Q1 2020 Earnings Call

Emission future developments or otherwise.

A web cast of this call will be available on the I.R. page of metrics web site at nectar dot com as a replay.

Before turning over the call to Howard I'd like to comment on a small housekeeping item.

Due to the shelter in place restrictions in San Francisco each of us are calling in from different locations.

So in order to facilitate is food call flow I will moderate the q. and I.

Session for our team. So we can avoid technical issues during this session.

Thank you very much and we appreciate your patients as we work to ensure there are no technology disruptions for those listening.

With that said Oh hand, the call over to our President and C.E.O. Howard Ron Howard.

Thank you Jennifer Thank you everyone for joining us on the call today.

I'd like to start to call by discussing what is certainly on everyone's mind managing the challenging circumstances caused by coping 19 in the past several months so wide range impact that this virus has has on the health and wellbeing of our communities is significant and like all of you were all working hard.

Two appropriately adapt our business practices office same time, leading an operating the business effectively.

Is it dynamic situation, we will continue.

To adapt our response, however, I want to highlight a few key areas.

As we start working we work together to navigate the current environment, we have three main priorities.

First is to protect the health of our employees well continuing are essential operations on site to advance our research and development such as laboratory and manufacturing activities.

Second to ensure that each of our trial investigators and their teams can continue to provide superior care, an uninterrupted access to study treatment patients fighting cancer.

Third to ensure that the conduct of our clinical trials is minimally impacted and not the integrity and quality of data being collected from these studies are maintained.

So to the first part on.

<unk> employees, who continue to work on clinical tasks political critical tasks in our facilities, including manufacturing and our laboratories, we have instituted additional safety precautions, including increase protective equipment in physical distancing practices for employees that can work effectively remotely nectar is adopted work from home.

Operator: future developments or otherwise. A webcast of this call will be available on the IR page of Nektar's website at Nektar.com as a replay. Before turning over the call to Howard, I'd like to comment on a small house... Due to the shelter-in-place restrictions in San Francisco, each of us is 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. Thank you very much, and we appreciate your patience as we work to ensure there are no technological disruptions for those listening. With that said, I will hand the call over to our President and CEO, Howard Robin. Howard?

<unk> and we're supporting these employees with the technology tools to continue to work on interrupted.

We've been hearing to all local state County in Federal guidelines in this regard.

At this time, we do not anticipate any supply interruptions for manufacturing, including our preparations for scale up of commercial supply of them pag that are underway.

Jennifer Ruddock: Thank you, Jennifer.

We have sufficient clinical trial material on hand to treat all patients in this study's prevent bag nectar to to to 62 nectar to 55, and after 358, which are either underway or plan to start in 2020.

Howard W. Robin: I'd like to start the call by discussing what is certainly on everyone's mind, managing the challenging circumstances caused by COVID-19 in the past several months. The wide-ranging impact that this virus has had on the health and well-being of our communities is significant.

We and our manufacturing partners are continuing to regularly assess the situation as well.

Howard W. Robin: And like all of you, we're all working hard to appropriately adapt our business practices while at the same time leading and operating the business effectively. This is a dynamic situation. We will continue to adjust our response. However, I want to highlight a few key areas.

Additionally, research team is continuing to work towards generating our next I. Indeed candidate so that we could achieve the company's next by Indy filing in early 2021.

To the second priority, we have over 200 investigator sites around the world participating in our on college you clinical studies.

Howard W. Robin: As we start working, as we work together to navigate the current environment, we have three main priorities. First, we protect the health of our employees while continuing our essential operations on site to advance our research and development, such as laboratory and manufacturing activities. Second, to ensure that each of our trial investigators and their teams can continue to provide superior care and uninterrupted access to study treatment to patients fighting cancer. And third, to ensure that the conduct of our clinical trials is minimally impacted and that the integrity and quality of data being collected from these studies are maintained. So it's through the first player. For employees who continue to work on critical tasks in our facilities, including manufacturing.

We've been actively engaging with citing investigators in R.C.R.O. partners in order to assess state status and staffing issues and to provide resources and support to these sites.

Conditions are fluid involving however, nectar is taking a strategy to allow sites to continue to enroll new patients into initiate new investigators sites. So far this strategy has been successful and way, we'll discuss more of these initiatives in a moment.

Our third but equally important priority is to ensure the integrity and conduct of our clinical trials.

Means capturing any protocol deviations if they arise during this time.

Fully collecting any patient information, which may be related to a covert diagnosis and being prepared to track any possible interruption of important treatment or scan, but it's related to <unk> travel restrictions.

Howard W. Robin: and our laboratories, we have instituted additional safety precautions, including increased protective equipment and physical distancing practices. For employees that can work effectively remotely, Nektar has adopted work-from-home policies, and we're supporting these employees with the technology tools to continue to work uninterrupted.

F.D.A. has issued guidance on clinical trial conduct and we expect this guidance to continue to evolve in light of this the most important activities for us or carefully monitor or study sites to ensure that patients meet the appropriate eligibility criteria under the protocol and that the data are being collected attract appropriately as well.

Howard W. Robin: We've been adhering to all local, state, county, and federal guidelines in this regard. At this time, we do not anticipate any supply interruptions for manufacturing, including our preparations for the scale-up of commercial supply of BEMPEG that are underway. We have sufficient clinical trial material on hand to treat all patients in the studies for BEMPEG, Nektar-262, Nektar-255, and Nektar-358, which are either underway or planned to start in 2020. We and our manufacturing partners are continuing to regularly assess the situation as well. Additionally, our research team is continuing to work towards generating our next IND candidate so that we can achieve the company's next IND filing in early 2021.

Now many of you have asked about the potential impact to clinical trial timelines related the code.

We have some preliminary insights to share, but cautioned that because of the fluidity of the situation.

There is significant uncertain.

We were therefore need to continually assess the pine ones throughout the year, we continue to get more visibility to the timing and extent of covert index.

How're nectar clinical development and operations teams are highly focused during this time on the oversight of the five clinical studies and you know on college you were nectar serves as the sponsor.

First line bladder cancer study at them take plus Nivo.

The first line real cell carcinoma study event that costs me about that propelled study of them take less Pembroke.

Howard W. Robin: To address the second priority, we have over 200 investigator sites around the world participating in our oncology clinical study. We've been actively engaging with site investigators and our CRO partners in order to assess site status and staffing issues and to provide resources and support to these sites. Conditions are fluid and evolving.

Connector to 60 to reveal study with bin bag.

And the next or 255 so.

First in response to some questions. We've received we've only had a few reports of patients in our studies web had suspected or confirmed coded diagnosis.

For the five clinical studies, but I just mentioned as of today. We have received only four reports of patients who have been diagnosed with coded. This is across our 200 plus investigator sites.

Howard W. Robin: However, Nektar is taking a strategy to allow sites to continue to enroll new patients and to initiate new investigator sites. So far, this strategy has been successful, and Wei will discuss more of these initiatives in a moment. Our third but equally important priority is to ensure the integrity and conduct of our clinical trials. This means capturing any protocol deviations if they arise during this time.

With respect to new studies starts nectar still on track to initiate <unk> melanoma studying the third quarter.

Based upon her assessment of the current situation in barring any negative external covert developments in the second half of the year. We believe this is very achievable.

Howard W. Robin: Carefully collecting any patient information which may be related to a COVID diagnosis and being prepared to track any possible interruption of important treatment or scan visits related to COVID travel. The FDA has issued guidance on clinical trial conduct, and we expect this guidance to continue to evolve. In light of this, the most important activities for us are to carefully monitor our study sites to ensure that patients meet the appropriate eligibility criteria under the protocol and that the data are being collected and tracked appropriately as well. Now, many of you have asked about the potential impact of clinical trial timelines related to COVID. We have some preliminary insights to share, but caution that because of the fluidity of the situation, there is significant uncertainty.

Protocol for the edge of it melanoma study is now being finalized and we're in the process of identifying recruiting investigator sites for initiation later this year.

With respect to the first line bladder cancer study.

We have not seen any impact on and Roman put pace today, and we're expect to achieve our enrollment goal. This summer.

Means that we will meet the timeline of achieving primary endpoint for this study sometime in mid 2021 as a reminder, the primary endpoint. In this study is are are independent review for patients with under 10 C.B.S. score.

For the first line renal cell carcinoma study, we are on track for our projections for a moment prior to cope with which means we are also on tracks, which you. The first interim analysis on the primary and point to the overall survival in the first quarter of 2022.

Howard W. Robin: We will, therefore, need to continually assess these timelines throughout the year, and we continue to get more visibility into the timing and extent of COVID's impact. Our Nektar clinical development and operations teams are highly focused during this time on the oversight of the five clinical studies in immuno-oncology where Nektar serves as a sponsor, the first-line bladder cancer study of BEMPEG plus NEVO, the first-line renal cell carcinoma study of BEMPEG plus NEMO, the PROPEL study of BEMPEG plus PEMBRO, the Nektar 262 Reveal Study with Venpeg First, in response to some questions we've received, we've only had a few reports of patients in our studies who have had a suspected or confirmed COVID diagnosis. For the five clinical studies that I just mentioned, as of today, we have received only four reports of patients who have been diagnosed with COVID.

For opera <unk> study at them Peg plus pembro in Nonsmall sell lung cancer that was initiated late in 2019 enrollment is ongoing.

Howard W. Robin: This is across our 200-plus investigator sites. With respect to new study starts, Nektar is still on track to initiate the adjuvant melanoma study in the third quarter. Based upon our assessment of the current situation and barring any negative external COVID developments in the second half of the year, we believe this is very achievable. The protocol for the adjuvant melanoma study is now being finalized, and we are in the process of identifying and recruiting investigator sites for initiation later this year, with respect to the first-line bladder cancer study. We have not seen any impact on enrollment pace to date, and we expect to achieve our enrollment goal this summer. This means that we will meet the timeline of achieving the primary endpoints of the study sometime in mid-2021.

Kobe situation delete initiation for the investigator sites in Europe for propel however, we're still initiating some of these European sites in countries that are less impact if I told it but we are doing this very carefully and only with sites that also have demonstrated that they can adequately provide clinical trial oversight in services along with patient care.

Oh.

We had previously provided guidance that we would have initial safety as well as preliminary or our data for between 10 and 20 patients that were enrolled in the dose escalation and nonsmall sell lung cancer cohorts of this study by November we know expect that this will either be by the end of this year or first quarter 2021.

Are phase one to reveal study is advancing.

We recently expanded the study to evaluate the recommended phase two dose of neck or 262 in up to 24 relapse and refractory melanoma patients. We we're in now for the first time.

Waiting simultaneous those thing of the two investigational agents.

And the dose escalation phase, we observed high levels of T.L.R. activation in a tumor microenvironment and we're able to characterize safety for next to to 62.

We're planning to submit these dose escalation data for potential presentation medical meeting or a manuscript publication later this year.

For an extra 255 are aisle 15 Agnes program in our newest clinical candidate were actively enrolling patients into the first and human clinical study of nature to 55, which began late last year.

Howard W. Robin: And as a reminder...

Howard W. Robin: The primary endpoint in the study is ORR, an independent review for patients with under 10 CPS. For the first-line renal cell carcinoma study, we are on track for our projections for enrollment prior to COVID, which means we are also on track to achieve the first interim analysis on the primary endpoint of overall survival in the first quarter of 2020. For our Propel study of BEMPEG plus PEMBRO in non-small cell lung cancer that was initiated late in 2019, enrollment is ongoing. The COVID situation delayed initiation for the investigative sites in Europe for Propel. However, we are still initiating some of these European sites in countries that are less impacted by COVID.

We're still initiating sites in this study and still have a goal to complete the dose escalation portion of the study by the end of this year.

Of course meeting this goal depend on how many does <unk>, we need to enroll before cheating a maximum tolerable ducks.

With the first several patients we enrolled into this study we already have good biomarker evidence at target engagements up the aisle 15 pathway.

We are planning to prevent present. These data later this year early 2021 as a reminder to study is evaluating nectar to 55 first as a motto therapy and then in combination with that <unk> <unk>.

Howard W. Robin: But we are doing this very carefully and only with sites that also have demonstrated that they can adequately provide clinical trial oversight and services along with patient care. We have previously provided guidance that we would have initial safety as well as preliminary ORR data for between 10 and 20 patients that were enrolled in the dose escalation and non-small cell lung cancer cohorts of this study by November. We now expect that this will either be by the end of this year or in the first quarter of 2021.

In multiple myeloma, non Hodgkin's lymphoma, respectively.

Now move onto discuss studies that are being run by our partners.

As many of you have like we listen to the conference calls from large pharmaceutical companies over the past several weeks management practices around ongoing implant clinical trial activities have buried it during the coded situation many companies or projecting that normal practices for clinical trial activities in most countries will resume and the second half of 2020.

In General this has been adjustment timelines for studies of anywhere from three to six months.

Howard W. Robin: Our Phase I-II Reveal Study is progressing. We recently expanded the study to evaluate the recommended Phase II dose of Nektar 262 in up to 24 relapsed and refractory melanoma patients. We are now, for the first time, evaluating simultaneous dosing of the two investigational agents. In the dose escalation phase, we observed high levels of TLR activation in the tumor microenvironment and were able to characterize safety for Nektar 262. We're planning to submit these dose escalation data for potential presentation at a medical meeting or manuscript publication later this year for Nectar 255, our IL-15 agonist program, and our newest clinical candidate.

Each of our partners has deployed different methodology.

With respect to our partner B.M.S.

During the ongoing Crovitz situation B.M.S. as publicly stated that they have caused initiation <unk> all new investigator sites in any clinical study, they're conducting across the company.

The M.S. is running two ongoing Ben pay clinical studies currently the first line melanoma study and the most movies of water cancer study as you know B.M.S.. It's Operationalizing. These studies and managing these studies timelines.

The M.S. continues to recruit patients pretty studies that investigators sites that are allowing unsafe monitor for notations.

This time, because the Kobe situation is ongoing and B.M.S. is not re projected any studies <unk> Nichter expects. This will have an impact on me a Romans, both studies, which could translate into delays of three to six months.

Howard W. Robin: are actively enrolling

Howard W. Robin: Patients into the First in Human Clinical Study of Nektar-255, which began late last year. We're still initiating sites in this study and still have a goal to complete the dose escalation portion of the study by the end of this year. Of course, meeting this goal will depend upon how many dose cohorts we need to enroll before achieving a maximum tolerable dose in the first several patients we enrolled into the study. We already have good biomarker evidence of target engagements of the IL-15 pathway, and we're planning to present these data later this year or early 2021. And as a reminder, the study is evaluating Nektar 255 first as monotherapy, and then in combination with daratumumab or rituximab and multiple myeloma and non-contagious lymphoma.

We're not working closely with the M.S. to determine when B.M.S. will remove or modified any restrictions that impact and wrong.

Also as a reminder, we received the 25 million dollar milestone payments in the first quarter of this year under the revise B.M.S. agreement for the start of the Muslim late base of bladder cancer study per pound bag plus neither.

The M.S. is also planning to start later in the year for the T.K.I. combo renal cell carcinoma study and the face to study at them take plus Nivo and first line Nonsmall so lung cancer.

With respect to our partner Lily and after 358, R.T. Reg stimulus already program.

Howard W. Robin: Now I'll move on to discuss studies that are being run by our partners. As many of you have likely listened to conference calls from large pharmaceutical companies over the past several weeks, management practices around ongoing and planned clinical trial activities have varied during the COVID situation. Many companies are projecting that normal practices for clinical trial activities in most countries will resume in the second half of 2020. In general, this has meant an adjustment of timelines for studies of anywhere from three to six months. Each of our partners has deployed different methodologies.

The phase one multiple dose studies in psoriasis and the topic dermatitis temporarily suspended recruitment during the coconut situation. However, <unk> tenuous to assess the situation and evaluating the status and investigator sites to determine when the best time is to reopen these studies per patient recruitment.

We're still anticipating two phase two studies to the initiated by Lily This year one in lupus patients in one in an additional auto immune disease state.

Slated to start in the second half of 2020.

We know that the team it lilies evaluating all options to start these studies, including focused on initiating investigator sites and countries with low impact or minimal current impact from go ahead.

Howard W. Robin: With respect to our partner, BMS. During the ongoing COVID situation, BMS has publicly stated that they have paused enrollment for all new investigator sites in any clinical study they're conducting across the country. The MS is running two ongoing BEMPEG clinical studies currently, the first-line melanoma study and the muscle-invasive bladder cancer study. As you know, BMS is operationalizing these studies and managing these studies' timelines. BMS continues to recruit patients for these studies at investigator sites that are allowing on-site monitoring. At this time, because the COVID situation is ongoing and BMS has not reprojected any study timelines, Nektar expects this will have an impact on enrollment for both studies, which could translate into delays of three to six months. We're now working closely with BMS to determine when BMS will remove or modify any restrictions that impact enrollment.

And so we appreciate their dedication to creative with finding types forward to initiate these new studies overall, we're very pleased with <unk> continued commitment connector 358, as well as the broad plan spurts development, which reflect the potential of his novel mechanism to treat autoimmune disease.

Before I had to call over the way I'd like to mention several additional data presentations were planning for this year.

First for the melanoma cohort for pivotal to.

As many of you know last year, we obtained F.D.A. breakthrough therapy designation for Ben take plus Nivo in patients with medicine melanoma based on the positive data, including it high C.R. rate from our Pivotals to set.

At City last year November we presented data from this court with a median follow up approximately 18 months [laughter] excuse me at that time.

Howard W. Robin: Also, as a reminder, we received a $25 million milestone payment in the first quarter of this year under the revised BMS agreement for the start of the muscle invasive bladder cancer study for BEMPEG plus NEVA. BMS is also planning to start later in the year the TKI combo renal cell carcinoma study and the phase two study of BEMPEG plus NEVO in first-line non-small cell lung cancer. With respect to our partner Lilly and Nektar 358, our Treg Stimulatory Program. The Phase I Multiple Dose Studies in Psoriasis and Atopic Dermatitis have temporarily suspended recruitment during the COVID situation. However, Lilly is continuing to assess the situation and evaluating the status of investigator sites to determine when the best time is to reopen these studies for patient recruitment.

34% of patients had a complete response as determined by blinded independent Central review.

42% had a 100% reduction in target lesions and 47% almost half had a greater than 75% reduction in target lesions.

We recently completed an additional blinded review pivot o. two melanoma cohort at the end of December 2019.

And this data cut added three additional months a follow up from our prior city presentation and I'm pleased to inform you today that up to 21 month median follow up point, we it's still not achieve median P.F.S. for the patients in this <unk>.

We also continue to see deepening of responses for these patients and we plan to present updated data from even later data cut like a city 2020.

Howard W. Robin: We're still anticipating two phase two studies to be initiated by Lilly this year, one in lupus patients and one in an additional autoimmune disease study. Both are slated to start in the second half of 2020. We know that the team at Lilly is evaluating all options to start these studies, including focusing on initiating investigator sites in countries with low impact or minimal current impact.

Also prevent take data from the dose escalation portion of pivot, though too well, we'll be recognized in a publication <unk> in may.

And finally, we were planning to submit prepublication additional manuscripts for the bladder and kidney cancer patient cohorts from pivotal too.

For next 358, we recently completed the phase one b. multiple sending dose studying lupus patients that <unk> conducted as part of our Lily collaboration.

Howard W. Robin: COVID. And so we appreciate their dedication to creatively finding paths forward to initiate these new studies. Overall, we're very pleased with Lilly's continued commitment to Nektar 358 and the broad plans for its development, which reflect the potential of this novel mechanism to treat autoimmune diseases. And before I hand the call over to Wei, I'd like to mention several additional data presentations we're planning for this. First, for the melanoma cohort for PivotO2, as many of you know, last year, we obtained FDA breakthrough therapy designation for BEMPEG plus NEBO in patients with metastatic melanoma based on the positive data, including a high CR rate from our PivotOS 2 study. At CISI last year, in November, we presented data from this cohort with a median follow-up of approximately 18 months. And it's, excuse me, at that time.

And the initial data from this phase one B. study were accepted for presentation at the upcoming virtual you are conference.

We also intend to present additional data from the same study at the 2020 American College of Rheumatology meeting A.C.R.

Howard W. Robin: 34% of patients had a complete response as determined by blinded independent central review, 42% had a 100% reduction in target lesions, and 47%, almost half, had a greater than 75% reduction in target lesions. We recently completed an additional blinded review of the PIVOT-02 melanoma cohort at the end of December 2019. And this data cut added three additional months of follow-up from our prior CITI presentation. And I'm pleased to inform you today that at the 21-month median follow-up point, we have still not achieved median PFS for the patients in this cohort. We also continue to see deepening of responses for these patients, and we plan to present updated data from an even later data cut at the CITSE 2020. Also, for BEMPEG, data from the dose escalation portion of PivotO2 will be recognized in a publication at a canceled journal in May.

Howard W. Robin: And finally, we're planning to submit for publication additional manuscripts for the bladder and kidney cancer patient cohorts from Pivotal. For Nektar 358+, we recently completed the Phase 1b multiple ascending dose study in lupus patients that Nektar conducted as part of our Lilly collaboration, and the initial data from this Phase 1b study were accepted for presentation at the upcoming virtual UARC conference. We also intend to present additional data from the same study at the 2020 American College of Rheumatology meeting, ACR, later this year. With that, I'll turn the call over to Wei to review in more detail some of the techniques we're deploying across the Nektar-run clinical trials to address the COVID situation and to ensure the integrity and conduct of the studies during this challenging,

This year.

Without altering the call over the weights review in more detail some of the techniques, we're deploying across the nectar run clinical trials to address the covert situation and to ensure the integrity and conduct of this study's during this challenging time white.

Thank you hard and I can discuss briefly the comprehensive plan, we can all to ensure that we're meeting the two priorities Howard mentioned earlier one piece your patients have an interrupted access to study treatments clinical trials and to to ensure that the conduct integrity of <unk>.

Aren't intact.

So those patients currently enrolled in our clinical trials <unk>.

I'm, making every effort to ensure that patients in highly affected areas and in areas like heavy restrictions I bow to continue with their <unk> and we see that <unk> care and monitoring.

Conditions allow and within <unk> guidelines when he point extra patient comes here services.

Transportation options and resources for patients in there are studies.

Both along patients to visit local facilities for scheduled steady treatment and scan digits, rather than having to travel longer distances when possible.

And were heavily focused on utilizing every method possible to provide our investigators sites with the proper resources necessary to maintain care and monitoring a patients.

Including virtue monitoring and telling medicine.

And what are you pretend patient inside staff safety.

Increased our efforts to monitor site activities.

In in continue communication with <unk>.

We focused on providing size town with information on appropriate data entry and understanding available options for patients.

We are also checking to ensure that size staff are available and able to comply with any new measures being put in place.

Wei: Thank you, Howard. I'd like to discuss briefly the comprehensive plan we've developed to ensure that we're meeting the two priorities Howard mentioned earlier, one, to ensure patients have uninterrupted access to study treatments in our clinical trials, and two, to ensure that the conduct and integrity of our clinical trials are intact. So those patients currently enrolled in our clinical trials that Nektar is running. We're making every effort to ensure that patients in highly affected areas and in areas with heavy restrictions are able to continue their study treatment and receive appropriate care and monitoring, as conditions allow and within the applicable guidelines. We're deploying extra patient concierge services to provide transportation options and resources for patients in their RR study. We're also allowing patients to visit local facilities for scheduled study treatment and scan visits, rather than having to travel longer distances when possible, and we're heavily focused on utilizing every method possible to provide our investigators sites with the proper resources necessary to maintain care and monitor a patient, including virtual monitoring and telemedicine, in order to protect patient and staff We've increased our efforts to monitor SIDOC, and we've been in continual communication with site investigators and staff.

Our political monitors are focused on collecting oh relevant data with respect to any protocol deviations data entry or any study conduct.

We may need to provide to the F.D.A. in the future.

Wei: We focused on providing site staff with information on appropriate data entry and understanding available options for patients. We are also checking to ensure that site staff are available and able to comply with any new measures being put in place. Our clinical monitors are focused on collecting all relevant data with respect to any protocol deviation, that entry, or any study conduct that we may need to provide to the FDA in the future. As Howard stated, the FDA has issued guidance on clinical trial conduct, and we continue to monitor this guidance. We're also engaged, along with our industry peers, in providing input back to FDA on various clinical trial conduct issues that arise due to the COVID-19 pandemic. We're allowing sites to continue to enroll new patients, and we continue to initiate new study sites. However, we are highly focused on the appropriate eligibility of the patients being enrolled and ensuring that all enrollment criteria are met.

As How're stated.

He has issued guidance on <unk>.

And we can change monarchy this guidance.

We're also engaged along with our industry peers in providing input back to F.D.A. on various clinical trial contact issues.

Rise due to the Kobe 19 pandemic.

Where permitting sides to continue T. road, new patients and we continue to negotiate new steady sites.

However.

We're highly focused on the appropriate eligibility of the patients being road.

Hand, insuring that Oh enrollment criteria are met.

In addition.

Want to make sure I site is <unk> staffed and it's not only in packet by Kobe 19, before bringing new site into any of our clinical studies.

He's report that to date.

We have seen exceptional patient compliance in our clinical studies, particularly in terms of receiving steady treatment and schedule scans with only one patient across all of our necktie runs studies, who has missed a scan and none have missed a steady treatment.

We have been tremendously impressed with a high degree of engagement from our investigators and their style and extraordinary care, they're providing to their patients <unk> difficult time.

We believe that.

With the measures were taking.

We can appropriately navigate the current situation.

So that we can advance our clinical programs forward.

Beforehand, I hand, the call K.Z. to discuss how work with <unk>.

<unk> and that car to five five.

I want to address question, we've been getting on the changing of the interim response rate endpoint in our first find melanoma and.

Wei: [inaudible] We want to make sure a site is appropriately staffed and is not overly impacted by COVID-19 before bringing a new site into any of our clinical studies. I'm pleased to report that, to date... We have seen exceptional patient compliance in our clinical studies, particularly in terms of receiving study treatment and scheduled scans, with only one patient across all of our Nektar-run studies who has missed a scan, and none have missed a study treatment. We have been 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 difficult time. We believe that with the measures we're taking... we can appropriately navigate the current situation so that we can advance our clinical programs forward. Beforehand, I hand the call to Jay-Z to discuss our work with Nektar 358 and Nektar 255.

I see no. We you see that Bray through therapy destination for band Pag plus me about in this setting.

Based upon the high compete response rate we observed in the first line melanoma population.

Interface, we studied being run by being nice we have we end points.

Over response rates are higher.

Increase your Bible, P.F.X. and hobos here Bible away.

The first 10 point, it's an interim analysis, where a very small amount of alcohol expand to compare the or are in a double.

Applet combination of Ben <unk> to the or and then you bullet map monetary arm.

We are looking for a six monkey <unk> follow up for a specific number of patients in the study.

Because of our high complete response rate. Many of you have to ask whether we could change the interesting to look at compete response rate anytime he said.

This is something we and our apartment or B.N. nice alright, Valuating and we hope to have an update on this question before the end of the year.

In the meantime, the city continues to have our tree racial standpoint.

Or R.P.F.S. and all that.

The original design of the study, which.

Based upon Checkmate series six seven.

<unk> the P.F.S. endpoint had roughly six to seven months following Oprah responsibly.

But that's reminder, this was only a projection and event driven and based upon enrolling rate.

And so that timing could change.

For both or are in P.F. that the results will be analyzed by blind date independent legality review.

Wei: I want to address questions we've been getting on the changing of the interim response rate endpoint in our first-line melanoma study. As you know, we received breakthrough therapy designation for BAMPEG plus NEVO in this setting, based upon the high complete response rate we observed in the first-line melanoma population. In the Phase 3 study being run by BMS, we have three endpoints, Overall Response Rate, ORR, Progression Pre-Survival, PFS, and Overall Survival, OS. The first endpoint is an interim analysis where a very small amount of ALQA is spent to compare the ORR in the double, double combination of BAMPAC plus Nebo to the OR and then your Volumap monotherapy arm. We are looking for a six-month duration of follow-up for a specific number of patients in the study.

So this process will affect timing for the completion of any data analyses as well.

I think they're closer to achieving these hand points.

We should be able to refine our time.

Actually reminder, for our it designed that's an accelerated approval endpoint.

Spent only a small amount of alcohol on this and P.F. that will be the basis for a full approval.

With that.

<unk> he could discuss more on our next car 358 in that car to fight fight programs.

[noise]. Thank you <unk>.

Like to spend a little more time discussing two programs. The first is the neck or 358 program in our plans for the Lupus study and the second is our aisle 15 program nectar to five five.

First for an extra 358 is Howard stated we will present, our first data from the phase one be multiple descending dose study, which was conducted in patients with mild to moderate lupus at this year's European League against Rheumatism or you are meeting in early June.

Wei: Because of our high complete response rate, many of you have asked whether we could change the interim to look at complete response rate in each arm instead. This is something we and our partner, BMS, are evaluating, and we hope to have an update on this question before the end of the year. In the meantime, the city continues to have our three original employees.

As the conferences virtual we will also host of virtual web Cam to review the data with investors an analyst on the morning of June.

Many auto immune disorders, including systemic lupus are associated with D. crest regulatory t. cell numbers reduce t. Rex function and are reduced production a vial too.

Wei: ORR, PFS, and OS. The original design of the study, which was based upon Checkmate 067, modeled the PFS endpoint at roughly six to seven months following over-response. But, as a reminder, this was only a projection and is event-driven and based upon enrollment rate. And so that timing could change. For both ORR and PFS, the results will be analyzed by blinded independent radiology review. So this process will affect timing for the completion of any data analysis as well; as we get closer to achieving these endpoints, we should be able to refine our timetable. As a reminder, ORR is designed as an accelerator approval endpoint. We spent only a small amount of alpha on this, and PFS will be the basis for a full approval. With that, I'll hand the call to Jay Z to discuss more our Nektar 358 and Nektar 255 programs.

T Rag deficiencies are important in the past the Genesis.

Diseases.

358, our goal is to address the T. rag abnormalities disease.

To develop a nail to molecule that could selectively stimulate tea bag in a much more effective manner the native bio too.

You will recall that at last year's EULAR Congress, we presented results from our first in human single dose study, which showed that nectar 358 was safe.

Well tolerated and exhibited those proportional P.K. profile prolonged exposure, but the half life at approximately eight to nine dead.

Importantly.

The 358 resulted in the market and selective those dependent expansion C.D. 25, right T. Rex.

In contrast, there were no measurable effect on the numbers or percentages of C.D. for C.D.A. conventional t. cells. It all goes to test.

In the study we will presented this year's EULAR Congress reevaluated multiple offending dose regimens, an extra 358 and lupus patients in order to study the safety Tolerability and pharmacodynamics nectar 358, and also to inform the design of the phase to study of nature 358.

Jay Olson: Thank you, Wei. I'd like to spend a little more time discussing two programs. The first is the Nektar 358 program and our plans for the lupus study. And the second is our IL-15 program, Nektar 255.

Howard's dated this space to study lupus patients his plan to start in the second half of this year and we are excited about the advancement of this program.

Jay Olson: First...

Jay Olson: For Nektar 358, as Howard stated, we will present 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, meeting in early June. As the conference is virtual, we will also host a virtual webinar to review the data with investors and analysts on the morning of June 5th.

Moving on connector to five five.

The dose escalation portion of this days one to study is proceeding.

The study is evaluating with safety pharmacokinetics, M. pharmacodynamics and that can to five five is monotherapies.

Then we'll expand into combination of antibodies at work through an 80 C.C. mechanism, including <unk> <unk>.

Jay Olson: Many autoimmune disorders, including systemic lupus, are associated with decreased regulatory T-cell numbers, reduced Treg function, and or reduced production of IL-2. These Treg deficiencies are important in the pathogenesis of these autoimmune diseases.

We plan to enroll up to 40 patients relapse to refractory multiple myeloma non hodgkin's lymphoma in the dust escalation part the study.

We have also introduced a robust biomarker program into this trial, including measurements of the nectar to five five it that multiple immune cell population.

Jay Olson: With Nectar 358 and other IL-2 molecules, our goal is to address the TRAG abnormalities and to develop an IL-2 molecule that could selectively stimulate Tregs in a much more effective manner than native IL-2. You will recall that at last year's ULR Congress, we presented results from our first in-human single-dose study, which showed that Nectar 358 was safe, well-tolerated, and Importantly, Nektar 358 resulted in a marked and selective dose-dependent expansion of CD25 bright Tregs. In contrast, there were no measurable effects on the numbers or percentages of CD4 and CD8 conventional T-cells at all doses tested.

Specially on expansion and then k. cell numbers as well as their activation assumption.

Ran to provide a deep assessment of the next year or 255 mechanism of action.

As a reminder, unlike other <unk> 15 approaches nectar to five five was designed to capture the full biology of the aisle 15 pathway.

Typically meaning it connected to five five is designed to capture all the receptor lie again interaction available through targeting the aisle 15 agonists pathway.

This gives nectar to five five the ability to act as a significant expand or natural killer cells as well as the ability to promote the survival and expansion of memory C.D.A.T. cells.

As Howard stated our goal is to complete the dose escalation monotherapies 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.

Jay Olson: In the study we will present at this year's UR Congress, we evaluated multiple ascending dose regimens of Nektar 358 in lupus patients in order to study the safety, tolerability, and pharmacodynamics of Nektar 358 and also to inform the design of the phase two study of Nektar 358. As Howard stated, this Phase 2 study of lupus patients is planned to start in the second half of this year, and we are excited about the advancement of this program. Moving on to Nektar 255.

But that update let me now turn the call over to Gill for a review of the financial.

Hmm.

Thank you Jay Z. and good afternoon, everyone.

In this call.

I will review, our 2020 financial guidance, which is unchanged.

Starting with our exceptionally strong financial position, we ended the first quarter with 1.5 billion in cash and investments.

Jay Olson: The dose escalation portion of this Phase 1-2 study is proceeding. Our study is evaluating the safety, pharmacokinetics, and pharmacodynamics of NETQ-255 as monotherapy. And then we'll expand to combinations with antibodies that work through an ADCC mechanism, including Daratumumab and Rituximab. 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 this study. We have also introduced a robust biomarker program into this trial, including measurement of the Nektar 255 effect on multiple immune cell populations, especially on expansion of NK cell numbers as well as their activation. We aim to provide a deep assessment of the Nektar 255 mechanism of action. As a reminder, unlike other IL-15 approaches, Nektar-255 was designed to capture the full biology of the IL-15 pathway, specifically meaning that Nektar-255 is designed to capture all the receptor-ligand interactions available through targeting the IL-15 agonist pathway.

As we discussed on our last earnings call.

We plan to repaid the 250 million in outstanding Senior notes in the second quarter of this year.

We indeed completed this repayment April so this will be reflected in our Q2 2020 balance sheet.

The senior note repayment has strengthened our balance sheet and will result in approximately 20 million annual interest savings on a go forward basis.

After taking into account the repayment of our senior notes.

And are projected cash usage this year.

We still plan to N. 2020 would at least a billion in cash and investments.

As we discussed that our last earnings call and consistent with our guidance.

We recorded a 45.2 million dollar impairment charge in the first quarter that concludes our natural one any one activities.

Are lost per share of 78 cents for the first quarter includes the 25 cent lost per share attributable to this impairment charge.

Jay Olson: This gives Nektar 255 the ability to act as a significant expander of natural killer cells, as well as the ability to promote the survival and expansion of memory CD8 T-cells. As Howard stated, our goal is to complete the dose escalation monotherapy portion of the Phase 1 trial by the end of this year, and we are excited about the early biomarker results we've observed in the first patients enrolled. With that update, let me now turn the call over to Gil for a review of the financials.

I will now turned to our 2020 financial guidance, which remains unchanged.

At the outset I'd like to note that we are not changing our full year financial forecasts based on cool bid 19 impacts given that are clinical pipeline progress remains largely on track as Howard reviewed earlier on the call.

[noise], our full year gap revenue guidance remains between 140 and 145 million for 2020.

Gil: Thank you, Jay-Z, and good afternoon, everyone. On this call, I will review our 2020 financial guidance, which is unchanged. Starting with our exceptionally strong financial position, we ended the first quarter with $1.5 billion in cash and investments. As we discussed on our last earnings call, we plan to repay the $250 million in outstanding senior notes in the second quarter of this year. We indeed completed this repayment in April, so this will be reflected in our Q2 2020 balance sheet. The Senior Note repayment has strengthened our balance sheet and will result in approximately $20 million of annual interest savings on a go-forward basis.

This includes 50 million of milestone payments from B.M.S., and 90 to 95 million of royalties product sales and other revenue.

Howard stated.

We recognized and receive the first 25 million dollar milestone for B.M.S. The start of the muscle invasive bladder cancer study, which occurred in January of this year.

The second 25 million dollar milestone is in connection with the start of the <unk> melanoma study and is still plan for Q3 of this year.

As a reminder, that 90 to 95 million of remaining gap revenue is still expected to be recognized on a fairly reasonable basis over the four quarters of this year.

Gil: After taking into account the repayment of our senior notes and our projected cash usage this year, we still plan to end 2020 with at least a billion in cash and investments. As we discussed on our last earnings call and consistent with our guidance, we recorded a $45.2 million impairment charge in the first quarter that concludes our Nectar 181 activity. Our loss per share of $0.78 for the first quarter includes the $0.25 loss per share attributable to this impairment charge.

Are gap R. and D. expense Guy and is also one change we anticipate 2020 gap R. and D. expense will range between 475 in 500 million.

Which includes approximately 70 million.

Noncash appreciation in stock compensation expense.

R.G.N.A. expense for 2020 is still projected to be between 105 and 115 million.

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

And as I reviewed earlier.

Operator: I will now turn to our 2020 financial guidance, which remains unchanged. At the outset, I'd like to note that we are not changing our full year financial forecast based on COVID-19 impact, given that our clinical pipeline progress remains largely on track, as Howard reviewed earlier in the call. 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. As Howard stated, we recognized and received the first $25 million milestone for BMS' start of the muscle-invasive bladder cancer study, which occurred in January of this year. The second $25 million milestone is in connection with the start of the AGIVIT melanoma study and is still planned for Q3 of this year.

We still plan to end the year with at least a billion in cash in investments. After we completed the repayment of our 250 million in senior that this quarter.

Operator: As a reminder, the $90 to $95 million of remaining GAP revenue is still expected to be recognized on a fairly rateable basis over the four quarters of this year. Our GAAP R&D Expense Guidance is also subject to change. 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 expense. 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 expenses. And as I reviewed earlier, we still plan to end the year with at least a billion in cash and investments after we complete the repayment of our $250 million in senior debt this quarter. And with that, I will open the call to questions. Operator.

And with that I will open the call the question operator.

Thank you ladies and gentlemen, if you have a question that that sounds impressive start.

<unk> when you touch tone telephone.

The question has been answered or you wish to remove yourself from the queue. Please press the pound key.

Then the question.

Star well one one now.

And that's our question comes from Peter I'm, often from by plane airline is open.

Hi, I said, taking my questions I guess first questions just probably around the <unk> 255, just.

Timing around the initial data nations and could see and.

What would you want to see to move up project for Woods.

Sure.

Later.

Oh, sorry, John <unk>. Thank you Peter the so yeah, so with neck or 255, as we stated earlier in the call. So we've been.

Starting into the dust escalation now.

And we have seen some very interesting target engagement data from the first few patient that we've been rolled into the study.

And they kind of results that we're looking to see obviously isn't assessment of the overall safety and the Tolerability and the pharmacokinetics pharmacodynamics all of the things that are typical in every kind of first in humans study when you advance into the clinic for the first time and you and you perform the dose escalation.

But specifically in the case of 255, you know we had built a wealth of understanding from our pre clinical study, where we remember we evaluated the molecule the nonhuman primates and mice and other species and we saw the effect on the immunological changes that the molecule could make though we saw a natural killer <unk>.

<unk>.

Some of their persistence, we saw it changes in the activation state of the cells and you know we also even of course of public data presented data on the overall differentiation of the natural killer sell compartment as well. This is the kind of biology, Peter that's only possible to achieve with an aisle 15 mechanism.

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 my questions. I guess the first question is probably about the GDZ, just around 255. Climbing around the initial data, what would you want to see to move that project forward?

It was removed into the clinic, we're looking to translate all of those kinds of finding.

And the clinical trial had built into it and extensive biomarker program that allows us to measure these kind of changes it allows us to assess the natural killer cells and the C.D.A.T. cells and access them in multiple compartments, such as the blood as well as in the tissue.

So we'd be very excited to present the data that we're seeing in this study we think it's reasonable to either later. This year. Early next is a is a time and we can do that assuming the dose escalation continues as planned.

The kind of things, we'd like to see out of that does that relation or or as I described combination of safety Tolerability P.K. and the biomarkers in the program.

Peter Lawson: Thanks, Peter. Oh, sorry, Jennifer. Yeah. Thank you, Peter. So, yeah.

Jay Olson: So, with Nectar 255, as we stated earlier in the call, we've been... Starting into the dose escalation now, and we have seen some very interesting target engagement data from the first few patients that we've enrolled into the study. And the kind of results that we're looking to see obviously are an assessment of overall safety and tolerability and pharmacokinetics and pharmacodynamics, all of the things that are typical in every kind of first in human study when you advance into the clinic for the first time and you perform the dose escalation. But specifically, in the case of 255, we had built a wealth of understanding from our preclinical studies.

<unk> <unk> <unk>.

<unk>, it's difficult during this time.

Interim retail so first line melanoma to assess between the two homes do any sense of tightly around and how's that.

<unk> changed or you have sent a dialogue with the F.D.A. around but [noise] engineer.

So I think <unk> I'm going to halfway to address that.

Right.

Jay Olson: Where we remember we evaluated the molecule in non-human primates.

Yeah. Thank senator Yeah, I think so the question. So we are actually working with our partner P.M.S. engaging the health authorities. So we'll definitely provide a feedback once we computed he held court discussions in this definitely involved not only the F.D.A., but not the you health authorities were.

Jay Olson: and other species, and we saw the effect on the immunological changes that the molecule could make. For example, we saw natural killer cell elevations. We saw their persistence. We saw changes in the activation state of these cells, and, you know, we also even, of course, proposed data, presented data on the overall differentiation of the natural killer cell compartment as well. So as we move into the clinic, we're looking to translate all of those kinds of findings. And the clinical trial has built into it an extensive biomarker program that allows us to measure these kinds of changes. This allows us to assess the natural killer cells and the CD8 T-cells in multiple compartments, such as the blood as well as in the tissue.

I think our plan for.

<unk> authorization should be global and 10 skating obtaining feedback globally from Oh, how twenties all day major one it's really critical for us to make the change the current design with a three endpoint has been you would improve by the relevant help forties. So before we make a change it's not only that game.

H meant but also other helpfully engagement that we need to obtain <unk> the change.

And once that's done then we'll be share information.

<unk>.

Sure.

Thank you My next question come from Tyler Van Deren from Piper Sandler their line in open.

Jay Olson: So we'd be very excited to present the data that we're seeing in this study. We think it's reasonable that either later this year or early next is a time when we can do that, assuming the dose escalation continues as planned. And the kind of things we'd like to see out of that dose escalation are, as I described, a combination of safety, tolerability, the PK, and the biomarkers in the program.

Because good afternoon. Thanks for taking the question I guess the first one is on the melanoma up to the to update that you gave with December cut off I think you said that medium p. effects was not a cheap 21 month and if I look back to the.

Jay Olson: Thank you. And then, I guess, maybe from Howard. Do you have a question?

It was 18.6 month follow up and at that point.

Peter Lawson: Howard, I know it's difficult during this time, but the interim readout for first-line melanoma to assess ORR between the two arms, is there any sense in timing?

You guys said that meeting people could be no worse than 15 months. So is that kind of three month different fair to apply here, maybe we didn't get that can be no worse than 18 months or curious your thoughts there.

Jennifer Ruddock: Timing around that, and how's the dialogue changed, or have you had further dialogue with the FDA? So thanks, Peter. This is Jennifer. I'm going to ask Wei to address that, if possible.

<unk> have to answer that.

Okay sure. Thanks, Hannukah, Yeah, I think for that question. So.

So he it's not always directly linear definitely with longer follow up then he minimum wood.

Wei: Yeah, thanks, Jennifer. Yeah, thanks for the question.

Wei: So, we are actually working with our partner, BMS, in engaging the health authorities. We'll definitely provide feedback once we've completed the health authority discussions. And this definitely involved not only the FDA but the EU health authorities, where I think our plan for obtaining market authorization should be global. And hence, getting feedback globally from all health authorities, all the major ones, really critical for us to make the change. The current design, with the three endpoints, has been reviewed and approved by the relevant health authorities. So, before we make a change, it's not only the FDA's engagement but also other health authorities' engagement that we need to obtain before proceeding. And once that's done, then we'll be sure not to.

[noise] on T.I. at the minimum P.F.S., but also be extended like because well we present it as a uncle and look as we.

<unk> data review and we we're not ready to present this publicly yet so I would not you know we have not done analysis to really project out what the minimum PS has with the at this time it that's definitely longer than it was back at city and we do plan in the second half a year to update melanoma data.

And that time, we can provide the detail what what it means in terms of P.F. as as we continue our follow up.

Okay, and that's a follow up is it possible to.

I guess what medium <unk>.

At what point of medium <unk>, how many months you guys would be really confident that you're seeing a significant difference here with the combination.

Operator: Thank you. Our next question comes from Tyler Van Buren on behalf of Piper Sandler. The line is open.

Tyler Van Buren: Hey guys, good afternoon. Thanks for taking the questions.

Because you know if you look at other phase two studies some clients have pointed out that they've shown you know 20 months medium P.F.S. and then in phase three you have shown no effect you know even the.

Tyler Van Buren: The first one is on the Melanoma Pivot 2 update that you gave with the December cutoff. I think you said that median PFS was not achieved at 21 months.

The these time quite seem to be an impressive relative to nivo motto therapy at seven months, a needle would it be 11 in the huh.

Tyler Van Buren: And if I look back at SITC,

Tyler Van Buren: ...

Well I'm going to ask you to answer that as well.

Tyler Van Buren: It was 18.6 months.

Sure. So the <unk> I I think Oh kind of break this into kind of two parts are they attract one is sort of the meeting and the others to hash ratio. So he ultimately one F.T.A. and other health 40 review the data for a for approval based on on P.F. as it's really the combination of.

Tyler Van Buren: of follow-up.

Tyler Van Buren: And at that point, you guys said that the median PFS could be no worse than 15.

Those two values. So two meetings certainly it's it it's it's very important but the halfway show give you they come <unk>. After two cops in our curves flooding tar laying out the curve. So those two elements have really important too. So it's a it's <unk>, it's always difficult to really say that.

Tyler Van Buren: [inaudible]

Tyler Van Buren: fair to apply here, meaning maybe medium PFS can be

Tyler Van Buren: No worse than 18 months, or I'd be curious to hear your thoughts there.

Oh. This is a particular meeting is sufficient because it's.

It's really need to compete shape of the curve on sometimes the meeting can bubbles, sometimes the meeting may not I can't cave a bit but if the rest of the at the curb contribute to a really strong has ratio difference. That's also very meaningful too so but I think the current data certainly say jester purely big separation between.

<unk>, but that's based on a pivotal two data now incomes are translatability onto the second part I I want to really talk but it's really a translatability I'll find out if phase two data from kibodeaux too onto a recreational phase to me and that's where it gets to the clock seven your question, which is you know certainly.

Historically, there's been many studies, where the phase two data, there's not translate into a phase three and two what level of competency you actually happy doing that.

Granted that's there's so many historical examples of that and I want to really point out the largely to non translatability has to do with the lack of connection with the endpoint being studied in the phase two and the endpoint being study in the face to eat so taking samples there are many.

He is where the phase two it's actually based on a P.S.N. coins and then the phase three it's based on O.S. endpoint in in certain diseases, those too I end points to not really connect really well. It does connect for instance, in C.R.C. really well, but in many other tumor types of that's not really connect really well.

Ray: Ray, I'm going to ask you to answer that. Thank you.

Ray: Sure. Thanks, Jennifer. Yeah, thanks for that question.

Ray: So, it's not always directly linear. Definitely, with longer follow-up, then the minimum PFS would also be extended, but because what we presented is an ongoing look as we are doing periodic data review, and we are not ready to present this publicly yet, so I would not, you know, we have not done the analysis to really project out what the minimum PFS would be at this time. It is definitely longer than it was back at 60, and we do plan to update melanoma data in the second half of the year. At that time, we can provide details of what it means in terms of PFS as we continue our follow-up.

Ray: Okay.

Ray: I guess what median PFS, at what point is the median PFS?

Ray: The End. I hope you enjoyed this video. If you did, please subscribe to my channel. I upload videos every week.

For lack of a good endpoint Dan people, it's kind of how to base it on something and often times, it's based on P.S. and hoping with trying to say to laugh and that's where the lack of connections needs to some of that failure sleeping observed in the past now in our particular case in the first one not attack melanoma.

What give us particular competent is the analysis done by.

F.T.A. that was presented at ask cold in on on pointing 19 and in that F.T. analysis any of you are familiar.

<unk> took nearly 5000 worth a patient data from all directions shouldn't trials that were submitted to them for approval in first one at a static melanoma and get it very comprehensive not analysis and what they asked the question is how well do response rate when he connect with both.

Ray: you guys would.

Crashing priest or Bible, and overall survival and in particular, how well it gets a definite response not the arbitrary resist a 1.1 quite here, which is 30% reduction tumor size, but actually cross okay point they looked at.

Ray: I would be really confident that you're seeing a significant difference here with the combination because, you know, if you look at other phase two studies, some clients have pointed out that they've shown, you know, 20 months median PFS and then in phase three have shown no effects, even though these time points seem to be impressive relative to NEVO monotherapy at seven months, and NEVO would be at 11 and a half. I'm going to ask you to answer that question as well. Thanks.

Ray: Sure. So, I think I'll kind of break this into kind of two parts to really address that. One is sort of the median, and the other is the HASS ratio. So, ultimately, when FDA and other health authorities review the data for a full approval based on PFS, it's really the combination of those two values. So, the median is certainly very important, but the HASS ratio will give you the complete separation of the two Koppener curves for the entire length of the curve. So, those two elements are really important, too. So, it's always difficult to really say that, you know, oh, this particular median is sufficient because it's really the complete shape of the curve. Sometimes the median can bubble.

Ray: Sometimes the median may not concave a bit, but if the rest of the curve contributes to a really strong HASS ratio difference, that's also very, very meaningful, too. So, but I think the current data certainly suggests a fairly big separation between the NEBO-BANPEC arm versus the NEBO arm, but that's based on the Pivotal 2 data. Now, in terms of translatability, so the second part I want to really talk about is the translatability of the Phase 2 data from Pivotal 2 onto a recreational Phase 3, and that sort of gets to the crux of your question, which is, you know, certainly historically there have been many studies where the Phase 2 data does not translate into a Phase 3, and to what level of confidence do you actually have in doing that? And granted, there are many historical examples of that, and I want to really point out that much of the non-translatability has to do with the lack of connection between the endpoint being studied in Phase 2 and the endpoint being studied in Phase 3.

25 per cent tumor reception 50 per cent <unk> 75 per cent <unk> and also.

T I disappearance of all the target lesions and with each helped those <unk>. They took a look at what is there a P.S. what if there are <unk> and so strong correlation across obese <unk> and they see extremely strong trend not only with.

Ray: So, taking an example, there are many diseases where the Phase 2 is actually based on a PFS endpoint, and then the Phase 3 is based on an OS endpoint, and in certain diseases, those two endpoints do not really connect really well. They do connect, for instance, in CRC really well, but in many other tumor types, they do not really connect really well. But for lack of a good endpoint, then people kind of have to base it on something, and oftentimes it's based on PFS and hoping it will translate to OS, and that's where the lack of connection leads to some of the failures we've observed in the past.

Target therapy, like P.B. rap and <unk> like it's specially with immunotherapy, such as nibble map and <unk> and <unk> and the conclusion neat come to a sound. The depth response really correlates extremely strongly with on survival. Both in terms of P.F.S. and <unk>.

Oh and in particular, the strongest came to when you look at patients who have more than 75% reduction and also especially with complete disappearance, and it's really pay on that basis looking aren't the biggest difference that we observed between <unk> and ultimately connecting to.

Ray: Now, in our particular case, in the first metastatic melanoma, what gave us particular confidence was the analysis done by... FDA that was presented at ASCO in 2019. And in that FDA analysis, many of you are familiar. FDA took nearly 5,000 patients from all the resolution trials that were submitted to them for approval, first by metastatic melanoma, and did a very comprehensive meta-analysis. And what they asked was the question, how well do response rates really connect with both progression-free survival and overall survival? And in particular, how well the depth response, not the arbitrary RISC 1.1 criteria, which is 30% reduction in tumor size, but actually across all cut points, they looked at 25% tumor reduction, 50% tumor reduction, 75% tumor reduction, and also the complete disappearance of all the TARC lesions.

<unk>, it's really.

Are C.R. rate and based on the F.T. analysis, if you if for the patient compete disappeared yourself there <unk>.

At the P.S.S. at one year and the <unk> and O.S. at one year, it's extremely high and it's really so they're say clear demonstration given on T. extensive <unk> have done all fine Translatability were strong connection between what <unk> death response.

And now and the final P.S. <unk> <unk> by the sound Rhetorician studies and distance where it locate our C.R. rate, we we think they're saying a high like with like that this may translate into some type of Serb Apple benefit and restaurants are no benefits. So.

That I hope that answer your question.

That's very helpful. Thank you.

Okay.

Thank you next question comes from Chris <unk> found <unk> airline adult then.

Ray: And with each of those subgroups, they took a look at what their PFS, what their OS, and was there a strong correlation across all these cut points. And they saw extremely strong trends, not only with target therapy, like VA wrap and neck inhibitors, but especially with immunotherapies such as nivolumab and pampolypsumab and ipilimumab. And the conclusion they come to is that the depth response really correlates extremely strongly with survival, both in terms of PFS and overall survival. And in particular, the strongest came through when you look at patients who had more than 75% reduction and also especially with complete disappearance. And it's really on that basis, looking at the biggest difference that we observed between the PIFO2 data and ultimately connecting to PFS, survival is really our CR rate.

Great. Thanks, very much maybe this is for K.Z. I know that certainly in propel the condo weren't they couldn't doing.

All the opportunity to explore different doses of the M. peg in particular, I think higher doses and I think that some commentary that you began describing over six months ago now I'm just curious to know if there's anything at this stage that you have been observing or learning that is making you contemplate approaching any further development work with them.

God or an existing or additional indication in any other way.

Thanks, Thanks, Chris actually I'm I'm I'm gonna halfway to comment on that he's been working on that does that place component per Pal.

And then I'll actually it would come in after way. Thanks like Yeah sure absolutely. So you know <unk>. So d. at the proposed study maybe helpful Me too I took a step back and look at the bigger picture. Some propels tell you only have two parts. They start out there said those top impatient part and then Thursday, there's a there's a focus expansion.

Ray: And based on the FDA analysis, if for the patient, the complete disappearance of their TART lesions, the PSS at one year and the OS at one year are extremely high. And it's really, so there's a clear demonstration given the extensive meta-analysis the FDA has done of translatability or a strong connection between what's observed in terms of death response and the final PSS and OS delivered by these registration studies. And this is where, looking at our CR rate, we think there's a high likelihood that this may translate into some type of survival benefit and a strong survival benefit. So, I hope that answered your question. That's very helpful. Thank you.

Sort of a face to face to study embedded in their looking.

And also lung cancer in the first time setting so the rationale for it to undertake hate those docking station, even though the molecules already in the registration page is it's actually a couple of code. One is we have learned a tremendous amount above this molecule us pay progress this is still.

A a clinical development stage molecule and while we have confidence in detail of six micrograms per kilogram <unk> you have all the map in our current recent studies.

And that's highlight about it by the fact that caught the data is good enough to K.A.F.D.A. based through Dec nation, which is kind of the highest I watch me out that potential benefit the combination between two patients and <unk> company I mean.

Chris Shibutani: Thank you. Our next question comes from Chris Shibutani from Cowen. Your line is open. Great, thanks very much. Maybe this is for Jay-Z.

The ship with our P.M.S. colleague <unk>, a number of recent studies Oh based on data or we can read intro to so we we frame believed that the 96 micrograms per tool kind of those since they're very I kept those and have complete back to back it up and sort of he and that's really also supported by <unk>.

Chris Shibutani: I know that certainly in Propel, the combination work that you're doing involved the opportunity to explore different doses of Benpeg, in particular, I think, higher doses. And I think that's some of the commentary that you began describing over six months ago now. I'm curious to know if there's anything at this stage that you have been observing or learning that is making you contemplate approaching any further development work with Benpeg, either in existing or additional indications, in any other way.

I believe pen investment from I.B.M.S. colleagues and also <unk> from the F.T.A., but that means said, we have learned tremendous amount as we there was a lot of patients and managed to a profile that we think we can actually improves the management all fun <unk> in pace.

Chris Shibutani: Thanks. Thanks, Chris. Actually, I'm going to ask Wei to comment on that. He's been working on the dose escalation component for Propel, and then I'll ask you to comment afterward.

And perhaps can you didn't push that those even higher and and that's you know different diseases have kept insensitivity to <unk> any lung cancer and compared to say melanoma. The degree of sensitivity if it's <unk>.

Wei: Yeah, sure, absolutely. So, you know, the Profile Study may be helpful to take a step back and look at the bigger picture. So, the Profile Study really has two parts. There's a dose optimization part, and then there's a focus expansion, sort of a phase two study embedded in there, looking at specifically non-small cell lung cancer in the first-line setting. So, the rationale for us to undertake a dose optimization, even though the molecule is in the registration phase, is actually a couple of things. One is that we have learned a tremendous amount about this molecule as we progress.

It's not as strong so for instance, no monotherapies <unk>, it's active across <unk> sub groups and melanoma, but not so in in long. So the current approval is released who are just <unk> not what the old calmer population and the predominant use the pen <unk>.

And that 50% above pop population and given that we thought to be really helpful to to Glee puts it though it's a bit see if we can with a new management guideline in place identify even a higher dose and produce even stronger benefit to patients anything he used that's more challenging ban on again.

Wei: This is still a clinical development stage molecule, and while we have full confidence in the dose of 6 micrograms per kilogram, in combination with the Ebola map, in all our current registration studies, And that's highlighted by the fact that the data is good enough to obtain a FDA race 3 designation, which is kind of the highest acknowledgment of the potential benefit the combination may bring to patients. And in partnership with our BMS colleague, we've carried out a number of recent studies all based on data that we've generated in PIVO2.

Melanoma in terms stuff on how how sensitive it is t. know therapy. So that that's the those half nation and the rationale why we're undertaking that at the same time working the expansion in first find nonsmokers, how lung cancer and and combining with with pen and then list map there.

<unk> well in in a combination because temple currently is to establish first line center care in the first time study so.

So anyway.

Wei: So we firmly believe that the 6 micrograms per kilogram dose is a very active dose, and we have clinical data to back it up, and that's really also supported by the belief and investment from our BMS colleagues and also the race 3 designation from the FDA. But that being said, we have learned a tremendous amount as we dosed a lot of patients and managed the AE profile that we think we can actually improve the management of adverse events in patients and perhaps could even push the dose even higher. And as you know, different diseases have different sensitivity to immunotherapy, and in lung cancer compared to, say, melanoma, the degree of sensitivity is actually a little different, and is not as strong.

About whether it seems promising or.

What the at the studies Ancona, we've noticed a handful patients and then we have as Howard mentioned, we have plans to on really sure a part of that data at at a few whose picture conference either at the end of this year, we're beginning next year.

Okay, while you're away there so well behaved I know you're not going to spell maybe [laughter] partnership.

So you know I mean thinking about historically you guys really set up a terrific relationship with personal going back and that was structured with kind of that timeline objective, which I remember a year ago you guys extended into September and then we'd had the renegotiated contract and I think that was kind of announced at the end of September really <unk>.

Wei: So, for instance, monotherapy in vivo or monotherapy in PEMBRO is active across all PDR1 expressions, subgroups in melanoma, but not so in lungs. So the current approval is really for just PDR1 positive patients, not for the old-comer population. And given that, we thought it would be really helpful to really push the dose a bit, see if we can, with a new management guideline in place, identify even higher doses and produce even stronger benefits to patients in a disease that's more challenging than melanoma in terms of how sensitive it is to immunotherapy. So that's the dose definition and the rationale why we're indicating that. At the same time, we're doing the expansion in first-line non-small-cell lung cancer and then combining it with PEMBRO nilizumab, well, in combination because PEMBRO currently is the established first-line standard of care in the first.

Kind of <unk> now the <unk> prove it environment, where everyone is looking to buy time, just curious about the renegotiated contract is there some sort of in a scoop Clark that allows them to legal in an extra three or six months. If there's some sort of timeline that we should think of her get out of jail card and just curious to know give 'em clinical trial.

Kloosterman completion time lines are obviously, all sort of encumbered now and wondering in particular about the Bristol renegotiated or maybe some of the other materials. Other at material you know partnerships you have recovered Pfizer regularly.

Thank Chris I'm Gonna Howard if he can answer that Howard.

Sure I, Chris look there's there's there's certainly nothing in the contract that gives one an escape for this kind of horse manure situation, obviously, but I woke, but I will tell you that look clinic every company has its own method of of moving trials forward and and this situation you know nektars.

Actors being fairly successful in recruiting sites in recruiting patients they'll always be some delays, but generally we're moving things along quite nicely other companies such as B.M.S. have set across all their across all their programs, they're not going to be you know, they're not going to be recruiting any new sites until they get a better handle on what's going on with Kobe 19.

Chris Shibutani: So any willingness to share hints about whether it seems promising or not?

Wei: With the studies ongoing, we've dosed a handful of patients, and then we have, as Howard mentioned, we have plans to really share a part of that data at a future conference, either at the end of this year or beginning of next year.

So we sat there could be there could be a three to six months away. It doesn't really change anything in the agreement I think we're <unk>. We're we're still working very closely with B.M.S. The move these programs for the ones that we're running a in the collaboration or moving forward nicely <unk>. They will they will figure out shortly I'm sure how to how to started rolling sites again and how to run.

Chris Shibutani: Okay, well, you're in a way you're so well behaved. I know you're not going to spill. Maybe I can ask you a question about partnership. So, you know, what I mean.

Chris Shibutani: Partnership

Group patients again remotely is as every other companies doing and I. So I I think there could be a delay there's there, but most likely will be able to like in in some of those studies, but I don't think it's anything that has any contractual impact and as long as long as we have a great relationship with them and and we do at the teams of teams of.

Chris Shibutani: for Going Back. And that was structured with kind of a timeline objective, which I remember a year ago, you guys extended into September. And then we've had the renegotiated contract. And I think that was kind of announced at the end of September, really in the pre-COVID era. Now that we're in the COVID environment, where everyone is looking to buy time, I'm just curious about the renegotiated contract. Is there some sort of an escape clause that allows them to wiggle in an extra three or six months? Is there some sort of timeline that we should think about? Is there a get out of jail card?

I have changed involved and I think together with B.M.S. everything is going smoothly outside of cold outside of coded 19, I think there's always gonna be delays, there's always challenges in any clinical study, but I think everybody believes that assert certainly better pagan nivo in in <unk>.

Chris Shibutani: Just curious to know, given clinical trial pacing and completion timelines are obviously all sort of encumbered now, and wondering in particular about the Bristol deal renegotiated, or maybe some of the other material partnerships you have with folks like Pfizer. Thanks, Chris. I'm going to ask Howard if he can answer.

Have a <unk> melanoma have a significant benefit and if you look at the if you look at the the P.S.S. data that we have so far in the pivotal to study of you know where I don't I don't see how will be lower than 21 months that would be I would think the 21 21 and a half months would be the the the the lower limit.

Howard W. Robin: Sure. Hi Chris.

Of of medium P. Fs, So would that said I think when you compare that to you know leave alone, which is you know six and a half months I think that's fairly dramatic and remember as as way said earlier.

Howard W. Robin: Look, there's certainly nothing in the contract that gives one an escape clause for this kind of force majeure situation, obviously. But I will tell you that, look, every company has its own method of moving trials forward in this situation. You know, Nektar's being fairly successful in recruiting sites and recruiting patients. There'll always be some delays, but generally, we're moving things along quite nicely. Other companies, such as BMS, have said across all their programs that they're not going to be recruiting any new sites until they get a better handle on what's going on with COVID-19. So, we said there could be a three to six-month delay. It doesn't really change anything in the agreement.

What everybody I think it's excited about would waste that earlier is I don't think you can compare this necessarily to other challenges that companies obscene. When they went from phase two to phase three <unk> number one we have the same endpoints number two we didn't we didn't see any toxicity in phase two that would require us to lower the that was going into phase, three which which some other companies have had to do.

So I think it's just it's it's apples to apples as you're going to get and I think the M.S. It should be and is is excited about it as we are but no. There's no. There's no contractual provisions for this type of signal one could have ever envision. This so is as far as I'm considering the companies are behaving well together and I'd like to see it all move forward in a in a respectable fashion.

Howard W. Robin: I think we're still working very closely with BMS to move these programs forward. The ones that we're running in the collaboration are moving forward nicely. They will figure out shortly how to start enrolling sites again and how to recruit patients again remotely, as every other company is doing. And so, I think there could be a delay. There will most likely be a delay in some of those studies, but I don't think it's anything that has any contractual impact. And as long as we have a great relationship with them, and we do, the teams have changed and evolved. And I think, together with BMS, everything is going smoothly outside of COVID-19. But I think there's always going to be delays. There are always challenges in any clinical study, but I think everybody believes that, certainly, Fempeg and Nevo and Firstline Melanoma, Metastatic Melanoma, have a significant benefit. And if you look at the PFA...

Great and then lastly winger team is sitting on the Zoom conference calls really really add folks.

Going to put one of your assets into encoded therapeutics trial might be good for a retail pop in the stock.

Well I can say this week with what we've certainly looked at all the literature and there's there's an awful lot of literature that suggests that patients who have low lymphocyte counts leukemia don't do very well with cobin 19, and if you can increase their lymphocyte levels. There is those patients with higher.

Lymphocyte levels actually too much better with Cobra 19, So it's something we're looking at if something were talking about and we haven't we haven't made any plans yet, but it's something that if we decide to if we come up with an approach to move forward will certainly share it with everybody.

Great. Thanks for telling me my question. Thanks, then.

Thank you. All next question comes from just have five from J.P. Morgan airline is okay.

Howard W. Robin: So far in the PIVOT-02 study, you know, I don't see how we'll be lower than 21 months. That would be, I would think that 21, 21, and a half months would be the lower limit of median PFS.

Hi, this a vehicle on the call for a job to God. Thank you for taking our question regarding 180 patient phase one to those optimization expansion study and not from also lung cancer.

Howard W. Robin: So, with that said, I think when you compare that to, you know, NEVO alone, which is, you know, six and a half months, I think that's fairly dramatic. And remember, as Wei said earlier, and this is what everybody I think is excited about, as Wei said earlier, I don't think you can compare this necessarily to other challenges that companies have seen when they went from phase two to phase three. Number one, we have the same endpoints. Number two, we didn't see any toxicity in phase two that would require us to lower the dose going into phase three, which some other companies have had to do.

That yeah.

Can you provide an overview of that study, including that doesn't that you'll be evaluating and that does optimization bands and then you plan to for like decent based on P.D.L., one sided for any other biomarkers.

Thank you go I'm going to its way to walk through what the structure of the the M.S. study would be for Ah Ben type stuff or not.

Thanks Bye.

Howard W. Robin: So I think it's as apples to apples as you're going to get, and I think CMS should be and is as excited about it as we are. But no, there's no contractual provision for this type of thing. No one could have ever envisioned this. So as far as I'm concerned, the companies are behaving well together. And I'd like to see it all move forward in a respectable fashion.

Yeah. Thanks so.

The so that study Oh, so very similar to propel study in design now that study not finalized yet so so I cannot share too much d. details now, but I had a very high level concept it'd be very similar to the Pal in the sense that will be pushing that though is higher beyond.

Howard W. Robin: And then lastly, when your team is sitting on those Zoom conference calls with the Gilead folks, are they begging to put one of your assets into a COVID therapeutics trial? Might be good for a retail pop in the stock.

Micrograms and in addition, well the willing patients on a cross ocarroll expression uh-huh too.

Howard W. Robin: Well, look, I can say this, we have certainly looked at all the literature, and there's an awful lot of literature that suggests that patients who have low lymphocyte counts or leukemia don't do very well with COVID-19.

To really try to absurd if the combination of <unk> plus people map can expand the activity checkpoint.

To the low pressure population of spotlights than naked upon population so that that.

Data coming from that study along with the Palace study would help.

Howard W. Robin: And if you can increase their lymphocyte levels, those patients with higher lymphocyte levels actually do much better with COVID. So it's something we're looking at, it's something we're talking about, and we haven't made any plans yet, but it's something that if we decide to, if we come up with an approach to move forward, we'll certainly share it with everybody.

Wheat, and our partners can make an assessment won't meet them appropriate and best charges on going into pastry.

<unk>.

Great. Thank you.

Thank you well take our next question from the Fey Yang friendly they while you're line is open.

Howard W. Robin: Great, thanks for tolerating my questions. Thanks, Jen. Thank you. The next question comes from Jessica Fye from J.P. Morgan. Your line is open. Hi, this is Yuko on the call for Jessica. Thank you for taking our questions. Are you starting the 180 patient phase one to dose optimization and expansion study in non-small cell lung cancer? that CMI will be running. Can you provide an overview of that study, including the doses that you'll be evaluating and the dose optimization phase? And then do you plan to select patients based on PD-L1 status or any other biomarkers? Thanks, Yuko. I'm going to ask Wei to walk through what the structure of the BMS study would be for benpeg-bisnevo and non-small cell lung cancer. Thanks, Wei.

Hi.

Good Act anyway.

My question just a quick on.

Yeah 255.

You have a couple of <unk>.

Mmm.

I think about.

Opportunities for solid till now where do you see the biggest opportunity for.

Oh 15.

Taking things I'm gonna have changed to answer that candy.

Yeah, certainly so <unk>. So there are a number of interesting opportunities in the solid tumors space. When you consider or combination with targeted antibodies there'll be no have a component of their mechanism associated with antibody effect or function. So you know that in in the.

Tissues right that we typically see lower levels of national killer cells right. So we rely on antibodies that work through direct signalling like for example, EG F.R. engaging antibodies. You know for example, then we also hope that they can engage it bag of civic mechanism as part of their effect or function in the tissue.

Corinne Jenkins: Yeah, thanks. So.

Wei: So that study is also very similar to the PROPEL study in design. Now that study is not finalized yet, so I cannot share too many details now, but at a very high-level concept, it'd be very similar to PROPEL in the sense that we'll be pushing the dose higher, beyond six micrograms, and in addition, we'll be enrolling patients across OPR1 expression 2, to really try to observe if the combination of NPEG plus EbolaMAP can expand the activity checkpoint to the So the data coming from that study, along with the PAL study, would help us and our partners to make an assessment of what would be the appropriate and best trial design going into phase two.

And one of our overarching hypotheses. The 255 is that in addition to all those mechanism you know we should be able to drive natural killer so into the tumor as well.

And I think you saw some of the data that we presented at Sydney. Another car instances that showed that even in the mouse model, where you had an intact immune system or in one that you had a dina graph, but it was skids still incase l. competent even if you implanted tumors into peripheral tissue like the flanker, though I.

You gave to 55, you could still driving in case, though into these peripheral tumors.

And you know this very well right that that's not a limb Floyd kind of a tumor is not a liquid tumor by any means this is a traditional solve the tumor that N.K. cells can populate.

Wei: Great, thank you. Thank you. We'll take our next question from Defea Yang from Azuho. Your line is open. Hi, good afternoon, and thanks for taking the time. Just a quick one on the NKPR 255.

We demonstrated that whether you're combined with antibodies like you know you G.F.R. Engagers <unk> stepped in types of bindings like herceptin, her twos and and others that in a range of different tumor model either in the xena graph during the fully competent nor even P.D.F.K. you can.

Defea Yang: So you have a couple of trials ongoing in liquid tumors. How do you think about... the opportunities for solid tumors? Where do you see the biggest opportunity for?

Gauge those kind of activities during the solid tumors space. So as we I opportunities in the clinic some of the things it's quite interesting to us or combination for example, with agents like Ducks about.

Jay Olson: Thank you, Gise. I'm going to ask Jay-Z to answer that. Jay-Z?

Jay Olson: Yeah, certainly. So there are a number of interesting opportunities in the solid tumor space when you consider a combination with targeted antibodies that we know have a component of their mechanism associated with antibody effect or function. So you know that in tissues, right, that we typically see lower levels of natural killer cells, right? So we rely on antibodies that work through direct signaling, like, for example, EGFR-engaging antibodies, you know, for example, but then we also hope that they can engage a phagocytic mechanism as part of their effector function.

We already know their opportunities and targeting the encased, though compartment and the combination was to talk some we've seen some other antibody combination to do that so big that represents one very unique opportunity and then of course that there's really a whole wealth of other opportunities because you can quickly moved.

Beyond.

<unk> two additional solid tumor targeting antibodies and consider additional lines a therapy.

Hoped that answers your question to thing.

Yeah, they have like.

Jay Olson: And one of our overarching hypotheses with 255 is that, in addition to all these, we should be able to drive natural killer cells into the tumor as well. And I think you saw some of the data that we presented at SIDSI and other conferences that showed that even in a mouse model where you had an intact immune system, or in one that you had a xenograft, but it was skid, so it was still NK cell competent, even if you implanted tumors into peripheral tissues like the flank or the thigh. If you gave 255, you could still drive NK cells into these peripheral tumors. And you know this very well, right?

I have one quick follow up with then pack <unk>, Yeah and Kiki.

Full band Pag for the <unk>.

That'd be like a pen into those escalate to 10 micrograms per kilo <unk> M.T.V.

Wait what you'd like to take that question sure. Yeah. So the to the current design allows us to to those have play all the way up to 12 micrograms per kilogram, which is twice the current those Ah you know <unk> studies, so now obviously into.

Jay Olson: That's not the lymphoid kind of a tumor. It's not a liquid tumor by any means. This is a traditional solid tumor that NK cells can populate. And we demonstrated that whether you combine with antibodies like, you know, EGFR engagers like Cetuximab or septin types of binding like Herceptin, HER2s, and others, that in a range of different tumor models, either in the xenograft or in the fully competent, or even in the PDX case, you can engage those kinds of So as we eye opportunities in the clinic, some of the things that are quite interesting to us are combinations, for example, with agents like Sudoxone. We already know that there are opportunities to target the NK cell compartment in combination with cituximab. We've seen some other antibody combinations do that, so I think that represents one very unique opportunity. And then, of course, there's really a whole wealth of other opportunities because you can quickly move beyond to additional solid tumor targeting antibodies and consider additional lines of therapy. Hope that answers your question, Daphne.

And M.T.D. is that it's one of element that contributed to fishing for our P. tricky, but in addition, what can I look at the totality of data both in terms of 18 apathy and from the safety Oh, So <unk> it treated longer whether the <unk> continues to be to be well behaved.

Yeah.

Yeah, I think you're away and think about taking sure okay.

Absolutely.

Thank him I'd have to question comes from part has what from D.T. aging airline adult then.

Yeah. So thanks for taking a question I'm not sure if this got us yet but.

The pivot Oh, two melanoma cohort is it possible then you already have a minimum of of 21 month in terms of P.F. for that cohort just an update on on the pivotal to melanoma cohort <unk> would be great.

<unk> Daisy do you want to take that one.

Yeah sure <unk> nice to speak with you and yeah that I wanted to definitely clarify you you're diagnosed that correctly. So in the current assessment of the data you know we're at a minimum of a 21 month duration in the P.F.S. This is very exciting data right, we're continuing to watch.

Jay Olson: Yes, very helpful. I have just one quick follow-up with BAMPAC. Wei, would you remind us what the MTD for BAMPAC is? For the perpetual study, something like you're planning to dose escalate to 10 micrograms per kilo. But what is the MTD? Wei, would you like to take that question? Sure.

This cohort developed continuing to see the patients. Obviously this is indicative of the kind of durability that we've already presented on last year, we're seeing that kind of durability extended we're seeing a further extension of the P. at best we're really looking forward Bert together again additional update on this cohort.

We'd be looking to do that you know perhaps at a medical meeting you know later this year.

Wei: Yeah, so the current design allows us to dose escalate all the way up to 12 micrograms per kilogram, which is twice the current dose in our registration studies. Now, obviously, in the end, MTD is one of the elements that contributes to the decision for RP2D. But, in addition, we're going to look at the totality of data, both in terms of safety and efficacy, and from the safety perspective, also, as patients get treated longer, whether tolerability continues to be well behaved.

Okay. Thank you.

We're looking forward to it as well.

Thank you.

Next question comes from George Farmer from the M.L. capital markets, Yeah lines open.

Hi, good afternoon kinds for take my question more on pivot O. two in the melanoma cohort I recall it sits see that while you had not hit your median after 18 months and P.F. fast it looked like the 12 month P.F.S. was probably around 53% so that implies maybe.

Wei: Yeah, thank you Wei, and thanks for taking the time.

<unk> by one or two patients would throw the curve off into the into the lower part lower lower half of the.

Bert Hazlitt: Absolutely.

Bert Hazlitt: Thank you. Our next question comes from Bert Hazlitt from DTIG. Your line is open. Yes, so thanks for taking the question.

Of the graph is it safe to say that no patients have progressed since that time and are you. In fact, following all the patience or have some patience been I lost a follow up and they're just censored at various times. Once you could comment I mean that any of that that'd be great.

Bert Hazlitt: and I'm not sure if this has been asked yet, but...

Bert Hazlitt: The PivotO2 melanoma cohort, is it...

Bert Hazlitt: It's possible that you are already at the minimum of 21 months in terms of PFS for that cohort. Just an update on the PivotO2 melanoma cohort would be great.

Mm.

Way do you want to start or Jason.

Give to either one of you.

<unk>.

Casey do you want to.

Start personal yeah, Oh, adding.

Jay Olson: Jay Z, do you want to take this one?

Yeah sure. So so you know George those are those are good questions and well we would like to do is to update you know the data at a medical meeting later. This year then we can go through all of the details of the data because in addition to any like the question you asked about durability right also.

Jay Olson: Yeah, sure. Hey Bert, nice to speak with you. And yeah, I definitely want to clarify that you diagnosed that correctly. So in the current assessment of the data,

Jay Olson: We're at a minimum of a 21-month duration in the PFS. This is very exciting data. We're continuing to watch this cohort develop, continuing to see the patients. Obviously, this is indicative of the kind of durability that we already presented on last year. We're seeing that kind of durability extend, and we're seeing a further extension of the PFS. We're really looking forward, Bert, to giving an additional update on this cohort. We'd be looking to do that perhaps at a medical meeting later this year.

You know, we can cover deepening or responses the additional kinds of overall effect that the patients have seen how's that you. Remember these are patients that are now being treatment for a very long time as well right. So we were also as you saw last time on the gave it updated 50, we saw patients that achieved maximal benefit.

Maintaining very very deep responses or complete responds many cases for over 12 months of additional treatment. So we wouldn't provided that kind of detail and that kind and assessment and you know even we can walk through that kind of spider classes, we do right like one on one like we would do that at the future meeting, where we could really <unk>.

Jay Olson: Okay, thank you. We're looking forward to it as well. Thank you. Our next question comes from George Farmer from BMO Capital Markets. Your line is open.

The data later this year Hmm well you <unk> do you think you'll be sharing overall survival data as well.

George Farmer: Hi, good afternoon.

George Farmer: Thanks for taking my questions.

George Farmer: and more on PivotO2 and the melanoma cohort. I recall at CITSE that while you had not hit your median after...

So.

Yeah, Yeah. Okay go ahead way.

George Farmer: 18 months in PFS. It looked like the 12-month PFS was probably around.

Oh, Yeah, I think so the on right now the data, it's really quite long. So I think our primary coby really focus on on describing the p. I pad since that in the end is the primary endpoint for this study on the basis, which will be wise to obtain a poor.

George Farmer: around 53%. So that implies maybe progression by one or two patients would throw the curve off into the lower part, lower half of the graph. Is it safe to say that no patients have progressed since that time?

<unk>.

George Farmer: And are you in fact following all the patients, or have some patients been lost to follow up, and they're just censored at various time points?

That's probably more meaningful I think as writing out the hard classmate without <unk>, yes.

Given how I'll call it covers booking.

George Farmer: If you can comment on any of that, that would be great.

Okay, and then J.C. regarding 358 and the.

Wei: Wei, do you want to start or Jay Z? Give it to either one of you.

The presentation of the lupus to the phase one be lupus data.

Wei: Casey, do you want to start first? No. Yeah.

You're you're presenting it to conferences that you <unk> you are and A.A.C.L.A.C.R., what what what will be different different between those two presentations if anything.

Jay Olson: Uh, yeah.

Jay Olson: Yeah, sure.

Jay Olson: So George, those are good questions, and what we would like to do is to update the data at a medical meeting later this year. Then we can go through all of the details of the data because, in addition to any, like the questions you asked about durability, right? Also, we can cover deepening of responses, the additional kinds of overall effect that the patients have seen. Also, I have to remember, these are patients that have now been in treatment for a very long time, right? So we also, as you saw last time when we gave an update at 50, saw patients that achieved maximal benefit maintaining very, very deep responses or a complete response in many cases for over 12 months of additional treatment. So we would provide that kind of detail and that kind of assessment. And even we could walk through the kind of spider classes we do, right? Like one-on-one, so we would do that at a future meeting when we could really unveil the data.

George Farmer: Thank you.

Mhm, Yeah. She was big doors. Good question. So so one of the things as because you are is going to be a virtual conference.

We we know that it's it's harder to get the same kind of visibility you know the program because you're normally used to that large conference you know all the people there and the ability to socialize the results.

We expected A.C., our main cause rheumatology, which comes in November yeah, we expected that.

Not going to be a virtual conference I I mean with coded aside you know, but we're projecting that the situation is different you know roughly six months from now and so are there we would be looking for the actual real time conference field one of the things that we did last year when we presented the single sending dose data.

Is that we covered you know kind of the clinical data into parts. So for example, if the U.R. conference and the Sad study recovered the safety Pharmaco kinetics, and then the T. Rag pharmacodynamics showing the dust dependent expansion there'll be presented remember we showed up about.

George Farmer: Do you think you'll be sharing overall survival?

George Farmer: Do you think you'll be sharing overall survival data as well? So, I can say that we are...

Ray: Yeah, okay. Go ahead, Ray.

Ray: Yeah, I think so far the survival data is really quite long, so I think our primary goal will be really focused on describing the PFS since that, in the end, is the primary endpoint for the study on the basis of which we will obtain approval. So I think that's probably the more meaningful one. I think it's really hard to estimate what the OS is right now, given how the curve is looking.

17 fold increase in N.T. rag levels over baseline at the top does that we evaluated in that study and then it A.C.R. We go much deeper into the female type of the patients treated with extra three five it. So there we looked very closely then cytokine responses.

We look very closely at the T. rags in their activation status and we even did do recall it methylation studies in the Fox P. three promoter you know together really really diving deeper into the analogy. So that's one thing that you can consider or how we will ours. The data you know and consideration for you.

George Farmer: Okay, and then Jay-Z, regarding 358 and the...

Jay Olson: The present.

Jay Olson: of the phase 1B lupus.

Jay Olson: Data. You're presenting at two conferences, at ULAR and AACR. What will be different between those two conferences?

R. and D.C.R. and then of course, the key point of the multiple ascending does study is this is then lupus patients. So we're evaluating 358 and the disease immune system and of course, we're evaluating multiple doses of the drugs not just the single those.

Jay Olson: Thank you. Thank you. Thank you.

Jay Olson: Have a nice day!

Operator: Mm-hmm.

Operator: Yeah, sure thing, George. Good question. So, one of the things is that because ULAR is going to be a virtual conference, you know, we know that it's harder to get the same kind of visibility, you know, of the program, because you're normally used to that large conference, you know, all the people there and the ability to socialize the results. We expect that ACR, American College of Rheumatology, which comes in November, you know, we expect that that is I mean, with COVID aside, we're projecting that the situation will be different, you know, roughly six months from now.

So you guys really right around the corner barely a month away. So you'll see the the early presentation of the data and then a much bigger time showcase up as to commit a C.R. later this year.

Okay, and finally do you think 358 could treat side of kind storm associated with <unk>.

<unk>.

So that's a very interesting question. So 358 definitely induces regulatory t. cells, yeah, you're familiar with our data it can induce polyclonal regulatory t. cell response, so it's a very interesting concept in new on one of the things that we do know about.

Jay Olson: And so, for there, we would be looking for the actual real-time conference field. One of the things that we did last year when we presented the single ascending dose data is that we covered, you know, kind of the clinical data in two parts. So, for example, at the ULAR conference in the SAD study, we covered safety, pharmacokinetics, and then Treg pharmacodynamics, showing the dose-dependent expansion that we presented. Remember, we showed about a 17-fold increase in Treg levels over baseline at the top dose that we evaluated in that study. And then at ACR, we went much deeper into the phenotype of the patients treated with Nektar 358. So, there we looked very closely at any cytokine responses. We looked very closely at the Tregs and their activation status.

You know <unk> decided kind storm as those are seem to be non limb Floyd derived side of crimes right. There, they're typically innate trying to cytokine say tile six.

You know others linked to C.R.P. for example, so we typically do think that lymphoid cells can antagonize that those are very interesting thought very interesting idea, but you know right now our our plans with 358 or more much very squarely focus in the auto immune to the space.

Okay, great. Thanks very much.

<unk> Oh My next question come from Ireland to leave from Cannacord airline is open.

Jay Olson: And we even did, as you recall, the methylation studies of the FOXP3 promoter. You know, again, really diving deeper into immunology. So that's one thing that you can consider for how we will parse the data, you know, in consideration for UR and ACR. And then, of course, the key point of the multiple ascending dose study is that this is in lupus patients, so we're evaluating 358 in the disease immune system. And, of course, we're evaluating multiple doses of the drug, not just a single dose. So ULAR is really right around the corner; it's barely a month away. So you'll see an early presentation of the data, and then a much bigger kind of showcase of it will come at ACR later this year. Okay.

Please check the Carolinas on on you.

Sorry, I was on the thank you. Thanks for taking my question I had maybe.

Follow up question on your 15.

I can add on to five five.

And you really talked a little bit about what you guys are looking to see in the data set in the initial phase one data.

Curious that <unk> you know other I'll 15 entering the clinic.

Ah recently.

With different strategies.

Might also talk a little bit more in depth about how you guys design trial 15, and what kind is.

Differentiate are slightly look for in that early data that you that you guys are hoping to have that around here and thank you.

Jay Olson: And finally, do you think 358 could create a cytokine storm associated with COVID?

Oh I'm going to have two wars at all.

Jay Olson: So, that's a very interesting question. So, 358 definitely induces regulatory T-cells, and yeah, you're familiar with our data. It can induce a polyclonal regulatory T-cell response. So, it's a very interesting concept and nuance. One of the things that we do know about COVID and the cytokine storm is that those seem to be non-lymphoid-derived cytokines, right? They're typically the innate kind of cytokines like IL-6, you know, others linked to CRP, for example. So we typically do think that lymphoid cells can antagonize that. So it's a very interesting thought, a very interesting idea. But, you know, right now, our plans with 358 are much, very squarely focused on the autoimmune disease. Okay, great, thanks very much.

They are higher Linda.

So one of our goals that as as you know from our 255 program was that we really wanted to maintain all of the possible receptor lie again interaction that I'll 15 uses when it naturally signals as decided time you know like a naked cytokine into human body and we know that.

Has at least two well, but at least three different kinds of binding modes. So it can signal through the dime, Eric made a gamma receptor complex.

Wherever that complex than existed on a cell type, but then it can also signals through a try America preceptor complex, where there's an aisle 15 receptor alpha specific seven you know.

That them complexes with beta gamma and that <unk> signaling is different than the aisle too pathway because in this case the aisle 15 alpha receptor Sabina.

Jay Olson: Thank you. The next question comes from Arlinda Lee from Canaccord.

There'd be expressed on the same so they together we call that this seemingly.

Or it can be expressed on a neighboring sell where'd hand off to a beta gamma on a nearby so that so it is kind of like a self doubt contact mediated signalling and we call that trans presentation.

Jay Olson: Your line is open. Please check that your line is now on mute. Sorry, I was on mute.

Arlinda Lee: Thank you. Thanks for taking my question. I had, maybe, a follow-up question on your IL-15 agonist 255. You already talked a little bit about what you guys are looking to see in the data sets from the initial phase one data. I'm curious that with other IL-15s entering the clinic, with different strategies, whether you might also talk a little bit more in depth about how you guys designed your aisle, and what kind of differentiators might we look for in that early data set that you guys are hoping to have. Thanks, everyone. I'm going to have Jay Z answer that. Jay Z. Sure.

So those are all three modes of natural I'll 15 depend in biology, and the immune system uses all three so we wanted to make sure that the biology to 55 could recapitulate all of the biology, the native Ohio, 15 house available to it. So fundamentally this approach is very different than a lot of.

Competing pipelines because almost all of those design involve the aisles 15 cytokine generated as a drug product complex, but the extra cellular domain, a bio 15 receptor alpha.

And they're very a variation on that theme you know some use the entire receptor others just use a sushi domain as you know others using F.C. fusion to make it to arm cytokine bus receptor complex, but they all have that same sort of basic underlying design principles.

Jay Olson: Hi Erlinda. So, one of our goals, as you know from our 255 program, was that we really wanted to maintain all of the possible receptor-ligand interactions that IL-15 uses when it naturally signals as a cytokine, you know, like a naked cytokine in the human body. And we know that it has at least two, well, at least three different kinds of binding modes. Thus, it can signal through the dimeric beta-gamma receptor complex wherever that complex can exist on any cell type. But then it can also signal through a trimeric receptor complex where there's an IL-15 receptor alpha specific subunit that then complexes with beta-gamma. And that mode of signaling is different than the IL-2 pathway because, in this case, the IL-15 alpha receptor subunit can either be expressed on the same cell as beta-gamma, we call that cis-signaling, or it can be expressed on That cell is kind of like a cell-cell contact mediated signaling, and we call that trans-present. So those are all three modes of natural IL-15 dependent biology.

And there are some unique differentiating properties.

Presented recently at city last year, we presented some studies that evaluated head to head the assemblies that have the receptor and complex to decide occurring.

Comparison to either native vile 15 or or neck or two by by.

And we saw a lot of unique differences, we saw differences in receptor internalisation between the different designs versus the native or 255 weeks differences in grandes I'm be production intercellular early and in case cells and and even when you evaluating attack P.B.M.C. culture.

Even side differences in C.D. 14, monocytes that could express interest cellular inner as we can 18, and we saw those kinds of changes in grants I'd be induction really in either the native I'll 15, or the 255 molecule those kind of things, we're not really well supported or induced with the assembly is that.

The receptor and complex with decided crime.

So we think that's one difference there should be a very sort of significant modification of how the immune system can be targeted with the aisles 50 pathway using this kind of two by five design and we think that could translate into things like reduced happy Phalanxes repeated those thing and number of other.

Jay Olson: all three. And so we wanted to make sure that the biology of 255 could recapitulate all of the biology that the native IL-15 has available. So fundamentally, this approach is very different from

The other kinds of potential improvements.

And carried thanks.

Jay Olson: because almost all of those designs involve the IL-15 cytokine generated as a drug product in complex with the extracellular domain of IL-15 receptor alpha. And there are variations on that theme. For example, some use the entire receptor, others just use the sushi domain, and, as you know, others use an FC fusion to make a two-armed cytokine plus receptor complex.

Well My next question comes from.

Eight in half an hour found benchmark airline is open.

Hi, Thanks for taking my question sound appreciate it would be saving measures to provide across the site.

I've got a couple of questions on done folk melanoma study and growing pull up about the gardens. So on melanoma wanted to confirm the status of pasted in almost a study how many patients has been role so far.

Jay Olson: They all have that.

Jay Olson: and...

Jay Olson: And there are some unique differentiating properties. We recently presented at CITSE last year some studies that evaluated head-to-head the assemblies that have the receptor and complex to the cytokine in comparison to either native IL-15 or Nektar 255, and we saw a lot of unique differences.

And given that it looks like the <unk> is expected to be in the first quarter Pleasant 21.

Well, they would would be able to see the completely <unk> earlier than that let's say maybe early the and the end of this year or maybe in the beginning of the very beginning the next year.

Jay Olson: We saw differences in receptor internalization between the different designs versus the native or 255. Additionally, we saw differences in Gramzyme B production intracellularly in NK cells. And even when we evaluated an intact PBMC culture, we even saw differences in CD14 monocytes that could express intracellular interleukin-18. And we saw those kinds of changes in Gramzyme B induction, really in either the native IL-15 or the 2-5-5 molecule; those kinds of things were not really well supported or induced with the assemblies that had both the receptor and complex with cytokines. So we think that's one difference. There should be a sort of significant modification of how the immune system can be targeted with the IL-15 pathway using this kind of 2-5-5 design. And we think that could translate into things like reduced tachyphylaxis, repeated dosing, and a number of other kinds of potential benefits.

They said in a way I'm going to ask you to.

Address that question.

Sure.

Question, So just a a crack on the <unk>, it's not the P.S. will be you know next year, it's <unk> in bed on T.V. eat their response rate based standpoint that per standpoint, what public her potentially in Q1 next year, so and all kinds.

This has been dead on based on that study design. The current studied design initial projection has been but the P.S. has could potentially come in <unk> <unk> <unk> <unk> now, let's be discussed before I got currently where in discussion with health toward he's.

Central change in the first endpoint wish from or to see our and then in addition, with with the Pat change and then on the current ongoing building up the study.

On P. they took place in the C.R. weed out and the whole in the past beat out if World War, two upset that change could be different than to six to seven months. So some of that release, because that's really a event driven you beat out so I want to be clear about deep.

Aiden Hopenov: Thank you. And our next question comes from Aiden Hopenov from Benchmark. Your line is open.

Wei: Thank you for taking my questions, and I appreciate all the safety measures you provide across the site. I've got a couple of questions on the Benfect melanoma study and one follow-up about the guidance. So, on melanoma, I wanted to confirm the status of the phase 3 melanoma study, how many patients have been enrolled so far, and given that it looks like the PFS is expected to be in the first quarter of 2021, whether we would be able to see the complete response numbers earlier than that, let's say maybe early at the end of this year or maybe in the beginning, at the very beginning of the next year. Thanks, Aiden. Wei, I'm going to ask you to address that question.

Newspaper by get Hi to date and regarding your first question. How many pasting team goes that is actually a study conduct in the ongoing study we could do not provide those numbers once studies completing boat and that he competed <unk> information <unk>.

<unk>.

Okay <unk>, just just want a concurrent so we're going to see see our number to get out of it or a number in the beginning of cousin plenty lot right.

That's our current guide Yep.

Okay Krisher that [noise].

Another question on financial guidance. So I was just curious to understand the given that certain studies would be postponed to push the the late all the or on or something maybe even the push for the next year trying to understand the cash for and.

Wei: Sure. Thanks for the question. So, just to correct, the guidance is not that PFS will be beginning next year. It's – our guidance has been that the response rate-based endpoint, that first endpoint, would probably occur in Q1 next year. So – and our guidance has been that based on the study design, the current study design, the initial projection has been that the PFS could potentially come in 6 to 7 months after the OR endpoint. Now, as we discussed before, we are currently in discussion with health authorities about the potential change in the first endpoint, which is from OR to CRR. And then, in addition to that change and then the current ongoing enrollment of the study, the difference in the CRR readout and the PFS readout, if we were to affect that change, could be different than the six to seven months. So some of that release because PFS is really an event-driven readout. So I want to be clear about the guidance we have provided to date. And regarding your first question, how many patients are being enrolled, that is really a study design.

Why would kind of stays the same as previously guided given that there might be a less expenses associated with a research and development.

Overhead expenses.

Yeah right.

Yeah.

Yeah <unk> yeah.

Thanks for the question Yeah, as we talked about in the call and Howard reviewed you know many of the studies that were running in the ones in particular that we have in house you know remain on track. So that obviously would have no effect on or expense guidance and some of the other potential changes are more minor in nature.

So we don't as we sit here today I think that's gonna how the impact on our on our R. and D. expenses, you know some of them or activity based some of them or not.

So we're we're comfortable with the current guidance aren't making any changes at this time.

Okay. Thank you appreciate it.

Thank you.

Next question comes from Jane Olson from Oppenheimer Airlines open.

Oh, I think for taking the questions I had one on R.C.C., where it seems like the goals line keeps moving with all the combinations and now the check made 90 our study results.

Wei: in an ongoing study.

Wei: We typically do not provide those numbers. Once the study is completely enrolled, then the completion enrollment information will be provided. Thank you.

Look pretty solid her nivo plus condo. So I was wondering if those steady results change your views the opportunity for then take plus Nivo in R.C.C. and then I had to follow up on 358, if they could.

Aiden Hopenov: Okay. Appreciate that. Just want to confirm. So we're going to see the CR number together with the ORR number at the beginning of 2021, right?

That's great. Thank you way I'm Gonna ask you to address the R.C.C. question. Okay. Thanks.

Wei: That's our current guidance, yeah.

Aiden Hopenov: Okay, I appreciate that. And another question on financial guidance. So I was just curious to understand that given that certain studies would be postponed or pushed to the end of the year or some maybe even pushed for the next year, trying to understand the cash burn, why it kind of stays the same as previously guided given that there might be less expenses associated with research and development and overhead expenses. Yeah, great, and thank you so much.

Sure Yeah. So I think definitely it's ours, you see that say pension you ball and so so so right now you have a evil plus hippie combination I know so checkpoint plus on T.K.I., both involving Pembro us and.

About 19 now most recently with me unable so it's the way we think about it is truly.

Two things one is the combination of bands have close unable not desktop or another treat an option now D.T.K. I can be used in mostly settings. It can be used on in combination with a checkpoint in the first time studying or can be used later or some monotherapies treatment. So I think are so different.

Gil: Yeah, thanks for the question. Yeah, as we talked about on the call and Howard reviewed, many of the studies that we're running and the ones in particular that we have in-house remain on track. So that obviously would have no effect on our expense guidance. And some of the other potential changes are more minor in nature. So we don't, as we sit here today, I think that's gonna have an impact on our R&D expenses. Some of them are activity-based; some of them are not. So we're comfortable with the current guidance and aren't making any changes.

If you if you talk into print on positions around the world people are really taking advantage of these options and using them differently. There's still some position who would prefer to use the I.O. combo in first sign setting and other like to use 80, ACAC humble and and then use to set that option up a T.K.I. Uh huh.

The purse find setting I think huh our goal here is to introduce another exceeding option now we expect to have a different safety profile, Dan is opera <unk> combination.

Gil: Okay, thank you. I appreciate it. Thank you. Our next question comes from Jay Olson from Oppenheimer. Your line is open.

Then also depends on the F.C. were able to deliver I think that desktop or a different treatment option and also give that.

Doctors eight inopportune kick me surf a T.T.I. lots of later on therapy, rather exhausting. The first line. So that's one and second of all it's a as being just close previously P.M.S. is undertaking they face one study with a couple of combination <unk> plus people and then T.K.I. So.

Jay Olson: Hi, thanks for taking the questions. I had one on RCC, where it seems like the goal line keeps moving with all the combinations, and now the Checkmate 9 ER study results look pretty solid for Nevo plus Cabo. So I was wondering if those study results change your view of the opportunity for Ben Pegg plus Nevo in RCC? And then I had a follow-up on 358 if I could. That's great, Jay. Thank you. Wei, I'm going to ask you to address the RCC question in landscape.

And and that that's tiniest expected some start.

And so that's up a combination <unk> progressive sound too recent study can offer additional treatment options that me involved eight Ben Ben tag within that line of therapy.

Wei: Sure, yeah, so I think definitely the RCC landscape continues to evolve, and so right now, you have a NEBO plus IP combination and also Check Point plus PKI, both involving Pembroke and a value mapping now, most recently with Neo-NEBO. So the way we think about it is really two things.

Oh, great teams, it's super help listening to it <unk>, hence is.

Virginia, and then I guess just on three fight age it seems like there's been a few new drug approvals for lupus over the past 50 years, I I need them needs to might be one of the only ones, but and now there's a few promising treatment options and development, including including a astrazenecas and I always.

Wei: One is the combination of BenPak plus Nivolumab does offer another treatment option. Now, the TKI can be used in multiple settings. It can be used in combination with a checkpoint in the first-round setting, or it can be used later as a monotherapy treatment. So I think it's so different if you talk to different physicians around the world; people are really taking advantage of these options and using them differently. There are still some physicians who prefer to use the IO-IO combo in the first-line setting, and others like to use a TKI combo and then use that option of a TKI in the first-line setting. I think our goal here is to introduce another treatment option. Now, we expect to have a different safety profile than is offered by a checkpoint plus a TKI combination, and that also depends on the efficacy we're able to deliver.

<unk> I was wondering how you see the lupus landscape evolving.

And how the 358 mechanism compares to.

And their food in that in big five nine.

That's crazy Yeah, Hey.

Yeah, I think that happy to answer that yeah, you you definitely diagnosing characterize the problem of very very well so outside of Benlysta right, which you know can you know several years ago. They really haven't been any approvals and frankly I'm there hasn't really been even any kind of really.

Exciting trial results until Anifrolumab, you know and they've gone came along and and you know the thing that we saw some pretty exciting dated phase two and then we saw phase three data phase three data for anything, but a little bit more confusing right. As you know and also what we see in that case is but.

Wei: I think it does offer a different treatment option and also gives doctors an opportunity to reserve a TKI as a later-line therapy rather than exhausting the first line. So that's one. And second of all, as has been disclosed previously, BMS is undertaking a phase one study with a triple combination of BenPak plus Nivolumab and then TKI. And that study is expected to start soon. And so that type of combination, once it progresses on to a retribution study, can offer additional treatment options that involve a BAM-BAM PEG within that line of therapy.

Tends to the yet again, changing and some of the endpoints and loop of studies.

That the first time, you know was then list as approval and potentially going to see it again in the case of any.

One of the things, though that's an important take away is if you look at the landscape of mechanisms that have been tested or treatment targeting they're all highly overlapping right. They're targeting the same kind a pathway focused on the same kinds of specific subset of immunology and and we keep telling a lot of.

Studies, but very very similar kind of mechanisms.

Wei: Oh, great. Thank you. It's super helpful.

And one of the thing is it's really exciting about considering t. rags as a treatment option and lupus is that Lucas patients are known to have a very specific dysfunction in there to wreck compartment.

Wei: Thanks for that comprehensive review, and then I guess just on 358. It seems like there's been a few new drug approvals for lupus over the past 50 years. I think Ben-Lista might be one of the only ones. And now there are a few promising treatment options in development, including AstraZeneca's and Biogen's new molecules. And I was wondering how you see the lupus landscape evolving and how the 358 mechanism compares to Anirfolumab and BIP59. That was great, Jay Z. I appreciate that.

We know that lupus patients have progression to moderate to severe disease. They have low level file to even in response to normal stimuli that would induce inner look into expression.

So have reduced levels regulatory t.. So they have been kind of bad imbalance between T. age 17, and T. rags cells, where you see an over preponderance of T. 17, and a drop in T. read numbers and they're also reports as he would reduce oppressive capacity of T. Rex and station.

Daina Michelle Graybosch: Yeah, thanks. Yeah, happy to answer that.

Of all of the things that make up lupus and it isn't heterogeneous disease, we have to accept that.

Daina Michelle Graybosch: So, yeah, you definitely diagnosed and characterized the problem very, very well. So, outside of Ben Lista, right, which came, you know, several years ago, there really haven't been any approvals. And, frankly, there haven't really ever been any kind of really exciting trial results until Annie Frohman. The thing that we saw was some pretty exciting data in Phase 2, and then we saw Phase 3 data. Phase 3 data, Franny, was a little bit more confusing, right, as you know. And also, what we see in that case is potentially, yet again, changing some of the end points in lupus studies. We saw that the first time with Ben List's approval and potentially are going to see it again in the case of Annie. One of the things, though, that's an important takeaway is if you look at the landscape of mechanisms that have been tested for treatment targeting.

Rags or a very unique.

Kind of biological feature.

Seems to be associated with you know the dysfunction in the patients that presented with this disease.

And we've now I've seen multiple clinical studies, where lodos style too has been applied for treatment of lupus.

And we've seen both T. rag elevations by Moto style to the to multiple studies forgot belongs in telling everyone was Germany.

Also seeing nothing could see you know they came out of those trials. So this is kind of the application of a person class kind of a mechanism for the treatment of loop and so I think that represents one kind of exciting opportunity.

Other exciting opportunity for US is that of course, we've already shown that extra 358 can induce tea bags, both in their number and their duration of expansion and even in their suppressive functional enhancement in a way that I'll too just can't you can't use any kind of lotus out to regimen to produce the mass qual.

Daina Michelle Graybosch: highly overlapping, right? They're targeting the same kind of pathways, they're focused on the same kinds of specific subset of immunology, and we keep doing a lot of studies with very, very similar mechanisms. So one of the things that's really exciting about considering Tregs as a treatment option in lupus is that lupus patients are known to have a very specific dysfunction in their Treg compartment.

<unk>.

The huge amounts of T. rag induction they were able to produce for 358. So we think all of those things together represents a very reasonable and strong scientific rationale to advance into lupus and that's why this will be the first to study that we're going to be initiating with Lily and is Howard said it.

Daina Michelle Graybosch: So we know that lupus patients have progression to moderate to severe disease.

Not going to be blah, and see additional base two studies and other indications lupus and contractually. The two companies we've agreed to run up to four days to study. So we'll be looking for the full expansion of that.

Daina Michelle Graybosch: They have low levels of IL-2, even in response to normal stimuli that would induce interleukin 2 expression. They also have reduced levels of regulatory T cells. They have kind of that imbalance between Th17 and Treg cells, where you see an over preponderance of Th17 and a drop in Treg numbers. And there are also reports of even reduced suppressive capacity and Lucas Patience.

You know this year and internet.

Let's Super helpful. Thank you very much taken the questions.

Thank you.

And we'll take our next question from Paul Choice from Goldman Thatcher line is open.

Daina Michelle Graybosch: So.

Daina Michelle Graybosch: Of all of the things that make up lupus, and...

Hi, this is <unk>.

Daina Michelle Graybosch: heterogeneous disease. We have to accept that, and Tregs are a very specific kind of biological feature that seems to be associated with, you know, the dysfunction in the patients that present with this disease. And we've now seen multiple clinical studies where low-dose IL-2 has been applied for treatment, and we've seen Treg elevations by low docile to these two multiple studies. For example, one was in China, and one was in Germany. And we've also seen some efficacy, you know, that came out of those trials. So this is kind of the application of a first-in-class kind of mechanism for the treatment of lupin. So I think that represents only one.

If you to talk.

About what your ability is good bands like there are three five a. outside.

Early that even if you explore any potential indications, where you could there's still either in different partnerships right around.

Basically I'm going to let you answer that.

Yeah. So so what that you're 358, you know we signed.

Basically like a licensing kind of a collaboration with Eli Lily. So so we work with them exclusively on extra 358 as I mentioned the scope of the three five a. programs pretty large right you could think of outlining the t. rag mechanism to a range of auto immune diseases and that's what we're doing together.

But it's really a program to leave exclusively partnered with Lily and all of its development is in direct collaboration Eli Lily.

I think yeah, and then I think he said that eat it still had 10 to 20 patients in to propel up there, but that's then punched a couple months.

Daina Michelle Graybosch: You know, you can't use any kind of low docile two regimen to produce the mass quantity, you know, the huge amount of Treg induction that we're able to produce with 358. So we think all of those things together represent a very reasonable and strong scientific rationale to advance into lupus. And that's why this will be the first phase two study that we're gonna be initiating with Lilly. And as Howard said, it's not gonna be the last. You'll see additional phase two studies and other indications after lupus. And contractually, the two companies, we've agreed to run up to four phase two studies. So we'll be looking for the full expansion of that this year and into next.

In addition to the delay should we expect any impact on patient enrollment it wouldn't cause we in fact, maybe the lower end of the range due to kill that or anything like that.

Way I'll, let you answer that.

Sure Yeah. So the <unk>. The study is revolting globally. That's her plan in U.S.U.N., Australia <unk>.

Based on T. size, we selected we expect a majority of Haitian will come from Europe.

Inside activation getting to the effect of pandemic in Europe.

<unk> looking at the sites in Europe, there's a high degree of variability a cheap therapy.

Daina Michelle Graybosch: That's super helpful. Thank you very much for taking the questions. Thank you. And we'll take our next question from Paul Choi of Goldman Sachs. Your line is open. Hi, this is Corinne Jenkins. I'm with Paul. I was wondering if you could talk a little bit about your ability to advance Nektar 358 outside of some of these Lilly studies and if you've explored potential indications that you could pursue either in different partnerships or on your own.

We have two which depend dynamically affected from country calm country.

Difference between what has happened in Italy, and Spain versus what's happened in Germany.

So we're taking a very measured approach trying to understand at this site level. In addition to their country level look at the impact and trying to be bear optimist opportunistic and how we open up sites and go patients. So it's been mentioned earlier in the call what's outlets important too.

Officially to make sure that the right patients get put on the study and not compromise on Alex eight because of the ongoing pandemic and in addition, we would only activated site enrolled patients.

Daina Michelle Graybosch: Yeah, so with Nektar 3...

Daina Michelle Graybosch: Yeah.

Daina Michelle Graybosch: signed basically like a licensing kind of collaboration with Eli Lilly. So we work with them exclusively on Nektar 358. As I mentioned, the scope of the 358 program is pretty large, right? You could think of applying the TRAG mechanism to a range of autoimmune diseases, and that's what we're doing together. But it's really a program that we've exclusively partnered with Lilly, and all of its development is in direct collaboration with Eli Lilly.

At his side if that site has demonstrated and.

A a full capacity to follow through with a protocol to really care for patients and to execute Oh, the treatment as well as the humor assessments.

So it's under those circumstances that we plan to contain shouldn't go into the study. So I think since we're really only a couple of month into the pandemic exactly projecting out. The next next month intact it'd be really difficult at the at this time.

Daina Michelle Graybosch: Okay, thank you. And then I think you said that you did still have 10 to 20 patients in the Propel update, but that's been pushed back a couple months. In addition to the delay, should we expect any impact on patient enrollment? Could we expect maybe the lower end of the range due to COVID or anything like that? Wei, I'll let you answer that.

But our team, which would be working hard to fulfill those criteria and making sure that this study does advance as we had when he hoped.

Yeah. Thank you.

Wei: Sure, yeah, so the study is rolling globally, that's our plan, in the US, EU, and Australia. Based on the sites we selected, we expect the majority of patients will come from Europe. There's a delay in site activation due to the effective pandemic in Europe, but we're actively looking at sites in Europe. There's a high degree of variability, as you observed, the degree to which the pandemic really affected different countries. There's a big difference between what has happened in Italy and Spain versus what has happened in, say, Germany.

Thank you and we'll take our last question from <unk> from S.V., mainly rank your line is open.

Great. Thank you credit questions I had to get them, both and you can answered on one of the order. The first one <unk> or B.M.S. Just studied that that you guys are planning and <unk> lung cancer.

There's any way that might be a small randomized study as we have seen more companies cake with I.L.I.O. combination.

And when you might make that decision and the second as I'm 358, you know there's other companies with their own I'll tune their t. run interrupted therapies and they're going after different indication.

Wei: And so we're taking a very measured approach, trying to understand at the site level, in addition at the country level, what the impact could be, and trying to be very opportunistic in how we open up sites and enroll patients. So, as mentioned earlier in the call, what's utmost important to us is really to make sure that the right patients get put on the study and not compromise on eligibility because of the ongoing pandemic. And in addition, we would only activate a site, enroll patients at a site, if that site has demonstrated the full capacity to follow through with the protocol, to really care for the patients, and to execute all the treatments as well as the tumor assessment. So, it's under those circumstances that we plan to really continue to enroll people into the study. So, I think since we're really only a couple of months into the pandemic, exactly projecting out for the next six-month impact would be really difficult at this time. But our team is really working hard to fulfill those criteria and make sure that this study does advance as we had really hoped.

You can talk to how you in a really are prioritizing your indications beyond lupus I'm, not and well they I guess you'd probably not going to say you can go they got interrupted but just what criteria you're using to make that next decision. Thank you.

So I'd like to start with <unk> 358 question, and then move on to way to address.

Question that then how about round randomized controlled trials. Thanks.

Sure.

A nice big view, so with 358, you know as you know so the T. Rex can be applied to a range of different diseases and so when we consider the different indication of the Lily and vector would be working on we looked at a number of factors we looked at of course the strategic.

Actors that that the areas that Lily is heavily engaged in in prioritizing and we also looked very scientifically almost from a bottom up approach, where we looked at where the kinds of underlying disease pathology is most heavily driven by a dysfunctional t. cell compartment.

Where the nature of that T. cell compartment is antigen, driven where we'd or habit, we have a kind of understanding of at least some of the key antigenic drivers and then where we think weekend of course generate antigens specific tea bags that can antagonize a reactive immune cells that are.

Wei: And we'll take our last question from Daina Graybosch from SVB Lyrinc. Your line is open. Great. Thank you for the questions. I have two.

Daina Michelle Graybosch: I'll give you both, and you can answer them in whatever order. The first is PROPEL or BMS's study that you guys are planning in first line non-small cell lung cancer. I'm wondering if there's any way that might be a small randomized study as we have seen more companies do with IO-IO combinations and when you might make the decision. And the second is on 358.

Responding to that same management.

So we have ways of kind of classifying auto immune diseases from ones that having different types of information depending on the Oregon versus involved the underlying immunity in that Oregon and that can go all the way from diseases that are highly inflammatory and drive they diseases like you know.

Crowns for example, yeah, very very highly t. cell driven the phone Tory disease, probably very little auto immune or humor will respond and then it can ranging spectrum and all the way to diseases that are completely auto immune. So for example, the disease like <unk> were completely driven by an auto.

Daina Michelle Graybosch: There are other companies with their own IL-2s or TREB-directed therapies, and they're going after different indications. And I wonder if you can talk through how you and Lily are prioritizing your indications beyond lupus. I guess you're probably not going to say if you could go to gut-directed decisions but just what criteria you're using to make that next decision. Thank you. So I'd like to start with Daisy answering Question 358 and then move on to Wei to address the question that Dan had about randomized controlled trials.

Antibody. So you can imagine that a t. rag and those two different kinds of diseases. The two different things on the first type you would really be antagonizing t. cells that are trafficking to the guts as you pointed it out or blocking their inflammatory response to the types of antigen that they're reacting to but.

Daina Michelle Graybosch: Sure. Hey Daina, nice to speak with you.

The latter case that autoimmune disease, you ever expect to antagonize people. The color help herself cells that are controlling B.S.L.T. cell reactions, and priming and dropping down any kind of model and the body you know kind of the production. So we can prioritize diseases based on their underlying immunology.

Daina Michelle Graybosch: So, with 358. You know, as you know, the Tregs can be applied to a range of different diseases. And so when we considered the different indications that Lilly and Nektar would be working on, we looked at a number of factors. We looked at, of course, the strategic factors that fit the areas that Lilly is heavily engaged in and prioritizing. And we also looked very scientifically, almost from a bottom-up approach, where we looked at where the kinds of underlying disease pathology are most heavily driven by a dysfunctional T-cell compartment, where the nature of that T-cell compartment is antigen-driven, where we have a kind of understanding of at least some of the key And then, we think we can, of course, generate antigen-specific Tregs that can antagonize the autoreactive immune cells that are responding to that same antigen.

Daina Michelle Graybosch: So...

Look at where 358 and the cell populations that induces could make biggest impact and then use that to select for indications for assessment now with Lily you know, we we don't have now those indications ahead of time, so we would be announcing them as we got much closer to the start of those.

<unk> so stay tuned as we get to later this year as we know the additional indication that will be working on together.

Hey, thanks.

Right.

Oh, yeah. Thanks, let that has concluded the question and answer session starts at a time from I like to turn the topic like a little heiligbrodt him for closing remarks.

Daina Michelle Graybosch: We have ways of kind of classifying autoimmune diseases for ones that have different types of inflammation, depending on the organ that's involved, the underlying immunity in that organ. And that can go all the way from diseases that are highly inflammatory and drive, say, diseases like Crohn's, for example, very, very highly T cell driven inflammatory disease, probably with very little autoimmune or humoral response. And then it can range in the spectrum all the way to diseases that are completely autoimmune.

Okay well. Thank you thanks, everyone for joining us today and I also made me want to think our employees for the incredible amount of hard work and commitment to the company and particularly during this time, we're environment is changing so rapidly and we've had to adopt or work practices behave in a different way exceptionally <unk>.

Daina Michelle Graybosch: [inaudible]

Out of her employees have risen to overcome our daily challenges keep our business on track and make tremendous progress so I have to pick them off.

We both very valuable pipeline, and then you know ontology and immunology <unk> meeting addressing areas of high on medical need and we're focused on moving these programs forward and shareholders. We want to thank you for your support and we will continue to provide updates on our progress and we also want to wish.

Daina Michelle Graybosch: So, for example, a disease like pemphigus or myasthenia where it's completely driven by an autoantibody. So, you can imagine that a TRAG and those two different kinds of diseases would do two different things. On the first type, you would really be antagonizing T cells that are traveling to the gut, as you pointed out, or blocking their inflammatory response to those types of antigens that they're reacting to. But in the latter case of that autoimmune disease, you would expect to antagonize T-follicular helper cells, cells that are controlling B-cell and T-cell reactions and priming and dropping down any kind of autoantibody So we can prioritize, based on their underlying immunology, look at where 358 and the cell populations that it induces could make the biggest impact, and then use that to select indications for assessment.

All of you and your families are sick can't help during this time. So thank you for joining us.

Well, ladies and gentlemen, thank you for our kids hating in today's conference. It's technically with the programming email disconnect everyone has a wonderful thing.

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Daina Michelle Graybosch: Now.

Daina Michelle Graybosch: With Lilly, you know, we don't announce those indications ahead of time, so we would be announcing them as we get much closer to the start of those studies. So stay tuned as we get closer to later this year as we announce the additional indications that we'll be working on.

Daina Michelle Graybosch: Great. Thanks, Davey. Thank you. And that does conclude the question and answer session for today's conference. I'd now like to turn the conference back over to Howard Robin for closing remarks.

Howard W. Robin: Okay, well, thank you. Thanks, everyone, for joining us today. And I also mainly want to thank our employees for the incredible amount of hard work and commitment to the company, and particularly during this time when our environment is changing so rapidly, and we've had to adapt our work practice and behave in a different way. I'm exceptionally proud of how our employees have risen to overcome our daily challenges, keep our business on track, and make tremendous progress. So I have to thank them all. You know, we built a very valuable pipeline in immuno-oncology and immunology, meeting and addressing areas of high unmet medical need, and we're focused on moving these programs forward. and we will continue to provide updates on our progress. We also want to wish all of you and your families safety and health during this time. So, thank you for joining us.

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.

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