Q2 2024 Nektar Therapeutics Earnings Call

[music].

Operator: Good day, and thank you for standing by. Welcome to the Nektar Therapeutics second quarter 2024 financial results conference call. At this time, all participants are in a listen-only mode.

Good day, and thank you for standing by.

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 11 on your telephone. You will then hear an automated message advising that your hand is raised.

Speaker Change: I come to the Nektar Therapeutics second quarter 2024 financial results Conference call.

Speaker Change: At this time all participants are in a listen only mode.

After the speaker's presentation, there will be a question and answer session.

To ask a question during the session you will need to press star one on your telephone you will then hear an automated message advising your hand is raised.

To withdraw your question. Please press star one again.

Speaker Change: Be advised that today's conference is being recorded.

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: I'd now like to hand, the conference over to your Speaker today Vivian will please go ahead.

Vivian Wu: 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 Zalevsky, our Chief Research and Development Officer, Dr. Mary Tagliaferri, our Chief Medical Officer, and Sandra Gardiner, our Chief Financial Officer. On today's call, we expect to make forward-looking statements regarding your business, including statements regarding the therapeutic potential of and future development plans for drug candidates in research programs.

Vivian: Thank you Crystal and good afternoon, everyone. Thank you for joining us today.

Speaker Change: With us on the call are Howard Robin, our President and Chief Executive Officer, Dr. Jonathan Zalewski, Our Chief Research and development Officer, Dr. Mary Tagliaferri, our Chief Medical Officer, and Sandra Gardner, our Chief Financial Officer.

Vivian Wu: The timing of the initiation of clinical studies and the availability of clinical data for drug candidates. The timing and plans for future clinical data presentations. The formation, future development plans, or success of our collaboration agreements, financial guidance, and certain other statements regarding the future for business. Because forward-looking statements relate to the future, they are subject to uncertainties and risks that are difficult to predict, many of which are outside of our control.

Speaker Change: On today's call, we expect to make forward looking statements regarding our business, including statements regarding the therapeutic potential of and future development plans for drug candidates and research programs.

Vivian: Timing of the initiation of clinical studies and availability of clinical data for drug candidates, the timing and plans for future clinical data presentations the formation future development plans or successive or collaboration agreements financial guidance and certain other statements regarding feature for our business.

Vivian: 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.

Speaker Change: Our actual results may differ materially from these statements.

Speaker Change: Risks and uncertainties are set forth in our Form 10-Q that was filed on May 10th 2024, which is available at SEC Gov.

Unknown Executive: MUSIC PLAYS MUSIC PLAYS[inaudible] MUSIC PLAYS MUSIC PLAYS MUSIC PLAYS MUSIC PLAYS MUSIC PLAYS MUSIC PLAYS MUSIC PLAYS MUSIC PLAYS MUSIC PLAYS MUSIC PLAYS MUSIC PLAYS MUSIC PLAYS MUSIC[inaudible] Rezpeg is designed to both dampen the inflammatory response and simultaneously restore immune balance by directly expanding functional T-reg cells and engaging multiple immunoregulatory pathways in patients with autoimmune disorders. Rezpeg is generated promising data which supports its potential to become a highly differentiated novel treatment for immune disorders.

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 webcast of this call will be available on the IR page of doctors website and Doctor Dotcom.

Vivian Wu: Our actual results may differ materially from these statements. Important risks and uncertainties are set forth in our Form 10-Q that was filed on May 10, 2024, which is available at sec.gov. We undertake no obligation to update any of these forward-looking statements, whether as a result of new information, future developments, or otherwise. A webcast of this call will be available on the Investor Relations page of Nektar's website, at Nektar.com. With that said, I would like to hand the call over to our President and CEO, Howard Robin. Thank you, Vivian, and thank you all for joining us today.

Howard Robin: With that said I would like to hand, the call over to our President and CEO Howard Robin Howard.

Howard Robin: Thank you Vivian and thank you all for joining us today.

Howard Robin: We've made good progress in the second quarter towards our goal of building a highly promising best-in-class pipeline focused on immunology and inflammation. In this quarter, we continue to make significant advancements with our lead program, ResPeg Aldoflucan. 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 autoimmune disease. ResPeg has generated promising data, which supports its potential to become a highly differentiated, novel treatment for immune disorders.

Howard Robin: We've made good progress in the second quarter towards our goal of building a highly promising best in class pipeline focused on immunology and inflammation and this quarter. We continued to make significant advancements with our lead program <unk>, obviously been a big.

Howard Robin: <unk> is designed to book.

Howard Robin: The inflammatory response and simultaneously restore immune balance.

Howard Robin: Direct lead expanding functional T reg cells, and engaging multiple immuno regulatory pathways in patients with autoimmune disorders.

Howard Robin: <unk> has generated promising data, which supports its potential to become a highly differentiated novel treatment for immune disorders.

Howard Robin: These data include phase 1b efficacy data in ectopic dermatitis, which is the most common chronic inflammatory skin disease and is marked by dysregulation of the immune system and specifically excessive activation of autoreactive and inflammatory T-cells. ResPeg is designed to address this root dysfunction.

Howard Robin: These data include the phase <unk> efficacy data in atopic dermatitis, which is the most common chronic inflammatory skin disease and as mark.

Howard Robin: This regulation of the immune system, and specifically excessive activation of auto reactive and inflammatory T cells.

Howard Robin: <unk> is designed to address this route dysfunction dysregulation by proliferating regulatory T cells, which can act on multiple inflammatory pathways at once.

Howard Robin: Disregulation by proliferating regulatory T cells that can act on multiple inflammatory pathways at once. Respec is a first-in-class agent in the most clinically advanced program of its kind targeting ectopic dermatitis, which has traditionally focused on signal pathway antagonists. I'll let Jay-Z talk more about this in a moment, but I'm proud to announce that we have an upcoming paper accepted in Nature Communications and a presentation at the EADV conference in September, which illustrates ResPec's mechanism.

Howard Robin: <unk> is a first in class agents and the most clinically advanced program of its kind targeting atopic dermatitis, which is traditionally focused on signal pathway antagonists.

Howard Robin: I'll, let Jason talk more about this in a moment, but im proud to announce that we have an upcoming paper accepted in nature communications.

Jason: In our presentation at the <unk> conference in September, which illustrate risk pigs mechanism.

Howard Robin: These publications will feature extensive biomarker analyses from our Phase 1b studies in immune-driven skin-related disorders of ectopic dermatitis and psoriasis. ResPeg is advancing nicely in the two Phase 2b studies that Nektar is conducting in ectopic dermatitis and alopecia areata, and enrollment for both studies remains on track.

Jason: These publications will feature extensive biomarker analysis from our phase <unk> studies and immune driven skin related disorders.

Speaker Change: Topic dermatitis in psoriasis.

Speaker Change: <unk> is advancing nicely.

Jason: Two phase <unk> studies that mixture is conducting an atopic dermatitis and alopecia.

Jason: Enrollment for both studies remains on track.

Howard Robin: The ectopic dermatitis study is enrolling 400 patients across approximately 110 clinical investigators in the US, Canada, Europe, and Australia. Patients who are enrolling in the study are diagnosed with moderate to severe ectopic dermatitis and are also biologic naive and have failed topical treatment. Importantly, this is the identical patient population studied in the Phase 1b study of residents. Jay-Z will talk more about this study design later in the call, and as I just stated, enrollment is on track for top-line data readout from the study's 16-week induction treatment stage in the first half of 2025.

Jason: Topic dermatitis studies enrolling 400 patients throughout approximately a 110 clinical investigator sites in the U S, Canada, Europe, and Australia patient.

Jason: Patients are enrolling in this study are diagnosed with moderate to severe atopic dermatitis and are also biologic naive and a failed topical treatment options. Importantly, this is the identical patient population studied in the phase <unk> study of resume.

Jason: J P will talk more about this study design later in the call and as Ive. Just stated enrollment is on track for top line data readout from the study 16 week induction treatment stage in the first half of 2025 months data from the maintenance stage, which looks at maintenance dosing every four weeks and every 12 weeks will be.

Howard Robin: Data from the maintenance stage, which looks at maintenance dosing every four weeks and every 12 weeks, will be available towards the end of 2025 and early 2026. There is a high unmet need for distinctive new mechanisms to treat ectopic dermatitis.

Jason: Available towards the end of 2025 early 'twenty six.

Jason: It is a high unmet need for distinctive new mechanisms to treat atopic dermatitis.

Howard Robin: With the extent and breadth of studies being conducted right now and the competition for patient recruitment, I am proud that we're achieving our enrollment. We believe that this is driven by a combination of the compelling ResPeg Phase 1b data presented at EADV 2023 and, of course, the hard work of our clinic. In the U.S., there are approximately 30 million people living with ectopic dermatitis, and half of these patients are diagnosed with moderate to severe disease.

Speaker Change: The extent and breath of studies being conducted right now in the competition for patient recruitment.

Unknown Executive: These data include the phase 1B efficacy data and ectopic dermatitis which is the most common chronic inflammatory skin disease and is marked by dysregulation of the immune system and specifically excessive activation of auto reactive and inflammatory T-cells. Rezpeg is designed to address this root dysfunction, dysregulation by proliferating regulatory T-cells which can act on multiple inflammatory pathways at once. Rezpeg is a first-in-class agent in the most clinically advanced program of its kind targeting its topic dermatitis which is traditionally focused on signal pathway antagonists.

Speaker Change: Route that we're achieving our enrollment goals. We believe that this is driven by a combination of the compelling <unk> phase <unk> data presented at <unk> 2023 and of course, the hard work of our clinical team.

Jason: And the U S. There are approximately 30 million people living with atopic dermatitis and half of the patients are diagnosed with moderate to severe disease and its estimated that under 10% of patients who could receive biologics today are actually receiving treatment. We believe that new mechanisms are the key to growing this market and that there is.

Howard Robin: And it's estimated that under 10% of patients who could receive biologics today are actually receiving treatment. We believe that new mechanisms are the key to growing this market and that there is a high unmet medical need for novel treatment. So we are excited that Respeg is poised to emerge as a highly differentiated potential treatment for these patients. Now, as you know, we have a second Phase 2 study for ResPeg that is enrolling 84 patients with alopecia areata. Enrollment for this study opened in March, and enrollment also remains on track for this study.

Speaker Change: High unmet medical need for novel treatment options. So we are excited that <unk> is poised to emerge.

Howard Robin: I'll let Jay Z talk more about this in a moment but I'm proud to announce that we have an upcoming paper accepted in nature communications and a presentation at the EADV conference in September which illustrates ResPEG's mechanism. These publications will feature extensive biomarker analyses from our phase 1B studies in immune driven skin-related disorders of its topic dermatitis and psoriasis. Rezpeg is advancing nicely in the two phase 2B studies that nectar is conducting in its topic dermatitis and alopecia are added.

Jason: Highly differentiated potential treatment for these patients now.

Jason: Now as you know we have a second phase III study for <unk> that is enrolling 84 patients with alopecia area.

Jason: For this study opened in March and the enrollment also remains on track for this study we are looking forward to top line data from this trial in the middle of 2025, which is estimated to be a few months. Following the top line readout from the phase II study in atopic dermatitis.

Howard Robin: We're looking forward to top-line data from this trial in the middle of 2025, which is estimated to be a few months following the top-line readout from the Phase 2 study in ectopic dermatitis. We believe there's a significant potential for Respec to help people with this devastating disease. Nearly 7 million people in the U.S. alone have or will develop alopecia areata.

Jason: We believe there is significant potential for <unk> to help people with this devastating disease nearly 7 million people in the U S alone have or will develop our PCL.

Howard Robin: Enrollment for both studies remains on track. The topic dermatitis study is enrolling 400 patients throughout approximately 110 clinical investigator sites in the US, Canada, Europe, and Australia. Patients are enrolling in the study are diagnosed with moderate to severe topic dermatitis and are also biologic naive and have failed topical treatment options. Importantly, this is the identical patient population studied in the phase 1B study of ResPEG. Jay Z will talk more about this study design later in the call and as I just stated enrollment is on track for top line data readout from the study's 16 week induction treatment stage in the first half of 2025.

Howard Robin: This disorder significantly affects the quality of life for patients, and the currently available JAK inhibitor therapies are not durable, have high relapse rates, and carry significant safety. Therefore, there is an urgent unmet medical need for these new therapies. On the preclinical side, we continue to advance Nektar 0165, our novel TNFR2 agonist antibody program. In June, we reported the first preclinical data on this program at ULAR. These data show that Nektar O165 is a unique antibody with monomeric activity that selectively binds to TNFR2 on Tregs to enhance their immunoregulatory function. Given the importance of TNFR receptor 2 in certain autoimmune diseases,

Speaker Change: This disorders significantly affects the quality of life for patients and the currently available JAK inhibitor therapies are not durable have high relapse rates and carry significant safety risks. Therefore, there is an urgent unmet medical need for these new therapies.

Speaker Change: On the preclinical side, we continue to advance Victor <unk> five our novel TNF agonist antibody program.

Jason: In June we reported the first preclinical data on this program at <unk>.

Speaker Change: These data showed that <unk> 106, five is a unique antibody with mono Derek activity that selectively binds to TNF or two on T regs to enhance their immuno regulatory function.

Howard Robin: Data from the maintenance stage which looks at maintenance dosing every four weeks and every 12 weeks will be available towards the end of 2025 and early 26. There's a high unmet need for distinctive new mechanisms to treat a topic dermatitis. When the extent and breadth of study is being conducted right now and the competition for patient recruitment, I am proud that we're achieving our enrollment goals. We believe that this is driven by a combination of the compelling ResPEG phase 1B data presented at EADV 2023 and of course the hard work of our clinical fee.

Jason: Given the importance of TNF receptor two in certain autoimmune diseases, nichter own 65% to potentially become a first in class treatment for autoimmune diseases, such as multiple sclerosis, ulcerative colitis lupus and vitiligo.

Howard Robin: Nektar 0165 could potentially become a first-in-class treatment for autoimmune diseases, such as multiple sclerosis, ulcerative colitis, lupus, and vitiligo. We're currently conducting IND-enabling studies with the goal of preparing for an IFD submission in the middle of 2025.

Speaker Change: We're currently conducting IND, enabling studies with the goal of preparing for an <unk> submission in the middle of 2025.

Howard Robin: Next, I'd like to give you an update on Nektar 255, our IL-15 program in oncology. As you know, Nektar is completing a study in large B-cell lymphoma, or LBCL, and Mary will be discussing this later in the call. In addition to the clinical study we're completing in LBCL, there are clinical studies ongoing for Nektar 255 being funded by our collaborators, Merck KGA in bladder cancer and AbleZeta in non-small cell lung cancer.

Jason: Next I'd like to give you an update on <unk> 255, our IL 15 program in oncology.

Mary Tagliaferri: As you know nectar is completing a study in large b cell lymphoma, or <unk> and Mary will be discussing this later in the call. In addition to the clinical study were completing an LPL. There are clinical studies ongoing for an extra $2 55 being funded by our collaborators Merck <unk> in bladder cancer and <unk>.

Howard Robin: In the US, there are approximately 30 million people living with a topic dermatitis and half of the patients are diagnosed with moderate to severe disease and it's estimated that under 10% of patients who could receive biologic today are actually receiving treatment. We believe that new mechanisms are the key to growing this market and that there's a high unmet medical need for novel treatment options. So we are excited that ResPEG is poised to emerge as a highly differentiated potential treatment to these patients.

Mary Tagliaferri: <unk> Zeta and non small cell lung cancer.

Howard Robin: We also have an ISP study ongoing at the Fred Hutchinson Cancer Center and an ISP that recently concluded at Stanford. Stanford University recently published data from their IST in the peer-reviewed journal of the American Society of Hematology, Blood. The online manuscript has been posted, and it will be in print shortly.

Mary Tagliaferri: We also have an ISP study ongoing at the Fred Hutchinson cancer Cancer Center and in ISG that recently concluded at Stanford.

Howard Robin: Now, as you know, we have a second phase two study for ResPEG that is enrolling 84 patients with alopecia area added. Enrollment for this study opened in March and the enrollment also remains on track for this study. We're looking forward to top line data from this trial in the middle of 2025, which is estimated to be a few months following the top line readout from the phase two study in a topic dermatitis.

Jason: Stanford University recently published data from their ISG in the peer review journal of the American Society of Hematology blood.

Jason: Online manuscript has been posted and it will be in print shortly.

Howard Robin: Stanford reported data that showed a doubling of recurrence-free survival at 12 months when Nektar 255 was combined with their investigational CD1922 CAR-T therapy compared to historical controls with their investigational therapy alone. In addition to these studies, Mary will discuss more about the other studies for Nektar-255 and the strength of the data to support combination with cell therapy. As data emerged this year, we believe that Nektar 255 can become an important component of cell therapy in cancer, and we continue to evaluate strategic partnership opportunities for this program.

Speaker Change: Stanford reported data that showed a doubling of recurrence free survival at 12 months when <unk> $2 55 was combined with their investigational CD 1922 car T therapy compared to historical controls with their investigational therapy alone.

Howard Robin: We believe there's a significant potential for ResPEG to help people with this devastating disease. Nearly seven million people in the US alone have or will develop alopecia area added. This disorder significantly affects the quality of life for patients, and the currently available Jack inhibitor therapies are not durable, have high relapse rates, and carry significant safety risks. Therefore, there's an urgent unmet medical need for these new therapies.

Jason: In addition to these studies Mary will discuss more on the other studies for an extra $2 55, and the strength of the data to support combination with cell therapies.

Jason: As the data emerge this year.

Jason: We believe that <unk> $2 55 can become an important component of cell therapy in cancer, and we continue to evaluate strategic partnership opportunities for this program.

Unknown Executive: On the preclinical side, we continue to advance Nektar 0165, our novel TNFR-2 agonist antibody program. In June, we reported the first preclinical data on this program as you are. These data show that Nektar 0165 is a unique antibody with monomeric activity that's selectively bind to TNFR-2 on T-regs to enhance their immunoregulatory function. Given the importance of TNFR receptor 2 in certain autoimmune diseases, Nektar 0165 could potentially become a first-in-class treatment for autoimmune diseases such as multiple sclerosis, ulcerative colitis, lupus, and vitilato. We're currently conducting IND enabling studies with the goal of preparing for an IFD submission in the middle of 2025.

Howard Robin: Before I hand the call over to Jay-Z, I just want to say that Nektar remains in a strong financial position with a cash runway that extends into the third quarter of 2026, giving us more than a year's cash at the time of ResPeg's top-line data release. And with that, I'd like to hand the call over to Jay-Z for an R&D discussion. Jay-Z?

Jason: Before I hand, the call over to Jay Z I, just wanted to say that <unk> remains in a strong financial position with a cash runway that extends into the third quarter of 2026, giving us more than a year's cash at the time of risk pegs topline data readouts.

Jason: I would like to hand, the call over to Jay Z <unk> R&D discussion Jay Z.

Jay Z: Thank you Howard.

Jonathan Zalevsky: Thank you, Howard. I'd like to begin with, This program is the most advanced IL-2 Treg mechanism in the field, and we believe there are major opportunities in both atopic dermatitis and alopecia areata that RASPEC could potentially address. Our Phase 1b ResPeg data in atopic dermatitis demonstrated dose-dependent efficacy and encouraging durability observed long after patient. The 12-Week Induction Period

Jay Z: I'd like to begin with rest pain.

Jay Z: This program is the most advanced IL two T Reg mechanism in the field.

Speaker Change: We believe there are major opportunities in both atopic dermatitis and alopecia area that debt.

Speaker Change: <unk> could potentially address.

Speaker Change: Our phase one be pegged data in atopic dermatitis demonstrated dose dependent efficacy and encouraging durability observed long after patients completed the 12 week induction period.

Unknown Executive: Next, I'd like to give you an update on Nektar 0255, our IL-15 program in oncology. As you know, Nektar is completing a study in large B cell lymphoma or LBCL, and Mary will be discussing this later in the call. In addition to the clinical study with completing in LBCL, there are clinical studies ongoing for Nektar 0255 being funded by our collaborators. Merck KGA and bladder cancer enables that up in non-small cell lung cancer.

Jonathan Zalevsky: In fact, 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. Does the Rapid Onset of Action and the Type of Extended Disease Control After the End of, rival or outperform that of Tupilumab or Jaca? These promising data have us and KOLs very enthusiastic about the potential for long-lasting responses and frequent maintenance dosing with ResPeg and atopic dermatitis. Our Phase 2B study in atopic dermatitis is enrolling roughly 400 patients with three different regimens of ResPag versus Clifton being evaluated over a 16-week induction period.

Speaker Change: For both patient reported outcomes and physician assessed endpoint, we observed the same trends.

Speaker Change: Rapid onset of effect.

Speaker Change: Less dependence and long durability of control.

Jay Z: The rapid onset of action and the type of extended disease control. After the end of dosing rivals are outperformed added to pillar mab or JAK inhibitors.

Unknown Executive: We also have an ISP study ongoing at the Fred Hutchinson Cancer Center and an ISP that recently concluded at Stanford. Stanford University recently published data from their ISP and the peer review journal of the American Society of hematology blood. The online manuscript has been posted and will be in print shortly. Stanford reported data that showed a doubling of recurrence-free survival at 12 months when Nektar 0255 was combined with their investigational CD-1922 CAR-T therapy compared to historical controls with their investigational therapy alone.

Speaker Change: These promising data have us and kols very enthusiastic about the potential for long lasting responses and infrequent maintenance dosing with <unk> in atopic dermatitis.

Speaker Change: Our phase <unk> study in atopic dermatitis is enrolling roughly 400 patients with three different regimens of <unk> versus placebo.

Speaker Change: <unk> over a 16 week induction period.

Jonathan Zalevsky: After the induction period, patients that meet a threshold to advance from induction to make will be re-randomized into one of two maintenance regimens at their original dosage, to receive that dose level once a month or once every three months, to best position our program for registration. We've recently amended the protocol to extend the time on treatment during the maintenance portion of this study. The maintenance portion of the Phase 2b study was originally designed as a 26-week treatment period.

Speaker Change: 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 their original dose level to receive that dose level on either a once a month or once every three months regimen.

Unknown Executive: In addition to these studies, Mary will discuss more on the other studies from Nektar 0255 and the strength of the data to support combination with cell therapies. As the data emerged this year, we believe that Nektar 0255 can become an important component of cell therapy and cancer, and we continue to evaluate strategic partnership opportunities for this program.

Speaker Change: To best position our program for registration.

Speaker Change: Our recently amended the protocol to extend the time on treatment during the maintenance portion of this study.

Speaker Change: The maintenance portion of the Phase <unk> study was originally designed as a 26 week treatment period, but we have now extended that to 36 weeks.

Jonathan Zalevsky: But we have now extended that to 36, which will in total provide 52 weeks of treatment duration for patients in the study. This will strengthen the robustness of our dataset with long-term exposure in this disease and increase the number of patients in our safety analysis to support registrational trial work following this phase two study. We also extended the off-treatment follow-up to be one year, beginning upon the conclusion of the 52-week treatment, in order to allow us to evaluate the potential remittive effect of REST.

Howard Robin: Before I hand the call over to Jay-Z, I just want to say that Nektar remains in a strong financial position with a cash runway that extends into the third quarter of 2026, giving us more than a year's cash at the time of breast vagueness top-line data. With that, I'd like to hand the call over to Jay-Z for an R&D destruction. Jay-Z?

Speaker Change: Which will in total provide 52 weeks of treatment duration for patients in the study.

Speaker Change: This will strengthen the robustness of our dataset with long term exposure in that disease, setting and increase the number of patients in our safety analysis to support Registrational trial work. Following this phase III study.

Jay Z: Thank you, Howard. I'd like to begin with Respeg. This program is the most advanced aisle to T-reg mechanism in the field. We believe there are major opportunities in both atopic dermatitis and alopecia areas that Respeg could potentially address. Our Phase 1B Respeg data in atopic dermatitis demonstrated dose-dependent efficacy and encouraging durability observed long after patients completed the 12-week induction period. In fact, 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.

Speaker Change: We also extended the off treatment follow up to be a one year period that begins upon the conclusion of the 52 week treatment period.

Speaker Change: In order to allow us to evaluate the potential repeat of effective breast pack in patients after one year of treatment.

Jonathan Zalevsky: Inpatients after one year of treatment. As Howard stated, we still anticipate top-line data from the 16-week induction period of this Phase IIb study in the first half of 2025, and data from the 36-week maintenance period will be available towards the end of 2025 or early 2025. Now turning to alopecia areata, which is a dermal disease localized to hair fall. In this disease, the patient's immune system attacks the hair follicle. Disrupting its normal ability to keep and grow hair, leading to hair loss.

Speaker Change: As Howard stated, we still anticipate topline data from the 16 week induction period of this phase <unk> study in the first half of 2025 and.

Howard Robin: And data from the 36 week maintenance period of the study will be available towards the end of 2025 or early 2026.

Speaker Change: Now turning to alopecia, Areata, which is a dermal disease localized to hair follicle and.

Jay Z: The rapid onset of action and the type of extended disease control after the end of dosing rivals or outperformed that of de-pilimab or jack inhibitors. These promising data have us and KOLs very enthusiastic about the potential for long-lasting responses and in frequent maintenance dosing with Respeg in atopic dermatitis. Our Phase 2B study in atopic dermatitis is enrolling roughly 400 patients with three different regimens of Respeg versus placebo, evaluated over a 16-week induction period.

Speaker Change: And this disease the patients immune system attacks, the hair follicle disrupting its normal ability to keep and grow hair.

Howard Robin: Leading to hair loss.

Jonathan Zalevsky: We believe there is a strong rationale for ResPag in this indication based on the role of Tregs in the underlying pathology. Normal hair follicles exist in a state of immune privilege. So, in other words, there are essentially no immune cells, no MHC expression, and minimal immune system components inside the hair follicles. We know this exclusion of the immune system is needed to maintain healthy, long-lived, and continuously functioning stem cells to grow hair during our lifetimes, and in people with alopecia areata. There is a breakdown of immune privilege and hair fall. Infiltration of the Immune System, and inflammation. And all this leads to hair loss and eventually complete baldness.

Speaker Change: We believe there is strong rationale for <unk> in this indication based on the role of T. Regs on the underlying pathology of this disease.

Speaker Change: Normal hair follicles to exist in a state of immune privilege.

Speaker Change: Other words, there are essentially no immune cells, no MHC expression and minimal immune system components inside the hair follicle.

Speaker Change: We know this exclusion of the immune system is needed to maintain healthy long lived and continuously functioning stem cells to grow hair during our lifespan.

Jay Z: 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 their original dose level to receive that dose level on either a once a month or once every three month regimen. To best position our program for registration, we've recently amended the protocol to extend the time-on treatment during the maintenance portion of this study. The maintenance portion of the Phase 2B study was originally designed as a 26-week treatment period, but we have now extended that to 36 weeks, which will in total provide 52 weeks of treatment duration for patients in the study.

Speaker Change: And people with alopecia area that there is a breakdown of the immune privilege and the hair follicle.

Speaker Change: Filtration of the immune system inflammation.

Speaker Change: All of this leads to hair loss and eventually complete baldness.

Jonathan Zalevsky: Biologically speaking, RezPeg, through its central pathway of Treg rescue, is uniquely poised to address the diversity of immunopathology, providing broad potential for targeting and treating alopecia areata, as well as other dermatitis. In published pre-clinical studies, both in vitro and in mice implanted with human alopecia skin cells, studies have shown that Tregs are essential for restoring and maintaining immune privilege, And consequently, we believe the Treg mechanism of RASPAG can restore immune function..., and could provide durable disease.

Speaker Change: Biologically speaking <unk> through its central pathway of T. Reg rescue is uniquely poised to address the diversity of immuno pathology, providing broad potential for targeting treating alopecia area that.

Speaker Change: As well as other terminal diseases.

Speaker Change: And published preclinical studies, both in vitro and in mice implanted, but human alopecia skin samples and studies have shown the T. Regs are essential for restoring and maintain immune privilege and therefore, a novel therapeutic strategy for the treatment of this disease.

Jay Z: This will strengthen the robustness of our data set with long-term exposure in the disease setting and increase the number of patients in our safety analysis to support registration or trial work following this Phase 2 study. We also extended the off-treatment follow-up to be a one-year period that begins upon the conclusion of the 52-week treatment period. In order to allow us to evaluate the potential remittive effect of Respeg, in patients after one year of treatment.

Speaker Change: Consequently, we believe the T. Reg mechanism of <unk> can restore immune privilege and could provide durable disease control.

Jonathan Zalevsky: There is a high unmet need in this patient population for tolerable treatment options and durable responses that currently available treatments like JAK inhibitors cannot provide. We believe there is an opportunity for ResPAG to become a novel and potentially game-changing biologic therapy in alopecia areata. The Phase 2B study is well underway and plans to recruit 84 participants, severe to very severe, that will be randomized to REST tag.

Speaker Change: There is a high unmet need in this patient population for tolerable treatment options with durable responses that currently available treatments like JAK inhibitors cannot provide.

Speaker Change: And we believe there is an opportunity for <unk> to become a novel and potentially game changing biologic therapy in alopecia areata.

Jay Z: As Howard stated, we still anticipate top-line data from the 16-week induction period of this Phase 2B study in the first half of 2025, and data from the 36-week maintenance period of the study will be available towards the end of 2025 or early 2026.

Speaker Change: The phase <unk> study is well underway and plans to recruit 84 patients with severe to very severe disease that will be randomized to red tag or placebo pay.

Jonathan Zalevsky: Patients will be treated for a period of 36 weeks and observed up to 60 weeks in total. Our primary endpoint for the study is mean percent improvement in SALT, or the severity of alopecia 2, at week 36, including her portion of patients that were observed to have varying degrees of improvement in salt. We are well underway with enrolling patients into this study, and we expect top-line data near the middle of 2025, a few months following the top-line data readout from our atopic dermatitis study.

Speaker Change: Patients will be treated for a period of 36 weeks and observed up to 60 weeks in total.

Jay Z: Now, turning to Alopecia Ariata, which is a dermal disease localized to hair follicle. In this disease, the patient's immune system attacks the hair follicle. Medical, disrupting its normal ability to keep and grow hair, leading to hair loss. When we believe there is strong rationale for redspag in this indication based on the role of T-Rags, on the underlying topology of this disease. Normal hair follicles exist in a state of immune privilege. So in other words, there are essentially no immune cells, no MHC expression, and minimal immune system components inside the hair follicle.

Speaker Change: Our primary endpoint for this study is the mean percent improvement in salt or the severity of alopecia tool at week 36.

Speaker Change: We will also be looking at a number of other secondary endpoints, including the proportion of patients that were observed to have varying degrees of improvement in salt score.

Speaker Change: We are well underway with enrolling patients into this study.

Speaker Change: We expect top line data near the Middle of 2025, a few months following top line data readout from our atopic dermatitis studies.

Jay Z: We know this exclusion of the immune system is needed to maintain healthy, long lived, and continuously functioning stem cells to grow hair during our life span. In people with alopecia ariata, there is a breakdown of the immune privilege in the hair follicle, infiltration of the immune system, inflammation, and all this leads to its central pathway of T-Rag rescue, is uniquely poised to address the diversity of immunopropology, providing broad potential for targeting treating alopecia ariata as well as other dermal diseases.

Jonathan Zalevsky: Now, turning to NECTAR 0165, our TNFR2 agonist antibody. TNFR2 is highly expressed on Tregs, myeloid suppressor cells, regulatory B cells, and neuronal cells. In Tregs, TNFR2 agonism has been shown to potentiate the effector function. Impressive Functions and Maintenance

Speaker Change: Now turning to <unk>, 165, or TNF or two agonist antibody.

Speaker Change: <unk> is highly expressed on T. Reg myeloid suppressor cells regulatory beef neuronal cells and others.

Speaker Change: In tea bags TNF are two agonism has been shown to potentiate, the effector function suppressor functions and maintenance of T Reg lineage stability.

Jonathan Zalevsky: T-Rag Linear Stability, especially in non-lymphoid tissue compartments. Genetic studies show that if TNF-R2 is absolutely... The phenotypic effect is autoimmunity, as well as other conditions that resemble FOXP3 loss of function. In contrast, it's present, and Activation of its signaling has been associated with immunoregulatory function and tissue protection. The TNS R2 agonist program, built upon many years of TRIG experience that we've gained from studying RAD. ResPag is an IL-2 receptor pathway agonist, DRIVE, JAKSTAT, SIGNALING, which is critical to drive TBAC proliferation and function in primary and secondary lymphoid organs.

Speaker Change: Specialty and non lymphoid tissue compartment.

Speaker Change: Genetic studies show that a TNF part two is absent that phenotypic effect as auto immunity as well as other conditions that resemble Fox P. Three loss of function.

Speaker Change: In contrast, its presence and activation of <unk> signaling has been associated with immuno regulatory function and tissue protection.

Jay Z: In published preclinical studies, both in vitro and in mice implanted by human alopecia skin samples, studies have shown that T-Rags are essential for restoring and maintaining immune privilege, and therefore a novel therapeutic strategy for the treatment of this disease. And consequently, we believe the T-Rag mechanism of redspag can restore immune privilege and could provide durable disease control. There is a high-endment need in this patient population for tolerable treatment options with durable responses that currently available treatments like jack inhibitors cannot provide.

Speaker Change: The TNF or two agonist program is built upon many years of <unk> experience that we've gained from studying resume.

Speaker Change: <unk> is an IL two receptor pathway agonist drives JAK stat signaling and T regs, which is critical to drive teabag proliferation and function in primary and secondary lymphoid organs.

Jonathan Zalevsky: TNFR2 is the most abundant TNF superfamily member expressed on and the key activator of NF-kappa-B, which also controls FOXP3 protein expression and is critical to maintain Treg function, especially in non-lymphoid organelles. Thus, with the ResPag and TNF-R2 agonist programs, Nektar's pipeline provides target rationale for both lymphoid and non-lympho And this is why we are so excited about Nektar 0165.

Speaker Change: TNF or two is the most abundant TNF superfamily member expressed on T regs and the key activator of Nf Kappa B, which also controls the Fox P. <unk> protein expression and is critical to maintain T reg function, especially in non lymphoid organs.

Jay Z: And we believe there is an opportunity for redspag to become a novel and potentially game-changing biologic therapy in alopecia ariata. The Phase II B study is well underway and plans to recruit 84 patients with severe to very severe disease that will be randomized to redspag work placebo. Patients will be treated for a period of 36 weeks and observed up to 60 weeks in total. Our primary endpoint for the study is mean percent improvement in salt or the severity of alopecia tool at week 36.

Speaker Change: Thus with the Red Tag and Ken Fr two agonist programs <unk> pipeline provide target rationale for both lymphoid and non lymphoid T. Rex and this is why we are so excited about <unk> <unk> five.

Jonathan Zalevsky: As Howard mentioned, we presented the first preclinical data for this program at UR in June. In the presentation, we demonstrated several novel and innovative properties of the antibodies that we discovered and are developing. Firstly, the TNF-R2 agonist we discovered came from AI-based de novo, and consequently, they provide novel PNFR2 binding and cell signaling properties.

Speaker Change: As Howard mentioned, we presented the first preclinical data for this program at <unk> This year.

Jonathan Zalevsky: One example of that novelty is a demonstration that these antibodies are able to signal through the TNFR2 multimeric receptor a single-arm monovalent antibody. This is a very novel effect for a TNF-R2 agonistic animal. We grafted these into a regular bivalent antibody format, a Nektar 0165, and demonstrated the very high specificity of this antibody for binding and signaling through TNFR2 on T-Ref, with little to no binding and signaling in conventional T-cells and K-cells or monocytogenes.

Speaker Change: In the presentation, we demonstrated several novel and innovative properties of the antibody that we discovered and are developing.

Jay Z: We will also be looking at a number of other secondary endpoints, including the proportion of patients that were observed to have varying degrees of improvement in salt score. We are well underway with enrolling patients into this study, and we expect top-line data near the middle of 2025, a few months following the top-line data readout from our atopic dermatitis study.

Speaker Change: Firstly the TNF are two agonists, we discovered came from AI based de Novo design.

Speaker Change: And consequently, they provide novel TNF are two binding and cell signaling property.

Speaker Change: One example of that novelty is a demonstration that these antibodies are able to signal to the TNF are two multi America receptor is single arm monovalent antibodies.

Speaker Change: This is a very novel effect for a TNF are two agonistic antibody.

Jay Z: Now, turning to NX-0165, our TNFR-2 agonist antibody. TNFR-2 is highly expressed on T-Rag's myeloid suppressor cells, regulatory b-cells, neuronal cells, and others. In T-Rag's TNFR-2 agonism has been shown to potentiate the effector function, suppressor functions, and maintenance of T-Rag lineage stability, especially in non-limpoid tissue compartments.

Speaker Change: We grafted these two irregular bivalent antibody format and Metro one <unk> or 165 and demonstrated the very high specificity of this antibody for binding and signaling through <unk> on T Rex with little to no binding and signaling and conventional T cells NK cells are monocytes.

Jonathan Zalevsky: Nectar 0165 also drove Treg proliferation, upregulation of FOXP3, and other activation of Primary Human T-Rex, and importantly, Nectar 0165 drove these effects as a single agent, without need for CD3 ligation, co-stimulation, cytokine, or mitogen. We also studied Nectar O165 in a human TNFR2 knock-in mouse and used that model to confirm the Treg selective PKPD profile of the antibody and also demonstrated single agent efficacy in a mouse model of KLHDTH established in the same TNFR2 knock-in mouse model.

Speaker Change: <unk> hundred 65 also drove T. Reg proliferation Upregulation of Fox P. III and other activation markers in primary human T Rex and importantly.

Jay Z: Genetic studies show that if TNF-2 is absent, the phenotypic effect is autoimmunity, as well as other conditions that resemble FOX-P3 loss of function. In contrast, its presence and activation of its signaling has been associated with immunoregulatory function and tissue protection effect. The TNF-R2 agonist program is built upon many years of T-Rig experience that we've gained from studying RASPEG. RASPEG is an IL-2 receptor pathway agonist, drives jacks that signaling in T-Rags, which is critical to drive T-Rag proliferation and function in primary and secondary lymphoid orchid.

Speaker Change: <unk> a 165 drove these effects as a single agent.

Speaker Change: Without need for CD, three litigation co stimulation cytokines or mitogen support.

Speaker Change: We also studied natural 165% and a human TNF or to knock in mouse and use that model to confirm the T. Regs selective PK PD profile of the antibody and also demonstrated single agent efficacy in a mouse model of KLA Dth established in the same TNF or to knock in mouth strength.

Jonathan Zalevsky: We are very excited with the unique and differentiated profile of the antibodies that were discovered, and we are rapidly advancing Nectar 0165. We expect to initiate first human studies in the middle of 2025. Examples of indications that could be addressed include multiple sclerosis, mucosal immunology conditions such as ulcerative colitis and GI or other orals, lupus, and even dermal autoimmune diseases like vitiligo. We note the growing interest in a novel and selective TNF-R2 agonist like Nektar Therapeutics.

Speaker Change: We are very excited with the unique and differentiated profile of the antibodies that were discovered and we are rapidly advancing <unk> 106, five to the clinic we expect.

Jay Z: TNF-R2 is the most abundant TNF super family member expressed on T-Rags and the key activator of NFKAP-B, which also controls the FOX-P3 protein expression and is critical to maintain T-Rag function, especially in non-limphoid organ. Thus, with the RASPEG and TNF-R2 agonist programs, Nektar's pipeline provides target rationale for both lymphoid and non-limphoid T-Rag, and this is why we are so excited about Nektar O-1s X-5.

Speaker Change: To initiate first in human studies in the middle of 2025.

Speaker Change: Examples of indications that could be addressed include multiple sclerosis <unk>.

Mr. Lim: Mr. Lim analogy conditions, such as ulcerative colitis in Gi or other oral bicoastal disease, lupus and even dermal autoimmune diseases like vitiligo.

Speaker Change: We note the growing interest for our novel selective TNF are two agonist like Metro 165 and <unk>.

Jonathan Zalevsky: 5, and as we move forward with our IND-enabling studies, we will continue to be open to the opportunity of working with companies that have an interest in these areas to strategize the best path forward. And with that, I'll hand the call over to Mary to discuss Nektar 255. Mary.

Speaker Change: We move forward with our IND, enabling studies, we will continue to be open to the opportunity of working with companies that have interest in these areas to strategize and the best path forward.

Jay Z: As Howard mentioned, we presented the first pre-clinical data for this program at U-R in June of this year. In the presentation, we demonstrated several novel and innovative properties of the antibodies that we discovered and are developing. Firstly, the TNF-R2 agonist we discovered came from AI-based de novo design, and consequently, they provide novel TNF-R2 binding and cell signaling properties. One example of that novelty is a demonstration that these antibodies are able to signal through the TNF-R2 multimeric receptor as single-arm monovalent antibodies.

Speaker Change: And with that I'll hand, the call over to Mary to discuss <unk> 255.

Speaker Change: <unk>.

Mary Tagliaferri: Thank you, Jay-Z. And finally, turning to our IL-15-based oncology program, Nektar 255. We believe the IL-15-based mechanism of action has promising potential in combination, particularly with cell therapy. However, while autologous CAR T-cell therapy transformed the management of patients with large B-cell lymphoma after the first cellular therapies were approved, clinical responses were not durable, and roughly 60% of patients receiving CAR T-cell therapy for large B-cell lymphoma eventually progressed. In 2017, the NCI and KITE, and months later, the Fred Hutch Group published data showing that high serum IL-15 levels were associated with a higher C-max and AUC of CAR T cells, both factors correlated with responses in lymphoma.

Mary Tagliaferri: Thank you J P and finally, turning to our IL 15 based oncology program <unk> 295.

Mary Tagliaferri: We believe the IL 15 based mechanism of action has promising potential in combination, particularly with cell therapy.

Speaker Change: Well ill call a gift car T cell therapy transform the management of patients with large b cell lymphoma. After the first cellular therapies were approved clinical responses were not durable and roughly 60% of patients receiving car T cell therapy for large b cell lymphoma eventually progressed.

Jay Z: This is a very novel effect for TNF-R2 agonistic antibodies. We grafted these into a regular bivalent antibody format and Nektar O-1s X-5 and demonstrated the very high specificity of this antibody for binding and signaling through TNF-R2 on T-Rags, with little to no binding and signaling in conventional T-cells and K-cells or monovalent. Nektar O-1-6-5 also drove T-Rags proliferation of regulation of FOX-B3 and other activation markers in primary human T-Rags. And importantly, Nektar O-1-6-5 drove these effects as a single agent without need for CD-3 ligation, co-stimulation, cytokine, or mitogen support.

Mary Tagliaferri: In 2017.

Speaker Change: I N type and months later, the Fred Hutch group published data showing that high serum IL 15 levels were associated with a higher C. Max and AUC of car T cells, both factors correlated with responses in lymphoma.

Mary Tagliaferri: Thus, our initial development strategy aimed to improve the long-term efficacy of CAR T-cell products with the administration of exogenous IL-15, given the wealth of data about this cytokine's importance. Dr. Cameron Turtle from Fred Hutch completed preclinical experiments showing that Nektar 255 enhanced the in vivo persistence and anti-tumor efficacy of CD19-directed CAR T-cells in As predicted, mice treated with the CAR T cell Nektar 255 combination maintain significantly higher CAR T cell peak levels and continue tumor suppression, translating into durable efficacy. Following Dr.

Speaker Change: Thus our initial development strategy aimed to improve the long term efficacy of car T cell products with the administration of exogenous IL 15, given the wealth of data about this cytokines important.

Speaker Change: Dr. Cameron turtle from Fred Hutch completed preclinical experiments showing that <unk> hundred five enhance the in vivo persistence and anti tumor efficacy of CD 19, directed car T cells in a dose dependent manner.

Jay Z: We also studied Nektar O-1-6-5 in a human TNF-R2 knock-in mouse and used that model to confirm the T-Rags selective PKP-D profile of the antibody and also demonstrated single agent efficacy in a mouse model of KLH-DTH established in the same TNF-R2 knock-in mouse string.

Speaker Change: As predicted mice treated with the car T cell <unk> five combination maintained significantly higher car T cell peak levels and continued tumor suppression translating into durable efficacy.

Jay Z: We're very excited with the unique and differentiated profile of the antibodies that were discovered and we are rapidly advancing Nektar O-1-6-5 into the clinic.

Mary Tagliaferri: After reading Turtle's published results in Blood Advances, we all shared a strong conviction that Nektar 255 could lead to re-expansion of CAR T-cells when dosed in patients to enhance efficacy. Fred Hutch began an IST to evaluate Nektar 255 as an adjuvant treatment to CAR T-cells to improve the complete response rate in patients with large B-cell lymphoma. Drs

Speaker Change: Following Dr Turtles published results in blood advances, we all shared a strong conviction that an extra 255 could lead to re expansion of car T cells when dosing patients to enhance efficacy.

Jay Z: We expect to initiate first in human studies in the middle of 2025. Examples of indications that could be addressed include multiple sclerosis, ucocell immunology conditions such as ulcerative colitis and GI or other and Coastal Diseases, Lupus, and even dermal autoimmune diseases like Vidal Aga. We note the growing interest for a novel and selective TNFR-2 agonist-like Nektar-165, and as we move forward with our IND enabling studies, we will continue to be open to the opportunity of working with companies that have interest in these areas to strategize in the best path forward.

Speaker Change: Fred Hutch began an ISP to evaluate <unk> hundred five as an adjuvant treatment to car T cells to improve the complete response rate in patients with large b cell lymphoma.

Mary Tagliaferri: Crystal McCall and Lori Muffley also evaluated Nektar 255 to enhance the efficacy of Stanford's proprietary CD1922 CAR T-cell for B-cell acute lymphoblastic leukemia. Their data was published in Blood Last Month, compared to a control group previously treated with the CAR T-cell therapy. Nektar 255, when added to the CD1922 CAR T-cell therapy, increased the 12-month relapse-free survival from 38% to 67%. The median RFS for the CAR T-cell only cohort was 3.9 months. And for the cohort treated with Nektar 255 and the proprietary CAR T-cell therapy, it has not been reached with over 14.4 months of follow-up. So why does Nektar 255 work?

Speaker Change: Factors Crystal Mccall and Lori Luckily also evaluated <unk> hundred five to enhance the efficacy of Stanford proprietary CD 1922 car T cell for B cell acute lymphoblastic leukemia.

Mary Tagliaferri: And with that, I'll hand the call over to Mary to discuss Nektar-255. Mary? Thank you, Jay-Z. And finally, turning to our IL-15 based oncology program, Nektar-255. We believe the IL-15 based mechanism of action has promising potential in combination, particularly with cell therapies. While opologous CAR-T cell therapy transformed the management of patients with large B cell lymphoma after the first cellular therapies were approved, clinical responses were not durable and roughly 60% of patients receiving CAR-T cell therapy for large B cell lymphoma eventually progressed.

Speaker Change: Dan first data was published in blood last month.

Speaker Change: <unk> to Stanford control group.

Speaker Change: We treated with the car T cell therapy.

Speaker Change: <unk> five when added to the CD 1922 car T cell therapy increased the 12 months relapse free survival from 38% to 67%.

Speaker Change: The median RF act for the car T cell only cohort with $3 nine months and for the cohort treated with <unk> five and the proprietary car T cell therapy. It has not been reached with over 14 four months of follow up.

Speaker Change: So why does <unk> five work.

Mary Tagliaferri: In 2017, the NCI Enkite, and months later, the Fredhudge group, published data showing that high serum IL-15 levels were associated with a higher CMax and AUC of CAR-T cells, both factors correlated with responses in lymphoma. Thus, our initial development strategy aimed to improve the long-term efficacy of CAR-T cell products with the administration of exogenous IL-15 given the wealth of data about this cytokines importance. Dr. Cameron Turtle from Fredhudge completed preclinical experiments showing that Nektar-255 enhanced the in vivo persistence and anti-tumor efficacy of CD-19 directed CAR-T cells in a dose-dependent manner.

Mary Tagliaferri: We've now confirmed in patients the re-expansion of CAR T cells following Nektar 255 that we saw pre-clinical. In the Stanford study, we observed re-expansion of CAR T cells in the CNS following Nektar 255 administration. At Fred Hutch, where they're combining Nektar 255 with Brionzi in patients with large B-cell lymphoma, we have confirmed re-expansion of the CAR T-cells after Nektar 255 as well, leading to a second peak and increase in AUC. Additionally, an additional observation from Stanford suggests that Nektar 255 also influences lymphocyte trafficking to diseased tissue.

Speaker Change: We've now confirmed in patients three expansion of car T cells. Following <unk> five that we saw pre clinically.

Speaker Change: And the Stanford study, we observed re expansion of the car T cells in the CNS following <unk> five administration.

Speaker Change: As Fred Hutch, where they are combining <unk> with <unk> in patients with large b cell lymphoma.

Speaker Change: Confirmed re expansion of the car T cells after an extra <unk> five as well leading to a second peak and increase in AUC.

Mary Tagliaferri: As predicted, mice treated with the CAR-T cell Nektar-255 combination maintained significantly higher CAR-T cell peak levels and continued tumor suppression, translating into durable efficacy. Following Dr. Turtle's published results in blood advances, we all shared a strong conviction that Nektar-255 could be to re-expansion of CAR-T cells when doses in patients to enhance efficacy. Fredhudge began an IST to evaluate Nektar-255 as an adjuvant treatment to CAR-T cells to improve the complete response rate in patients with large B cell lymphoma.

Speaker Change: And additional observation from Stanford suggests that <unk> <unk> five also influences lymphocyte trafficking into disease tissue.

Mary Tagliaferri: As you know, we've been running our own trial where we've enrolled 15 patients with large B-cell lymphoma. In this study, Nektar 255 is administered after autologous CD19 CAR T cell therapy. We are concluding treatment for the patients randomized in our study, and we have now observed, in a third trial, the same re-expansion phenomenon of CAR T-cells following Nektar 255 treatment in these patients. And We look forward to presenting the full data set from this study at a future medical meeting.

Speaker Change: As you know we've been running our own trial, where we've enrolled 15 patients with large b cell lymphoma.

Speaker Change: This study <unk> five is administered after autologous CD 19 car T cell therapy.

Speaker Change: We are concluding treatment of the patients randomized in our study.

Speaker Change: And we have now observed in a third trial. The same re expansion phenomenon of car T cells. Following <unk> 55 treatment in these patients and we look forward to presenting the full dataset from this study at a future medical meeting.

Mary Tagliaferri: This compounding effect has the potential to extend beyond CAR T cell therapy. We continue to collaborate with AbleZeta, a leading cell therapy company, to evaluate Nektar 255 in combination with their tumor infiltrating lymphocytes, or TILs, in an ongoing Phase I clinical trial in patients with advanced non-small cell lung cancer who do not respond to anti-PD-1 therapy.

Speaker Change: This compounding effect has the potential to extend beyond car T cell therapies, we continue to collaborate with April's EDA, a leading cell therapy company to evaluate <unk> five in combination with their tumor infiltrating lymphocytes or til in an ongoing phase one clinical trial in patients with advanced non.

Mary Tagliaferri: Dr. Crystal McCall and Lori Muffley also evaluated Nektar-255 to enhance the efficacy of Stanford's proprietary CD-1922 CAR-T cell for B cell acute lymphoblastic leukemia. Stanford's data was published in blood last month. Compared to Stanford's control group, previously treated with the CAR-T cell therapy, Nektar-255 when added to the CD-1922 CAR-T cell therapy increased the 12 month relapsed free survival from 38% to 67%. The median RFS for the CAR-T cell only cohort was 3.9 months, and for the cohort treated with Nektar-255 and the proprietary CAR-T cell therapy, it has not been reached with over 14.4 months of follow-up.

Speaker Change: Small cell lung cancer.

Speaker Change: Not respond to anti PD one therapy.

Mary Tagliaferri: Lastly, we are continuing to work with Merck KGA, who is conducting the Phase II Javelin Bladder Medley Study, which is evaluating Nektar 255 in combination with Provencia. Merck is projecting the first potential PFS analysis from this study around the end of this year. As a reminder, there are three separate combinations being evaluated in this study, each being compared separately to the Bovencio Monotherapy Arm. And with that, I will turn the call over to Sandra for a review of our financial guidance. Sandra. Thank you, Mary, and good afternoon, everyone. We ended the second quarter with $290.6 million in cash and investments, with no debt on our balance sheet.

Speaker Change: Lastly, we are continuing to work with Merck Kgs, who is conducting the phase III javelin bladder medley study, which is evaluating <unk> five in combination with <unk>.

Speaker Change: Merck is projecting the first potential PFS analysis from this study around the ended this year.

Speaker Change: As a reminder, there are three separate combinations being evaluated in this study each being compared separately to the both NCR monotherapy arm.

Speaker Change: And with that I will turn the call over to Sandra for a review of our financial guidance Sandra.

Sandra Gardiner: Our financial position remains strong, and we still plan to end 2024 with $200 million to $225 million in cash and investments. Our CACHE runway extends into the third quarter of 2026, which will take us through several key data milestones, including top-line data for both our Phase IIb ResPeg studies. I'll now briefly review our quarterly financials and reiterate our financial guidance for 2024. Our revenue was $23.5 million for the second quarter of 2024.

Sandra Gardner: Thank you Mary and good afternoon, everyone. We ended the second quarter with $296 million in cash and investments with no debt on our balance sheet.

Mary Tagliaferri: So, why does Nektar 255 work? We've now confirmed in patients the re-expansion of CAR-T cells following Nektar 255 that we saw pre-clinically. In the Stanford study, we observed re-expansion of the CAR-T cells in the CNS following Nektar 255 administration. At Fred Hutch, where they're combining Nektar 255 with Breonzi and patients with large B cell lymphoma, we have confirmed re-expansion of CAR-T cells after Nektar 255 as well, leading to a second peak in increase in AUC.

Sandra Gardner: Our financial position remains strong and we still plan to end 2024, with 200 million to $225 million in cash and investments.

Speaker Change: Our cash runway extends into the third quarter of 2020, and she'll take us through several key data milestones, including top line data for both our phase <unk> study.

Sandra Gardiner: We still expect our revenue for the full year 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. For the second half of the year, we expect the remaining revenue to be weighted more heavily toward the fourth quarter. R&D expense for the second quarter of 2024 was $29.7 million, and we still anticipate full-year R&D expense to range between $120 million and $130 million. G&A expense for the second quarter of 2024 was $20.5 million. We continue to expect G&A expenses for the full year to be between $70 and $75 million.

Speaker Change: I'll now briefly review, our quarterly financials and reiterate our financial guidance for 2024.

Mary Tagliaferri: An additional observation from Stanford suggests that Nektar 255 also influences lymphocyte trafficking to disease tissues. As you know, we've been running our own trials where we've enrolled 15 patients with large B cell lymphoma. In this study, Nektar 255 is administered after autologous CD-19 CAR-T cell therapies. We are concluding treatment of the patients randomized in our study, and we have now observed in a third trial the same re-expansion phenomenon of CAR-T cells following Nektar 255 treatment in these patients, and we look forward to presenting the full data set from this study at a future medical meeting.

Sandra Gardiner: Lastly, our 2024 non-cash interest expense remains unchanged and is expected to be between $20 million and $25 million. In Q2, we recorded $13.3 million in non-cash impairment charges for our real estate obligations due to the continuous decline of the San Francisco life sciences and office real estate market. Our net loss for the second quarter of 2024 was $52.4 million, or $0.25 basic and diluted loss per share. Excluding the $13.3 million in non-cash impairment charges, our net loss on a non-GAAP basis was $39.1 million, or $0.19 basic and diluted loss per share.

Speaker Change: Our revenue was $23 5 million for the second quarter of 2024.

Sandra Gardner: So expect our revenue for the full year to be between $75 million and $85 million, which includes $55 million to $65 million and noncash royalties and 29% to $25 million in product sales.

Sandra Gardner: For the second half of the year, we expect the remaining revenue to be weighted more heavily towards the fourth quarter.

Sandra Gardner: R&D expense for the second of 2024 was $29 7 million and we still anticipate full year R&D expense to range between $120 million and $130 million.

Mary Tagliaferri: This compounding effect has the potential to extend beyond CAR-T cell therapies. We continue to collaborate with Abel Zeta, a leading cell therapy company, to evaluate Nektar 255 in combination with their tumor infiltrating lymphocytes or chills, and an ongoing Phase I clinical trial in patients with advanced non-small cell lung cancer, who do not respond to anti-PD1 therapy. Lastly, we are continuing to work with Merck KGA, who is conducting the Phase II javelin bladder medley study, which is evaluating Nektar 255 in combination with the VenCO.

Sandra Gardner: G&A expense for the second quarter of 2024 with $25 million. We continue to expect G&A expense for the full year to be between 70 and $75 million.

Speaker Change: Lastly, our 2020 for noncash interest expense remains unchanged and is expected to be between 20 million and $25 million.

Sandra Gardner: In Q2, we recorded $13 3 million in noncash impairment charges for our real estate obligations due to the continuous decline of the San Francisco Lifesciences and office real estate market.

Mary Tagliaferri: Merck is projecting the first potential PFF analysis from this study around the end of this year. As a reminder, there are three separate combinations being evaluated in this study, each being compared separately to the VenCO monotherapy arm.

Sandra Gardner: Our net loss for the second quarter of 2024, it was $52 4 million or 25 basic and diluted loss per share excluding the $13 3 million in noncash impairment charges net loss on a non-GAAP basis was $39 1 million or 19.

Sandra Gardiner: And with that, I will turn the call over to Sandra for a review of our financial guidance.

Sandra Gardiner: Sandra, thank you, Mary, and good afternoon everyone. We ended the second quarter with $290.6 million in cash and investments with no debt on our balance sheet. Our financial position remains strong, and we still plan to end 2024 with $200 million to $225 million in cash and investments. Our cash run rate extends into the third quarter of 2026, which will take us through several key data milestones, including top line data for both our Phase II B ResPEG study.

Sandra Gardner: Basic and diluted loss per share.

Sandra Gardiner: And as I mentioned earlier, we still plan to end 2024 with $200 million to $225 million in cash and a runway that extends into the third quarter of 2026. And with that, I'll now open the call to questions. Crystal?

Sandra Gardner: And as I mentioned earlier, we still plan to end 2024 with $200 million to $225 million in cash and a runway that extends into the third quarter of 2026.

Crystal: And with that I'll now open the call for questions Crystal.

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.

Crystal: Thank you.

Crystal: A reminder to ask a question. Please press star one on your telephone and wait for your name to be announced to withdraw your question. Please press star one again.

Operator: In the interest of time, we do ask that you please limit yourselves 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 Oppenheimer. Your line is open.

Speaker Change: In the interest of time, we do ask that you. Please limit yourself to one question at this time please.

Sandra Gardiner: All now briefly review our quarterly financials and reiterate our financial guidance for 2024. Our revenue was $23.5 million for the second quarter of 2024. We still expect our revenue for the full year 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. For the second half of the year, we expect the remaining revenue to be weighted more heavily towards the fourth quarter.

Crystal: Please standby, while we compile the Q&A roster.

Crystal: And our first question will come from Jay Olson from Oppenheimer. Your line is open.

Jay Olson: Oh, hey, congratulations on all the progress and thank you for taking our question. That Nektar 255 data in collaboration with Stanford looks great. Can you talk about the next steps and if there's potential synergy for Nektar 255 with CAR-T for autoimmune diseases? Thank you. Jay-Z, do you want to take that call, that question?

Jay Olson: Oh, Hey, congrats on all the progress and thank you for taking our question.

Jay Olson: That Nektar 255 data in collaboration with Stanford looks great can you talk about the next steps and if theres potential synergy for Nektar to five five with car T for autoimmune diseases. Thank you.

Jay Olson: Jason you want to take that call.

Sandra Gardiner: R&D expense for the second quarter of 2024 was 29.7 million and we still anticipate full year R&D expense to range between 120 million and 130 million. DNA expense for the second quarter of 2024 was 20.5 million. We continue to expect DNA expense for the full year to be between 70 and 75 million. Lastly, our 2024 non-cash interest expense remains unchanged and is expected to be between 20 million and 25 million.

Jason: A question.

Jonathan Zalevsky: Sure, yeah, thanks Jay for the question. So I'll start off, and maybe Mary can add a little bit of color to that, but I think that that study with Stanford was a very important study for us because it was the first time that treatment was evaluated. Very close to the time of the administration of the car, right?

Jason: Sure, yes, so thanks.

Mary Tagliaferri: Thanks, Jay for the question, so I'll start off and maybe Mary you can add also a little bit of color on to that but I think that study was effort was a very important study for us because.

Mary Tagliaferri: It was the first time that the treatment was evaluated very close to the time of the administration of the car that was just the short offset of a couple of weeks. After the car was delivered before.

Jonathan Zalevsky: There was just a short offset of a couple of weeks after the car was delivered before. We, really large amount of carbon, really impacting positively. patient. And then, of course, the duration of effect, as Mary described, in terms of the really extent of efficacy that was observed relative to what's known historically for that car, where the durability of the effect. Mary, maybe you could talk medically about adding some more of the context and how it fits together with the other studies that are ongoing. Yeah, hi Jay. This is Mary.

Jason: $2 five was treated and we observed some very exciting findings were published by the Stanford group.

Sandra Gardiner: In Q2, we recorded $13.3 million in non-cash impairment charges for our real estate obligations due to the continuous decline of the San Francisco life sciences and office real estate markets. Our net loss for the second quarter of 2024 was 52.4 million or 25 cents basic and diluted loss per share excluding the 13.3 million in non-cash impairment charges net loss on a non-gap basis was 39.1 million or 19 cents basic and diluted loss per share. And as I mentioned earlier, we still plan to end 2024 with 200 million to 225 million in cash and a runway that extends into the third quarter of 2026.

Crystal: Those included changes in the cellular <unk> changes in the migration, including into one patient that had in CNS disease.

Mary Tagliaferri: A really large amount of car moving into the CNS really impacting positively the patient and then of course the duration of effect as Mary described in terms of the extent of that.

Mary Tagliaferri: You can see that was observed relative to what's known historically for that car where durability of the effect wanes.

Speaker Change: Maybe if you could talk medically about adding some more of the context and how it fits together with the other studies that are ongoing.

Mary Tagliaferri: You know, what we were really excited about is that in three different studies now, we wanted to look at the safety, the feasibility, and the efficacy so we could hone in on the recommended phase three dose. And across all three studies, we have not seen a dose-limiting toxicity. We see a consistent safety profile that's highly favorable to patients.

Crystal: Yes, Hi, Jay this is Mary.

Speaker Change: We were really excited about is in three different studies now we wanted to look at the safety the feasibility and the efficacy. So we could hone in on the recommended phase II dose and across all three studies, we have not seen a dose limiting toxicity, we see consistent safety profile.

Unknown Executive: And with that, I'll now open the call for questions. Crystal, thank you. As a reminder to ask a question, please press star one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. In the interest of time, we do ask that you please limit yourselves to one question at this time. Please stand by when we compile the Q&A roster.

Crystal: Hi, highly favorable to patients.

Crystal: As you can imagine that's remarkable when you're combining the drug with car T cell treatment.

Mary Tagliaferri: And as you can imagine, that's remarkable when you're combining a drug with CAR T cell treatments. It's also feasible to dose this drug in the adjuvant setting right after patients receive CAR T cells, but they continue to receive Nektar 255 every three weeks, which is also highly favorable to patients. And when we think about next steps and where we can go, I believe with the combination and aggregate of the data from the three trials, we have identified our recommended phase three dose.

Crystal: It's also feasible to not only dose this drug in the adjuvant setting right after.

Crystal: Patients receive car T cells, but they continue to receive <unk> <unk> five.

Jay Olson: And our first question will come from Jay Olson from Oppenheimer. Your line is open. Oh, hey, congrats on all the progress. And thank you for taking our question. That Nectar 255 data in collaboration with Stanford looks great. Can you talk about the next steps? And if there's potential synergy for Nectar 255 with CAR-T for autoimmune diseases? Thank you. Jay, do you want to take that call? That question. Sure. Yeah. So thanks Jay for the question.

Crystal: Every three weeks, which is also highly favorable to patients and when we think about next steps and where we can go I believe with the combination in aggregate the data from the three trials, we have identified a recommended phase III dose.

Mary Tagliaferri: The other thing that—the other place where we're developing the drug, as I mentioned, is in combination with TIL therapy. And as you know, right now, Iovance combines their TIL therapy with high-dose IL-2, and that's really fraught with error because there are—it's very difficult to tolerate high-dose IL-2. Patients have to be in the inpatient setting to receive high-dose IL-2, and certainly, in the area of non-small cell lung cancer, patients who actually receive TILs and high-dose IL-2 in a very small study of roughly 50 patients, you know, there were two deaths in that trial conducted by Dr. Scott Antonia and published in Nature.

Crystal: The other thing that.

Crystal: The other place where we're.

Crystal: Developing the drug as I mentioned is in combination with til therapy, and as you know right now Io Vance combines their til therapy with high dose IL, two and Thats really fraught with error because there are it's very difficult to tolerate high decile two patients have to be.

Jay Olson: So I'll start off and maybe Mary, you can add also a little bit of color onto that. But I think that that study was Stanford was a very important study, Jay, for us, because it was the first time that treatment was evaluated very close to the time of administration of the car. There was just a short offset of a couple of weeks after the car was delivered before Nectar 255 was treated.

Crystal: In the inpatient setting to receive high dose IL, two and certainly in the area of non small cell lung cancer patient to actually receive tills and high dose IL two in a very small study.

Jay Olson: And we observed some very exciting findings that were published by the Stanford group. Those included changes in the cellularity, changes in the migration, including into one patient that had a CNS disease with a really large amount of car moving into the CNS, really impacting positive, and then of course the duration of effect has Mary described in terms of the really extent of efficacy that was observed relative to what's known historically for that car, where durability of the effect went.

Speaker Change: Patients there were two deaths in that trial conducted by Dr. Scott Antonia and published in nature, and so I think that the opportunities here are very broad in the area of cellular therapy both.

Mary Tagliaferri: And so I think that the opportunities here are very broad in the area of cellular therapy, both with autologous and allogeneic cells and CAR-T cells as well as TILs. And then again, we're awaiting the data in combination with a checkpoint inhibitor, and, you know, if the data prove to be compelling and strong, there's, you know, an additional indication for combining with checkpoint inhibitors. And I would add to that that, of course, we've shifted over to immune disease and inflammation.

Speaker Change: Tal I guess, an allogeneic and car T cells as well as tills and then again, we're awaiting the data in combination with a checkpoint inhibitor and <unk>.

Crystal: Data prove to be.

Crystal: Compelling and strong there is an additional indication for combining with checkpoint inhibitors.

Jay Olson: Mary, maybe if you could talk medically about adding some more of the context and how it fits together with the other studies that are ongoing. Yeah, hi Jay, this is Mary, you know what we were really excited about is in three different studies now we wanted to look at the safety, the feasibility and the efficacy so we could hone in on the recommended phase three dose and across all three studies we have not seen a dose limiting toxicity.

Crystal: And I would I would add to that that of course, we've shifted over to.

Howard Robin: But clearly, we have data with IL-15 that demonstrates its potential, how there's a great potential for it to be used in combination with cell therapies. And I think that's going to, that may very well play an important role in the future of cell therapy. So we're talking to a number of companies, and I do think we can find an important collaboration. Super helpful, thank you so much. And Jay, this is Jay Z.

Crystal: Immune disease and inflammation.

Crystal: But clearly we have data with IL 15 that demonstrates.

Crystal: How its potential.

Crystal: A great potential for it to be used in combination with cell therapies, and I think thats going to that may very well play an important role on the future of cell therapy. So we're talking to a number of companies and I do I do think we can find a important collaborations.

Jay Olson: We see a consistent safety profile that's highly favorable to patients and as you can imagine that's remarkable when you're combining a drug with CAR T cell treatments. It's also feasible to not only dose this drug in the adjuvant setting right after patients receive CAR T cells but they continue to receive Nektar 255 every three weeks which is also highly favorable to patients. And when we think about next steps and where we can go I believe with the combination and aggregate of the data from the three trials we have identified our recommended phase three dose.

Speaker Change: Super helpful. Thank you so much.

Jonathan Zalevsky: Your other question about autoimmune disease is a really good question. It's a kind of theoretical question at this time, but based on what we saw in the data and published at Stanford, as Mary described, which from a totality of both safety as well as pharmacodynamic effects would make it feasible to also add this in the setting of autoimmune disease, you know, car cell therapy use. We're focused on oncology now, but theoretically, from first principles, it should be possible. Okay, great.

Speaker Change: And Jay This is Jason your other question about autoimmune disease.

Jason: It's a really good question.

Speaker Change: Kind of a theoretical question at this time, but based on what we saw in the data published at Stanford as Mary described which from a totality of both safety as well as Pharmacodynamic effects.

Jason: Would make it feasible to also add this in the setting of autoimmune disease cart.

Crystal: Our cell therapy use.

Speaker Change: <unk> focus on oncology now, but theoretically first principles that should be possible.

Jay Olson: Really impressive data. Thank you. Thank you. Our next question will come from Chris Shibutani from Goldman Sachs. Your line is open. Hi, this is Kevin on behalf of Chris.

Jay Olson: The other thing you know that the other place where we're developing the drug as I mentioned is in combination with TIL therapy. And as you know right now I events combines their TIL therapy with hydrocile two and that's really you know fought with error because there are it's very difficult to tolerate hydrocile two patients have to be in the inpatient setting to receive hydrocile two. And certainly in the area of non-small cell lung cancer patients who actually received TILs and hydrocile two in a very small study of rough patients you know they were two deaths in that trial conducted by Dr. Scott and Tonya and published in Nature.

Speaker Change: Okay, great really impressive data thank you Jim.

Speaker Change: Yeah.

Speaker Change: Thank you.

Crystal: Our next question will come from Chris <unk> from Goldman Sachs. Your line is open.

Crystal: Hi, This is Kevin on for Chris Thanks for taking my question and congrats on the progress.

Chris Shibutani: Thanks for taking the time to answer my question. The primary completion is the same on clinicaltrials.gov, but I was wondering about the timeline to mid-25 versus first half. And then also, you know, understanding the value proposition there versus JAK inhibitors which are approved, it makes sense with the safety profile. How are you talking about efficacy? Are you going to want or need to match the efficacy of JAK inhibitors now? Why don

Speaker Change: Just wanted to focus on alopecia.

Speaker Change: They're so just for housekeeping I know that.

Speaker Change: Enrollment is on track and there is.

Crystal: The primary completion is the same on clinical trials Gov, but just wondering about the timeline to mid 25 versus first half and then also.

Crystal: Understanding the value proposition there versus JAK inhibitors, which are approved.

Jay Olson: And so I think that the opportunities here are very broad in the area of cellular therapy both autologous and allogeneic and CAR T cells as well as TILs. And then again you know we're awaiting the data and combination with the checkpoint inhibitor and you know it's the data proved to be compelling and strong there's you know an additional indication for combining with checkpoint inhibitors. And I would I would add to that that of course we've shifted over to the immune disease and inflammation but clearly we have data with aisle 15 that demonstrates how how it's potential.

Speaker Change: It makes sense with the safety profile. How are you talking about efficacy are you are you going to want or need to match the efficacy of JAK inhibitors in alopecia. Thanks.

Speaker Change: And then I'll, let Mary answer your question on that.

Mary Tagliaferri: Yep, thank you, Howard. And Kevin, yes, you know, we started the alopecia areata study in March. And, you know, we are on track, and we will have top-line data based on our enrollment today in mid 2025. And I think, you asked a great question about what success looks like in alopecia areata and what our bar for us is. And, you know, as you know, JAK inhibitors are effective.

Mary Tagliaferri: Yes, Thank you Howard and Kevin Yes, we started the alopecia area to study in March and we are on track and we do we will have top line data based on our enrollment today.

Speaker Change: 2025.

Speaker Change: You asked a great question.

Speaker Change: What does success look like in alopecia, Areata and what's the bar.

Speaker Change: For us and as you know JAK inhibitors are efficacious for alopecia, Areata and <unk> clinical trials that were conducted had asphalt.

Jay Olson: So have is a great potential for it to be used in combination with with cell therapies and I think that's going to that may very well play an important role on the future of cell therapy so we're talking to a number of companies and I do I do think we can find a important collaboration there.

Mary Tagliaferri: For alopecia areata, and, you know, the clinical trials that were conducted had a salt end point at 36 weeks of treatment. And before I go into the efficacy data, you know, there are two main issues that dermatologists share with us. One is, you know, there's absolutely no durability of effect with a JAK inhibitor, and patients immediately start to lose their hair when they stop taking the JAK inhibitor. And that hair loss is very rapid.

Speaker Change: And point at 36 weeks of treatment.

Speaker Change: Before I go into the efficacy data.

Speaker Change: Two main issues that the dermatologist share with US one is there's absolutely no durability of effect with a JAK inhibitor in patients immediately start to lose their hair when they stop taking the JAK inhibitor and that her losses very rapid.

Jay Z: Super helpful thank you so much. Jay this is a year other question about autoimmune disease it's a it's a really good question it's a kind of a theoretical question at this time but based on what we saw in the data and were published as I'd stand for Mary described which from a totality of both safety as well as pharmacodynamic effects. Would make it feasible to also add this in the setting of autoimmune disease cars you know car cell therapy use we're focused on oncology now but theoretically first principles it should be possible. Okay, great, really impressive data. Thank you, Vivian. Thank you.

Mary Tagliaferri: The second, of course, is that 80% of patients who have alopecia areata are younger than age 40. And nobody really knows what kind of risks, you know, a JAK inhibitor would pose. Obviously, you know, the black box warnings are for serious heart-related events like heart attacks and stroke and blood clots and thrombosis and cancer and serious infections. So there is just the general worry about exposing a patient to a JAK inhibitor for their entire life. So in terms of terms—so those are the problem statements.

Speaker Change: Second of course is that 80% of patients who have alopecia area other younger than age 40, and nobody really knows what kind of risks a JAK inhibitor. We pose obviously you know the black box warning, therefore serious heart related events like heart attacks and stroke and blood clots in from both.

Speaker Change: As in cancer and serious infection. So there is just the general worry about exposing a patient to a JAK inhibitor for their entire life. So and in terms. So those are the problem statements and in terms of efficacy, we believe similar efficacy to say parasitic nib.

Chris Shibutani: Our next question will come from Chris Shibutani from Goldman Sachs. Your line is open. Hi, this is Kevin on for Chris. Thanks for taking our question and congrats on the progress. Just wanted to focus on alopecia there. Just for housekeeping, I know that you know enrollment is on track, and there's the primary completion is the same on ClinicalTrials.gov, but I'm just wondering about the timeline to mid 25 versus first half. And then also, you know, understanding the value proposition there versus Jack inhibitors, which are approved, it makes sense with the safety profile.

Mary Tagliaferri: And in terms of efficacy, we believe similar efficacy to, say, paracetamol would establish a differentiated compound because, one, we're not—we don't have an association, you know, certainly with our 600 patients we've treated to date with these serious side effects. And number two, we believe based on the phase 1B in atopic dermatitis that there's a potential for a remittive effect or a maintenance regimen that, you know, wouldn't be daily like you see with a JAK inhibitor, but rather we could potentially dose patients after a 36-week induction period with a frequency that's longer than every two weeks in the maintenance phase.

Speaker Change: Would establish a differentiated compound because one we're not we don't have an association certainly with our 600 patients we've treated to date with the serious side effects and number two.

Speaker Change: Belief based on the phase, one b and atopic dermatitis that theres, a potential for primitive effect or a maintenance regimen.

Speaker Change: That wouldn't be daily like you see with a JAK inhibitor, but rather we could potentially dose patients. After 36 week induction period with a frequency that's longer than every two weeks in the maintenance phase.

Chris Shibutani: How are you talking about efficacy? Are you going to want or need to match the efficacy of Jack inhibitors in alopecia? Thanks. When I let Mary answer your question on that. Yep. Thank you, Howard. And Kevin, yes, you know, we started the alopecia area to study in March. And, you know, we are on track and we do, we will have top line data based on our enrollment today in mid 2025. And I think, you know, you have a great question, you know, which is what the success looks like in alopecia area, then what's the bar.

Mary Tagliaferri: You know, we've spoken a lot to doctors about even an induction time period, and, you know, their belief is, it doesn't even matter if it takes these patients a year to grow their hair back if you actually have a biologic that would provide a remittive benefit and not be associated with so many side effects. That would be critically important. And then specifically for the phase 3 trials with baricitinib, you know, the salt change at 36 weeks was less than 10% for placebo, which is nice.

Speaker Change: We've spoken a lot to doctors about even an induction time period in their belief is it doesn't even matter. If it takes these patients a year to grow their hair back. If you actually have a biologic that they would that would provide a remitted to benefit and not be associated with so many side effects that would be critic.

Speaker Change: <unk> important and then specifically for the phase III trials that they're sitting at.

Speaker Change: The salt change at 36 weeks.

Chris Shibutani: For us, and, you know, as you know, Jack inhibitors are efficacious for alopecia area, and the clinical trials that were conducted had a salt endpoint at 36 weeks of treatment. And before I go into the efficacy data, you know, there are two main issues that the dermatologist share with us. One is, you know, there's absolutely no durability of a fact with a Jack inhibitor in patients. And immediately start to lose their hair when they stop taking the Jack inhibitor.

Speaker Change: It was less than 10% for placebo, which makes it a nice you can run smaller size studies, because the placebo effect as well as approximately 30% for the low dose of <unk>, two milligram per day dose and about 49%.

Mary Tagliaferri: You can run smaller size studies because the placebo effect is low and is approximately 30% for the low dose of baricitinib, the 2 milligrams per day dose, and about 49% salt reduction for the high dose of 4 milligrams.

Chris Shibutani: And that hair loss is very rapid. The second, of course, is that 80% of patients who have alopecia area are younger than age 40. And nobody really knows what kind of risks, you know, a Jack inhibitor would pose. Obviously, you know, the black box warnings are for serious heart related events like heart attacks and stroke and blood clots and from doses and cancer and serious infections. So there is just the general, you know, worry about exposing a patient to a Jack inhibitor for their entire life. So in terms, so those are the problem statements.

Speaker Change: Salt reduction for the high dose at four milligrams.

Speaker Change: Great. Thank you.

Speaker Change: Thank you.

Roger Song: Great. Thank you. And our next question will come from Roger Song from Jeffries. Your line is open.

Roger Song: And our next question will come from Roger song from Jefferies. Your line is open.

Kambiz Pashneh: Hi, this is Kambiz on behalf of Roger. Can you provide us with an update on your litigation with Lily? Yeah, sure. Look, we're still having discussions with Lily, as you know, and as you can see from the excellent Phase 1B data, clearly a mathematical mistake was made, and the data is somewhat compelling after we corrected for that math error that we discovered.

Speaker Change: Hi, This is <unk> on for Roger can.

Speaker Change: Can you provide us an update on your litigation with Lilly.

Speaker Change: Yes sure.

Speaker Change: Look we're still we're still having discussions with Lilly as you know and as you can see from.

Speaker Change: The excellent phase <unk> data.

Speaker Change: Clearly a mathematical mistake was made.

Speaker Change: And the data is somewhat compelling.

Speaker Change: After we corrected for that matter that we discovered.

Speaker Change: We're still having discussions with Lilly we had a mediation.

Howard Robin: We're still having discussions with Lily. We had mediation. The court has ordered us to continue mediation, and we expect to do that in the near future, so obviously, I can't spend a lot of time talking.

Mary Tagliaferri: And in terms of efficacy, we believe similar efficacy to state bar, sitnab would establish a differentiated compound because one, we're not, we don't have an association, you know, certainly with our 600 patients, we've treated to date with these serious side effects. And number two, we believe based on the phase one, be in a topic dermatitis that there's a potential for a remittive effect or a maintenance regiment that, you know, wouldn't be daily like you see with a Jack inhibitor, but rather we could potentially dose patients after a 36 week induction period with a frequency that's longer than every two weeks in the maintenance phase.

Speaker Change: The court has ordered us to continue mediation and we expect to do that in the near future. So obviously I can't spend a lot of time talked I can't spend I can't discuss in detail on ongoing litigation, but I can I can say that we are.

Howard Robin: I can't discuss in detail an ongoing litigation, but I can say that we firmly believe that we've been harmed by their behavior, and consequently, we will continue mediation. Thank you. And our next question will come from Andy Shea of William Blair. Your line is now open.

Speaker Change: Firmly believes that we've been harmed by their behavior and consequently, we will continue mediation with them.

Speaker Change: Thank you.

Speaker Change: And our next question will come from Andy Shay from William Blair. Your line is now open.

Andy Shea: Hi, thanks for taking our question. So the paper for the book is pretty, pretty intriguing. I'm curious about your interpretation of the historical controls, just, you know, given the non-randomized nature of the study. There's some, you know, kind of push and pulls regarding baseline patient characteristics. It seems like, you know, the historical control might be a little bit more heavily pretreated, and the dosing is a little bit lower. So I'm just curious, just kind of looking at the baseline characteristics, how would you characterize the similarities and differences? How alike are those two populations?

Andy Shay: Alright, thanks for taking our question so the blood papers.

Mary Tagliaferri: You know, we've spoken a lot to doctors about even, you know, an induction time period and, you know, their belief is, you know, it doesn't even matter if it takes these patients a year to grow their hair back if you actually have a biologic that they, you know, that would provide a remittive benefit and not be associated with so many side effects. That would be critically important. And then specifically for the phase three trials with bar, sitnab, you know, the, the salt change at 36 weeks was less than 10% for placebo, which makes it nice.

Speaker Change: Pretty intriguing.

Speaker Change: Yeah.

Speaker Change: I'm curious about your interpretation of that.

Speaker Change: The historical controls.

Speaker Change: Given the.

Speaker Change: Non randomized nature of the study.

Speaker Change: There are some.

Speaker Change: Pushing pause regarding baselines.

Speaker Change: Characteristics it seems like.

Speaker Change: The historical control might be a little bit.

Speaker Change: More heavily pre treated dosing is a little bit lower.

Mary Tagliaferri: You can run smaller size studies because the placebo effect as low is approximately 30% for the low dose of bar, sitnab, the two milligram per day dose and about 49% salt reduction for the high dose of four milligrams. Great. Thank you.

Speaker Change: So I'm just curious just kind of looking at.

Speaker Change: The baseline characteristic how would you characterize the similarities and differences.

Speaker Change: Or are those two populations. Thank you Mary Mary could you. It's a good question Mary could you give some insight into the Stanford historical controls.

Mary Tagliaferri: Thank you. Mary, Mary, could you? It's a good question. Mary, could you give some insight into the Sanford historical controls? Yes. So really important, Andy, so first of all, I just want to talk a little bit about the person who conducted this trial. You know, Crystal McCall is the founding director of the Stanford Center for Cancer Cell Therapy, and she's really, you know, one of the godmothers of cell therapy.

Mary Tagliaferri: And if you look at Crystal's Nature paper, she actually dosed 17 patients, you know, not eight that are used as the control patients for this study. So she actually selected patients that had comparable baseline characteristics traits to be matched with the patients of this second study. So you can imagine, you know, with her academic background and her vast experience with treating ALL patients, she was very, very mindful of these baseline characteristics, as well as the burden of disease. So she very carefully selected the control group, which is a subset of the total number of patients she originally reported upon in Nature. That's helpful, thank you.

Speaker Change: Yes.

Speaker Change: So really importantly, Andy so first of all I just wanted to talk a little bit about the person who conducted this trial crystal Mccall's the founding director of the Stanford Center for cancer cell therapy, and she is really one of the godmothers.

Roger Song: And our next question will come from Roger Song from Jeffries. Your line is open.

Howard Robin: Hi, this is Kambiz on Ferrantiya. Can you provide us an update on your litigation with Lily? Yeah, sure. Look, we're still having discussions with Lily, as you know. And as you can see from the excellent phase 1B data, the clearly a mathematical mistake was made. And the data is somewhat compelling after we corrected for that math error that we discovered. We're still having discussions with Lily. We had a mediation, the court has ordered us to continue mediation and we expect to do that in the near future.

Speaker Change: Cell therapy, and if you look at Crystal nature paper, she actually had dosed 17 patients.

Speaker Change: Not a feather used as the control patients for this study so she actually selected patients that had comparable baseline characteristic trades to be matched with the patients of this second study. So you can imagine.

Speaker Change: With her academic.

Speaker Change: Ground and her vast experience with treating <unk> patients. She was very very mindful of these baseline characteristic traits as well as burden of disease. So she she's very carefully actually selected the control group, which is a subset of the total number of patients. She originally.

Howard Robin: So obviously, I can't spend a lot of time. I can't spend I can't discuss in detail, not going litigation, but I can I can say that we are we firmly believe that we've been harmed by their behavior. And consequently, we will continue mediation with it. Thank you.

Speaker Change: Reported a pod in nature.

Speaker Change: Okay.

Speaker Change: That's helpful. Thank you.

Speaker Change: Thank you.

Operator: Thank you. And as a reminder, to ask a question, please press star 11 and again to ask a question, that's star 11. One moment for our next question, please. Our next question will come from Arthur He from H.C. Wainwright. Your line is open. Hey, good afternoon, Howard team. I just had a quick question on the 165.

Andy Shea: And our next question will come from Andy Shea from William Blair. Your line is now open. Hi, thanks for taking our question. So the book papers are pretty, pretty intriguing. I'm curious about your interpretation of the historical point falls just given the non randomized nature of the study. There's some, you know, kind of push and pause regarding basic patient characteristics. It seems like, you know, the historical control might be a little bit more heavily pre-treated.

Speaker Change: And as a reminder to ask a question. Please press star one one and again to ask a question Thats Star 111 moment for our next question. Please.

Speaker Change: Yeah.

Speaker Change: Our next question will come from Arthur Heat from H C. Wainwright Your line is open.

Arthur Heat: Hey, good afternoon.

Arthur Heat: I just had a quick question on the 165.

Arthur He: Obviously, it's very interesting, pretty clinical data. Maybe, Jay-Z, could you give us more color on the 165, the binding to the T-regs receptor, but not the other ones on the CD4 T cell or monocyte, because we know the TNFR2 is also expressed on those two cells. Just curious about the mechanism of action there.

Arthur Heat: Obviously very interesting preclinical data.

Speaker Change: Okay.

Speaker Change: Maybe Jason could you just give us more color on the.

Speaker Change: 165.

Speaker Change: The binding to the T regs receptive, but not the other ones on the CD four T cell or amongst side, because we know that.

Andy Shea: The dosing is a little bit lower. So I'm just curious, it's kind of looking at the, you know, the baseline characteristics. How would you characterize the similarities and differences to how, how would like are those two populations?

Speaker Change: Two also expressed on those two sales just curious about the mechanism action yet thanks.

Jonathan Zalevsky: Thanks. Sure. Thanks, Arthur.

Jason: Sure. Thanks, Arthur Thanks for the question, yes, so one of the things that we found is that our antibody definitely has.

Mary Tagliaferri: Thank you. Mary, Mary, could you, it's a good question. Mary, could you give some insight into the Stanford historical controls? Yes. So really importantly, Andy, for first of all, I just want to talk a little bit about the person who conducted this trial. You know, Crystal McCall is the founding director of the Stanford Center for Cancer Self Therapy. And she's really, you know, one of the Godmothers of, you know, self therapy.

Jonathan Zalevsky: Thanks for the question. Yeah, so one of the things that we found is that our antibody definitely has some form of conformational selectivity in terms of the epitope that it recognizes. And in that EULAR poster, there was a panel that showed binding to two different forms of TNFR2. So you know that TNF-R2, primarily it's a transmembrane receptor like... to answer questions. And the antibody bound the surface receptor with much, much higher affinity, much more greatly, and it barely interacted with the shed form. So it indicates to us that there's a conformational, you know, specificity or conformational component to the binding.

Speaker Change: Some form of confirmation selectivity in terms of the epitopes that it recognizes and in that Youll are poster. There was a panel that showed binding to two different forms of <unk>.

Speaker Change: So you know the TNF are two primarily its a transmembrane receptor like TNF.

Mary Tagliaferri: And if you look at Crystal nature paper, she actually had those 17 patients, you know, not eight that are used as the control patients in for the study. So she actually selected patients that had comparable baseline characteristic traits to be matched with the patients of this second study. So you can imagine, you know, with her academic background and her vast experience with treating ALL patients, she was very, very mindful of these baseline characteristic traits as well as burden of disease. So she, she very carefully actually selected the control group, which is a subset of the total number of patients she originally reported upon in nature.

Speaker Change: TNF receptor, but it can also be shed.

Speaker Change: Dominion shutting through normal metallic proteases, Adam 17, cleaves TNF or two and then that liberate so shed form that can circulate it but.

Speaker Change: And so we tested the binding of our antibody to the surface receptor into the shed form.

Speaker Change: Antibody bound the surface receptor much much higher affinity much more greatly and it barely interacted with the shed form so it indicates to us that there is a conformational specificity or conformational component to the binding and to to assess that we're actually doing a lot of biophysical studies.

Jonathan Zalevsky: And to assess that, we're actually doing a lot of biophysical studies right now. So, first of all, we're mapping the epitope and the peritope of the antibodies. So those experiments are ongoing, and we're also doing structural modeling using, you know, some of the structural approaches that you can do computationally to assess the epitope, and then we aim to put all that together. We might even possibly go as far as solving the crystal structure of the antibody. But our hypothesis, you know, right now, is that it's very conformational, and that's why we see cellular selectivity because while you're right But yeah, we're very excited because that's not like a typical finding, as you can imagine, for an antibody, which is why we think this is such an innovative idea. Thanks, Jude.

Speaker Change: Right now.

Speaker Change: So first of all we're mapping the epitope and the parity of the antibody. So those experiments are ongoing and we're also doing structural modeling.

Speaker Change: Using some of the.

Speaker Change: Structural approaches that you could do computationally to assess the epitope.

Unknown Executive: Thank you. And as a reminder, to ask a question, please press star 11. And again, to ask a question that's star 11. One moment for our next question, please.

Speaker Change: And then we aim to put all that together and we might even possibly goes far as solving the crystal structure of the antibody, but our hypothesis right now is that it's very conformational and Thats why we see cellular cell activity because while you are right. The receptor is expressed on multiple cell types. Its function is not the same multiple cell.

Arthur Heath: Our next question will come from Arthur, he from HC Wing, right? Your line is open. Hey, good afternoon, Howard team. I just had a quick question on the 165. Obviously, it's very interesting to make a data.

Speaker Change: Types and also the traffic components that signal intra cellular we are also not the same across those cell types and we think that's the reason.

Jay Z: But maybe Jay, could you give us more color on the 165, the binding to the key rags, but not the other ones on the city 14 or a month like, because we know the team FR2 also expressed on those two sales. Just curious about the neck and the action. Thanks, thank you, Arthur. Thanks for the question. Yes, so one of the things that we found is that our antibody definitely has some form of conformational selectivity in terms of the epitope that it recognizes.

Speaker Change: But yes, we're very excited because it's not like a typical finding as you can imagine for an antibody which is why why we think this is such an innovative molecule.

Speaker Change: Yes.

Dave: Great. Thanks, Dave.

Speaker Change: Sure.

Speaker Change: Thank you.

Howard Robin: Thank you. And I am showing no further questions on the phone lines, and I'd like to turn the conference back over to Howard Robin for any closing remarks. Okay, well, thank you everyone for joining us today. And, as you can see, we're making excellent progress on our strategic plan to focus Nektar's efforts. Immunology and Inflammation. And we're advancing multiple models and innovative therapies in and towards the clinic. So I wanna thank all of our employees for their hard work, and I wanna thank our investors for their continued support. And please stay tuned. Thanks for joining us today.

Speaker Change: And I am showing no further questions on the phone lines I would now like to turn the conference back over to Howard Robin for any closing remarks.

Operator: Thank you. This concludes today's conference call. Thank you for your participation. You may now disconnect. Everyone have a wonderful day. [music] Thank you for watching!

Howard Robin: Okay, well. Thank you everyone for joining us today and as you can see we're making excellent progress in our strategic plan to focus <unk> efforts on immunology and inflammation and we are advancing multiple novel and innovative therapies inventory the clinics.

Jay Z: And in that ULAR poster, there was a panel that showed binding to two different forms of TNFR2. So, you know, the TNFR2, primarily, it's a transmembrane receptor, like, you know, TNF receptor. But it can also be shed by extra domain shedding through normal metallic proteases, and Adam 17, Cleve TNFR2, and then that liberates the shed form that can circulate in the blood. And so we tested the binding of our antibody to the surface receptor and to the shed form.

Speaker Change: I want to thank all of our employees for their hard work and I want to thank our investors for their continued support and please stay tuned thanks for joining us today.

Operator: [music] Transcription by Trans-Expert at Fiverr.com https://www.youtube.com.uk www.youtube.com.uk [music] Good day, and thank you for standing by. Welcome to the Nektar Therapeutics second quarter 2024 financial results conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 11 on your telephone. You will then hear an automated message advising that your hand is raised.

Vivian Wu: 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. Please go ahead. Crystal, and good afternoon, everyone.

Speaker Change: Thank you. This concludes today's conference call. Thank you for your participation you may now disconnect everyone have a wonderful day.

Speaker Change: Okay.

Speaker Change: [music].

Jay Z: And antibody bound the surface receptor much, much higher affinity, much more greatly, and it barely interacted with the shed form. So it indicates to us that there's a conformational, you know, specificity or a conformational component to the binding. And to assess that, we're actually doing a lot of biophysical studies right now. So we're, first of all, we're mapping the epitope and the peritope of the antibody so those experiments are ongoing. And we're also doing structural modeling, using, you know, some of the structural approaches that you could do computationally to assess the epitope.

Jay Z: And then we aim to put all that together. We might even possibly go as far as solving the crystal structure of the antibody. But our hypothesis, you know, right now, is that it's very conformational. And that's why we see cellular selectivity because while you're right, the receptor is expressed of multiple cell types. Its function is not the same on multiple cell types. And also the, the draft components that signal intracellularly are also not the same across those cell types.

Speaker Change: Yes.

Speaker Change: [music].

Speaker Change: Okay.

Speaker Change: [music].

Speaker Change: Yes.

Speaker Change: [music].

Speaker Change: Yes.

Speaker Change: [music].

Speaker Change: Okay.

Speaker Change: Dan.

Speaker Change: [music].

Jay Z: And we think that's, that's the reason. But yeah, we're very excited because that's, it started like a typical farting, as you can imagine, for an antibody, which is why, why we think this is such an innovative model. Great. Thanks, David.

Unknown Executive: Thank you and I am showing no further questions on the phone lines and I like to turn the conference back over to Howard Robin for any closing remarks.

Speaker Change: Okay.

Speaker Change: [music].

Howard Robin: Okay well thank you everyone for joining us today and as you can see we're making excellent progress in our strategic plan to focus Nektar's efforts on immunology and inflammation and we're advancing multiple model and innovative therapies in and towards the clinic. So I want to thank all of our employees for their hard work and I want to thank our investors for their continued support and please stay tuned thanks for joining us today.

Speaker Change: Yes.

Speaker Change: Yeah.

Vivian Wu: [music].

Vivian Wu: Thank you this concludes today's conference call thank you for your participation you may now disconnect everyone have a wonderful day, you you you you you you you you you . . [inaudible] Please be advised that today's conference is being recorded. I will now let the hand of the conference over to your speaker today, Vivian Wu. Please go ahead. Thank you, Crystal and good afternoon everyone. Thank you for joining us today. What does on the call or how Robin or President and Chief Executive Officer, Dr. Jonathan Zalevsky, or Chief Research and Development Officer, Dr. Mary Tagliaferri, or Chief Medical Officer, and Sandra Gardiner, or Chief Financial Officer?

Speaker Change: [music].

Vivian Wu: [music].

Vivian Wu: Thank you for joining us today. With us on the call are Howard Robin, our President and Chief Executive Officer, Dr. Jonathan Zalevsky, our Chief Research and Development Officer, Dr. Mary Tagliaferri, our Chief Medical Officer, and Sandra Gardiner, our Chief Financial Officer. On today's call, we expect to make forward-looking statements regarding your business, including statements regarding the therapeutic potential of and future development plans for drug candidates in research programs, as well as the timing of the initiation of clinical studies and the availability of clinical data for drug candidates.

Vivian Wu: Good day and thank you for standing by welcome to the Nektar Therapeutics second quarter 2024 financial results Conference call.

Speaker Change: 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.

Speaker Change: To ask a question during the session you will need to press star one on your telephone.

Speaker Change: We'll then hear an automated message advising your hand is race.

Speaker Change: To withdraw your question. Please press star one again.

Speaker Change: Please be advised that today's conference is being recorded.

Vivian Wu: The timing and plans for future clinical data presentations. The formation, future development plans, or success of our collaboration agreements, financial guidance, and certain other statements regarding our future business. Because forward-looking statements relate to the future, they are subject to uncertainties and risks that are difficult to predict, many of which are outside of our control.

Speaker Change: I would now like to hand, the conference over to your Speaker today Vivian will please go ahead.

Vivian Wu: Thank you Crystal and good afternoon, everyone. Thank you for joining us today.

Speaker Change: With us on the call are Howard Robin, our President and Chief Executive Officer, Dr. Jonathan <unk>, Our Chief Research and development Officer, Dr. Mary Tagliaferri, our Chief Medical Officer, and Sandra Gardner, our Chief Financial Officer.

Vivian Wu: On today's call, we expect to make forward looking statements regarding our business, including statements regarding the therapeutic potential of and future development plans for drug candidates and research programs.

Speaker Change: The timing of the initiation of clinical studies and availability of clinical data for drug candidates, the timing and plans for future clinical data presentations the formation future development plans or success of or collaboration agreements financial guidance and certain other statements regarding the future for our business.

Vivian Wu: Because forward looking statements relate to the future theyre subject to uncertainties and risks that are difficult to predict many of which are outside of our control.

Our actual results may differ materially from these statements important risks and uncertainties are set forth in our Form 10-Q that was filed on May 10th 2024, which is available at SEC Gov.

Vivian Wu: We undertake no obligation to update any of these forward looking statements, whether as a result of new information future developments or otherwise.

Vivian Wu: A webcast of this call will be available on the IR page of doctors website and Doctor Dotcom.

Vivian Wu: Our actual results may differ materially from these statements. Important risks and uncertainties are set forth in our Form 10-Q that was filed on May 10, 2024, which is available at sec.gov. We undertake no obligation to update any of these forward-looking statements, whether as a result of new information, future developments, or otherwise. A webcast of this call will be available on the Investor Relations page of Nektar's website, at Nektar.com. With that said, I would like to hand the call over to our President and CEO, Howard Robin. Thank you, Vivian, and thank you all for joining us today.

Howard Robin: With that said I would like to hand, the call over to our President and CEO Howard Robin Howard.

Howard Robin: Thank you Vivian and thank you all for joining us today.

Howard Robin: We've made good progress in the second quarter towards our goal of building a highly promising best-in-class pipeline focused on immunology and inflammation. In this quarter, we continue to make significant advancements with our lead program, ResPeg Aldoflucan. 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 autoimmune disease. ResPeg has generated promising data, which supports its potential to become a highly differentiated, novel treatment for immune disorders.

Howard Robin: We've made good progress in the second quarter towards our goal of building a highly promising best in class pipeline focused on immunology and inflammation and this quarter. We continued to make significant advancements with our lead program <unk>.

Howard Robin: <unk> is designed to book Dampens, the inflammatory response and simultaneously restore immune balance by directly expanding functional T reg cells and engaging multiple immuno regulatory pathways in patients with autoimmune disorders.

Speaker Change: <unk> has generated promising data, which supports its potential to become a highly differentiated novel treatment for immune disorders.

Howard Robin: These data include Phase 1b efficacy data in ectopic dermatitis, which is the most common chronic inflammatory skin disease and is marked by dysregulation of the immune system and specifically excessive activation of autoreactive and inflammatory T-cells. ResPeg is designed to address this root dysfunction.

Howard Robin: These data include the phase <unk> efficacy data in atopic dermatitis, which is the most common chronic inflammatory skin disease and as mark.

Howard Robin: This regulation of the immune system, and specifically excessive activation of auto reactive and inflammatory T cells.

<unk> is designed to address this route dysfunction dysregulation by proliferating regulatory T cells, which can act on multiple inflammatory pathways at once.

Howard Robin: Dysregulation by proliferating regulatory T cells which can act on multiple inflammatory pathways at once. Respec is a first-in-class agent in the most clinically advanced program of its kind targeting ectopic dermatitis, which has traditionally focused on signal pathway antagonists. I'll let Jay-Z talk more about this in a moment, but I'm proud to announce that we have an upcoming paper accepted in Nature Communications and a presentation at the EADV conference in September, which illustrates RESPEG's mechanism.

Vivian Wu: On today's call, we expect to make forward-looking statements regarding your business, including statements regarding the therapeutic potential of and future development plans for drug candidates in research programs. The timing of the initiation of clinical studies and the availability of clinical data for drug candidates, the timing and plans for future clinical data presentations, the formation, future development plans, or success of our collaboration agreements, financial guidance, and certain other statements regarding the future for business.

Jay-Z: <unk> is a first in class agents and the most clinically advanced program of its kind targeting atopic dermatitis, which is traditionally focused on signal pathway antagonists.

Howard Robin: I'll, let Jason talk more about this in a moment, but I am proud to announce that we have an upcoming paper accepted in nature communications and.

Jay-Z: In our presentation at the ATV conference in September, which illustrate risk pigs mechanism.

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. Our actual results may differ materially from these statements. Important risks and uncertainties are set forth in our form 10 key that was filed on May 10, 2024, which is available at SEC.gov. We urge you to take no obligation to update any of these forward-looking statements, whether as a result of new information, future developments, or otherwise.

Howard Robin: These publications will feature extensive biomarker analyses from our Phase 1b studies in immune-driven skin-related disorders of atopic dermatitis and psoriasis. ResPeg is advancing nicely in the two Phase 2b studies that Nektar is conducting in ectopic dermatitis and alopecia areata, and enrollment for both studies remains on track.

Jay-Z: These publications will feature extensive biomarker analysis from our phase <unk> studies and immune driven skin related disorders.

Jay-Z: Topic dermatitis in psoriasis.

Jay-Z: <unk> is advancing nicely.

Jay-Z: Two phase <unk> studies that nectar is conducting an atopic dermatitis and alopecia or enrollment for both studies remains on track.

Howard Robin: The ectopic dermatitis study is enrolling 400 patients across approximately 110 clinical investigators in the US, Canada, Europe, and Australia. Patients who are enrolling in the study are diagnosed with moderate to severe ectopic dermatitis and are also biologic naive and have failed topical treatment. Importantly, this is the identical patient population studied in the Phase 1b study of RISD. Jay-Z will talk more about this study design later in the call, and as I just stated, enrollment is on track for top-line data readout from the study's 16-week induction treatment stage in the first half of 2025.

Jay-Z: The atopic dermatitis studies enrolling 400 patients throughout approximately a 110 clinical investigator sites in the U S, Canada, Europe and Australia.

Vivian Wu: A webcast of this call will be available on the IRA page of NectarsWebsite and Nectar.com. With that said, I would like to hand the call over to our President and CEO, Howard Robin. Howard? Thank you, Vivian, and thank you all for joining us today. We've made good progress in the second quarter towards our goal of building a highly promising, best-in-class pipeline focused on immunology and inflammation. In this quarter, we continue to make significant advancements with our lead program, ResPEG Alvis Lupin, or ResPEG.

Speaker Change: <unk> are enrolling in this study are diagnosed with moderate to severe atopic dermatitis.

Speaker Change: And are also a biologic naive and a sale topical treatment options.

Fortunately this is the identical patient population studied in the phase <unk> study of respect.

Howard Robin: Jamie will talk more about this study design later in the call and as I. Just stated enrollment is on track for topline data readout from this study 16 week induction treatment stage in the first half of 2025 months data from the maintenance stage, which looks at maintenance dosing every four weeks and every 12 weeks will be.

Vivian Wu: ResPEG is designed to both dampen the inflammatory response and simultaneously restore immune balance by directly expanding functional TRAG cells and engaging multiple immunoregulatory pathways in patients with autoimmune disorders. ResPEG has generated promising data, which supports its potential to become a highly differentiated novel treatment for immune disorders. These data include the phase 1B efficacy data and a topic dermatitis, which is the most common chronic inflammatory skin disease, and is marked by dysregulation of the immune system, and specifically excessive activation of auto reactive and inflammatory TRAG cells.

Howard Robin: Data from the maintenance stage, which looks at maintenance dosing every four weeks and every 12 weeks, will be available towards the end of 2025 and early 2026. There is a high unmet need for distinctive new mechanisms to treat ectopic dermatitis.

Jay-Z: <unk> towards the end of 2025 and early 'twenty six.

Yes.

Speaker Change: It is a high unmet need for distinctive new mechanisms to treat atopic dermatitis.

Howard Robin: With the extent and breadth of studies being conducted right now and the competition for patient recruitment, I am proud that we're achieving our enrollment. We believe that this is driven by a combination of the compelling ResPeg Phase 1b data presented at EADV 2023 and, of course, the hard work of our clinic. In the U.S., there are approximately 30 million people living with ectopic dermatitis, and half of these patients are diagnosed with moderate to severe disease.

Jay-Z: The extent and breath of studies being conducted right now in the competition for patient recruitment I am proud that we are achieving our enrollment goals. We believe that this is driven by a combination of the compelling Roes peg phase <unk> data presented at <unk> 2023.

Speaker Change: Of course, the hard work of our clinical team.

Vivian Wu: ResPEG is designed to address this root dysfunction, dysregulation, by proliferating regulatory TRAG cells, which can act on multiple inflammatory pathways at once. ResPEG is a first-in-class agent in the most clinically advanced program of its kind targeting a topic dermatitis, which is traditionally focused on signal pathway antagonists. I'll let Jay-Z talk more about this in a moment, but I'm proud to announce that we have an upcoming paper accepted in nature communications, and a presentation at the EADD conference in September, which illustrates ResPEG's mechanism.

Howard Robin: And the U S. There are approximately 30 million people living with atopic dermatitis and half of the patient diagnosed with moderate to severe disease and its estimated that under 10% of patients who could receive biologics today are actually receiving treatment. We believe that new mechanisms are the key to growing this market and that there was a.

Howard Robin: And it's estimated that under 10% of patients who could receive biologics today are actually receiving treatment. We believe that new mechanisms are the key to growing this market and that there is a high unmet medical need for novel treatment. So we are excited that Respeg is poised to emerge as a highly differentiated potential treatment for these patients. Now, as you know, we have a second Phase 2 study for ResPeg that is enrolling 84 patients with alopecia areata. Enrollment for this study opened in March, and enrollment also remains on track for this study.

Howard Robin: High unmet medical need for novel treatment options. So we are excited that <unk> is poised to emerge as a highly differentiated potential treatment for these patients now.

Howard Robin: Now as you know we have a second phase III study for <unk> that is enrolling 84 patients with alopecia area.

Vivian Wu: These publications will feature extensive biomarker analyses from our phase 1B studies in immune-driven skin-related disorders of a topic dermatitis and psoriasis. Respeck is advancing nicely in the two phase 2B studies that Nektar is conducting in a topic dermatitis and alopecia errat. Enrollment for both studies remains on track. The topic dermatitis study is enrolling 400 patients throughout approximately 110 clinical investigator sites in the US, Canada, Europe, and Australia. Patients are enrolling in the study are diagnosed with moderate to severe ectopic dermatitis and are also biologic naïve and have failed topical treatment options.

Speaker Change: For this study opened in March and the enrollment also remains on track for this study we are looking forward to top line data from this trial in the middle of 2025, which is estimated to be a few months. Following the top line readout from the phase II study in atopic dermatitis.

Howard Robin: We're looking forward to top-line data from this trial in the middle of 2025, which is estimated to be a few months following the top-line readout from the Phase 2 study in ectopic dermatitis. We believe there's a significant potential for Respec to help people with this devastating disease. Nearly 7 million people in the U.S. alone have or will develop alopecia areata.

Howard Robin: We believe this is a significant potential for <unk> to help people with this devastating disease nearly 7 million people in the U S alone have or will develop our PCL.

Howard Robin: This disorder significantly affects the quality of life for patients, and the currently available JAK inhibitor therapies are not durable, have high relapse rates, and carry significant safety. Therefore, there is an urgent unmet medical need for these new therapies. On the preclinical side, we continue to advance Nektar 0165, our novel TNFR2 agonist antibody program. In June, we reported the first preclinical data on this program at ULAR. These data show that Nektar O165 is a unique antibody with monomeric activity that selectively binds to TNFR2 on Tregs to enhance their immunoregulatory function. Given the importance of TNFR receptor 2 in certain autoimmune diseases,

Howard Robin: This disorders significantly affects the quality of life for patients and the currently available JAK inhibitor therapies are not durable have high relapse rates and carry significant safety risks. Therefore, there is an urgent unmet medical need for these new therapies.

Howard Robin: On the preclinical side, we continue to advance Victor <unk> five our novel TNF agonist antibody program.

Vivian Wu: Importantly, this is the identical patient population studied in the phase 1B study of Respeck. Jay-Z will talk more about the study design later in the call and as I just stated, enrollment is on track for top line data readout from the study's 16 week induction treatment in the first half of 2025. Data from the maintenance stage, which looks at maintenance dosing every four weeks and every 12 weeks, will be available towards the end of 2025 and early 26.

Howard Robin: In June we reported the first preclinical data on this program at <unk>.

Howard Robin: These data showed that <unk> hundred six five is a unique antibody with mono Derek activity that selectively binds to TNF or two on T regs to enhance their immuno regulatory function.

Howard Robin: Given the importance of TNF receptor two in certain autoimmune diseases, Nichter 165 could potentially become a first in class treatment for autoimmune diseases, such as multiple sclerosis, ulcerative colitis lupus and vitiligo.

Howard Robin: Nektar 0165 could potentially become a first-in-class treatment for autoimmune diseases, such as multiple sclerosis, ulcerative colitis, lupus, and vitiligo. We're currently conducting IND-enabling studies with the goal of preparing for an IFD submission in the middle of 2025.

Vivian Wu: There's a high unmet need for distinctive new mechanisms to treat a topic dermatitis. When the extent and breadth of studies being conducted right now and the competition for patient I am proud that we're achieving our enrollment goals. We believe that this is driven by a combination of the compelling Respeck phase 1B data presented at EADV 2023 and of course the hard work of our clinical fee. In the US, there are approximately 30 million people living with ectopic dermatitis and half of the patients are diagnosed with moderate to severe disease and it's estimated that under 10 percent of patients who could receive biologists today are actually receiving treatment.

Howard Robin: We're currently conducting IND, enabling studies with the goal of preparing for an <unk> submission in the middle of 2025.

Howard Robin: Next, I'd like to give you an update on Nektar 255, our IL-15 program in oncology. As you know, Nektar is completing a study in large B-cell lymphoma, or LBCL, and Mary will be discussing this later in the call. In addition to the clinical study we're completing in LBCL, there are clinical studies ongoing for Nektar 255 being funded by our collaborators, Merck KGA and Bladder Cancer and AbleZeta in non-small cell lung cancer.

Speaker Change: Next I'd like to give you an update on an extra $2 55, our IL 15 program in oncology.

Howard Robin: As you know nectar is completing a study in large b cell lymphoma, or <unk> and Mary will be discussing this later in the call. In addition to the clinical study were completing an LPL. There are clinical studies ongoing for an extra $2 55 being funded by our collaborators Merck <unk> in bladder cancer and <unk>.

Vivian Wu: We believe that new mechanisms are the key to growing this market and that there's a high unmet medical need for novel treatment options. So we are excited that Respeck is poised to emerge as a highly differentiated potential treatment for these patients. Now as you know, we have a second phase 2 study for Respeck that is enrolling 84 patients with alopecia area. Enrollment for this study opened in March and the enrollment also remains on track for this study.

Speaker Change: <unk> Zeta and non small cell lung cancer.

Howard Robin: We also have an ISP study ongoing at the Fred Hutchinson Cancer Center and an ISP that recently concluded at Stanford. Stanford University recently published data from their IST in the peer-reviewed journal of the American Society of Hematology, Blood. The online manuscript has been posted, and it will be in print shortly.

Speaker Change: So havent ISP study ongoing at the Fred Hutchinson cancer Cancer Center and in ISG that recently concluded at Stanford.

Howard Robin: Stanford University recently published data from their ISP and the peer review journal of the American Society of Hematology blood.

Howard Robin: <unk> manuscript has been posted and it will be in print shortly.

Vivian Wu: We're looking forward to top line data from this trial in the middle of 2025 which is estimated to be a few months following the top line readout from the phase 2 study in a topic dermatitis. We believe there's a significant potential for Respeck to help people with this devastating disease. Nearly 7 million people in the US alone have or will develop alopecia area. This disorder significantly affects the quality of life for patients and the currently available Jack inhibitor therapies are not durable have high relapse rates and carry significant safety risks.

Howard Robin: Stanford reported data that showed a doubling of recurrence-free survival at 12 months when Nektar 255 was combined with their investigational CD1922 CAR-T therapy compared to historical controls with their investigational therapy alone. In addition to these studies, Mary will discuss more about the other studies for Nektar-255 and the strength of the data to support combination with cell therapy. As data emerged this year, we believe that Nektar 255 can become an important component of cell therapy in cancer, and we continue to evaluate strategic partnership opportunities for this program.

Speaker Change: Stanford reported data that showed a doubling of recurrence free survival at 12 months when <unk> $2 55 was combined with their investigational CD 1922 car T therapy compared to historical controls with our investigational therapy alone.

Howard Robin: In addition to these studies Mary will discuss more on the other studies for an extra $2 55, and the strength of the data to support combination with cell therapies.

Howard Robin: As the data emerge this year, we believe that an extra $2 55 can become an important component of cell therapy in cancer, and we continue to evaluate strategic partnership opportunities for this program.

Vivian Wu: Therefore there's an urgent unmet medical need for these new therapies. On the preclinical side, we continue to advance Nectar O165, our novel TNFR2 agonist antibody program. In June, we reported the first preclinical data on this program as you are. These data show that Nectar O165 is a unique antibody with monomeric activity that's selectively bind to TNFR2 on T-regs to enhance their immunoregulatory function. Given the importance of TNFR receptor two in certain autoimmune diseases, Nektar O165 could potentially become a first in class treatment for autoimmune diseases such as multiple sclerosis, ulcerative colitis, lupus, and vitilato.

Howard Robin: Before I hand the call over to Jay-Z, I just want to say that Nektar remains in a strong financial position with a cash runway that extends into the third quarter of 2026, giving us more than a year's cash at the time of ResPeg's top-line data. And with that, I'd like to hand the call over to Jay-Z for an R&D discussion. Jay-Z?

Speaker Change: Before I hand, the call over to Jay Z I, just wanted to say that <unk> remains in a strong financial position with a cash runway that extends into the third quarter of 2026, giving us more than a year's cash at the time of <unk> top line data results.

Howard Robin: And with that I'd like to hand, the call over to Jay Z <unk> R&D discussion Jay Z.

Jay-Z: Thank you Howard.

Howard Robin: Thank you, Howard. I'd like to begin with saying this program is the most advanced IL-2 Treg mechanism in the field. We believe there are major opportunities in both atopic dermatitis and alopecia areata that RASPEC could potentially address. Our Phase 1b ResPeg data in atopic dermatitis demonstrated dose-dependent efficacy and encouraging durability observed long after patient. The 12-Week Induction Period.

Jay-Z: Like to begin with respect.

Howard Robin: This program is the most advanced IL two T Reg mechanism in the field.

Howard Robin: We believe there are major opportunities in both atopic dermatitis, and alopecia area that <unk> could potentially address.

Vivian Wu: We're currently conducting IND enabling studies with the goal of preparing for an IFD submission in the middle of 2025. Next up, I'd like to give you an update on Nektar 255, our IL-15 program in oncology. As you know, Nektar is completing a study in large B cell lymphoma, or LBCL, and Mary will be discussing this later in the call. In addition to the clinical study we're completing in LBCL, there are clinical studies ongoing for Nektar 255 being funded by our collaborators, Merck KGA, and Bladder Cancer, and Ablesetta, and Nonsmoso lung cancer.

Howard Robin: Our phase one be pegged data in atopic dermatitis demonstrated dose dependent efficacy and encouraging durability observed long after patients completed the 12 week induction period.

Jonathan Zalevsky: In fact, 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. The Rapid Onset of Action and the Type of Extended Disease Control After the End of Treatment rivals or outperforms that of Tupilumab or Jaca. These promising data have us and KOLs very enthusiastic about the potential for long-lasting responses and frequent maintenance dosing with ResPeg and atopic dermatitis. Our Phase 2B study in atopic dermatitis is enrolling roughly 400 patients with three different regimens of ResPag versus Clitopin, evaluated over a 16-week induction period.

Howard Robin: In fact for both patient reported outcomes and physician assessed endpoints, we observed the same trends.

Jonathan Zalevsky: Rapid onset of effect dose dependence and long durability of control.

Jonathan Zalevsky: The rapid onset of action and the type of extended disease control. After the end of dosing rivals are outperformed added to pillar map or JAK inhibitors.

Vivian Wu: We also have an ISP study ongoing at the Fred Hutchinson Cancer Center, and an ISP that recently concluded at TNFR. TNFR University recently published data from their ISP, and the peer-reviewed journal of the American Society of hematology, blood. The online manuscript has been posted, and it will be in print shortly. Stanford reported data that showed a doubling of recurrence-free survival at 12 months when Nektar 255 was combined with their investigational CD-1922 CARP therapy, compared to historical controls with their investigational therapy alone.

Jonathan Zalevsky: These promising data have us and kols very enthusiastic about the potential for long lasting responses and in frequent maintenance dosing with <unk> in atopic dermatitis.

Jonathan Zalevsky: Our phase <unk> study in atopic dermatitis is enrolling roughly 400 patients with three different regimens of <unk> versus placebo.

Speaker Change: <unk> over a 16 week induction period.

Jonathan Zalevsky: After the induction period, patients that meet a threshold to advance from induction to make will be re-randomized into one of two maintenance regimens at their original dosage, to receive that dose level on either a once a month or once every three months regimen, to best position our program for registration. We've recently amended the protocol to extend the time on treatment during the maintenance portion of this study. The maintenance portion of the Phase 2b study was originally designed as a 26-week treatment period.

Jonathan Zalevsky: 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 their original dose level to receive that dose level on either a once a month or once every three months regimen.

Vivian Wu: In addition to these studies, Mary will discuss more on the other studies from Nektar 255, and the strength of the data to support combination with cell therapies. As the data emerged this year, we believe that Nektar 255 can become an important component of cell therapy in cancer, and we continue to evaluate strategic partnership opportunities for this program. Before I hand the call over to Jay-Z, I just want to say that Nektar remains in a strong financial position with a cash runway that extends into the third quarter of 2026, giving us more than a year's cash at the time of ResPEG's top-line data reduction.

Jonathan Zalevsky: To best position our program for registration we have recently amended the protocol to extend the time on treatment during the maintenance portion of this study.

Jonathan Zalevsky: The maintenance portion of the Phase <unk> study was originally designed as a 26 week treatment period, but we have now extended that to 36 weeks.

Jonathan Zalevsky: But we have now extended that to 36, which will in total provide 52 weeks of treatment duration for patients in the study. This will strengthen the robustness of our dataset with long-term exposure in this disease and increase the number of patients in our safety analysis to support registrational trial work following this phase two study. We also extended the off-treatment follow-up to be one year, beginning upon the conclusion of the 52-week treatment, in order to allow us to evaluate the potential remittive effect of REST.

Jonathan Zalevsky: Which will in total provide 52 weeks of treatment duration for patients in the study.

Jonathan Zalevsky: This will strengthen the robustness of our dataset with long term exposure.

Jonathan Zalevsky: <unk> setting and increase the number of patients in our safety analysis to support Registrational trial work. Following this phase III study.

Vivian Wu: And with that, I'd like to hand the call over to Jay-Z for an R&D discussion. Jay-Z? Thank you, Howard. I'd like to begin with ResPEG. This program is the most advanced aisle to g-reg mechanisms in the field. We believe there are major opportunities in both atopic dermatitis and alopecia areata that ResPEG could potentially address. Our phase 1B ResPEG data in atopic dermatitis demonstrated dose-dependent efficacy and encouraging durability observed long after patients completed the 12-week induction period.

Vivian Wu: In fact, 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. The rapid onset of action and the type of extended disease control after the end of dosing, rivals or outperformed that of tipilimab or jack inhibitors. These promising data have us and KOLs very enthusiastic about the potential for long-lasting responses and infrequent maintenance dosing with ResPEG in atopic dermatitis. Our phase 2B study in a topic dermatitis is enrolling roughly 400 patients with three different regimens of ResPag versus placebo, evaluated over a 16-week induction period.

Jonathan Zalevsky: We also extended the off treatment follow up to be a one year period that begins upon the conclusion of the 52 week treatment period.

Jonathan Zalevsky: In order to allow us to evaluate the potential remit of effect of <unk> in patients after one year of treatment.

Jonathan Zalevsky: Inpatients after one year of treatment. As Howard stated, we still anticipate top-line data from the 16-week induction period of this Phase IIb study in the first half of 2025, and data from the 36-week maintenance period will be available towards the end of 2025 or early 2025. Now turning to alopecia areata, which is a dermal disease localized to hair fall. In this disease, the patient's immune system attacks the hair follicle. Disrupting its normal ability to keep and grow hair, leading to hair loss.

Jonathan Zalevsky: As Howard stated, we still anticipate top line data from the 16 week induction period of this phase <unk> study in the first half of 2025.

Jonathan Zalevsky: And data from the 36 week maintenance period of the study will be available towards the end of 2025 or early 2026.

Jonathan Zalevsky: Now turning to alopecia, Areata, which is a dermal disease localized to hair follicle.

Jonathan Zalevsky: This disease, the patients immune system attacks hair follicle disrupting its normal ability to keep and grow hair.

Jonathan Zalevsky: Leading to hair loss.

Jonathan Zalevsky: Well, we believe there is a strong rationale for ResPag in this indication based on the role of Tregs in the underlying pathology. Normal hair follicles exist in a state of immune privilege. So, in other words, there are essentially no immune cells, no MHC expression, and minimal immune system components inside the hair follicles. We know this exclusion of the immune system is needed to maintain healthy, long-lived, and continuously functioning stem cells to grow hair during our lifetime, and in people with alopecia areata, there is a breakdown of the immune system. Hair Follicle, Infiltration of the Immune System, and inflammation.

Speaker Change: We believe there is strong rationale for <unk> in this indication based on the role of T. Regs on the underlying pathology of this disease.

Jonathan Zalevsky: And all this leads to hair loss and eventually complete baldness. Biologically speaking, Rezpec, through its central pathway of Treg rescue, is uniquely poised to address the diversity of immunopathology, providing broad potential for targeting and treating alopecia areata, as well as other dermal diseases. In published preclinical studies, both in vitro and in mice implanted with human alopecia skin, studies have shown that Tregs are essential for restoring and maintaining immune function, and therefore a novel therapeutic strategy for the treatment.

Jonathan Zalevsky: Normal hair follicles to exist in a state of immune privilege.

Jonathan Zalevsky: Another words, there are essentially no immune cells, no MHC expression and minimal immune system components inside the hair follicle.

Jonathan Zalevsky: We know this exclusion of the immune system is needed to maintain healthy long lived and continuously functioning stem cells to grow hair during our lifestyle.

Vivian Wu: 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 their original dose level to receive that dose level on either a once a month or once every three months regimen. To best position our program for registration, we've recently amended the protocol to extend the time on treatment during the maintenance portion of this study. The maintenance portion of the phase 2B study was originally designed as a 26-week treatment period, but we have now extended that to 36 weeks, which will in total provide 52 weeks of treatment duration for patients in the study.

Jonathan Zalevsky: And people with alopecia area, there is a breakdown of the immune privilege and the hair follicle.

Jonathan Zalevsky: Infiltration of the immune system inflammation.

Jonathan Zalevsky: And all of this leads to hair loss and eventually complete baldness.

Jonathan Zalevsky: Biologically speaking <unk> through its central pathway of T. Reg rescue is uniquely poised to address the diversity of immuno pathology, providing broad potential for targeting treating alopecia area.

Jonathan Zalevsky: As well as other terminal diseases.

Jonathan Zalevsky: And published preclinical studies, both in vitro and in Mikes implanted with human alopecia skin samples and studies have shown the T. Regs are essential for restoring and maintain immune privilege and therefore, a novel therapeutic strategy for the treatment of this disease.

Vivian Wu: This will strengthen the robustness of our data set with long-term exposure in this disease setting and increase the number of patients in our safety analysis to support registration trial work following this phase 2 study. We also extended the off treatment follow-up to be a one-year period that begins upon the conclusion of the 52-week treatment period. In order to allow us to evaluate the potential remittive effect of ResPag in patients after one year of treatment.

Jonathan Zalevsky: And consequently, we believe the Treg mechanism of RASPAG can restore immune function and could provide durable disease. There is a high unmet need in this patient population for tolerable treatment options. Durable responses that currently available treatments like JAK inhibitors cannot provide. We believe there is an opportunity for RASPAG to become a novel and potentially game-changing biologic therapy for alopecia areata. The Phase 2B study is well underway and plans to recruit 84 participants, severe to very severe, that will be randomized to REST tag. Patients will be treated for a period of 36 weeks and observed up to 60 weeks in total.

Speaker Change: Consequently, we believe the T. Reg mechanism of <unk> can restore immune privilege and could provide durable disease control.

Jonathan Zalevsky: There is a high unmet need in this patient population for tolerable treatment options with durable responses that currently available treatments like JAK inhibitors cannot provide.

Jonathan Zalevsky: And we believe there is an opportunity for <unk> to become a novel and potentially game changing biologic therapy in alopecia areata.

Vivian Wu: As Howard stated, we still anticipate top-line data from the 16-week induction period of this phase 2B study in the first half of 2025, and data from the 36-week maintenance period of the study will be available to over the end of 2025 or early 2026. Now, turning to alopecia ariata, which is a dermal disease localized to hair follicles. In this disease, the patients immune system attacks the hair follicle, disrupting its normal ability to keep and grow hair, leading to hair loss.

Jonathan Zalevsky: The phase <unk> study is well underway and plans to recruit 84 patients with severe to very severe disease that will be randomized to red tag or placebo.

Jonathan Zalevsky: <unk> will be treated for a period of 36 weeks and observed up to 60 weeks in total.

Jonathan Zalevsky: Our primary endpoint for the study is mean percent improvement in SALT, or the severity of alopecia 2, at week 36, including her portion of patients that were observed to have varying degrees of improvement in salt. We are well underway with enrolling patients into this study. And we expect top-line data near the middle of 2025, a few months following the top-line data readout from our atopic dermatitis study. Now, turning to Nektar 0165, our TNFR2 agonist antibody.

Speaker Change: Our primary endpoint for this study is the mean percent improvement in salt.

Jonathan Zalevsky: The severity of alopecia tool at week 36.

Jonathan Zalevsky: We will also be looking at a number of other secondary endpoints, including the proportion of patients that were observed to have varying degrees of improvement in salt score.

Vivian Wu: When we believe there is strong rationale for ResPag in this indication, based on the role of T-regs, on the underlying pathology of this disease. Normal hair follicles exist in a state of immune privilege, so in other words, there are essentially no immune cells, no MHC expression, and minimal immune system components inside the hair follicle. We know this exclusion of the immune system is needed to maintain healthy, long-lived, and continuously functioning stem cells to grow hair during our lifespan.

Jonathan Zalevsky: We are well underway with enrolling patients into this study.

Jonathan Zalevsky: And we expect top line data near the middle of 2025.

Jonathan Zalevsky: Few months following top line data readout from our atopic dermatitis studies.

Jonathan Zalevsky: Now turning to <unk>, 165, or TNF or two agonist antibody.

Jonathan Zalevsky: TNFR2 is highly expressed on Tregs, myeloid suppressor cells, regulatory B cells, and neuronal cells. In Tregs, TNFR2 agonism has been shown to potentiate the effector function. Impressive Functions and Maintenance. T-Rag Linear Stability, especially in non-lymphoid tissue compartments.

Speaker Change: <unk> is highly expressed on T. Reg myeloid suppressor cells regulatory b cell neuronal cells and others.

Vivian Wu: In people with alopecia ariata, there is a breakdown of the immune privilege in the hair follicle, infiltration of the immune system, inflammation, and all this leads to hair loss and eventually complete baldness. Biologically speaking, ResPag, through its central pathway of T-reg rescue, is uniquely poised to address the diversity of immunopropology, providing broad potential for targeting treating alopecia ariata, as well as other dermal diseases. Impublished preclinical studies, both in vitro and in mice implanted by human alopecia skin The studies have shown that T-Rags are essential for restoring and maintaining immune privilege and therefore a novel therapeutic strategy for the treatment of this disease.

Jonathan Zalevsky: In tea bags TNF are two agonism has been shown to potentiate the effector function.

Jonathan Zalevsky: Functions and maintenance of T Reg lineage stability, especially in non lymphoid tissue compartment.

Jonathan Zalevsky: Genetic studies show that if TNF-R2 is absolutely... The phenotypic effect is autoimmunity, as well as other conditions that resemble FOXP3 loss of function. In contrast, it's present, and Activation of its Signaling has been associated with Immunoregulatory Function and Tissue Protection. The TNS R2 agonist program, built upon many years of TREG experience that we've gained from studying RAD. ResPag is an IL-2 receptor pathway agonist that drives Jackstab signaling, which is critical to drive TBAC proliferation and function in primary and secondary lymphoid organs.

Jonathan Zalevsky: Genetic studies show that a TNF part two is absent that phenotypic effect as auto immunity as well as other conditions that resemble Fox P. Three loss of function.

Jonathan Zalevsky: In contrast, its presence and activation of its signaling has been associated with immuno regulatory function and tissue protection effects.

Jonathan Zalevsky: TNF or two agonist program is built upon many years of <unk> experience that we've gained from studying resume.

Jonathan Zalevsky: <unk> is an IL two receptor pathway agonist drive JAK stat signaling and T regs, which is critical to drive teabag proliferation and function in primary and secondary lymphoid organs.

Vivian Wu: And consequently, we believe the T-Rag mechanism of ResPag can restore immune privilege and could provide durable disease control. There is a high-endment need in this patient population for tolerable treatment options with durable responses that currently available treatments like Jack inhibitors cannot provide We believe there is an opportunity for ResPag to become a novel and potentially game-changing biologic therapy in alopecia, Ariana. The Phase II B study is well underway and plans to recruit 84 patients with severe to very severe disease that will be randomized to ResPag or placebo.

Jonathan Zalevsky: TNFR2 is the most abundant TNF super family member expressed on and the key activator of NF-kappa-B, which also controls FOXP3 protein expression and is critical to maintain Treg function, especially in non-lymphoid organs. Thus, with the ResPag and TNF-R2 agonist programs, Nektar's pipeline provides target rationale for both lymphoid and non-lympho And this is why we are so excited about Nektar 0165.

Jonathan Zalevsky: TNF or two is the most abundant TNF superfamily member expressed on T regs and the key activator of Nf Kappa B, which also controls the Fox P. <unk> protein expression and is critical to maintain T reg function, especially in non lymphoid organs.

Jonathan Zalevsky: Thus with the Red Tag and Ken Fr two agonist programs <unk> pipeline provide target rationale for both lymphoid and non lymphoid T. Regs and this is why we are so excited about <unk> 65.

Vivian Wu: Patients will be treated for a period of 36 weeks and observed up to 60 weeks in total. Our primary endpoint for the study is mean percent improvement in salt or the severity of alopecia tool at week 36. We will also be looking at a number of other secondary endpoints, including the proportion of patients that were observed to have varying degrees of improvement in salt score. We are well underway with enrolling patients into this study and we expect top line data near the middle of 2025, a few months following the top line data readout from our topic dermatitis study.

Jonathan Zalevsky: As Howard mentioned, we presented the first preclinical data for this program at ULAR in June. In the presentation, we demonstrated several novel and innovative properties of the antibodies that we discovered and are developing. Firstly, the TNF-R2 agonist we discovered came from AI-based de novo; consequently, they provide novel TNFR2 binding and cell signaling properties.

Speaker Change: As Howard mentioned, we presented the first preclinical data for this program at <unk> in June.

Jonathan Zalevsky: One example of that novelty is a demonstration that these antibodies are able to signal through the TNFR2 multimeric receptor a single-arm monovalent antibody. This is a very novel effect for a TNFR-2 agonistic animal. We grafted these into a regular bivalent antibody format, Nektar 0165, and demonstrated the very high specificity of this antibody for binding and signaling through TNFR2 on T-Ref, with little to no binding and signaling in conventional T-cells and K-cells or monocytes. Nectar 0165 also drove Treg proliferation, upregulation of FOXP3, and other activation of Primary Human T-Rex. And importantly,

Jonathan Zalevsky: Year.

Jonathan Zalevsky: In the presentation, we demonstrated several novel and innovative properties of the antibodies that we discovered and are developing.

Jonathan Zalevsky: Firstly the TNF are two agonists, we discovered came from AI based de Novo designs.

Jonathan Zalevsky: And consequently, they provide novel TNF are two binding and cell signaling properties.

Speaker Change: One example of that novelty is a demonstration that these antibodies are able to signal to the TNF are two multi America receptor is single arm monovalent antibodies.

Jonathan Zalevsky: This is a very novel effect for a TNF are two agonistic antibody.

Vivian Wu: Now, turning to Nectar O165, our TNFR-2 agonist antibody. TNFR-2 is highly expressed on t-regs, myeloid suppressor cells, regulatory b-cells, neuronal cells and others. In t-regs, TNFR-2 agonism has been shown to potentiate the effector function, suppressor functions and maintenance of t-reg lineage stability, especially in non-limphoid tissue compartment. Genetic studies show that if TNFR-2 is absent, the phenotypic effect is autoimmunity, as well as other conditions that resemble Fox P3 loss of function. In contrast, its presence and activation of its signaling has been associated with immunoregulatory function and tissue protection effect.

Jonathan Zalevsky: We grafted these two irregular bivalent antibody format and extra one metric of 165 and demonstrated the very high specificity of this antibody for binding and signaling through TNF or two on T. Rex.

Jonathan Zalevsky: With little to no binding and signaling and conventional T cells NK cells or monetize.

Jonathan Zalevsky: <unk> hundred 65 also drove T. Reg proliferation Upregulation of Fox P. III and other activation markers in primary human T Rex and importantly.

Jonathan Zalevsky: Nektar 0165 drove these effects as a single agent, without need for CD3 ligation, co-stimulation, cytokine, or mitogen. We also studied Nektar O165 in a human TNFR2 knock-in mouse, and used that model to confirm the Treg selective PKPD profile of the antibody, and also demonstrated single agent efficacy in a mouse model of KLHDTH established in the same We are very excited about the unique and differentiated profile of the antibodies that were discovered, and we are rapidly advancing Nectar 0165.

Jonathan Zalevsky: <unk> a 165 drove these effects as a single agent.

Jonathan Zalevsky: Without need for CD, three litigation co stimulation cytokines or mitogen support.

Jonathan Zalevsky: We also studied <unk> six 5 million of human TNF or to knock in mouse and use that model to confirm the T. Regs selective PK PD profile of the antibody and also demonstrated single agent efficacy in a mouse model of KLA HDD H established in the same TNF are two knockin mouth strength.

Vivian Wu: The TNFR-2 agonist program is built upon many years of t-reg experience that we've gained from studying RASPEG. RASPEG is an IL-2 receptor pathway agonist, drives jacks that signaling in t-regs, which is critical to drive t-reg proliferation and function in primary and secondary lymphoid orchids. TNFR-2 is the most abundant TNFR-superfamily member expressed on t-regs, and the key activator of NF-capability, which also controls the Fox P3 protein expression and is critical to maintain t-reg function, especially in non-limphoid organ.

Jonathan Zalevsky: We are very excited with the unique and differentiated profile of the antibodies that were discovered and we are rapidly advancing <unk> 106, five to the clinic we expect.

Jonathan Zalevsky: We expect to initiate the first human studies in the middle of 2025. Examples of indications that could be addressed include multiple sclerosis, mucosal immunology conditions such as ulcerative colitis and GI or other oral diseases, lupus, and even dermal autoimmune diseases like vitiligo. We note the growing interest in a novel and selective TNF-R2 agonist like Nektar Therapeutics, 5, and as we move forward with our IND-enabling studies, we will continue to be open to the opportunity of working with companies that have an interest in these areas to strategize the best path forward. And with that, I'll hand the call over to Mary to discuss Nektar 255. Mary.

Jonathan Zalevsky: To initiate first in human studies in the middle of 2025.

Jonathan Zalevsky: Examples of indications that could be addressed include multiple sclerosis, mucosal immunology conditions, such as ulcerative colitis in Gi or other oral bicoastal diseases.

Vivian Wu: Thus, with the RASPEG and TNFR-2 agonist programs, Nectors Pipeline provides target rationale for both lymphoid and non-limphoid T-regs, and this is why we are so excited about Nectoral-1-6-5. As Howard mentioned, we presented the first pre-clinical data for this program at U-R in June- this year. In the presentation, we demonstrated several novel and innovative properties of the antibodies that we discovered and are developing. Firstly, the TNF-R2 agonist we discovered came from AI-based day-novo design.

Jonathan Zalevsky: Lucas and even dermal autoimmune diseases like vitiligo.

Mary Tagliaferri: We note the growing interest for our novel selective TNF are two agonist like Metro 165 and <unk>.

Mary Tagliaferri: We move forward with our IND, enabling studies, we will continue to be open to the opportunity of working with companies that have interest in these areas to strategize as the best path forward.

Jonathan Zalevsky: And with that I'll hand, the call over to Mary to discuss <unk> Wi Fi.

Mary Tagliaferri: Thank you, Jay-Z. And finally, turning to our IL-15-based oncology program, Nektar 255. We believe the IL-15-based mechanism of action has promising potential in combination, particularly with cell therapy. However, while autologous CAR T-cell therapy transformed the management of patients with large B-cell lymphoma after the first cellular therapies were approved, clinical responses were not durable, and roughly 60% of patients receiving CAR T-cell therapy for large B-cell lymphoma eventually progressed. In 2017, the NCI and KITE, and months later, the Fred Hutch Group published data showing that high serum IL-15 levels were associated with a higher C-max and AUC of CAR T cells, both factors correlated with responses in lymphoma.

Jonathan Zalevsky: <unk>.

Mary Tagliaferri: Thank you J P and finally, turning to our IL 15 based oncology program <unk> 295.

Vivian Wu: And consequently, they provide novel TNF-R2 binding and cell signaling properties. One example of that novelty is a demonstration that these antibodies are able to signal through the TNF-R2 multimeric receptor as single arm monovalent antibodies. This is a very novel effect for TNF-R2 agonistic antibodies. We grafted these into a regular bivalent antibody format, Nektar O165, and demonstrated the very high specificity of the antibody for binding and signaling through TNF-R2 on T-Rex, with little to no binding and signaling in conventional T-cells and K-cells or monocells.

Mary Tagliaferri: We believe the IL 15 based mechanism of action has promising potential in combination, particularly with cell therapy.

Mary Tagliaferri: Well ill call against car T cell therapy transform the management of patients with large b cell lymphoma. After the first cellular therapies were approved clinical responses were not durable and roughly 60% of patients receiving car T cell therapy for large b cell lymphoma eventually progressed.

Mary Tagliaferri: In 2017.

Mary Tagliaferri: <unk> tight and months later, the Fred Hutch group published data showing that high serum IL 15 levels were associated with a higher C. Max and AUC of car T cells, both factors correlated with responses in lymphoma.

Vivian Wu: Nektar O165 also drove T-Rex proliferation, upregulation of FOX-B3, and other activation markers in primary human T-Rex. And importantly, Nektar O165 drove these effects as a single agent. Without stimulation, cytokine, or mitogen support. We also studied Nektar O165 in a human TNF-R2 knock-in mouth, and used that model to confirm the T-Rex selective PKP-D profile of the antibody, and also demonstrated single agent efficacy in a mouse model of K-L-H-D-D-H established in the same TNF-R2 knock-in mouth string. We were very excited with the unique and differentiated profile of the antibodies that were discovered, and we are rapidly advancing Nektar O165 into the clinic.

Mary Tagliaferri: Thus, our initial development strategy aimed to improve the long-term efficacy of CAR T cell products with the administration of exogenous IL-15, given the wealth of data about this cytokine's importance. Dr. Cameron Turtle from Fred Hutch completed preclinical experiments showing that Nektar 255 enhanced the in vivo persistence and anti-tumor efficacy of CD19-directed CAR T cells in a dose- As predicted, mice treated with the CAR T cell Nektar 255 combination maintain significantly higher CAR T cell PEEP levels and continue tumor suppression, translating into durable, Following Dr.

Mary Tagliaferri: Thus our initial development strategy aimed to improve the long term efficacy of car T cell products with the administration of exogenous IL 15, given the wealth of data about this cytokines important.

Mary Tagliaferri: Dr. Cameron turtle from Fred Hutch completed preclinical experiments showing that <unk> hundred five enhanced the in vivo persistence and anti tumor efficacy of CD 19, directed car T cells in a dose dependent manner.

Mary Tagliaferri: As predicted mice treated with the car T cell <unk> five combination maintained significantly higher car T cell peak levels and continued tumor suppression translating into durable efficacy.

Mary Tagliaferri: With Turtle's published results and blood advances, we all shared a strong conviction that Nektar 255 could lead to re-expansion of CAR T-cells when dosed in patients to enhance efficacy. Fred Hutch began an IST to evaluate Nektar-255 as an adjuvant treatment to CAR T-cells to improve the complete response rate in patients with large B-cell lymphoma. Drs.

Speaker Change: Following Dr Turtles published results in blood advances, we all shared a strong conviction that <unk> 255 could lead to re expansion of car T cells, when dosing patients to enhance efficacy.

Jay Z: We expect to initiate first-in-human studies in the middle of 2025. Examples of indications that could be addressed include multiple sclerosis, eucosol immunology conditions such as ulcerative colitis and GI or other oral eucosal diseases, lupus, and even dermal autoimmune diseases like middle aga. We note the growing interest for a novel and selective TNF-R2 agonist like Nektar O165, and as we move forward with our IND enabling studies, we will continue to be open to the opportunity of working with companies that have interest in these areas to strategize as the best path forward.

Mary Tagliaferri: Fred Hutch began an ISP to evaluate <unk> hundred five as an adjuvant treatment to car T cells to improve the complete response rate in patients with large b cell lymphoma.

Mary Tagliaferri: Crystal McCall and Lori Muffley also evaluated Nektar 255 to enhance the efficacy of Stanford's proprietary CD1922 CAR T-cell for B-cell acute lymphoblastic leukemia. Their data was published in Blood last month, compared to a control group previously treated with the CAR T-cell therapy. Nektar 255, when added to the CD1922 CAR T-cell therapy, increased the 12-month relapse-free survival from 38% to 67%. The median RFS for the CAR T-cell only cohort was 3.9 months. And for the cohort treated with Nektar 255 and the proprietary CAR T-cell therapy, it has not been reached with over 14.4 months of follow-up. So why does Nektar 255 work?

Speaker Change: Doctors Crystal Nicol and Lori Luckily also evaluated <unk> hundred five to enhance the efficacy of Stanford's proprietary CD 1922 car T cell for B cell acute lymphoblastic leukemia.

Mary Tagliaferri: And with that, I'll hand the call over to Mary to discuss Nektar 255. Mary? Thank you, Jay-Z, and finally, turning to our IL-15 based oncology program Nektar 255. We believe the IL-15 based mechanism of action has promising potential in combination, particularly with cell therapies. While opologous CAR-T cell therapy transformed the management of patients with large B cell lymphoma after the first cellular therapies were approved, clinical responses were not durable, and roughly 60% of patients receiving CAR-T cell therapy for large B cell lymphoma eventually progress.

Speaker Change: Dan first data was published in blood last month.

Mary Tagliaferri: <unk> to Stanford control group.

Mary Tagliaferri: We treated with the car T cell therapy.

Mary Tagliaferri: <unk> hundred five when added to the CD 1922 car T cell therapy increased the 12 months relapse free survival from 38% to 67%.

Mary Tagliaferri: The median RF for the car T cell only cohort with $3 nine months and for the cohorts treated with <unk> five and the proprietary car T cell therapy. It has not been reached with over 14 four months of follow up.

Mary Tagliaferri: So why does <unk> five work.

Mary Tagliaferri: In 2017, the NCI Enkite, and months later the Fred Hudge Group, published data showing that high serum IL-15 levels were associated with a higher C-MAX and AUC of CAR-T cells, both factors correlated with responses in lymphoma. Last, our initial development strategy aimed to improve the long-term efficacy of CAR T cell products with the administration of exogenous IL-15, given the wealth of data about this cytokines importance. Dr. Cameron Turtle from Fred Hutch, completed pre-clinical experiments showing that Nektar-255 enhanced the in vivo persistence and anti-tumor efficacy of CD-19 directed CAR T cells in a dose-dependent manner.

Mary Tagliaferri: We've now confirmed in patients the re-expansion of CAR T cells following Nektar 255 that we saw pre-clinical. In the Stanford study, we observed re-expansion of CAR T cells in the CNS following Nektar 255 administration. At Fred Hutch, where they're combining Nektar 255 with Brionzi in patients with large B-cell lymphoma, we have confirmed re-expansion of the CAR T-cells after Nektar 255 as well, leading to a second peak and increase in AUC.

Mary Tagliaferri: We've now confirmed in patients three expansion of car T cells. Following <unk> five that we saw pre clinically.

Mary Tagliaferri: The Stanford study, we observed re expansion of the car T cells in the CNS following <unk> five administration.

Mary Tagliaferri: As Fred Hutch, where theyre, combining <unk> with <unk> in patients with large b cell lymphoma.

Mary Tagliaferri: Confirmed re expansion of the car T cells after an extra 255 as well.

Mary Tagliaferri: Moving to a second peak and increase in AUC.

Mary Tagliaferri: An additional observation from Stanford suggests that Nektar 255 also influences lymphocyte trafficking to diseased tissue. As you know, we've been running our own trial where we've enrolled 15 patients with large B-cell lymphoma. In this study, Nektar 255 is administered after autologous CD19 CAR T cell therapy.

Mary Tagliaferri: And additional observation from Stanford suggests that <unk> <unk> five also influences lymphocyte trafficking to disease tissues.

Mary Tagliaferri: As you know we've been running our own trial, where we've enrolled 15 patients with large b cell lymphoma.

Mary Tagliaferri: As predicted, mice treated with the CAR T cell, Nektar-255 combination, maintained significantly higher CAR T cell peak levels and continued tumor suppression, translating into durable efficacy. Following Dr. Turtle's published results in blood advances, we all shared a strong conviction that Nektar-255 could lead to re-expansion of CAR T cells when those sensations to enhance efficacy. Fred Hutch began an IST to evaluate Nektar-255 as an adjuvant treatment to CAR T cells to improve the complete response rate in patients with large B cell lymphoma.

Mary Tagliaferri: In this study <unk> five is administered after autologous CD 19 car T cell therapy.

Mary Tagliaferri: We are concluding treatment for the patients randomized in our study, and we have now observed, in a third trial, the same re-expansion phenomenon of CAR T-cells following Nektar 255 treatment in these patients. And we look forward to presenting the full data set from this study at a future medical meeting. This compounding effect has the potential to extend beyond CAR T cell therapy. We continue to collaborate with AbleZeta, a leading cell therapy company, to evaluate Nektar 255 in combination with their tumor-infiltrating lymphocytes, or TILs, in an ongoing Phase I clinical trial in patients with advanced non-small cell lung cancer who do not respond to anti-PD-1 therapy.

Mary Tagliaferri: We are concluding treatment of the patients randomized in our study.

Mary Tagliaferri: And we have now observed in a third trial. The same re expansion phenomenon of car T cells. Following <unk> hundred five treatment in these patients and we look forward to presenting the full dataset from this study at a future medical meeting.

Mary Tagliaferri: This compounding effect has the potential to extend beyond car T cell therapies, we continue to collaborate with April's EDA, a leading cell therapy company to evaluate <unk> five in combination with their tumor infiltrating lymphocytes or til in an ongoing phase one clinical trial in patients with advanced non.

Mary Tagliaferri: Dr. Crystal McCall and Laurie Muffley also evaluated Nektar-255 to enhance the efficacy of Stanford's proprietary CD-1922 CAR T cell for B cell acute lymphoblastic leukemia. Stanford's data was published in blood last month. Compared to Stanford's control group, previously treated with the CAR T cell therapy, Nektar-255 when added to the CD-1922 CAR T cell therapy increased the 12 month relapsed free survival from 38% to 67%. The median RFS for the CAR T cell only cohort was 3.9 months and for the cohort treated with Nektar-255 and the proprietary CAR T cell therapy, it has not been reached with over 14.4 months of follow-up.

Mary Tagliaferri: Small cell lung cancer.

Speaker Change: Not respond to anti PD one therapy.

Mary Tagliaferri: Lastly, we are continuing to work with Merck KGA, who is conducting the Phase II Javelin Bladder Medley Study, which is evaluating Nektar 255 in combination with Provencia. Merck is projecting the first potential PFS analysis from this study around the end of this year. As a reminder, there are three separate combinations being evaluated in this study, each being compared separately to the Bovencio Monotherapy Arm. And with that, I will turn the call over to Sandra for a review of our financial guidance. Sandra. Thank you, Mary, and good afternoon, everyone. We ended the second quarter with $290.6 million in cash and investments, with no debt on our balance sheet.

Mary Tagliaferri: Lastly, we are continuing to work with Merck KDA, who is conducting the phase III javelin bladder medley study, which is evaluating <unk> five in combination with <unk>.

Mary Tagliaferri: Mercury is projecting the first potential PFS analysis from this study around the ended this year.

Mary Tagliaferri: As a reminder, there are three separate combinations being evaluated in this study each being compared separately to the both NCR monotherapy arm.

Mary Tagliaferri: And with that I will turn the call over to Sandra for a review of our financial guidance Sandra.

Sandra Gardiner: Our financial position remains strong, and we still plan to end 2024 with $200 million to $225 million in cash and investments. Our CACHE runway extends into the third quarter of 2026, which will take us through several key data milestones, including top-line data for both our Phase IIb ResPeg studies. I'll now briefly review our quarterly financials and reiterate our financial guidance for 2024. Our revenue was $23.5 million for the second quarter of 2024.

Sandra Gardiner: Thank you Mary and good afternoon, everyone. We ended the second quarter with $296 million in cash and investments with no debt on our balance sheet.

Mary Tagliaferri: So why does Nektar-255 work? We've now confirmed in patients the re-expansion of CAR T cells following Nektar-255 that we saw pre-clinically. In the Stanford study, we observed re-expansion of the CAR T cells in the CNS following Nektar-255 administration. At Fred Hutch, where they're combining Nektar-255 with Brianzi and patients with large B cell lymphoma, we have confirmed re-expansion of the CAR T cells after Nektar-255 as well, leading to a second peak in increase in AUC.

Sandra Gardiner: Our financial position remains strong and we still plan to end 2024, with 200 million to $225 million in cash and investments.

Speaker Change: Our cash runway extends into the third quarter of 2020, but she'll take us through several key data milestones, including top line data for both our phase <unk> study.

Sandra Gardiner: We still expect our revenue for the full year 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. For the second half of the year, we expect the remaining revenue to be weighted more heavily toward the fourth quarter. R&D expense for the second quarter of 2024 was $29.7 million, and we still anticipate full-year R&D expense to range between $120 million and $130 million. G&A expense for the second quarter of 2024 was $20.5 million. We continue to expect G&A expenses for the full year to be between $70 and $75 million.

Sandra Gardiner: I'll now briefly review, our quarterly financials and reiterate our financial guidance for 2024.

Mary Tagliaferri: An additional observation from Stanford suggests that Nektar-255 also influences lymphocyte trafficking to disease tissues. As you know, we've been running our own trial where we've enrolled 15 patients with large B cell lymphoma. In this study, Nektar-255 is administered after autologist CD-19 CAR T cell therapy. We are concluding treatment of the patients randomized in our study. And we have now observed in a third trial the same re-expansion phenomenon of CAR T cells following Nektar-255 treatment in these patients.

Sandra Gardiner: Lastly, our 2024 non-cash interest expense remains unchanged and is expected to be between $20 million and $25 million. In Q2, we recorded $13.3 million in non-cash impairment charges for our real estate obligations due to the continuous decline of the San Francisco life sciences and office real estate market. Our net loss for the second quarter of 2024 was $52.4 million, or $0.25 basic and diluted loss per share. Excluding the $13.3 million in non-cash impairment charges, our net loss on a non-GAAP basis was $39.1 million, or $0.19 basic and diluted loss per share.

Sandra Gardiner: Our revenue was $23 5 million for the second quarter of 2024.

Sandra Gardiner: We expect our revenue for the full year to be between $75 million and $85 million, which includes $55 million to $65 million and noncash royalties and 29% to $25 million in product sales.

Sandra Gardiner: For the second half of the year, we expect the remaining revenue to be weighted more heavily towards the fourth quarter.

Sandra Gardiner: R&D expense for the second quarter of 2024 was $29 7 million and we still anticipate full year R&D expense to range between $120 million and $130 million.

Mary Tagliaferri: And we look forward to presenting the full data set from this study at the future medical meeting. Foundation. This compounding effect has the potential to extend beyond CART cell therapies. We continue to collaborate with Abel Zeta, a leading cell therapy company, to evaluate Nektar 255 in combination with their tumor infiltrating lymphocytes or TILs. In an ongoing phase one clinical trial in patients with advanced non-small cell lung cancer, who do not respond to anti-PD1 therapies.

Sandra Gardiner: G&A expense for the second quarter of 2024 with $25 million. We continue to expect G&A expense for the full year to be between 70 and $75 million.

Sandra Gardiner: Lastly, our 2020 for noncash interest expense remains unchanged and is expected to be between 20 million and $25 million.

Mary Tagliaferri: Lastly, we are continuing to work with Merck KGA, who is conducting the phase two javelin bladder medley study, which is evaluating Nektar 255 in combination with the venceo. Merck is projecting the first potential PFF analysis from this study around the end of this year. As a reminder, there are three separate combinations being evaluated in this study, each being compared separately to the venceo monotherapy arm.

Sandra Gardiner: In Q2, we recorded $13 3 million in noncash impairment charges for our real estate obligations due to the continuous decline of the San Francisco Lifesciences and office real estate market.

Sandra Gardiner: Our net loss for the second quarter of 2024, with $52 4 million or <unk> 25, basic and diluted loss per share excluding the $13 3 million in noncash impairment charges net loss on a non-GAAP basis was $39 1 million or 19.

Sandra Gardiner: And with that, I will turn the call over to Sandra for a review of our financial guidance. Sandra? Thank you, Mary, and good afternoon everyone. We ended the second quarter with $290.6 million in cash and investments with no debt on our balance sheet. Our financial position remains strong, and we still plan to end 2024 with $200 million to $225 million in cash and investments. Our cash run rate extends into the third quarter of 2026, which will take us through several key data milestones, including top line data for both our phase two B ResPEG studies.

Sandra Gardiner: Basic and diluted loss per share.

Sandra Gardiner: And as I mentioned earlier, we still plan to end 2024 with $200 million to $225 million in cash and a runway that extends into the third quarter of 2026. And with that, I'll now open the call to questions. Crystal?

Sandra Gardiner: And as I mentioned earlier, we still plan to end 2024 with $290 million to $225 million in cash and a runway that extends into the third quarter of 2026.

Sandra Gardiner: And with that I'll now open the call for questions Crystal.

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.

Crystal: Thank you.

Crystal: A reminder to ask a question. Please press star one on your telephone and wait for your name to be announced to withdraw your question. Please press star one again.

Operator: In the interest of time, we do ask that you please limit yourselves 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 Oppenheimer. Your line is open. Oh, hey, congratulations on all the progress and thank you for taking our question. That Nektar 255 data in collaboration with Stanford looks great.

Speaker Change: In the interest of time, we do ask that you. Please limit yourself to one question at this time please.

Sandra Gardiner: I'll now briefly review our quarterly financials and reiterate our financial guidance for 2024. Our revenue was $23.5 million for the second quarter of 2024. We still expect our revenue for the full year 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. For the second half of the year, we expect the remaining revenue to be weighted more heavily towards the fourth quarter.

Speaker Change: Please standby, while we compile the Q&A roster.

Operator: And our first question will come from Jay Olson from Oppenheimer. Your line is open.

Operator: Oh, Hey, congrats on all the progress and thank you for taking our question.

Jay Olson: That Nektar 255 data in collaboration with Stanford looks great can you talk about the next steps and if there is potential synergy for Nektar two five with car T for autoimmune diseases. Thank you.

Jay Olson: Can you talk about the next steps and if there's potential synergy for Nektar 255 with CAR-T for autoimmune diseases? Thank you. Jay-Z, do you want to take that call, that question?

Jay Olson: Jason you want to take that call.

Sandra Gardiner: R&D expense for the second quarter of 2024 was $29.7 million, and we still anticipate full year R&D expense to range between $120 million and $130 million. GNA expense for the second quarter of 2024 was $20.5 million. We continue to expect GNA expense for the full year to be between $70 and $75 million. Lastly, our 2024 non-cash interest expense remains unchanged and is expected to be between $20 million and $25 million. In Q2, we recorded $13.3 million in non-cash impairment charges for our real estate obligations due to the continuous decline of the San Francisco life sciences and office real estate markets.

Jay-Z: A question.

Jonathan Zalevsky: Sure, yeah, so thanks Jay for the question. So I'll start off, and maybe Mary you can add a little bit of color to that, but I think that that study with Stanford was a very important study Jay for us because it was the first time that treatment was evaluated very close to the time of the administration of the car, like there was just a short offset of a couple of weeks after the car was delivered before.

Jay-Z: Sure, yes, so thanks.

Jonathan Zalevsky: Thanks, Jay for the question, so I'll start off and maybe Mary you can add also a little bit of color on to that but I think that study was effort was a very important study for us because.

Jonathan Zalevsky: It was the first time that the treatment was evaluated very close to the time of the administration of the car. There was just the short offset of a couple of weeks. After the car was delivered before.

Jonathan Zalevsky: There has been a significant impact on the brain, as well. We study different brain features, for the different functional languages it's using, a really large amount of car moving into the CNS, really impacting positive patients. And then, of course, the duration of effect, as Mary described, in terms of the really extent of efficacy that was observed relative to what's known historically for that car, where the durability of the effect, Mary, maybe if you could talk medically about adding some more of the context and how it fits together with the other studies that are ongoing. Yeah, hi Jay. This is Mary.

Speaker Change: Two five is treated.

Mary Tagliaferri: We observed some very exciting findings were published by Stanford Group.

Mary Tagliaferri: Those included changes in the cellular <unk> changes in the migration, including into one patient that had in CNS disease.

Speaker Change: A really large amount of car moving into the CNS really impacting positively the patient and then of course the duration of effect as Mary described in terms of the extent of efficacy that was observed relative to what's known historically for that car or durability of the effect.

Sandra Gardiner: Our net loss for the second quarter of 2024 was $52.4 million or $25 cents basic and diluted loss per share. Excluding the $13.3 million in non-cash impairment charges, net loss on a non-gap basis was $39.1 million or $19 cents basic and diluted loss per share, and, as I mentioned earlier, we still plan to end 2024 with $200,000,000 to $225,000,000 in cash and a runway that extends into the third quarter of 2026.

Mary Tagliaferri: Maybe if you could talk medically about adding some more of the context and how it fits together with the other studies that are ongoing.

Mary Tagliaferri: You know, what we were really excited about is that in three different studies now, we wanted to look at the safety, the feasibility, and the efficacy so we could hone in on the recommended phase three dose. And across all three studies, we have not seen any dose-limiting toxicity. We see a consistent safety profile that's highly favorable to patients, and as you can imagine, that's remarkable when you're combining a drug with CAR T cell treatments.

Jonathan Zalevsky: Yes, Hi, Jay this is Mary.

Mary Tagliaferri: We were really excited about is in three different studies now we wanted to look at the safety the feasibility and the efficacy. So we could hone in on the recommended phase II dose and across all three studies, we have not seen a dose limiting toxicity, we see a consistent safety profile.

Unknown Executive: And with that, I'll now open the call for questions. Crystal, thank you. As a reminder to ask a question, please press star one on your telephone and wait for your name to be announced. To withdraw your question, please press star one on again. In the interest of time, we do ask that you please limit yourselves to one question at this time. Please stand by when we compile the Q&A roster.

Mary Tagliaferri: Hi, highly favorable to patients and as you can imagine that's remarkable when youre, combining the drug with car T cell treatment.

Mary Tagliaferri: It's also feasible to not only dose this drug in the adjuvant setting right after patients receive CAR T cells, but they continue to receive Nektar 255 every three weeks, which is also highly favorable to patients. And when we think about next steps and where we can go, I believe with the combination and aggregate of the data from the three trials, we have identified our recommended phase three dose. The other thing, the other place where we're developing the drug, as I mentioned, is in combination with TIL therapy.

Mary Tagliaferri: It's also feasible to not only dose this drug in the adjuvant setting right after.

Mary Tagliaferri: Patients receive car T cells, but they continue to receive <unk> <unk> five.

Jay Olson: And our first question will come from Jay Olson from Oppenheimer. Your line is open. Oh, hey, congrats on all the progress. And thank you for taking our question. That Nektar 255 data and collaboration with Stanford looks great. Can you talk about the next steps and if there's potential synergy for Nektar 255 with CAR-T for autoimmune diseases? Thank you. Jay, do you want to take that call? That question? Sure. Yeah. So thanks, Jay, for the question.

Mary Tagliaferri: Every three weeks, which is also highly favorable to patients and when we think about next steps and where we can go I believe with the <unk>.

Mary Tagliaferri: Combination in aggregate the data from the three trials, we have identified a recommended phase II dose.

Mary Tagliaferri: And as you know, right now, Iovance combines their TIL therapy with high-dose IL-2, and that's really fraught with error because it's very difficult to tolerate high-dose IL-2. Patients have to be in the inpatient setting to receive high-dose IL-2, and certainly, in the area of non-small cell lung cancer, patients who actually receive TILs and high-dose IL-2 in a very small study for patients, you know, there were two deaths in that trial conducted by Dr. Scott Antonia and published in Nature.

Mary Tagliaferri: The other thing that.

Speaker Change: The other place where were developed.

Mary Tagliaferri: Developing a drug as I mentioned is in combination with til therapy, and as you know right now I events combines their til therapy with high dose IL, two and Thats really fraught with error because there are it's very difficult to tolerate high dose IL two patients have to be in.

Jay Olson: So I'll start off and maybe Mary, you can add also a little bit of color onto that. But I think that study was Stanford was a very important study, Jay, for us because it was the first time that treatment was evaluated very close to the time of administration of the car. There was just a short offset of a couple of weeks after the car was delivered before Nektar 255 was treated. And we observed some very exciting findings that were published by the Stanford group.

Mary Tagliaferri: On the inpatient setting.

Mary Tagliaferri: To receive high dose IL, two and certainly in the area of non small cell lung cancer patients to actually receive tills and high dose IL two in a very small study.

Mary Tagliaferri: Patients there were two deaths in that trial conducted by Dr. Scott Antonia and published in nature, and so I think that the opportunities here are very broad in the area of cellular therapy both.

Jay Olson: Those included changes in the cellularity, changes in the migration, including into one patient that had a CNS disease with a really large amount of car moving into the CNS, really impacting positively that patient. And then of course the duration of a fact has Mary described in terms of the really extent of efficacy that was observed relative to what's known historically for that car, or durability of the effect weight. Mary, maybe if you could talk medically about adding some more of the context and how it fits together with the other studies that are ongoing.

Mary Tagliaferri: And so I think that the opportunities here are very broad in the area of cellular therapy, both with autologous and allogeneic and CAR T cells as well as TILs. And then again, we're awaiting data in combination with a checkpoint inhibitor, and if the data proves to be compelling and strong, there's, you know, an additional indication for combining with checkpoint inhibitors. And I would add to that that, of course, we've shifted over to immune disease and inflammation.

Tom: Tom I guess, an allogeneic and car T cells as well as tills and then again.

Mary Tagliaferri: Waving the data in combination with a checkpoint inhibitor and the data.

Mary Tagliaferri: Data prove to be.

Mary Tagliaferri: Appellant and strong there is an additional indication for combining with checkpoint inhibitors.

Mary Tagliaferri: I would add to that that of course, we've shifted over to.

Mary Tagliaferri: But clearly, we have data with IL-15 that demonstrates its potential, how there's a great potential for it to be used in combination with cell therapies. And I think that's going to, that may very well play an important role in the future of cell therapy. So we're talking to a number of companies, and I do think we can find an important collaboration. Super helpful, thank you so much. Jay, this is Jay Z.

Mary Tagliaferri: Immune disease and inflammation.

Mary Tagliaferri: But clearly we have data with IL 15 that demonstrates how its potential.

Jay Olson: Yeah, hi, Jay. This is Mary. You know, what we were really excited about is in three different studies. Now we wanted to look at the safety, the feasibility, and the efficacy so we could hone in on the recommended phase three dose. And across all three studies, we have not seen a dose limiting toxicity. We see a consistent safety profile that's highly favorable to patients. And as you can imagine, that's remarkable when you're combining a drug with CAR T cell treatments.

Mary Tagliaferri: Great potential for it to be used in combination with cell therapies, and I think thats going to that may very well play an important role on the future of cell therapy. So we're talking to a number of companies and I do I do think we can find a important collaborations there.

Mary Tagliaferri: Super helpful. Thank you so much.

Jonathan Zalevsky: Your other question about autoimmune disease is a really good question. It's kind of a theoretical question at this time, but based on what we saw in the data and were published at Stanford, as Mary described, which from a totality of both safety as well as pharmacodynamic effects would make it feasible to also add this in the setting of autoimmune disease, you know, car cell therapy use. We're focused on oncology now, but theoretically, from first principles, it should be possible. Okay, great. Really impressive data. Thank you. Thank you. Our next question will come from Chris Shibutani of Goldman Sachs. Your line is open. Hi, this is Kevin on behalf of Chris.

Mary Tagliaferri: And Jay This is Jay Z. Your other question about autoimmune disease.

Speaker Change: It's a really good question.

Jay Olson: It's also feasible to not only dose this drug in the adjuvant setting right after patients receive CAR T cells, but they continue to receive Nektar 255 every three weeks, which is also highly favorable to patients. And when we think about next steps and where we can go, I believe with the combination and aggregate of the data from the three trials, we have identified our recommended phase three dose. The other thing that the other place where we're developing the drug, as I mentioned, is in combination with TIL therapy.

Jonathan Zalevsky: Kind of a theoretical question at this time, but based on what we saw in the data published at Stanford as Mary described which from a totality of both safety as well as Pharmacodynamic effects.

Speaker Change: Would make it feasible to also add this in the setting of autoimmune disease cart car.

Speaker Change: Our cell therapy use.

Jonathan Zalevsky: Focused on oncology now, but theoretically first principles that should be possible.

Kevin: Okay, great really impressive data. Thank you again.

Kevin: Thank you.

Speaker Change: Our next question will come from Chris <unk> from Goldman Sachs. Your line is open.

Jay Olson: And as you know, right now, IOVANCE combines their TIL therapy with high dose IL-2. And that's really fought with error because it's very difficult to tolerate high dose IL-2. Patients have to be in the inpatient setting to receive high dose IL-2, and certainly in the area of non-small cell lung cancer, patients who actually receive TILs in high dose IL-2, in a very small study of recommendations. You know, there were two deaths in that trial conducted by Dr. Scott and Tonya and published in Nature.

Chris Shibutani: Thanks for taking our, Just wanted to focus on alopecia, for house keepers. I know that enrollment is on track, thanks to www.zeoranger.co.uk. The primary completion is the same on clinicaltrials.gov, but just wondering about the timeline to mid-25 versus first half, and then also, you know, understanding the value proposition there versus JAK inhibitors, which are approved; it makes sense with the safety profile. Are you going to want or need to match the efficacy of JAK inhibitors now? Why don't I let Mary answer your question?

Jonathan Zalevsky: Hi, This is Kevin on for Chris Thanks for taking my question and congrats on the progress.

Chris Shibutani: Just wanted to focus on alopecia.

Speaker Change: They're so just for housekeeping I know that.

Mary Tagliaferri: Enrollment is on track and there is the <unk>.

Chris Shibutani: Completion is the same on clinical trials dot Gov, but just wondering about the timeline to mid 25 versus first half and then also.

Speaker Change: Understanding the value proposition there versus JAK inhibitors, which are approved.

Jay Olson: And so, I think that the opportunities here are very broad in the area of cellular therapy, both you with autologous and allogeneic and CAR T cells as well as TILs. And then again, you know, we're awaiting the data and combination with the checkpoint inhibitor. And you know, it's the data proved to be compelling and strong. There's an additional indication for combining with checkpoint inhibitors, and I would add to that, that of course we've shifted over to immune disease and inflammation, but clearly we have data with IL-15 that demonstrates how it's potential, how there's a great potential for it to be used in combination with cell therapies.

Mary Tagliaferri: It makes sense with the safety profile, how are you talking about efficacy.

Speaker Change: Are you going to want or need to match the efficacy of JAK inhibitors in alopecia. Thanks.

Speaker Change: One I'll, let Mary answer to your question on that.

Mary Tagliaferri: Yep, thank you, Howard. And Kevin, yes, you know, we started the alopecia areata study in March. And, you know, we are on track. And we will have top-line data based on our enrollment today in mid-2025.

Mary Tagliaferri: Thank you Howard and Kevin Yes, we started the alopecia area to study in March and we are on track and we do we will have top line data based on our enrollment today in mid 2025, and I think you asked a great question.

Speaker Change: What does success look like in alopecia, Areata and what's the bar.

Mary Tagliaferri: For us and as you know JAK inhibitors are efficacious for alopecia Areata.

Mary Tagliaferri: And I think, you know, you ask a great question about what success looks like in alopecia areata and what the bar for us is. And, you know, as you know, JAK inhibitors are efficacious in alopecia areata, and the clinical trials that were conducted had a salt endpoint at 36 weeks of treatment.

Speaker Change: The clinical trials that were conducted had asphalt.

Jay Olson: And I think that's going to, that may very well play an important role on the future of cell therapies, so we're talking to a number of companies. And I do, I do think we can find an important collaborative collaboration now. Super helpful, thank you so much. And Jay, this is Jay's a year other question about auto immune disease. It's, it's a, it's a really good question. It's a kind of a theoretical question at this time, but based on what we saw in the data and we've published it.

Mary Tagliaferri: Endpoint at 36 weeks of treatment.

Speaker Change: Before I go into the efficacy data there are two main issues that the dermatologist share with US one is there's absolutely no durability of effect with the JAK inhibitor in patients immediately start to lose their hair when they stop taking the JAK inhibitor and that her losses very rapid the circa.

Mary Tagliaferri: And before I go into the efficacy data, you know, there are two main issues that dermatologists share with us. One is, you know, there's absolutely no durability of effect with a JAK inhibitor, and patients immediately start to lose their hair when they stop taking the JAK inhibitor. And that hair loss is very rapid.

Jay Olson: I'd stand for Mary described, which from a totality of both safety as well as pharmacodynamic effects, would make it feasible to also add this in the setting of auto immune disease, car, you know, car cell therapy use. We're focused on oncology now, but theoretically, for us principals, it should be possible. Okay, great, really impressive data. Thank you.

Mary Tagliaferri: And of course is that 80% of patients who have alopecia area other younger than age 40, and nobody really knows what kind of risks a JAK inhibitor with <unk>, obviously, the black box warnings, therefore serious heart related events like heart attacks and stroke and blood clots in thrombosis.

Mary Tagliaferri: The second, of course, is that 80% of patients who have alopecia areata are younger than age 40. And nobody really knows what kind of risks, you know, a JAK inhibitor would pose. Obviously, you know, the black box warnings are for serious heart-related events like heart attacks and stroke and blood clots and thrombosis and cancer and serious infections. So there is just a general worry about exposing a patient to a JAK inhibitor for their entire life. So in terms of terms—so those are the problem statements.

Mary Tagliaferri: Cancer in serious infections. So there is just the general worry about exposing a patient to a JAK inhibitor for their entire life.

Mary Tagliaferri: Our next question will come from Chris Shabitani from Goldman Sachs. Your line is open. Hi, this is Kevin on for Chris. Thanks for taking our question and congrats on the progress. Just wanted to focus on alopecia there. So just for for housekeeping, I know that, you know, enrollment is on track, and there's the primary completion is, is the same on clinical trials.gov, but just wondering about the timeline to mid 25 versus first half.

Mary Tagliaferri: And in terms of efficacy, we believe similar efficacy to, say, paracetamol would establish a differentiated compound because, one, we don't have an association, you know, certainly with our 600 patients we've treated to date with these serious side effects. And, number two, we believe based on the phase 1B in atopic dermatitis that there's a potential for a remittive effect or a maintenance regimen that, you know, wouldn't be daily like you see with a JAK inhibitor, but rather we could potentially dose patients after a 36-week induction period with a frequency that's longer than every two weeks in the maintenance phase.

Mary Tagliaferri: In terms. So those are the problem statement and in terms of efficacy, we believe similar efficacy to say parasitic nib.

Mary Tagliaferri: Would establish a differentiated compound because one we're not we don't have an association certainly with our 600 patients we've treated to date with the serious side effects and number two we believe based on the phase one b in atopic dermatitis that theres a potential for <unk>.

Mary Tagliaferri: And then also, you know, understand the value proposition there versus Jack inhibitors, which are approved. It makes sense with with the safety profile. How are you talking about efficacy? Are you, are you going to want or need to match the efficacy of Jack inhibitors in alopecia? Thanks. Want to let Mary answer your question on that.

Mary Tagliaferri: The fact or a maintenance regimen that wouldn't be daily like you see with a JAK inhibitor, but rather we could potentially dose patients. After 36 week induction period with a frequency that's longer than every two weeks in the maintenance phase.

Mary Tagliaferri: You know, we've spoken a lot to doctors about even, you know, an induction time period, and, you know, their belief is, it doesn't even matter if it takes these patients a year to grow their hair back.

Mary Tagliaferri: We've spoken a lot to doctors about even an induction time period.

Mary Tagliaferri: Yep. Thank you, Howard. And Kevin, yes, you know, we started the alopecia area to study in March. And, you know, we are on track and we do, we will have top line data based on our enrollment today in mid 2025. And I think, you know, you have to great question, you know, which is what the success looks like in alopecia area, and what's the bar for us. And, you know, as you know, Jack inhibitors are efficacious for alopecia area.

Mary Tagliaferri: Our belief is it doesn't even matter if it takes these patients a year to grow their hair back if you actually have a biologic that day.

Mary Tagliaferri: That would provide a remitted to benefit and not the associated with so many side effects that would be critically important and then specifically for the phase III trials with parasitic nib.

Mary Tagliaferri: The salt change at 36 weeks.

Mary Tagliaferri: Was less than 10% for placebo, which makes it nice you can run smaller size studies, because the placebo effect as low as approximately 30% for the low dose of <unk>, two milligram per day dose and about 49%.

Mary Tagliaferri: If you actually have a biologic that they—you know, that would provide a remittive benefit and not be associated with so many side effects, that would be critically important. And then specifically for the phase 3 trials with baricitinib, the salt change at 36 weeks was less than 10% for placebo, which is nice. You can run smaller-sized studies because the placebo effect is low and is approximately 30% for the low dose of baricitinib, the 2 milligrams per day dose, and about 49% salt reduction for the high dose of 4 milligrams.

Mary Tagliaferri: And, you know, the clinical trials that were conducted had a fault endpoint at 36 weeks of treatment. And before I go into the efficacy data, you know, there are two main issues that the dermatologist share with us. One is, you know, there's absolutely no durability of a fact with a Jack inhibitor and patients immediately start to lose their hair when they stop taking the Jack inhibitor and that hair loss is very rapid.

Mary Tagliaferri: Salt reduction for the high dose at four milligrams.

Roger Song: Great. Thank you. And our next question will come from Roger Song from Jeffries. Your line is open.

Speaker Change: Great. Thank you.

Roger Song: Thank you.

Speaker Change: And our next question will come from Roger song from Jefferies. Your line is open.

Kambiz Pashneh: Hi, this is Kambiz on behalf of Roger. Can you provide us with an update on your litigation with Lily? Yeah, sure. Look, we're still having discussions with Lily, as you know, and as you can see from the excellent phase 1b data, clearly a mathematical mistake was made. And the data is somewhat compelling. After we corrected for that math error that we discovered, we're still having discussions with Lily; we had mediation, and the court has ordered us to continue mediation.

Mary Tagliaferri: The second, of course, is that 80% of patients who have alopecia area are younger than age 40. And nobody really knows what kind of risks, you know, Jack inhibitor would pose. Obviously, you know, the black box warnings are for, you know, serious heart related events like heart attacks and stroke and blood clots and from both is in cancer and serious infections. So there is just the general, you know, worry about exposing a patient to a Jack inhibitor for their entire life.

Speaker Change: Hi, This is <unk> on for Roger.

Speaker Change: Can you provide us an update on your litigation with Lilly.

Speaker Change: Yes sure.

Kambiz Pashneh: Look we're still we're still having discussions with Lilly as you know and as you can see from.

Kambiz Pashneh: The excellent phase <unk> data.

Kambiz Pashneh: Clearly a mathematical mistake was made.

Kambiz Pashneh: And the data is somewhat compelling.

Kambiz Pashneh: After we corrected for that matter that we discovered.

Mary Tagliaferri: So in terms, so those are the problem statements. And in terms of efficacy, we believe similar efficacy to say paracetinib would establish a differentiated compound because one we're not associated with, we don't have an association, you know, certainly with our 600 patients, we've treated to date with these serious side effects. And number two, we believe based on the phase one, be in a topic dermatitis that there's a potential for a remittive effect or a maintenance regimen that, you know, wouldn't be daily like you see with a Jack inhibitor, but rather we could potentially dose patients after a 36 week induction period with a frequency that's longer than every two weeks in the maintenance phase.

Kambiz Pashneh: We're still having discussions with Lilly we had a mediation.

Kambiz Pashneh: The court has ordered us to continue mediation and we expect to do that in the near future. So obviously I can't spend a lot of time talked I can't spend I can't discuss in detail on ongoing litigation, but I can I can say that we are.

Howard Robin: And we expect to do that in the near future. So obviously, I can't spend a lot of time talking, I can't spend, I can't discuss in detail an ongoing litigation. But I can, I can say that we firmly believe that we've been harmed by their behavior. And consequently, we will continue mediation. Thank you. And our next question will come from Andy Shea of William Blair. Your line is now open.

Howard Robin: We believe that we've been harmed by their behavior and consequently, we will continue mediation with them.

Andy Shea: Thank you.

Speaker Change: And our next question will come from Andy Shay from William Blair. Your line is now open.

Andy Shea: Hi, thanks for taking our question. So the book paper is pretty, pretty intriguing. I'm curious about your interpretation of the historical controls.

Andy Shea: Alright, thanks for taking our question.

Mary Tagliaferri: You know, we've spoken a lot to doctors about even, you know, an induction time period and, you know, their belief is, you know, it doesn't even matter if it takes these patients a year to grow their hair back if you actually have a, a biologic that they, you know, that would provide a remittive benefit and not be associated with so many side effects. That would be critically important. And then specifically for the phase three trials with paracetinib, you know, the, the salt change at 36 weeks was less than 10% for placebo, which makes it nice.

Speaker Change: Paper is pretty pretty intriguing.

Speaker Change: I'm curious about your interpretation of the historical controls.

Andy Shea: Just, you know, given the non-randomized nature of the study, there's some, you know, kind of push and pulls regarding baseline patient characteristics. It seems like, you know, the historical control might be a little bit more heavily pretreated, the dosing is a little bit lower. So I'm just curious, just kind of looking at the baseline characteristics, how would you characterize the similarities and differences, how alike are those two populations?

Speaker Change: Given the.

Andy Shea: Non randomized nature.

Andy Shea: Eddie.

Speaker Change: There is some.

Andy Shea: Kind of pushing pause regarding baseline patient characteristics it seems like.

Andy Shea: Historical.

Andy Shea: Control might be a little bit.

Speaker Change: More heavily pre treated <unk>.

Andy Shea: <unk> is a little bit lower.

Mary Tagliaferri: You can run smaller side studies because the placebo effect is low is approximately 30% for the low dose of paracetinib, the two milligram per day dose and about 49% salt reduction for the high dose of four milligrams. Great. Thank you.

Andy Shea: So I'm just curious just kind of looking at the.

Andy Shea: The baseline characteristic how would you characterize the similarities and differences.

Andy Shea: Like are those two populations. Thank you Mary Mary could use its a good question Mary could you give some insight into the Stanford historical controls.

Mary Tagliaferri: Thank you. Mary, could you, it's a good question, Mary, could you give some insight into the Stanford Historical Control Center? Yes. So, really important, Andy, so first of all, I just want to talk a little bit about the person who conducted this trial. You know, Crystal McCall is the founding director of the Stanford Center for Cancer Cell Therapy, and she's really, you know, one of the godmothers of cell therapy.

Mary Tagliaferri: And if you look at Crystal's Nature paper, she actually dosed 17 patients, you know, not eight that are used as the control patients for this study. So she actually selected patients that had comparable baseline characteristics traits to be matched with the patients of this second study. So you can imagine, you know, with her academic background and her vast experience with treating ALL patients, she was very, very mindful of these baseline characteristics, as well as the burden of disease. So she very carefully selected the control group, which is a subset of the total number of patients she originally reported upon in Nature.

Mary Tagliaferri: Yes.

Mary Tagliaferri: So really importantly, Andy so first of all I just wanted to talk a little bit about the person who conducted this trial crystal Mccall's the founding director of the Stanford Center for cancer cell therapy, and she is really one of the godmothers.

Roger Song: And our next question will come from Roger Song from Jeffries. Your line is open.

Howard Robin: Hi, it's Kambizan Farajar. Can you provide us an update on your litigation with Lily? Yeah, sure. Look, we're still having discussions with Lily, as you know. And as you can see from the excellent phase 1B data, the clearly a mathematical mistake was made and the data is somewhat compelling after we corrected for that math error that we discovered. We're still having discussions with Lily. We had a mediation. The court has ordered us to continue mediation and we expect to do that in the near future.

Mary Tagliaferri: Yes.

Mary Tagliaferri: Cell therapy, and if you look at Crystal nature paper, she actually had dosed 17 patients.

Speaker Change: Not a feather used as the control.

Mary Tagliaferri: And for this study so she actually selected patients that had comparable baseline characteristic traits to be matched with the patients of this second study. So you can imagine.

Mary Tagliaferri: Her academic background and her vast experience with treating AML patients. She was very very mindful of these baseline characteristic traits as well as burden of disease. So she she very carefully actually selected the control group, which is a subset.

Howard Robin: So obviously I can't spend a lot of time. I can't spend. I can't discuss in detail, not going litigation, but I can I can say that we are we firmly believe that we've been harmed by their behavior and consequently we will continue mediation with it. Thank you.

Speaker Change: The total number of patients. He originally reported a pod in nature.

Mary Tagliaferri: That's helpful. Thank you. Thank you. And as a reminder, to ask a question, please press star 1 1. And again, to ask a question, that's star 1 1.

Speaker Change: That's helpful. Thank you.

Speaker Change: Thank you.

Andy Shea: And our next question will come from Andy Shea from William Blair. Your line is now open. Hi, thanks for taking our question. So the bus papers are pretty, pretty intriguing. I'm curious about your interpretation of the historical clinicals just given the non randomized nature of the study. There's some kind of push and pause regarding basic patient characteristics. It seems like, you know, the historical control might be a little bit more heavily pre-treated.

Mary Tagliaferri: And as a reminder to ask a question. Please press star one one and again to ask a question that is star one line one moment for our next question. Please.

Operator: One moment for our next question, please. Our next question will come from Arthur He from H.C. Wainwright. Your line is open. Hey, good afternoon, Howard team. I just had a quick question on the 165.

Speaker Change: Our next question will come from Arthur Heat from H C. Wainwright Your line is open.

Arthur He: Hey, good afternoon team.

Arthur He: Had a quick question on the <unk>.

Operator: 165.

Arthur He: Obviously, it's very interesting preclinical data. Maybe, Jay-Z, could you give us more color on the 165, the binding to the T-regs receptor, but not the other ones on the CD4 T cell or monocyte, because we know the TNFR2 is also expressed on those two cells. Just curious about the mechanism of action there.

Operator: Sure.

Arthur He: Obviously very interesting preclinical data.

Speaker Change: Maybe could you give us more color on the <unk>.

Arthur He: 165.

Jay-Z: Binding to the T regs, but not the other ones on the CD four T cell or a month, because we know that.

Andy Shea: The dosing is a little bit lower. So I'm just curious, it's kind of looking at the, you know, the baseline characteristics. How would you characterize the similarities and differences? How would like are those two populations? Thank you.

Arthur He: Fr.

Speaker Change: <unk> also expressed on those two sales just curious about the Mexican action yet.

Speaker Change: Thanks, Sharon Thanks, Arthur Thanks for the question, yes, so one of the things that we found is that our antibody definitely has.

Jonathan Zalevsky: Thanks. Sure. Thanks, Arthur. Thanks for the question. Yeah, so one of the things that we found is that our antibody definitely has some form of conformational selectivity in terms of the epitope that it recognizes. And in that EULAR poster, there was a panel that showed binding to two different forms of TNFR2. So you know that TNFR2, primarily it's a transmembrane receptor, like.., and to the shelf. And the antibody bound the surface receptor with much, much higher affinity, much more greatly, and it barely interacted with the shed form. So it indicates to us that there's a conformational, you know, specificity, or conformational component to the binding.

Mary Tagliaferri: Mary could you, it's a good question. Mary, could you give some insight into the Stanford historical controls? Yes. So really importantly, Andy, so first of all, I just want to talk a little bit about the person who conducted this trial. You know, Crystal McCall is the founding director of the Stanford Center for Cancer Self Therapy and she's really, you know, one of the Godmothers of, you know, self therapy. And if you look at Crystal nature paper, she actually had dose 17 patients, you know, not eight that are used as the control patients in for this study.

Jonathan Zalevsky: Some form of conformational selectivity in terms of the epitope that it recognizes and in that Youll are poster there was a panel.

Speaker Change: <unk> binding to two different forms of TNF far too so.

Jonathan Zalevsky: So you know the TNF are two primarily its a transmembrane receptor like TNF.

Jonathan Zalevsky: TNF receptor, but it can also be shed.

Jonathan Zalevsky: Domain shutting through normal metallic proteases items that the team <unk> TNF or two and then that liberate the shed form that can circulate it but.

Mary Tagliaferri: So she actually selected patients that had comparable baseline characteristic traits to be matched with the patients of this second study. So you can imagine, you know, with her academic background and her vast experience with treating ALL patients, she was very, very mindful of these baseline characteristic traits as well as a burden of disease. So she very carefully actually selected the control group, which is a subset of the total number of patients she originally reported upon in nature.

Jonathan Zalevsky: And so we tested the binding of our antibody to the surface receptor into the shed form.

Jonathan Zalevsky: Antibody bound the surface receptor much much higher affinity much more greatly and it's barely interacted with the shed forum. So it indicates to us that there is a conformational specificity or conformational component to the binding and to to assess that we're actually doing a lot of biophysical studies.

Jonathan Zalevsky: And to assess that, we're actually doing a lot of biophysical studies right now. So we're, first of all, we're mapping the epitope and the peritope of the antibodies. So those experiments are ongoing. And we're also doing structural modeling using, you know, some of the, Structural approaches that you can do computationally to assess the epitope and then we aim to put all that together We might even possibly go as far as solving the crystal structure of the antibody But our hypothesis, you know right now is that it's very conformational and that's why we see cellular Selectivity because while you're right the receptors express of multiple cell types Its function is not the same on multiple cell types and also the the trough Components that signal intracellularly are also not, Transcripts provided by Transcription Outsourcing, LLC.

Jonathan Zalevsky: Right now.

Jonathan Zalevsky: First of all we're mapping the epitope and the parity of the antibodies to those experiments are ongoing and we're also doing structural modeling.

Unknown Executive: That's helpful. Thank you. And as a reminder, to ask a question, please press star 1-1. And again, to ask a question that's star 1-1. One moment for our next question, please.

Jonathan Zalevsky: Using some of the.

Jonathan Zalevsky: Structural approaches that you could do computationally to assess the epitope.

Jonathan Zalevsky: And then we aim to put all that together, we might even possibly goes as far as the solving the crystal structure of the antibody, but our hypothesis right now is that it's very conformational and Thats why we see cellular selectivity because while you are right. The receptors expressed on multiple cell types. Its function is not the same multiple cell.

Jay Z: Our next question will come from Arthur Heath from H.C. Wainwright. Your line is open. Hey, good afternoon, Howard team. I just had a quick question on the 1-6-5. Obviously, it's a very interesting three-connected data. But maybe, Jay, could you give us more color on the 1-6-5 that's binding to the T-rags, but not the other ones on the city 40s or a month, because we know the team FR-2 also expressed on those two sales.

Jonathan Zalevsky: Types and also the traffic components that signal intra cellular we are also not the same across those cell types and we think that that's the reason.

Howard Robin: But yeah, we're very excited because it's not like a typical finding, as you can imagine, for an antibody, which is why we think this is such an innovative idea. Thanks, Jay. Thank you. And I am showing no further questions on the phone lines, and I'd like to turn the conference back over to Howard Robin for any closing remarks. Okay, well, thank you everyone for joining us today. And as you can see, we're making excellent progress in our strategic plan to focus Nektar's efforts on Immunology and Inflammation.

Jonathan Zalevsky: But yes, we're very excited because it's not.

Howard Robin: Like a typical finding as you can imagine for an antibody which is why we think this is such an innovative molecule.

And we're advancing multiple novel and innovative therapies in and towards the clinic. So I wanna thank all of our employees for their hard work, and I wanna thank our investors for their continued support, and please stay tuned. Thanks for joining us today. Thank you. This concludes today's conference call. Thank you for your participation. You may now disconnect. Everyone have a wonderful day.

Speaker Change: Oh, great. Thanks, Ed.

Howard Robin: Sure.

Howard Robin: Thank you.

Howard Robin: And I am showing no further questions on the phone lines I'd now like to turn the conference back over to Howard Robin for any closing remarks.

Jay Z: Just curious about the necking action myth. Thanks. Thank you, Arthur. Thanks for the question. Yes, so one of the things that we found is that our antibody definitely has some form of conformational selectivity in terms of the epitope that it recognizes. And in that ULAR poster, there was a panel that showed binding to two different forms of TNFR-2. So you know that TNFR-2, primarily it's a transmembrane receptor, like, you know, TNFR-2, but it can also be shed by ectodomane shedding through normal metallic proteases, atoms that the team cleaves TNFR-2, and then that liberates the shed form that conserculated the blood.

Speaker Change: Okay, well. Thank you everyone for joining us today and as you can see we're making excellent progress in our strategic plan to focus <unk> efforts on immunology and inflammation and we are advancing multiple novel and innovative therapies inventory the clinics.

Jay Z: And so we tested the binding of our antibody to the surface receptor and to the shed form. And the antibody bound the surface receptor much, much higher affinity, much more greatly, and is barely interacted with the shed form. So it indicates to us that that there's a conformational, you know, specificity or a conformational component to the binding. And to assess that, we're actually doing a lot of biophysical studies right now. So we're, first of all, we're mapping the epitope and the peritope of the antibodies to those experiments are ongoing.

Jay Z: And we're also doing structural modeling using, you know, some of the structural approaches that you can do computationally to assess the epitope. And then we aim to put all that together. We might even possibly go as far as solving the crystal structure of the antibody. But our hypothesis, you know, right now is that it's very conformational. And that's why we see cellular selectivity because while you're right, the receptors express the multiple cell types.

Howard Robin: I want to thank all of our employees for their hard work and I want to thank our investors for their continued support and please stay tuned thanks for joining us today.

Howard Robin: Thank you. This concludes today's conference call. Thank you for your participation you may now disconnect everyone have a wonderful day.

Jay Z: Its function is not the same on multiple cell types. And also the, the draft components that signal intracellularly are also not the same across those cell types. And we think that's that's the reason. But yeah, we're very excited because that's, it's not like a typical farting as you can imagine for an antibody, which is why, why we think this is such an innovative model. Oh great, thanks to you too. Thank you.

Unknown Executive: and I am showing no further questions on the phone lines and I'd like to turn the conference back over to Howard Robin for any closing remarks.

Howard Robin: Okay well thank you everyone for joining us today and as you can see we're making excellent progress in our strategic plan to focus Nektar's efforts on immunology and inflammation and we're advancing multiple model and innovative therapies in and towards the clinic so I want to thank all of our employees for their hard work and I want to thank our investors for their continued support and please stay tuned. Thanks for joining us today. Thank you.

Unknown Executive: This concludes today's conference call. Thank you for your participation. You may now disconnect.

Unknown Executive: Everyone have a wonderful day.