Q3 2019 Earnings Call
Ladies and gentlemen, thank you for standing by and welcome to the Nektar Therapeutics third quarter 2019 financial results Conference call.
Operator: Ladies and gentlemen, thank you for standing by, and welcome to the Nektar Therapeutics 3rd Quarter 2019 Financial Results Conference Call. At this time, all lines are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star then 1 on your telephone. Please be advised that today's conference may be recorded. If you require any further assistance, please press star then zero. I would now like to hand the conference over to your speaker today, Ms. Jennifer Ruddock, Head of Investor Relations. Madam, you may begin.
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I like to hand, the conference over to your speaker today, Ms., Jennifer ready head of Investor Relations Ma'am you may begin.
Thank you Crystal.
Jennifer Ruddock: Thank you, Crystal. Good afternoon, everyone, and thank you for joining us today.
Good afternoon, everyone and thank you for joining us today with us or Howard Robin, our president and CEO .
Jennifer Ruddock: With us on today's call are Howard Robin, our President and CEO, Gil Labroucherie, our COO and CFO, and Dr. Jonathan Zalevsky, our Head of R&D. During today's call, we expect to make forward-looking statements regarding our business, including clinical trial results, timing and plans for future clinical trials, timing and plans for future clinical data presentations at medical meetings, and the therapeutic potential of our drug candidates. Outcomes and Plans for Health Authority Regulatory Actions and Decisions, Financial Guidance, and certain other statements regarding the future of our business. Because 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 the Form 8K filed today and the Form 10-Q that we filed on August 8, 2019, 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 IR page of Nektar's website at Nektar.com. With that said, I will hand the call over to our President and CEO, Howard Robin. Howard?
Ill Abreu, Sri our COO and CFO .
And Dr., Jonathan Dylewski, our head of R&D.
On today's call, we expect to make forward looking statements regarding our business, including clinical trial results timing and plans for future clinical trials.
Timing and plans for future clinical data presentations at medical meetings.
The therapeutic potential of our drug candidates.
Outcomes and plans for health authority regulatory actions and decisions financial guidance and certain other statements regarding the future of our business because 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 the form eight.
Okay filed today and the Form 10-Q that we filed on August eight 2019, which is available at FCC Dot Gov. We undertake no obligation to update any of these forward looking statements whether as a result of new information future developments or otherwise.
Webcast of this call will be available on the IR pieces Nektars website, Nektar dotcom with that I will hand, the call over to our president and CEO Howard Robyn Howard.
Howard W. Robin: Thank you, Jennifer. Good afternoon, everyone, and thank you for joining us on today's call. Today we will provide several updates on our programs in our clinical pipeline and update our financial guidance for 2019. I'll start with several updates on our pipeline programs. First, Nektar 181.
Thank you Jennifer good afternoon, everyone and thank you for joining us on todays call.
Today, we will provide several updates on our programs in our clinical pipeline and update our financial guidance for 2019.
I'll start with several updates on our pipeline programs first nektar wanted to be one.
Howard W. Robin: As you will recall, the FDA issued a general advice letter in July which was sent to several sponsors, including us. And the letter stated that, at the time, the FDA would be postponing product-specific opioid analgesic advisory committee meetings. Well, we're pleased to report today that the FDA recently informed us that they are now moving forward to schedule product-specific advisory committee meetings again. And the agency also told us, based upon this, that they are actively working to schedule an advisory committee conference meeting for Nektar 181, which we currently expect will occur in the next several months. So we will be able to announce the data once it is published in the date, once it is published in the federal register.
As you will recall the F.D.A. had issued a general advice letter in July which was sent to several sponsors including us and the letter stated that at the time, the FDA would be postponing product specific opioid analgesic Advisory Committee meetings, where we're pleased to report today that the FDA recently informed us that they are now movie.
Forward to schedule product specific advisory Committee meetings again, and the agency also told US based upon this that they're actively working to schedule. One Advisory Committee conference meeting for Nektar 181, which we currently expect will occur in the next several months. So we'll be able to announce the data once it is published in the date once it is.
Published in the Federal Register.
Howard W. Robin: We believe that Nektar 181, as the first new opioid molecule designed in decades, has the potential to be a step forward and an important building block to help address the opioid crisis that plagues our country. We've recently published a significant number of manuscripts that detail the data supporting this program. This includes our Human Abuse Potential Study results and our Long-Term Safety Study results, which were published in the Pain Medicine Journal in September and July, respectively, as well as our Phase 3 efficacy results that were published in June in the journal Pain. We look forward to a scientific discussion at the rescheduled advisory committee meeting and continue to collaborate with the FDA team. Our wholly owned subsidiary, Inharis Biopharma, is preparing to launch Nektar 181 upon its potential approval. As we head into 2020, Inharis is carefully gating its spending prior to the potential FDA approval and commercial launch of Nektar 181. We are in the process of finalizing a capital structure with one or more potential capital partners in order to support the launch and distribution activities of Nektar 182.
We believe that Nektar 181, as the first new opioid molecule designed in decades has the potential to be a step forward and an important building block to help address the opioid crisis that plays our country. We've recently published a significant number of manuscripts that detail the data supporting this program. This.
It includes our human abuse potential study results and our long term safety study results, which were published in the pain Medicine Journal in September in July respectively as well.
As our phase three efficacy results that were published in June in the journal pain.
We look forward to a scientific discussion at the rescheduled Advisory Committee meeting and continue to collaborate with the FDA team.
Our wholly owned subsidiary and Harris Bio pharma is preparing to launch Nektar one anyone upon its potential approval as we head into 2020 and Harris is carefully gating it spending prior to the potential of the approval and commercial launch of Nektar 181.
We're in the process of finalizing a capital structure with one or more potential capital partners in order to support the launch and distribution activities for Nektar one anymore.
Next I'd like to briefly update you on Nektar 358, our I O two pathway agonist that specifically activates inexpensive T regulatory cells.
Howard W. Robin: Next, I'd like to briefly update you on Nektar 358, our IL-2 pathway agonist that specifically activates and expands T-regulator. Eli Lilly and Nektar have made great progress on this program over the last quarter, and Nektar 358 is now in the clinic under evaluation in three separate autoimmune disease conditions. As Lilly stated on their recent quarterly results call, Nektar 358 is a potential first-in-class opportunity for a medicine that preferentially stimulates the expansion of T-regulators. We are currently studying Nektar 358 in a Phase 1b multiple ascending dose study in lupus patients, which is expected to complete by the end of the year. We plan to submit data from this study at an upcoming medical meeting in 2020. Lilly then plans to start a Phase IIb dose-ranging study in lupus in the first half of 2020.
Eli Lilly in Nektar has made great progress on this program over the last quarter and Nektar 358 is now when the clinic under evaluation in three separate auto immune disease conditions.
As Lou we stated on their recent quarterly results call Nichter 358, as a potential first in class opportunity for a medicine that preferentially stimulates expansion of T regulatory cells.
We're currently studying Nektar 358, and a phase one be multiple ascending dose study in lupus patients, which is expected to complete by the end of the year.
We plan to submit data from this study at an upcoming medical meeting in 2020.
Well, we then plans to start a phase to be dose ranging study in lupus and the first half of 2020.
Howard W. Robin: Lilly also recently initiated Phase 1B studies in psoriasis and ectopic dermatitis, and they plan to add an additional Phase 2 autoimmune indication to the development program in 2020. As you know, we presented our first single ascending dose study data at the June 2019 ULAR conference, which demonstrated that Nektar 358 achieved robust expansion of T-regulatory cells in a dose-dependent fashion without expansion of conventional T-cell We plan to present additional mechanistic and pharmacodynamic data from this study in healthy volunteers at the American College of Rheumatology meeting this weekend in Atlanta.
Well, we also recently initiated phase one be studies in psoriasis, and atopic dermatitis and they plan to add an additional phase two auto immune indication to the development program in 2020.
As you know we presented our first in human single ascending dose study data at the June 2019, you are conference, which demonstrated that Nektar 358 achieved robust expansion of T regulatory cells in a dose dependent fashion without expansion of conventional T cells, we plan to present additional mechanistic.
And Pharmacodynamic data from this study in healthy volunteers at the American College of Rheumatology meeting this weekend in Atlanta.
Howard W. Robin: Lilly and Nektar are very excited about Nektar 358 and its potential to become the first in class therapeutic for multiple autoimmune and inflammatory indications. Moving on to Nectar 255, our IL-15 agonist program, we are excited to report that we recently initiated our first in-human clinical trial this quarter in patients with relapsed refractory non-Hodgkin's lymphoma or multiple myelom The study will first evaluate the safety of Nektar-255 as a monotherapy and will then expand to combine it with targeted antibody drugs that work through an antibody-dependent cell-mediated cytotoxicity (or ADCC) mechanism. Jonathan will talk more about this trial and the program in a moment.
Lillian Nektar are very excited about Nektar 358, and its potential to become the first in class therapeutic for multiple autoimmune and inflammatory indications.
Moving onto Nektar 255, our I O 15 agonist program. We're excited to report that we recently initiated our first in human clinical trial this quarter in patients with relapsed refractory non hodgkin's lymphoma or multiple myeloma.
The study will first evaluate the safety of Nektar 255, as a monotherapy and will then expand to combine with targeted antibody drugs that worked with antibody dependent so mediated cytotoxicity or ADCC mechanism.
Jonathan will talk more about this trial in the program in a moment.
Howard W. Robin: As Nektar, like IL-15, strongly promotes the expansion, activation, and survival of natural killer cells, we are excited about its potential to successfully combine with many significant therapies that utilize the ADCC mechanism. As you know, we have a preclinical collaboration in place with Janssen for Nektar 255, and they are currently evaluating the agent in combination with several different therapies in their oncology portfolio. And we have our ongoing preclinical collaboration with Gilead for Nektar 255 and virology. Gilead is evaluating Nektar 255 and various non-human primate models with a number of agents in their antiviral portfolio. As an IL-15 agonist, Nektar 255's proliferative effect on memory T-cells and other immune cells makes it a potentially compelling mechanism to combine with antivirals.
As Nektar EZ Io 15 strongly promotes the expansion activation in survival of natural killer cells. We are excited about its potential to successfully combined with many significant therapies that utilize the ADCC mechanism. As you know we had a preclinical collaboration in place with Janssen for Nektar 255, and they're currently a valve.
Are you waiting the agent in combination with several different therapies in their oncology portfolio, and we have or ongoing preclinical collaboration with Gilliat for new connector to 55 and virology go. We had is evaluating nektar 255 in various non human primate models with a number of agents in their anti viral portfolio.
As an Io 15 agonist nektar 255 prolific or effect on memory T cells and other immune cells make it potentially compelling mechanism to combined with anti virus.
We expect to have our first preclinical data from these collaborations in 2020 and are pleased with the advancement of Royal 15 program.
Howard W. Robin: We expect to have our first preclinical data from these collaborations in 2020 and are pleased with the advancement of our IL-15 program. Now, I'd like to move on to discuss our BEMPEG program. In the Registrational Trial Program with BMS, we currently have three registrational studies ongoing in combination with NEVO, one in first-line metastatic melanoma, one in first-line cis-ineligible urophilial cancer, and one in first-line metastatic renal cell carcinoma. To reiterate from last quarter, with respect to the differences that we discovered in two of the 22 lots of BEMPEG produced to date, we have put These two lots were produced very early in development, and neither of these two manufacturing lots have been used in any of the ongoing registrational trials.
Now I'd like to move on to review, our Ben Peg problem.
And the Registrational trial program with BMS. We currently have three Registrational studies ongoing in combination with Nivo. One in first line metastatic melanoma. One in first line assists in old wrote Urothelial cancer and one in first line metastatic renal cell carcinoma.
To reiterate from last quarter with respect to the differences that we discovered in two of the 22 lots of Mpeg produced today.
We have put into place a control strategy and ensures these variances will not occur again.
Two lots were produced very early in development and neither of these two manufacturing lots have been used in any of the ongoing registrational trials.
Howard W. Robin: We and BMS are also working together to ensure constant and comprehensive quality control is implemented for the commercial-scale manufacturing of BEMF. I know that many of you are highly interested in how we are progressing with our next steps with BMS. We're having ongoing discussions to finalize the balance of the joint development plan in the collaboration with BMS, and BMS has reiterated to us that they are highly committed to developing BEMPEG and preparing for future commercialization so we can bring this new immuno-oncology mechanism to patients. We in BMS are currently focusing on five to six key registrational trials. These include the ongoing registrational trials in first-line metastatic melanoma, first-line CIS-ineligible urethoid cancer, and first-line metastatic renal cell carcinoma. The next set of trials with BMS, including a strategy to develop BEMPEG with nivolumab in non-small cell lung cancer, are currently being planned. Both companies are working collaboratively in order to finalize this joint development plan by the end of this year.
We and BMS. We're also working together to ensure a constant and comprehensive quality control is implemented for the commercial scale manufacturing for Ben Peg.
I know that many of you are highly interested in how we are progressing with our next steps with BMS.
We're having ongoing discussions to finalize the balance of the joint development plan in the collaboration with BMS.
And BMS has reiterated to us that they are highly committed to developing Ben peg and preparing for future commercialization. So we can bring this new immuno oncology mechanism to patients.
We had BMS are currently focusing on five to six key Registrational trials. This includes the ongoing registrational trials in first line metastatic melanoma.
First line Sison eligible urothelial cancer in first line metastatic renal cell carcinoma. The next set of trials with BMS include a strategy to develop Mpeg wouldn't nivolumab in non small cell lung cancer are currently being planned.
Both companies are working collaboratively in order to finalize this joint development plan by the end of this year.
In addition, our propel studies now actively enrolling patients with first line non small cell lung cancer. This study is evaluating Ben peg with Merck's Pembrolizumab and as you know Pembro has emerged as the standard of care with or without chemotherapy in first line non small cell lung cancer across all PDL one.
Howard W. Robin: In addition, our PROPEL study is now actively enrolling patients with first-line, non-small-cell lung cancer. This study is evaluating BEMPEG with Merck's Pembrolizumab, and as you know, Pembro has emerged as the standard of care, with or without chemotherapy, in first-line, non-small-cell lung cancer across all PD-L1 expression populations. Jonathan will discuss more the design of this study in a moment.
Sure populations, Jonathan will discuss more on the design of this study in a moment.
We're pursuing additional indications outside of the BMS joint development plan in partnership with other collaborators. For example, we have several ongoing clinical collaborations with Ben Peg in other indications. These collaborations include one with Pfizer in head and neck cancer with of Allomap and prostate cancer with a bill.
Howard W. Robin: We are pursuing additional indications outside of the BMS joint development plan in partnership with other collaborators. For example, we have several ongoing clinical collaborations with BEMPEG and other indications. These collaborations include one with Pfizer in head and neck cancer with vilumab and prostate cancer with vilumab and teloprazib or enzatulamide. One of these, one with Vaxibodi in combination with multiple checkpoint inhibitors and with Vaxibodi's personalized neoantigen vaccines in head and neck cancer, and another collaboration with Bioxcell Therapeutics in combination with Pfizer' Of course, both BMS and Nektar were very pleased that in August of this year, the doublet of BEMPEG plus NEVO was granted a breakthrough therapy designation in first-line metastatic melanoma on the basis of its unique profile and a high complete response rate as compared to standard of care.
Meb and telepresence or Insitumain.
One of the.
One with vaccine body in combination with multiple checkpoint inhibitors and with vaccine bodies personalized neo antigen vaccines in head and neck cancer and another collaboration with Biogen cell therapeutics in combination with Pfizer's Villa Mab with bio excels DPP inhibitor in pancreatic cancer.
Of course, both BMS and Nektar, we're very pleased than in August of this year. The doublet, a Ben Peg plus Nivo was granted a breakthrough therapy designation in first line metastatic melanoma on the basis of its unique profile and a high complete response rate as compared to standard of care.
Howard W. Robin: The potential of this doublet in this indication is significant, and there is a possibility to expand it in other melanoma indications as well. Our Phase III trial in the first-line metastatic melanoma population is continuing to enroll, and data for the first endpoint in this study, ORR, could be available as early as Q4 of next year. As you know, in the cohort of patients with first-line metastatic melanoma from the PIVOTO2 study, we saw a significant depth of response with a large percentage of patients achieving 100% reduction of target lesions and complete response. At CITSE this coming weekend, Dr. Adi Diab will present an update on the cohort of melanoma patients in the PivotO2 study at an 18-month follow-up. We're very excited about this presentation, and it will include, for the first time, a presentation of PFS for this cohort.
The potential of this doublet in this indication is significant and there was a possibility to expand and other melanoma indications as well.
Phase three trial in the first line metastatic melanoma population is continuing to enroll and data for the first endpoint in this study or our could be available as early as Q4 of next year.
As you know in the core to patients with first line metastatic melanoma from the pivotal phase two study.
We saw a significant depth of response with a large percentage of patients achieving 100% reduction of target lesions and complete responses.
It sits see this coming weekend Dr. idea will present, an update on the cohort of melanoma patients in the pivotal to study at an 18 month follow up we're very excited about this presentation and would include for the first time a presentation a PFS for this cohort we will also host a webcast for investors and those.
Howard W. Robin: We will also host a webcast for investors and those of you who can't attend CITSI in person. The webcast will include a re-presentation of the data from the oral presentation with Dr. Diab, and this will be held on Sunday morning at 9 a.m. Eastern Time. We hope you'll join us for a review of that data. With that, I'd like to hand the call over to Jonathan for a brief clinical examination.
Have you who cannot attend sits in person.
The webcast will include a re presentation of the data from the oral presentation with Dr. de mob and this will be held on Sunday morning at nine am Eastern time, and we hope you'll join us for a review of that data.
With that I'd like to hand, the call over to Jonathan for belief brief clinical discussion.
Jonathan Zalevsky: Thanks, Howard. Before I review the clinical study design for Nektar 255, I'd like to comment briefly on our Propel program, which is evaluating the combination of BEMPEG with Merck's Pembrolizumab. Propel will evaluate different dose levels of BEMPEG with a single regimen of pembrolizumab to ensure that we identify the proper recommended phase 2 dose for the combination. Importantly, the BEMPEG drug supply now being used in Propel matches the supply from the ongoing registration.
Thanks Howard.
Before I review the clinical study design for Nektar, two fivefive I'd like to comment briefly on our propelled study, which is evaluating the combination of them with the marks pembrolizumab.
Propel we'll evaluate different dose levels.
With a single regimen of Pembrolizumab.
To ensure that we identified the proper recommended phase two dose for the combination.
Importantly, the Ben pegged drug supply now being used in propel matches drug supply from the ongoing Registrational studies.
Jonathan Zalevsky: And from a global program perspective, this study design allows us to generate important data in first-line non-small cell lung cancer, with the Standard of Care in Non-Small Cell Lung Cancer, Pemberley. With respect to the initiation of additional combination trials for BEMPEG, as Howard stated, Pfizer and Nectar have already begun screening patients for the Phase 1b-2 study in head and neck cancer and castration-resistant prostate cancer.
From a global program perspective. This study design allows us to generate important data in first line non small cell lung cancer with the standard of care in non small cell lung cancer pembrolizumab.
With respect to the initiation of additional combination trials for Ben Pag, It's Howard stated Pfizer and Nektar have already begun.
To screen.
Patients for the phase one be slash two study in head and neck cancer and castration resistant prostate cancer.
The study will evaluate various doublet and triplet combinations with Ben Pag, and Pfizer and Merck Seronos anti PD L. One agent of Allomap.
Jonathan Zalevsky: The study will evaluate various doublet and triplet combinations with BEMPEG and Pfizer and Merck-Sorono's anti-PD-L1 agent Avelimar, Pfizer's PARP inhibitor, talazoparib, and Pfizer and Astellas' enzalutamide. We're very excited to work with Pfizer on this because of the opportunity in these two solid tumor settings for BEMPEG, particularly in patients with PD-L1 negative tumors. We are also evaluating different indications that could be pursued with other collaborators in 2020. Now moving on to Nektar 255, our IL-15 receptor agonist. The first in human study, which recently initiated with the first patient dosed last month, will evaluate the safety and dose schedule of Nektar 255 as monotherapy, and then expand into combination with antibodies that work through an ADCC mechanism, such as daratumumab and rituximab.
Pfizer's PARP inhibitor tell is operated and Pfizer and establishes enzalutamide.
We're very excited to work with Pfizer on this because of the opportunity in these two solid tumor settings for Ben Peg, particularly in patients with PDL one negative tumors.
We're also evaluating different indications that could be pursued with other collaborators in 2020.
Now moving on to Nektar, two by five our aisle 15 receptor agonist.
The first in human study, which recently initiated with the first patient dose last month, we will evaluate the safety and dose schedule of Nektar 255, as a monotherapy and then expand into combination with antibodies that work through an 80 cc mechanism such is there a tumor mob and rituximab.
Jonathan Zalevsky: We plan to enroll patients with relapsed or refractory multiple myeloma or non-Hodgkin's lymphoma. The study is designed as a dose-escalation and dose-expansion study. The dose-escalation phase of the study will evaluate the safety and tolerability of Nektar 255 as monotherapy in approximately 40 patients in order to establish a recommended phase 2 dose for Nektar 255. The subsequent dose expansion phase of the study will enroll patients in two separate cohorts.
We plan to enroll patients with relapsed or refractory multiple myeloma or non Hodgkin's lymphoma.
The study is designed as a dose escalation and dose expansion study the dose escalation phase of this study will evaluate the safety and Tolerability of Nektar 255, as monotherapy and approximately 40 patients in order to establish a recommended phase two dose for Nektar 255.
The subsequent dose expansion phase of this study will enroll in two separate cohorts. The first cohort will enroll patients with relapsed salvage multiple myeloma or non Hodgkin's lymphoma to evaluate nektar 255 at the recommended phase two dose as a monotherapy.
Jonathan Zalevsky: The first cohort will enroll patients with relapsed, salvaged multiple myeloma or non-Hodgkin's lymphoma to evaluate Nektar 255 at the recommended phase 2 dose as a monotherapy. The second cohort will enroll patients with relapsed, refractory, or salvaged multiple myeloma or NHL to evaluate Nektar 255 at the recommended phase 2 dose in combination with targeted antibodies The study will also evaluate pharmacokinetic and pharmacodynamic effects, anti-tumor activity, and biomarker assessments in blood and tissue. IL-15 stimulates the production, activation, survival, and function of natural killer cells.
The second cohort will enroll patients with relapsed refractory or salvage multiple myeloma or NHL to evaluate nektar 255 at the recommended phase two dose in combination with targeted antibodies, including the anti Cdthirty eight monoclonal antibody daratumumab as well as the anti Cdtwenty monoclonal antibody written.
So Matt.
The study will also evaluate pharmacokinetic and pharmacodynamic effects anti tumor activity and biomarker assessments and blood and tissue.
I'll 15 stimulates the production activation survival and function of natural killer cells, and we have introduced a robust biomarker program into this trial to provide a deep assessment of the Nektar 255 mechanism of action.
Jonathan Zalevsky: And we have introduced a robust biomarker program into this trial to provide a deep assessment of Nektar 255's mechanism of action. Besides NK cells, we will also evaluate total and subpopulations of CD4 and CD8 memory T cells to study the effect of Nektar 255 on their expansion, activation, and survival. This biomarker-rich early clinical development approach allows us to follow the science and the development planning for Nektar 255. Now, Nektar 255's unique ability to target the NK cell compartment provides us with an exciting opportunity in combination with targeted therapy. One of the big challenges in treating cancer patients with targeted monoclonal antibodies, such as rituximab, or cituximab, or trastuzumab, is that cancer patients can exhibit a deficiency in the key effector cells that execute the ADCC reaction, specifically in the case of cancer. There are examples of patients with reduced numbers of NK cells or non-functional NK cells that are unable to execute effect In addition, NK cells are rate-limiting. They tend to be consumed in the ADCC reaction, which can further limit the targeted therapy.
Besides NK cells, we will also evaluate total and sub populations of CD for in CD eight memory T cells to study the effective next Gen 255 on their expansion activation and survival.
This biomarker rich early clinical development approach allows us to follow the science and the development planning for Nektar two by five.
Now nektar two by fives unique ability to target the NK cell compartment provides us with an exciting opportunity in combination with targeted therapies.
One of the big challenges in treating cancer patients with targeted monoclonal antibodies such as Rituximab. So it took some advertisers twos mob is that cancer patients can exhibit a deficiency in the key effector cells that execute the ADCC reaction, specifically NK cells.
There are examples of patients with reduced numbers of NK cells or non functional NK cells that are unable to execute effector function and thus limit the therapeutic potential of antibodies. In addition, NK cells are rate limiting.
They tend to be consumed in the ADCC reaction, which also further can limit the targeted therapy.
We believe that by increasing the number and activity of NK cells. Nektar 255 has the potential to enhance the tumor fighting response, particularly when administered within ADCC antibody.
Jonathan Zalevsky: We believe that by increasing the number and activity of N-Case, Nektar 255 has the potential to enhance the tumor fighting response, particularly when administered with an ADCC antibody. For example, in non-human primates, Nektar 255 could provide continuous NK cell expansion with each cycle of dosing. And we look forward to evaluating these same effects in; the broad utility of targeted antibody therapy coupled with the immune-enhancing properties of Nektar 255 make this a very exciting combination, and we are looking forward to the progression of this first in human clinical trial. In preclinical studies, Nektar 255 exhibited anti-tumor activity and substantially enhanced in vivo proliferation and activation of NK cells to provide sustained cytotoxic function in a preclinical lymphoma model where single-agent daratumumab was ineffective.
For example, the non human primates, Nektar 255 could provide continuous NK cell expansion with each cycle of dosing.
And we look forward to evaluating these same effects in patients.
The broad utility of targeted antibody therapy, coupled with the immune enhancing properties of Nektar 255 make this a very exciting combination and we're looking forward to the progression of this first in human clinical trial.
In Nonclinical studies, Nektar 255 exhibited anti tumor activity and substantially enhanced in vivo proliferation and activation of NK cells to provide sustained cytotoxic function.
In a preclinical lymphoma model, where single agent Daratumumab with ineffective.
Next year to five five treatment in combination with Daratumumab increased NK cell numbers in activity in bone marrow tissue and enhanced ADCC mediated tumor cell clearance and the bone marrow compartment.
Jonathan Zalevsky: Nektar 255 treatment in combination with Duratumumab increased NK cell numbers and activity in bone marrow and enhanced ADCC-mediated tumor cell clearance in the bone marrow compartment. As Howard stated earlier, we also have a preclinical collaboration with Janssen, and they plan to combine Nektar 255 with multiple agents in their oncology portfolio in animal models of cancer. In addition, our Gilead program is advancing nicely, and they are working with Nektar 2x5 in various non-human primate virology models. This coming week at CIDSE, we will also present new preclinical data on Nektar 255. There will be two poster presentations.
As Howard stated earlier, we also have a preclinical collaboration with Janssen and they plan to combine Nektar 255 with multiple agents in their oncology portfolio in animal models of cancer.
In addition, our Gilly add program is advancing nicely and they are working with Nektar two by five in various non human primate virology models.
And this coming week at city, we will also present, new preclinical data Nektar 255, there will be two poster presentations one will focus on the scientific differentiation of Nektar 255, which is able to bind ansys or trends to all forms of the aisle 15 receptor complex.
Jonathan Zalevsky: One will focus on the scientific differentiation of Nektar-255, which is able to bind in cis or trans to all forms of the IL-15 receptor complex, IL-15R-alpha, IL-2R-beta, and IL-2R-gamma, versus the competing pipelines, which can only bind to the IL-2R beta and IL-2R gamma dimeric complex. The second poster We also look forward to presenting additional preclinical data from the Nektar 255 program at the ASH meeting in December, including data evaluating Nektar 255 in combination with CD19 CAR-T cells. We then expect additional preclinical data from one or both of our Nektar 255 collaborations in 2020 and expect to have the first data from the phase one clinical study in the second half of 2020. In closing, we are very excited about the start of the first Nektar 255 clinical trial, as it not only represents our next clinical program of cytokine therapy, but it has significant potential in oncology as well as virology. And with that, I will hand the call to Gil to update our financial guidance for 2019.
15, <unk> Alfa aisle to our beta and aisle to our gamma.
Versus the competing pipelines, which can only bind to the aisle to our beta and aisle to our gamma die Merrick complex.
The second poster will focus on ADCC applications for solid tumor targeting monoclonal antibodies, including mouse tumor studies evaluating the combination of Nektar two by five with this it talks about and tries to them out.
We also look forward to presenting additional preclinical data from the Nektar 255 program at the Ash meeting in December including data evaluating Nektar 255 in combination with Cdnineteen car T cells.
We then expect additional preclinical data from one or both of our Nektar 255 collaborations in 2020 and expect to have the first data from the phase one clinical study in the second half of 2020.
In closing, we're very excited about the start of the first Nektar 255 clinical trial.
As it not only represents our next clinical program with the cytokine therapy, but it has significant potential in oncology as well as virology.
With that I will hand, the call to Gil to update our financial guidance for 2019.
Gil Labroucherie: Thank you, Jonathan, and good afternoon, everyone. Today we issued our financial results for the quarter ended September 30, 2019. I will briefly review our updated 2019 financial guidance. Starting with our cash position, we now anticipate ending 2019 with approximately $1.6 billion of cash and investments. Our full year GAAP revenue guidance remains at between $100 million and $110 million for 2019. We now anticipate full year 2019 GAAP R&D expense will range between $430 and $450 million, which includes approximately $65 million of non-cash depreciation and stock compensation expense. We project G&A expense for 2019 to be approximately $100 million, which includes approximately $45 million of non-cash depreciation and stock compensation expenses. Our G&A expense forecast is lower than we originally estimated as a result of the FDA's delay in holding the Nektar 181 Advisory Committee meeting.
Thank you Jonathan and good afternoon, everyone.
Today, we issued our financial results for the quarter ended September Thirtyth 2019.
Will briefly review our updated 2019 financial guidance.
Starting with our cash position, we now anticipate ending 2019 with approximately 1.6 billion of cash and investments.
Our full year GAAP revenue guidance remains that between 100 million and 110 million for 2019.
We now anticipate full year 2019, GAAP R&D expense will range between 430 and 450 million.
Which includes approximately 65 million of noncash depreciation and stock compensation expense.
We project DNA expense for 2019 to be approximately 100 million, which includes approximately 45 million of noncash depreciation and stock compensation expense.
Our DNA expense forecast is lower than we originally estimated as a result of the Deejays delay and holding the Nektar 181 Advisory Committee meeting.
Gil Labroucherie: As Howard stated earlier, we continue to carefully gate and harass commercial readiness spending until a successful approval of Nektar 181 is achieved. We are in a very fortunate position with a strong balance sheet. As we develop our 2020 operating budget, we plan to be prudent in our capital allocation with the objective of getting BEMPEG approved as quickly as possible and advancing our pipeline with the resources on hand. Operator.
As Howard stated earlier, we continue to carefully gate in Harris commercial readiness spending until its successful approval of Nektar 181 is achieved.
We are in a very fortunate position with a strong balance sheet.
As we develop our 2020 operating budget, we plan to be prudent in our capital allocation with the objective of getting Ben Peg approved as quickly as possible and advancing our pipeline with the resources on hand.
And with that I will open the call for questions operator.
Thank you.
Operator: Thank you. Ladies and gentlemen, if you have a question at this time, please press the star followed by the number one key on your touchtone telephone. If your question has been answered or you wish to remove yourself from the queue, please press the pound key. Once again, to ask a question, please press star and then one now. And our first question comes from Chris Shibutani from Cowan. Your line is open.
Ladies and gentlemen, if you have a question at this time. Please press the star followed by the number one key on your Touchtone telephone. If your question has been answered all your wish or move yourself from the Q. Please press the pound key once again to ask a question. Please press Star then one now.
And our first question comes from Chris Shibutani from Cowen Your line is open.
Thank you very much a question on propel you described that you're going to be doing several different doses can you remind us what those dose levels will be in how that compares with the dose of Ben peg that you've been using in the pivot studies.
Chris Shibutani: Thank you very much. A question on Propel. You described that you're going to be doing several different doses. Can you remind us what those dose levels will be and how that compares with the dose of Benpeg that you've been using in the PIVOT studies? Secondly, as far as inclusion criteria for that Propel study are concerned, will patients be able to receive chemotherapy as part of that regimen as well in this first line setting?
Secondly, as far as inclusion criteria for that.
Propel study will patients be able to receive chemotherapy as part of that regimen as well in this first line setting.
Sure Hey, Chris This is Jay Z. So to the first question you asked about the dose levels being evaluated in propel and so yeah. One of the things that we're doing as we will be evaluating if the dose level that we identified in combination with Nivolumab, which was 0.006 makes per keurig if that's the.
Jonathan Zalevsky: Sure. Hey Chris, this is Jay Z.
Jonathan Zalevsky: So to the first question, you asked about the dose levels being evaluated in Propel. And so, yeah, one of the things that we're doing is we will be evaluating if the dose level that we identified in combination with nivolumab, which was 0.006 mgs per kg, if that's the same appropriate dose for a combination with pembrolizumab. And so in order to do that, in the Propel study, we were going to open evaluating two dose levels, the 0.006, the same dose level as with nivo, and also a little bit of a higher dose level, 0.008 mgs per kg as well. And we're really looking to see if there's, you know, an opportunity or a need, for example, or necessity in order to define a different dose range with a different checkpoint inhibitor. And then in regards to the design of PROPEL.
Same appropriate dose for a combination with pembrolizumab and so in order to do that in the propel study will gonna open evaluating two dose levels.
0.006, the same dose level as with Nivo and also a little bit of a higher dose level 0.008 mics per keurig as well and we're really looking to see if there's an opportunity you are in need of for example, or necessity in order to define a different dose range with the different checkpoint inhibitor.
And then in regards to the design of propel so really this study is designed to focus and on the Io doublet and so in that case short answer is no will not be treating patients with chemotherapy. In addition to the doublet well, we will be evaluating the doublet, Ben Pag plus pembrolizumab in three different PD.
Jonathan Zalevsky: So really, this study is designed to focus on the IO doublet. And so in that case, the short answer is no; we'll not be treating patients with chemotherapy in addition to the doublet. But we will be evaluating the doublet of BEMPEG plus pembrolizumab in three different PD-L1 expressor populations. In the PD-L1 low, less than 1%. In the PD-L1 intermediate, the 1 to 49% population, and the PD-L1 high, the greater than 50% population.
Alwan expresser populations in the PDL, one low less than 1% and the PDL, one intermediate and I want to 49% and the PDL one high the greater than 50% populations.
And then just to be clear, we're after what I understood September Thirtyth, two have been kind of the demarcation line as far as.
Howard W. Robin: And then just to be clear, we are after what I understood September 30th to have been kind of the demarcation line as far as the Bristol relationship is concerned. It did sound as if you were describing that there are ongoing discussions. But in particular for Propel with Pembro, which is obviously Merckx, do they – can you provide us with any clarity in terms of who's sort of commercialization rights, et cetera? Is there anything formalized in terms of whether this continues to develop successfully given that the first line indication is really standard of care with Pembro? Thanks.
Just a relationship it didn't sound as if you are describing that there's ongoing discussion, but in particular for propel with Pembro, which is obviously merck's.
Do they can you provide us any clarity in terms of who's sort of commercialization rights etcetera is there anything formalized in terms of if this continues to.
Developed successfully given that the first line indication is really standard of care with Pembro. Thanks.
Yeah. Thanks, Chris This Howard.
Howard W. Robin: Yeah, thanks, Chris. This is Howard.
Chris Shibutani: Good question. Look, we're doing the PROPEL study, and we've shifted the PROPEL study, as Jay-Z said, principally to first-line non-small-cell lung cancer, and we certainly have the right to do that under the agreement. In the final analysis, though, the marketability of this still rests with Nektar and BMS. In other words, the relationship between Nektar and BMS is such that we both jointly market PEMPEG, and we keep 65% of the profits, and they keep 35% of the profits. Now where we go with a combination with PEMBRO, let's look at the data, let's see how important it looks, let's see how important it is to patients. Obviously, if it's a very important compound, a combination for patients with first-line non-small cell lung cancer, we will bring it to those patients, and we will bring it to market. But it can't become Merck's product at that point. Obviously, PEMPEG stays with Nektar and PEMBRO. Thanks for the helpful clarification.
Good question look we're doing we're doing the propel studying we've shifted the propel study as Jay said principally to.
First line non small cell lung cancer, and we certainly have the right to do that under the agreement in the final analysis, though it the marketability of this.
Still rests with Nektar and BMS in other words the relationship between Nektar and BMS is such is such that we both jointly market.
Mpeg and we keep 65% of the profits and they keep 35% of the profits now where we go with with the combination with Pembro, let's look at the data, let's see how important it looks let's see how important it looks to patients.
Obviously, if it's a a very important compound a combination for patients with first line non small cell lung cancer. We will we will bring it to those patients will bring it's a market, but it doesn't it can't become merck's product at that point, obviously, mpeg stays with Nektar and BMS.
Thanks for that for clarification I'll get back into queue.
Chris Shibutani: Thanks for the helpful clarification. I'll get back in the queue.
Our next question comes from Jessica Fye from JP Morgan Your line is open.
Jessica Macomber Fye: Thank you. Our next question comes from Jessica Fye from J.P. Morgan. Your line is open.
Hey, guys. Good evening. Thanks for taking my question you mentioned the all our our data from the phase three melanoma trial could come in the fourth quarter of 2020 would that be based on a subset of the total number of patients and the trial and if so how many patients.
Jessica Macomber Fye: Hey guys, good evening. Thanks for taking my questions. You mentioned the ORR data from the phase 3 melanoma trial could come in the fourth quarter of 2020. Would that be based on a subset of the total number of patients in the trial, and if so, how many patients?
Yeah, Hey, Jessica this is jeezy. So yeah, just too to update you on so definitely.
Jonathan Zalevsky: Hey Jessica, this is Jay Z. So yeah, just to update you. So definitely, we've updated the clinicaltrials.gov posting for that trial, and as it states, in the second half of 2020, for example, as early as Q4 of 2020, is when the ORR endpoint from the melanoma study can be achieved and can be reported. We haven't indicated how many patients that is, but it is a subset of the patients in the trial. And I will also remind you that this is a trial that BMS is operating. So we work very closely with BMS, but the specific timelines and cadences under BMS's operationalization, and very much as the update that they gave at ESMO was very current with the most recent information about that.
We've updated the clinical trials dot Gov, posting for that trial and as its AIDS in the second half of 2020 for example, as early as Q4 of 2020 is when the or our endpoint from the melanoma study can be achieved and can be reported.
We haven't indicated how many patients that is but it is a subset of the patients in the trial and I will also remind you that this is a child that BMS is operationalizing. It. So so we work very closely with BMS, but the specific timelines and cadences under BMS is operationalization and very much.
The update that they gave at ESMO was very current with the most recent information about that study.
Okay. So what's the latest expectation for the timing of the PFS read out for that trial.
Jonathan Zalevsky: Okay, so what's the latest expectation for the timing of the PFS readout for that trial?
So right now that is targeted for the middle of 2021.
Jonathan Zalevsky: So right now, that's targeted for the middle of 2021.
Okay.
Jonathan Zalevsky: Okay. And when you guys were talking about the registrational trials for BEMPEG and NEVO, including melanoma, urothelial, and RCC, are you guys still looking at that 100-patient, second-line, non-small cell cohort as being potentially registrational? And what's the timing for that data?
When you guys were talking about the Registrational trials for bandwagon, nivo, including melanoma Urothelial and RCC.
You guys still looking at that 100 patients second line non small cell cohort as being potentially registrational and what's the timing for that data.
Yes, so the this arm and pivot is still enrolling and as you point out it's focused on enrolling the relapse patient populations. So specifically these are patients that have relapse following pembro plus chemo combination.
Jonathan Zalevsky: Yeah, so this arm in PIVOT is still enrolling patients, and as you point out, it focuses on enrolling relapsed patient populations. So specifically, these are patients that have relapsed following PEMBRO plus chemo combination therapy. And this is a first-line combination therapy. And, as Howard stated, we're currently planning a potential strategy with BMS, and in totality, that includes non-small cell lung cancer, and we'll be able to update you and everyone on the overall strategy for lung cancer when we complete that process.
And this is a first line combination.
And as Howard stated, we're currently planning potential strategy with BMS and in totality that includes non small cell lung cancer, and we'll be able to update you and everyone on the overall strategy.
For lung cancer, when we complete that process.
Okay got it I know Bristol's had some recent updates with their.
Jessica Macomber Fye: Okay, got it. I know Bristol's had some recent updates with their long trials, and you mentioned that you were hoping to have the kind of collaboration. The new registrational trial is hammered out by year-end. Does that give you enough time to kind of incorporate the relatively recent news on the Bristol I.O. front?
One trial and you mentioned that you are hoping to have the kind of collaboration.
Yeah.
The new registration on trap hammered out by year end does that give you enough time to kind of incorporate the relatively recent news on the kind of Bristol Io from.
Yes, Jessica well, we will we did say that we will we are getting close to finalizing what the new with a new set of clinical trials looked like the additional clinical trials.
Howard W. Robin: Yeah, Jessica. Well, we did say that we were getting close to finalizing what the new set of clinical trials look like, the additional clinical trials, and I did say we'd have that completed by the end of the year, and that's an assurance I have from BMS, and we're working actively on that. I think that whatever data we have now will be included in that process, and I'm fairly confident now that we'll be adding to the three studies that we're currently running, and at the end of the year or at the JPMorgan conference, we'll certainly be talking about the new clinical trial set in that collaboration. But remember, in the final analysis, it's still an incredibly impressive and important collaboration in that five or six registrational trials combined with an enormous economic commitment from BMS are very important to us.
I would say we'd have that completed by the end of year and that's an assurance I have from from BMS and we're working actively on that I think.
What whatever data we have now will be included in that in that process and I'm I'm I'm fairly confident now that will you know we'll be adding to the study to the three studies that we're currently running and at the ended the year more or that.
The JP Morgan Conference, we'll certainly be talking about.
The.
New clinical trial set in that collaboration.
But remember it's still in the in the final analysis, it's still a it's still an accretive credibly impressive and important collaboration in that.
Five or six Registrational trials.
Combined with combined with an enormous.
Economic commitment from BMS is very important to us.
Okay got it maybe just the last one on RCC and when we could next he data I think you had talked about maybe that come in as well I O. When should we expect the next to look at.
Jessica Macomber Fye: Okay, got it. Maybe just the last one on RCC and when we could next see data. I think you had talked about maybe that coming at SML-IO. When should we expect the next look at the pivot data and first line RCC?
Pivot data in first line RCC.
Yeah, Hey, Hey, there Jessica this is Jay Z. So in the context of that data when we looked at all of it.
Tyler Van Buren: Hey there, Jessica. This is Jay Z. So in the context of that data, when we looked at all of it, it became clear to us that presenting it in the context of a publication was a much more appropriate way to present that data because it allows us to cover the context of all of the changes in the manufacturing batches that were used in Pivot 02. So you can expect to see next year our upcoming publications, which will be peer-reviewed manuscripts and that will cover that data as well.
It became clear to us that presenting it in the context of a publication was a much more appropriate way to present that data because it allows us to cover the context of all of the changes in the manufacturing batches that were used in pivotal too. So you can expect to see next year our upcoming publication.
You'll see a peer reviewed manuscripts and that will cover that data as well.
Tyler Van Buren: Okay, I got it. Thank you.
Howard W. Robin: Our next question comes from Tyler Van Buren from Piper Jaffray. Your line is open. Hey, guys, good afternoon. Can you provide updated thoughts?
Okay got it thank you.
Yes.
Thank you.
Next question comes from Tyler Van Buren from Piper Jaffray. Your line is open.
Tyler Van Buren: Hey guys, good afternoon. Can you provide updated thoughts on timing for the bladder and RCC registrational trials?
Hey, guys. Good afternoon can you provide updated thoughts on timing for the bladder and RCC Registrational trials.
All right Tom do you mind repeating the question again.
Jonathan Zalevsky: Alright, Tyler. Do you mind repeating the question again?
Tyler Van Buren: ..
Tyler Van Buren: Yeah, just update thoughts on timing for the bladder and RCC registrational trials when we should get the initial top line data.
Yeah, just updated thoughts on timing for the bladder in RCC Registrational trials, when we should get the initial topline data.
Jonathan Zalevsky: Absolutely. So for the bladder clinical study, mid-2021 is an update on when we could see top-line data. This is a study that utilizes ORR and the DOR, the duration of response, as the two components. And then for RCC, it would be the year after, either the very end of 2021 or 2029.
Absolutely so.
So for the bladder clinical study mid 2021 is an update on when we could see topline data.
This is a study that utilizes our and the DLR the duration of response as the two components.
And then for RCC it would be the year after.
At the very end of 2021 or 2022.
Okay.
Jonathan Zalevsky: I I I I I
Tyler Van Buren: I guess just across melanoma and bladder and RCC and the registrational trials, we're clearly experiencing some delays here, so could you guys just help put that into context? Is enrollment just taking a little bit longer than anticipated, or how should we think about it?
Yes, just you know across melanoma and bladder in RCC and Registrational trials, we're clearly experiencing some delays here. So could you guys are so put that in context as enrollment just taking a little bit longer than anticipated or how should we think about it.
Yeah. So as some of the those studies started there was a little bit of a slower rate of initiating the sites. A this is a little bit slower than what we'd like to see.
Jonathan Zalevsky: Yeah, so as some of those studies started, there was a little bit of a slower rate of initiating sites. This is a little bit slower than we like to see. But now we're starting to see studies that have hit the large majority of the sites already open. So take, for example, in the case of melanoma; now almost all of the sites are open and enrolling patients. And it's essentially enrolling at scale at this time, so you'll see these studies now all move and pick up.
But now we're starting to see the studies that have now hit.
Large majority of the sites already open so take for example in the case of melanoma now almost all of the sites are open and enrolling patients and it's essentially enrolling at scale at this time. So you'll see these studies now I'll move and pick up.
Okay. That's helpful context, and just a final question as.
Tyler Van Buren: Okay, that's helpful context. And just a final question is, with the three registrational ongoing plus lung, that's four. So, you know, with five or six, potentially one or two more registrational trials. I guess can you guys just help us think about the potential different indications that would make sense for those one or two or what you guys are currently thinking about at the moment?
With the three registration ongoing plus long that's four so.
With five or six a potentially one or two more registrational trials.
I guess can you guys just help us think about the potential different indications that would make sense for those one or two or what you guys are currently thinking about at the moment.
Yeah look we as we said we have the the the bladder the melanoma and the.
Howard W. Robin: Yeah, look, we, as we said, we have the bladder, the melanoma, and the renal running. I think I think we will also, as I said, we're also working actively with BMS to design a non-small cell lung cancer program. And I think in the context of the three trials that are running, I think you'll see some additional trials clearly in melanoma where we have, you know, breakthrough designation because of the results we've had to date that I think are quite impressive. I think we're likely to see increases in studies there as well as in bladder and renal. And these are, you know, these are the most immunosensitive tumor types.
Renal running I think.
I think we will also were I. Just said, we're also working actively with BMS to design a long non small cell lung cancer program and I think in the context of the three trials that are running I think you'll see some additional trials clearly in melanoma.
Where we have broken.
Resignation because of the results we've had to date that I think are quite impressive I think we're likely to see increases in studies, there as well as bloodily bladder and renal and these are these are the you know these are the most.
You know sensitive tumor types and I think thats of course, where we have the the largest chance for success and these are also a fairly large market opportunity, especially in in melanoma and it gives it certainly gives BMS the opportunities that dominate the melanoma space for for the.
Howard W. Robin: And I think that's, of course, where we have the largest chance for success. And these are also fairly large market opportunities, especially in melanoma, and it certainly gives BMS the opportunity to dominate the melanoma space for the foreseeable future. So we're pretty excited about those programs, and remember, we do have a number of other programs that we're running with other companies, as I talked about, head and neck and prostate with Pfizer. So, and there'll probably be more. There will probably be other collaborations that we put together in the near future with other companies. So I think you'll see a pretty broad range of opportunities with BEM.
For the foreseeable future. So we're pretty excited about those programs and remember we do have we do have a number of other programs that were running where other companies as I talked about head and neck in prostate with Pfizer, so they'll probably be more they'll probably be other collaborations that we put together in the near future with other companies.
So I think you'll see a pretty broad portfolio of opportunities with impact.
Great. Thanks for taking the questions.
Tyler Van Buren: Great, thanks for taking the questions.
Thank you. Our next question comes from Difei Yang from Mizuho. Your line is open.
Desai Yang: Thank you. Our next question comes from Desai Yang from Mizuho. Your line is open. Please check that your line is not on mute.
Please check that your line is not on you.
Hey, sorry, guys I was on mute.
Desai Yang: Hey, sorry guys, I was on mute. This is Alex from DFAY. Thank you for taking the question. Just coming back to the bladder indication, are you still considering a trial for muscle invasive bladder cancer?
Yes, Alex for Difei. Thank you for taking question.
Just coming back to the bladder indication are you still considering a trial in muscle invasive bladder.
Bladder cancer.
Jonathan Zalevsky: Hey, this is Jay Z. Yes, indeed we are considering that trial. So, as you know, PIVOT-10 is an accelerated approval kind of opportunity. And so, definitely, a confirmatory study is necessary, right, in order to support that. And muscle-invasive bladder cancer is, indeed, the study that we are considering to fulfill that role.
Hey, this is Jay the yes, indeed, we are considering that trial. So as you know the pivot 10 is in the accelerated approval kind of opportunity and so definitely a confirmatory study is necessary in order to support that and muscle invasive bladder cancer is is indeed the study that.
We are considering to fulfill that role.
Okay, great. Thank you.
Desai Yang: Okay, great. Thank you.
Our next question comes from George Farmer from BMO capital markets. Your line is open.
George Farmer: Thank you. The next question comes from George Farmer from BMO Capital Markets. Your line is open. Hi, this is Govind Singh on behalf of George Farmer. Thanks for taking our questions. I guess the first one I have is for BEMPEG. Can you tell us a little bit? So the PFS data, I think you guys confirmed is gonna be presented at SET-C. Can you give us an idea of how we should be thinking about the overall survival data?
Hi, This is gogan seeing on for George Farmer, Thanks for taking my question.
So I guess the first one I have is for Ben.
Can you tell us a little bit so.
PFS data if you guys Im just going to be presented that the can you give us an idea of how we should be thinking about the overall survival data.
Govind Singh: Sure, so the new data that we'll be presenting at CITSI will be the PFS for the melanoma first line cohort in PivotO2. OS is obviously something that we track, but it really is something that will be out much more into the future. So that's something that in a future update, you know, that could be something that we update. It's too early to focus on that, so I'm focusing on PFS. Sure. OK.
Sure. So so yes, so the new data there will be presenting it since he will be the PFS for the melanoma first line cohort in pivotal to Oh, I guess, it's obviously something that we track, but it really is something that would be how much more into the future. So that's something that in the future update.
It could be something that we update but really it it's too early focus on that so focusing on PFS at this time.
Sure Okay.
Jonathan Zalevsky: you know.
Jonathan Zalevsky: [inaudible]
Well I'll, just sort of out of that one of the really sort of interesting components. Since you asked about overall survival is at ASCO. This year right that you provided data from a matter analysis, where they looked at different treatment therapies for melanoma and they looked at the depth of response and then they compare the depth of response to long term.
Jonathan Zalevsky: Well, I'll just sort of add that one of the really sort of interesting components, since you asked about overall survival, is that at ASCO this year, the FDA provided data from a meta-analysis where they looked at different treatment therapies for melanoma, and they looked at the depth of response, and then they compared the depth of response to long-term survival, essentially to overall survival. And what they did find is that patients that had a 75% tumor shrinkage or better, including a complete response, and particularly from treatment with an IO agent, like a checkpoint inhibitor or a checkpoint combo, they really had the most improvement in their overall survival, reaching extremely high survival over periods of time, so that the depth of response was very positively correlated.
Survival essentially the overall survival and what they did find is that patients that had a 75% tumor shrinkage or better including a complete response and particularly from treatment from an Io agents like a checkpoint inhibitor or a checkpoint combo. They really has the most improvement in their overall survival, reaching extremely high.
Hi survival over periods of time, so that the depth of response was very positively correlated. This is something that of course, we see in our melanoma data as well, we see a 34% of patients with a complete response and a large number of patients, reaching 75% or greater tumor shrinkage. So we're very very excited about that day.
Jonathan Zalevsky: This is something that, of course, we see in our melanoma data as well. We see 34% of patients with a complete response, and a large number of patients reaching 75% or greater tumor shrinkage. So we're very, very excited about that data, and we also had the opportunity to present that data to the FDA, and it really was one of the big reasons, the complete response rate and the depth of response, that led to the breakthrough therapy designation that we were awarded in first-line melanoma for the combination of BEMPEG plus NEVO. So all of these factors are coming together, and they look very, very promising and encouraging for the combination, especially for the patient.
And we also had the opportunity to present that data to the FDA FDIC and it really was one of the big reasons. The complete response rate in the death of response that led to the breakthrough therapy designation. The we were awarded in first line melanoma for the combination of them type plus nivo. So all of these factors are.
Our coming together and they look very very promising and encouraging for the combination, especially for the patients.
Jonathan Zalevsky: Thank you, that's a very helpful color. With another one on BEMPEG, with RCC specifically, it's a very competitive landscape. It's constantly evolving. How do you guys see BEMPEG fitting in that overall treatment landscape?
Thank you that's very helpful color within you know with another one and then take with RCC specifically at the very competitive landscape are constantly evolving how do you guys didn't take sitting in that overall treatment landscape.
Jonathan Zalevsky: Yeah, it's a really good question and certainly the results with Exitinib that have been presented lately, both with Merck's Keytruda as well as Pfizer's Avelamab, are very important to the landscape. So for us, it's very important to also consider what the addition of a TKI can bring to the doublet of BEMPEG plus a checkpoint like Nivolumab. So that's something that we're looking into. We have an overall holistic strategy, and in that strategy, you would like to see both TKI inclusive as well as a TKI-sparing set of combinations because not all patients will be able to take TKIs whether they're in single or in combination. So our strategy, working closely with BMS, we'll explore all of that space where BEMPEC can add to multiple combinations in that tumor type.
Yeah, It's a really good question and certainly the results with big sitting there that have been presented lately are both with merck's keytruda as well as Pfizer's Avella Mab are very important to the landscape. So for US. It's very important to also consider what the addition of a T.K. I can bring to the doublet have been peg plus.
Tech point like Nivolumab. So that's something that we're looking into now we have an overall a holistic strategy and in that strategy, you know you'd like to see both teekay inclusive as well as a T.K. I sparing sat at combinations because not all patients will be able to take teekay eyes, whether they're in single or income.
The nation form so our strategy working closely with BMS, we'll explore all of that space, where bamtech can add to multiple combinations in the tumor type.
Okay and then just my last question for that's going on to 358 now with a couple other compounds. There I think earlier in development, but we're just trying to get a feeling of how your compound is differentiated from a lot of these other compounds that are also following.
Jonathan Zalevsky: Okay, and then just my last question, just going on to 358 now, there's a couple other compounds that are, I think, earlier in development, but we're just trying to get a feeling of how your compound is differentiated from a lot of these other compounds that are also following the footsteps that you guys are creating here, and maybe, like, why Lilly and you guys, what was the rationale for going after, like, ps If there was any reasoning for that, that would be helpful, too.
What steps that you guys are creating here and maybe like wise Lilly and you've got what was the.
Rationale for going after like right now.
And they topic dermatitis and loop its whereas there's a couple other diseases that we can think of that would also be a good said there was any reason for that that would be helpful. Too. Thanks <unk> sure.
Jonathan Zalevsky: Sure, so firstly, with regard to differentiation, so one of the features of Nektar 358 is that, as you know, our approach at Nektar is we use our polymer conjugation core competency to modify the properties of the biologic. We do that without the need for mutagenesis or the introduction of any amino acid substitutions into the molecule. Now, when you consider the competing molecules, for example, Amgen has one, Roche has one, Celgene has one, they all have very, very similar amino acid mutations where they reduce the binding to the beta receptor. In some cases, they've even increased the binding to the alpha receptor in order to sort of guide the molecule to have a certain kind of receptor binding profile at the Treg.
So firstly with regards to differentiation. So one of the the features of Nektar 358 is that as you know our approach. It Nektar is we use our polymer conjugation core competency to modify the properties of the biologic, we do that without the need for me to Genesis or introduction.
Any amino acid substitutions into the molecule now when you consider that competing molecules. For example, Amgen has one Roche has one celgene have one they all have very very similar I mean, I said mutations where they reduce the binding to the beta receptor.
Some cases, they've even increase the binding to the alpha receptor in order to sort of guide the molecule to have a certain kind of a receptor binding profile at the T. Reg and then they also all use an FC extension strategy or in the case of Roche and immunoglobulins dimer rises the aisle too.
Jonathan Zalevsky: And then they also all use an FC extension strategy, or in the case of Roche, an immunoglobulin that dimerizes the IL-T. We're able to achieve all of the things that we need to achieve in a completely differentiated manner. Ours is the only molecule compared to that bunch that has no amino acid mutations. And with our polymer, we have a very, very long half-life.
We're able to achieve all of the things that we need to achieving a completely differentiated manner ours is the only molecule compared to that bunch that has no amino acid mutations and with our polymer we have a very very long half life and we've already demonstrated not only in non human primates, but now also in healthy volunteers that we're able to.
Jonathan Zalevsky: And we've already demonstrated, not only in non-human primates but now also in healthy volunteers, that we're able to get the right kind of Treg elevation, the right duration of Treg expansion, and the persistence of Tregs in the blood, following just a single administration of Nektar 358 in the healthy volunteer study. And as Howard mentioned, we will also be concluding our Phase 1b MAD study at the end of this year There, we gave the drug multiple cycles to patients with lupus, and we were able to also follow the Treg expansion and all of those other pharmacodynamic endpoints. So we really have a unique way of differentiating from the pipelines, and it's very much akin to the kind of differentiation that we have with BEMPEG relative to those pipelines as well.
To get the right kind of T. Reg elevation, the right duration of T. Reg expansion and the persistence of tea bags and the blood. Following just a single administration of Nektar 358 in healthy volunteers study and as Howard mentioned, we also will be concluding the end of this year, our phase one be Mad study.
There are we gave the drug multiple cycles into patients with lupus and we were able to also follow the T. Reg expansion and all of those other pharmaco dynamic endpoints. So we really have a unique way of differentiating from the pipelines and it's it's you know very much akin to the kind of differentiation that we have.
With them pag relative to those pipelines as well.
Jonathan Zalevsky: Now, specifically in the context of indications, the TRAG targeting mechanism has a very broad application, as you can imagine, since these cells are involved in maintaining peripheral tolerance against pretty much any kind of T-cell mediated autoimmune or self-reactivity trigger. And so you can apply that broadly to dermatological diseases, to systemic autoimmune diseases like lupus or rheumatoid arthritis, and even to diseases that have a central So what we've done is we've worked closely with Lily to prioritize some of the different biological features that some of these indications share in common, like some of them have some common pathologies, some of them have a certain kind of mode of inflammation that's unique. So in the case of lupus, specifically, this is a case where there's a well-known IL-2 dysfunction.
Now specifically in the context of indications you know I'm. The T. Reg targeting mechanism has very broad application as you can imagine since these cells are involved in maintaining peripheral tolerance against pretty much any kind of T cell mediated auto immune or self reactivity trigger.
And so you can apply that broadly to dermatological diseases to systemic auto immune diseases, like lupus or rheumatoid arthritis, and even to diseases that have essential component like like I Miss.
So what we've done as we work closely with Lilly to prioritize some of the different biological features that some of these indications Sharon common like some of them have some common pathologies some of them have a certain kind of mode of inflammation, that's unique to that either tissue type or that kind of auto immune disease, and so weve been them into.
Groups and buckets and that's why we focused on those indications. So in the case of lupus. Specifically this is the case, where there's a well known aisle to dysfunction lupus patients have reduced levels of T regs and the tier eggs as they do have or non are low functioning there lowly suppressive and a lot of times. They have an expansion of th 17 cells.
Jonathan Zalevsky: Lupus patients have reduced levels of Tregs, and the Tregs that they do have are low-functioning, they're lowly suppressive, and a lot of times they have an expansion of Th17 cells that negatively, sort of like a negative ratio, the Tregs go down, and the Th17 cells go up. So that's a disease where you have a rationale for IL-2, and we've also seen low And in the case of the derm diseases, there again, there are multiple examples where Tregs can impact the skin compartment, whether that's in the setting of atopic dermatitis or psoriasis. And then what you'll see next year is additional indications that Lilly and Nektar will be adding to our partnership. So you'll be seeing those roll themselves out throughout the end of the year, and there'll be new indications different than the three.
That negatively sort of in Pelican negative ratio. The T. Regs go down in the Th 17 cells go up so that's a disease, where you have a rationale for aisle to and we've also see low dose aisle to have the level of efficacy in that disease.
In the case of the derm diseases. There again, there are multiple examples where.
We know the tea bags can impact the skin compartment, whether that's in the setting of atopic dermatitis or psoriasis and then what you'll see next year is additional indications that Lilly and nektar will be adding in our partnership so you'll be seeing those roll themselves out throughout the ended the year and they'll be new indications different.
In the three I just mentioned.
That's perfect. Thank you and I'm sorry, just one more quick question just piggybacking off impressive earlier question with the 0.08 milligram per kilogram dose dumping can you remind us what the safety profile would that and I'll go back I'll go back into queue. Thank you.
Jonathan Zalevsky: That's perfect, thank you. And I'm sorry, just one more quick question, just piggybacking on Chris's earlier question. With the.008 milligram per kilogram dose of Benpeg, can you remind us what the safety profile was with that? And I'll go back into the queue. Thank you.
Jonathan Zalevsky: Yeah, sure. In the monotherapy study, we dosed up to 0.009 mg per kg. We also dosed to 0.012 mg per kg in one patient, so the dose 0.08 is definitely within our window of safety. And if you would actually like to see some of the detailed safety information, we recently published our monotherapy Excel manuscript in Cancer Discovery, and that has the full details of all of the AE profiles across these dose levels, including the 009 and the 012.
Yes sure in the monotherapy study, we dosed up 2.009.
Makes for Keurig, we also does to 0.01 to make for Kagan one patient.
Excuse me I'm. So we the dose 0.08 is definitely within our window of the safety profile and if you actually would like to also see some the detailed safety information. We recently published our monotherapy excel manuscripts in cancer discovery and that has a full details of all of the AG profiles across.
He's dose levels, including the Oh, nine and 012 dose levels.
Jonathan Zalevsky: Thank you. Thank you. Our next question comes from Andy Shea from William Blair. Your line is open.
Thank you.
Thank you. Our next question comes from Andy Zhang from William Blair. Your line is open.
Andy Shea: Great, thanks for taking my question. So, two for Jay-Z, in terms of the Phase 1-235 study, for the monotherapy arm, is it there just for comparative purposes, or is there a specific immunology question they're asking specifically in the CAR-T refractory patient populations?
Great. Thanks for taking my question. So two for JV in terms of the phase one two things I study.
For the monotherapy arm.
Is it they're just for comparative purposes, or if there is a terrific immunology question. There. They are asking specifically in the car T refractory patient population.
Yeah. So it is one of the so one of things we'd like to know is if the kinds of immunological changes that we expect to see with an extra 255 across the NK cell and a subset of the T cell compartments is able to be seen both in NHL patients that have had you know many lines of prior treatment because well.
Jonathan Zalevsky: Yeah, so one of the things we'd like to know is if the kinds of immunological changes that we expect to see with Nektar 255 across the NK cell and the subset of the T cell compartments are able to be seen both in NHL patients that have had, you know, many lines of prior treatment because we're essentially looking at like third-line, you know, very late, late stage kind of salvaged patients. So we really want to make sure that we can induce immunological changes in those as well. And then in the case that they, for example, might have been CAR T refractory, there's also an opportunity to sort of study that kind of immune system in the setting of, again, a patient that has, you know, really failed a lot of prior therapies.
Essentially looking at like third line you know very late late stage kinda salvage patients. So really want to make sure that we can induce the immunological changes in those as well and then in the case that they for example might have been car T. Refractory. It's also an opportunity to it sort of study that kind of an immune system in the said.
Adding up again the patient that has you know really failed a lot of prior therapies.
Okay, and just a follow up on this if he poster I think it did it head to head comparison to 55 versus IL 15 Super agonists.
Andy Shea: Okay. And just to follow up on the SITC poster, I think you did a head-to-head comparison, 255 versus IL-13 super agonist. Yeah. So just curious about your thoughts and, you know, potential clinical implications there.
Yes, so just curious about your thought and you know potential clinical implications there.
Yeah, well I think you know if you're interested in that question I think you'll do very interested in this poster so but the poster does is it takes two different forms of the Io 15, Super agonist sort of families and there's basically two different kinds of that I know you know if there are all of the molecules, where the I'll 15 receptor.
Jonathan Zalevsky: Yeah, well, I think you know, if you're interested in that question, I think you'll be very interested in this poster. So what the poster does is it takes two different forms of the IL-15 super agonist sort of families, and there are basically two different kinds that I know you know of. There are all of the molecules where the IL-15 receptor alpha is in complex with IL-15, and that's usually in an FC kind of background, so that's very similar to like the Altor molecule that NantWest has, or Xencor's molecule is very similar to that, for example. So there's a whole range of molecules that are that kind of complex. And then there's the sushi domain, right, which is just that small 65-amino acid fragment of the alpha receptor bound and complex to IL-4. Both of those are being developed, you know, by numerous companies.
Alpha is in complex with 15, and that's usually in an FC kind of background.
So that's very similar to like the outdoor molecule that Wes has a or xencor as molecule is very similar to that for example, so there's a whole range of molecules that are that kind of complex and then there's the sushi domain right, which is just that small 65 amino acid fragment of the alpha receptor bound and complex.
To the Io 15, both of those are being developed by numerous companies and they both share the binding mode that they're unable to interact with aisle 15 receptor alpha in the body. They can only bind to the die Merrick beta gamma aisle to subset or the diamond receptor.
Jonathan Zalevsky: And they both share the binding mode where they're unable to interact with IL-15 receptor alpha in the body. They can only bind to the dimeric beta-gamma IL-2 subset or the dimeric receptor. And in contrast, in that poster, we take those two molecules as exemplars, and we compare them to Nektar-255. And Nektar-255 is really a lot more like IL-15 in the sense that, A, it can bind to IL-15 receptor alpha anywhere it exists in the body, so wherever it's unoccupied. And then secondly, it can participate in cell-cell mediated signaling interactions. And that's the kind of trans-presentation or trans-binding mode that the other agents that are complexed to the receptor are unable to interact with. And so we take those exemplars through six different kinds of biological test systems, studying everything from receptor internalization, pathway activity, the assessment of STAT versus ERK versus AKT pathways, PI3 kinase pathways, all the things that assess what you'd consider for a full or partial agonism across the pathway, as well as assessing cell-cell mediated contact and assessing multiple cell populations. It's a very interesting So it should be, I think, a poster you might enjoy very much, and certainly, after it's presented, we'll be happy to send it to you.
In contrast in a poster we take those two molecules as exemplary somebody compare them to Nektar 255.
Nektar 255 is really a lot more like aisle 15 in the sense that a combined to aisle 15 receptor alpha anywhere it exists in the body. So wherever it's on occupied and then secondly, it can participate in cell cell mediated signaling interactions and that's the kind of trends presentation or trends binding.
Good.
The other agents that are complex to the receptor unable to interact and and so we take those exemplars through six different kinds of biological test systems setting everything from receptor internalization pathway activity the assessment of stat versus ERC versus 8-K T pathways Pithree kinase.
Pathways, all the things that assess what you'd consider for full or partial agonism across the pathway as well as assessing sell cell mediated contact and assessing multiple cell populations.
It is very interesting kind of scientific work and it really profiles. The difference between these two classes of molecules and it shows a lot of really surprising differences.
I think a poster you might enjoy very much and certainly after it's presented will be happy to send it to.
Andy Shea: Great. Thanks. I appreciate the very detailed answer. Just two quick ones, if you don't mind.
Great. Thanks appreciate the very detailed answer I, just two quick ones.
Few don't mind or any update in terms of timing when are we going to here from the 262 program and also for the pivotal studies ongoing.
Andy Shea: Any updates in terms of timing? When are we going to hear from the 262 program? And also, for the pivotal studies ongoing, are you planning on utilizing the real-time oncology review pathway?
Are you planning on utilizing the real time oncology review pathway.
Jonathan Zalevsky: Sure. So starting with 262, we're still dose escalating in that protocol. And so as we continue to dose escalate, we're still dosing up till we find our recommended phase two dose. And then that will move into an expansion cohort that will basically evaluate the co-administration of 262 along with BEMPEG as a doublet or in a triplet with Nectar 262 as BEMPEG as well as Nivolumab
Sure. So starting with 262, we're still dose escalating in that protocol.
And so as we continue to dose escalate, we're still dosing up until we find our recommended phase two dose and then that will move into an expansion cohort that will basically evaluate the co administration of to 62, along with pag as a doublet or in the triplet.
What's next for Twosix to spend pag as well as Nivolumab and so we expect that we should be able to give an update on the program again next year, it's been roughly a year since the last time, we gave an update in February of 2019 of this year at ASCO City was the last time, we gave an update so yeah, you can expect to see an update of that.
Andy Shea: And so we expect that we should be able to give an update on the program again next year. It's been roughly a year since the last time we gave an update in February of this year at ASCO-CITSE was the last time. So yeah, you can expect to see an update on that program next year. And then regarding oncology, sort of the registrational trials, so we kind of gave you the sort of the cadence of the updates in the earlier question. So the earliest study that we expect to provide data would be around the fourth quarter of 2020. And that could come from a melanoma clinical trial. So that is an opportunity to potentially move into an early approval process, and that's, very much as we've stated before, as you know.
That program next year.
And then regarding the oncology sort of the Registrational trials. So we kind of gave you the sort of the cadence of the updates in an earlier question. So the the earliest study that we expect to provide data would be around the fourth quarter 2020.
Come from them and that will come from the melanoma clinical trial.
So that is an opportunity to potentially move into an early approval process.
And that's assuming that we reached that interim analysis successfully so very much as as Weve stated before as you know.
Jonathan Zalevsky: So, what I meant was the real-time oncology review by the FDA. So basically, what that program allows for is, as the data matures, you basically share that with them in real-time. And therefore, you basically get a very abbreviated review time. Just wondering if you guys are kind of thinking about that.
So yeah, so what I meant what the real time I'll call. It review by the FDA. So so basically what that program allows for it is basically as the data matures you basically share that with in real time, and therefore, you basically get a very abbreviated review time, just wondering if you guys.
I think it yes, sorry, I misunderstood your question Yeah, well. So you know we already have breakthrough therapy designation for example in first line no no right. So yeah, yeah, we're taking every opportunity to leverage the fastest possible review process that we can with the division. So all of the components are in play and as you.
Jonathan Zalevsky: Yeah, well, so you know, we already have breakthrough therapy designation, right, designation, for example, in First Line, Illinois. And so, yeah, we're taking every opportunity to leverage the fastest possible review process that we can with the division. So all of the components are in play. And as you know, the breakthrough therapy designation is very powerful. It allows us additional touch points with the FDA.
No. The breakthrough therapy designation is very powerful it allows us additional touch points with the FDA and it really allows us to move much more quickly through the agency.
Andy Shea: Got it. Great. Thank you very much.
Got it.
Daina Michelle Graybosch: Thank you. And again, ladies and gentlemen, to ask a question, please press star and then 1 now. And our next question comes from Daina Graybosch from SVB Leerink. Your line is open.
Thank you very much.
Thank you and again, ladies and gentlemen to ask a question. Please press Star then one now.
And our next question comes from Dana Gray Bosh from SVB Leerink. Your line is open.
Hi, Thank you for the question a couple of quick ones in a couple wanker, one I didn't hear anything about triple negative breast cancer I Wonder. If you guys can talk about any plans for taking that Florida as well as Glenn you might see some of the non small cell lung data from period to and how.
Daina Michelle Graybosch: Hi, thank you for the question. There are a couple of quick ones and a couple of longer ones.
Howard W. Robin: I didn't hear anything about triple negative breast cancer. I wonder if you guys can talk about any plans for taking that forward, as well as when we might see some of the non-small cell lung data from PivotO2 and Propel. Will it be next year or later than that?
Well the next year or later than that.
Yeah, well with regard to triple negative breast cancer, it's certainly something we're still discussing with BMS and.
Jonathan Zalevsky: Yeah, well, with regard to triple negative breast cancer, it's certainly something we're still discussing with BMS, and we're deciding how we want to approach these new clinical trials, these additional clinical programs. I can tell you that the data that we have so far at pivot was very impressive, and I think we believe that it should be developed for triple negative breast cancer. We'll see how that evolves into the expansion of the new trials that we put together with BMS. And, in any case, if it doesn't go in that direction, I think it's highly likely that we will move it into the clinic with another partner. Jay-Z, do you want to answer the question...
We're deciding how we want to approach these new clinical these additional clinical programs I can tell you that the data that we have so far to pivot.
Was was very impressive and I think we we believe that it should be developed in triple negative breast breast cancer, and we'll see how that evolves into the expansion of the.
The new trials that we put together were with BMS in any case.
It if it doesn't go in that direction I think it's highly likely that we move it into the clinic with another partner.
James You do you want to answer the yes, absolutely. So yeah. So in regards to the first line a non small cell lung cancer cohort and pivot so staying as we did state in our last conference call. The enrollment in that's cohort has been slower than it was anticipated, but there were a number of patients who were.
Howard W. Robin: Absolutely. So, in regards to the first-line non-small-cell lung cancer cohort and pivot, so as we did state in our last conference call, the enrollment in this cohort has been slower than it was anticipated, but there were a number of patients who were enrolled more recently in the second and third quarters. Overall, the early data we're observing in the few patients in the first line, non-small cell lung cancer sub-cohorts, support the BEMPEG mechanism of action and its potential benefit in the below 50% PD-L1 expressors, as well as the PD-L1 negative baseline patients. And we've reported that same kind of effect in other tumor types as well. For example, where we've seen PD-L1 conversion in bladder cancer. However, in the greater than 50% PD-L1 expression sub-cohort, we haven't seen the same benefit, and we're trying to understand this observation in light of the manufacturing issue.
Enrolled more recently in the second and third quarters.
Overall, the early data, we're observing and the few patients in the first line non small cell lung cancer sub cohorts support the Ben Peg mechanism of action and its potential benefit in the below 50% PDL, one expressers as well as the PDL one negative baseline patients and we reported that same kind of effect and other tune.
Her types as well for example, where we've seen PDL, one conversion bladder cancer and so forth in.
In the greater than 50% PDL, one expression sub cohort, we haven't seen the same benefit and we're trying to understand this observation in light of the manufacturing issues.
Howard W. Robin: When we examine the depth of tumor reduction by LOTS, there is some early evidence that patients are benefiting more when they started on LOTS 1 and 3. We're enrolling additional patients in these cohorts, and those patients are starting treatment with BEMPEG LOTS that are not LOTS 2 and 5. And as a result, overall, of the current immaturity of the data and the desire to continue to assess drug lot references, yeah, we did withdraw the abstract from the ESMO meeting, as you know. We want the data to mature more fully, and then we'll make a decision on when and where to present this data.
Well, we examine the depth of tumor reduction by lots. There is some early evidence that patients are benefiting more when they started on lots one in threeq.
We were enrolling additional patients in these cohorts and those patients are starting treatment with Mpeg lots that are not lots to in five.
And as a result overall of the current immaturity of the data and the desire to continue to assess drug lot references yeah. We did withdraw that abstract from ESMO meeting as you know we want the data to mature more fully and then we'll make a decision on one where to present this data in the future.
Jonathan Zalevsky: Now maybe a more theoretical question on Nektar 255. You mentioned the combination of daratumumab, which I think you and many of us know that daratumumab actually knocks down NK cells, targeting T38 on the NK cells themselves. Does combining Nektar 255 help counteract that? Are you just getting more cells, and then daratumumab knocks them down? How are you thinking about that interaction when deciding to combine daratumumab versus other monoclonal antibodies that don't harm NK cells?
Got it. Thank you and then maybe a more theoretical question on Nektar 255, you mentioned a combination if there are two American which I think you know in many other no guarantees are now the actually knocks down NK cells targeting T 38 on the NK cells themselves, that's combining oh nexstar to.
Five five help counteract that you're just getting more thousands air Andexxa, Dan how are you thinking about that interaction when deciding to combine outside their team first is the other monoclonal antibodies that don't Harman case, though.
Jonathan Zalevsky: Yeah, that's a great question, Daina, and it's one of the reasons why we're looking at both rituximab and daratumumab, right, in this early study, and it's precisely for this very reason. It kind of addressed two different questions.
Yeah, that's a great question day in and it's one of the reasons why we're looking at both talks about Bandera tumor Mab right. In this early study and it's precisely for this very reason they kind of address two different questions. So because cdthirty eight as expressed on NK cells and you know there as cdthirty eight positive entity uthreeoeight negative NK cells and they do have some deferred.
Jonathan Zalevsky: So, because CD38 is expressed on NK cells, and you know there are CD38 positive and CD38 negative NK cells, and they do help in roles, and you can see differences in the repletion, right, following DERA in multiple myeloma patients, right, that's been published. So one of the things that we'd like to address in that combination is precisely that effect: we can help sort of replenish the NK cell compartment, and we can help it in two ways. One is that we would prevent DERA direct targeting and also by sort of replenishing the cell populations, but in addition, we can also help the DERA-mediated ADCC because again there would be more NK cells. So it is very much a component of why.
Roles and you can see differences in the repletion right following Dara and a multiple myeloma patients right. That's been published so one of the things that we'd like to addressing that combination is precisely that effect as we can help sort of replenished the NK cell compartment and we can help it in two ways. One is we would prevent.
The Dara direct targeting and also by sort of replenishing the cell populations. But in addition, we can also help the dara mediated ADCC because again, there would be more NK cells. So so it is very much a component of why.
Daina Michelle Graybosch: We want to evaluate those two liquid tumor-targeting ADCC antibodies to really address that kind of difference between their biologies and address the effect of 255 on NK cells in those two different kinds of depletion modes.
We want to evaluate those two liquid tumor targeting ADCC antibodies to really address that that kinda difference between their biology and address the effective to five five on NK cells in those two different kinds of depletion modes.
Great. Thank you that's awesome.
Daina Michelle Graybosch: Great. Thank you. That's all for me. 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.
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.
Well. Thank you everyone for joining us on todays call and of course I'd like to thank all of our employees for their hard work this past quarter and most importantly, we look forward to seeing many of you at the city conference. This weekend. So thank you very much.
Howard W. Robin: Well, thank you everyone for joining us on today's call, and, of course, I'd like to thank all of our employees for their hard work this past quarter. And, most importantly, we look forward to seeing many of you at the CITSE conference this weekend. So, thank you very much.
Ladies and gentlemen, thank you for participating in today's conference. This does conclude the programming you may all disconnect everyone have a wonderful day.
Operator: Ladies and gentlemen, thank you for participating in today's conference. This does conclude the program. You may all disconnect. Everyone, have a wonderful day.
Operator: BF-WATCH TV 2021