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Nektar Therapeutics (NASDAQ:NKTR) Q4 2018 Earnings Conference CallFeb. 28, 2019 5:00 p.m. ET
Contents: Prepared Remarks Questions and Answers Call Participants Prepared Remarks:
Operator
Good day, ladies and gentlemen, and welcome to the Nektar Therapeutics Q4 2018 financial results. [Operator instructions] As a reminder, this conference call may be recorded. I would now like to introduce your host for today's conference, Ms. Jennifer Ruddock, head of investor relations.
Ma'am, you may begin.
Jennifer Ruddock -- Head of Investor Relations
Thank you, Crystal. Good afternoon, everyone, and thank you for joining us this afternoon. With us are Howard Robin, our president and CEO; Gil Labrucherie, our chief financial officer; Steve Doberstein, our head of R&D; Dr. Jonathan Zalevsky, our CFO; and Dr.
Mary Tagliaferri, our CMO. On today's call, we expect to make forward-looking statements regarding our business, including the timing of future clinical trials and clinical trial results; clinical development plans, including the plans to start future clinical trials; the therapeutic potential of certain drugs and drug candidates as well as those of our partners; our financial guidance for 2019 and certain other statements regarding the future of our business. Because these forward-looking statements relate to the future, they are subject to inherent uncertainties and risks that are difficult to predict and many of which are outside of our control. Important risks and uncertainties are set forth in our Form 10-Q that was filed on November 8, 2018, and is available at www.sec.gov.
We undertake no obligation to update any of these statements whether as a result of new information, future developments or otherwise. A webcast of this call will be available on the IR page at Nektar's website at nektar.com. With that, I will now turn the call over to our President and CEO, Howard Robin. Howard?
Howard Robin -- President and Chief Executive Officer
Thank you, Jennifer, and thank you to everyone for joining us on the call today. On today's call, we'll review our planned milestones over the coming months, including the continued trial starts for the registrational program for NKTR-214, now known as bempegaldesleukin or bempeg; the additional trials with the other bempeg collaborators; new studies being initiated for NKTR-358 with our partner, Lilly; and the start of our first clinical trials with NKTR-255, our IL-15 agonist program and next I-O candidate. We will also provide our financial guidance for 2019. As you know, tomorrow, we are presenting early translational and gene expression data from the initial dose escalation patients in the reveal study of NKTR-262 plus bempeg at the 2019 ASCO SITC meeting in San Francisco.
For those of you who can't travel to San Francisco, we will host a call for investors on Friday afternoon at 3 p.m. Pacific Time with Dr. Adi Diab of MD Anderson following his oral presentation. So we look forward to speaking with many of you tomorrow.
So starting first with chronic pain and an update for NKTR-181. As we've stated in the past, we believe that a significant and necessary building block to addressing the opioid crisis is providing new pain medications that don't carry the same profiles as the existing opioid medications on the market. To this end, we remain confident that NKTR-181 can provide a step forward as part of the opioid crisis solution. We continue to work closely with the FDA during the review of NKTR-181 as we've done throughout its development.
This month, we received a notification from the FDA that the review period for NKTR-181 has been extended. Our new PDUFA date is now August 29, 2019. The FDA informed us that they extended the action date to allow time to review data from two additional preclinical abuse liability studies that Nektar conducted, which were first requested by the FDA early on in the review process. We completed these studies quickly, and the new data were submitted to the agency at the end of January.
The new preclinical data from these studies further support our abuse liability package in the NDA filing. When the studies were requested, we didn't anticipate that the FDA would require more time in the review cycle to incorporate these data into the NDA. However, the FDA indicated that the additional information was determined to constitute a major amendment to the NDA, resulting in an extension of the PDUFA goal date by three months. We remain very confident in our entire package supporting our NDA submission, and as I stated, we've been engaged in active dialogue with the FDA throughout the review process.
The FDA has informed us that they plan to hold an advisory committee meeting to review our NDA, however, the meeting date has not yet been set. With the changed PDUFA, we are currently preparing for an advisory committee meeting this summer. We have established a separate subsidiary company to commercialize NKTR-181 and are working on finalizing a structure with one or more capital partners to support the commercialization of this important molecule. Our goal is to complete this process before the potential approval of NKTR-181.
In the meantime, we're completing the production of launch inventory and conducting other prelaunch commercial readiness activities such as market access preparation and distribution agreements. We believe this will allow us to ensure that the commercial launch of NKTR-181 is optimized. We continue to be very excited about the future for NKTR-181 in its role on the treatment of chronic pain. Moving now to immuno-oncology.
We continue to execute on our strategy to develop a full pipeline of new potential medicines that address the key components of the immune cycle in order to restore immune surveillance and properly harness the body's immune system to fight cancer. Starting with bempeg and our collaboration with Bristol-Myers Squibb, which was established just one year ago, we now have a broad platform to rapidly develop this important IL-2 pathway molecule. In the fourth quarter of 2018, with our partner BMS, we initiated the first registrational trials for the bempeg and nivo doublet combination in first-line metastatic melanoma, renal cell carcinoma and bladder cancers. And we added a new expansion arm to PIVOT focused on enrolling second-line non-small cell lung cancer patients following treatment in relapse in first line with chemo and checkpoint therapy.
As you can see, we have made tremendous progress in less than a year. We recently presented exciting data from the ongoing bladder cancer cohort in the PIVOT-02 study at the ASCO GU meeting here in San Francisco. We believe these data are highly supportive of our registrational strategy in bladder cancer. Our first registrational study is under way and is an accelerated approval strategy in 165 patients who are not eligible for cisplatin therapies and who express low levels of PD-L1 in their tumors at baseline.
This indication represents a high unmet medical need as checkpoints are no longer used in these patients. Importantly, it allows us to capitalize on the unique mechanism of bempeg, specifically the conversion of PD-L1 non-expressing tumors to PD-L1 expressing tumors. You'll recall that in the PIVOT study, 70% of the baseline negative patients in bladder cancer cohort for which we have matching biopsy results converted to expressers of PD-L1 by the third week of treatment. As Dr.
Siefker-Radtke of MD Anderson highlighted on our call last week, the data represented at ASCO GU for bempeg and nivo clearly shows a significantly better ORR and CR rate than has been reported with single-agent checkpoint inhibitors in this patient population. And this is why we're so excited that our registrational trial in bladder cancer is already under way, and we expect it to be the first of our registrational trials to complete and read out. The projected readout from this study will be in the middle of 2020. As we stated earlier in the year, as data from additional PIVOT cohorts and other tumor types mature over the next 12 months, Nektar and Bristol are planning to present the datasets at various medical meetings, including tumor-specific conferences.
We're currently targeting several presentations of PIVOT data in 2019, including lung cancer data at this year's ESMO meeting. And Nektar and BMS are currently planning to submit data from the triple-negative breast cancer cohort for presentation at the quadruplet CRI meeting in September. And for renal cell carcinoma, we're targeting the 18th International Kidney Cancer Symposium in November. As you know, the joint development plan with Bristol includes about 20 registrational trials across multiple tumor types.
And so far, the first 10 of these traits in a joint development plan, including our accelerated approval strategy in bladder cancer, have been initiated or in the process of starting. And Mary will talk more about these in a moment. As we stated at JP Morgan, BMS and Nektar are also currently working on the design of the next wave of trials in lung, breast, gastric and colorectal cancers as well as carcinoma. The BMS and Nektar teams have been working very closely together on the program, and we've made tremendous progress over a short period of time in building out a comprehensive registrational strategy across the tumor types in this collaboration.
We recently announced another development collaboration for bempeg with Pfizer to develop various doublet and triplet combinations with bempeg and Pfizer and Merck Serono's anti-PD-L1 agent avelumab, Pfizer's PARP inhibitor and Pfizer and Astellas' anti-androgen agent. Pfizer and Nektar are currently working on the design of the Phase Ib/II study in head and neck cancer and castration-resistant prostate cancer. And the study will start in the second half of this year. As you know, Pfizer will serve as the sponsor of the study, and we will each retain ownership of our individual molecules.
We're very excited to work with Pfizer on this because of their expertise in head and neck and prostate cancers and because they also recognize the importance of the unique mechanism of bempeg in I-O, particularly, in patients with PD-L1 negative tumors. We also have a collaboration with Takeda to combine bempeg with Takeda's TAK-659, which is a dual SYK, FLT inhibitor in liquid tumors. We know that the three mechanisms together, IL-2, SYK and FLT, showed a dramatic effect in our preclinical model, so we're excited about the first study, which has already started and advanced in HL patients. Moving on to updates for NKTR-255, our IL-15 agonist cytokine, which we're putting into the clinic later this year.
We know that targeting the IL-15 pathway in addition to creating memory T cells strongly promotes the expansion activation and survival of natural killer cells, which is very important in a number of diseases, particularly in lymphomas where the mechanism could greatly enhance ADCC antibodies, such as daratumumab. We plan to file the IND in the middle of this year and initiate a Phase I trial of NKTR-255 in patients with multiple myeloma. We also have a collaboration with the Fred Hutchinson Cancer Center, looking at whether we can use NKTR-255 to enhance CAR-T persistence and improve overall responses following CAR-T. Fred Hutch is planning the first presentation of this preclinical data at ASCO this year.
In the fourth quarter of last year, we entered into a collaboration with Gilead to explore NKTR-255 with a number of different Gilead compounds in their portfolio in the area of virology. Gilead will initiate these preclinical studies this year and fund 100% of the costs of these studies. I'd like to move on to highlight the great progress we've made with our partner, Eli Lilly, on the development of NKTR-358. We have an ongoing Phase Ib multiple ascending dose study in lupus patients that is proceeding nicely through dose escalation.
Lilly and Nektar plan to present the first clinical data for NKTR-358 at UR this summer. The data will be from our completed single ascending dose study of NKTR-358 in healthy volunteers. In addition, Lilly is designing two new Phase Ib studies that will start this year in two new autoimmune indications. We're very excited about 358 emerging as a potential resolution therapeutic in the treatment of autoimmune disease.
Before I hand the call to Mary, I'd like to comment on the incredibly successful and productive year that we've had at Nektar that positions us with a deep clinical pipeline and also puts us in an exceptionally strong financial position as we start 2019 with over $1.9 billion in cash on our balance sheet. We signed a landmark collaboration with BMS that allowed us to execute on a full registrational program for bempeg with substantial operational and financial support from our partner. Additional collaborations with Takeda and Pfizer for NKTR-214, and with Gilead for NKTR-255 highlight the science and innovation within Nektar that is being recognized by our new partners. We advanced two new clinical candidates in I-O, NKTR-265 and NKTR -- NKTR-262 and NKTR-255.
NKTR-358 also moved forward rapidly and positions us in the field of immunology with a strong partner in Eli Lilly. So I'm exceptionally proud of our team, their hard work to continue to advance our novel therapies in I-O, immunology and pain. And with that, I'd like to turn the call over to Mary to review our clinical programs.
Mary Tagliaferri -- Chief Medical Officer
Thank you, Howard. I'd like to start with a review of our plans for the first set of registrational trials with our partner, BMS. As you know, our strategy with BMS is to prioritize and secure as many potential approvals in early and first-line settings across multiple solid tumor types to establish NKTR-214 plus OPDIVO as the standard of care. To that end, our first 10 trials, as we've previously disclosed, will be in melanoma, renal cell carcinoma, urothelial carcinoma and non-small cell lung cancer.
First, in melanoma, we are enrolling 760 patients with advanced or metastatic melanoma into our Phase III trial of bempeg plus nivo. Patients will be stratified by PD-L1 status, stage of disease and BRAF status. The primary endpoints are PFS and OS with the projected 22-month time line for the final PFS analysis. This pivotal study in melanoma is designed to secure the doublet of bempeg plus nivo as the first-line I-O standard of care, and we're very excited that this study is well under way.
In renal cell carcinoma, Bristol-Myers and Nektar are planning to launch multiple registrational trials in advanced patients, which will include separate trials to evaluate the doublet and triplet regimens of bempeg plus nivo and also bempeg plus nivo and ipilimumab in this indication. The first Phase III trial in RCC, PIVOT-09, is already under way in first-line metastatic patients and is evaluating bempeg plus nivo versus a TKI of physician's choice, either sunitinib or cabozantinib in approximately 600 patients with intermediate or poor risk classification. Patients will be randomized 1:1 and will be stratified in the trial based upon multiple factors, including PD-L1 status, IMDC risk score and choice of TKI agent. The primary endpoint of the study is overall survival, and we estimate the time to first interim analysis on the primary endpoint is 27 months.
The second Phase III trial in RCC being initiated shortly will evaluate the triplet combination of bempeg, nivo and ipi compared to the nivo and ipi doublet in patients with previously untreated metastatic RCC. The study will enroll approximately 800 patients with intermediate or poor IMDC risk scores, and we'll also stratify by PD-L1 status. The third registrational trial in RCC will evaluate a TKI-inclusive regimen with bempeg plus nivo and a TKI compared to nivo plus a TKI in first-line patients with all IMDC risk levels. The study will include a safety read in to determine the TKI combination dose for the second part of the study, which will then evaluate ORR, PFS and OS.
In bladder, we are planning a registrational program to gain approvals in first-line metastatic bladder cancer and other settings. As we just reviewed on our call with Dr. Siefker-Radtke at ASCO GU, cis-ineligible bladder cancer patients are a population that are in need of better therapeutic options. For those patients whose tumors are low expressers of PD-L1 at baseline, for whom single-agent checkpoint inhibitors are no longer the preferred standard of care, the only option is to be treated with a gem/carbo chemo regimen.
As Howard stated earlier, we just showed that treatment with bempeg plus nivo converted 70% of the baseline negative PD-L1 expressers to PD-L1 positive expressers in our UC cohort in PIVOT-02. We also observed this conversion with NKTR-214 monotherapy in the first Phase I trial of bempeg. With this in mind, our first registrational trial in bladder cancer, PIVOT-10, is a potential accelerated approval study that is already under way, and is being conducted in cisplatin-ineligible patients that have a low baseline PD-L1 expression or less than 10 combined positive score using the 22C3 pharmDx diagnostic. The trial will enroll approximately 110 patients on the bempeg plus nivo arm and approximately 55 patients to a chemo reference arm of gem/carbo.
Patients will be able to cross over to bempeg plus nivo after progressing on the gem/carbo reference arm. We will also collect specific PD-L1 conversion data from patients in the study to support our data package as this conversion is a unique and differentiating feature observed with the mechanism of bempeg and nivo. The next bladder cancer trial broadens our development strategy to earlier stage disease and can also serve as the confirmatory trial for the PIVOT-10 potential accelerated approval study. This second trial will enroll patients with muscle invasive bladder cancer who are also cisplatin ineligible, and we will stratify by PD-L1 status and disease classification.
During an induction pre-surgical phase, 540 patients will be enrolled and randomized 1:1:1 to receive three cycles of bempeg plus nivo, nivo or no treatment. All patients will undergo surgery and then go on to receive bempeg plus nivo or nivo only for observation in the adjuvant setting. The primary endpoint will be event-free survival. Finally, we are planning to initiate a third trial in metastatic bladder cancer that we will include first-line metastatic patients who are both cis eligible and cis ineligible.
Moving on to non-small cell lung cancer. I'll first talk about the PIVOT expansion in second-line non-small cell lung cancer, which is currently under way. As Howard stated earlier, we are enrolling a 100-patient cohort in PIVOT that include only second-line relapse non-small cell lung cancer patients who received a checkpoint inhibitor combined with chemotherapy in first-line. The original design of PIVOT envisions that an expansion arm in an appropriate patient population could potentially serve as an accelerated registrational pathway.
As this particular patient population in lung cancer has limited options once their disease has progressed following a checkpoint inhibitor with chemotherapy in first line, we believe this cohort could also allow us to pursue an accelerated approval pathway. With this strategy, we are also planning a trial in second, third-line non-small cell lung cancer that could serve as a potential confirmatory trial and would compare NKTR-214, nivo and chemotherapy to chemotherapy alone. In addition, BMS and Nektar are planning a first-line non-small cell lung cancer study with the doublet of bempeg plus nivo compared to the pembrolizumab single agent, which provides a chemo sparing regiment approach. We are also designing a second study in first-line non-small cell lung cancer, which combines the doublet of bempeg plus nivo with chemotherapy.
To that end, we have already incorporated several dose finding cohorts into the PIVOT-02 that are evaluating various chemotherapy regimens with the doublet in patients with non-small cell lung cancer. As Howard mentioned, we are also finalizing our clinical designs with Pfizer in prostate and head and neck cancer. We are very excited to work with the Pfizer oncology group to explore the potential of combining multiple mechanisms in these two tumor settingsUnder the new clinical collaboration, Pfizer oncology will conduct the planned Phase Ib/II clinical trial that will include multiple patient arms. One will be a Phase II cohort to evaluate bempeg plus avelumab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck, who have not received any prior systemic treatment for metastatic disease.
Enrollment will include patients with both PD-L1 negative and PD-L1 positive baseline tumors. The second and third cohort to the study will feature 1b dose escalation followed by a Phase II component to evaluate bempeg plus avelumab combined with either talazoparib or with enzalutamide in patients with metastatic CRPC who have progressed on one or more prior regimens. Cohorts will include 20 to 40 patients, and we will measure clinical success based on the specific combinations and reference outcomes in the various settings being investigated in the study. As Howard also communicated, bempeg is being evaluated with Takeda's oral dual SYK, FLT inhibitor known as TAK-659 in a Phase I/II clinical trial in non-Hodgkin lymphoma.
Since bempeg and TAK-659 target different cell populations, the two compounds provide unique nonoverlapping and highly complementary mechanism. As the first trial with Bempeg in a liquid tumor setting, the study provides a strategic opportunity for us to expand bempeg's development in this area. The trial's enrolling patients who are relapsed or refractory to at least two prior lines of therapy but no more than three prior treatments. With that clinical update, I'd like to hand the call to Gil.
Gil Labrucherie -- Chief Financial Officer
Thank you, Mary, and good afternoon, everyone. I will start with a brief review of highlights from our fourth-quarter and full-year 2018 financial results, and then I will review our 2019 financial guidance. We ended 2018 with $1.9 billion of cash and investments. Revenue for the fourth quarter ended December 31, 2018, was $39.8 million as compared to $95.5 million in the fourth quarter of 2017.
Revenue totaled $1.2 billion for the year ended December 31, 2018, compared to $307.7 million for the 12 months ended December 31, 2017. 2018 revenue included the recognition of $1.06 billion of license revenue as a result of the NKTR-214 Bristol-Myers Squibb collaboration. 2017 included the recognition of $130.1 million of license and collaboration revenue as a result of the NKTR-358 Eli Lilly collaboration. R&D expense in the fourth quarter of 2018 was $108.9 million as compared to $81.4 million in the fourth quarter of 2017.
R&D expense totaled $399.5 million in 2018 as compared to $268.5 million in 2017. Our R&D expense is accounted for net of BMS' share of bempeg development costs. R&D expense increased primarily as a result of advancing and expanding clinical development of bempeg, NKTR-262, NKTR-358, and IND-enabling activities for NKTR-255. 2018 R&D expense also included a significant expansion of manufacturing activity to supply sufficient inventory of bempeg to support the broad clinical development program with BMS, other collaboration programs as well as our combination program with NKTR-262.
G&A expense was $23.8 million in the fourth quarter and $81.4 million for the year ended December 31, 2018, as compared to $12.3 million and $52.4 million in the fourth quarter and the full year of 2017. G&A expense increased in 2018 compared to 2017 primarily due to an increase in noncash stock compensation expense. For the year ended December 31, 2018, we recognized net income of $681.3 million or $3.78 diluted earnings per share as compared to a net loss of $96.7 million or 62% basic and diluted net loss per share in 2017. Now let's turn to our 2019 financial guidance.
Starting with our cash position. We expect to end 2019 with approximately $1.5 billion with a receivable balance of approximately $65 million to $75 million due from BMS at the end of 2019 as a result of the annual funding cap. As a reminder, our collaboration with BMS includes a $125 million annual cash funding obligation cap for joint development activities prior to the commercialization of bempeg. To the extent this occurs in the fourth quarter, the collaboration expenses incurred by us in excess of the cap will be a receivable at the end of the year and reimbursed by BMS in Q1 of 2020.
We project that we will reach the R&D reimbursement cap of $125 million during 2019 and anticipate a receivable balance of approximately $65 million to $75 million due from BMS at the end of 2019. GAAP revenue is expected to be between $100 million and $110 million in 2019, which we expect to be fairly ratable over the four quarters of 2019. 2019 GAAP revenue includes approximately $40 million to $45 million of royalty revenue from ADYNOVATE and MOVANTIK and $30 million to $32 million of noncash royalty revenue related to the CIMZIA and MIRCERA royalty monetization. We anticipate 2019 GAAP R&D expense will range between $500 million and $525 million, which includes approximately $80 million of noncash depreciation and stock compensation expense.
We expect to incur R&D expense on a fairly ratable basis over the four quarters of 2019. As a reminder, our GAAP R&D guidance includes amounts we expect to incur beyond the R&D joint development funding cap of $125 million, which is reimbursed to us by BMS quarterly in arrears. There are a few key points that I want to highlight in our 2019 R&D investment plan. A significant amount of our R&D budget represents our portion of the investment in the broad a registrational development plan for bempeg that we are executing with our partner BMS.
We have multiple registrational studies under way with many more registrational studies planned. Nektar's share of joint development planned costs is approximately 33% of clinical study costs and 65% of bempeg manufacturing and supply costs. In addition, we are also making important investments in bempeg in combination with other mechanisms of action under our collaborations, including Takeda, Pfizer, BioXcel and Vaccibody. We expect our bempeg manufacturing investment to be significant in 2019 as we build drug supply inventory to support the multiyear clinical development plan for bempeg.
As a reminder, BMS generally shares in approximately 35% of bempeg manufacturing and supply costs. For a NKTR-358, we expect to complete the Phase Ib multiple ascending dose study in lupus in the second half of this year. Eli Lilly is planning to conduct two new Phase Ib studies in autoimmune conditions and will lead the clinical development program from Phase II through approval. Nektar's share of Eli Lilly's Phase Ib and Phase II costs will be 25%.
We expect to complete the Phase I clinical study for NKTR-262 in combination with bempeg this year with plans to initiate a Phase II study later this year. For NKTR-255, we plan to file an IND in the middle of the year and initiate the first phase I clinical study for this program. For NKTR-181, we continue to invest in activities necessary to support regulatory approval and commercial readiness to launch NKTR-181 following a potential approval later this year. In addition, we will complete the manufacture of NKTR-181 commercial launch supplies that are included in our R&D expense and not capitalized into inventory prior to the potential NKTR-181 approval.
G&A expense for 2019 is projected to be between $110 million and $120 million, which includes approximately $35 million of noncash depreciation and stock compensation expense. In 2019, G&A expense includes an initial investment in commercialization and marketing costs for NKTR-181 in preparation for commercial launch following potential approval later this year. For 2019, interest expense will be approximately $22 million and interest income will be approximately $40 million. We expect to recognize approximately $24 million in noncash interest expense related to the CIMZIA and MIRCERA royalty monetization.
As I stated earlier, we plan to end 2019 with approximately $1.5 billion in cash and investments together with a receivable from BMS for development cost reimbursement of approximately $65 million to $75 million. And with that, operator, I'll open the call for questions.
Questions and Answers:
Operator
[Operator instructions] And our first question comes from Jessica Fye from JP Morgan. Your line is open.
Jessica Fye -- J.P. Morgan -- Analyst
Hey, Guys. Good evening. Thanks for taking my questions. I appreciate the additional detail on upcoming data releases.
I just want to make sure I caught when we should expect the next 214 clinical updates besides the data coming tomorrow. Are there any clinical updates before the fall? I think a number of the conferences you mentioned were kind of in September and beyond. Should we think of something potentially coming at ASCO? Sorry if I missed that. And then a couple just on ongoing trials.
Is there any way you could comment on the enrollment progress with the melanoma pivotal study? And I'm also curious about the -- how enrollment's going in that 100-patient second-line cohort and when we might think about seeing that data. I think you mentioned back in November that it might take about a year to enroll that cohort. Is that still your expectation?
Mary Tagliaferri -- Chief Medical Officer
Jessica, it's Mary. Thank you for the questions. So we haven't made any announcements about any presentations from PIVOT-02 prior to the fall. And as Howard mentioned, we have plans to present the lung data at ESMO this year, which will be in Barcelona in September.
And then also, we plan to present data from our triple-negative breast cancer cohort at the quadruplet CRI meeting in Paris in September. And then finally, we're targeting the 18th International Kidney Cancer Symposium, which is in Miami this year in November. In terms of our registrational trials, these are all on schedule, and I think we've shared with you previously that for the melanoma Phase III, the progression-free survival primary endpoint, we have a readout in approximately 22 months after the first patient was in. And our first patient was in the study in September of this year.
And then in terms of the bladder Phase II study in PD-L1 negative, cisplatin-ineligible patients, which we shared with you is our potential study for accelerated approval, we plan to have data for that study in the summer of 2020. And then in PIVOT-02, as you asked, we have the 100-patient non-small cell lung cancer cohort, and we expect to have data in the second half of 2020.
Jessica Fye -- J.P. Morgan -- Analyst
Awesome. Thank you.
Mary Tagliaferri -- Chief Medical Officer
Thank you, Jess.
Operator
Our next question comes from Chris Shibutani from Cowen. Your line is open.
Chris Shibutani -- Cowen and Company -- Analyst
Thanks very much. Appreciate all the updates, including some of the partnerships that you have outside of Bristol. The relationship that you have with the Pfizer, it's interesting that we're seeing more data develop in the prostate data in general. Can you remind us how restrictive that relationship is with Pfizer? Are you, for instance, able to do any other combinations? Are you prevented from combining with any other I-O agents?
Howard Robin -- President and Chief Executive Officer
Well, yes, we -- thanks for the question, Chris. Look, we're free to work outside of the BMS collaboration with any company as long as it is not -- as long as the clinical studies and the indications are not -- do not fall within the BMS contract. Now head and neck cancer and prostate cancer do not fall within the BMS contract, and consequently, we're free to work with anyone we like.
Chris Shibutani -- Cowen and Company -- Analyst
And so you're able to do that with Pfizer. And then are you still able to do any work within prostate or head or neck with someone other than Pfizer?
Howard Robin -- President and Chief Executive Officer
Good question. That's right. And yes, we are. The relationship with Pfizer is not exclusive, so we can work in prostate and head and neck with other companies as well.
Chris Shibutani -- Cowen and Company -- Analyst
OK. And then we look forward to the lung data coming up at ESMO in the fall. Way back when there was some initial work there with them with pembro in the PROPEL study, is there a thought to being able to share some component of that data at some point in the future?
Mary Tagliaferri -- Chief Medical Officer
Chris, it's Mary. We definitely -- as you know, some of the cohorts in the PROPEL study did change. The standard of care changed. And we do anticipate in the second half of this year to have data from the PROPEL study.
Chris Shibutani -- Cowen and Company -- Analyst
And then, Gil, in terms of the accounting for the subsidiary that you described for the pain group, will that be a distinct breakout separate from this guidance? Are you going to have that dependent somewhat based upon what the regulatory process happens with 181? Can you just help us think about that as we're looking at our models in the year ahead?
Gil Labrucherie -- Chief Financial Officer
Yes, Chris, so it'll be a wholly owned subsidiary that we'll consolidate the financials. So we probably will -- we will include some segment information on the subsidiary as we begin to account for it separately.
Chris Shibutani -- Cowen and Company -- Analyst
Great. Thanks very much.
Operator
Thank you. Our next question comes from Paul Choi from Goldman Sachs. Your line is open.
Paul Choi -- Goldman Sachs -- Analyst
Hi, thanks for taking our questions. I have two clinical trial design questions for Mary. First just regard to RCC. Just given the slew of data in the past two months and the fact that pembrolizumab, axitinib combination have PDUFA coming up here in June, how are you thinking about comparator agents for some of the future trials that you plan versus using a TKI monotherapy in the front line? And then second, with respect to planning for the lung trial, just the rate limiting step here, the potential label for pembrolizumab that decision that's coming up in the near term, are you waiting to see what updates you -- with regards to the data at ESMO?
Mary Tagliaferri -- Chief Medical Officer
Thank you. So we spend a lot of time with GU oncologists, and there is not one unified consensus about how to treat a first-line patient. Some patients prefer to treat patients with a pure I-O regimen and then save the TKI for second line if their patients progress, whereas other people prefer to move forward with the combination of a checkpoint inhibitor with a TKI. Had a really interesting conversation with one physician who said, the median PFS with pembro plus axitinib was 15 months, and with that comes a lot of toxicity.
He said in contrast, "I could treat my patient with a single-agent TKI, have a median progression-free survival of around 9 or 10 months and then treat with a single-agent checkpoint inhibitor. And that patient would have a median progression-free survival of five to six months. And at the end of sequential treatment, my patient with less toxicity would end up around the same place of progression." And so people have various mindsets about how the front-line patient should be treated. And to that end, we've created a very broad clinical development strategy that will allow patients to be treated with a pure I-O regimen versus TKI plus an I-O combination.
And then in terms of the lung cancer trials, and you raised a really great point, nobody knows yet how the FDA is going to perceive the KEYNOTE-042 data and if pembrolizumab will have an expanded label to include not only the greater than 50% patients who have PD-L1 positive disease at baseline but will they approve single-agent pembro for the 1% to 49% population. And certainly, we will modify our strategy based on what is the current standard of care. Today, our plan is to compare to pembrolizumab in the greater than 50% population, where that is monotherapy as standard of care only in the one top tercile patients who express PD-L1 positive disease at baseline. Thank you for your questions.
Operator
Thank you. Our next question comes from George Farmer from BMO Capital Markets. Your line is open.
George Farmer -- BMO Capital Markets -- Analyst
Hi, thanks for taking my questions. And yes, thank you for all the update on the progress. I have another question about RCC in the phase -- in your Phase III study. On ClinicalTrials.gov, it also says there's a co-primary endpoint of overall response.
I'm wondering if that's still the case. And why not include PFS as a primary as a lot of these other trials have also done?
Mary Tagliaferri -- Chief Medical Officer
So in terms of ORR, we only allocate a small amount of alpha, and that allows us to include ORR in our label. And then in terms of overall survival, we believe looking at the CheckMate 214 data that we can achieve an overall survival endpoint at about 27 months. And if you look closely at the CheckMate 214 data, you'll see that when you look at the PD-L1 positive patients versus the PD-L1 negative patients, you can see that the progression-free survival hazard ratio for those patients with PD-L1 positive disease actually had a hazard ratio of 1. And so we actually believe that moving forward and allocating the largest amount of our alpha to the definitive endpoint of overall survival provides the highest probability of technical success and also, of course, really is the endpoint that's the most important to patients.
George Farmer -- BMO Capital Markets -- Analyst
OK. And then on 181, can you describe a little bit on your -- of what sort of pre-commercial activities you're engaging in? Do you expect to actually launch this drug right when you receive approval? Or is there anything else that needs to happen before you can do that?
Howard Robin -- President and Chief Executive Officer
I think we're -- I think the most important thing we're doing now in addition to building sufficient inventory for product launch is working with payer engagement and making sure that we have that well squared away as well as setting up the appropriate distribution channels. So we have to -- the DEA scheduling typically can take a couple months after approval, so we have to, of course, wait for that. But in the meantime, the process of getting payer engagement done, making sure that we -- that the people in the appropriate communities understand what NKTR-181 is and making sure that we have those distribution channels set up is what we're working on currently.
George Farmer -- BMO Capital Markets -- Analyst
OK. Thanks very much.
Operator
Thank you. Our next question comes from Alexander Duncan from Piper Jaffray. Your line is open.
Alexander Duncan -- Piper Jaffray -- Analyst
Hi, good evening. Thanks for the questions. Based on evidence in the cell therapy space, IL-15 is associated with many positive characteristics for immune cell activity. So how are you going to demonstrate the value of 255 beyond the planned presentation at AACR? And what are your intention for significant clinical collaboration with players in the cell therapy space to extract full value out of this asset?
Jonathan Zalevsky -- Chief Financial Officer
This is Jonathan Zalevsky. So -- yes, so first and foremost, the collaboration with colleagues at the Fred Hutch Cancer Center up in Seattle is a very important component of how we're aiming to develop NKTR-255. There, we're working closely with Stan Riddell and Cameron Turtle, who are some of the original founders of the field. And we're conducting studies there, demonstrating the effect of NKTR-255 on maintaining the persistence of CAR-T cells, also maintaining their immunological active states and then controlling some of the dynamics that really govern how well they can maintain an anti-tumor attack in these preclinical models.
And then these models are exactly the kind of studies that we do to inform us how we move into the early clinical studies. And so there, our long-term plans are to evaluate NKTR-255 in the setting CAR-T cell therapy, where we can use it to potentiate the overall effectiveness of CAR-T.
Operator
Our next question comes from Andy Hsieh from William Blair. Your line is open.
Andy Hsieh -- William Blair and Company -- Analyst
Thanks for taking my question. So one follow-up for JZ. So in terms of the CAR-T IL-15 combination, are you administering IL-15 during the expansion phase ex vivo? Or it will be administered concurrently to the patient?
Jonathan Zalevsky -- Chief Financial Officer
Yes. Well, great question. So first off, the studies that we're conducting now are preclinical studies. And there, our intention, which is what we're modeling ultimately for the clinic is to use NKTR-255 after or along with CAR-T administration.
So our aim is not to use it while you're culturing the cells or doing any of the transductions or so in the normal sort of CAR-T protocol. That stays as is. Our goal is to use IL-15 to maintain the activity, the function and the tumor killing capacity of the CAR-T after they're administered to the patient.
Andy Hsieh -- William Blair and Company -- Analyst
Interesting, OK. So it's basically not induction but more of a maintenance dosing throughout the treatment duration.
Jonathan Zalevsky -- Chief Financial Officer
Yes, one of the ways you could think about it is that we've seen that in patients that undertake CAR-T treatment. The levels of IL-15, you can start to see those change even during the conditioning regimen but particularly as the levels of IL-15 maintain. We tend to see a correlation in patients that have higher and higher levels of circulating IL-15. They tend to have a better response to the CAR-T administration and the persistence and longevity and the overall efficacy of the CAR-T that was given to those patients.
So what we're trying to do is to use 255 to completely recapitulate that biology and then give the patient that full maximum benefit that the CAR-T can bring to them.
Andy Hsieh -- William Blair and Company -- Analyst
OK. And in terms of UC, I know you guys have talked about this before at ASCO GU, but just educate us on how -- just from a histological or biology perspective, how different is metastatic UC versus muscle invasive? And the reason is because I just want to get some clarification in terms of -- from FDA's perspective, is -- are those two histologies close enough that would allow you to use that as a confirmation for the accelerated approval.
Mary Tagliaferri -- Chief Medical Officer
Yes. So prior to going to ASCO GU, we had an opportunity to have a face-to-face meeting with the FDA, and we did lay out our plan for potential accelerated approval with the study of 165 patients. And we did -- we were able to have a discussion about how to get to a potential accelerated approval should the benefit and risks of the doublet be superior to standard of care. And during that meeting, we also had the opportunity to talk to the agency about our confirmatory trial.
And because that study in muscle invasive bladder cancer will be conducted in patients who are cisplatin ineligible, the agency did say that that could serve as our confirmatory trial with an event-free survival endpoint.
Andy Hsieh -- William Blair and Company -- Analyst
OK. Cool. Got it. Thank you very much.
Operator
Thank you. Our next question comes from Difei Yang with Mizuho Securities. Your line is open.
Unknown speaker
Good afternoon, guys. This is Alex actually on for Difei. I had one on NKTR-262 plus 214 on the combo. When you're looking here at patients with metastatic cancer, how do you decide where to inject 262? And as part of the protocol, can you inject in more than one lesion?
Jonathan Zalevsky -- Chief Financial Officer
Yes, sure. This is JZ. So the way the protocol is designed, we permit NKTR-262 to only be injected to nontarget lesions. And so this is a very important component of the design because as you know by the normal RECIST scoring criteria, the radiologist will assign target lesions at the screening when the patient's first enrolled into the trial.
And those are the tumors that are going to be measured by their dimensions overall for assessment of efficacy as the trial concludes. In addition, we not only require these target lesions. We require that all patients have at least one and preferably more than one nontarget lesions. Those nontarget lesions have to be between 20 and 90 millimeters in size, and those are what are injected by the interventional radiologist.
And then we'd like to have more than one of those lesions because, in some patients, we can sample by biopsy, both injected and non-injected nontarget lesions. And then in terms of the number of lesions that are permitted to be injected, the radiologist is allowed to inject up to two nontarget lesions per occasion of administration of 262, and that's given once every three weeks on a Q3-week cycle.
Unknown speaker
OK. Great. Thank you very much.
Operator
[Operator instructions] And our next question comes from Asthika Goonewardene from Bloomberg Intelligence. Your line is open.
Asthika Goonewardene -- Bloomberg Intelligence -- Analyst
Hi, guys. Thanks for taking my questions. I have a small flurry of them if you don't mind. First off, with the second-line non-small cell lung study that you started, could you tell me, are you recruiting squamous as well as non-squamous patients? And then are you also considering PD-L1 high patients who might have had single-agent PD-1 in the first-line setting?
Mary Tagliaferri -- Chief Medical Officer
Yes, this is Mary. Thank you for your question. So in the second-line non-small cell lung cancer study, we will allow both patients who have squamous and non-squamous cell carcinoma. We -- you have to have had a checkpoint inhibitor plus chemotherapy for that cohort.
And these patients had to have a stable disease for 120 days in order to be enrolled to this cohort.
Asthika Goonewardene -- Bloomberg Intelligence -- Analyst
OK. And then what's the endpoint on this study, please, Mary?
Mary Tagliaferri -- Chief Medical Officer
Yes. So the way we've designed this trial is to show superiority to standard of care. And as you probably know, standard of care in second line would be docetaxel, and the objective response rate with docetaxel is roughly 9%. And so you can imagine, if you could double the response rate, you would really show significant benefit over standard of care.
Asthika Goonewardene -- Bloomberg Intelligence -- Analyst
Right. OK, yes, that was exactly what I was going at because I remember sitravatinib plus PD-1 had a response rate of 29%, and the FDA still told them to go into a confirmatory Phase III study. So I was just wondering about your thoughts about that.
Mary Tagliaferri -- Chief Medical Officer
Yes. In our entire program, we've had the good fortune to have a number of conversations with the FDA, and we certainly had a conversation with the FDA about the use of PIVOT-02 for one potential accelerated approval. This is always an ongoing discussion with the agency. And again, you have to show superiority to all available therapies at the time of the readout of your data.
Just one other point I just wanted to add too, we also have and we shared this on this call that we're planning a confirmatory trial in second and third-line non-small cell lung cancer. In that trial specifically, we will be looking at NKTR-214, nivo plus chemotherapy versus chemotherapy.
Asthika Goonewardene -- Bloomberg Intelligence -- Analyst
Brilliant. OK. Thank you for that. Then just to shift gears really quick to the bladder cancer, that first-line PD-L1 negative, has the FDA agreed to use the gem/carbo arm to potentially give you a second-line indication in this setting?
Mary Tagliaferri -- Chief Medical Officer
Yes. So just to let you know, this is PD-L1 low population. And that's the patient population that the FDA has said when you treat with monotherapy checkpoint inhibitor such as atezolizumab or pembrolizumab that you don't see an overall survival benefit compared to the gemcitabine plus carboplatin. In this study, we are going to be focusing exclusively on the cis-ineligible PD-L1 low population.
And as you may be aware, that's actually 70% of the cis-ineligible patients. And cis-ineligible, as you may know, in first-line bladder cancer study is 50% of the population. We would be going for an approval in the PD-L1 low 70% of those patients who are cis-ineligible with that study.
Asthika Goonewardene -- Bloomberg Intelligence -- Analyst
Yes. Sorry but -- you have two arms in that study. One is going to be with bempeg plus nivo, and then you have the gem/carbo arm as well. But you're going to put patients on gem/carbo onto bempeg/nivo on progression, right?
Mary Tagliaferri -- Chief Medical Officer
Yes, that's correct. So in that situation, we will really have to look at an overall survival endpoint, or you can look at what a third-line ORR would be and look at that patient population of about 55 patients. And we could potentially allow for an accelerated approval in benchmarking to third-line response rates for patients and analyzing what our response rate is with the doublet.
Asthika Goonewardene -- Bloomberg Intelligence -- Analyst
OK. Last one, and on the first-line RCC bempeg, nivo versus TKI, how are you randomizing that? Is it 1:1? I'm just trying to understand how you will show a statistically robust data versus specifically cabo in your subgroup analysis given that that's the superior agent versus sunitinib?
Mary Tagliaferri -- Chief Medical Officer
Yes. So we are going to be randomizing 1:1. And I think if you actually look at the progression-free survival of cabo in the CABOSUN trial, actually, the -- it performed similar to sunitinib in the CheckMate 214 study. And so we've designed our study to mimic CheckMate 214.
And so we believe that if cabo performs the way it did in CABOSUN, it'll be similar to sunitinib of CheckMate 214, and therefore, we feel like we have accounted for that. Our randomization scheme is 1:1 for the 600 patients, so we'll have 300 patients in each arm. And of course, we will stratify by patients who receive cabo versus sunitinib.
Asthika Goonewardene -- Bloomberg Intelligence -- Analyst
Great. Thank you so much for all the detail. Looking forward to a fun year with you guys.
Mary Tagliaferri -- Chief Medical Officer
Thank you.
Operator
Thank you. And that does conclude our question-and-answer session for today's conference. I'd now like to turn the call back over to Howard Robin for any closing remarks.
Howard Robin -- President and Chief Executive Officer
Well, thank you, everyone, for joining us today. Look, we've had a great year in 2018. We have an exceptionally broad and exciting I-O pipeline. And we have an incredible number of shots on goal.
So we're very excited about that. And along with that comes some pretty impressive financial strengths. So for all of this, I want to thank our employees for their hard work and dedication, and I think you'll see a lot of good results from Nektar this year. So thank you for joining us.
Operator
[Operator signoff]
Duration: 58 minutes
Call Participants:
Jennifer Ruddock -- Head of Investor Relations
Howard Robin -- President and Chief Executive Officer
Mary Tagliaferri -- Chief Medical Officer
Gil Labrucherie -- Chief Financial Officer
Jessica Fye -- J.P. Morgan -- Analyst
Chris Shibutani -- Cowen and Company -- Analyst
Paul Choi -- Goldman Sachs -- Analyst
George Farmer -- BMO Capital Markets -- Analyst
Alexander Duncan -- Piper Jaffray -- Analyst
Jonathan Zalevsky -- Chief Financial Officer
Andy Hsieh -- William Blair and Company -- Analyst
Asthika Goonewardene -- Bloomberg Intelligence -- Analyst
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