Q2 2020 Nektar Therapeutics Earnings Call

Ladies and gentlemen, please stand by your conference call will begin momentarily. Thank you for your patience in please standby.

Operator: Ladies and gentlemen, please stand by. Your conference call will begin momentarily. Thank you for your patience, and please stand by.

[music].

Operator: Ladies and gentlemen, thank you for standing by, and welcome to the Nektar Therapeutics second quarter 2020 financial results conference call. At this time, all lines are in a listen-only mode.

Ladies and gentlemen, thank you for standing by and welcome to the Nektar Therapeutics second quarter 2020, <unk> financial results Conference call.

At this time, all participants' lines are in listen only mode.

Operator: After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star and then one on your telephone. Please be advised that today's conference may be recorded. If you require any further assistance, please press star and then zero.

After the speakers presentation, there will be a question answer session to ask a question. During this session you need to press Star then one of your telephone.

Please be advised the today's conference maybe recorded if you require any further assistance. Please press Star then Bureau.

Jennifer Ruddock: I would now like to hand the conference over to your speaker today, Ms. Jennifer Ruddock, Head of Corporate Affairs. Ma'am, you may begin. Thank you, Crystal. Good afternoon, everyone, and thank you for joining us today.

I'd now like to hand, the conference over to your speaker today Ms., Jennifer Ruddock head of corporate Affairs, Ma'am you may begin.

Thank you Crystal.

Good afternoon, everyone and thank you for joining us today.

Jennifer Ruddock: With us are Howard Robin, our president and CEO, Gil Laboucherie, our COO and CFO, Dr. Jonathan Zalevsky, our Chief of Research and Development, and Dr. Wei Lin, our Head of Development. On today's call, we expect to make forward-looking statements regarding our business, including clinical trial enrollment and clinical trial results. Timing and Plans for Future Clinical Trials Timing and plans for future clinical data presentations. The Therapeutic Potential of our Drug Candidates

With us or Howard Robin, our president and CEO.

Well, the bursary, our COO and CFO.

Dr., Jonathan So lucky our chief of research and development.

Dr Whalen, our head of development.

On today's call, we expect to make forward looking statements regarding our business.

Including clinical trial enrollment and clinical trial results.

Timing and plans for future clinical trials.

Timing and plans for future clinical data presentation.

The therapeutic potential of our drug candidates.

Jennifer Ruddock: Outcomes and Plans for Health Authority Regulatory Actions and Decisions. Estimates and predictions of the COVID-19 pandemic's impact on our business and clinical trials. Financial Guidance, and certain other statements regarding the future of our business. Because these forward-looking statements relate to the future, they are subject to inherent uncertainties and risks that are difficult to predict, and many of which are outside of our control. Important risks and uncertainties are set forth in our Form 10-Q that we filed on May 8, 2020, 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, Nektar.com.

Outcomes and plans for health authority regulatory actions and decisions.

Estimates and predictions of the Cobot 19, pandemics impact on our business and clinical trials.

Financial guidance and certain other statements regarding the future of our business.

Because these forward looking statements relate to the future. They are subject to inherent uncertainties and risks that are difficult to predict and many of which are outside of our control.

Important risks and uncertainties are set forth in our form 10-Q that we filed on May eight once you 20, which is available as you see stuck up.

We undertake no obligation to update any of these forward looking statements, whether its result of new information future developments or otherwise.

A webcast of this call will be available on the IR Puget Nexus website Nektar dotcom.

Jennifer Ruddock: Before turning the call over to Howard, I'd like to comment on a small housekeeping item. Due to the continued shelter-in-place restrictions in San Francisco, each of us is again calling in from different locations. So in order to facilitate a smooth call flow, I will moderate the Q&A session for our team so we can avoid technical issues during the session. We appreciate your patience as we work to ensure that there are no technological disruptions for those who are listening. With that said, I will hand the call over to our President and CEO.

Before turning the call over to Howard I'd like to comment on a small housekeeping item due to the continued children place restrictions in San Francisco each of US are again, calling in from different locations. So in order to facilitate a smooth calc, though I will moderate the QNX session protein. So we can avoid technical issues. During the session. We appreciate your patience as we work towards.

Sure that there are no technology disruption for those who are listening.

With that said I will hand, the call over to our President and CEO Howard Robyn Howard.

Howard W. Robin: Thank you, Jennifer.

Thank you Jennifer and thank you everyone for joining us on the call today I'd like to start the call by reviewing the ways in which we've successfully led our business as well as our accomplishments during the second quarter and year to date.

Howard W. Robin: joining us on the call today. I'd like to start the call by reviewing the ways in which we've successfully led our business as well as our accomplishments during the second quarter and year to date. For all of us located in the many areas where we operate our business and our clinical trials, we continue to face a complex environment caused by COVID-19. Our key focus has been to navigate this dynamic situation with minimal disruption to our business, and as a result of these efforts, we've seen continued progress in the advancement of our registrational and earlier stage clinical trials as well as the continuation of our research and manufacturing activities in spite of the challenges posed by the COVI We ended the second quarter in a position of exceptional strength. We have built a robust pipeline in oncology and immunology, with multiple registrational and earlier stage clinical trials underway. And we ended the second quarter in a strong financial position, with $1.2 billion in cash and investments and no debt on our balance sheet.

For all of US located in many areas that we operate on business on our clinical trials, we continue to face a complex environment caused by Cobot 19, our key focus has been to navigate this dynamic situation with minimal disruption to our business as a result of these efforts we've been.

We've seen continued progress in the advancement over Registrational earlier stage clinical trials as well as the continuation of our research in manufacturing activities in spite of the challenges posed by the carpet liking that Dan.

We ended the second quarter in a position of exceptional strength, we built a robust pipeline in oncology and immunology multiple registrational, an earlier stage clinical trials underway and we ended the second quarter and a strong financial position with $1.2 billion in cash and investments and no debt on our balance.

<unk>.

During this time, we've adopted our practices to allow us to both portrait.

Howard W. Robin: During this time, we've adapted our practices to allow us to both protect the health of our employees and continue essential operations at our locations, such as research and manufacturing laboratory-based activities, which are essential to our business. We've also worked tirelessly with our trial investigators and their teams to ensure that they can continue to provide superior care and uninterrupted access to study treatment to patients fighting cancer in our clinical trials. And finally, we've been diligently working to ensure that the conduct of our clinical trials is minimally impacted by the evolving situation and that the integrity and quality of data being collected from these studies are maintained and tracked appropriately. We will review these items in more detail later in the call.

Health of our employees and continue with central operations at our locations such as research and manufacturing laboratory based activities, which are central to our business. We've also worked tirelessly with our trial investigators and their teams to ensure that they can continue to provide superior care and uninterrupted access to study treatment.

Two patients fighting cancer, our clinical trials finally, we've been diligently working to ensure that the conduct of our clinical trials is minimally impacted by the evolving situation and that the integrity and quality of data being collected from these studies are maintained detract appropriately.

We will review these items in more detail later in the call.

Howard W. Robin: With these things in mind, we made great progress on a number of fronts during the second quarter, including continuing to enroll new patients in our clinical studies in order to meet our enrollment timelines, while at the same time providing effective oversight of trial conduct and support to our trial staff. We've worked closely with our pharmaceutical partners on this front as well, and I will provide more updates on this in a moment. We've experienced no supply interruptions for manufacturing, and our continued preparations for commercial supply of BEMPEG remain on track. Many of you continue to ask about our assessment of current clinical trial timelines or impacts on any of our clinical studies related to COVID, and I'll provide a review of the current timelines for our studies today.

[laughter] would these things in mind, we made great progress and a number of fronts during the second quarter, including continuing to enroll new patients in our clinical studies in order to meet our enrollment timelines off the same time, providing effect of oversight of trial conduct and support to our trial sites.

We worked closely with our pharmaceutical partners on this front as well and I will provide more updates on this in a moment, we've experienced no supply interruptions for manufacturing and our continued preparations for commercial supply then peg remain on track.

Many of you continue to ask about our assessment of current clinical trial timelines or impacts.

Any of our clinical studies related to called <unk> and.

And I'll provide a review of the current time ones work studies today, we've been tracking timelines for all of our studies very closely during the fluid and uncertain time, and we will need to continually assess these timelines as Walker said any impact to patients and our clinical studies throughout this year.

Howard W. Robin: We have been tracking timelines for all of our studies very closely during a fluid and uncertain time, and we will need to continually assess these timelines as well as assess any impact on patients in our clinical studies throughout this year. This quarter, we continue to laser-focus on oversight and advancement of the five registrational studies for Benpeg Plus Nivo and the BMS Nektar Joint Development Program. These are the first-line metastatic melanoma study, the first-line bladder cancer study, the first-line renal cell carcinoma study, the muscle-invasive bladder cancer study, and the adjuvant melanoma study. In addition to these registrational trials, we're also advancing nicely in the PROPEL study of BEMPEG plus PEMBRO, the Nektar 262 REVEAL study with BEMPEG, and finally, the Nektar 255 study in hematological malignancy, first starting with adjuvant.

This quarter, we continue to laser focus on oversight and advancement of the five Registrational studies for Ben What's Nivo and the Dms Nektar joint development projects. These are the first line metastatic melanoma study. The first line bladder cancer study the first slide renal cell carcinoma study the Muslim.

It's a bladder cancer study and the adjuvant melanoma study. In addition to these registrational trials. We're also advancing nicely into propel study have been peg plus pembro.

Sector to 60 to reveal study with 10 peg.

Finally, the Nektar 255 study and Haematological malignancies.

First starting with argument melanoma, we're particularly pleased to announce today that nektar achieved our goal to start this phase three study of Mpeg plus nivolumab, which points to enroll 960 patients. Our team was able to initiate this trial in early Q3, which was ahead of our original schedule.

Howard W. Robin: We are particularly pleased to announce today that Nektar achieved our goal to start this Phase 3 study of BEMPEG plus nivolumab, which plans to enroll 950 patients. Our team was able to initiate this trial in early Q3, which was ahead of our original schedule, with the first patients in the study entering screening just last. This is an important study that builds on our breakthrough designation achieved with a doublet in metastatic melanoma. In Q2, we recognized a new $25 million milestone payment from BMS related to this study. I'm very proud of our team and the progress and execution on this.

With the first patients in the study entering screening just last week. This is an important studied that builds on our breakthrough designation achieved with the doublet in metastatic melanoma in Q2, we recognized a new 25 billion dollar milestone payment from BMS related to the study started very proud of our team and the progress and execution on this.

Okay.

With respect to the first line metastatic melanoma study, which is being run by our partner BMS starting in July.

Howard W. Robin: With respect to the first-line metastatic melanoma study, which is being run by our partner, BMS, starting in July, BMS has successfully restarted enrollment activities for this study in many countries. They also have a plan to bring on more sites for this study in order to make up for the lost time related to the COVID pause. At their recent analyst event, BMS indicated that the first data from the melanoma study would be expected in Q4 of 21 or Q1 of 22, and this is relatively consistent with our assessment of the situation, which we provided last quarter, that we expected enrollment delays related to COVID could push timelines out by as long as six months. While we are all disappointed in the timeline delay relative to COVID-19, we're very pleased to see that BMS Many of you have listened to the BMS Analysts' Call this morning.

This has successfully restarted enrollment activities for this study in many countries. They also plans to bring on more sites through this study in order to make up for the last time related to the cold pause.

At the recent analyst event Dms indicated that the first data from the melanoma study would be expected in Q4 21 for Q1 of 22 and this is relatively consistent with our assessment of the situation, which we provided last quarter that we expect that enrollment delays related to cold it could push timelines out by as long as six months.

What we are all disappointed in the timeline delay relative relative to called would like team. We're very pleased to see that CMS is actively bringing back enrollment activities, which were paused as a result of dependent and that they're working to meet these revised timelines for this very important study.

Many of you have listened to the BMS analyst call. This morning.

Howard W. Robin: Bentag is an important next-generation late-stage medicine in I.O. that has achieved proof-of-concept in their development pipeline.

And where they highlighted Mpeg as an important next generational late stage medicine.

No that is a cheap proof of concept in their development pipeline.

With respect to the first line bladder cancer study, we expect to be on track to reach our enrollment goal late this summer as a reminder of the primary endpoints for this study or or or and duration of response by independent review for patients with under 10 Cps for <unk>.

Howard W. Robin: With respect to the first-line bladder cancer study, we expect to be on track to reach our enrollment goal late this summer. As a reminder, the primary endpoints in this study are ORR and duration of response by independent review for patients with a under 10 CPS score. Depending upon how long we follow patients for duration of response, we're projecting a timeline to achieve top-line results for this study in the second half of 21, consistent with our prior guidance. For the first-line renal cell carcinoma study, we remain on track for our projections for enrollment in this study, which means we also expect to potentially achieve the first interim analysis on the primary endpoint of overall survival in the first quarter of 22, consistent with our prior guidance.

Depending upon how long we follow patients for duration of response, we're projecting a time wanting to achieve topline results for this study and the second half of 21 consistent with our prior gods.

For the first line renal cell carcinoma study, we remain on track for our projections for enrollment with the study which means we also expect to potentially cheap to first interim analysis on the primary endpoint overall survival in the first quarter of 22 consistent with our prior guidance.

The first line muscle invasive bladder cancer study, which is being run by BMS to studies enrolling approximately 540 patients who receive Mpeg plus nivo or nivo for 12 months treatment period following surgery.

Howard W. Robin: For the first-line muscle-invasive bladder cancer study, which is being run by BMS, this study is enrolling approximately 540 patients who will receive BEMPEG plus NEVO or NEVO for a 12-month treatment period following surgery. The study is actively recruiting patients, and more sites are being initiated throughout the year. As this study is longer, we expect the first data readouts to be in 2024.

The studies actively recruiting patients and more sites are being initiated throughout the year. As this study is longer we expect first data read outs to be in 2024.

With respect to earlier stage studies have been taken the BMS and Nektar development program. You missed is also planning to start and additional study beg placebo in combination with a T.K. API and patients in the first line renal cell carcinoma study. This study builds on the Registrational study in RCC that we're running.

Howard W. Robin: With respect to earlier stage studies of BEMPEG in the BMS and Nectar Development Program, BMS is also planning to start an additional study of BEMPEG plus NEVO in combination with a TKI in patients in the first-line renal cell carcinoma setting. This study builds on the registrational study in RCC that we're running of the doublet of BEMPEG plus NEVO versus. With respect to first-line non-small cell lung cancer, as you know, Nektar has been running the PROPEL study of BEMPEG plus PEMBRO as a separate independent study from the BMS development program with the goal of moving forward with a registrational strategy in non-small cell lung cancer that combines BEMPEG with the existing and preferred standard of care, which is PEMBRO-elizabethan. However, the development and regulatory BMS recently informed us that they will not start the Phase 2 study in first-line non-small cell lung cancer with BEMPEG plus NEVO, as that was outlined in our amended agreement.

The doublet have been peg plus nivo versus a teacher.

With respect to first line non small cell lung cancer as you know Nektar has been running the propelled study of Mpeg plus pembro as a separate independent study from the BMS development program with the goal that moving forward with a registrational strategy in non small cell lung cancer, the combined impact with the existing and.

Offered standard of care, which is pembrolizumab.

A development and regulatory pathway for been pig plus nivo is very challenging given the volume ABS lack of a single agent labeled in first line non small cell lung cancer.

Yeah, Messes recently informed us that they will not start the phase two study in first line non small cell lung cancer with them take less nivo that was outlined in our amended agreement with us in line with disagreement Nichter no longer has any exclusivity obligations related to advancing registrational auger or other trials in non small cell lung cancer with me.

Howard W. Robin: Thus, in line with this agreement, Nektar no longer has any exclusivity obligations related to advancing registrational or other trials in non-small cell lung cancer with BMS. With Pembrolizumab firmly established as the preferred standard of care, we are now in, and The PROPEL study is actively enrolling patients in line with our timeline objectives. Although last quarter we mentioned that the COVID situation delayed initiation for some investigator sites in Europe for PROPEL, we were able to successfully bring several new European sites online during the second quarter, and these sites are now actively enrolling patients.

Yes, Weve pembrolizumab firmly established as the preferred standard of care. We're now in a position to move quickly on the strategy for a registrational trial in first line non small cell lung cancer with pembro upon successful outcomes with the propel study.

The propel studies actively enrolling patients in line with our timeline objectives, although last quarter, we mentioned that the cobot situation delayed initiation for some investigator sites in Europe for propel we were able to successfully brings several new European sites online during the second quarter and these sites are now actively enrolling patients.

Howard W. Robin: We expect to be on track to generate initial safety as well as preliminary ORR data for between 10 and 20 patients with a minimum of two scans on treatment from both the dose escalation and non-small cell lung cancer cohorts of this study by the end of this year or first quarter of 2020. Our Phase I-II Reveal Study of Nektar-262 is also on track. We're in the expansion phase of this study, which is evaluating simultaneous dosing of the recommended Phase II dose of Nektar-262 administered in combination with Benpeg, either with or without nivolumab, and up to 24 relapsed and refractory melanoma. As we stated last quarter, we observed high levels of TLR activation in the tumor microenvironment during the sequential dosing of Nektar-262 and Bempeg, and we were able to characterize safety for Nektar-262.

We expect to be on track to generate initial safety as well as preliminary or our data for between 10 20 patients with a minimum of two scans on treatment from both to dose escalation and non small cell lung cancer cohorts of this study by the end of this year or first quarter 21.

Our phase one to reveal study of Nektar 262 is also on track. We're in the expansion phase of the study, which is evaluating simultaneous dosing of the recommended phase two dose of Nektar 262 administered in combination with Ben peg either with or without in of old Matt.

24, relapse and refractory melanoma patients.

As we stated last quarter, we observed high levels of fuel our activation in the tumor micro environment. During the sequential dosing of metrics to 62 in bed and were able to characterize safety for Nektar 262. These data are being submitted for presentation at the city Congress. This November.

Howard W. Robin: These data are being submitted for presentation at the CITI Congress this November and support our advancement into the relapsed and refractory melanoma patient population post-IO treatments with this program. For Nektar 255, our IL-15 agonist program, and our next cytokine therapy and clinical development, we are actively enrolling patients into the first in-human clinical study of Nektar 255 in patients with hematological malignancies, which began late last year. Our goal is to complete the dose escalation monotherapy portion of this study by the end of this year. Of course, meeting this goal will depend on how many dose cohorts we need to enroll before achieving a maximum tolerated dose. As a reminder, this study is evaluating Nektar 255 versus a monotherapy in dose escalation, after which we will expand into several arms that will evaluate Nektar 255 as a monotherapy at the recommended phase 2 dose and also evaluate Nektar 255 in combination with daratumumab in multiple myeloma and with rituximab in non-Hodgkin's lympho

And support our advancement into the relapse and refractory melanoma patient population post IPO treatments with this program.

For Nektar 250, Fives are 15 agonist program and our next cytokine therapy in clinical development. We are actively enrolling patients into the first in human clinical study of Nektar 255 in patients with Hematological malignancies, which began late last year. Our goal is to complete the dose escalation monotherapy.

Portion of the study by the end of this year.

Course meeting this call will depend on how many dose cohorts, we need to enroll before achieving the maximum tolerated tolerate ducks as reminder, this studies evaluating nektar 255, first as a monotherapy dose escalation.

After which we will expand into several alarms that we'll evaluate nektar 255, as a monotherapy as a recommended phase two dose and also evaluate nektar 250 side in combination with that rituximab in multiple myeloma and with Rituximab and non Hodgkin's lymphoma.

We have already reserved observed target engagement of the Io 15 pathway starting from the first dose level study and we're very excited to submit these preliminary data for presentation at this year's City conference.

Howard W. Robin: We have already observed target engagement of the IL-15 pathway, starting from the first dose level studied, and we are very excited to submit these preliminary data for presentation at this year's CITI conference. There has been an increasing interest in natural killer cell therapies, and we are taking a comprehensive approach to developing Nektar 255 in several cancer patients, in addition to the studies ongoing in hemolygamy. We're also planning to initiate a study of Nektar 255 in patients with solid tumors before the end of this year. Jay Z will talk more about this study in a moment.

There's been an increasing interest in natural killer cell therapies, and we are taking a comprehensive approach to developing nektar 255, several cancer settings. In addition to the studies ongoing and he malignancies. We're also planning to initiate a study of Nektar 255 in patients with solid tumors before the end of this year.

And JC, we'll talk more about this study in a moment.

Moving onto our partner Eli Lilly Nektar 358, our T Reg simulate Tory program.

Howard W. Robin: Moving on to our partner Eli Lilly and Nektar 358, our Treg Simulatory Program, we recently presented data at the EULOR Congress from the Phase 1B study of Nektar 358 in patients with mild to moderate disease. These exciting data led to the phase two study, which is also being run by Lilly, in patients with moderate to severe lupus. And I'm excited to announce that Lilly began initiating clinical sites in late July and screening patients in this study just this week. Jay-Z will again talk more about this study later in the call.

We recently presented data at the Youre Congress from the Phase one be study of Nektar 358, and patients with mild to moderate Lucas. These exciting data led to the phase two study, which is also being run by Lilly in patients with moderate to severe lupus and I'm excited to announce that really began initiating clinical sites in late June.

Why and screening patients in this study just this week Shacey will again talk more about this study later in the call.

Howard W. Robin: In addition, the phase 1 multiple dose study in psoriasis and ectopic dermatitis being conducted by Lilly is enrolling patients again after a three-month pause in response to the COVID-19 situation. Finally, we are planning to present additional data on Nectar360A from the Phase 1B study at the 2020 American College of Rheumatology Congress, also known as ACR, which occurs in early November. So we're all looking forward to sharing new data on Nektar 358 with you. Finally, Lilly plans to start another phase two study in an additional autoimmune disease in the second half of this year. We are very pleased with Lilly's continued commitment to Nektar 358 and their broad plans for its development, which reflect the potential of this truly novel mechanism to play an important role in the treatment of a wide range of autoimmune diseases.

In addition, the phase one multiple dose study in psoriasis and atopic dermatitis being conducted by Lilly are enrolling patients again after a three month pause in response to the Cobot 19 situation. Finally, we're planning to present additional data on Nektar 358.

From the phase one be study at the 2020 American College of Rheumatology Congress also known as a CR.

Which occurs in early November so we're all looking forward to sharing new data Nektar Threefifty would you folks.

Yes.

Finally, we plan to start another phase two study in an additional auto immune disease in the second half of this year, where are very pleased with Luis continued commitment to Nektar 368, as well as their broad plans for its development, which reflect the potential of this truly novel mechanism to play an important role in the treatment of a wide range of auto mute.

Jesus.

Howard W. Robin: Before I hand the call to Wei, I'd like to mention an additional data presentation for BEMPEG that we're planning this year. First, for the melanoma cohort from PIVOT-02, as many of you know, last year we obtained an FDA breakthrough therapy designation for BEMPEG plus NEVO in patients with metastatic melanoma based upon the positive data from the PIVOT-02 study, including a high resistance complete response rate of 34%, with 42% of patients experiencing complete regression of their resistance target. As we stay here...

Before I hand, the call to way I'd like to mention additional data presentation for Ben Peg that we're planning this year.

First for the melanoma cohort from pivot to as many of you know last year, we obtained FDA breakthrough therapy designation for Ben Peg plus nivo in patients with metastatic melanoma based upon the positive data from the pivotal two studies, including a high resist complete response rate of 34% with 42% of.

Patients experiencing complete regression of there was this target lesions as we stated on our last call up to 21 months median follow up point for patients in this cohort we had still not achieve median PFS. We continue to see deepening of response for these patients and are very excited to submit updated data.

Howard W. Robin: As we stated on our...

Howard W. Robin: At the 21-month median follow-up point for patients in this cohort, we had still not achieved median PFS. We continue to see deepening of response for these patients and are very excited to submit updated data from the melanoma cohort with an even later data cut closer to this year's CITSE 2020 meeting. We also plan to present some initial landmark survival techniques. As we've stated in the past, we are very excited about the potential of this doublet combination for melanoma. So, at this year's SITSE Congress, our plans are to present data from three Nektar programs, updated data from the first-line metastatic melanoma cohort, as I just stated, data from the first patients in the Nektar 255 study in hematological malignancies, and data from the dose escalation phase of the Nektar 262 study. And with that, I'd like to turn the call over to Wei to review in more detail the BENPEG development plan.

From the melanoma cohort with an even later data cut closer to this year's 62020 meeting.

We also plan to present, some initial landmark survival.

As we've stated in the past, we're very excited about the potential of this double accommodation for melanoma patients. So for this year's city Congress. Our plans are to present data from three Nektar probes updated data from the first line metastatic melanoma cohort as I've just stated data from the first patients in the Nektar 255 study in hematologic.

Well malignancies and data from the dose escalation phase of the Nektar 262 study.

And with that I'd like to turn the call over to way.

To review in more detail, but then take development.

Thank you Howard as Howard stated, we continue to take all possible measures to ensure that our clinical etcetera remain on track can cope pandemic.

In addition to their vigorously our sales teams conducting clinical trials are monitors and data collection systems are also capturing any corporate related protocol deviations what changes in Saudi contract that we may need to provide FDA and the future.

Wei Lin: Thank you, Howard. As Howard stated, we continue to take all possible measures.

As you know the FDA issue guidance on clinical trial conduct do independent Nick and we are closely following FDA guidance as we track any impact Colby on the patients in our steady.

Wei Lin: to ensure that our...

Wei Lin: that are clinically said to remain on track during the COVID pandemic. In addition to the rigorous ways our study teams conduct our clinical trials, our monitors and data collection systems are also capturing any COVID-related protocol deviations or changes in study conduct that we may need to provide to the FDA in the future. As you know, the FDA has issued guidance on clinical trial conduct during the pandemic, and we're closely following FDA guidance as we track any impact of COVID on the patients in our study. We have seen very good patient compliance, particularly in their visits to study sites to receive study treatments, and for scheduled scans. We continue to be tremendously impressed with the high degree of engagement from our investigators and their staff and the extraordinary care they're providing to their patients during this very challenging time for all of us.

We have seen very good patient compliance, particularly in their visits to study sites, we see steady treatments and for schedule. Its cans, we can seem to be tremendously impressed with high degree of engagement from our investigators and their staff and extraordinary care, they're providing care patients can because.

Very challenging time role device.

In response to some questions, where we see being we have received only a few reports ill patients in our studies have had suspected or confirmed coke infection.

As of today, what the clinical studies nexstars running across our 200, plus and battery sites globally.

We have very few record for patients who have been diagnosed with cobi or have missed that treatment or missed steady scans Q2 Colby.

Wei Lin: In response to some questions we're receiving, we have received only a few reports of patients in our studies who have had suspected or confirmed COVID infection. Also today, for the clinical studies that Nektar is running across our 200 plus investigator sites globally, we have very few reports of patients who have been diagnosed with COVID or have missed study treatment or missed study scans due to COVID.

We're carefully collecting information pertaining to these cases and any other impact to the studies.

Related to Colgate and our following FDA guidance to enable us to communicate any protocol deviations.

Related to the FDA Kishore future registration.

Wei Lin: We're carefully collecting all information pertaining to these cases and any other impact on the studies that could be related to COVID and are following FDA guidance to enable us to communicate any protocol deviations related to COVID to the FDA to ensure future registration. Before I hand the call to Jay Z to discuss our work with Nektar 358 and Nektar 255, I want to follow up on continued inquiries we've received on the changing of the interim, response rate endpoint from overall response rate ORR to complete response rate CRR in our first-line melanoma study. As you know, we received a breakthrough therapy designation for BAMPAC placebo based on the high complete response rate we observed in this patient population in the Phase 3 study. We have three endpoints.

Before I hand, the call to chase he to discuss how works with NASCAR 358, and Nexstar to fight fight.

I wanted to follow up on continued increase we've received on the changing off the interim.

Response rate and point from overall response rate are to complete response rate CR.

Our first line melanoma study.

If you know we received breakthrough therapy designation for Bamtech plus evil based on the high complete response rate.

We observed in this patient population.

In the phase three study.

We have three endpoints.

Overall response rate were Hawaii, Har progression free survival or PFS and overall survival Oh, yes.

First standpoint, the interim analysis, where a very small amount Alf lifespan to compare at the whole are in the doublet harm bamtech plus people to double our human Nivo monotherapy arm.

Wei Lin: Overall Response Rate, or ORR, Progressionally Free Survival, or PFS, and Overall Survival (OS). The first endpoint is an interim analysis where a very small amount of alpha is spent to compare the ORR in the doublet arm of BandPak Plus to the OR in the Nevo Monotherapy Ombudsman, which will be done in a specific number of patients with at least six months of follow-up. This endpoint will allow a potential early accelerator filing for the doublet so that we could bring innovative treatment to patients early. The full approval filing in the U.S. and in Europe will be based on PFS and OAS because of our high..., and Pre-Response. Many of you have asked whether we could change.

Which would be done in a specific number of patients with at least six month I'll follow up.

Standpoint will allow potential or the accelerator filing.

When you calculate that we could.

Innovative treatment to patients earlier.

The full approval filing in the U.S. and in Europe.

I would be based on PFS and OS.

Because of our high complete response rate.

Many of you have asked whether we could change.

Interim or are you point to look at the complete response rate instead.

Wei Lin: Interim ORR Endpoint to look at the company's response rate instead. We and our partner, BMS, continue to explore this possibility, including outreach to global health authorities, to discuss how best to support this veterinarian path, of utmost importance to both companies. During this process, we maintain the integrity of the ongoing Phase 3 trial so that we can use the data from the study for global registration of MPEG-plus levels in first-line melanoma. This process may take some time. However, we are hopeful that we can provide an update on this before the end of this year. In the meantime, the study continues to have the original three endpoints of ORR, PFS, and OS. The original design of this study, based on Checkmate 67, the PFS analysis, is projected to occur approximately six to seven months after the first interim analysis of ORR. However, this projection is affected by the rate of enrollment and the rate at which PFS events occur in the study. Thus, that timing could change for both ORR and PF. The results will be analyzed by a blinded, independent radiology review.

We know our partner BMS continue to export this possibility, including outreach to global health authorities to discuss how best to support dispatch recession path.

Uh huh out most importance to both companies given this process is that we maintained integrity ongoing phase three trial.

So we can use the data from this study for global registration or Bamtech placebo.

In first line melanoma.

This process may take some time.

However, we.

Our hopeful.

We could provide an update.

Before the end of this year.

In the meantime to study continues to have the worsening sweet and point of or our PFS and Alas.

The original design with the steady.

Its base.

Correct Me 67.

PFS analysis.

Is projected to occur approximately six to seven month.

After the first interim analysis for our.

However, this projection is the second beta enrollment rate, which PFS events occur on the study.

Yes.

Timing could change.

For both or our NPS nice.

Results will be analyzed pipeline to independent Greek LNG review.

Wei Lin: So this process will affect timing for the completion of any data analysis as well. As we get closer to achieving these endpoints, we will be able to refine our timeline and share it publicly. As I just stated, OR is designed as an accelerated program point. We spent only a small amount of alpha on this, and PFS is a true approval endpoint. With that, I'll hand the call to Jay Z to discuss more on our Nektar 358 and Nektar 355 programs. Jay Z.

So this process.

We will affect timing with the completion of any data analyses as well.

As we get closer to achieving these endpoints.

We'll be able to refine our timeline.

And share them publicly.

I just stated for RF design seen accelerated approval and point.

We spent only a small amount alpha on this and PFS is that who who approvable endpoint.

With that I'll hand, the call if you JV could discuss more on our Nexstar 358, and Nexstar to reclassify program JV.

Thanks way.

Jonathan Zalevsky: Thanks, Wei. I'd like to spend a little more time discussing two programs. The first is the Nektar 358 program in our plans for the lupus study, and the second is our IL-15 program, Nektar 255. First, for Nektar 358, as Howard stated, we presented our first data from the Phase 1b multiple ascending dose study, which was conducted in patients with mild to moderate lupus, at this year's European League Against Rheumatism, or EULAR, conference in We are the only company that has presented data from a multiple ascending dose study of a novel Treg stimulating therapy in patients. We are tremendously pleased that these promising data have now led to our partner Eli Lilly initiating a phase two study in lupus patients with plans for a second phase two study in another auto by year's end.

I'd like to spend a little more time discussing two programs. The first is the Nektar 358 program in our plans for the Lupus study and the second is our I'll 15 program Nektar two five but.

First for Nektar 358, as Howard stated, we presented our first data from the phase one be multiple ascending dose study, which is conducted in patients with mild to moderate lupus at this year's European leak against rheumatism more EULAR conference in early June.

We are the only company that has presented data from multiple ascending dose study of a novel T regs stimulating therapy in patients.

We are tremendously pleased that these promising data have now led to our partner Eli Lilly initiating a phase two study lupus patients with plans for a second phase two and another auto indication by years end.

Many auto immune disorders, including systemic lupus are associated with decrease T. Reg numbers reduced T reg function and or reduce production profile too.

Jonathan Zalevsky: Many autoimmune disorders, including systemic, are associated with decreased Treg numbers, reduced Treg function, and or reduced production of IL-2. Treg deficiencies are important in the pathogenesis of these autoimmune diseases. And with Nektar 358; our goal is to address these Treg abnormalities and disease and to develop an IL-2-like molecule that could selectively stimulate Tregs in a much more effective manner than IL-2. The results from the phase one study presented at ULAR concluded that Nektar 358 was safe and well tolerated when multiple doses were administered to patients with lupus. This reinforces our earlier study findings with single dose administration and healthy volunteers. Additionally, demonstrating that the safety profile was similar between single and repeat administrations is critically important for potential treatments for chronic disease. The data also showed dose-proportional PK and prolonged exposure with a half-life of 10 to 13 days that easily enabled every two-week dosing in the Phase II study. Importantly, Nectar 358 led to a marked, selected, and dose-dependent expansion of proliferating Tregs in patients with lupus. And this was maintained through multiple dose administration.

T. Reg deficiencies are important in the pathogenesis of these auto immune diseases.

And with Nektar 3008, our goal is to address these T vec abnormalities and disease and to develop an aisle to like molecule that could selectively stimulate tea bags in a much more effective manner than I or II.

The results from the Phase one study presented it you are concluded that Nektar 3.8 was safe and well tolerated on multiple doses were administered in patients with Lucas.

This reinforces our earlier study findings with single dose administration in healthy volunteers.

Additionally, demonstrating safety profile the similar between single and repeated administration is critically important for potential treatments for chronic disease.

The data also showed dose proportional PK and prolonged exposure with the half life of 10 to 13 days that easily enables every two weeks dosing in the phase two study.

Importantly, nektar three Fiveeight listed a market selected and dose dependent expansion that proliferating T regs and patients with Lucas and this was maintained through multiple dose administrations.

As Howard stated earlier the phase Twob study is now underway being run by Lilly.

Jonathan Zalevsky: As Howard stated earlier, the Phase 2B study is now underway and being run by Lilly. The patient population is similar to other Phase 2b lupus studies in regards to required diagnosis of SLE using ACR classification criteria, positive autoantibodies characteristic of lupus, and active clinical disease activity despite standard of care treatment. In this study, patients must have a systemic lupus erythematosus disease activity index, or SLIDI2K, that is greater than six points at screening. In addition, patients must have a measurable level of clinical activity at baseline, including secondary organ manifestations such as arthritic joints or skin involvement. Patients will be randomized to one of three dosages of Nektar 358 administered every two weeks or placebo for a treatment period of six months or 24 weeks. The primary endpoint in the Phase 2 study is the percent of patients achieving at least a 4-point reduction in the SLEAD-I2K scale. Important secondary endpoints include the percent of patients who achieved an SRI-4 response, phylag-based syphilis response, and the level of low disease as defined by the Lupus Low Disease Activity State, or LLDAS.

The patient population is similar to other phase to be this study in regards to required diagnosis of esselte using HCR classification criteria positive auto antibodies characteristic of business and active clinical disease activity. Despite standard of care treatment.

In this study patients must have a systemic lupus erythematosus disease activity index or sleep die to K.

That's greater than six point at screening.

In addition patients must have a measurable level of clinical activity at baseline, including secondary Oregon manifestations, such as I've critic joints or skin involvement.

Patients will be randomize to one of three dosages of Nektar 358 administered every two weeks or placebo for treatment period at six months or 24 weeks.

The primary endpoint in the phase two study as percent of patients achieving at least a four point reduction in discrete I to pay scale.

Important secondary endpoints include the percent of patients who achieved in Sri for response.

By lag base they put response.

And the level of loaded the as defined by the lupus slow disease activity state.

Yes.

Jonathan Zalevsky: We will also characterize pharmacokinetics, pharmacodynamics, and immunogenicity in treated patients. The primary and key secondary endpoints will all be measured at week 24, and we expect the study to be completed within 18 to 24 months.

We will also characterize pharmacokinetics pharmacodynamics immunogenicity treat patients.

The primary and key secondary endpoints will all be measured at week 24, and we expect this study to be completed within 18 to 24 month.

And moving on connector to buy side, It's Howard stated the dose escalation portion of this phase one phase two study in patients with heme malignancies is proceeding and we plan to present initial data from the first patients at the dose escalation. This years since the Congress in November.

Jonathan Zalevsky: As Howard stated, the dose escalation portion of this phase 1-2 study in patients with heme malignancies is proceeding, and we plan to present initial data from the first patients of the dose escalation at this year's 50 Congress in November. The study is evaluating the safety, pharmacokinetics, and pharmacodynamics of Nektar 2-5-5 in hematological malignancies in order to establish a phase two dose to be used either as monotherapy or in parallel, tested in combination with antibodies that work through an ADCC mechanism, including daratumumab and rituximab. Depending upon how many dose cohorts we proceed through, we plan to enroll up to 40 patients with relapsed or refractory multiple myeloma and non-Hodgkin's lymphoma in the dose escalation part of the study. We have also introduced a robust biomarker program into this trial, including measurement of the Nektar-255 effect on multiple immune cell populations of both peripheral blood and lymphoid tissue. We are especially focused on expanding NK cell numbers and analysis of NK cell subsets, as well as their activation and function.

The study is evaluating safety pharmacokinetics and pharmacodynamics Nektar two pie five implement a logical malignancies in order to establish a phase two dose to be views either as a monotherapy and in parallel tested in combination antibodies that works through in ADCC mechanism, including Daratumumab Advertiser.

So Matt.

Depending upon how many dose cohort. We proceed through we plan to enroll up to 40 patients with relapsed or refractory multiple myeloma and non Hodgkin's lymphoma in the dose escalation part of the study.

We have also introduced several biomarker program into this trial, including measurement of the next three to five five attack on multiple immune cell populations of both peripheral blood lymphoid tissue.

We are especially focused on expansion of NK cell numbers.

And analysis of NK cell subsets as well as their activation function.

That's how it stated our goal is to complete the dose escalation monotherapy portion of the phase one trial by the end of this year. We are excited about the early biomarker results. We've observed in the first patient growth.

So we look forward to sharing these with you in November.

Additionally, we are planning to initiate a second phase one class two study next the to 55 in solid tumors before the end of the year.

Jonathan Zalevsky: As Howard stated, our goal is to complete the dose escalation monotherapy portion of the phase one trial by the end of this year, and we are excited about the early biomarker results we've observed in the first patients enrolled. We look forward to sharing these with you in November.

This study will evaluate nektar 255 into solid tumor setting in combination with the tux amount.

Well first setting has had a net cancer enrolling patients who have progressed on platinum therapy in a checkpoint.

Gil Laboucherie: Additionally, we are planning to initiate a second Phase 1-2 study of NECTRS-255 in solid tumors before the end of the year. This study will evaluate Nektar 2-5-5 in two solid tumor settings in combination with Suntuximab. The first setting is for neck cancer, enrolling patients who have progressed on platinum therapy and a check. The second setting is metastatic colorectal cancer, enrolling patients who have received two prior metastatic treatments. The overall study will enroll up to 75 patients and will include a dose escalation component for the combination regimen and then expand into dedicated cohorts for head and neck and colorectal cancer. And with that update, let me turn the call over to Gil for a review of the financials.

Second setting as metastatic colorectal cancer enrolling patients who have received two prior metastatic treatments.

The overall study will enroll up to 75 patients and will include a dose escalation component. So the combination regiment and then expand into dedicated cohorts in head and neck and colorectal cancer.

And with that update let me turn the call over to kill for a review of the financials.

Thank you Jay Z and good afternoon, everyone.

On this call I'll review, our 2020 financial guidance, which is unchanged.

Starting with our strong financial position during the second quarter, we repaid 250 million an outstanding senior notes.

Ending the quarter with 1.2 billion in cash and investments and no debt on our balance sheet.

We still plan to end 2020 with over 1 billion in cash and investments.

Turning to our annual financial guidance.

Gil Laboucherie: Thank you, Jay-Z, and good afternoon, everyone. On this call, I'll review our 2020 financial guidance, which is unchanged. Starting with our strong financial position, during the second quarter, we repaid $250 million in outstanding senior notes, ending the quarter with $1.2 billion in cash and investments, and no debt on our balance sheet. We still plan to end 2020 with over $1 billion in cash and investment. Turning to our annual financial guidance. Our full year GAAP Revenue Guidance remains between $140 and $145 million for 2020. This includes 50 million in milestone payments from BMS and 90 to 95 million in royalties, product sales, and other revenue. We recognized a $25 million milestone for the start of the muscle invasive bladder cancer study in Q1. And, as Howard mentioned, we successfully initiated the adjuvant melanoma study ahead of schedule and recognized a second $25 million milestone under the BMS collaboration in Q2 rather than Q3 as we projected last quarter. The $90 to $95 million of remaining GAAP revenue is still expected to be recognized on a fairly routable basis over the four quarters of this year.

Our full year GAAP revenue guidance remains between 140 and 145 million for 2020.

This includes 50 million of milestone payments from BMS.

And 90 to 95 million of royalties product sales and other revenue.

We recognized a $25 million milestone for the start of the muscle invasive bladder cancer study in Q1.

And as Howard mentioned, we successfully initiated the judgment melanoma study ahead of schedule and recognized a second $25 million milestone under the BMS collaboration in Q2, rather than Q3, as we projected last quarter.

The 90 to 95 million of remaining GAAP revenue is still expected to be recognized on a fairly ratable basis over the four quarters of this year.

Our GAAP R&D expense guidance is also on changed as our clinical pipeline progress remains largely on track.

We anticipate 2020 GAAP R&D expense.

Will range between 475 and 500 million.

Which includes approximately 70 million of noncash depreciation and stock compensation expense.

Our DNA expense for 2020 is still projected to be between 105, an 115 million.

Which includes approximately 45 million of noncash depreciation and stock compensation expense.

We continue to closely manage your operating expenses and remain highly focused on the execution of our broad portfolio of research and development programs.

Gil Laboucherie: Our GAP R&D expense guidance is also subject to change as our clinical pipeline progress remains largely on track. We anticipate 2020 GAAP R&D expense will range between $475 and $500 million, which includes approximately $70 million of non-cash depreciation and stock compensation expenses. Our GNA expense for 2020 is still projected to be between $105 and $115 million, which includes approximately $45 million of non-cash depreciation and stock compensation. We continue to closely manage our operating expenses and remain highly focused on the execution of our broad portfolio of research and development programs.

And as I reviewed earlier, we plan to in 2020 with at least a billion in cash and investments.

And with that I'll open the call through the questions operator.

Thank you.

Ladies and gentlemen, if you have a question at this time is the star followed by the number one key on your Touchstone telephone.

Your question has answered or you wish to remove yourself from the Q. Please press the pound key once again to ask the question. Please press Star then one now.

And our first question comes from Peter Lawson from Barclays. Your line is open.

Hi, Thanks for taking the questions just really on the the early clinical data that we see.

Yes, it's too early to fight fight said something that.

We should focus on what should we expect and is there anything we should your attention too.

TV Im going to ask you to answer that question. Thanks.

Yeah. Thanks, Peter So certainly both programs are giving early data both of them from first in human studies. So the things that we pay attention to our really what the focus and design in the studies, where these studies are designed to assess the overall tolerability and safety of the agents.

Operator: And as I reviewed earlier, we plan to end 2020 with at least a billion in cash and investment. And with that, I'll open the call to questions, Operator. Thank you. Ladies and gentlemen, if you have a question at this time, please press the star followed by the number one key on your touchtone telephone. If your question has been answered or you wish to remove yourself from the queue, please press the pound key. Once again, to ask a question, please press the star and then one now. And our first question comes from Peter Lawson from Barclays. Your line is open. Hi, thanks for taking the questions. Just really on the early clinical data that we see for 262 and 255, is there something that we should focus on? What should we expect? And is there anything we should pay attention to?

Also to assess the pharmacokinetics and also the pharmacodynamics.

Now as you know, we really pay a lot of attention onto the mechanism.

These drugs have and really that's that's really built in and to how we do our drug development and especially at the early stages. So both of the studies have robust biomarker program still thin.

So in this setting of Nektar twosix tuned reveal we are looking at key biomarkers associated with TLR, seven and eight activation and remember we can analyze those as a monotherapy first cycle and then also in combination with Ben Pag on successive cycles, because remember that study has kind of a staggered.

Design because it was the first in human or a novel novel combination. So in that setting we'll be looking very closely and the interferon responses type one induced by until our activation and the type two interferon responses induced by impact and then looking at the combination of the two patents patients receive.

Operator: Jay Z, I'm going to ask you to answer that question. Thanks.

Jonathan Zalevsky: Yeah, thanks, Peter. So certainly both programs are giving early data, both of them from first in human studies. So the things that we pay attention to are really what the focus and design of the studies were. So these studies are designed to assess the overall tolerability and safety of the agents, as well as to assess the pharmacokinetics and also the pharmacodynamics. Now, as you know, we really pay a lot of attention to the mechanism that these drugs have. And really, that's really built in into how we do our drug development, and especially at the early stages.

Continue treatment.

In the setting a to 55 you know that's a different cytokine than impact ended engages a different set of immunological pathways. So as I mentioned earlier in my presentation never really diving very very deeply into certain immunological tissue and blood based cellular compartment.

In particular, we're focusing a lot of natural killer cells NK cells are very robust target pile 15 pathway engagement, an extra 255 really targets that compartment very well. So we don't just look at total book numbers will even look at the different subsets of NK cells even.

Jonathan Zalevsky: So both of the studies have robust biomarker programs built in. So, in the setting of Nektar 262 and Reveal, we are looking at key biomarkers associated with TLR7 and 8 activation. And remember, we can analyze them as monotherapies in the first cycle and then also in combination with BEMPEG on successive cycles because remember, that study had a kind of a staggered design because it was the first in humans for a novel-novel combination. So, in that setting, we'll be looking very closely at the interferon responses, type 1 induced by TLR activation, and the type 2 interferon responses induced by BEMPEG, and then looking at the combination of the two. In the setting of 255, you know, that's a different cytokine than BEMPEG, and it engages a different set of immunological pathways.

Precursor we know in early maturing in cells as well and then we'll study markers of activation and even extend that overall markers of effector function.

So that's the nature of the data that we will be focusing on.

Kind of the gives you a flavor you know the kind of data that you can expect to see later this year.

Okay. Thank you and then how many patients could we potentially see and could we see it you think initial clinical efficacy or is it too too early.

Yeah, so with the 255 it'll be subs as as we mentioned that study is still ongoing dose escalation. So thatll be no early set of cohorts and in the reveal study we have the entire dose escalation.

Jonathan Zalevsky: So, as I mentioned earlier in my presentation, they're really diving very, very deeply into certain immunological tissues and blood-based cellular compartments. In particular, we're focusing a lot on natural killer cells. NK cells are a very robust target of IL-15 pathway engagement, and Nektar-255 really targets that compartment very well. So we don't just look at total book numbers; we'll even look at the different subsets of NK cells, even precursor cells, you know, and early maturing immune cells as well. And then we'll study markers of activation and even extend that to overall, you know, markers of effector function. So that's the nature of the data that we will be focusing on and kind of gives you a flavor of the kind of data that you can expect to see later this year.

Moving through the identification of the recommended phase two dose, which is being studied now in larger cohorts.

Well definitely present all of the data that's available.

Presented earlier that we had instances of responses observed in the reveal study we presented that data last year. So we'll continue to build on all of those but to your point you know, it's really when we move into the larger cohorts that the studies start because enroll patients with well large enough patient cohorts.

Right that review zero in on efficacy.

Thanks for the question Peter Great.

Great. Thanks much.

Thank you.

Our next question comes from Tyler Van Buren from Piper Sandler Your line is open.

Hey, guys. Good afternoon, Congrats and all the progress I guess.

I have two questions. The first one is on.

Hello.

The first line non small cell lung cancer troll combo with Pembroke, we're gonna get.

Operator: And then how many patients could we potentially see? And could we see, do you think, initial clinical efficacy, or is that too early?

Actual data potentially your and early next year and you noted.

We could get overall response rate data in 10 20 patients greater than two scans. So I guess can you just help us understand exactly what Pembro monotherapy would show at that time point and therefore, what overall response rate with the combo you'd like to see to really be confident in the combo move.

Jonathan Zalevsky: Yeah, so, you know, with the 255, it'll be, as we mentioned, that study is still ongoing, dose escalation. So, that'll be an early set of cohorts.

Jonathan Zalevsky: And in the reveal study, you know, we have the entire dose escalation moving through the identification of the recommended phase two dose, which is being studied now in larger cohorts. So, we'll definitely present all of the data that's available. We presented earlier that we had instances of responses observed in the reveal study, and we presented that data last year. So, we'll continue to build on all of those. But to your point, you know, it's really when we move into the larger cohorts that the studies start to enroll, you know, patients with, well, large enough patient cohorts, right, that really zero in on efficacy. Thanks for the question, Peter.

And cord and then.

Second question is just related to.

The process that you are undergoing to potentially in first line melanoma to move that interim readout from overall response rate too.

The CR rate interim look which is of course encouraging given the wider.

Ultra there, but maybe just I'd like to here you know the argument that you're going to make to the FDA regulatory agencies to get that changed.

Hey, Thanks, Tyler way I'm going to ask you to remind folks that the propelled design and the different cohorts that we're looking.

Operator: Great. Thank you so much.

Operator: Thank you. Our next question comes from Tyler Van Buren from Piper Sandler. Your line is open. Hey guys, good afternoon, and congrats on the...

We expect your out from there.

First question. Thank you Okay sure absolutely yes. Thanks for the question, Yes, certainly I think on non small cell lung cancer on even with the recent advancements still remains a high unmet medical need Uh huh.

Operator: I guess I have two questions. The first one is on...

Operator: ProPel, the first-line non-small cell lung cancer trial combo with Pembro. We're going to get initial data potentially year-end or early next year, and you noted that we could get overall response rate data in 10, 20 patients greater than two scans. So I guess, can you just help us understand exactly what Pembro monotherapy would show at that time point, and therefore, what overall response rate with the combo you'd like to see to really be confident in the combo moving forward? And then, the second question is just related to the process that you're undergoing to, potentially, in first-line melanoma, move that interim readout from overall response rate to a CR rate interim look, It's encouraging given the wider delta there, but maybe just, I'd like to hear the argument that you're going to make to the FDA and the regulatory agencies to get that changed. Thanks, Tyler. Wei, I'm going to ask you to remind folks of the Propel design and the different cohorts that we're looking at. With respect to your alpha learner, to help Tyler with his first question, thank you.

I think so we're building on pung these kind of care Pembro monotherapy and as you know that non small cell lung cancer. It really is segmented into three different population based on peak I want to status.

The 2% above PDL, one expression and want to 49 and less than 1%.

And there are different benchmarks.

In dug.

In the on.

Could present above and want to 49th response with single agent is certainly different and that's also with different than the less than 1%, where mano, it's not actually approved because we have available east response data hub temporal monotherapy, we can evaluate.

What the additive value or potential synergy that Ben packing combination with temple does not come green and so that is how what kind of would evaluate the guidance so with our on.

Propelled study design. So first of all we have to parse the study there say optimization cohort and Theres. So expansion cohort non non small cell lung cancer and to really address your question I'll focus on the expansion cohorts non small cell lung cancer and in there we have actually sub divided the groups of patients into on.

Wei Lin: Okay, sure, absolutely. Yeah, thanks for the question.

Wei Lin: Yeah, certainly, I think non-small cell lung cancer, even with recent advances, still remains a high medical need. I think, so we're building on the standard care of Pembro monotherapy, and as you know, non-small cell lung cancer really is segmented into three different populations based on PD-L1 status. You have the 50% above PD-L1 expression and 1 to 49 and less than 1%, and there are different benchmarks for the – in the – [inaudible] what the added value or potential synergy that BAMPAC in combination with Tempolizumab can bring. And so that is how we're going to really value the data. So with our propel study design, first of all, we have two parts to the study.

Enrolling separately patient care, a 50% above one to 49, no so less than 1%.

20 with the current connect.

The segmentation of Hughes.

On.

Either temporal monotherapy or pimple, plus chemo, indeed segments and also known to different benchmarks and so that is how what can I really look at that died so we'll grow 20 patients roughly each of these ups for total roughly 60 patients and then based on dips response, we we would sell that served from the 50% above.

Wei Lin: There's the optimization cohort, and there's an expansion cohort for non-small cell lung cancer. And to really address your question, I'll focus on the expansion cohort, non-small cell lung cancer. [inaudible] either Pembroke Monotherapy or Pembroke Plus Chemo in these segments, and also know the different benchmarks. And so that is how we're going to really look at the data. So we'll enroll 20 patients in each of these subgroups for a total of roughly 60 patients. And then based on the response rate, we will observe that in the 50% above, in the 1 to 49, and less than 1%. And benchmarking, again, Pembroke Monotherapy, that's how we'll make an assessment whether there's activity or synergy that we can potentially observe with a combination of Pembrolizumab and BAMPEG, and a future registration trial in non-sparse and non-small cell lung cancer will be entirely based on what we have to observe in each of these subgroups and what population will be ideally Jennifer, should I go on and try to answer the email?

149, and last 1% and benchmarking against Pemble monotherapy, that's how we will make an assessment whether.

Theres out activity or synergy that we can potentially observed with a combination on with pimple, less Matt and and Bam Tech and and our Reggie future registration trial.

In non first time, non small cell lung cancer wouldn't probably based on what we optune therapy. Each of these subgroups and what population will be ideally you go into the future Recreation study so.

Yes, it addresses the.

On how we're going to look at the Guy in regard to making a recognition decision in non small cell lung cancer.

Temperature take a long and to answer yes.

Sure it little bit into how were thinking about the CR endpoint and what sort of thing yeah were at their thank you sure sure absolutely.

Or our historic has always been used test on the benchmark for assessing.

[music].

On the people in reactivity up any truck in oncology now I think.

Keith response rate endpoint are somewhat arbitrary and their strengths we license how they correlate with progression free survival and clean overall survival and what really helped us our assessment and certainly its argument we we are.

Wei Lin: I'd like to share a little bit on how we're thinking about the CR endpoint and what sort of things that we're looking at.

Wei Lin: at their. Thank you.

Making to both ft air quality.

Wei Lin: Thank you.

Wei Lin: Sure, sure, absolutely. ORR has always been used as sort of a benchmark for assessing, you know, the preliminary activity of any drug in oncology. Now, I think, you know, these response rate endpoints are somewhat arbitrary, and their strength relies on how they correlate with progression-free survival and ultimately overall survival. And what really helped us, our assessment, and certainly it's an argument we were making to both FDA as well as other non-U.S. health authorities, including the EU and other places, is really based on the bend analysis presented by FDA back in around ASCO 2019. And just a reminder, back at that time, FDA had Food Together, all the patient data in Firstline Metastatic Melanoma, from all the phase III trials, regardless of type of agent, whether it be TKIs, BRAF, and MEK, or IO therapy, whether it be PD-1, PD-L1, or even CTLA-4.

Ex us health, where he's including you and and other places it's really based on the Bend analysis presented by FDA back in on Iraq, Asacol 29 team and just a reminder back at that time after he had.

Well together.

All that.

Pacing data in first line metastatic melanoma from all the registration trials, regardless of type of aging whether it be teekay, Ais b rap and Mac or I O therapy, whether beyond.

PD, one PDL, one or on where you can see Kelly for based on all these first time data at the half on in their database K performed analysis look at the correlation of various response rate endpoints to question increase survival horse survival and what he is actually demonstrating their.

Wei Lin: Based on all these first-line data they have in their database, they perform meta-analysis, looking at the correlation of various response rate endpoints to progression-free survival or overall survival. And what they even beyond just the over-response rate, ORR, the depth of the response, the deeper the response, the stronger the correlation to PFS and over-survival. So the correlation to long-term survival is higher for 50% depth response compared to 25% and even higher for a patient who achieved 75% shrinkage of the tumor compared to 25%, and the best patients who did the best were the patients who achieved 100% shrinkage of their tumor. So, and that is really the strength with which we're proposing a change from OR to CRR because of this stronger correlation with a deeper response. And the highest response, or the most definite response you can achieve is, of course, a complete response. And this is what we've been seeing with our data, generally from Pivotal 2, for the combination of BANPACK for Nebola maps.

Alice is up nearly 5000 patients is sound on.

Even beyond just overall response rate for our depth response deeper the response the stronger the correlation to PFS and overall in overall survival so onto equation to long term survival.

Higher plus 50% death response, compared to 25, and even higher for piece from a cheap 75% trinkets that schumer compared to 25 and the best patient would get the best.

Our the patient who achieved.

100% shrinkage.

For your tumor so and that is really the screen.

With which we're we're proposing a change from all our two CR because at this stronger correlation with a deeper response in the ending to the highest response would most depth of response can achieve its of course, a complete response and this will be seeing where card not ask Ken from could go to for the combination.

Ben Petrifying Ebola, Matt we've cheap at 34% response rate with just a year follow up and now we have beyond 21 month follow up and that's a number 34% is higher than what.

Wei Lin: We've achieved a 34% response rate with just a year of follow-up, and now we have gone beyond 21 months of follow-up. And that number 34% is higher than what NEVO or even NEVO-IPI, which is the best available standard care, achieved with five years of follow-up. They had only a 21% complete response rate with five years of follow-up. And this is with a number that continues to evolve and deepen over time.

Evil, where even evil if he would just on the best available. It's kind of care had achieved with five years have problems. They had only at 21% complete response rate was five years follow up and get this with a number that continue to evolve and deepen overtime, which is very characteristic of fun.

Wei Lin: risk of immunotherapy. So it is certainly our aspiration and hope that with longer follow-up, the complete response rate will both improve in the PIVO2 cohort and also especially in the restoration study that's actually operationalized by our partner, BMS. So I think this is really – I think the argument we're making for the health world is based on the FDA analysis, the death response correlates the strongest with long-term survival, and the complete response of all the death responses correlates the strongest. And if there's one serogenin point that can be used based on response rate, it should be a CRR endpoint. And with that strong linkage, it should be used for the early assessment accelerated approval. So that is the argument we're making. Great. Thank you.

RFP. So it is certainly our aspiration and hope that with longer follow up on to complete response rate before improving the pivotal cohort and also if especially in the recreation study on on the tax to operationalize by our partner Pms. So I think this is really.

I think argument, we're we're making good health, where geese is basically ft analysis. The death response correlates to strongest with long term survival and be complete response, all that Jeff response correlates to strongest and if theres one surrogate endpoint catch be used based on response rate it should be a CR.

Endpoint and with that strongly encourage that should be used for key early assessment accelerated approval. So asked them the arc argument for me.

Great. Thanks for taking the questions sure.

Operator: Great, thanks for taking the questions. Sure. Thank you. Our next question comes from Chris Shibutani of Cowen. Your line is open. Great. Thanks very much. I have two questions, if I may.

Thank you. Our next question comes from Chris Shabby tiny from Cowen Your line is open.

Great. Thanks, very much two questions. If I may on 358 can you just remind us and I apologize if you already mentioned psoriasis and H D will we see data on this and if so when it.

Operator: On 358, can you just remind us, and I apologize if you already mentioned this, psoriasis and AD. Will we see data on this, and if so, when? Sounds like Lilly has commenced some Phase II trials in one of those during the year, or that is the plan. And when we see that data, will it just be PKPD, similar to lupus, or is there a possibility of seeing some early efficacy endpoints as well?

Sounds like Lilly has commenced some phase two and one of those during the year or that is the plan and when we see that data will just be PK PD similar to lupus or is your profitability is seeing some early efficacy endpoints as well.

Thanks, Chris Chambers.

It to 330 question. Thanks.

Yeah, sure Hey, Chris.

So just to clarify Lilly is running two phase one be studies that one is in psoriasis and the other is in atopic dermatitis and we mentioned in the call. So when the coded you know pandemic broke out Lilly's first response was to pause the studies and you know any real.

Jonathan Zalevsky: Thanks, Chris. Jay, I'm going to ask you to take the 358 question. Thanks.

Jonathan Zalevsky: Yeah, sure. Hey Chris.

Jonathan Zalevsky: So, yeah, just to clarify, Lilly is running two Phase 1B steady. One is in psoriasis, and the other is in atopic dermatitis. And as we mentioned in the call, when the COVID, you know, pandemic broke out, Lilly's first response was to pause those studies. And, you know, and it really made sense. Those are non-oncology studies, for example, so they're really, they're chronic, non-life-threatening diseases. But as we did also mention earlier in the call, those studies have now been restarted, and they're enrolling patients. So we would expect that

We made sense those are non oncology studies for example, so there really are chronic non life threatening diseases.

But I do we did also mentioned earlier in the call. Those studies have now been we started.

There are enrolling patients.

So we would expect that data from those studies will not be presented this year. You know those studies are still in the enrollment phase, but it's reasonable that perhaps at the end of next year that would be reasonable to see some data from these studies and then in terms of what kind of data you could see these studies are phase one to be so.

Jonathan Zalevsky: Thank you.

Jonathan Zalevsky: Data from those studies will not be presented this year because those studies are still in the enrollment phase, but it's reasonable that perhaps at the end of next year, it would be reasonable to see some data from these studies. And then in terms of what kind of data you can see, these studies are phase 1B, so they definitely have a substantial pharmacokinetic as well as pharmacodynamic component to them. But the other thing that's also present here is there are a lot of biomarkers that have been put in, especially, as you know, Chris, with your familiarity with a lot of skin studies, skin biopsies, and punch biopsies So there's also going to be an assessment of what's happening locally in the skin, for example, with the different keratinocytes, things that are happening, lesions, and in particular looking for infiltration of Tregs, which could be very disease-dependent. I hope that answers your question.

They definitely have a substantial pharmacokinetics as well as pharmacodynamic component to that.

The other thing. That's also present here is there a lot of biomarkers that have been put it, especially as you know Chris with your familiarity with a lot of skin studies, you know skin biopsies and punch biopsies are very very doable. So there is also going to be an assessment of what's happening locally in the skin.

Example, but different keratinocytes things that are happening within disease lesions on in particularly looking for infiltration of T. Regs that could be very disease is beneficial.

I hope that answers your question.

Yes. So then how will that be determined which one they'll start a phase two trial in terms of the two indications and will we get a visibility into that decision during 2020.

Oh, yes, so in the deal that we signed with Lilly you know a few years ago in that deal for phase two studies.

Lilly very much likes to use the practice of of not announcing what the indications are too early to.

Jonathan Zalevsky: Yeah, so how will we determine which one they'll start a Phase 2 trial in terms of the two indications, and will we get visibility into that decision during 2020? Yeah, so.

We maintain competitive but not a strategy. So so the Lukas study that was announced because that study just kicked off as we stated as a second phase two study that will begin later this year than a different autoimmune indications not lupus a different one and as we get closer to the start of that study.

Jonathan Zalevsky: So in the deal that we signed with Lilly a few years ago, in that deal, there were four phase two studies, and Lilly very much liked to use the practice of not announcing what the indications were too early to maintain competitive and other advantages.

I expect Lilly will announce that indication.

And then there are two more indications that are coming.

Jonathan Zalevsky: So the lupus study was announced because that study just kicked off. As we stated, there's a second phase two study that will begin later this year. And it's in a different autoimmune indication, not lupus, a different one. And as we get closer to the start of that study, I expect Lilly will announce that indication. And then there are two more indications that are coming that will be announced later. And we expect those two studies to begin next year.

But again will be announced later and we expect those two studies to begin next year.

Great My quick second follow up.

The conference calls have tended to be totally Easter egg moments during Q anywhere you give us some sort of a bed and peg pivot to melanoma update did I Miss that is there anything you can share with us.

[noise], we're going to save that for kids secret [laughter] had.

Okay.

Yes.

Jonathan Zalevsky: Great. My quick second follow-up. The current conference calls have tended to be toys, Easter egg moments during Q&A where you give us some sort of a Ben Pegg pivot O2 melanoma update. Did I miss that?

Thank you.

Thank you.

And our next question comes from Difei Yang from Mizuho. Your line is open.

Hey, good afternoon, everyone. This is Alex for the sake.

I was had a question on.

The bladder cancer setting I guess I was wondering if you could comment on how do you see the market opportunity there for Ben Peg it.

Operator: Is there anything you can share with us? We're going to save that for TISD, Chris. Okay. Thank you. Thank you. Bye. Thank you. And our next question comes from Defe Yang from Mizzou. Your line is open. Hey, good afternoon, everyone. This is Alex on for D-Fate. I had a question about the bladder cancer setting.

Where do you see the biggest unmet need.

Given the involving competitive dynamics competitive landscape there.

So why do you want to.

Answer that question sure Yeah, I'd be happy too so I think Scott so on.

Over the last year I think the landscape for first fund.

Operator: I guess I was wondering if you could comment on how you see the market opportunity there for BAMPEG and where you see the biggest unmet need, given the involving competitive dynamics inside of that landscape there. So, Wei, do you want to..., answer that question?

Sonic bladder cancer has continued evolved and we'll gain some clarity.

With the on.

With the success of value map.

In that disease, setting we see that.

Wei Lin: Sure, yeah, I'd be happy to. So, I think, over the last year, the landscape for first-line metastatic bladder cancer has continued to evolve and will gain some clarity. I think, you know, with the success of ValueMap in that disease setting, we see that maintenance therapy has now been introduced for bladder cancer in the first-line setting. And then with the failure of PEMBRO in their registration trial in combination with chemotherapy, I think combination therapy with chemotherapy looks like it won't be the de facto, the dominant standard care in first-line. So it remains fairly segmented in the sense that you still have disease entities that are classified as CISPOP and eligible, and CISPOP and ineligible.

Maintenance therapy, now see introduced into bladder cancer in the first time setting and then with the failure pembro in their retribution trucking companies chemotherapy I think on.

He combination with chemotherapy and looks like on it won't be de facto should keep dominant stand of care in first line. So do we minds means could be segmented in a sense. It theres you still have Kentucky, Eric classified as just talking how much will insist upon you knowledgeable and the standard care I think.

Changed dramatically.

In the sense that in the spot eligible remains to be segmented for aisle quite appealing positive and negative right. I think what has done on gain cleared he is.

Wei Lin: And standard care hasn't changed dramatically in the sense that in CISPOP, and ineligible remains to be segmented for IO, for the PON positive and PON negative, right? I think what has gained clarity is that probably IO plus chemo is not going to be a dominant therapeutic option, unlike say non-small cell lung cancer or head and neck cancer, and remains fairly open for novel agents that can bring significant benefit to patients in that therapy. So providing that context first, I think the promising treatments that are currently in development certainly include not only our combination of the MPEG plus Ebola map but also passive from cytogenics plus pembrolizumab. And there are pros and cons to different regimens.

Probably high O plus chemo and it's not going to be a dominant therapeutic option. Unlike say non small cell lung cancer or in head neck cancer.

And to remain fairly open for novel agents on that can bring significant benefit to patients not therapy. So.

Providing that context first 18 come I think a promising on treatment that are currently devolvement certainly include not only our combination of impact plus.

All of that but also on.

Passive from Savage next plus Pembrolizumab, and there's time, theres pros and cons with different regimen.

The Rx meets a pure Ohio regimen debt still be served on chemotherapy option for later line therapy.

Wei Lin: I think our regimen is a pure IO regimen that still reserves chemotherapy options for later lines of therapy, whereas the passive pembrol combinations is really a combination that, while it's the ADC, it's effectively a really smart chemo backbone. And so I think, you know, the activity looks like it's higher based on early phase data, but the safety profile is actually probably worse compared to BenPak plus Nego And so I think the jurors throughout depend on how they will have the early phase data that we have presented publicly, as well as the autogenetics and Merck. And I think it remains to be seen what the restoration trials really deliver in terms of clinical activity. Now, the highest in that need we still recognize as being the patients who are CIS-spotting ineligible, and hence the most powerful and most effective chemotherapy for treating a lot of cancer is not available to these patients on the one hand.

Where we stand on T. patches on PEMCO combinations usually.

As a combination that pass it Paul it's 80 see is effectively a could be smart chemo.

Backbone and so I think.

The activity looks like it's higher based on early phase data for the safety profile. It is actually on I'm, probably worse compare to Bamtech, plus neagle and still taking.

George to out.

Then sound how they will have early phase data that we have presented publicly small business counter genetics Hancock and Mark I think I remains to be seen what the registration trials will be delivers in terms of contract activity.

Now the highest unmet need we still recognized.

Speaking that patients who are responding ineligible enhance not the most powerful on and most effective chemotherapy for.

For treating bladder cancer and are not available to these patients on one hand and on the other hand on.

Wei Lin: And on the other hand, you know, the PD-L1 negative population, IO therapy is not available to them as first line therapy. So that's why I think our development strategy is still very relevant at this stage, even with all the evolving treatment landscape, that we still believe the highest need remains to be in the patients who are CIS-spotting eligible and PD-L1 negative, and that subgroup of patients. And I think our restoration strategy still positions us as a potential new therapeutic option if we can successfully deliver on the PIVOT-10 study. So we're certainly optimistic that we can replicate what we have seen in PIVOT-02, that we can still bring certain value to patients. And I think, you know, the usage in this disease area really depends ultimately on both the safety as well as efficacy delivered by our combination and the combination of PEMBRO plus PATCYF.

The the P. Dauman negative population I O therapy is not available to them as first line therapy. So that's why I think archibong strategy is still very relevant.

At this stage, even with all the evolving treatment landscape that we still believe the hisun that need remains to be in the patients square Sichuan eligible and p. going negative for down.

Got subgroup population and I can call retribution strategies to position us as a potential on your new therapeutic option. If we can successfully deliver on the pivot time can study. So we're certainly optimistic that can replicate what we have seen pivot twoq can we still have.

Kim Queens and value to patients.

And I can come the usage in English Tcs area really ultimately can give it depends on the both the safety as cost efficacy delivered by our.

Our combination and the combination of Pembroke as Pat said.

Wei Lin: And I think the safety consideration will probably be another key factor. I think there's certainly room for both potentially to have a restoration path, and ultimately, it's really going to be tailored by individual physicians based on the need and the health status of bladder cancer patients, many of whom have had the bladder removed and have comorbid conditions that may not allow them to tolerate a fairly toxic chemo regimen or treatment options that have sort of a chemo-like toxicity profile.

And I think the safety consideration will probably be another key factor.

I think theres, so I certainly would mean form boats.

Potentially to have a registration path and ultimately, it's really kind of be tailored by the individual traditions pay sound they need and to health status of bladder cancer patients many of whom I have had to platter, we move and half on cold water conditions that may not allowed them to tolerate have truly toxic.

On chemo regimen or or or treatment options to happens for bank chemo like toxicity profile. So.

Operator: Okay, thanks very much for the color. And then just on Pivot 2, do you guys have any plans to provide an update on Pivot 2 and bladder cancer by any chance before the Phase 3 data?

Okay. Thanks, very much for the color and then just just on the pivot to.

Do you guys have any plans to provide an update from from pivot to and bladder cancer by any chance before that the phase three data.

Operator: Yes, the data we have provided to date publicly, both in public congresses as well as in earnings calls, has been pretty mature data. I think for future updates, we do plan to collate our data from Pivotal 2, including our bladder cancer data, in a follow-up publication where we can more finely and in greater detail dissect out all the nuances of the data and provide a much richer set of data in a publication than can otherwise be presented in a 5-10-minute congress presentation.

Yes, picante data, we provided kind to date.

Publicly on both in.

The Congress business was over earnings calls have been pretty mature data I think on poor for future update we do plan to co lead our data from pivotal to including our bladder cancer data.

In a hello publication, where we can more.

Finally at more in greater detail tax headcount older nuances of the data and provide much richer set a downtick true.

Hi, any publication, Dan can otherwise be presenting a five to 10 minute hi conquest presentation.

Great. Thanks for taking my questions.

Operator: Great. Thanks for taking my questions. Thank you. Our next question comes from George Farmer from BMO Capital Markets. Your line is open. Great, thanks. This is Govind on behalf of George.

Thank you.

Our next question comes from George Farmers from BMO capital markets. Your line is open.

Great. Thanks, This is going on for George.

Operator: There are two questions, one on 358.

Two questions one on three cents.

Operator: and the other on the begging prayer program. But the 358, as we think about the data coming up, I believe

And the other on the.

Program, but grew 58 or they are as we think about the data coming up.

I believe the mild moderate data and then they do you mentioned the lupus disease activity index for the upcoming president of the six and above or this one it was probably below that so I'm just trying to figure out here.

Operator: The mild-moderate data and then

Operator: And I think Daisy mentioned the Lupus disease activity index for the upcoming trial is gonna be six and above. But for this one, it was probably below.

Operator: Below six, so I'm just trying to figure out here if we there's an

We are going biomarker data is going to be some public debt metrics is going to activity. In this is going to be shown how should we be thinking about.

Operator: Biomarker data, there's going to be some, probably this metric is going to be, the activity index is going to be shown. What should we be thinking about...

Operator: Thank you.

What would be.

A meaningful change.

Operator: totally understanding that this is not a trial designed for F50 short duration of treatment

Totally understanding that this is not so not a trial design 50 short duration of treatment and all of that and then the second question on the Ben take part was [noise].

Operator: and all of that. And then the second question on the BEMPEG part was about the BEMPEG Q-TRUDA program.

For the Ben Pega Keytruda program.

Operator: Can you remind us again how BEMPEG was able to go higher?

Can you remind us again, how then pay was able to go higher I believe you guys are dose escalating that led to a higher than what you've done without peto and and would that higher dose and thats something that you guys did you guys extend into other tumor indications we would be at this higher Jessica thanks.

Operator: I believe you guys are dose-escalating that drawing higher than what you've done with the opportunity.

Operator: , and with that higher dose, is that something that you guys could expand it into other areas?

Operator: Other tumor indications, you would be at this higher dose as well. Thanks.

Operator: Thanks, Govind. I'm going to ask Jay-Z to take the first question on 358 and the ACR data that we plan on presenting, and then I'll have Wei take the second one on back to the Propel design and the dose escalation component of it.

Thanks, Kevin I'm going to have changed it take the first question on three TV and the HCR.

Data that we plan on presenting and then I'll have way you take the second one.

Back to the propel design and tenant dose escalation company.

Thanks Casey.

Operator: Yeah, thanks, Jennifer. Gobind, very insightful questions.

Yes, Thanks, Jennifer Golden very insightful questions.

Operator: So you're absolutely right. The MAD study in 358 was in mild to moderate lupus patients. So there's really a range of baseline disease, including very mild in some cases, because remember the patients are on steroids and, you know, they could be under control, which is in stark contrast to the Phase 2B, where all patients will have at least a baseline lead I of six. So those patients are going to be much more advanced, and they'll all have clinical presentation of disease, which is not the case in the Phase 1B MAD. So the patient population is different. And then, of course, the duration of treatment is very different, right? It was a six-week treatment in phase 1B, whereas it will be a six-month treatment in phase 2B. So then, given all of those important differences, what are some of the things that you should look for?

So you're you're absolutely right.

Mad study in 358 wasn't mild to moderate.

Lupus patients. So so there's really a range of baseline disease, including very mild right in some cases, because remember the patients on steroids and you know they could be under control, which is in Stark contrast to the phase to be where all patients will have at least a baseline lead item.

Six so they've got those patients are going to be much more advanced and all have clinical presentation of disease, which is not the case in the phase one be Matt.

So the patient populations different.

And then of course, the duration of treatment is very different right. It was a six week treatment in the phase one be whereas it will be a six months treatment in the phase Twob. So then given all of those important differences what are some of the things that you could look for so when we present additional data from that study.

Operator: So when we present additional data from that study, firstly, we'll be presenting the same kind of additional constellation of data that we presented for the single descending dose study in healthy volunteers. There's quite a bit more biomarker data. There's quite a bit more FOXP3 and other Treg-associated data, as well as the potential for some gene expression data as well, so that we presented at ACR last year in the SADD data. So we'll present the same additional biomarkers, and then there's one additional set of features, which is that we do have measures of disease activity, anything that we measure. And we measured a range of different endpoints, like the Speed Eye Scale, the Classy Scale, and so forth.

Firstly, we'll be presenting a same kind of sort of additional constellation the data that we presented for the single ascending dose study in healthy volunteers, there's quite a bit more biomarker data, there's quite a bit more Fox P. Three and other T regs associated data well is essential for some genetic gene.

A question data as well.

So that we presented at a CR last year in the sad data. So we'll present same additional biomarkers and then there is one additional set of features which is that we do have measures of disease activity anything that we measured.

And we measured a range of different endpoints, such as the lead I scale classy scaled and so forth. So at this kind of in early study early setting what I really look for it makes me excited do I see dose dependent changes.

Operator: So at this kind of early study, in this early setting, what I really look for that makes me excited is do I see dose-dependent changes? And, you know, you wouldn't expect that under such a short amount of treatment you would have a very profound effect on the disease course. But if I see dose-dependent changes in a clinically measurable marker, that would make me really excited. It would certainly be the kinds of information that would make you feel really confident to move into the Phase IIB setting. So our aim will be, we'll be working with Lily, and we're going to present many additional features of that study. So please stay tuned for that. That's also coming up in November, Goldstein. Now, what I'll do is I'll turn it over to Yiwei to talk about the dose escalation and optimization portion of the BEMPEG plus PEMBRO program.

And you know you don't expect that under such a short amount of treatment you would have a very profound depending on the disease course, but if I see dose dependent and changes in a clinically measurable marker that would make me really excited.

Certainly be the kinds of information that would make you feel really confident to move into the phase two consent.

So our aim will be we'll be working with Lilly and we're going to present. Many additional features of that study. So please stay tuned for that that's also coming up in November Goldman.

And now I'll do the I'll turn it over to you way to talk about the dose escalation and optimization portion of the impact plus Pembroke program.

Operator: Thanks, Ajayji. So that's a really great question about the, so why are we still optimizing the dose when the molecule is already registered? So first of all, I think it's helpful to remind people that the six micrograms per kilogram dose, in combination with EbolaMap, in registration in several of our programs, is still a very efficacious dose. That's the dose on which we have obtained breakthrough therapy destination from the FDA. So, and so it's highly active, and so it's actually a very good dose and provides an outstanding safety profile where we basically, as far as immune-related AE is concerned, we observed the same rate of IMAE as EbolaMap monotherapy.

Thanks, Casey So thats a really great question about the on time. So why are we still optimizing the dose finding the molecule has already registration.

So first of all I think I'd say, it's helpful to remind people that the six microgram per kilogram dosed in combination Yuval mapping registration.

Instead of our programs, it's still it's a very efficacious dose that's it dose on which we have to obtain equate to test therapy designation from the FDA, So and so it's highly active and die. So it's actually a very good dose can provide outstanding safety profile, where we we basically as far as.

He knew where they use concern we observed the same way to hi, I am AG Sniffle monotherapy. So so that having said I think if you took a look at that on deemed hard on oncology landscape and rice. Your tumor types you kind of have can segue into roughly on on several different types.

Wei Lin: So that having been said, I think if you take a look at the entire oncology landscape and various tumor types, you kind of can separate them into roughly several different types in regard to the response to PD-L1. Then, in therapy, you have diseases like melanoma and RCC where a PD-L1 biomarker is not needed at all. So monotherapy, PEMBRO, and monotherapy NEVO work very, very well regardless of PD-L1 expression in melanoma. And when RCC is used in combination, you do not need a biomarker at all. Now, on the other hand, you have tumor types such as,

In regard to their response to PDL one.

Parent guarantee you have diseases, like melanoma, and RCC, where a pico lymphoma, Chris not eat at all so monotherapy on Pembro in monotherapy Nivo works very very well because its Peter arment expression in melanoma in RCC in combination you do not need.

A biomarker at all now again on the other Hank you have tumor types.

Such Hassan.

Wei Lin: and especially triple negative breast cancer where a biomarker is needed. Now, for both lung and head and neck, monotherapy only works for a certain cut point or higher of PD-L1 expression. Below that, you really need the boost from chemotherapy.

Uh huh.

Non small cell lung cancer head neck cancer, and especially triple negative breast cancer or a biomarker is needed now for both on long and forehead Mac monotherapy only works for a certain cut point or higher PDL, one expression below that you really need to boost from.

Chemotherapy and core for triple negative breast cancer on on both the Pembro and a test without at chemistry, even combination chemotherapy. The Pete on maybe the patients to not right benefit from the addition of a checkpoint. So so I think in some tumor types you definitely need.

Wei Lin: And for triple negative breast cancer, both the PEMBRO and the TESLA data demonstrate that even with combination chemotherapy, the PD-L1 negative patients do not derive benefit from the addition of a checkpoint. So I think in some tumor types, you definitely need some additional activity of inflammation to really change the immune status of these tumors. And BEMPEC, being a pro-inflammatory cytokine, we believe can provide that extra boost to immunotherapy. And we certainly have clinical evidence to suggest that, based on PED-L2, we have in several tumor types demonstrated the upregulation of PD-L1 and other inflammatory status markers in the tumor after receiving just a single dose of BEMPEC. In our bladder cancer cohort, we had 10 patients from whom we obtained on-treatment bio

Need.

Additional could be up inflammation to really changed the immune status of these tumors and.

Ben pack being probably of time Quesada kind would be can provide that extra boost to immunotherapy and we have certainly clinical evidence to suggest that based on pivotal Q. We have he several tumor types have demonstrated T. The upregulation of PDL, one and all the prime between odds status Mark.

Hers into tumor after we see in just a single dose of Antech, specifically in our bladder cancer cohort. We had 10 patients from whom we have data obtained on premium biopsies on so those patients were dosed with Bamtech placebo and then on.

Wei Lin: So those patients were dosed with BEMPEC placebo. And then before they received the second dose of BEMPEC placebo, prior to their 21-day follow-up, we obtained another biopsy. And that biopsy demonstrated that just a single dose of BEMPEC was able to turn 10 patients who were previously PD-L1 negative, really PD-L1 expression zero, into PD-L1 positive. So that's seven out of 10.

Be before they received the second dose of Antech Eagle prior to their 21 day.

Follow up we obtain another biopsy and that Pops he'd chemistry to kiss a single dose of Bamtech, We're able to turn 10 patients who were previously p. going negative really PD lone expression zero to compete on positive. So thats seven out of 10, so that being.

Wei Lin: So that being the case, you know, we certainly have a lot of motivation to try to tackle diseases that are previously either coded to checkpoint monotherapy alone, or even in the case of TMBC, or even additional chemotherapy, not able to really turn this into an immunosensitive state. That with additional BEMPEC, I think we certainly are eager to test the hypothesis whether BEMPEC can actually provide that immune inflammation to achieve checkpoint-wise efficacy across more tumor types. So that's our primary motivation. Now is that possible, right? Is it safe to do that? And we believe it can be done, probably also because of the wealth of data we've generated in our ongoing programs. As we treat more and more patients and develop improved management guidelines to really manage a lot of the adverse events observed associated with BEMPEC, especially cytokine-related toxicity, what we've seen is that these are very manageable, and especially with the treatment guidelines, one of which was a dose-limiting toxicity of BEMPEC, which is hypotension, can be very well managed by just proactive hydration during cycle one. And when we implemented that, the rate of hypotension dropped significantly, and then

On the case, we certainly have a lot of motivation to try to Taco diseases that are previously either on a coach too.

Point monotherapy alone were even in the case it can be C or even additional key more KPN not April two two really turned this country, meaning sensitive state.

With additional band pack I think.

Certainly our Eagle retest hypothesis, why depend pad can actually provide that immuno inflammation to to make chempoint weisler efficacy across more tumor types. So that's our primary motivation now it's not possible right. It's a safety do that and we believe it can be done are those who because of the bulk of data we have.

Generating in or Oncomed programs as we.

Treat more and more patients and default on improved management guidelines to really managed a lot of the adverse events up there a suit with NPAC, especially as cotter kind would need to toxicity, we'll be seeing is down these are very manageable and especially with nutrient guidelines, one of which which was a dose limiting toxicity of impact.

Just hypotension can pretty well managed.

Hi, just not proactive hydration cutting cycle, one and when we implemented that he did weighed upon hypotension crops to significantly and we don't see to high grade event that we had typically seeing.

Wei Lin: The high-grade event that we had typically seen at very early dose escalation when we did not have these management guidelines and hydration guidelines in place. So we actually believe with the current management guidelines, BAMPAC has a safety profile for which we can increase the dose even higher and deliver a similar safety profile on the one hand, and on the other hand, produce even more pro-inflammatory activity of our cytokine, and perhaps, really, in combination, can broaden the activity of a checkpoint to a broader population of patients. So those are kind of the two primary motivations, and I think there is some evidence that we can actually do that. And then, if we succeed in giving a higher dose, we can certainly take the combination to some of the tumor types I just highlighted, where PDOR expression is low in a large portion of patients, and the current IO therapy does not demonstrate significant activity in those patients. Thank you.

Very very early dose escalation when we could not have these management guidelines hi accretion guidance in place. So we actually believe with a current management guidelines Finpac has to take your profile.

For which we can increase the dose even higher.

Yeah.

Okay and deliver a similar safety profile on the one can you give the hand produce even more pulling primary activity.

First time to car.

And perhaps ruling combination checkpoint can broaden the activity of a checkpoint to progress population of patients. So those are kind of the two prime and motivations and I think some evidence that we can actually do that.

And then if we succeed and give them the higher dose we can certainly take the combination to some of the tumor types I, just highlighted where people expression as low for a large portion of patients and the current Io therapy on does not chemistry significant activity in those patients.

Thank you.

Operator: That's really helpful. Thank you.

That's really helpful. Thank you.

Operator: If I may just have one more question on top of that, does that mean you guys have figured out what the new BEMPEG dose is with this new protocol? And can you share that with us?

Made just have one more on top of that does that mean you guys have figured out what the new then peg dose is with this new protocol and can you share that with it.

And so thats, it's still in dose escalation on the optimization cohort and facts. We are actively going and then I think we so so that data we presented at a future conquest and so far.

Operator: And so that's, it's still in dose escalation, the optimization cohort, and it's actually active, it's going. And then I think we, so that data will be presented at a future congress. And so far, so far, we've not identified any DLGs in our ongoing dose escalation, but we would certainly be happy to share the data at a future conference. Great, thank you.

So far we've not I can find etiology piece in our ongoing dose escalation.

But would certainly be happy to share the data had few future Congress. Thanks.

Great. Thank you.

Operator: Thank you. Our next question comes from Aiden Hussonov from Benchmark. Your line is open. Hi, everyone.

Thank you Sir our next question comes from Hayden has enough from benchmark. Your line is open.

Hi, everyone. Thank if we're taking my questions and congrats on the progress this quarter.

Operator: Thank you for taking my questions, and congratulations on the progress this quarter. I have a question regarding the BAMPINC adjuvant melanoma study. Is there any accelerated approval kind of surrogate endpoint, just like CR and metastatic, just to make this argument for adjuvant melanoma? And also, regarding the enrollment, so I think it was previously 1,100 patients. Could you just clarify the target enrollment at this time? Wade, Wade, could you review the study design and address the question? Thanks.

A question.

Darren Bent bank a joint melanoma study is that any accelerated approval kind of surrogate end point, just like CRM metastatic or just to make this argument or for agile and melanoma case and also regarding enrollments. So I think was previously 1100 patients could you.

Just to clarify it's a target enrollment.

At this time.

Well great could you review the study design and OCA question. Thanks.

Operator: Yeah, so for the atrium study, it's a wonderful question. I think that's sort of the Holy Grail.

Yes, so 20 foot action steady on it. It's a wonderful question I think that's worth a hobby grow older bus would look like to have a surrogate endpoint that allow I heard you beat out for Ashwin study because actions. So you can do very very long.

Operator: All of us would like to have a surrogate endpoint that allows an early readout for atrium studies because atrium studies can be very, very long on the one hand and require a large number of patients. It's a huge investment, and then a lot of patients are certainly waiting because that's one area where we can provide a cure to a lot of patients. So, I think, you know, unlike, say, in the metastatic setting, Agilent really is challenging in having a certain amount of data to link up some type of surrogate to either disease-free survival or relapsed-free survival. And in melanoma, I think the most promising marker to date is probably some type of tumor DNA clearance. However, that has not been firmly established yet.

And.

On the one Henan you require large passionate patients since a huge investment.

And then a lot of patients hersha waiting because that's one area. We can provide a cure to to a lot of patients.

So I.

I think on.

You know.

Unlike stay in the metastatic setting.

Actually it really is challenging in having time.

Certain amount of data to being cut some type of a surrogate to either disease free survival relapse free survival and melanoma I think the most promising marker to date is probably some type of on.

Certainly tumor DNA clearance harbor that has not been firmly established yet it theres not a wealth of data like you pointed out with getting that analysis, where they have connected to death response with long term survival. There has not been a walk a data awful lot of patients tested with.

Wei Lin: There's not a wealth of data, as I pointed out, with the FDA meta-analysis where they have connected the death response with long-term survival. There has not been a wealth of data from a lot of patients tested with ccDNA in a completed retribution study and linked the clearance of ccDNA, say, with either DFS or RFS. So, with that lacking, I think the health-worthy feedback, and I've certainly attended a number of workshops on this, and I think that's – FDA made clear in one of the workshops that that is the kind of data they're looking for to really establish a marker such as ccDNA clearance as a potential surrogate for survival approval, correct? So, that's sort of the – what has not been – what's the missing piece in terms of registration for adjuvant therapy.

CCMA.

Any out any compete Irach recent study and link the clearance so ctdna say with either TFS far I fast. So so with that lacking I think the health, where the feedback and I I've certainly attended number workshops on this and and and I think Thats FDM made clear in one to workshops that that is the.

Got it they're looking for two to the establish.

Hey markers such CTM clearance.

Say pretentious haircut forks her approval right. So that's that's done sort of the.

What has not been could not should be on what's the missing piece.

In terms retribution your core actions setting now whether that we that data we merged between now and the completion our melanoma study in action setting I think that yes to be seen it's such a data will emerge and FDA fuel comps in spoke out guidance that was certainly has allowed them to come to provide opening up.

Wei Lin: Now, whether that data will emerge between now and the completion of our melanoma study in the adjuvant setting, I think that is yet to be seen. If such data were to emerge and FDA felt confident about that data, that would certainly, using, say, for instance, ccDNA as a surrogate to allow early approval in the actions technology study, followed by delivery of the DFS or RFS in that setting.

Eight you seen safe points needs to see seeking a surrogate for to allow early approval in the actions technology study follow up like delivery.

That's why I pass not setting.

Wei Lin: Thank you. Thank you. Yeah, absolutely. And for the target enrollment for this study.

Thanks for your thank you.

Yeah, absolutely and and the pulled the target enrollment for this study.

Oh, it will target enrollment.

Operator: I was just going to say, can you explain the difference between the 950 and the 1100? We landed on the 950 for the final protocol.

Yeah go ahead.

Yeah as you can say he explained the difference in the 915 11 hunter be landed on nine testing for the final protocol. Thanks.

Wei Lin: Yeah.

Yeah.

Operator: Is that what you were asking, just the number? Yeah. Yeah.

Is that what you're asking a chip the number or yes, yes, just curious.

Operator: Our next question comes from Jay Olson from Oppenheimer. Your line is open. Oh, guys, congrats on the progress and thanks for taking my questions. I had a question about 358 and I was wondering if you could comment on Amgen's recent decision to discontinue development of their IL-2 mutine NRA and focus on GI autoimmune disorders.

Yeah. Thanks Kerry.

Thank you.

Next question comes from Jay Olson from Oppenheimer. Your line is open.

Oh, Hey, guys congrats on the progress and thanks for taking my question.

I had a question about 358 and I was wondering if you could comment on amgen's recent decision to discontinue development of their aisle Q butane and our and focus on Gee I don't know immune disorders, there there's something.

Operator: Is there something about IL-2 that makes it particularly effective?

About aisle to that makes it particularly effective in the T. I tracked and would you consider developing 358 for any T.I. indication.

Operator: and the GI tract.

Operator: Would you consider developing...

Operator: Would you consider developing 358 for any GI indications?

Hey, I'm going ask you to take that one thanks.

Sure Yeah. So yes definitely that we noted that after you do you know through clinical trials.

Operator: Susie, I'm going to ask you to take that one. Thanks.

Jonathan Zalevsky: Sure, yeah, so, yeah, definitely that. We noted that.

Now some.

Modification to that study maybe that study has been a really on going through a very long time right.

Jonathan Zalevsky: [inaudible]

Jonathan Zalevsky: ongoing for a very long time.

Jonathan Zalevsky: Right. They never really reported on the 1B portion, and they moved into the expansion of lupus, and then announced that the RA part of that went away.

We've never really reported on the one be portion they moved into the expansion of lupus and then now so to our AG.

Part of that went away I'm not for me from my standpoint scientifically.

Jonathan Zalevsky: You know, you wouldn't say that Tregs are not appropriate for study in RA. There's definitely some scientific rationale for that.

You know you wouldn't say that T. Regs are not appropriate for study in our you know there's definitely some scientific rationale for that.

Jonathan Zalevsky: I would just probably guess that they were focusing on other indications. Now, we do know some data from a study that's going on in Europe called Transreg. This is a study that was run by David Klatzman, where he used low-dose IL-2, where, as you know, you can get a small amount of Treg induction using some, you know, kind of high-frequency dose administration regimens, no more than doubling or tripling the cells over baseline. But in that study, 12 different autoimmune disease indications were explored, and it was noted that some of the GI indications And scientifically, that makes a lot of sense, Jay, because we know that Tregs play an important role in the GI tract.

Which is probably guess that they were focusing on other indications now we do know some data from the study that's going on in Europe call. Trans Rag. This is the study those run by David Classman.

Where hughes low dose I, all too well.

Gary as you know you can get a small amount of T. Reg induction using some you know kind of high frequency dose administration regimens.

No more than doubling or tripling sell smoker baseline.

But in that study 12 different auto immune disease indications, where explored and it was noted that some of the G.I. indications such as ulcerative colitis crohns disease have a propensity.

And scientifically that makes a lot of sense JB, because we know that T. Regs played important role.

And the G. I track, they actually help control some of them co CIO immunology and happens you know in between all the microbes on one side of the guts and all of the immune cells I'm on the other side of the got and especially in areas like buyers passionate and other parts of immunological structures. So definitely makes a lot of.

Jonathan Zalevsky: They actually help control some of the mucosal immunology that happens, you know, in between all the microbes on one side of the gut and all of the immune cells on the other side of the gut, and especially in areas like the Peyer's patch and other parts of immunological structures. So, it definitely makes a lot of sense, you know, to focus on GI indications. And, of course, Amgen is continuing to focus on lupus, right, which has been an ongoing part of their ongoing clinical trial up to date.

Sense, you know to focus on G.I. indication and of course Amgen is continuing to focus on Lucas right, which has been the ongoing part of their of their ongoing clinical trial.

Jonathan Zalevsky: Great, thank you for that comprehensive overview. That's super helpful.

Great. Thank you for the comprehensive overview Super helpful.

Operator: We appreciate you taking the time to be here. Thank you. Thanks, Jay. Thank you. Our next question comes from Paul Choi from Goldman Sachs. Your line is open. Hi, this is Corinne Jenkins on for Paul. I was just hoping you could talk a little bit more about what you think about a registrational study in non-cell cell lung cancer and what the catalyst path will look like post that initial data from Propel later this year or early next year. Thanks, Corinne. Wei, I'm going to ask you to help Corinne with that question. Thanks.

Appreciate you taking the question.

Thanks Jay.

Thank you.

I think comes from Paul choice from Goldman Sachs. Your line is open.

Hi, This is creating Jenkins on for Paul I was just hoping you could talk a little bit more about how you think about a registrational study and non small cell lung cancer and what kind of pass will look like post that initial data from propel later this year are really not.

Thanks, Karen way I'm going ask you to help with that question Frank sure absolutely. So I discussed earlier.

Wei Lin: Sure, absolutely. So, as I discussed earlier, The current PROPEL study really has three sub-studies in the expansion cohort. It includes around 20 patients who are PDOA-positive, 50% above, and then another 18 or 20 patients in the 1 to 49 group, and then the less than 1% also has another 20 patients. And we're really looking for both the response rate as well as depth response and durability response in each of these subgroups. Now the benchmark number for PEMBRO in each of these subgroups are well known and those are publicly available, so we can easily benchmark, and the study is designed, our analysis plan is designed to benchmark against these numbers, and it's really going to be based on these comparisons to the historic numbers that we're going to make an assessment where our combinations deliver the greatest value, whether it's in the 50% above patients, making already inflamed tumor even more inflamed and bring out the activity of PEMBRO mono to even a higher level, and then even potentially longer durability, or is it in the 1 to 49% where PEMBRO mono seem to have comparable, provide comparable survival benefit to just platinum double chemotherapy, but does not provide any superiority to existing chemotherapy. But safety-wise, that's actually superior.

He at the current propel study really it's on.

Has three sub studies in the expansion cohort include town around 20 patients who are Peter one positive <unk> percent above and then another on 18 were 20 patients in the one to 49 group and then to less than 1% also has another 20 <unk>.

Patients and we're looking for.

Both the response rate as well as depth response, and do you really should response each of the sub groups.

Now he on the benchmark number four pembro each of East coast sub groups are well known and those who publicly available. So we can easily benchmark in the study is designed on our analysis plan is designed to benchmark against these numbers and it's really going to be based on.

These comparisons to the historic numbers that we're going to make assessment work.

A combination given where the greatest value whether it's in that 6% above patience on making already inflamed tumor you've been white plains and bring on Dr. <unk> pembro mono to even a higher level and then even potentially longer durability, whereas in the 1% to 49% where pemble model seem to have comparable provide.

Comparable survival benefit you just on platinum doublet chemotherapy, but just not providing you superiority to existing on chemotherapy, but at safety wise, that's actually superior. So thats. Another area I think really high high potential for A.A. cytokine based drugs like Ben Tag.

Wei Lin: So that's another area I think really has high potential for a cytokine-based drug like BEMPEG to really add a lot of substantial value by inflaming a tumor that's only low to moderately inflamed. And then, obviously, there are still patients who are basically effectively PDAL negative, less than 1%. And those are the patients for whom monotherapy does not work if it's inferior to available chemotherapy. And for those patients, typically... The standard of care today is chemo plus pembrolizumab or chemo plus atezolazepam. And so that obviously does deliver clinical benefit, but it really has the added toxicity of the combination chemotherapy. And I think what patients and their doctors are looking for is a chemo-free regimen that can provide similar or even superior benefits to what chemo plus a checkpoint can really deliver. And so these are really three different subgroups for which we're going to have independent decisions made. And the phase three trials are going to really be based on the observed activity and durability of our responses and the depth of response that we can see in the PROPEL study.

To the add a lot of substantial value by inflamed tumor that's only low commodity claimed and then obviously theres still a patients who have on basically effectively PD lone negative less than 1% and those the peep patients monotherapy does not work, it's inferior to available chemotherapy and.

For those patients typically.

On to stand of care today is chemo, plus pembrolizumab or chemo, plus a tesla snap and so that obviously, yet dusted liver clinical benefit, but really has the added toxicity of the combination chemotherapy and I think what patients and their doctor. So looking for is.

Chemo free regiment.

That can provide similar where youve any superior benefit to Blake chemo, plus a checkpoint can really deliver and so so these are really on almost three different sub groups for which we can I have independent decisions made and the phase three trials have going to really be base down what he.

On T.

He observed activity and your ability of our responses and the guest response that we can see into propel study.

Wei Lin: And then separately, can you talk about how you landed on the solid tumor indications you're looking at with Nektar 255, what's the rationale for IL-15 in head and neck and colorectal cancer, and are there any other indications where IL-15 really makes sense in your view?

Great. Thank you and then separately can you talk about how you landed on the solid tumor indications you're looking out with Nektar two by five what's the rationale for an alpha team in head and neck in colorectal cancer and are there any other indications where I'll 15 really makes sense in your view.

Wei Lin: Yeah, I think that the selection of those two tumor types is based on a couple of considerations. I think, you know, IL-15 really acts on two different cell populations, among others, in terms of therapeutic benefit. One is the Sector T cell population, and the other is the NK cell population.

Yeah. He got a discussion of those two tumor types are based on couple of considerations.

Thank you know the.

Now I'll 15.

Really act on two difference.

Cell populations among others.

The share of therapeutic benefit one effector T cell population and the others NK cell population.

Wei Lin: Apparently, the solid tumor study is really.., are leveraging or focusing in trying to harness the NK activity of our 2,255 molecule. And so the NK cells are instrumental for delivering the ADCC activity of monoclonal antibodies, which is the backbone of many of the current standard care in oncology. And when we look at the entire treatment landscape in cellular tumor and where you have benefit offered by monoclonal therapy, We were looking for tumor types and also drug combination that can still have substantial room for improvement and can provide a proof of concept after which they can expand the utility of 2,5,5 into many other solid tumor types because there are many other monoclonal antibodies that are in use in solid tumor in addition to such a TuxMap, which is the backbone we're adding onto here.

And the currently.

He solid tumor study it's really.

[laughter] leveraging are focusing in trying to harness P and K activity of our two to classify model molecule and so the NK cell tower eastern central forgive the bringing T. ADCC activity of monoclonal antibodies, which is the backbone of many aka Transcanada care in oncology.

And when we look at things hard treatment landscape, Insulet humor, and where you have on benefit offer by monoclonal therapy on.

We were looking for.

Tumor types and also drug combination 10 can.

Still has the potential moving from improvement and can provide a proof of concept.

After which where they can expand utility up to five five into many other solid tumor types.

There are many other.

Monoclonal antibodies that are in use.

In solid tumor in addition to such a touch snack, which is the backbone, we're adding on to here I think head neck and colorectal cancer offer a couple advantages as Hap first initial proof of concept because sound.

Wei Lin: I think head and neck and colorectal cancer offer a couple advantages as that first initial proof of concept because, you know, as monotherapy, TxMAP alone delivers a response rate in the 10-15% range. So it is active in the way that single-agent chemotherapy is active, but it's not so active that it's very hard to improve upon. And so that provides sort of an ideal platform for demonstrating and providing that proof of concept where there's still substantial room for improvement and an agent like 255 that can significantly expand the NK cell population and really grow the army upon which these monoclonal antibodies really rely on in executing the cell killing of these monoclonal antibodies. I think we can probably see the greatest signal and provide a really strong proof of concept by selecting ceteximab in head So that's sort of the clinical and biological consideration. And the other element is that both of these tumor types have a substantial population, right? And where the hell is the...

The as monotherapy.

T.

Sorry, so Texas not the loan collateral response rate in the 10% to 15% range. So it is accurate.

The way that seek lesion chemotherapy hit, but it's not so active debt.

It's very hard to improve.

Oh, and so that provide sort of the ideal platform for demonstrating in providing that proof of concept, where there's still substantial read from improvement and the agent like on 255 that can significantly expand NK cell population and really grow the army upon which on piece.

We antibody belief, we live in executing the cell killing.

Now I'll piece monoclonal antibodies I think how we can probably see happy to opportunities you see the greatest signal.

And provide a really a school sunk proof of concept I selecting subtypes, Matt in head neck, and colorectal cancer, So that's where they sort of the chemical and biological consideration and the other on element is both at east on tumor types are has potential population right and we're on.

The on.

Wei Lin: The EGFR monoclonal antibody, like the TuxMap, has really, really broad use and is part of the strong standard of care. Basically, every patient who has access to these antibodies always gets a SUD tax map as part of their standard care treatment, and colorectal cancer patients, as long as they're a KRAS wild type, they invariably, either as first line or second line, receive an HFR monoclo So the patient population and the opportunity is fairly large if we can demonstrate that proof-of-concept and there are clear registration paths to go forward. And if we are able to demonstrate clinical efficacy in these two tumor types, then I think we have substantial proof-of-concept with one monoclonal antibody in two different tumor types. That provides really a strength to our data and also the only 10 to 15 percent baseline response rate gives us substantial room to demonstrate how much improvement we can actually provide. And that allows us to really move on to other tumor types where monoclonal antibodies are also established as standard of care in cellular tumors.

Beyond.

Thank you, Jeff our monoclonal antibody like a tax Matt has really broad use and as part of the strong and the care basically every patient who have access to these antibodies.

Always get needs.

So tux map as part of their standard care treatment and colorectal cancer patients a sponsor a key Ras wild type a miserably either its first time, where second language.

On a.

HFR monoclonal antibody, so the patient population and B.

Kibaki opportunity, it's fairly in March I, if we can demonstrate our proof of concept.

And there are clear retribution path to go forward and if we are we put the chemistry and clinical efficacy in these two tumor types and I think we have substantial proof of concept with one long plant by over two different tumor types that provides relief as trained to our data and also.

T T don't meet on 10% to 15% baseline response rate give us central region could demonstrate how much improvement we can actually provide and that allow us to really move onto other tumor types, where monoclonal antibodies are also established kind of carrying solid tumors.

Operator: Great, thank you. Thanks.

Operator: Thanks.

Operator: Thank you. And again, ladies and gentlemen, to ask a question, please press star and then 1 now. And our next question comes from Daina Graybosch from SVB Levering. Your line is open.

Great. Thank you. Thanks.

Thank you and again, ladies and gentlemen to ask a question. Please press Star then one now.

And our next question comes from Dana Gray Bosh SVB Leerink. Your line is open.

Operator: Great, thank you. I have two questions for you, one two-part and one one-part. The two-part one on Nektar 358. Lilly is pretty excited about lupus, and they have multiple agents in the clinic for lupus, including their JAK and a BTLA inhibitor. And I wonder how Lilly's thinking about their portfolio, if they're going to take them all forward or pick one. And then sort of the second part to that, you know, Lupus has been a really hard place to do clinical trials.

Great. Thank you I've two questions for me.

One two part and why one part or the 2.1 on next year three Fiveeight Lilly is pretty excited about lupus and then they have multiple agents in the clinic for lupus, including their Jack cannot be till they inhibitor and I Wonder how you think lilly's thinking about their portfolio that they're going to pick them all Florida pick one.

And then for the second part to that no lupus has done a really hard place to do clinical trial and I Wonder. If you can talk about why that is and what about your design. It's going to help you avoid those pitfalls in the past and then one small question on next care to six too I wonder in the Biomarkers you've seen thus far.

Operator: And I wonder if you can talk about why that is and what about your design is going to help you avoid those pitfalls in the past. And then, one small question on Nektar 262. I wonder if, with the biomarkers you've seen thus far, and that we'll see in the fall, you're going to tease out the relative contribution of TLR7 and TLR8 agonism.

Our and that well see and the fall if you're going to tease out the relative contribution of TLR seven until or eight agonism. Thanks.

Operator: Thanks. Great. JV, do you mind taking the three-minute question?

Great JV do you mind, taking the three questions.

Jonathan Zalevsky: Sure. Yeah. So, okay. So, hey, Daina, thanks for the question. So, let's start off.

Sure, Yes, so okay. So hey, Dan Thanks for the question I'm. So let's start off you ask questions about Lily Lukas portfolio, yeah. They have multiple agents small and large molecule there.

Jonathan Zalevsky: You asked questions about Lilly's lupus portfolio. And yeah, they have multiple agents, small and large molecules, you know, Berry, as well as BTLA. And basically, those agents, right, as you know, they're targeting activation immunological mechanisms, right? So, a JAK inhibitor is blocking signaling through any JAK stat, you know, mediated pathway. So, primarily in the cytokine-driven way, and then BTLA is also blocking stimulatory, you know, co-adapter kinds of molecules. So one of the reasons why Lilly places so much excitement and importance around the 3-5-8 program is because that's what we call a resolution therapeutic. And so conceptually, it's targeting a different kind of mode of addressing the underlying pathology of the disease, or as opposed to other agents.

Barry as well as detailed <unk> and basically those agents right as you know, they're targeting activation immunological mechanisms right. So JAK inhibitor as blocking signaling through any JAK stat mediated pathway. So primarily in the cytokine you know driven way.

And then detail as also blocking one of the co stimulatory, you know I'm come adapter kinds of molecules. So one of the reasons why Lilly places so much excitement in importance around the three five a program is because that's what we call resolution therapeutic and so conceptually its target.

Moving to a different kind of mode of addressing the underlying pathology disease.

Whereas the other agents in the these pipeline and even all the ones, including Anifrolumab and others are blocking mechanisms activation.

Jonathan Zalevsky: Release Pipeline, and even all the ones, including Anafolamab and others that are blocking mechanisms of activation of Immunological Pathways and Inflammatory Pathways, whether they're triggered by the release of, say, RNA from dying cells that, you know, trigger an event or other kinds of systemic chronic inflammation. But the TRAG mechanism is actually aiming to activate the body's natural immune restoration or homeostatic or immune- So it's really a different arm and a different approach, right, for targeting these kinds of diseases. And one important component of that is it also works even if you really have the long view in mind, which you do if you're building, you know, say, a pipeline of multiple agents targeting lupus. You also start to imagine having opportunities for combination.

Immunological pathways and inflammatory pathways, whether they're triggered by release of say are in a dying. So lets you know triggering event more or other kinds of systemic chronic inflammation.

But the T. Reg mechanism is actually aiming to activate the bodys natural immune restoration or homeostatic or resolving halfway.

So it's really a different arm and a different approach right for targeting these kinds of diseases and one corden component of that is it also does even if you really have long view in mind, which do if you're building you know say a pipeline of multiple agents targeting lupus you also.

I started to envision having the opportunities for combinations and if you have a drug that say blocks activation and say another drug stimulates resolution now you're starting to talk about it really rational scientifically driven you know kinds of approach to treating them traditionally we know it's been difficult to stack.

Jonathan Zalevsky: And if you have a drug that, say, blocks activation and, say, another drug that stimulates resolution, now you're starting to talk about a really rational, scientifically-driven approach to treating these diseases. And traditionally, we know it's been difficult to stack agents that block activation as they have a lot of overlapping toxicity profiles. But again, that's not the case if you have resolution therapeutics. So that's one of the ways that I think Novartis is really eyeing their long-term vision in autoimmune disease and really building, you know, an industry-leading pipeline in lupus and in other indications. Now, your next question was about sort of the concept of doing lupus trials, and I think that, you know, historically, we've sort of walked away with the understanding and notion that it's just very hard to develop in this field, and that notion was driven by a couple of things, like the kind of heterogeneity of the patient population and then the fact that there wasn't a clear-cut instrument to measure the disease.

Agents the block activation as they have a lot of overlapping toxicity profiles, but again, that's not the case if you have the resolution therapeutics. So so that's one of the ways and I think really really I'm, saying their long term vision in autoimmune disease and really in building, you know and industry, leading pipeline and Lukas ended.

Other indications.

Your next question was about sort of the the concept of doing Lukas trials and I think that historically, we've sort of walked away with the understanding and notion that so it's very hard to develop and field and that notion was driven by a couple of things like the kind of the heterogeneity.

Of the patient population and then the fact that there wasn't a clear cut instrument to measure the disease. While there is salinas lead I become them by lag. There are other you know measures that you see coming in more recently for example, with that are full about and it's starting to help clarify something about the.

Jonathan Zalevsky: While there's selenoceledi and Bicolam-Bilak, there are other measures that you see coming in more recently, for example, with anaphylomab, that have started to help clarify some of that, so I think that's one of the pitfalls, and then the other is that I think we just haven't seen very strong mechanisms, mechanisms that can be measured on top of the standard of care steroids that So we've addressed that in...

I think that's one of the falls within the other is that I think you just we haven't seen very strong mechanisms mechanisms that can be measured on top of the standard of care steroids. The patients are getting.

So we've addressed that in a couple of ways.

Jonathan Zalevsky: One of the ways we're including...

One of the way, we're including all of the possible endpoints to measure the disease. So while the primary it's based on.

Jonathan Zalevsky: [inaudible] SLEAD-I2K reduction, and secondary metabolites, as you know, include Zikla-Bi-Lag, as well as SRI-4, and even other low-disease activity scoring. So those are really addressing all of the different ways that rheumatologists address and measure the disease. We're also trying to clarify the patient population, you know, by really zeroing in on patients with the right kind of severe disease, and all of them stratified to at least have active disease.

Street I to K reduction and secondaries as you know include the club by lag well as far I for and even other mode disease activity, scoring system. So those are really addressing all of the different ways that rheumatologists address and measured the disease. We're also trying to clarify the patient population.

Issue by really zeroing in on patients with the right kind of severe diseases all of them stratified to these having active disease and then of course, we're also allowing the opportunity to taper sterile use throughout the study.

Jonathan Zalevsky: And then, of course, we're also allowing the opportunity to taper sterile use throughout the study. And then the last point for us is that one of the sort of hallmarks of lupus, particularly severe lupus, is a well-documented dysfunction of the IL-2 compartment. And that manifests itself both in terms of not just low cytokine levels but also in a reduction in Treg numbers and really also a reduction in Treg suppressive capacity. And that's often, as you know, balanced by an abundance or an increase in the amount of TH17 cells that you see in these patients. And so what we are really also addressing is, I think, really an underlying disease pathology also by targeting a disease with Nektar 358. So we're very hopeful that with this design and with this mechanism, we'll have the opportunity to see activity of Nektar 358 in the phase 2p study.

And then the last point for us is that.

One of the sorta hallmarks of lupus, particularly severe list.

It is a well documented the function of the aisle to compartment and that manifests itself. Both in terms as much as low cytokine levels, but also in a reduction in T. Reg numbers and really also reduction and to Greg suppressive capacity.

And that's often.

Alan by over.

Kind of a.

Abundance or an increase in the mountains th 17 cells.

I see in these patients.

And so we're really also addressing is I think really an underlying disease pathology also by targeting a disease that affects the threefive. It. So we're very hopeful that with this design and with this mechanism will have the opportunity to see activity.

Nektar three by they and their phase two study when we're obviously very excited as is really the study is now underway.

Jonathan Zalevsky: And we're obviously very.

Jonathan Zalevsky: Obviously, I am very excited, as is Lily, that the study is now underway. Now, the next question you asked was about Nektar 262 and whether, in our biomarker program, we'll zero in and look for signs of target engagement for both TLR7 and TLR8 as well as different. And, you know, it's a very insightful question because... You know, the base drug that we conjugated to the polymer is And so that's dual TLR7, 8.

The next question you asked was about next year Twosix too and if in our biomarker program will zero in and look for signs of target engagement for both.

TLR seven NTL our rate as well the difference between US and you know your it's a very insightful question because.

The based drugs.

We conjugated to the polymer physical month right. So that's the dual TLR seven eight.

Jonathan Zalevsky: Ah, I'm haggardness.

Hi, good.

Jonathan Zalevsky: And so we do have the opportunity, using gene expression with various, you know, mRNA networks, to focus in on networks that are more TLR7 and more TLR8 related. In addition, as you know, certain cell types have more or less of one or the other. In particular, if you consider things like plasmocytoid dendritic cells, right, those are TLR8 specific and TLR8 only. They don't even express TLR7. So the biomarker program that we've put in, which includes all of the deep biopsy analysis. It includes cellular composition analysis in the biopsies as well as gene networks. And so our aim is very much to demonstrate that when we say we're gauging the target, we can say it's TLR7, TLR8, or both, or either one. Thanks for the question, Daina.

And so we do have the opportunity using gene expression.

Various marinade networks to focus in on networks that are more him TLR seven and more until our age related. In addition, as you know certain cell types.

Have more or less at Warner the other in particular, if you consider things like plasma Cytori dendritic cells right. Those are telerik specific until I read only down even expressed to us seven so the biomarker program that we've put in which includes all of the deep biopsy analysis. It includes other comp.

Position analysis in the biopsies as well Gee networks and so our aim is very much to demonstrate that won't say were gauging the target we can say TLR seven.

Both are either one or the other.

Thanks for the question there.

Great. Thank you.

Howard W. Robin: Thank you. And that does conclude our question and answer session for today's conference. And I'd like to turn the conference back over to Howard Robin for any closing remarks.

Thank you.

That does conclude our question and answer session for today's conference and I like to turn the conference back over to Howard Rodney for any closing remarks.

Well, thank you everyone for joining us today.

Operator: Well, thank you everyone for joining us today. I'd like to thank our employees for their hard work and commitment during very difficult times for business, in general. We're very proud of our employees who have worked tirelessly to advance our clinical studies, keep our business on track, and navigate this environment with both optimism and perseverance. We're fortunate and proud that Nektar has built a highly valuable pipeline of programs in immunology that address significant areas of unmet medical need in solid and liquid tumors across many potential treatment indications and across multiple autoimmune and chronic inflammatory disease states.

Like to thank our employees for their hard work and commitments. During these very difficult times for business in general.

The proud of our employees have worked tirelessly to advance our clinical studies keep our business on track and navigate this environment with both optimism and perseverance. We're fortunate proud that nektar has built a highly valuable pipeline of programs in immuno oncology and immunology.

That address significant areas of unmet medical needs and solid and liquid tumors across many potential treatment indications and across multiple autoimmune and chronic inflammatory disease states and as I stated earlier, we're in a unique position of financial strength with a robust balance sheet with $1.2 billion of cash and no debt.

Operator: And as I stated earlier, we're in a unique position of financial strength with a robust balance sheet of $1.2 billion of cash and no debt. This enables us to continue our important work on advancing potential new medicines that can transform patient care. And we thank you all for your support as shareholders. We look forward to continuing to provide you with updates on our progress. And we also wish you and your families safety and health during this time. So, thank you for joining us today. I appreciate it.

This enables us to continue are important works out advancing potential new medicines that can transform patient care and we thank you all for your support a shareholders. We look forward to continuing to provide you with updates on our progress and we also wish you and your families safety and health. During this time. So thank you for joining us today appreciate it.

Operator: Ladies and gentlemen, thank you for participating in today's conference. This does conclude the program. You may all disconnect. Everyone, have a wonderful day.

Ladies and gentlemen, thank you for participating in today's conference. This does conclude the program you may now disconnect everyone. So wonderful day.

[music].

Operator: [inaudible]