TNF-R2 agonism include multiple sclerosis, mucosal immunology conditions, such as ulcerative co We have identified several lead TNFR2 antibody programs from an artificial intelligence-based antibody discovery campaign with our partner, Biologic Design. The lead antibody is called Nektar-0165, and it has highly desirable properties, including exquisite TNFR2 selectivity. TNFR2 agonism in primary human cells, activity in multiple preclinical efficacy models, and a very well-tolerated profile in early non-GLP toxicology.
Jay Olson: Consequently, a bonafide TNF or <unk> agonist would be an incredibly exciting addition to our pipeline.
Jay Olson: Examples of indications that could be addressed by TNF are two agonism include multiple sclerosis, new coastal immunology conditions, such as all startup colitis of the Gi or other oral Newcastle diseases, and even dermal auto immune diseases like vitiligo.
Jay Olson: We have identified several leading TNF are two antibody program from an artificial intelligence based antibody discovery campaign with our partner biologic design.
Jay Olson: Our lead antibody called <unk> 165, and it has highly desirable properties, including exquisite TNF or to selectivity.
<unk> agonism in primary human cells activity in multiple preclinical efficacy models and they're very well tolerated profile in early non GOP toxicology studies.
Jay Olson: We have developed the manufacturing cell lines for the lead and are conducting upstream and downstream process development with the aim to enter the clinic for this program in the first half of 2025.
Later this year, we plan to present, the first preclinical data for <unk> hundred 65 at an upcoming medical conference as.
Jay Olson: As we move forward with our IND, enabling studies there is growing interest for our novel selective TNF are two agonist like Nektar 165.
Jonathan Zalevsky: We have developed a manufacturing cell line for the lead and are conducting upstream and downstream process development with the aim of entering the clinic for this program in the first half of 2025. Later this year, we plan to present the first preclinical data for Nectar 0165 at an upcoming medical conference. As we move forward with our IND-enabling studies, there is growing interest in a novel selective TNFR2 agonist like Nektar 0165, and thus we remain open to the opportunity of working with companies that have an interest in these areas to strategize on the best path forward. Now let's switch gears to our IL-15-based oncology program, Nektar 2x5. Nectar 255 is an IL-15 based mechanism of action, holds great promise as a combination agent with cell therapies and other mechanisms such as checkpointing, and we are exploring the best partnering paths for continued development of this drug candidate. Our Nektar sponsored trial combining Nektar 255 with the approved CD19 CAR-T used Brionzi and Cardo for the treatment of patients with Large B-cell Lymphoma has enrolled 15 patients in the dose escalation portion of the study.
Jay Olson: We remain open to the opportunity in working with companies that have interest in these areas to strategize on the best path forward.
Jay Olson: Now, let's switch gears to our IL 15, based oncology program <unk> two by five.
Jay Olson: Negative 255, its IL 15 based mechanism of action holds great promise as a combination agent with cell therapies and other mechanisms such as checkpoint inhibitors and we are exploring the best partnering paths for continued development for this drug candidate.
Jay Olson: Our <unk> sponsored trial, combining metric $2 55, with the approved CD 19 car T is briana Z in used cars.
For treatment of patients with the large b cell lymphoma has enrolled 15 patients in the dose escalation portion of the study.
The combination of mix or $2 55, and <unk> is also being studied in a separate investigator sponsored trial at Fred Hutch.
Jay Olson: We are targeting the potential submission of data from these studies at medical meetings in the second half of this year.
Jay Olson: Our clinical trial in non small cell lung cancer sponsored and funded by April data, which evaluates the combination enables that.
Jay Olson: Tumor infiltrating lymphocyte cell therapy, plus electric <unk> and checkpoint inhibitor is also ongoing and enrolling patients.
Jay Olson: And with our partner Merck <unk>, we have also been evaluating an extra $2 55 in combination with <unk> versus single agent of NPL in the phase II javelin medley study and that study is on track to potentially report interim PFS data later this year.
Jay Olson: And with that I will turn the call over to Sandeep for a review of our financial guidance pending.
Jonathan Zalevsky: The combination of Nektar-255 embryology is also being studied in a separate investigator-sponsored trial at Pratt-Hutton. We are targeting the potential submission of data from these studies at medical meetings in the second half of the year. Clinical Trial in Non-Sponsored Lung Cancer, sponsored and funded by AbleZeta, which evaluates the combination of AbleZeta's tumor-infiltrating lymphocyte cell therapy plus Nektar-255 and a checkpoint inhibitor is also ongoing and enrolling patients.
Sandeep: Thank you Jamie and good afternoon, everyone.
Sandeep: Ended the year in a very strong financial position with 329 $4 million in cash and investments and no debt on our balance sheet.
Sandeep: Sure. It's David earlier, today's announcement of a $30 million financing further strengthens our cash position.
Sandeep: Our revenue was $23 $9 million for the fourth quarter of 2023 and $91 million for the full year of 2023.
Jonathan Zalevsky: And with our partner, Merck KGA, we have also been evaluating Nektar 255 in combination with defense versus single-agent da Vincio in the Phase 2 Javelin Bladder Medley Study, and that study is on track to potentially report interim PFS data later this year. With that, I will turn the call over to Sandy for a review of our financial guidance. Sandy?
Sandeep: Our operating costs and expenses for the fourth quarter of 2023.
Sandeep: 57, $4 million and $353 $8 million for the full year 2023.
Sandeep: Our non operating expenses for the fourth quarter of 2023, or $8 6 million and $12 6 million for the full year 2023 Q.
Sandra A. Gardiner: Thank you, Jay-Z, and good afternoon, everyone. We ended the year in a very strong financial position with $329.4 million in cash and investments and with no debt on our balance sheet. As Howard stated earlier, today's announcement of a $30 million financing further strengthens our cash position. Our revenue was $23.9 million for the fourth quarter of 2023 and $90.1 million for the full year of 2023. Our operating costs and expenses for the fourth quarter of 2023 were $57.4 million and $353.8 million for the full year 2023. Our non-operating expenses for the fourth quarter of 2023 were $8.6 million and $12.6 million for the full year 2023.
Q4, 2023 included a non cash charge of $6 1 million or three cents per share for the reclassification of the foreign currency translation adjustment to income related to the wind down of our India legal entity.
Sandeep: As a reminder, our India facility was sold in December 2022 for approximately $12 million with the wind down of the entity occurring in 2023.
Sandeep: Our net loss for the fourth quarter of 2023 with $42 1 million or 22.
Sandeep: Per share for the full year of 2023, our net loss was $276 $1 million or $1 45 per share.
Sandra A. Gardiner: Q4 2023 included a non-cash charge of $6.1 million, or $0.03 per share, for the reclassification of the foreign currency translation adjustment to income related to the winding down of our India legal entity. As a reminder, our India facility was sold in December 2022 for approximately $12 million, with the winding down of the entity occurring in 2023. Our net loss for the fourth quarter of 2023 was $42.1 million, or 22 cents per share. For the full year of 2023, our net loss was $276.1 million, or $1.45 per share. Excluding $111.8 million in non-cash goodwill and other impairment charges, the net loss on a non-gap basis for the full year 2023 was $164.3 million, or 86 cents a basic and diluted loss per share.
Sandeep: Excluding 111 8 million in non cash goodwill and other impairment charges net loss on a non-GAAP basis for the full year 2023 was $164 3 million or <unk> 86 cents.
Sandeep: Basic and diluted loss per share.
Looking forward to 2024 and beyond our financial position remains strong in part reflecting the cost savings initiatives. We undertook last year, we plan to end 2024 with $200 million to $225 million in cash and investments.
Sandeep: In addition to the $30 million Pie, we announced this morning, our 2024, our cash guidance also includes $15 million, resulting from an amendment executed today on a former 2020 agreement with certain entities of healthcare royalty.
Sandeep: Our cash runway now extends out extend well into the third quarter of 2026, which will take us through key value generating milestones, including phase II <unk> data in atopic dermatitis in alopecia Areata.
Sandra A. Gardiner: Looking forward to 2024 and beyond, our financial position remains strong, in part reflecting the cost savings initiatives we undertook last year. We plan to end 2024 with $200 to $225 million in cash and investments. In addition to the $30 million pipeline we announced this morning, our 2024 cash guidance also includes $15 million resulting from an amendment executed today on a former 2020 agreement with certain entities of healthcare royalty. Our CASH runway now extends well into the third quarter of 2026, which will take us through key value-generating milestones, including Phase II ResPeg data in atopic dermatitis and alopecia areata. Our revenue for the full year of 2024 is expected to be between $75 million and $85 million, which includes $55 to $65 million in non-cash royalties and $20 million to $25 million in product sales. We anticipate full-year R&D expenses will range between $120 million and $130 million. This includes approximately $5 to $10 million of non-cash depreciation and stock-based compensation expense.
Sandeep: Our revenue for the full year of 2024 is expected to be between $75 million and $85 million, which includes 55 to 65 million in noncash royalties and 20 million to 25 million and product sales.
Sandeep: We anticipate full year R&D expense will range between $120 million and $130 million.
This includes approximately $5 million to $10 million of noncash depreciation and stock based compensation expense.
Sandeep: Increase in R&D spend for 2024 over 2023 represents an increased investment in <unk> phase <unk> studies in atopic dermatitis, and alopecia area as well as innate.
Sandeep: Enabling studies for our antibody program nectar 165.
Sandeep: This increase is partially offset by decreased spending on <unk> 255 clinical studies in cell therapy, which are completing in 2024.
Sandeep: The remaining ongoing clinical studies for <unk> $2 55 are primarily funded by our external partners.
Sandeep: We expect G&A expense for the full year of 2024 to be between 70 million and $75 million switching.
Which includes five to 10 million of noncash depreciation and stock based compensation expense.
Sandra A. Gardiner: The increase in R&D spend for 2024 over 2023 represents an increased investment in two RISPG Phase IIb studies in atopic dermatitis and alopecia areata, as well as I&D enabling studies for our antibody program Nektar-0165. This increase is partially offset by decreased spending on Nektar 255 clinical studies and cell therapy, which are completed in 2024. The remaining ongoing clinical studies for Nektar 255 are primarily funded by our external partners. We expect G&A expense for the full year of 2024 to be between $70 million and $75 million, which includes $5 to $10 million of non-cash depreciation and stock-based compensation expense. Our full-year non-cash interest expense is expected to be between $20 and $25 million.
Sandeep: Full year non cash interest expense is expected to be between 20 and $25 million as I stated earlier, we expect to end this year with $200 million to $225 million in cash and investments.
Sandeep: And with that we will now open the call for questions Crystal.
Crystal: Thank you.
Crystal: As a reminder to ask a question. Please press star one on your telephone and wait for your name to be announced.
Speaker Change: Your question. Please press star one again.
Crystal: In the interest of time, we do ask that you. Please limit yourself to one question at this time.
Crystal: Please standby, we compile the Q&A roster.
Crystal: And our first question will come from Jay Olson from Opco. Your line is open.
Crystal: Oh, Hey, this is Joe on the line for Jay. Thank you for taking the question congrats on the progress.
Joe: Maybe just on Revpar 80 study wondering if you can talk about the initial feedback from doctors and patients participating in the study.
Sandra A. Gardiner: As I stated earlier, we expect to end this year with $200 to $225 million in cash and investments. And with that, we will now open the call for questions. Crystal?
Speaker Change: Especially in the context that there are many other competing trials out there.
Joe: Also if you also could comment on the recruitment program, thus far versus your internal expectation that will be great and I have a quick follow up question after that thank you.
Operator: Thank you. As a reminder, to ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again.
Joe: Mary do you want to take that question.
Joe: Yes sure Howard. Thank you Hi, Joe This is Mary Tagliaferri.
Operator: In the interest of time, we do ask that you please limit yourself to one question at this time. Please stand by while we compile the Q&A roster. And our first question will come from Jay Olson from OPCO. Your line is open. Oh, hey, this is Ching on the line for Jay.
Mary Tagliaferri: When we look at the aggregate.
Mary Tagliaferri: Data from site activation screening activities and enrollment we are on track to have our topline induction data.
Steady in the first half of 2025 and in terms of the feedback we're really pleased with the type of screening we are seeing and we believe this is driven by the data that was presented by Jonathan silver bearing at the 2023, the doctors really do you see.
Chong: Thank you for taking the question and congrats on the progress. Maybe just on the RAS-PAC-80 study, I'm wondering if you can talk about the initial feedback from doctors and patients participating in the study, especially in the context that there are many other competing trials out there. Also, if you could also comment on the recruitment progress thus far versus your internal expectation, that would be great.
Mary Tagliaferri: That one <unk> is a very rapid onset of action number two the depth of response that was seen with <unk>.
Mary Tagliaferri: Mean percent change in easy after only 12 weeks of treatment.
Mary Tagliaferri: And I have a quick follow-up question after that. Thank you. Mary, do you want to take that question? Yeah, sure, Howard. Thank you. Hi, Joe. This is Mary Tagliaferri.
Mary Tagliaferri: In most studies looking at reduction period of 16 weeks. The doctors have been very impressed with that and then certainly if their patients. They really love. The durability that we saw in patients were off treatment for nine consecutive months and they were able to maintain that very deep response and easy.
Mary Tagliaferri: You know, when we look at the aggregate of data from site activation, screening activities, and enrollment, we are on track to have our top line induction data from the AD study in the first half of 2025. And in terms of feedback, you know, we're really pleased with the type of screening we're seeing, and we believe this is driven by the data that was presented by Jonathan Silverberg at EADV 2023. The doctors really do see that one, RISD has a very rapid onset of action.
Mary Tagliaferri: This is all very very attractive to our recruiting patients to the study so we're doing very well.
<unk>.
Speaker Change: Thank you Sir.
Speaker Change: Pleased with enrollment and we're not experiencing that.
Speaker Change: Got it. Thank you and just a quick follow up just wondering to what extent you can leverage the clinical sites for the study for the upcoming alopecia Areata initiation. So can you just use the same sites or are there some other.
Mary Tagliaferri: Number two, the depth of response that we're seeing with the mean percent change in EADV after only 12 weeks of treatment, when most studies look at an induction period of 16 weeks, doctors have been very impressed with that. And then, certainly, for the benefit of their patients, they really love the durability that we saw when patients were off treatment for nine consecutive months, and they were able to maintain that very deep response in EADV. This is all very, very attractive for recruiting patients for the study. So we're doing very well. I have heard that other studies are pleased with enrollment, and we're not experiencing that.
Speaker Change: Layer of work to do.
Speaker Change: Yes. So we are going to use 12 sites that are participating in the AEP.
Speaker Change: <unk> study in our <unk> study and.
Speaker Change: Physicians are very excited to have an opportunity for a second skin disease to evaluate <unk> in alopecia then.
Speaker Change: Again, they are really eager to see durability.
Speaker Change: Your ability at response because of course, when they see their patients with JAK inhibitors.
Speaker Change: You're back.
Speaker Change: They start to lose their hair Wednesday discontinued treatment with a JAK inhibitor. So the promise.
Speaker Change: In Asia.
Speaker Change: And your probability and restore immune privilege is definitely really encouraging and exciting.
Mary Tagliaferri: Got it. Thank you. And just a quick follow-up. I'm just wondering to what extent you can leverage the clinical sites for the AD study for the upcoming alopecia areata initiation. So can you just use the same sites, or is there another layer of work you need to do?
Speaker Change: Since I've been speaking to.
Okay. Thank you so much.
Thank you.
Speaker Change: And our next question will come from Roger song from Jefferies. Your line is open.
Speaker Change: Hi team this is <unk> on for Roger.
Roger Song: Maybe just following up on the alopecia Areata study.
Mary Tagliaferri: Yes, so we are going to use 12 sites that are participating in the AD study in our alopecia study, and those physicians are very excited to have an opportunity for a second skin disease to evaluate RezPeg in alopecia areata. And again, they're really eager to see a durability of response because, of course, when they treat their patients with JAK inhibitors, and they grow their scars back, immediately, they start to lose their hair once they discontinue treatment with the JAK inhibitors. So the promise of an age of durability and restored immune privilege is definitely really encouraging and exciting to the patients I've been speaking to. Okay, thank you so much.
Speaker Change: How many total clinical sites will you be enrolling and what's kind of the geographic distribution of those sites.
Speaker Change: For some key baseline characteristics for the patients in those studies.
Speaker Change: Most of them be.
Speaker Change: JAK inhibitor refractory.
Speaker Change: Detail there would be I appreciate it.
Speaker Change: Sure Gary you want to.
Speaker Change: Okay.
Gary: Yeah. Thanks, Eric we'll have slightly over their site, we're going to be in Canada, and the United States and in Poland.
As you may imagine when youre.
Gary: Oh, and they definitely have an access issue and it also takes a very long time for those patients to get in to see a dermatologist. So.
Mary Tagliaferri: Thank you. And our next question will come from Roger Song from Jeffries. Your line is open. Hi team.
Gary: It's actually a very favorable environment to enroll patients these patients.
Kami: This is Kami, Don, for Roger. Maybe just following up on the alopecia areata study, how many total clinical sites will we be enrolling? And what's the geographic distribution of those sites?
Gary: We are going to be Jack.
Gary: Inhibitor naive patients and then our key.
Gary: <unk> criteria is this for the year to very severe alopecia.
Mary Tagliaferri: And then for some key baseline characteristics for the patients in these studies will be, most of them will be JAK inhibitor refractory. Any detail there? Mary, do you want to take that again? Yeah, thanks, Howard. We'll have slightly over 30 sites. We're going to be in Canada, the United States, and Poland. You know, as you may imagine, when you're in Poland, they definitely have an access issue, and it also takes a very long time for those patients to get in to see a dermatologist.
Gary: These patients all have to have a salt great evening.
Gary: <unk> hundred 50 and of course this is the same patient population.
Gary: Where theyre sitting here at Lilly.
Gary: Lilly's jacket, and Pfizer's JAK inhibitor.
Gary: And the eligibility criteria for the pivotal trial.
Gary: Yes.
Speaker Change: Great. Thank you.
Speaker Change: Thank you.
Speaker Change: Our next question will come from Jessica Fye from Jpmorgan. Your line is open.
Yeah.
Jessica Macomber Fye: Hey, Thanks for taking my question.
Jessica Macomber Fye: Thanks to the atopic derm trial.
Mary Tagliaferri: So, you know, it's actually a very favorable environment to enroll patients. These patients are going to be JAK inhibitor-naive patients, and then our key, you know, inclusion criteria is severe to very severe alopecia patients. So, these patients all have to have a SALT greater than or equal to 50, and of course, this is the same patient population where they're SYNTIV and Lilly's JAK and Pfizer's JAK inhibitor at the same eligibility criteria for their pivotal trial. Thank you. Our next question will come from Jessica Fye from J.P. Morgan. Your line is open.
<unk> efficiencies need to be considered very responder and be re randomized at week 16.
Jessica Macomber Fye: Then also curious what's your latest thinking on whether the age or the alopecia trial will read out first and why.
Speaker Change: Yes, Hi, Jessica Mary Jo.
Speaker Change: Re randomize the patient has to have EC.
Speaker Change: 54.
Speaker Change: When they are re randomized to the maintenance dose.
Speaker Change: Once a month once every three months they will be on the same dose that they were randomized to in the injection period.
Okay.
Speaker Change: Hi.
Speaker Change: And so you have a second question.
Speaker Change: Just the timing of alopecia versus 80 data, yes, yes. So.
Jessica Macomber Fye: Hey, thanks for taking my question. For the Phase 2 BA topic DERM trial, what's the threshold patients need to meet to be considered a responder and be re-randomized at week 16? And then also, I was wondering what your latest thinking is on whether the AB or the alopecia trial will read out first and why. Yeah, hi Jessica, it's Mary.
Speaker Change: We expect the trial readout.
Speaker Change: Great. Thank you.
Speaker Change: Thank you.
Speaker Change: Thank you.
Speaker Change: Our next question will come from Julian Harrison from <unk>. Your line is open.
Gregory Allen Harrison: Hi, Congrats on the progress and thank you for taking my questions. I'm curious if you could remind us how youre thinking about efficacy beyond 12 weeks of dosing with <unk> in atopic derm do.
Mary Tagliaferri: So to be re-randomized, the patient has to have EZ50 or above. When they are re-randomized to the maintenance dose once a month or once every three months, they will be on the same dose that they were randomized to in the induction period. And do you have a second question? Oh, just the timing of alopecia versus A.D. data? Yeah, yeah, so we expect the A.D. trial to read out first. Thank you. Our next question will come from Julian Harrison from BTIG. Your line is open.
Gregory Allen Harrison: Do you expect the plateau at some point or do you expect response rates, maybe be progressive through 44 weeks of dosing.
Gregory Allen Harrison: And then with regards to the Lilly litigation, sorry, if I Miss It I'm wondering if you could comment on its current status and timing of next steps.
Gregory Allen Harrison: Mary I wanted to take the first part and I'll take the second part.
Gregory Allen Harrison: Yes.
Mary Tagliaferri: I definitely think that as we.
Speaker Change: Our induction period from 12 to 16 weeks.
Speaker Change: We're going to see a greater number of patients.
Gregory Allen Harrison: Hi, congrats on the progress and thank you for taking my questions. I'm curious if you could remind us how you think about efficacy beyond 12 weeks of dosing with the breast peg and atopic derm. Do you expect a plateau at some point, or do you expect response rates to maybe be progressive through 44 weeks of dosing? And then, with regard to the Lilly litigation, sorry if I missed it. I'm wondering if you could comment on its current status and timing of next steps. Mary, why don't you take the first part, and I'll take the second.
Speaker Change: Experienced a deeper response.
Speaker Change: Very much look forward to seeing what the mean percent change is as you know are the mean percent change from baseline to 12 weeks was 83% and as such that greater than any of the biologic agents. If you look at <unk> leverage or need.
Speaker Change: <unk>, our roka, we definitely saw the Dps response, but I do believe that we'll probably see more patients.
Speaker Change: <unk> seven.
Speaker Change: 75, and Ethernet benign DSV go out additional four weeks in an induction period.
Speaker Change: With regard to Lilly.
Lilly after after we filed our complaint in federal courts.
Mary Tagliaferri: Yeah, you know, I definitely think that as we extend our induction period from 12 weeks to 16 weeks, we're going to see a greater number of patients experience a deeper response. So, I very much look forward to seeing what the mean percent change is. As you know, our easy mean percent change from baseline to 12 weeks was 83%, and, as such, that was greater than any of the biologic agents.
Speaker Change: <unk> tried to convince the federal Court judge dismissed the case as you know and last week the federal Judge refused globally request.
Speaker Change: And the judge agreed to allow knickers claims primary claims to move forward and we expect the judge to settle trial date in 2025.
Howard W. Robin: So, if you look at DUPI or Odbrey or Ledbrey or NEMO or Roka, you know, we definitely saw the deepest response, but I do believe that we'll probably see more patients who experience an ED75 and even an ED90 as we go out an additional 4 weeks in the induction period. With regard to Lily... You know, Lilly, after we filed our complaint in federal court, Lilly tried to convince the federal court judge to dismiss the case, as you know. And last week, the federal judge refused Lilly's request, and the judge agreed to allow Nektar's claims, the primary claims, to move forward. And we expect the judge to set a trial date in 2025. The court also ordered the parties to engage in mediation within the next three months to try to resolve the issue. And so we're very, very happy the case is moving forward. The judge did not dismiss the case,
Speaker Change: The court also ordered the parties to engage in mediation within the next three months to try to resolve the issue.
And so we're very very happy the cases moving forward. The judge did not dismiss the case and we look forward to vindicating ourselves through the litigation process.
Speaker Change: Excellent thanks very much.
Speaker Change: Thank you.
Speaker Change: And as a reminder to ask a question. Please press star one one.
Speaker Change: And our next question will come from Andy Shay from William Blair. Your line is open.
Andy Shay: Great. Thanks for taking our questions.
Andy Shay: Two quick ones for us.
Andy Shay: One is can you talk about this ebb and flow dynamic.
Andy Shay: Especially with hair loss in alopecia.
Andy Shay: Enrolling kind of severe and really severe patients kind of <unk>.
Andy Shay: Mitigate that variability and the second question has to do with the TNF receptor 165 program.
Howard W. Robin: And we look forward to vindicating ourselves through the litigation process. Excellent. Thanks very much. Thank you. And as a reminder, to ask a question, please press star 11. And our next question will come from Andy Shea from William Blair. Your line is open.
Andy Shay: We know that the receptor family is a trimer. So I guess to maximally agonizes receptor you might have to have like a trimer design I'm. Just curious if that's kind of a part of the design that goes into.
Andy Shay: 165, and downstream from there Theres also kind of clustering. So is that also a part of.
Andy Shea: Great. Thanks for taking our questions. We have two quick ones for you. One is, can you talk about this ebb and flow dynamic associated with hair loss in alopecia? Would enrolling kind of severe and really severe patients kind of mitigate that variability?
Andy Shay: The design of the molecule.
Andy Shay: Mary do you want to take the hair loss and then JV.
Andy Shay: Yes, So hi, Andy it's Mary So you're exactly right one patients go into the year into very severe gen.
Andy Shea: And the second question has to do with the TNF receptor 165 program. We know that the receptor family is a trimer. So I guess to maximally agonize this receptor, you might have to have a trimer design. I'm just curious if that's kind of a part of the design that goes into 165.
Speaker Change: Generally speaking there is.
Speaker Change: Not.
Mary Tagliaferri: Ah regrowth of hair, and Youre exactly right that that slide the eligibility criteria, even the threshold for approval by the FDA is this patient population.
Andy Shea: And downstream from that, there's also kind of clustering. So is that also a part of the design of the molecule? Thanks. Mary, do you want to take the hair off? Yeah. And then Jay, you can take the peanuts off too.
Mary Tagliaferri: It does patients do start out with experienced feed patchy hair loss.
Mary Tagliaferri: But as the disease progresses, certainly becomes more extreme and even towards baldness Ah.
Patient loses their hair.
Mary Tagliaferri: Yeah. So, hi, Andy. It's Mary. So you're exactly right. Once patients go into the severe and the very severe, generally speaking, there is no regrowth of the hair.
Speaker Change: Very fair.
Speaker Change: For they tend to have rebirth of their hair without.
Speaker Change: Medical intervention and then I'll pass over to the second question Jason.
Jason: Yes, Thanks, Marion Thanks, Andy for your question.
Mary Tagliaferri: And that's you're exactly right. But that's why the eligibility criteria and even the threshold for approval by the FDA are this patient population. You know, patients do start out experiencing just patchy hair loss, but as the disease progresses, certainly, the hair becomes more extreme and, you know, even towards baldness. But once the patient loses their hair, it's very rare for them to have regrowth of their hair without some sort of medical intervention.
Jason: So you are right so TNF.
Jason: Our teams are drivers, but as we've learned more and more about the biophysics of the receptors and the way the plot domains right, which are the associated rich domains of hold together the receptor subunits. They actually work to create dimers a receptor.
Jason: And then a trimer comes along in clusters six.
Receptors or three pairs of dimers.
Jason: And then you can get additional clustering. Some of this ultra structure has been published and some structural studies have been done well.
Mary Tagliaferri: And then I'll pass the second question to Jay. Yeah, thanks, Mary. Thanks, Andy, for your question. So, you're right. So TNF. Proteins or trimers? But as we learn more and more about the biophysics of the receptors and the way the PLAD domains, which are these 16 rich domains that hold together the receptor subunits, they actually work to create dimers of receptors. And then a trimer comes along in cluster six.
Jason: We've come to understand through learning about the cell biology of these receptors. The way these divers need to <unk> and the way the epitopes for binding to the receptor is peak to work.
Jason: The epitope is actually fundamentally important.
One of the things we've discovered with nectar 015 is that it's an epitope that has its own unique properties and it can signal and a completely cluster independent fashion for example, it doesn't need FC Desert DVD balancing.
Jonathan Zalevsky: Receptors, or Three Pairs of Diary. So, and then you can get additional clustering, and some of this ultrastructure has been published, and some structural studies have been done. Well, we've come to understand A, through learning about the cell biology of these receptors, the way these divers need to multimerize, and the way the epitopes for binding to the receptors need to work. One of the things we discovered with Nektar 0165 is that it's an epitope that has its own unique properties, and it can signal in a completely cluster-independent fashion. For example, it doesn't need FC; it doesn't even need valence. That's one of the things that's really unique and highly differentiated about the antibodies that we've created. And keeping in mind all of these ultrastructural forms of the receptor and then the different states that the receptor can occupy is obviously one of the key things that's important for developing a successful drug. Thanks for the question.
Jason: That's one of the things Thats really unique and highly differentiated about the antibodies that we've created and keeping in mind all of these ultra structural forms of the receptor.
Jason: And then the different states that the receptor can occupy is obviously one of the key things that is important for developing a successful outcome.
Speaker Change: Thanks for the question.
Speaker Change: Yeah.
Speaker Change: Thank you.
Speaker Change: And I am showing no further questions from the phone lines I'd now like to turn the conference back over to Howard Robin for any closing remarks.
Howard W. Robin: Well. Thank you everyone for joining us today and as we stated on our call. We really remain focused on executing the development of <unk> in our immunology focused research programs I'd like to thank all of our employees for their very hard work and thank all of our shareholders new and existing for their continued support and we look forward to providing you with ups.
Howard W. Robin: Based on our progress so stay tuned and thanks for joining us again.
Howard W. Robin: Thank you. And I am showing no further questions from the phone lines, and I'd like to turn the conference back over to Howard Robin for any closing remarks. Well, thank you, everyone, for joining us today, and as we stated on our call, we really remain focused on executing the development of RESPEG in our immunology-focused research programs. I'd like to thank all of our employees for their very hard work and thank all of our shareholders, new and existing, for their continued support. We look forward to providing you with updates on our progress, so stay tuned. Thanks for joining us again. This concludes today's conference call. Thank you for your participation. You may now disconnect. Everyone have a wonderful day. [inaudible] www.globalonenessproject.org www.globalonenessproject.org Thank you for watching!
Speaker Change: Thank you. This concludes today's conference call. Thank you for your participation you may now disconnect everyone have a wonderful day.
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