Q4 2021 Nektar Therapeutics Earnings Call

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Please standby here conflicts call will begin momentarily once again please remain on the line you conference call will begin momentarily.

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Operator: Please stand by. Your conference call will begin momentarily. Once again, please remain on the line. Your conference call will begin momentarily. [music] Good day, and thank you for standing by. Welcome to the Nektar Therapeutics fourth quarter 2021 financial results conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press the star and then one on your telephone. Please be advised that today's conference may be recorded. If you require any further assistance, please press the star and then zero.

Good day, and thank you for standing by.

So the Nektar Therapeutics fourth quarter 2021 financial results conference call.

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

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

Ask the question during the session you will need to press Star and then one on your telephone.

Please be advised that today's conference maybe recorded if you require any further assistance. Please press star and then zero.

Jennifer Ruddock: I would now like to hand the conference over to your speaker today, Jennifer Ruddock, head of corporate affairs. Please go ahead. Thank you, Crystal, and good afternoon, everyone. Thank you for joining us today. With us on the call are Howard Robin, our President and CEO, Gil LaBrushery, our COO and CFO, Dr. Jonathan Zalevsky, our Chief of Research and Development, and Dr. Dimitri Nelton, our Chief Medical Officer. On today's call, we expect to make forward-looking statements regarding our business, including clinical trial enrollments and clinical trial results, timing and plans for future clinical trials, timing and plans for future clinical data presentations, They are subject to inherent uncertainties and risks that are difficult to predict, and many of which are outside of our control.

Now like to hand, the conference over to your Speaker today, Jennifer Ruddock head of corporate Affairs. Please go ahead.

Jennifer Ruddock: Our actual results may differ materially from these statements. Important risks and uncertainties are set forth in the Form 10-Q that we filed on November 5, 2021, which is available at sec.gov. We undertake no obligation to update any of these forward-looking statements, whether as a result of new information, future developments, or otherwise. A webcast of this call will be available on the Investor Relations page of Nektar's website, www.nektar.com. Before turning the call over to Howard, I'd like to remind you that since we're calling in from different locations, I will moderate the Q&A session for our team so we can avoid technical issues during the session. We appreciate your patience during this time. With that said, I would like to hand the call over to our president and CEO, Howard Robin. Howard?

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

With us on the call are Howard Robin, our President and CEO Gil of Bruce Uri, Our C O O and CFO Dr.

Dr. Jonathan <unk>, our chief of research and development.

Doctor Dimitri Mountain, our Chief Medical Officer.

On today's call, we expect to make forward looking statements regarding our business, including clinical trial enrollment and clinical trial results timing and plans for future clinical trials timing and plans for future clinical data presentations at the <unk>.

Therapeutic potential of our drug candidates.

Outcomes and plans for health authority regulatory actions and decisions.

Guidance and certain other statements regarding the future of our business.

Because these forward looking statements relate to the future. They are subject to inherent uncertainties and risks that are difficult to predict and many of which are outside of our control. Our actual results may differ materially from these statements important risks and uncertainties are set forth in our Form 10-Q that we filed in November 5th 2021 which is available at SEC Gov.

We undertake no obligation to update any of these forward looking statements whether as a result of new information future developments or otherwise a webcast of this call will be available on the Investor Relations page of <unk> website at <unk> Dot com.

Before turning the call over to Howard I'd like to remind you that since we're calling in from different locations I will moderate the Q&A session for our teams. So we can avoid technical issues. During this session. We appreciate your patience. During this time with that said I would like to hand, the call over to our president and CEO Howard Robin Howard.

Howard Robin: Thanks, Jennifer. Thank you all for joining us today. 2021 was highlighted by advancement and execution across many areas of our business, and we continue to establish Nektar's leadership in the development of cytokine therapeutics for the treatment of cancer and autoimmune disease. And we are excitedly awaiting three late-stage registrational study readouts in the first half of this year from our BEM Tech program, which are successful. These studies will put us on a path to regulatory approvals and global commercialization in multiple large frontline cancer settings in melanoma, renal cell carcinoma, and bladder. Our organization is preparing for potential regulatory filings and the commercialization of this product, and moreover, with a breakthrough designation.

Thanks, Jennifer and thank you all for joining us today.

2021 highlighted by advancements in execution across many areas of our business and we continue to establish connectors leadership position in the development of cytokine therapeutics for the treatment of cancer and autoimmune disease.

And we are excitingly awaiting three late stage Registrational study readouts in the first half of this year from our <unk> program.

If successful these studies will put us on a path to regulatory approvals and global commercialization and multiple large frontline cancer settings, and melanoma renal cell carcinoma.

Our organization is preparing for potential regulatory filings and the commercialization of ethics, and Moreover, with a breakthrough designation in first line melanoma, we believe that positive phase III data for <unk>.

Howard Robin: First-Line Melanoma, we believe that positive Phase III data will enable us to expedite the U.S. regulatory filing for BEMFEG in this setting, and this means we could potentially make Ben Pegg available to cancer patients beginning in the latter part of this year or early 2023. Beyond these three studies, reading out the first half, [inaudible] We have several additional registrational studies underway with nivolumab in the adjuvant setting of melanoma and in the periadjuvant setting of bladder cancer, and with pembrolizumab in first-line adnexation.

To expedite the U S regulatory filing for <unk> in this setting and this means we could potentially make that available to cancer patients beginning in the latter part of this year or early 2023.

Beyond the three studies reading out in the first half of this year, we have several additional registrational studies underway with Ebola bad in the adjuvant setting in melanoma and the peri adjuvant setting of bladder cancer and with embolism, App and first line head and neck cancer.

Howard Robin: A broad global registrational program for BEMPEG has been designed to capture the most significant cancer types where we believe BEMPEG, in combination with a checkpoint inhibitor, has the potential to demonstrate significant clinical benefit for a large number of patients. Current sales of checkpoint inhibitors and these settings are in excess of $6 billion, and we believe we have positioned BEMPEG as a first in class IL-2 therapeutic with the development strategy to establish BEMPEG and first line settings targeting large BEMPEG is a first in class IL-2 therapeutic. PEMPEG is the only IL-2 agent in development that possesses three key differentiated attributes in one therapeutic candidate. So first, FPEG is designed to allow preferential signaling to the beta gamma portion of the IL-2 pathway with some retained transient binding to the alpha receptor, which is necessary for T-cell priming.

Our broad global Registrational program for <unk> was designed to capture the most significant cancer types. We believe that taken in combination with a checkpoint inhibitor has the potential to demonstrate significant clinical benefit for a large number of patients.

Current sales of checkpoint inhibitors in these settings are in excess of $6 billion and we believe we are positioned.

As a first in class <unk> therapeutic with a development strategy to establishment take first line settings targeting large number of patients.

<unk> is the only IL two agents in development that possesses three key differentiating attributes and one therapeutic candidate.

So first I think is designed to allow preferential signaling to the beta gamma portion of the IL two pathway with some retained transient binding to the alpha receptor, which is necessary for T cell priming in the lymph nodes.

Howard Robin: Second, we leveraged full-limb IL-2 to avoid. Treatment Challenges that could arise in the new team structures. [inaudible] and third, Betheg as a ProDrug design which allows us to maintain sustained pathway signaling and mitigate the toxicities associated with high dose IL-2 and achieve an antibody-like dosing schedule that could be combined easily with a checkpoint inhibitor resonance. These attributes and our first line registrational clinical program are important competitive advantages and make the development path and these indications very difficult for all other IL-2 programs being pursued by others, that are in much earlier stages of research and development, as the leader in cytokine therapeutic development on next program, Nektar 255, target the IL-15 pet, enabling us to stimulate the immune system with natural killer cell proliferation, which we believe has broad therapeutic potential, not just in solid, but also in lipid tumors, and Jay-Z will share our progress with that program later in the call, in the area of auto-muted.

Second we leveraged who live out soon to avoid treatment challenges that could arise when you change structures.

And third.

The prodrug design, which allows us to maintain sustained pathway signaling and mitigate the toxicities associated with high dose IL, two and achieve an antibody like dosing schedule.

That could be combined easily with a checkpoint inhibitor regimen.

These attributes and our personal line Registrational clinical program.

<unk> competitive advantages and make the development path. These indications very difficult for all other IL two programs being pursued by others.

We're in much earlier stages of research and development.

As the leader in cytokine therapeutic development. Our next program, an extra $2 55 targets. The IL 15 pathway, enabling us to stimulate the immune system with natural killer cell proliferation, which we believe has broad therapeutic potential not just in solid tumors, but also in liquid tumors and Jay Z.

He will share our progress with that program later in the call.

In the area of autoimmune disease.

Howard Robin: [inaudible] Our next 358 program, Partner Eli Lilly, is also advancing very rapidly. We're pursuing significant settings for Nectar 358 in lupus, ulcerative colitis, and atopic dermatitis, where sales of current agents range from $12 to $15 billion. So this key program has very significant value.

At 358 program partnered with Eli Lilly is also advancing very rapidly we're pursuing significant settings protector $3 58 lupus.

Sort of colitis, atopic dermatitis, where sales of current agents range from $12 billion to $15 billion. So this key program has very significant value to an actor and our agreement with Lilly had significant double digit royalties in the mid teens and low twenties.

Howard Robin: And our agreement with Lilly has significant double-digit royalties in the mid- and Low-20s. And we have the option to co-promote, for Broad Manufacturing, the birth mechanism of Nektar 358 and its potential in a number of autoimmune and inflammatory conditions. We were truly excited about how large the operation was. Nektar 358 is designed to be a monotherapy biologic therapeutic that is administered subcutaneously to treat a range of autoimmune conditions. In December, we were pleased to see our partner Eli Lilly announce their annual investment, the first proof-of-concept data for Nektar 358 in the setting of a topic term of title.

And we have the option to co promote as well.

With the broad manufacturing the mechanism of <unk> to $3 58, and its potential in a number of autoimmune and inflammatory conditions. We're truly excited about how large the opportunity.

<unk> hundred 58 is designed to be a mono therapy biologic therapeutic that is administered subcutaneously to treat a range of autoimmune conditions. In December we were pleased to see our partner Eli Lilly announced that there.

Annual Investor meeting the first proof of concept data for <unk> 358 and <unk>.

Setting up the topic dermatitis.

Howard Robin: These data underscore the great promise that Nektar C and its potential resolution. Lilly now has three phase two studies announced for the development program for Nectar 358 in lupus, ulcerative colitis, and ectopic dermatitis, with a fourth phase two study planned as well. Nektar 358 is the clear leader in capitalizing on the novelty of regulatory cell biology with respect to both our scope and our stage of development. And again, Jay-Z will spend some time later in the call highlighting the tremendous progress, 2021 Pronected 358.

These data underscore the great promise that Lilly and Nektar seeing as potential resolution therapeutic.

Well, we now have three phase III studies announced with a development program for Nektar, Richard <unk> 58 in lupus ulcerative colitis, and atopic dermatitis with a fourth phase III study planned as well.

An extra 358 as the clear leader in capitalizing on the novel T regulatory cell biology with respect to both our scope and our stage of development and again, Jay Z will spend some time later in the call highlighting the tremendous progress we've made in 2021 predicted $3 58.

Howard Robin: Now, as this is front and center for many of you, I'll spend some time now on Dempeg, which is being developed in combination with checkpoint inhibitors, Evolumab and Pembrolizumab. As I mentioned earlier, three studies are in track for top-line data readouts in the first half of this year, beginning first with the phase three melanoma data, followed by renal cell carcinoma, and then bladder. Positive results from these studies would support a series of regulatory registrational filings for BEMPEG plus NEBO, followed by commercial launches for the doublet regimen beginning as early as late 2022 or early 2023. Nektar will lead all distribution, pricing, and market access activities for BEMPEC.

Now this is front of mind for many of you I'll spend some time peg, which is being developed in combination with checkpoint inhibitors. If all of them had been tremble Elizabeth.

As I mentioned earlier three studies are on track for top line data Readouts in the first half of this year.

Beginning first with the phase III melanoma data, followed by renal cell carcinoma, and bladder cancer data.

Positive results from these studies would support a series of regulatory Registrational filings for <unk>, plus nebo, followed by commercial launches for the doublet regimen beginning as early as late 2022 early 2023.

Howard Robin: Nektar and BMS will share in promotional activities. We look forward to working closely with BMS as we advance towards regulatory filings and launch. And, as a reminder, Nektar will book all revenue for BEMPEG and retain 65% of the profit.

Next year will be an old distribution pricing and market access activities for backpack, nektar and BMS will share and promotional activities.

Look forward to working closely with BMS as we advance towards regulatory filings and watch and as a reminder, nectar will book all revenue for bat bag and retaining 65% of the profit.

Howard Robin: We estimate the patent protection for the ben pay combination with an anti-PD1 antibody extends to at least February 2035. As I stated at the J.P. Morgan Conference in January, BMS and Nektar expect to have top-line results from the Phase III melanoma study before the end of April, and we expect shortly thereafter to have results from the two studies Nektar is running for renal cell carcinoma and bladder cancer. BMS and Nektar are not providing any additional detail on the timing of these top-line data.

We estimate the patients.

The patient excuse me the patent protection for the <unk> combination with an anti PD one antibody extends to at least February 2035.

As I stated at the Jpmorgan Conference in January BMS, and Nektar have guided to top line results from the phase III melanoma study before the end of April and we expect shortly thereafter to have the results from the two studies nectar is running a renal cell carcinoma and bladder cancer.

BMS and Nektar are not providing any additional detail on the timing of these top line data.

Howard Robin: As in most late-stage studies conducted in partnership, our companies plan to make a joint announcement. As a reminder, and as we've previously stated, we expect to report top-line results for the first two co-primary endpoints of ORR, and positive PFS results from the melanoma study. We plan to submit regulatory approval filings virtually simultaneously in both the US and Europe. The potential European approval and country launches would, of course, follow potential U.S. approval and launch as the process for European regulatory review and approval is typically long.

Is it mostly state studies conducted in partnership or companies plan to make a joint announcement.

A reminder, and as we've previously stated we expect to report top line results for the first two co primary endpoints or are in PFS.

With positive PFS results from the melanoma study, we plan to submit regulatory approval filings virtually simultaneously in both U S and Europe .

The potential European approval and country launches would of course follow potential U S approval and launch as the process for European regulatory review and approval is typically work.

Howard Robin: Now, as a reminder, Nektar is entitled to receive a total of up to $1.4 billion in milestones for BEMPEG filings and first commercial sales following approvals. Gil will provide more granularity on the timing and triggers for these milestones in a moment when he reviews our 2022 Financial Guide. As I mentioned earlier, Jay Dee will discuss the Nektar 2565 program later in the call, but I'd like to highlight a few key accomplishments for this program in 2021.

As a reminder, nektar is entitled to receive a total of up to $144 billion in milestones for <unk> filings and first commercial sales following approvals and Gil will provide more granularity on the timing of triggers for these milestones in a moment when he reviews, our 2022 financial guidance.

Howard Robin: So first, we generated some important early data in combination with the Tufts and added solid tumors in the early dose escalation work on our phase one clinical study of Nektar 2565, and this led to an exciting new collaboration for Nektar 2565 with Murk KGA at Pfizer. Thank you very much.

As I mentioned earlier, Jason He will discuss the next or 255 program later in the call, but I'd like to highlight a few key accomplishments for this program in 2021. So first we generated some important early data in combination with cetuximab in solid tumors and the early dose escalation work and a phase one clinical study of a record $2 50.

And this led to an exciting new collaboration.

<unk> 255, with Merck <unk> and Pfizer.

Howard Robin: The collaboration will combine Nectar 255 with Avilumab as part of Mertz Phase II Javelin Bladder Medley Umbrella Treatment. Merck will sponsor and conduct the study, and we will provide supply of Nectar 255. It is a relatively large phase two comparative study that has an Evelumab comparator arm and will evaluate treatment in a maintenance setting for bladder cancer, which is a label unique to Evelumab We're highly encouraged that Merck shares our enthusiasm for Nectar 255 and its potential to combine with Avelamad, which has shown an ADCC mechanism in preclinical studies.

The collaboration will combine that with $2 55, where they belong.

As part of Merck's phase II javelin bladder mentally umbrella trial.

Merck will sponsor and conduct the study and we will provide supply of an extra $2 55.

It's a relatively large phase II comparative study, which has been developed map comparator arm and we'll evaluate treatment in the maintenance setting a bladder cancer, which is a label unique to develop.

We're highly encouraged that Merck shares our enthusiasm for <unk> $2 55, and its potential to combine with development, which has shown an ADC mechanism and preclinical studies.

Howard Robin: Also, we recently presented data at ASH highlighting the potential role for Nektar-255 to serve as a CAR-T potentiator, with Nektar-255 eliciting a several-fold increase over baseline CAR-T cells even a year past the patient's CAR-T regimen. We're excited to announce today that we just received FDA clearance for the IND related to a study to evaluate Nektar This study will be initiated as an investigator-sponsored study at the Fred Hutchinson Cancer Institute. From an operational perspective, we have an exceptionally strong balance sheet and ended the year with approximately $800 million in cash.

Also we recently presented data at ash, highlighting the potential wall for metrics $2 55 to serve as a car T potentiate or with an extra $2 55, eliciting a several fold increase over baseline car T cells, even a year types of patients car T regimen.

Excited to announce today that we just received FDA clearance for the <unk> related to a study to evaluate an extra $2 55 in the setting of car T therapies, specifically CD 19 car T.

The study will be initiated.

As an investigator sponsored study at the Fred Hutchinson Cancer Center.

From an operational perspective, we have an exceptionally strong balance sheet and ended the year with approximately $800 million in cash this cash position together with the support of our strategic collaborations and potential for up to $1 $4 billion of regulatory filings and first commercial sales milestones were been pegged.

Howard Robin: This cash position, together with the support of our strategic collaborations and the potential for up to $1.4 billion in regulatory filings and first commercial sales milestones, provides us with a strong financial base to execute our robust development strategy. And with that, I'd like to turn the call over to our Chief Medical Officer, Dr. Dimitri Knight, to continue. Thank you, Dimitri. Thank you, Howard.

It provides us with a strong financial foundation to execute our robust development strategy.

I'd like to turn the call over to our Chief Medical Officer Dr. Dmitry.

To continue to.

Dmitry.

Thank you Howard before I dive into an update on our <unk> trials, let me take a moment to remind you of its mechanism in its approach our goal. When we started the development of <unk> quest to create a new and novel molecule that captured the positive attributes of IL two and also addresses the historical problems with high dose IL two.

Dimitri Nelton: Before I dive into an update on our BAMPAC trials, let me take a moment to remind you of its mechanism and its approach. Our goal when we started the development of BAMPAC was to create a new and novel molecule that captured the positive attributes of IL-2 and also addressed the historical problems with high-dose IL-2. Leveraging our technology platform, we were able to engineer a product candidate that we believe is best in class. Let me highlight some of the differentiating aspects of BAMPAC.

Leveraging our technology platform, we were able to engineer a product candidate that we believe is best in class. Let me highlight some of the differentiating aspects of <unk>.

Dimitri Nelton: First, we preferentially signal to the beta-gamma IL-2 receptors, which stimulates the growth of cytotoxic T-cells. We do this without over-activating the cell populations, which can lead to down-regulation of the immune system. And unlike mutated forms of IL-2 that only bind to the beta-gamma receptors, we retain some transient binding to the alpha receptor. And by doing so, we can enhance the priming of T-cells in lymph nodes, enabling T-cell proliferation and infiltration of those T-cells into tumors when the new tumor antigen is presented.

First we preferentially signal to the beta gamma IL, two receptors, which stimulates the growth of cytotoxic T cells. We do this without over activating the cell populations, which can lead to downregulation of the immune system and unlike mutated forms of IL two had only bind to the beta gamma receptors we retained.

Some trenching binding to the alpha receptor and by doing so we can enhance the priming of T cells in the lymph nodes, enabling T cell proliferation, and infiltration of dose T cells into tumors when the new tumor antigen is presented.

Dimitri Nelton: Second, we used the full-length IL-2 molecule with no amino acid substitutions rather than a mutated version. This ensures that we do not see any tech-filex as on the receptor or issues that mutant versions can exhibit over time in vivo, including anti-drug antibodies leading to diminished efficacy over time. Third, a pro-drug bent back avoids the risk of a cytokine storm that you may see with a non-pro-drug approach. This is something you really want to avoid in a medicine that could potentially be used in so many cancer patients.

We used the full length IL two molecule with no amino acid substitution is rather than a mutated portion. This ensures that we do not see any tachyphylaxis on the receptor or issues that mutant versions can exceed that over time in vivo, including antidrug antibodies, leading to diminished efficacy overtime third as a pro.

Rock manpack avoids the risk of a cytokine storm that you may see with a known pro Doc approach. Certainly this is something you really want to avoid in the medicine that could potentially be used in so many cancer patients and finally, we have achieved an antibody like dosing schedule in an outpatient setting that easily combined with checkpoint inhibitors.

Dimitri Nelton: And finally, we have achieved an antibody-like dosing schedule in an outpatient setting that easily combines with checkpoint inhibitors versus the intense and dense regimen for high-dose IL-2, usually given in an intensive care unit. We are combining BANPACK with checkpoint inhibitors, and the combination here is really quite simple and elegant. We know that targeting the PD-1 pathway may strengthen the immune response by reactivating cytotoxic T-cells that have been stopped by the PD-L1 and PD-1 signaling axon. We think of this as removing breaks in the immune system, an effective approach on its own.

First is the intense and dense regimen for high dose IL two usually given in an intensive care unit.

We are combining <unk> with checkpoint inhibitors and the culmination here is really quite simple and elegant we know that targeting the PD one pathway may strengthen the immune response by reactivating cytotoxic T cells that have been stopped by the PDL, one and PD one signaling axis, we think of this as removing breaks off the immune system in effect.

They've approach on its own than bipolar frenchly targeting the IL two pathway to significantly increase the number of cytotoxic immune cells in the tumor microenvironment, we put our foot on the gas in our previous clinical studies, we have shown two important things first the treatment with <unk> up regulates PD one on these new immune cells and cell.

Dimitri Nelton: Then, by preferentially targeting the IL-2 pathway to significantly increase the number of cytotoxic immune cells in the tumor microenvironment, we put our foot on the gas. In our previous clinical studies, we've shown two important things. First, treatment with BANPAC upregulates PD-1 on these new immune cells.

Dimitri Nelton: And secondly, that this ultimately leads to upregulation of PD-L1 in the tumor microenvironment. Both of these are expected biological outcomes after BANPAC treatment. And the end result is that the two together, BANPAC plus nivolumab, could potentially drive deeper and more durable responses in patients. Let me now provide a brief update on the timing for our registrational studies, which are tracking in line with our prior guidance. First, for the 760 patient phase three, first line metastatic melanoma study which is being conducted by a partner company BMS. We in BMS are very much looking forward to reporting top line data in the near term.

Lee that this ultimately leads to all regulation of PD L. One into tumor microenvironment. Both of these are expected biological outcomes. After <unk> treatment and the end result is that the two together then PEC plus navona map could potentially drive deeper and more durable responses in patients. Let me now provide a brief.

Date of the timing for a Registrational study each studies, which are tracking in line with our prior guidance.

Dimitri Nelton: As a reminder, this will include top-line results for the two co primary end points. We plan to present the full data and potentially subset analyses at a medical meeting later this year. We are not yet providing details at which meeting we plan to present, but we will target a significant oncology meeting. We plan to present the full data in the near term.

First for the 766 patient phase III first line metastatic melanoma study, which is being conducted by our partner BMS, We and BMS are very much looking forward to reporting top line data in the near term as a reminder, this will include top line results for the two co primary endpoints, we plan to present a full <unk>.

Data and potentially subset analyses at a medical meeting later this year, we are not yet providing details at which meeting we plan to present, but we will target a significant oncology meeting.

Dimitri Nelton: As a reminder, the Phase 3 study is a well-powered and well-designed study and has three co-primary endpoints, overall response rate, progression-free survival, and overall survival. As I just stated, the first analysis will include the two co-primary endpoints of overall response rate and progression freeze of I. For registration purposes, we only need to meet the progression-free survival end point in order to submit an application to the regulatory authority. Many of you have asked us specific details about the statistical analysis plan for this study.

As a reminder, the phase III study is a well powered and well designed study and has three co primary endpoints overall response rate progression free survival and overall survival as I. Just stated the first analysis will include the two co primary endpoint of overall response rate and progression free survival for Registrational purposes, we only need to.

The progression free survival endpoint in order to submit an application to the regulatory authorities.

Many of you have asked on specific details on the statistical analysis plan for this study and as most companies do we have not provided details on dish for the study prior to full data publication.

Dimitri Nelton: And as most companies do, we have not provided full details on this for the study prior to full data publication. In the past, we have provided the design of the Checkmate 67 study as an example for reference.

In the past we have provided to design of the Checkmate 67 study as an example for reference.

Dimitri Nelton: In our face-to-melanoma cohort, we saw a medium PFS of 30.9 months for our doublet. We know that the current IO doublet treatments available for first-line melanoma patients in phase three studies have reported medium PFS in the 10 to 11 month range, and the still commonly used global standard of care comparator in our phase 3 study, Novolumab, has reported a median PFS between four to six months in different studies.

In our phase II melanoma cohort, we saw a medium PFS of 39 months for our doublet, we know that the current Io doublet treatments available for first line melanoma patients in phase three studies have reported a median PFS in the 10 to 11 month range.

And there's still commonly used global standard of care comparator in our phase III study <unk> has reported a median PFS between four to six months in different studies header.

Dimitri Nelton: Heading into our top-line results, we are very enthusiastic, based on our previously reported Phase II results, that BANPAC plus Novolumab could potentially deliver results that position it well in the current treatment landscape. We envision a unique opportunity for BANPAC plus Novolumab doublet if we are able to emerge as a new standard of care in this setting. The next study which Nektar is running is a 620 patient phase 3 first-line renal cell carcinoma study comparing BMPEC plus nivolumab versus a TKI of physician choice, which can be either Sanitinib or Kevosan. We expect that we could reach our first interim analysis for the co-primary endpoint of overall survival sometime in the second quarter of 2022.

Headed into our topline results. We are very enthusiastic based on a previously reported phase two results and then third question of all the neb could potentially deliver results that position us well in the current treatment landscape, we envision a unique opportunity for <unk> plus in volume a doublet. If we are able to emerge as new standard of care and discerning.

The next study, which Nick Terry is running is a 620 patient phase III first line renal cell carcinoma study, comparing <unk> plus <unk> versus a teekay Io physician choice, which can be either sunitinib or cabozantinib. We expected we could reach our first interim analysis for the co primary endpoint of overall server.

Rival sometime in the second quarter of 2022 at that time, we could also conduct a final or our analysis for the co primary endpoint. If we do not pass the preset thresholds for statistical significance in the first interim analysis. The data monitoring committee will recommend a resizing of defense for the final analysis.

Dimitri Nelton: At that time, we could also conduct the final ORR analysis for the co-primary endpoint. If we do not pass the preset threshold for statistical significance in the first interim analysis, the Data Monitoring Committee will recommend a resizing of events for the final analysis for overall survival.

As for overall survival B.

Dimitri Nelton: BMS and Nektar are taking a comprehensive approach to the development of BAMPAC plus nivolumab in this particular tumor type. Additionally, BMS is conducting a 250 patient randomized phase two study in RCC that combines BAMPAC plus nivolumab with X-Alexis' cabocentinib, which allows us to compare it to the doublet regimen of nivolumab and ca Last year, BMS and Nektar expanded their strategy in RCC to include a new collaboration with Axel Axis, who will be conducting a study evaluating BMPAC plus nivolumab with their novel generation TKI, known as Axel 92.

BMS and Nektar are taking a comprehensive approach to the development of <unk> plus novo limit in this particular tumor type. Additionally, BMS is conducting a 250 patients randomized phase two study in RCC, there's combines bent a plus and a full limit would ask Alexis is cabozantinib, which allows us to compare it to the doublet regimen of Novo limit.

Cabozantinib to pave the way for our TK I inclusive regimen in RCC with benthic and of all the members last year BMS and Nektar expanded to strategy in RCC to include a new collaboration with extra Lexus, who will be conducting a study evaluating <unk> plus novo limit with their novel generation Teekay I known is excellent.

<unk> 92, and this study will also include auto do you cancers, including your Chilean cancer.

Dimitri Nelton: And this study will also include other GU cancers, including urotelial cancer. With respect to the Phase 2 study in first-line cisplatinum-ineligible urogyneal carcinoma which Nektar is running, the study is designed to serve as the basis for a potential filing for accelerated approval. This study includes about 110 cisplatinum-ineligible urogyneal carcinoma patients who have a baseline CPS score of 10 or lower as a measure of PD-L1 expression.

With respect to the phase two study in first line CIS platinum ineligible here until you carcinoma, which nectarous running the study is designed to serve as the basis for a potential filing for accelerated approval. The study includes about 100 tens is platinum ineligible urothelium carcinoma patients who have a baseline C. P. S.

Core of 10 or lower as a measure of PDL one expression and this is the group of patients with the highest unmet medical needs as they are not able to receive the most effective chemotherapy regimen available for bladder cancer and checkpoint inhibitors have shown most of their benefit in patients with PDL, one high tumors to primary.

Dimitri Nelton: And this is the group of patients with the highest unmet medical needs as they are not able to receive the most effective chemotherapy regimen available for bladder cancer, and checkpoint inhibitors have shown most of their benefit in patients with PD-L1 high tumors. The primary endpoints for this trial are overall response and duration of response as determined by central radiology. In order to have a robust and mature data set, we are looking to achieve a minimum follow-up of 18 months to measure the duration of response.

Endpoints for this trial are overall response and duration of response as determined by Central Radiology review.

In order to have a robust and mature dataset. We are looking to achieve a minimum follow up of 18 months measuring the duration of response and we expect our first data from this study to come out in the first half of 2022 as well as.

Dimitri Nelton: And we expect our first data from this study to come out in the first half of 2022 as well. As Howard noted earlier, the BMPAC Nivolumab program also has two large phase 3 studies, one in muscle-invasive bladder cancer and one in adjuvant melanoma. The Phase III periadjuvant muscle-invasive bladder cancer trial is being run by our partner BMS. It has a target enrollment of approximately 540 patients who are cisplatinum ineligible and who will receive BenPak plus nivolumab or nivolumab monotherapy, first in a neoadjuvant setting prior to radical cystectomy and then in the adjuvant setting for a The study also has a third reference arm where patients are receiving cystectomy alone and no further neoadjuvant or adjuvant treatment.

Dimitri Nelton: We expect the first data readout to be in 2024 or 2025. This study is also designed to serve as a confirmatory study for our planned potential accelerated approval for metastatic cis-ineligible urotelial carcinoma. The Phase III adjuvant melanoma trial is being run by Nektar. This study is enrolling a total of approximately 950 patients for a 12-month treatment period post-surgery with an endpoint of recurrence-free survival by blinded independent central review. Enrollment in this study has exceeded our timeline projections, and we are now expected to complete enrollment of the 950 patients study around the middle of the year.

As Howard noted earlier to <unk>, Nicole and that program also has two large phase III studies, one in muscle invasive bladder cancer and one in adjuvant melanoma.

The phase III purely adjuvant muscle invasive bladder cancer trial is being run by our partner BMS. It has a target enrollment of approximately 540 patients who are cisplatin ineligible and who will receive <unk> plus and of all the map or involved in that monotherapy first in the neo adjuvant setting prior to radical cystectomy and then into.

Adjuvant setting for a period of 12 months. Following surgery. The study is also a third reference arm, where patients are receiving cystectomy alone and no further neo adjuvant or adjuvant treatment.

We expect the first data readout to be in 2024 or 2025. This study is also designed to serve as a confirmatory study for a planned potential accelerated approval in metastatic CIS ineligible <unk> carcinoma.

The phase III adjuvant melanoma trial is being run by Nektar. This study is enrolling a total of approximately 950 patients for a 12 month treatment period post surgery with an endpoint of recurrence free survival by blinded independent Central review enrollment in this study has exceeded our timeline projections and we are now expected to.

Complete enrollment of the 950 patients study around the middle of the year. The adjuvant study is designed to build upon the recent approval of new volume up into setting and broaden the role for been thinking the adjuvant setting initial data from the study is estimated to be available in 'twenty 'twenty four.

Dimitri Nelton: The adjuvant study is designed to build upon the recent approval of nivolumab in this setting and broaden the role of BEMPEC in the adjuvant setting. Initial data from the study are estimated to be available in 2024.

Dimitri Nelton: For our combination studies with Permalizumab, we are enrolling patients in our 500+ patient phase two, three trial designed to support registration in first-line head and neck cancer. We have collaborations in place with both Merck and SFJ Pharmaceuticals for this study, and we are very excited about this opportunity to address a large patient population in the frontline setting. It includes an interim analysis of overall response rate after 200 patients are enrolled, and if overall response rate passes a pre-specified fertility boundary, the study will continue, and the remaining 300 patients will be enrolled in the phase three portion of the study.

For our combination studies with Perm, a little map, we are enrolling patients in our 500 plus patient phase two three trial designed to support registration in first line head and neck cancer, we have collaborations in place with both Merck and S. J Pharmaceuticals for this study and we are very excited about this opportunity to address a large patient population in the frontline setting.

It includes an interim analysis of overall response rate. After 200 patients are enrolled and if overall response rate passes a prespecified futility boundary to study will continue and the remaining 300 patients will be enrolled to the phase three portion of the study given the favorable competitive landscape, we seeded as a unique opportunity for us too.

Dimitri Nelton: Given the favorable competitive landscape, we see this as a unique opportunity for us to establish BEMPEC as the first IL-2 mechanism for the treatment of head and neck cancer. And then, finally, we are continuing to advance our PROPEL study with the addition of chemotherapy to BEMPEC plus pembrolizumab treatment regimen in both squamous and non-squamous non-small cell lung cancer patients with PD-L1 expression levels under The combination with chemotherapy here allows us to consider a broad registration strategy for BEMPEC in non-small cell lung cancer in these populations of patients with negative to low and medium PD-L1 expression in their tumors who are currently having the highest on-bed need for better therapeutic options. We are very much looking forward to providing future updates on our progress with BEMPEC in the future. And now, let me turn over the call to Jason.

Deb has been Piggish first IL two mechanism for the treatment of head and neck cancer and then finally, we are continuing to advance our propel study, which the addition of chemotherapy to benthic plus member Luiza map.

Penn militiamen treatment regimen in both squamous and non squamous non small cell lung cancer patients with PDL, one expression levels under 50% the combination with chemotherapy here allows us to consider a broad registrational strategy for <unk> in non small cell lung cancer in these populations of patients with negative to low and medium.

<unk> PDL one expression in their tumors, who are currently having the highest unmet need for better therapeutic options. We are very much looking forward to providing future updates on our progress with <unk> and <unk>.

In the future and let me now turn over the call to JC.

Thank you Dmitry.

Jonathan Zalevsky: Thank you, Dimitri. As Dimitri said, we are all very excited about the upcoming milestones for BEMPEG and the opportunity for this important IL-2-based therapeutic to treat a large number of patients battling cancer. As you know, Nektar has built a very strong and well-diversified clinical pipeline, and we've established ourselves as the leader in cytokine therapeutics. Our focus is on targeting significant opportunities in cancer and solid and liquid tumors, and even beyond cancer in a broad range of autoimmune disorders.

As Dmitry said, we are all very excited about the upcoming milestones for <unk> and the opportunity for this important IL two based therapeutic to treat a large number of patients battling cancer.

As you know Nektar has built a very strong and well diversified clinical pipeline and we've established ourselves as the leader in cytokine therapeutics or.

Our focus is on targeting significant opportunities in cancer, and solid and liquid tumors than even beyond cancer and a broad range of autoimmune disorders.

Jonathan Zalevsky: We are advancing clinical studies to capitalize on these significant opportunities with two large clinical programs, Nektar 255 and Nektar 358. And in addition, we have a robust research pipeline looking at immune-based agents in cancer and autoimmune diseases as well. So let me start with Nektar 255, an agent that engages the full biology of the IL-15 pathway to provide functional activation and homeostatic control of IL-15 responses in immune cells, namely natural killer cells, CD8 T-cells, and immune memory subsystems.

We're advancing clinical studies to capitalize on the significant opportunities with two large clinical programs next year or 255 and extra 358.

And in addition, we have a robust research pipeline looking at immune based agents in cancer and autoimmune diseases as well.

Jonathan Zalevsky: Now as a full agonist of the IL-15 pathway, Nektar 255 can thus be combined with multiple mechanisms, ranging from targeted agents to cell therapies including CAR-Ts and even immunological checkpoints in total to potentially improve the efficacy of these agents. In our early dose escalation work, we have observed a consistent increase of natural killer cells as well as CEAT cells across multiple tumor types, including multiple myeloma, non-Hodgkin's lymphoma, colorectal cancer, and had a neck, We have seen up to a nine-fold increase in NK cells, and our pharmacokinetic profile is highly predictable, allowing us to dose Nektar 255 every three or four weeks.

So let me start with an extra 255 and agent that engages the full biology of the IL 15 pathway to provide functional activation and homeostatic control of IL 15 responses of immune cells.

<unk> natural killer cells, CDA T cells and immune memory subsets.

Now as a full agonist of the IL 15 pathway nectar tooth by five can must be combined with multiple mechanisms ranging from targeted agents to cell therapies, including car Ts and even immunological checkpoints in total to potentially improve the efficacy of these agents.

In our early dose escalation work, we have observed a consistent increase of natural killer cells as well as CDA T cells across multiple tumor types, including multiple myeloma.

Non hodgkin's lymphoma, colorectal cancer, and head and neck cancer.

We have seen up to a nine fold increase in NK cells, and our pharmacokinetic profile is highly predictable, allowing us to dose metric to five five every three or four weeks.

Jonathan Zalevsky: And importantly, we see increases in NK and CD8 T-cells in even the toughest patients, including multiple myeloma patients with compromised bone, and this is a very important attribute of Nektar 255, and this should allow Nektar 255 to be given as a model therapy and in combination with targeted therapy. We also see potential for enhancing CAR T-PERSIST.

And importantly, we see increases in NK, and CDA T cells, and even the toughest patients, including multiple myeloma patients with compromised bone marrow.

And this is a very important attribute of Natura 255, and this should allow an extra 255 to be given as a monotherapy and in combination with targeted antibodies.

We also see potential in enhancing car T persistence.

Jonathan Zalevsky: So at ASH, we shared data from a set of four patients enrolled in our Nektar 255 study with highly relapsed and refractory NHL, who also had CAR T as one of their prior therapies. Three of these patients were well over a year past their CAR T infusion, and all of them had minimal levels of detectable CAR T at baseline prior to entering the Nektar 255 clinical study. We were very encouraged to see that in all four of these patients with detectable CAR-T at baseline, there was a substantial increase in these cells after treatment with Nektar 255. These initial data highlight the potential role of Nektar 255 as a CAR-T potentiator.

So at Ash, we shared data from a set of four patients enrolled in our sector to five five study with highly relapse and refractory NHL, who also had car T. As one of their prior therapies three.

Three of these patients were well over a year past their car T infusion and all of them had minimal levels of detectable car T at baseline prior to entering the next or 255 clinical studies.

We were very encouraged to see that in all four of these patients with detectable car T. At baseline there was a substantial increase in T cells after treatment with nectar to five five.

And these initial data highlight the potential role of an extra 255 is a car T potentiate or in our next steps in the clinic will be to evaluate dosing of <unk> 255, shortly after car T infusion.

Jonathan Zalevsky: And our next steps in the clinic will be to evaluate dosing of Nektar 255 shortly after CAR-T infusion, and we are doing a study with Dr. Cameron Turtle at the Fred Hutchinson Cancer Center to see if we can generate even more durable responses for patients. And as we announced earlier in this call, we just received FDA clearance for the study to proceed. This study will evaluate various dose regimens of Nektar 255 given close to the time of CD19 CAR T cell therapy.

And we are doing a study with Dr. Cameron turtle at the Fred Hutchinson Cancer Center to see if we can generate even more durable responses for patients.

And as we announced earlier on this call. We just received FDA clearance for the study to proceed.

This study will evaluate various dose regiments of nectar 255, given close to the time of CD 19 car T cell therapy.

Jonathan Zalevsky: Of course, our initial strategy has focused on combining it with antibodies that function through an ADCC mechanism of action, and we have a robust clinical program in place in both liquid and solid tumors. For our Phase I-II study of Nektar 255 plus Cetuximab in patients with relapsed or refractory head and neck cancer and colorectal cancer, we are still in the dose escalation portion of the trial with successive cohorts of patients being treated with ascending doses of Nektar 255 every 21 days plus Cetuximab weekly until we reach the maximum tolerated dose or the recommended dose to go For our study in B-lapse refractory hematological diagnoses, the agent has been very well tolerated at Monterey.

And of course, our initial strategy has focused on combining with antibodies that function through in a D. C. C mechanism of action and we have a robust clinical program in place in both liquid and solid tumors.

For our phase one two study of nectar 255, plus cetuximab in patients with relapsed or refractory head and neck cancer and colorectal cancer. We are still in the dose escalation portion of the trial with successive cohorts of patients being treated with ascending doses of an extra 2525 every 21 days plus a tux.

The Mab weekly.

Until we reach the maximum tolerated dose or the recommended dose to go forward into the expansion cohorts.

For our study in relapsed refractory hematologic malignancies, the agent has been very well tolerated as monotherapy and.

Jonathan Zalevsky: We expect to complete the dose escalation phase of the study in the first part of 2022 and then move into the expansion phase in combination with rituximab or Darzalex Vaspro. Now, the first arm in the study will evaluate Nektar 255 as monotherapy or in combination with rituximab in third-line or later follicular lymphoma or low-grade non-Hodgkin' The second arm will evaluate Nektar 255 as monotherapy and in combination with Darzalex Faspro in third line or greater multiple myeloma.

We expect to complete the dose escalation phase of the study in the first part of 2022, and then move into the expansion phase in combination with Rituximab for doors, <unk> bass pro and the <unk>.

First arm in the study will evaluate next year or 255 as monotherapy or in combination with Rituximab in third line or later, follicular lymphoma, or low grade non Hodgkin's lymphoma.

The second arm will evaluate an extra 255 as a monotherapy and in combination with Darvill ex bass pro in third line or greater multiple myeloma and finally, the third arm will evaluate <unk> 255, as a monotherapy for non Hodgkin's lymphoma patients who have previously progressed following improved CD 19 car.

Jonathan Zalevsky: And finally, the third arm will evaluate Nektar 255 as a monotherapy for non-Hodgkin's lymphoma patients who have previously progressed following approved CD19 CAR T-cell therapy. We have recently expanded our program through a collaboration agreement with Merck KGA to evaluate Nektar 255 in combination with Avelamab in the urothelial carcinoma maintenance setting after chemotherapy as part of the Javelin Bla The foundation of this collaboration is a unique scientific rationale, the combination of Nektar 255 with Velumax.

T cell therapy.

And we recently expanded our program through a collaboration agreement with Merck K G E to evaluate an extra 255 in combination with the Belo mob in the Euro Thelion carcinoma maintenance setting post chemotherapy as part of the javelin bladder medalist study.

The foundation of this collaboration is the unique scientific rationale of the combination of an extra 255 with the Vela map.

Which to remind you is a PD L. One inhibitor with an a D. C C active IGD one at sea region.

Jonathan Zalevsky: [inaudible] The Nectar 255 combination arm of the study plans to recruit 72 patients and will be compared to a NovellaMap control arm. Findings from this trial will help determine whether there is a Registration Pathway for Nektar 255 in this setting, where Velamav is already- and the Avelumab Alliance of Merck and Pfizer is sponsoring the trial, with Merck running the study, and they are on track to initiate the study next quarter.

The next you tube pipe by a combination arm in the study plans to recruit 72 patients and will be compared to a novella map controller.

Findings from this trial will help determine whether there is a registrational pathway for <unk> 255 in this setting where of Allomap is already approved.

And the development of alliance of Merck and Pfizer was sponsoring the trial with Merck running the study.

And they are on track to initiate the study next quarter.

Jonathan Zalevsky: And now, let's turn to our immunology program, Nektar 358. As Howard said earlier, we are very pleased with the broad scope of development and overall advancement of the Nektar 358 program being executed by our partner, Eli Lilly. Many autoimmune and inflammatory disorders, including systemic lupus and ulcerative colitis, are associated with decreased T-Rag numbers, reduced T-Rag function, and or reduced production of

And now, let's turn to our Immunology program next year 358.

Howard said earlier, we are very pleased with the broad scope of development and overall advancement of the nectar three five a program being executed by our partner Eli Lilly.

Many autoimmune and inflammatory disorders, including systemic lupus and alternative colitis are associated with decreased hearing numbers reduce T Rex function and our reduced production of IL two.

Jonathan Zalevsky: With Lecture 3-5-8, we've utilized a completely different approach with our pegalation chemistry to capture the immune-regulating potential of IL-2 by specifically stimulating T-Rex. Thus, our goal with Nektar 358 is to address the underlying Treg abnormalities in autoimmune disease and to develop an IL-2-like molecule that could selectively stimulate Tregs in a more effective manner than low-dose IL-2. The data emerging from the program has really reinforced our conviction in this approach. In our multiple ascending-dose study in lupus patients, Nektar 358 led to a dose-dependent reduction in lupus skin disease activity as measured by the CLASS-E activity score in the subset of 18 patients with a baseline score greater than or equal to 4.

With Doctor 358, we've utilized a completely different approach with our pegylation chemistry to capture the immune regulated potential of IL two by specifically stimulating T Rex thus.

Thus our goal with an extra 358 is to address the underlying T. Reg abnormalities in autoimmune disease and to develop an IL two like molecule that could selectively stimulate T regs and a more effective manner than low dose IL two.

The data emerging from the program has really reinforced our conviction in this approach.

And our multiple ascending dose study in lupus patients nectar 358 led to a dose dependent reduction in lupus skin disease activity as measured by the classy activity score in the subset of 18 patients with a baseline score greater than or equal to four.

Jonathan Zalevsky: Now this data, along with the PK, PD, and safety information we collected in this phase 1B Lupus trial led to Lilly launching a phase 2B dose range finding study in 280 patients. Late last year, Lilly announced exciting proof of concept data in a second dermal disease pathology, moderate to severe atopic dermatitis. The 12-week study tested two doses of Nektar 358 compared to placebo and then followed patients for quite a while after the last dose of the therapy.

Now this data along with the PK PD and safety information we collected in this phase one be lupus trial.

Led to Lilly launching a phase two b dose range finding study in 280, lupus patients, which is well underway and recruiting nicely.

Our late last year, Lilly announced exciting proof of concept data in a second terminal disease pathology.

Moderate to severe atopic dermatitis.

The 12 week study tested two doses of an extra 358 compared to placebo and then followed patients for quite a while after the last dose of therapy.

Jonathan Zalevsky: Treatment with Nektar 358 showed a dose-dependent reduction in eczema area and severity index scores and patients, with approximately a 70% maximum reduction in scores at week 12 at the highest dose test, and the efficacy that I was seeing in this study is well in line with the current standard of care and depictions, which require 16 weeks of treatment depending on the age of the patient. But clearly, the most fascinating observation from the study was that when we looked at patients 36 weeks after we stopped Nektar 358 therapy, their skin scores remained very low. And, in fact, it even dropped further.

Treatment with <unk> 358 showed a dose dependent reduction in eczema area and severity index scores in patients was approximately a 70% maximum reduction in scores at week 12, but at the highest dose tested.

And the efficacy that was seen in this study is well in line with the current standard of care to pixel.

Which requires 16 weeks of treatment with the agent.

But clearly the most fascinating observation from the study was that when we looked at patients 36 weeks. After we stopped dosing next year 358 therapy. Their skin scores remained very low and in fact, even dropped further during this extended period.

Jonathan Zalevsky: Standard Period. And this has us, and Lily, very excited about the potential for durability with Nektar 358. And, you know, these data really underscore our hypothesis that if you increase the function of regulatory T cells, you might, in fact, address the underlying immune pathology in the disease and see a durable clinical signal, like we see here in atopic dermatitis, well after the treatment. Nektar 358 is a first-in-class mechanism, and as we understood when we started this development program, Nektar 358 has the potential to treat the underlying disease pathology and provide disease-modifying effects.

And this has us and Lilly very excited about the potential for durability with an extra 358.

And these data really underscore our hypothesis that if you increase the function of regulatory T cells that you might impact address the underlying immune pathology in the disease and see a durable clinical signal like we see here in atopic dermatitis.

Well after the treatment ends.

Next year 358 is a first in class mechanism and as we understood. When we started this development program <unk> three five to eight has the potential to treat the underlying disease pathology and provide disease modifying effects.

Jonathan Zalevsky: This means that if we are successful... Nectar 358 could truly transform the treatment of autoimmune disease. The Phase 2 program for Nectar 358 includes the ongoing 280-patient Phase 2 study in lupus and a second ongoing Phase 2 study in 200 patients with ulcerative colitis.

This means that if we are successful and extra three five acre truly transformed the treatment of autoimmune diseases.

The phase II program for next year 358 includes the ongoing 280 patient phase II study in lupus.

A second ongoing phase II study in 200 patients with ulcerative colitis.

Jonathan Zalevsky: Third Phase 2 Study planned in Atopic Dermatitis and a Fourth Phase 2 Study in a yet-to-be-announced autoimmune indication expected to start later this year. With these trials making great progress, we are expecting a steady stream of data coming from these Lilly studies over the next 12 to 18 months. And with that, I will turn the call over to Gil. Thank you, Jonathan. And good afternoon, everyone.

A third phase II study planned in atopic dermatitis.

Fourth page two study and a yet to be announced autoimmune indication expected to start later this year.

With these trials, making great progress we are expecting a steady stream of data coming from these early studies over the next 12 to 18 months.

And with that I will turn the call over to Gil.

Gil LaBrushery: This afternoon, we announced our full-year financial results for 2021 in our earnings press release. On this call, I will provide our annual financial guidance for 2022, starting with our cash position.

Thank you Jonathan and good afternoon, everyone. This afternoon, we announced our full year financial results for 2021 and our earnings press release on this call I will provide our annual financial guidance for 2022.

Starting with our cash position, we finished 2021 with a very strong balance sheet with approximately 800 million in cash and investments and no debt.

Gil LaBrushery: We finished 2021 with a very strong balance sheet with approximately $800 million in cash and investments and no debt. In addition, under our collaboration with BMS. There are very significant near-term regulatory and commercial launch mile [inaudible] Associated with Successful Outcomes, from the Registration Studies [inaudible] Let me provide you with some more detail on how these milestones break? For the first indication, there are 60 million of milestones associated with health authority filings for BEMF, in the U.S. and E. David, David Rosmarin, David Rosmarin, David Rosmarin, David Rosmarin, 500 million in commercial launch milestones, split equally between the first commercial sale and the U.S. First Commercial Fail in the EU.

In addition, under our collaboration with BMS that are very significant near term regulatory and commercial launch milestones associated with successful outcomes from the Registrational studies for been pegged.

Let me provide you with some more detail on how these milestones breakdown.

For the first indication there are 60 million of milestones associated with health authority filings for Ben Peg in.

In the U S and EU.

500 million in commercial launch milestones split equally between the first commercial sale in the U S and the first commercial sale in the EU and.

Gil LaBrushery: [inaudible] 65 million in milestones associated with regulatory submissions, and commercial launch in Japan for each of the next three indications. There are 30 million milestones associated with health authority filings in the U.S. and EU, and 200 million in commercial launch miles.

And $65 million in milestones associated with regulatory submissions and commercial launch in Japan.

For the for each of the next three indications there are 30 million of milestones associated with health authority filings in the U S and EU.

200 million in commercial launch milestones split equally between the first commercial sale in the U S and the first commercial sale in the EU and $30 million in milestones associated with regulatory approval submissions and commercial launch in Japan.

Gil LaBrushery: Split equally between the first commercial sale in the U.S., and the first commercial sale in the EU, plus 30 million in milestones associated with regulatory approval submissions and commercial launch. Before I get into the line item projections for our 2022 financial guide, I wanted to review a few key assumptions that we made in formulating this guidance. If one or more of our registrational studies for BEMPEG are successful in the first half of 2022, it is possible that BEMPEG could be approved and launched as early as late 2022, dependent upon regulatory filing and review time. However,

Before I get into the line item projections for our 2022 financial guidance I wanted to review a few key assumptions that we made in formulating this guidance.

If one or more of our Registrational studies for been pegged our successful in the first half of 2020 to.

It is possible that <unk> could be approved and launched as early as late 2022 dependent upon regulatory filing and review timelines.

However.

Gil LaBrushery: In our financial guidance for this year, we have included only regulatory filing milestones for 2022 in our revenue and cash position estimates, with any revenue and cash receipts for the potential commercial launch milestones coming in 2023. We will, of course, update this guidance as appropriate based on additional information. Steve Durin, Steve Durin, Now turning to our 2022 financials, with respect to our cash position. We expect to end the year with approximately $400 million in cash and investment, with Netcast Useds in 2022 relatively consistent with 2021.

In our financial guidance for this year, we have included only regulatory filing milestones for 2022, and our revenue and cash position estimates with any revenue and cash receipts.

For the potential commercial launch milestones coming in 2023.

We will of course update this guidance as appropriate based on additional information we received during the year.

Now turning to our 2022 financial guidance with.

With respect to our cash position, we expect to end the year with approximately $400 million in cash and investments with net cash usage in 2022 relatively consistent with 2021.

Gil LaBrushery: [inaudible] Our projected 2022 cash position includes $100 million in BMS collaboration milestones associated with regulatory filings for. Our gap revenue is expected to be between 185 and 195 million in 2022, including the $100 million of BMS collaboration milestones related to BEMPEG regularity. We currently.

Our projected 2022 cash position includes 100 million in BMS collaboration milestones associated with regulatory filings for <unk>.

Our GAAP revenue is expected to be between 185 and $195 million in 2022 including the $100 million of BMS collaboration milestones related to <unk> regulatory filings.

We currently expect approximately 770 million of these milestones will be recognized in Q3 with a balance of $30 million being recognized in Q4.

Gil LaBrushery: We expect approximately 70 million of these milestones will be recognized in Q3, with a balance of 30 million being recognized in Q4. Greeny's Milestone We expect to recognize the remaining $85 to $95 million of GAP revenue fairly rapidly over the four quarters of 2020. The non-milestone portion of our revenue includes $70 to $75 million in non-cash royalty revenue and $15 to $20 million in product sales.

Excluding these milestones we expect to recognize the remaining $85 million to $95 million of GAAP revenue fairly ratably over the four quarters of 2022.

The non milestone portion of our revenue includes 70 to 75 million in noncash royalty revenue and $15 million to $20 million in product sales.

Gil LaBrushery: We anticipate 2022 GAAP R&D expense will range between $500 and $525 million, which includes approximately $65 to $70 million of non-cash depreciation and stock compensation expense and $30 to $35 million of non-cash development expenses for our head and neck program being funded by SFJ Pharmacy. Our 2022 R&D investment will further advance our deep pipeline of immune modulating medicines. Prepare BEMPEG for commercial. We and our partners are funding six registrational studies for bi- This year, we expect to complete enrollment of approximately 950 patients in the PIVOT-12 adjuvant melanoma study by approximately mid-year, and also to significantly ramp enrollment.

We anticipate 2022, GAAP R&D expense will range between 500 and $525 million.

Which includes approximately $65 million to $70 million of noncash depreciation and stock compensation expense.

And 30 to 35 million of noncash development expense for our head and neck program being funded by S. F J pharmaceuticals.

Our 2022 R&D investment will further advance our deep pipeline of immune modulating medicines and prepare been pegged for commercial launch we and our partners are funding six Registrational studies for <unk>. This.

This year, we expect to complete enrollment of approximately 950 patients in the pivot 12 adjuvant melanoma study by approximately mid year.

And also to significantly ramp enrollment in the head and neck study.

Gil LaBrushery: We are continuing to manufacture BEMPEG for commercial launch, and these expenses will continue to be reflected in R&D until approval of BEMPEG is achieved, in which case we will then capitalize our commercial manufacturing into inventory. Spent Through Cost of Goods Sold, from Nektar 358.

We are continuing to manufacture been pegged for commercial launch and these expenses will continue to be reflected in R&D until approval have been pegged as achieved in which case. We will then capitalize our commercial manufacturing into inventory and expense through cost of goods sold.

For nectar 358, we will be funding, our 25% share of development costs for four phase two Lilly clinical studies, and lupus ulcerative colitis, atopic dermatitis and one additional immune indication.

Gil LaBrushery: [inaudible] We will be funding our 25% share of development costs for four phase two Lilly clinical studies in lupus, ulcerative colitis, and atopic dermatitis and one Additional Immune Indication. We are completing the dose escalation studies for Nektar 255 in both hematologic and solid tumor settings and will be starting enrollment in multiple expansion cohorts this year in combination with A.D.C. Additionally, we will continue our research efforts to enable new programs to add to our clinical pipeline in the coming years. GNA expense for 2022 is projected to be between $175 and $195 million, which includes approximately $35 to $40 million of non-cash depreciation and stock compensation.

We are completing the dose escalation studies for a doctor to five five in both hematologic and solid tumor settings and will be starting enrollment in multiple expansion cohorts. This year in combination with a D. C C antibodies.

Additionally, we will continue our research efforts to enable new programs to address clinical pipeline in the coming years.

G&A expense for 2022 is projected to be between 175 and $195 million.

Which includes approximately $35 million to $40 million of noncash depreciation and stock compensation expense.

Gil LaBrushery: As I mentioned earlier, we are currently building our commercial capabilities in a carefully staged fashion with a focus on distribution and market action, preparing for Ben Paye's commercial launch as early as the end of 2022. We continue to carefully gate our commercial investments in the first half of 2022 prior to the receipt of positive top-line data from our registrational studies. Report Regulatory Approval, As a result, we do not expect GNA to be rateable through 2022 as commercial activities will increase in the second half of the year following positive top-line data from the BEMPEG registration. Non-cash interest, related to our royalty monetization, is expected to be between Additionally, I want to note that our non-operating expense includes the change in fair value of our development, derivative liability.

As I mentioned earlier, we are currently building our commercial capabilities and are carefully staged fashion with a focus on distribution and market access to prepare for bent a commercial launch as early as the end of 2022.

We continue to carefully gate, our commercial investments in the first half of 2022.

Prior to the receipt of positive topline data from our Registrational studies to support regulatory approval filings as.

As a result, we do not expect G&A will be ratable through 2020 two as commercial activities will increase in the second half of the year following positive topline data from the been pegged Registrational studies.

Our noncash interest expense related to our royalty monetization is expected to be between 25 and $30 million.

Additionally, I want to note that our non operating expense includes the change in fair value of our development derivative liability, which may change significantly this year based on the results of the metastatic melanoma study.

Gil LaBrushery: Which may change significantly this year based on the results of metastatic melanoma. And with that, we will now open the call to questions. Operator.

Operator: Thank you. As a reminder, to ask a question, you will need to press the star and then one on your telephone. To withdraw your question, please press the pound key. And in the interest of time, we do ask that you please limit yourself to one question at this time. And our first question comes from Peter Lawson from Barclays. Your line is open.

And with that we will now open the call to questions operator.

Thank you as a reminder to ask a question you will need to press Star and then wanting your telephone to withdraw.

Your question. Please press the pound key.

And in the interest of time, we do ask that you've proven yourself to one question at this time.

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

Peter Lawson: Thank you. Thanks for taking the question. Thanks for all the detail, Nicole, three, phase three readouts, just kind of your level of read through that we should be taking from melanoma to RCC to bladder for the BEMPAC trial. Thank you, Peter. I'm going to ask Dimitri to take that one. Dimitri?

Thank you. Thanks for taking the question. Thanks for all the details of the call.

Maybe as we think about the.

<unk> phase III Readouts, just kind of your level of them.

We treat that we should be taken for melanoma to OCC to bladder.

But the <unk> choice.

Yeah. Thank you Peter I'm going to ask Dmitry to take that one dmitry.

Dimitri Nelton: Yeah, thank you for the question. I think these are, as I like to call them, independent shot-on goals. On the one hand, of course, the indications have been carefully selected based on, let's say, IL-2 validation, specifically for melanoma and for renal cell carcinoma. Bladder cancer is a different indication. We built, let's say, strong early data across the different indications. However, if you think about read-through, they're very different tumor types. The studies are different in design,

Thank you for the question I think these are as I like to call them independent shot on goals are on one hand of course, the indications have been carefully selected based on let's say IL two validation specifically for melanoma and for renal cell carcinoma that.

Cancer is a different indication.

We built let's say strong early data across the different indications.

However, if you think about read through Theyre very different tumor types are the studies are different in design. Specifically, if you think about melanoma. We are building upon standard of care, combining with Navona map comparing it to new volume up alone. However in renal cell, we have a double I O approach versus a T. K I have.

Dimitri Nelton: Specifically, if you think about melanoma, we are building upon standard of care, combining it with nivolumab, comparing it to nivolumab alone. However, in renal cell, we have a double-IO approach versus a TKI approach. So, I would overall say there's limited read-through, and these are truly independent shots-on-goal.

Broach, So I would overall say downstairs limited read through and these are truly independent shots on goal.

Chris Shibutani: Thank you. Our next question comes from Chris Shibutani from Goldman Sachs. Your line is open. Hi, good evening. This is CJ Zaafon on behalf of Chris this evening.

Thank you.

Our next question comes from Chris Schott Litani from Goldman Sachs. Your line is open.

Hi, good evening as procedures off on for Chris. This evening, obviously, we're all waiting on Tenterhooks to see the phase III Readouts coming up this half.

Gil LaBrushery: Obviously, we are all waiting on Tenderhooks to see the Phase 3 readouts coming up this half. Gil, thanks so much for helping us think through what the spend might look like under the assumptions that you gave. In the unfortunate event that the trials are not positive, how should we be thinking about any potential spend trajectory changes? Yeah, Gil. Do you want to take that?

Gil Thanks, so much for helping us think through what the spend might look like and under the assumptions that you gave in the unfortunate event that the trials are not positive how should we be thinking about any potential spend trajectory changes.

Yeah, Gail do you want take that.

So of course as you as we outlined our assumptions in our guidance, we're expecting positive results out of the been pegged trials as I'm sure. You can imagine we have continued we have contingency plans in the unlikely event, we were not to have success, but I think it's way too early to even be contemplating or talking about those.

Jay Olson: So, of course, as we outlined our assumptions and our guidance, we're expecting positive results out of the BEMPEG trials. As I'm sure you can imagine, we have contingency plans in the unlikely event we were not to have success, but I think it's way too early to even be contemplating or talking about those plans. So we're certainly planning for success and are ready to make any adjustments as we go forward. Thank you. Our next question comes from Jay Olson from Oppenheimer. Your line is open. Oh, thank you. This is Trilanda Life or Jay.

Those plans. So we're certainly planning for success and ready to make any adjustments as we go forward.

Thank you.

Our next question comes from Jay Olson from Oppenheimer. Your line is open.

Dimitri Nelton: Thanks for taking the question. Maybe just one, four, two, fifty-five. I'm just wondering how you think about the collaboration opportunity for two, fifty-five with cell therapy. And separately, I'm just curious about the newly initiated study with Carti. When will you dose two, fifty-five following Carti?

So essentially this is Joe on the life of Jay.

Thanks for taking my question, maybe just one or 265 I'm just wondering how are you thinking about.

Collaboration Albert showing two for $2 55 with cell therapy and separately I'm just curious about the new newly initiated study.

With car T, where we would go for $2 55 for the car T and if you're going to dose for one time or you will be thoughtful periodically. Thank you.

Yeah. Thank you for that J C. Do you want to talk about our approach in cell therapy as well as the car T study a little bit more thank you.

Jessica Fye: And if you're going to dose just for one time, or you will be doseing three, [inaudible] Yeah, thank you for that. Jay-Z, do you want to talk about our approach to cell therapy as well as the CAR-T study a little bit more? Yeah, absolutely.

Dimitri Nelton: Thank you for the question. So one of the things that we observed when we started our collaboration with Cameron Turtle at the Hutch is that we ran a number of preclinical studies with him. And of course, remember he's really one of the founding fathers of this whole field.

Yeah, absolutely. Thank you for further questions. So one of the things that we observed when we started our collaboration with Cameron turtle at the Hutch is that we ran a number of preclinical studies with him and of course remember he is really one of the founding fathers of this whole field.

And we were really following on the understanding that patients that have the highest levels of IL 15 post conditioning seem to have some of the best outcomes. Following car T cell therapy transplant. So the opportunity here is really providing an exogenous IL 15 pathway source.

Gregory Harrison: And we were really following on the understanding that patients that have the highest levels of aisle 15 post conditioning seem to have some of the best out And we were really following on the understanding that patients have the highest levels of aisle 15 post conditioning seem to have some of the best out, following CAR-T self-therapy transplant. So the opportunity here is really providing an exogenous IL-15 pathway source to help in the setting.

Gregory Harrison: So what we were really excited about was that when we saw the early preclinical studies, we saw that administration of Nektar-255 could actually rescue subclinical doses of CAR-T cells applied in a preclinical model. So these are levels of CAR-T that are so low that they hardly provide any, you know, tumor control, but in combination with 255, not only did they kill the two... The animals maintain long-term persistence because you could keep re-challenging them with the same tumors, and they continue to be completely tumor-free, you know, for many, many months after treatment.

Help.

The static so we will be first really we're excited about is that what we saw the early preclinical studies. We saw that administration of an extra 255 could actually rescue sub clinical doses of car T cells applied in a preclinical model. So these are levels of car T. There so low that they hardly provide any.

You know tumor control, but in combination with 255, not only do they kill the tumors. The animals maintained long term persistence of effect you could keep re challenging them with the same tumors and they continued to be completely tumor free for many many months after treatment.

Dimitri Nelton: So the study that then extended to that that is also being run by Cameron Turtle at the Hutch is really now kind of leveraging forward from those early preclinical studies to the ASH data that I summarized in patients long since their prior transplant into the setting where we're going to be administering Nectar 255 much more contemporaneously with the CAR T therapy. So, very much like you pointed out, Pier 255 will be given very close in time to the CAR T administration.

So the study that then that extended to that that as also being run by by Cameron turtle at the Hutch is really now kind of leveraging forward from those early preclinical studies to the ash data that I summarized in patients long since their prior transplant into the setting.

We're gonna be administering neck or 255, much more contemporaneously with the car T therapy. So very much like you pointed out here to 55 will be getting very close in time to the car T administration.

Dimitri Nelton: And as you pointed out, you have this ability to continue treatment. So we will be continuing to treat with Nectar 255 for an extended period of time after the original CAR T transplant with the opportunity, in all these cases, to increase the persistence of the CAR T cells and ultimately, and hopefully, improve the efficacy and durability of these therapies.

And as you pointed out you have this ability to continue treatment. So we will be continuing to treat with nectar $2 55 for an extended period of time after the original car T transplant with the opportunity in all these cases to increase the persistence of the car T cells them ultimately and hope.

Fully improve the efficacy and durability seen with these therapies.

Bert Hazlitt: Thanks for the question. Thank you. Our next question comes from Jessica Fye from J.P. Morgan. Your line is open. Hey, guys, good evening.

Thanks for the question.

Thank you.

Next question comes from Jessica Fye from Jpmorgan. Your line is open.

Hey, guys. Good evening, Thanks for taking my question.

Dimitri Nelton: Thanks for taking my questions. When do you expect to have mature overall survival data from the frontline melanoma trial? And what's the minimum PFS hazard ratio you could detect in that study? Thanks. Hi Jess.

Howard Robin: Thanks. Dimitri, I'm going to ask you to take those, too. Yeah, sure. Thanks for the question. I'll start with the PFS as a ratio.

When do you expect to have mature overall survival data from the frontline melanoma trial.

And what's the minimum PFS hazard ratio you can detect in that study.

Hi, Jess Thanks, Dmitry Im going to ask you to take those two yeah sure. Thanks for the question I'll start with the PFS hazard ratio as we stated before we havent given additional guidance or detailed guidance on our statistical analysis plan.

Mara Goldstein: As we stated before, we haven't given additional guidance or detailed guidance on our statistical analysis plan. I would say this is fairly atypical for companies to disclose those details until a full publication is available. We've talked about clinical relevance before, and I've emphasized two things: first of all, as a benchmark or as a reference trial, the CheckMate 67 study can be looked at for a lot of details, and our study is well-designed to detect a clinically relevant, let's say, hazard ratio.

I would say that this is fairly atypical for companies to disclose those details until a full publication is available.

We've talked about clinical relevance before and I've emphasized two things first of all as a let's say benchmark or as a reference trial. The checkmate 67 study can be can be looked at for a lot of details.

In the study and our study is well designed to detect a clinically relevant.

That's a hazard ratio.

Mara Goldstein: When it comes to survival analysis, that's also something we haven't commented on. We're not providing any guidance on the number of events and the timing. I can only say that it's one of the three co-primary endpoints. We don't need survival data for a regulatory path. PFS by itself is a registrational endpoint, and survival data, as I think is known from many other trials in melanoma, lags significantly behind, which, of course, is a good thing for patients. They're living a lot longer than they would have without disease progression.

When it comes to the survival analysis. That's also something we haven't commented on where we're not providing any guidance on the number of he fends into timing Ah I can only say that it's one of the three co primary endpoints and we don't need to survival data for a regulatory path P. F. S by itself as a registrational endpoint and two five.

Rival data as I think is known for many auto trials in melanoma lack significantly behind which of course is a good thing for patients and their living a lot longer.

Then they live without disease progression. So that's something we'll give further updates on that in the future, but not not at this time.

Gil LaBrushery: So that's something we'll give, let's say, updates on in the future, but not now. Thank you. Your next question comes from Greg Harrison from Bank of America. Your line is open.

Thank you.

Our next question comes from Greg Harrison from Bank of America. Your line is open.

Andy Shea: Hey, good afternoon, and thanks for taking the question. If the melanoma data are positive but either maybe inline or just not clearly superior to ipinevo and TREC-Mate 67, how would this change your path forward for commercialization? In other words, are there other aspects of BenPeg that you would expect to be differentiated and help you gain some share there?

Hey, good afternoon, and thanks for taking the question.

If the melanoma data are positive.

Either maybe in line or just not clearly superior to <unk>.

It would be an evo in checkmate <unk> seven.

This change your path forward for commercialization.

In other words are there other aspects have been pegged.

That you would expect to be differentiated in and help you gain some share there.

Dimitri Nelton: Thanks, Craig. I'm going to ask Dimitri to take that one as well. Thank you, Dimitri. Yeah. Thank you for the question. I think it's complicated.

Thanks, Greg I'm going to ask to meet you should take that one as well I think thank you for the question I think it's it's complicated I I've said, a few times in earlier calls before the.

Operator: I've said a few times in earlier calls before, the median PFS, of course, is one of many things to look at. I think the hazard ratio is one thing to look at. If we assume your question about being similar hazard ratios, then there are a lot of other, let's say, differentiating elements in our clinical trial that we can read out and we can emphasize for the patient's value.

The median PFS of course is one of many things to look at I think the hazard ratio is one thing to look at our if we would assume your question about being similar hazard ratios than there are daresbury, let's say, there's a lot of clutter, let's say differentiating elements in and in our clinical trial that we can read out and we can emphasize or the patients fail you.

Howard Robin: One thing, as we've shown in the PIVOT-02 data, is our very impressive CR rate. That's something that obviously is an early readout for potentially long-term benefits. And the CR rate, of course, provides benefit to a substantial number of patients but perhaps not half the patients. So it might not capture the median PFS, but it might capture a very significant minority of patients who have very long-term benefits. So that's one important differentiator that we will be looking at. And based on the safety data we have presented, that's another potentially very strong differentiator, specifically for epinivo, with a over 50% grade 3, 4 AE ratio.

One thing as we've shown in the pivotal two data is a very impressive CR rate.

That's something that obviously is a that's a.

A a early readout for potentially long term benefits and the CR rate of course provides a benefit to a substantial number of patients, but perhaps not have to patients. So it might not captured the median P. F antibodies might capture a very significant minority of patients who has very long term benefits.

That's one important differentiator that we will be looking at.

And based on the safety data, we have presented that that's another what we think is potentially very strong differentiator specifically for a P. Knievel with a over 50% grade three four E rate.

Operator: Thank you. Our next question comes from Bert Hazlitt from BTIG. Your line is open. Thanks, and thanks for taking the question, and thanks for the additional detail on the upcoming milestone. Just two quick ones I'm going to slide in. First of all, could you remind us again of any similarities in the patient population enrolled between phase two and phase three in the first line metastatic melanoma studies, and then secondly, unfortunately, as we know. The sanctions have been mostly financial against the Russian Federation, but not all of them.

Thank you.

Next question comes from Bert Hazlett from <unk>. Your line is open.

Thanks, and thanks for taking the question and thanks for the additional detail on the milestones upcoming.

Just two quick ones I've got a slide in first on could you remind us again of any stimulus.

Any differences or similarities in patient population enrolled between phase II and phase III in first line metastatic melanoma studies and then secondly, Unfortunately, there is a war on as we know the sanctions have been mostly financial against the Russian Federation, but not all of them you have some start some centers there do you foresee any challenges.

unknown: So you have some centers there. Do you foresee any challenges in accessing any of the data for any of your upcoming trials? Thanks. So I'm going to start with the first part of that question for Demetri related to the patients involved in phase 3 versus phase 2. And the second part of the study, I'll ask Howard to comment on with respect to the evolving situation. Sure, thank you for the question.

Accessing any of the data for any of your trials upcoming thanks.

So I'm going to start with the first part of that question for Dmitry related to the patients enrolled in the phase III versus the phase two and the second part of the Telia I'll ask Howard to comment on with respect to the evolving situation in Ukraine.

unknown: So until we have a full publication of our data set, the exact patient characteristics will not be known or disclosed. So the percentage of patients with certain characteristics we can't comment on right now. As you know, it's a blinded trial. Overall, the inclusion criteria are very similar.

Sure. Thank you for the question so until we have a full publication of our data set the exact patient characteristics, we will not be known or disclosed so the percentage of patients with certain characteristics. We can't comment on right now as you know, it's a blinded trial overall the inclusion criteria are.

unknown: And we've made sure that we have, let's say, a good representation of the different risk factors. And also, as we have talked about before, we stratify for a number of important risk factors to make sure that the patients with the different risk factors are distributed equally between the two arms. So we're confident that the phase three trial, which is a global phase three trial, will capture, let's say, the broad array of different prognostic and predictive factors for patients with metastatic melanoma.

Similar and we've made sure that we have let's say a good representation of the different risk factors and also as we have talked about before we stratify for a number of important risk factors to make sure that the patients with the different risk factors are distributed equally between the two arms and so we're confident that the.

Phase III trial, which is a global phase III trial will capture let's say the broad array of different prognostic and predictive factor for patients with metastatic melanoma.

unknown: Dmitry Howard, do you want to talk about the evolving situation in Ukraine? Yeah, of course. Obviously, the whole situation. Nektar does not have any vendors, testing labs, raw material supply chain, or clinical sites in Ukraine. So none of these studies were conducted there, and we don't anticipate any, you know, we've looked at this very carefully, of course, and it's an excellent question, but we don't anticipate any risk to database locks, any plans to analyze top-line data, or any of the planned study results for BEMPEG as a result of what's going on in the Ukraine-Russian conflict.

Thank you Dmitry Howard do you want to talk about the evolving situation in Ukraine.

Of course look obviously the whole situation is devastating to watch and our Hearts go out to the Ukrainian people in.

It's very difficult to call out what's going on I think we would all agree I can tell you that <unk> does not have any vendors testing labs raw material supply chain or clinical sites in the Ukraine. So none of these studies were conducted there and we don't anticipate any we've looked at this very carefully of course.

And it's an excellent question.

But we don't anticipate any risks database locks and he plans to analyze topline data.

And any planned study results for <unk> as a result of what's going on in there.

Ukraine Russian conflicts.

unknown: And we don't see any filing risks either at this point. We're obviously gonna continue to monitor this situation. We will determine if there is any problem, but at this point, there doesn't appear to be anything that puts these trials or the database locks at risk. And again, we have no sites in the Ukraine at all.

And we don't see any firewood risks either at this point, we're obviously going to continue to monitor this situation, we're going to we will determine.

If there isn't any problem, but at this point.

There doesn't appear to be anything that puts these trials are the database locks at risk and again.

We have no sites in the Ukraine at all.

unknown: I hope that answers your question. Thank you. Our next question comes from Mara Goldstein from Mizuho. Your line is open.

I hope that answers it for you.

unknown: Oh, great. Thanks for taking the time to answer the question. I wanted to ask about 358 and the decision to opt in, and what are the sort of potential timing and gating factors for that? And would it be, is the timeframe consistent with this year when you're expecting clinical data from, you know, potentially registrational studies? Thank you, Mara. I'm going to ask Gil to take that question. [inaudible] Yeah, Mara, so the way our collaboration is structured with Lilly, when they make the determination to go into phase three, you know, we have a certain amount of time to elect to co-develop and co-fund the phase three program up to 25%. And that entitles us to the highest tier of royalties, which Howard mentioned earlier is in the mid teens to low 20s, very quickly into the low 20s.

Thank you. Our next question from Mara Goldstein from Mizuho. Your line is open.

Oh, great. Thanks for taking the question I asked about 358.

And to opt in.

And what are the sort of potential timing on gating factors for that and would it be is a timeframe consistent with this year, where youre expecting clinical data from you know potentially Registrational studies.

Thank you Maher I'm going to ask Gil to take that question Gil.

So the way our collaboration that structure with Lilly.

When they made the determination to go in phase III, we have a certain amount of time too.

Elect to co develop and co fund the phase III program up to 25% and that entitles us to the highest tier of royalties, which as Howard mentioned earlier is in the mid teens to low twenties very quickly into the low twenty's and.

unknown: While we haven't crossed that bridge yet, I can't say as we look out, and we look at the size of these indications, and we look at the results that we've seen already for Nektar 358, which are extraordinarily encouraging, you know. We would expect to fund our portion to get the maximum. But of course, we'll have to make the decision at that time when Lilly begins to take different indications into phase three. Thank you. Our next question comes from Andy Shea from William Blair. Your line is open.

While we havent crossed that bridge, yet I can't say as we look out and when you look at the size of these indications and.

When we look at the results that we've seen already for Doctor 358, which are extraordinarily encouraging we would expect to fund our portion to get the maximum royalties, but of course, we'll have to make the decision at that time or when Lily begins to take different indications into phase III based on the phase two data.

Thank you.

Question comes from Andrew <unk> from William Blair. Your line is open.

unknown: Great. Thanks for taking my question. So I have a question for Dimitri.

Great. Thanks for taking my question. So I have a question for Dmitry Dmitry you mentioned the RCC trial in the second quarter that could potentially undergo this resizing based on the recommendation of the SMB I'm curious about how that decision will be made is that based on.

unknown: Dimitri, you mentioned the RCC trial in the second quarter that could potentially undergo this resizing based on the recommendation of the DSMB. I'm curious about how that decision will be made. Is it based on overall survival response rate? And also, are you looking at the entire population or specifically just in the intermediate high-risk population? The second part of my question is also kind of related to RCC.

On.

Overall survival response rate and also are you looking at the entire population or typically just in the intermediate high risk population is.

The second part of my question also kind of related to RCC, you mentioned about the 250 triple it.

unknown: You mentioned the 250 triplet study. Is that ongoing? I'm just curious about the status of that trial. Thank you.

30 is that ongoing just curious about the status of that.

Trial. Thank you.

Sure. Thanks for the question so to start with the second part of that is relatively easy and that trial is ongoing.

unknown: Thanks for the question. So, to start with the second part, that's relatively easy, yeah, that trial is ongoing, so that's on its way. We haven't given any guidance for data readout, but it's ongoing. The first part of your question, just to, let's say, emphasize for everyone, it's not a resizing of the trial, so it's not a sample size re-estimation, it's an event size re-estimation for OS events, and it's based on, let's say, modeling that has been provided to the DMC by our statistical group before the trial started to optimize the, let's say, event rate for survival in the intermediate and poor risk patients in the trial.

unknown: I hope that answers the question. Thank you, and I am showing no further questions from our phone line.

So that said that's on its way and we haven't given any guidance for data readout, but it's ongoing.

First part of your question, just just a let's say emphasize for everyone.

It's not a resizing of the trial. So it's not a sample size re estimation. It's an event size re estimation for OFC fence and it's based on let's say.

Our modeling that has been provided to the D. M C by our statistical group before the trial started.

To optimize Ste and lets say event rate for survival in the intermediate and poor risk patients in.

In the trial I hope it answers your question.

Thank you.

I'm showing no further questions from our call line I'd now like to turn the conference back over to Howard Robin for any closing remarks.

unknown: I'd now like to turn the conference back over to Howard Robin for any closing remarks. Well, thank you, everyone, and thank you for joining us. When you consider the range of therapeutic areas where we are working and the sheer breadth of our pipeline, I'm really very proud of our company that has built such a strong and extensive clinical pipeline from an immune science platform. And we have 17 clinical trials running in the area of immuno-oncology and immunology.

unknown: In each of these programs we're pursuing, BEMPEG, NECR255, NECR358, represents on their own a distinct value in our pipeline, and each addresses a significant patient population. Of course, we have additional research programs which are preparing for the..., in the areas of cancer and autosuggestion. I remember something important about them. IL-2 is a well-understood mechanism, and using our technology

Well. Thank you everyone. Thank you for joining us today and when you consider the range of therapeutic areas, where we are working and the sheer breadth of our pipeline.

I'm really very proud of our company is built such a strong and extensive clinical pipeline from a platform of the new science and we have 17 clinical trials running in the area of immuno oncology and immune.

Each of these programs, where we're pursuing Mpeg 255.

Represent on their own.

It is snick value in our pipeline and each address significant patient populations.

Of course, we have additional research programs with preparing for the preparing for the clinic.

In the areas of cancer and autoimmune disease, I remember something important about IL two.

<unk> two is a well understood mechanism.

And using our technology and we invested in much better IL two.

unknown: We invented a much better aisle. And that's why we're looking forward to the BEMPEG melanoma results in the very near future. So we're certainly approaching a busy and exciting time for Nektar. I would like to thank our employees for their efforts and their hard work. And I want to thank our shareholders for their continued support. And we look forward to providing you with updates on our progress in the very near future. So, please stay tuned.

And that's why we're looking forward to the been pegged melanoma results in the very near future.

So we're.

Certainly approaching a busy and exciting time for nectar I would like to thank our employees and their efforts and their hard work and I want to thank our shareholders for their continued support and we look forward to providing you with updates on our progress in the very near future. So please stay tuned thank you very much.

unknown: Thank you very much. Thank you. This concludes today's conference call. Thank you for your participation, and you may now disconnect. Everyone have a wonderful day.

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

[music].

No.