Q3 2020 Nektar Therapeutics Earnings Call
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National if our drug candidates.
Speaker: Our Drug Canada. Outcomes and Plans for Health Authority Regulatory Actions and Decisions, Estimates and Predictions of the COVID-19 Pandemic's Impact on our Business and Clinical Trials, Financial Guidance, and certain other statements regarding the future of our business. Because these forward-looking statements relate to the future, they are subject to assumptions, parent uncertainties, and risks that are difficult to predict, and many of which are outside of our
Outcomes and plan for Health authority regulatory actions and decisions estimates and predictions of the COVID-19, pandemics impact on our business and clinical trial.
Financial guidance and certain other statements regarding the future of our business.
Because forward looking statements relate to the future they are subject to.
Speaker: Important risks and uncertainties are set forth in the Form 10-Q that we filed on August 7, 2020, which is available at www.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 replay of this call will be available on the Investor Relations page on Nektar's website at Nektar.com.
Speaker: Before turning over the call to Howard, as we are all dialing in from separate locations, I will moderate the Q&A session for our team so we can avoid technical issues during the session. We appreciate your patience as we work to ensure that there are no technological disruptions for all of those listening. With that said, I will hand the call over to our president and CEO, Howard Robin.
Howard W. Robin: Thank you, Jennifer, and thank you to everyone for joining us on the call today. Over the past quarter, we've continued to advance our joint development program for BEMPEG with our partner Bristol-Myers Squibb, including the start of two new studies in Q3, a Phase III registrational study in adjuvant melanoma patients that Nektar is sponsoring, and a new Phase I-II study that BMS is sponsoring, which expands the development of BEMPEG in renal cell carcinoma with a triple The BEMPEG Joint Development Program of BEMS now has six separate studies ongoing for our lead cytokine candidate, including five registrations. The Registrational Program for BEMPEG is designed to benefit quite a large patient population across melanoma, renal cell carcinoma, and bladder.
Well the Teekay outage.
The best Pic Joint development program with BMS now at six separate studies ongoing for our lead cytokine candidates, including five Registrational studies.
Howard W. Robin: And this joint development program for BEMPEG plus NEVO reflects a large investment in BEMPEG, and it underscores the excitement for how this unique and differentiated IL-2 agent may serve as an important backbone therapy with the checkpoint inhibitor nivolumab for the treatment of solid tumors. We're also advancing our development of BEMPEG with the checkpoint inhibitor pembrolizumab in the PROPEL study in non-small cell lung cancer, which is one of the largest solid tumor opportunities for BEMPEG. We're well ahead of our enrollment projections for the PROFEL study, and I'll let Wei share more about this program and more about the progress that we've made in the program in that study in a moment.
Speaker: Next week at CIDSE, we will present several new data sets, data for BEMPEG in melanoma with more than 30 months of follow-up for those patients, as well as the first data for our Nektar 255 program, our IL-15, as you know for PivotO2. We reported very strong results for BEMPEG plus NEVO in this cohort at last year's CT, with a high complete response rate of 34%, with 42% of patients experiencing a 100% reduction of their resistance target. And importantly, we recently reported that after 21 months, the cohort had not yet reached a median PFS. These results led to a breakthrough therapy designation for PEMPEG and two large phase three studies in melanoma, one in first-line metastatic melanoma and one in the... The addressable market opportunity for Benpeg in these two areas is quite significant. As a reference, combined Updevo and Katruda sales in this setting are approximately $2 billion.
She is experiencing a 100% reduction of their resis target lesions and importantly, we recently reported that after 21 months the cohort had not yet reached a median PFS.
These results led to a breakthrough therapy designation for peg in two large phase III studies in melanoma.
One in first line metastatic melanoma and one in the adjuvant setting.
The addressable market opportunity for Ben Peg in these two areas is quite significant as a reference combined up tivo and keytruda sales in this setting or approximately $2 billion.
We're excited to share these updated results from the pivotal to melanoma patients.
Howard W. Robin: We're excited to share these updated results from the PivotO2 melanoma patient. Next week at SITSE, we continue to be impressed with the efficacy benefit demonstrated by BMPaG plus Nevo in this study, and we maintain great optimism as we await the phase three data release. Our ultimate goal with BendPeg plus Nevo is to establish a new treatment paradigm in melanoma for the betterment of patients, and Nektar will host an analyst event on November 11th with key oncology experts to discuss these data as well as our additional CITSE presentations. And we hope you'll join us for that discussion.
Next week at city, we continue to be impressed with the efficacy benefit demonstrated by Ben Bank plus Nivo in this study and we maintained great optimism as we await the phase three data readout.
Howard W. Robin: We've also recently initiated a second Phase I-II study of Nektar 255, our IL-15 program and the next cytokine in our pipeline. The new trial will evaluate Nektar 255 in patients with psilocybin. This adds to the ongoing Phase 1 study for Nektar 255 in patients with non-Hodgkin's lymphoma and multiple myeloma. As a reminder, unlike other IL-15 approaches, Nektar-255 was designed to harness the full biology of the IL-15 pathway, meaning that it is specifically designed to capture all of the receptor-ligand interactions available for targeting the IL-15 agonist. We believe this gives Nektar 255 the ability to act as a significant expander of natural killer cells, as well as the ability to promote the survival and expansion of memory CD8 positive T cells. Natural killer cell agents are currently gaining great popularity, and this cancer cell killing mechanism is designed to boost and restore the immune response in patients, which can enable them to more effectively fight cancer. For Nectar 358, we presented new data yesterday at the American College of Rheumatology conference, and I know many of you listened to that presentation. Most notably,
In patients, which can enable them to more effectively fight their cancer.
Howard W. Robin: We observed a dose-dependent increase in T-regulatory cells in lupus patients treated with NECFA-358, with a corresponding order of magnitude of reduction in disease symptomology. In Q3, Lilly started a Phase II study in patients with lupus, and they are also planning a second Phase II study in patients with ulcerative colitis. These are in addition to Lilly's two ongoing Phase 1B studies of Nektar 358 in atopic dermatitis and psoriasis. Nektar 358 is a first-in-class investigational Treg stimulating agent designed to correct an underlying immune imbalance in patients with autoimmune conditions.
End, the Adjuvants melanoma study.
We will provide a thorough review of the entire Bamtech Registrational program momentarily, but I'd like to mention a few timeline highlights from the Registrational program.
Howard W. Robin: Many experience reduced numbers and impaired function of their own two regular arteries. We are very pleased that Lilly is advancing Nektar 358 and we look forward to the continued expansion of this development program. As all of you know, we continue to navigate the evolving COVID-19 landscape, and I'm very proud of our employees who are working hard to ensure the least amount of interruption to our business.
For the propel study in non small cell lung cancer.
We now have three Registrational studies for Ben Peg, where we can see our first data read outs in the same timeline.
He said the metastatic melanoma study this is planned and that was what bladder cancers.
Cancer study and the metastatic RCC study.
Howard W. Robin: To that end, I'm pleased to report that we remain largely on track with our previously discussed trial timelines, which were reviewed in our August financial results. As I stated earlier, we remain highly focused on the five ongoing registrational oncology studies with BEMPEG plus Nivolumab. These are the first-in-line metastatic melanoma study, the first-line bladder cancer study, the first-line renal cell carcinoma study, and the muscle embolization of bladder cancer, and the adjuvant melanoma.
Howard W. Robin: We will provide a thorough review of the entire BEMPEG Registrational Program momentarily, but I'd like to mention a few timeline highlights from the Registrational Program for the PROPEL study in Nansmolsa, London. We now have three registrational studies for BEMPEG where we can see our first data readouts at the same time. These are the Metastatic Melanoma Study, the Cisplatin Ineligible Bladder Cancer Study, and the Metastatic RCC Study. For the metastatic melanoma study, which is being run by BMS, as we've previously stated last quarter, because of COVID-19 delays in that study, we expect to report the first data in late 2021 or early 2022. This study has three endpoints, ORR, PFS, and OS. These are sequential endpoints, and PFS is the endpoint designed to support full approval.
Quarter with a strong balance sheet with over $1.2 billion in cash and investments and know that.
A strong financial position allows us to focus on advancing our pipeline up auto immune ecology candidates, including lead cytokine programs I L. Two and I owe 15, which have brought up likability and a wide range of tumor types and I will now turn it over the call to way to review the pen Pig development program in more detail.
Thank you Howard.
Howard W. Robin: For the bladder cancer study, we expect a similar timeline, reporting ORR and the duration of response in the first part of 2022. And for RCC, we expect our first interim analysis for overall survival around the same time. For non-small cell lung cancer, we are actively enrolling patients into the ongoing PROPEL study of BEMPEG plus Merck's embolism, which is the established standard of care in this setting.
And I can review the progress and timelines for our band packed by traditional program, which includes five separate bags regional studies designed to position Banpais.
The standard of care and frontline metastatic and add some settings in melanoma as well as a kidney cancer and bladder cancer.
Howard W. Robin: These data will inform our strategy for a registrational program for BEMPEG and first-line non-small cell lung cancer. There's been significant investigator interest in this study, and as a result, we've seen a recent increase in patient enrollment. We now expect that we will have preliminary ORR data in the first part of 2021 for approximately 30 patients with a minimum of two scans on treatment from the non-small cell lung cancer cohorts of this study. You'll recall that our original thought was that we would have data available for only 10 to 20 patients. So we're very pleased with the speed of enrollment. We ended the third quarter with a strong balance sheet with over $1.2 billion in cash and investments and no debt.
Wei: Our strong financial position allows us to focus on advancing our pipeline of autoimmunology candidates, including our lead cytokine programs, IL-2 and IL-15, which have broad applicability in a wide range of tumors. And I will now turn over the call to Wei to review the BEMPEG development program in more detail. Thank you, Howard.
Whether we could use it as an endpoint for registration instead of or are.
Speaker: I'd like to review the progress and timelines for our BANPAC Retreational Program, which includes five separate recreational studies designed to position BANPAC as the standard of care in frontline metastatic and action settings in melanoma, as well as kidney cancer and bladder. Let me begin with a first-line metastatic melanoma study, which is being run by our partner, BMS. This summer, BMS successfully restarted enrollment activities for this study in many countries. Since then, they have been able to bring more investigational sites online in an effort to make up for time lost as a result of the COVID-19 pandemic.
Speaker: As Howard mentioned earlier, we have received a breakthrough therapy designation for BAMPAC plus NEVO based on the high complete response rate we observed in the first-line melanoma population. In the Phase 3 study, we have three entities: Overall Response Rate, or ORR, Progression-Free Survival, or PFS, and Overall Survival, OA.
Potential salary to approval filing.
Speaker: The first readout will be an interim look comparing the ORR in the doublet arm of MPEG plus NEVO to the ORR in the NEVO monotherapy arm and will include about two-thirds of the patients in the study who have at least six months of follow-up. This endpoint was designed for a potential early accelerated approval submission for the W, which would enable us to bring this innovative therapy to patients more quickly if approved. The application for full approval of MPEG in the U.S. and in Europe will be based on PFS and the OAS.
Speaker: Because of our high complete response rate, many of you have asked whether we could use this as an endpoint for registration instead of ORR. After discussion with multiple global health companies, VMS and Nektar have made the decision to leave the current protocol intact with the existing end point. The study continues with the original three endpoints of ORR, PFS, and OX. The original design of the study assumes a medium PFS for the nivolumab arm to be comparable to the 6.7 months observed in the Checkmate-067 study. For our study, based upon its original design, the PFS analysis is projected to occur about six to seven months after the OR analysis. However, PFS, it's an event-driven system.
Respondent impact in this indication.
This ends and as Howard stated earlier.
Speaker: A number of other factors could impact this timing as well, including the time needed to review the data by independent blinded radiology review. With respect to the Registrational Study in First-Line Medifact Plata, we reached our enrollment goal in September for this. As a reminder, the primary and secondary endpoints in the study are ORR and duration of response, as determined by central radiology, for about 110 metastatic bladder cancer patients who have a confined PD-L1 positive baseline score of 10 or lower, which will serve as a basis for a potential salary approval file. The duration of response is a critical part, and an important endpoint in this cisplatin-ineligible patient population because this endpoint was the differentiating factor that led to accelerated approvals for single-agent checkpoint inhibitors in this study, as compared to a gem-soda-bean-carboplasm combination standard pair regimen.
Care for the treatment of melanoma and significantly increases the number of patients that can potentially benefit from this agent.
The trial will enroll 950 patients for the 12 month treatment period post surgery.
And the endpoint of event free survival.
Initial data from this study are expected in 2024 as well.
For propel our study in non small cell lung cancer in combination with Pembrolizumab.
We've had great interest in the study from leading thoracic cancer centers in the us in Europe and.
And consequently, we have surpassed our expect enrollment in the last few months.
Speaker: For this study, we are planning a minimum follow-up of 18 months to better assess the duration of response. This brings the timeline for our first data from this study to the first part of 2022 for first-line renal cell carcinoma. We remain on track with our enrollment projections for this study, which means we also expect to achieve the first interim analysis on the primary endpoint of overall survival in the first quarter of 2022, consistent with our prior guidance, based upon the early data generated for BEMtech plus NEBL in Reno, South Carolina. VMS and Nektar have formulated a comprehensive approach for the development of MPEC in this indication, to this end, and as Howard stated earlier
Speaker: In addition to the ongoing Phase III study, BMS recently started a Phase I-II study in this setting, which includes a tyrosine kinase inhibitor. The new study re-evaluates the triplet combination of BEMPEG and nivolumab plus either exsitinib or cobizantin, and we'll then be expanding to a second part, which will compare the triplet of The Muscle Invasive Bladder Cancer Study, which is being run by BMS, is enrolling approximately 540 patients who will receive ENTTEC plus nivolumab or nivolumab monoclonal for a 12-month treatment period following surgery.
Okay, and or reduce production I've been are looking to.
T read deficiencies are important in the pathogenesis of these auto immune diseases.
With an extra 358, our goal is to address these T rag abnormalities and to develop and I owe to like molecule that can selectively stimulate T rags into more effective manner than native I'll too.
Speaker: The study is actively recruiting patients, and more sites have been initiated throughout this year. As this study is longer, we expect the first data readout to be in 2024. Finally, for the adjuvant melanoma, in Q3, we initiated this important additional Phase 3 recreational trial well ahead of schedule. And the study is now active. As Howard stated, this study provides us with an opportunity to position BenPak as a new standard of care for the treatment of melanoma, and it significantly increases the number of patients that can potentially benefit from this age group. The trial enrolled 950 patients for the 12-month treatment period post-surgery and an endpoint of event-free survival. Initial data from this study are expected in 2024 as well. For Propel, our study in non-small cell lung cancer in combination with tembolizumab. We've had great interest in the study from leading thoracic cancer centers in the U.S. and Europe, and consequently, we have surpassed our expected enrollment in the last few months.
At a C. R yesterday, we shared new data from our phase one B study evaluated an extra 358 and patients with mild to moderate lupus and I'd like to call out a few key takeaways.
As we reported that you are earlier in the year nectar 358 led to a selective dose dependent expansion M. C. V 25, bright T. Rex and this was maintained multiple administrations in.
And the date of yesterday, we showed that an extra three finally resulted in dose dependent and increased T rag activation markers and jeans associated the T Rex functionality.
For the first time, we also reported on disease activity that was observed in patients treated with nectar 358.
The study enrolled patients with mild to moderate disease and the patient only received three doses of an extra 358. So it was very short and treatment duration.
Speaker: We now expect that we will have more data for each of the PDR1 patients, less than 1%, 1 to 49%, and 50% and greater PDR1 from this study with data from approximately 30 patients who have had two scans or more available in the first part of 2020 from approximately 30 patients who have had two scans or more available in the first part of 2021. Finally, as we noted last..., we have initiated a proof-of-concept clinical study of MPEG for the treatment of COVID-19 patients. As we all know, the United States continues to hit all-time highs in new daily coronavirus cases, so we saw an opportunity to evaluate them and potentially address an underlying phenomenon being observed in patients who go on to have more severe disease. And that is the observation of a low baseline lymphocyte count in these patients, which may be a result of a lack of an adequate adaptive immune response to the viral infection. For our first study, sites are now open in Texas and Florida, with another planned in Pennsylvania at 10.
J.B.: We're hopeful that BEMPEG could provide a unique approach and early intervention to patients who need to generate a more robust T cell response to this virus. Now I would like to hand the call over to J.B. to discuss more our Nektar 358 and Nektar 255 programs. Thanks, Wei.
Let's see though and.
The treatments are given on an every two week regimen for treatment period at 24 weeks.
Primary endpoint in the phase two study is the reduction in the Lehigh two case scale.
Secondary endpoints include the percent of patients who achieve an Sri for response.
By lag based Bichler response.
And the level of low disease as defined by the lupus low disease activity state or how the asset.
Speaker: Let me begin with a brief update on Nektar 358. Many autoimmune disorders, including systemic lupus, are associated with decreased Treg numbers, reduced Treg function, and or reduced production of interleukin-2. Treg deficiencies are important in the pathogenesis of these autoimmune diseases. With Nektar 358 and other IL-2-like molecules, our goal is to address these Treg abnormalities and to develop an IL-2-like molecule that can selectively stimulate Tregs in a more effective manner than native IL-2. At ACR yesterday, we shared new data from our Phase 1b study evaluating Nektar 358 in patients with mild to moderate lupus, and I'd like to call out a few key takeaways. As we reported at ULAR earlier... Nektar 358 led to a selective, dose-dependent expansion of CD25-Rite Tregs, and this was maintained through multiple administrations.
We will also characterize PK, PD and immunogenicity and treating patients.
The endpoints will be measured at week 24, and we expect the study to be completed within 18 to 24 months.
Now, let's turn to Nektar two high fives are aisle 15 agonist program and our neck cytokine therapy in clinical development.
As Howard stated earlier, the aisle 15 mechanism is being recognized by the scientific community is critically important for the engagement of natural killer cell biology, and the treatment of cancer.
And as you know this area of research is generating much excitement.
Next year to five five is designed to capture the full biology of the aisle 15 pathway.
Both proliferation of NK cells as well as the expansion that CD eight memory T cell.
And this provides us with a wide range of potential development pathways for Nektar 255 in both liquid and solid tumors.
And even virology as demonstrated in our early research collaboration with Gilliatt.
Given nektar two five fives pharmacological profile, we are advancing forward on multiple fronts, but this program.
We are currently conducting a phase one study in patients with relapsed refractory middle logic malignancy.
Speaker: Yesterday, we showed that Nektar 358 resulted in dose-dependent and increased Treg activation markers and genes associated with Treg functionality. For the first time, we also reported on disease activity that was observed in patients treated with Nektar 358. The study enrolled patients with mild to moderate disease, and the patients only received three doses of Nektar 358, so it was very short in treatment duration. In our analysis, we looked at a subset of patients who had moderate disease activity with classy activity scores that were greater than or equal to four. In these patients, Nectar 358 led to a dose-dependent reduction in Class EA score from baseline. Notably, patients at all dose levels with Nectar 358 experienced a reduction in Class EA, while placebo patients did not. And 7 of 18 patients had a 4 or more point score reduction by day 43 as compared to their baseline score. Furthermore, one patient at the highest dose level of 24 micrograms per kilogram experienced a reduction in Class EA score from 22 at baseline to 5 by day 43, two weeks after the last dose of Nektar 358.
Although this study enrollment has been a little slower than we'd like because of COVID-19 challenges in phase. One study sites. We have recently brought on new sites to the study is back on track.
We expect to complete the dose escalation monotherapy portion of this study in the first quarter of 2021.
After dose escalation study will expand into several arms that we'll evaluate nektar 255, as a monotherapy in NHL and will also evaluate nektar 255 in combination with their tumor mob in multiple myeloma and in combination with Rituximab in NHL.
We expect to enroll approximately 60 patients in this part of the study.
We are also very pleased to report today that we recently entered into a new drug supply collaboration with Janssen.
Canson will supply Darzalex fast growth, new subcutaneous version that Dara to AMAP, which was approved for multiple myeloma in may of this year and.
And we look forward to evaluating the combination of Nektar two pie five plus darzalex fast growth in multiple myeloma patients in our ongoing trial.
Speaker: And this is very exciting, see Nektar 358 demonstrated a dose-dependent reduction in class A composite clinical scores in patients with moderate SLE after only three treatment cycles, and it complements well what we're seeing with the PK data for Nektar 358 exposure and the PD data for Treg induction. Overall, we're very excited about these data at HCR 2020 because we have now demonstrated that an SLE patient, Nectar 358 can produce a much larger magnitude of Treg increase than low-dose IL-2. The effects of Nektar 358 are dose-dependent, and we can detect molecular, cellular, and clinical changes in these patients after treatment.
Speaker: The promising results from our Phase 1 studies of NECTA 358 led to the initiation and planning of a number of studies by our partner, Eli Lilly. These include two separate Phase 1b studies in atopic dermatitis and psoriasis, a new Phase 2 study in lupus patients, which started in Q3, and a Phase 2 study being planned in ulcerative colitis. In the phase two study in loop, patients are being randomized to one of three dose levels of Nectar 358 or placebo. And the treatments are given on an every-two-week regimen for a treatment period of 24 weeks. The primary endpoint in the Phase 2 study is the reduction in the SLEDI2K scale. Secondary endpoints include the percent of patients who achieve an SRI-4 response, a BILAG-based Zikla response, and a level of low disease activity as defined by the Lupus Low Disease Activity State or LLDAS.
For our GAAP R&D expense guidance.
Speaker: We will also characterize PK, TD, and immunogenicity in treated patients. The endpoints will be measured at week 24, and we expect the study to be completed within 18 to 24 months. Now, let's turn to Nectar 255, our IL-15 agonist program, and our next cytokine therapy in clinical development. As Howard stated earlier, the IL-15 mechanism is being recognized by the scientific community as critically important for the engagement of natural killer cell biology in the treatment of cancer. And as you know, this area of research is generating much excitement. Nektar 255 is designed to capture the full biology of the IL-15 pathway through both the proliferation of NK cells as well as the expansion of CD8 memory T cells.
We now anticipate 2020, GAAP R&D expense will range between 415, and $425 million, which includes approximately $60 million of noncash depreciation and stock compensation expense.
This decrease in our R&D expense forecast as a result of a number of factors, including the timing of R&D expenditures for certain of our earlier stage and non oncology programs due to coded.
Lower than projected noncash stock compensation, and depreciation expense and reduced travel and other costs due to the impact of the Cove in 19 pandemic.
Our DNA expense for 2020.
Is still projected to be between 105, and 115 million, which.
Which includes approximately $45 million of noncash stock compensation and depreciation expense.
Finally.
Due to the impact of the Cove in 19 pandemic on the financial markets and lower than expected yields on our investment portfolio. We now project that interest income will be approximately $20 million for 2020.
Speaker: And this provides us with a wide range of potential development pathways for Nektar 255 in both liquid and solid tumors, and even in virology, as demonstrated in our early research collaboration with Gilead. Given Nektar 255's pharmacological profile, we are advancing forward on multiple fronts with this program. We are currently conducting a phase one study in patients with relapsed refractory hematologic malignancy. Although study enrollment has been a little slower than we'd like because of COVID-19 challenges at Phase 1 study sites, we have recently brought on new sites, and the study is back on track. We expect to complete the dose escalation monotherapy portion of the study in the first quarter of 2021. After dose escalation, the study will expand into several arms that will evaluate Nektar 255 as monotherapy in NHL and will also evaluate Nektar 255 in combination with daratumumab in multiple myeloma and in combination with rituximab in NHL.
Importantly.
We have not experienced any significant realized or unrealized losses on our portfolio of investments.
We continue to closely manage our operating expenses and remain highly focused on the execution of our broad portfolio of research and development programs.
And as I stated earlier, we still plan to end 2020 with over $1 billion in cash and investments.
And with that I'll open the call to questions operator.
Thank you.
Ladies and gentlemen, if you have a question at this time. Please press the star followed by the number one key on your Touchstone telephone. If your question has been answered all analysts on the sell side and the capital. Please press the pound key once again to ask a question. Please press star and then one now.
And our first question comes from Peter.
Peter Lawson from Barclays. Your line is open.
Hi, guys. This is will lead on for Peter Thanks for taking the question.
So question here on your pivotal study in.
Frontline melanoma, just how we should be thinking about the bar here for efficacy what would be considered positive results.
In your pivotal data that could help support approval.
Thanks, Syed way I'm going to ask you to answer that thanks.
Yes, sure I think to add.
Speaker: We expect to enroll approximately 60 patients in this part of the study. We are also very pleased to report today that we've recently entered into a new drug supply collaboration with Janssen. Janssen will supply Darzilek's fast, their new subcutaneous version of daratumumab, which was approved for multiple myeloma in May of this year.
Speaker: And we look forward to evaluating the combination of Nectar 2x5 plus Darzal X-Faspro in multiple myeloma patients in our ongoing trial. And as mentioned, we expect to open the daratumumab combination cohort, as well as the rituximab combination cohort, after completing the dose escalation portion of the trial in the first quarter of 2021. We have introduced a robust biomarker program into the Phase 1 Nektar 2.5.5 study, which is measuring its effects on multiple immune cell populations that we know are important for tumor control. We're especially focused on the expansion of NK cells, analysis of NK cell subsets as well as their activation and function, and expansion of CD8 T cells. With initial patients treated in our phase one study, we have already observed evidence of target engagement of the IL And we look forward to sharing more details on this next week with Fitzy.
Specifically with regard to our melanoma cohort uhm.
The patient, who who were you <unk> have actually experienced fairly phenomenal Dennis it from the combination of band Peg plus Ebola map with I think at the last a prior earnings call with even 21 months a follow up we have not beach D D medium.
Speaker: We are also very excited that we recently initiated our second Phase 1-2 study of Nektar 255 to evaluate the combination with Tituximab in two distinct groups of highly refractory second and third line patients with metastatic colorectal cancer or metastatic head and neck cancer. The overall study will enroll up to 75 patients and will include a dose escalation component for the combination regimen, which will then be expanded into dedicated expansion cohorts for head and neck and colorectal cancer. We're building significant momentum with the Nectar 255 program, and we look forward to presenting early translational data from the initial dose escalation cohorts in our first In Human Phase I study at CIDCI next week. With that, I will now turn the call over to Gil for a review of the financials. Thank you, Jay-Z, and good afternoon, everyone. On this call, I will review our 2020 financial guidance. Starting with our strong financial position. We ended the quarter with $1.2 billion in cash and investments and no debt on our balance sheet.
She pretty survival. So so at the I'll come your city would be providing even further update with longer follow up and so all of US are certainly very encouraged by the data from pivotal too and if the state three graduation study where two people to replicate the data from pivotal too then.
We should have a fairly sickening margin improvement on N. P. F that compare with people who are single agent and that would bring huge value an extension of survival for patients with first time that no no static melanoma.
Great. Thank you. Thank you for taking the question Sir.
Thank you and our next question comes from Alexandra Duncan Uhm Piper Sandler Your line is open.
Alright, thanks for the questions one on them pig and one on 255, so for been pegged the recent uptick and propel enrollment is great to see just curious to understand the dynamics here a little bit more if you can elaborate on that is this largely due to just continuation indeed <unk> been pig trial.
And secondly for the 255 monotherapy dose escalation update it so let's see what safety signals are you pain, particularly close attention too and then whether or not you identify D. M. T. D. How are you going to use the 255 monotherapy biomarker data to inform.
Gil: We still plan to end 2020 with over a billion in cash and investment. Now, turning to our annual financial guidance. Our full year 2020 GAAP revenue projection remains between $140 and $145 million.
Safe dose selection to use with the combination cohorts I guess my question here is what's your confidence that the combination of 255 and Rituxan for example, well potentiate.
An adverse event such as infections in leather Cox.
Yep.
Gil: This includes $50 million of milestone payments from BMS and 90 to 95 million of royalties, product sales, and other revenue. Under the BMS collaboration, we recognized a $25 million milestone for the start of the muscle-invasive bladder cancer study in Q1, and recognized the second $25 million milestone related to the start of the adjuvant melanoma study in Q2, for GAP R&D Expense Guidance. We now anticipate that 2020 GAAP R&D expense will range between $415 and $425 million, which includes approximately $60 million of non-cash depreciation and stock compensation expense.
Thanks, Alex wait I'm gonna have to answer the first part of the question about the propel study and then JC I'll ask you to take the second one.
Yeah sure yeah. Thanks, Yeah. So uhm propels 30 is as you know it is a study that uhm, we hope that would actually engaged engaged registration study in first non non small cell lung cancer and to that and we're trying to January Diana currently with a doublet of <unk> plus pemble Bismarck.
Building upon the foundation of Pendulous map current standard of care N P O and passed it pay patients uhm. So the now D.
Right now with Covid pandemic happening everyone has experienced a lot of challenges <unk> and and our city team has really navigated. This extraordinary well is weird shared earlier in a earlier earnings call day with a palace dirty while we were planning to open decides in both your.
As well as in the U S. We had some challenges because the first wave pandemic hitting Europe coincided with our plan to initiate the sites, but the we were very vigilant in both on working with a sites finding out the best time to open the sides and and while initially we had a delay and opening besides in your.
Gil: This decrease in our R&D expense forecast is a result of a number of factors, including the timing of R&D expenditures for certain of our earlier stage and non-oncology programs due to COVID, lower than projected non-cash stock compensation and depreciation expense, and reduced travel and other costs due to the impact of the COVID-19 pandemic. Our GNA Expense for 2020 is still projected to be between 105 and 115 million, which includes approximately $45 million of non-cash stock compensation and depreciation expense.
Work, but as soon as the first way pandemic past, we over to get our size have <unk> and a moment has been really really a brisk I think that just reflects <unk> timbral has truly brought a huge improvement in over survival for patients suffering from non small cell lung cancer.
It's benefited still didn't hit with mono therapy to about two years or so so they're still with tremendous need for these patients for uhm better improve therapy, and especially you for things that are chemo spirit, and hence and that's reflected by how well. They study has been road after we have.
Gotten decides to the U S N E.
Gil: Finally... Due to the impact of the COVID-19 pandemic on the financial markets and lower than expected yields on our investment portfolio, we now project that interest income will be approximately $20 million for 2020. Importantly, we have not experienced any significant realized or unrealized losses on our portfolio of investors. We continue to closely manage our operating expenses and remain highly focused on the execution of our broad portfolio of research and development programs. And, as I stated earlier, we still plan to end 2020 with over 1 billion. And with that, I'll open the call to questions. Operator?
And in Europe up and calling so we've seen upgrade to in 2000 for the combination and and I know switched reflecting the need that the doctor can you can you see inside of a pencil monitor P being a wonderful established tend to care to really do it up on that and bleeding proof of them that extending paying patients five minutes and vacation. So we're sort of.
And to stop the study and to stop the data, we able to deliver next year and Oh, so the potential ashamed of data and they are evaluating the possibility of a phase three to follow up on that got analysis.
Thanks way and Alex. Thank you for the question. So regarding 255 uhm. So as you know this is the first and human study.
And in the dose escalation part, we're taking patients, but they're pretty advanced disease, either non hoskins of tele multiple myeloma and treating them with escalating doses of nectar 255 delivered intravenously now what we're looking for in terms of the key safety signals those things that both bird form for them.
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.
<unk> no preclinical toxicology another study, but also bovino experience wise from the groups of all good and others that I've also used I owe 15 as an agent you know clinically. So we're looking for those same kinds of effects were studying T cytokine related toxicities, an adverse events.
We're looking at secondary cytokines, which are essential cause of course, we expect I owe 15, I get to them.
Operator: Once again, to ask a question, please press star and then one now. And our first question comes from Peter Lawson from Barclays. Your line is open. Hi guys, this is Wally Dong from Barclays.
Sounds good express style 15 receptor complexes to induce cytokines responses and we're also study the downstream cellular dynamics associated with dial 15, and as you know it can have a lot of homeostatic effects.
So you were asking if the M. T V. In the study had been reached and he did not we're still dose escalating and we have a very rich biomedical program that we can use to inform does selection and this is you know again a page with a playbook that we played for example, you know <unk>, where we have a lot of markers that.
Waleed: Thanks for taking the question. Just a question here on your pivotal study in frontline melanoma, just how high we should be thinking about the bar here for efficacy. What would be considered positive results in your pivotal data that could help support approval? Thanks, Waleed. Waleed, I'm going to ask you to answer that.
It says the target engagement and I owe 15 with its receptors and you can assess that both of the natural colors solid compartment in terms of cellular response changes activation functional changes of themselves as well as their subsets well as in the C. D. A compartment and then you can assess that both in the blood as well.
Speaker: Thanks. Yeah, sure. I think the way we kind of look at this data is really looking at the control arm, which is the standard here right now is the Ebola map. And so our comparators set up very well and are well-recognized worldwide and would serve as a basis for worldwide registration. So our registration strategy really is a two-step process.
Secondary tissues as well so we use all of those things to inform our selection and you know give us a very very clear confidence. So we've engaged target or getting the kind of pharmacodynamic response, so we want.
Then when we identify a go forward recommended pays to go so the expansion cohorts, you're absolutely right. We're gonna pay a lot of attention to what happens when we combine either <unk> or rituxan map and in that case is you know these are both antibodies that have an I T. G. One.
Speaker: One is we're going to aim for accelerated approval based on ORR and then followed by full approval based on progression pre-survival with subsequent supplement by overall survival. So we're really looking at these two benchmark numbers. So EbolaMAP, in this setting, the baseline response rate is around 40%. So we would like to clear that with, or roughly 10 to 15% higher than the response rate of the Nebulobab single agent. I think then, in a statistically significant fashion, that we have a superior response rate compared to Nebulobab. So that, together with durable response and a safety profile, that will be the final package that will enable thorough approval based on ORR. Now, subsequently, the Progressive Three-Step Outward PFS, which would allow us to gain full approval, will be not only a second shot at gold but also a potential conversion if we gain thorough approval based on ORR.
They'll also antibodies that are known to have you know something like a tumor license syndrome that can be seen when you have a very rapid license a b cells for example, with Rituxan mad when it clears them. So quickly required padded through the living room to the screen fixtures yourself. So we'll be looking very closely at those things and we will be looking very closely.
At the cellular changes and also monitoring the patients very very closely to ensure that we're not seeing any kind of adverse events or a combination because in fact, we tried to the exact opposite which is substantially improve so clearance not just in the blood compartments, but particularly in the secondary lymphoid compartments worthy.
Two or three.
Thanks for the question.
Thank you.
And our next question comes from Jessica I from J P. Morgan Your line is open.
Hi, This is Daniel for just to confine. Thanks for taking a question staying with 255, you say that that you're going in colon cancer and head and neck. Initially install it tumors can you help us think about that I'll put you in a T of 255 install it too nice why you're even to choose those two different <unk>.
Types and then do you see combination of sent ideal approach for this program actually I'd pass it forward or is there an opportunity to evaluate it as a mono therapy as well.
Yeah. Thanks, Uhm <unk> ask you to take that.
Speaker: And that will be benchmarked against the six to seven month PFS that's been observed historically for Nebulobab in this setting. And so, as many of you know, we've been generating early phase data in PIFO2, and specifically with regard to our melanoma cohort. The patients who were enrolled in that cohort have actually experienced fairly phenomenal benefit from the combination of BANPED plus EbolaMAP, and I think, at the prior earnings call, with even 21 months of follow-up, we have not reached the median progressive pre-survival. So at the upcoming CITSE, we'll be providing even further updates with longer follow-up, and so all of us are certainly very encouraged by the data from Pivotal 2. And if this Phase 3 registration study were to be able to replicate the data from Pivotal 2, then we should have a fairly significant margin of improvement in PFA compared with Ebola as a single agent, and that would bring huge value in extension of survival for patients with first-time metastatic melanoma.
Sure the <unk>.
Yeah.
So we really see a tremendous opportunity in solid tumors for and how to agents like 255, because <unk> now monoclonal antibody has become to center care Uhm in and cancer in general, but both in here and tell it humorous and in fact.
Wanted to first approved come on.
Uhm Montgomery I anybody in any cancer type was Hershey herceptin in her to a pastor breast cancer. So there's a long history of traditional upon monoclonal antibody and now it's become while Stablish standard of care and many many tumor types and as we think about how did you fall off 255 within the solid tumor space we will.
Look at Mmm, which which are the indications word.
Did you say you have a monoclonal antibody still remain not in first line, but in later line and with at 10, a care. It's still these a lot of room for improvement and and that that's what really <unk> to really supposed to talk smack in vacation had neck cancer.
Well Ah so colorectal cancer so.
So something had neck cancer for for quite a while set texts math initial was approved as monotherapy uhm in a late mine setting, but eventually moved for the first time setting based on the extreme 12th and then the regiment off so it's <unk> plus plot and chemotherapy close five have you have you.
Speaker: Thank you. Thank you for taking the question. Thank you. And our next question comes from Alexander Duncan from Piper Fandler. Your line is open. Hi, thanks for the questions. One on BEMPEG and one on 255.
I'm in Santa care cannot cancer, <unk> first time setting for quite a while and kill more recent times when pemble isn't that plus chemotherapy has improved on that standard of care and then so then <unk> had returned back to a later mind us us mono therapy and with that.
Alex: So, for BEMPEG, the recent uptick in Propel enrollment is great to see. Just curious to understand the dynamics here a little bit more, if you can elaborate on that. Is this largely due to the discontinuation of the NEVO-BEMPEG trial? And secondly, for the 255 monotherapy dose escalation update at CYPSE, what safety signals are you paying particularly close attention to? And then, whether or not you identify the MTD, how are you going to use the 255 monotherapy biomarker data to inform safe dose selection to use with the combination cohorts? I guess my question here is, how confident are you that the combination of 255 and Rituxan, for example, won't potentiate an adverse event such as infections and liver attacks? Thank you. Thanks, Alex.
Change it creates an opportunity to really improve upon the late mine benefit that this is a tax time for me. Please if you take a look in the late line setting. This tech snap its monetary P. Only have the thought of 15% response rate and so that obviously leaves a lot of room for improvement and M. O a off are too.
Five five molecule, it's really to extend the N K cells, which are so critical and executing the a D. C. C activity of these chronicling the antibodies, including so I <unk>. So D E. D. M O a strongly aren't supports the hypothesis that the addition of 255 by standing Dang.
T cell population will significantly enhance the activities of ADC sand got a life size that tech's math and and improve upon to 15% response rate and late line had neck cancer. So that's the rationale we decided to pick such a text ma'am. That's one of the in heading out cancer just wanted the person Acacia.
Speaker: Wei, I'm going to ask you to answer the first part of the question about the PROPEL study, and then Jay-Z, I'll ask you to answer the second one. Thank you. Yeah, thanks.
Wei: Yeah, so the Propel study, as you know, is a study that we hope will actually engage, engage registration study in first-line non-small cell lung cancer. And to that end, we're trying to generate data currently with the doublet of BEMPEC plus Pembrolizumab, building upon the foundation of Pembrolizumab as the current standard of care in PLM-positive patients. So now, now, right now, with the COVID pandemic happening, everyone has experienced a lot of challenges in enrollment, and our study team has really navigated this extraordinarily well. As we had shared earlier in an earlier earnings call, with the Propel study, while we were planning to open the sites in both Europe as well as in the U.S., we had some challenges because the first wave of the pandemic hitting Europe coincided with our plan But we were very vigilant in both working with the sites and finding out the best time to open the sites, and while initially we had a delay in opening the sites in Europe, but as soon as the first wave of the pandemic passed, we were able to get our sites up and going, and enrollment has been really, really brisk.
To pursue.
In addition, a similar kind of fish nutritionals place out and colorectal cancer now worldwide Uhm cold correct with cancer as soon as much bigger disease now the says the tech not use it's it's somewhat divided so to a large extent so it's a test map, it's either Houston first.
Fine with <unk> setting together with with them a chemotherapy regimen, it's full fury.
Now, but but in some centers as well as some investigators use so I can touch map as a single agent as well so.
Due to the variety of different use we social saw an opportunity to be combined with such a text map a single agent in combination with 92552 pro probably improve upon the the benefit of <unk> and again it seemed to 15% what ancient in terms of <unk> activity and colorectal cancer.
Later line setting and where are we to be successful there in the soon for us to move into earlier on setting where it's in combination with chemotherapy as well so I think now.
It's because both had neck and colorectal cancer offers opportunity to leverage the.
Monica and Friday, a D C. C. M O a N has well established standard of care in use in a later line setting and with the efficacy bar that's <unk> tremendous room for improvement those were the reasons were you kind of pick these indication and picks that's a text that it's a combination partner to start.
Wei: I think that just reflects while Pembrolizumab has really brought a huge improvement in overall survival for patients suffering from non-small cell lung cancer, its benefit is still limited with monotherapy to about two years or so. So there's still a tremendous need for these patients for better, improved therapy, and especially for things that are chemo-sparing. And hence, and that's reflected by how well this study has enrolled after we have gotten the sites in the U.S. and in Europe up and going.
With.
Now if we generate the proof of concept with the text map and had neck cancer <unk> colorectal cancer that would that would allow us to move forward. After demonstrating does sound proof of concept based on this Emily to expand the combination to other 80 C. C based small for antibodies.
Install a tumor <unk> the generation data in Keene allow us to move forward and accumulate just used as well so and to go down upon that and I think too high five when he has huge potential and improve upon the current standard of care, which is whitman wide use of ADC longtime bodies that coverage. So.
Wei: So we've seen a greater enthusiasm for the combination, and also it's reflecting the need that doctors can even see inside of the pample monotherapy being a wonderful established standard of care to really build upon that and really improve on that and extend patients' lives and communications. So we're certainly interested in this study, interested in the data we're able to deliver next year, and also the potential for sharing the data and evaluating the possibility of a phase three to follow up on that data analysis. Thanks, Wei.
Different tumor types so.
Thanks for the question.
Thank you.
And our next question comes from George Farmer from BMO capital market. Your line is open.
Hi, good afternoon, and thanks for taking my questions way can you comment a bit on what the bar for success would be and propel 30 patients that are basically going to be distribute it in a distributed among different P. D. O. One step groups. You know are you expecting to see any differences there.
I know 30 patients as a good number to hit but it spread across all these different subgroups it might get a little thin first subgroup and then J Z I know there was some discussion about this yesterday, but could you talk about the significance of the classy a score and how that relates to to sleet I for in lupus.
Speaker: And, Alex, thank you for the question. Regarding 2-5-5, as you know, this is a first in human study. And in the dose escalation part, we're taking patients with pretty advanced disease, either non-Hodgkin's lymphoma or multiple myeloma, and treating them with escalating doses of Nektar 2-5-5 delivered intravenously. Now, what we're looking for in terms of the key safety signals are things that both are informed from our, you know, preclinical toxicology and other studies, So, we're looking for those same kinds of effects.
And how we can think about two.
Two different scoring systems.
Okay. Thanks for Ya.
Sure.
Yeah I'll take the first part of the credit question. Yeah. Thanks for that Great question. So it's simply something we've thought a lot about because that L. D. Freshly shall go decision is an important decision for give all minute or any any truck and it's four four been packed in particular for the <unk>.
Study as you well know that uhm. The current standard of care really segment that population in the first time metastatic non small cell lung cancer population into three subgroups and that's less than 1% of PDR expression, one 249, and 50 per cent above and and and and and we have.
Either early face that a rescue still got that we can use to benchmark against the historical numbers that pemble. This not has <unk> how populations. So first first of all looking at the the population.
Up less than 1% pemble listen up as a single agent based on the early phase Donna really had a response rate of 728, 8%. So you're really in a single digit range and 5% to 10% range and that's would expect alright. So that's the benchmark for that population of patients for the one 249%.
Jay-Z: We're studying key cytokine-related toxicities and adverse events. We're looking at secondary cytokines, which are essential because, of course, we expect IL-15 agonism in cells that express IL-15 receptor complexes to induce cytokine responses. And we're also studying the downstream cellular dynamics associated with IL-15. And, as you know, it can have a lot of homeostatic effects.
Response rate is typically hovering around 17% or so from from past past trials, specifically keen Oh 42, and so we're really looking at a benchmark pemble a snap in that population patience have one to 49, ranging about 15% to 20% response rate and then finally the <unk>.
Jay-Z: So, you were asking if the MTD in the study had been reached, and it had not. We're still dose escalating, and we have a very rich biomarker program that we can use to inform dose selection, and this is, you know, again, a page from the playbook that we played, for example, with BEMPEG, where we have a lot of markers that assess the target engagement of IL-15 with its receptors, and you can assess that both in the natural killer cell compartment, in terms of cellular response changes So, we use all of those things to inform our dose selection and, you know, give us very, very clear confidence that we've engaged the target or are getting the kind of pharmacodynamic response that we want.
<unk> for the citrus and above P. Delmar expression subgroup looking at data from.
Keynote 24 US was 42 will look at the numbers that are really in the 40% to 50% range. So so that's the baseline response rate for monotherapy pendulous map. So I think to your point I because of the subgroups. We we have when we to generate the 30 <unk>.
30, plus.
Patient worth of data, we'd be looking at data by segmenting into each of the subgroups and this would help us to really understand fully how are drop works and also help us to design a registration study. So I think I think would be.
The rest recent study for a double it up <unk> <unk>.
Jay-Z: So, then, when we identify a go-forward recommended phase 2 dose for the expansion cohort, you're absolutely right; we're going to pay a lot of attention to what happens when we combine daratumumab and rituximab. And in that case, as you know, these are both antibodies that have an IgG1. There are also antibodies that are known to have, you know, something like a tumor lysis syndrome. It can be seen when you have a very rapid lysis of B cells, for example, with rituximab when it clears them so quickly, with clearance either through the liver or to the spleen in the fixed tissue cells.
Putting that again sound pendulous Mad mono therapy will be limited to.
The 1% above population because temporal model, it's not approved and mess one at 1%. However, I think the less than 1% gotta generating from propelled will be extremely form a kid because I think I owe to be known as a pulling fine points.
<unk> is expected to claim that humor, we have shown in our early face data from pickled two entrees biopsy for instance, in our bladder cancer trial, we were able to demonstrate that seven out of 10 patients who previously was P. L negative, meaning perlman expressions at some one less than 1% waved to convert to be.
Jay-Z: So we'll be looking very closely at those things, and we'll be looking very closely at the cellular changes, and also monitoring the patients very, very closely to ensure that we're not seeing any kind of adverse events of the combination because, in fact, we will try to do the exact opposite, which is substantially improve cell clearance, not just in the blood compartments but particularly in the secondary lymphoid compartments where these tumors are. Thanks for the question. Thank you. And our next question comes from Jessica Fye from J.P. Morgan. Your line is open. Hi, this is Daniel for Jessica Fye.
P O on positive after treatment just one cycle treatment open then peg.
And so the I think this is where we really hope to be able to see.
Similar phenomenon in non small cell lung cancer and to propel study and hence L well.
E Uhm Timbral mono therapy as a cruise near broad spectrum of pay patients I think probably the subgroup that'd be most informative to us will be the less than 1% as well as to one 248 112, 49% because number one goes spent parks unknown number two is those benchmarks.
Car actually on for the low such that if we demonstrate I a cyclic improvement.
Daniel: Thanks for taking our question. Staying with 255, you stated that you're going to do colorectal cancer and head and neck, initially on solid tumors. Can you help us think about the opportunity of 255 in solid tumors? Why are you able to choose those two different tumor types? And then, do you see combination as an ideal approach for this program as you advance it forward? Or is there an opportunity to evaluate it as a monitor?
Say Ah doubling off to respond street, and we know that the deep impact US a molecule has truly follow through with Emily US we have seeing other tumor types of being claim that humor, especially in the pedal on low expressing or the non expressing tumors to really engage in your claim that humor along that to be.
Sensitive to a checkpoint hamburger such as temple isn't that so we'd be definitely looking at a doctor in a very nuanced way dissecting out each subgroups and interpreting them separately and looking for <unk> signals that will allow us to have confidence that we have a combination of <unk>.
Wei: Yeah, thanks. By the way, I'm going to ask you to take that. Sure, yeah. So, we really see a tremendous opportunity in cellular tumors for an IL-2 agent like 255, because monoclonal antibody therapy has become standard care in cancer in general, but both in heme and cellular tumors. In fact, one of the first approved monoclonal antibody therapy in any cancer type was HER-Cerceptin in HER2 positive breast cancer. So there's a long history and tradition And as we think about how to develop 255 within the cellular tumor space, we really look at which indications were... The usage of a monoclonal antibody still remains, not in the first line, but in the later line. And with standard care, there still remains a lot of room for improvement. And that's what really drew us to release Sustetoximab in the indication of head and neck cancer, as well as colorectal cancer. So...
I can certainly improve upon the benefit that pemble does that monetary P is given room to patients in first line non small cell lung cancer.
Thanks.
And J C. You Wanna take the coffee Guy.
Yeah, Hey, Hey, George <unk>. Thanks for the question. So so you asked about the classy versus three diet kind of how they're related so to start off with a classy is a score that specifically zeroes in on the cutaneous manifestations of lupus disease, you know so it really looking at the skin.
It's not directly linked to the psoriasis late I, though we always use classy along with those other instruments, because we use them to characterize lupus patients, but there is one important connection and remember lupus patients are characterized by their secondary Oregon involvement.
And the sweet I as well as by like they both take into account the additional accessory tissues and since these are multicomponent scales. You know you get scoring range and everything from the presence or absence of auto antibodies to the presence or absence of secondary Oregon involvement unless you have cutaneous lupus that will.
Wei: Specifically, in head and neck cancer, for quite a while, Cetuximab initially was approved as monotherapy in a late-line setting but eventually moved to the first-line setting based on the EXTREME trial. Then the regimen of Cetuximab plus platen chemotherapy plus 5-FU had become the standard care in head and neck cancer in the first-line setting for quite a while until more recent times when tembolizum And then, so then, the use of Cetuximab has returned to a later-line use as monotherapy. And with that... End of Audio, in demonstrating the ADCC activity of these monoclonal antibodies, including such a test-map. So the MOA strongly supports the hypothesis that the addition of 2,5,5 by expanding the NK cell population would significantly enhance the activities of ADCC antibody-like setzotuximab and improve upon the 15% response rate in late-line head and neck cancer.
Contribute to this really nice for so there is a level of relationships.
Now, we really focused in on it because we know that there is a really good longstanding biology about T rugs and T Rag action, particularly in the skin.
And you know that with Lily. We are currently in the process of two things one of your studies that focus on dermal application right. So there were treating patients in one study with atopic dermatitis. Another study, we're treating patients with psoriasis.
And even if you remember from David's presentation yesterday, he showed that loda style too showed quite a bit of efficacy and patience with psoriasis. Another skin diseases cause he showed that that large table a piece of types of patients treated in trans Rag study.
So really we're we're both extremely excited and encouraged that we saw it does depend a reduction in classy.
The effect was really quite pronounced.
As you saw one patient that was enrolled in the study.
Pretty severe skin involved with with the 22 scored baseline that patient has 17 point reduction in their classy over the course of treatment that patient wasn't and all the the highest dose level a better 358. So it's a very encouraging piece of information and it's very very consistent with the dose dependent relationship.
Wei: So that's sort of the rationale we decided to pick setzotuximab in head and neck cancer as one of the first indications to pursue. In addition, a similar kind of situation was tried in colorectal cancer. Now worldwide, colorectal cancer is something that's a much bigger disease. Now the setzotuximab used, it's somewhat divided. So to a large extent, setzotuximab is either used in a first-line or second-line setting together with a chemotherapy regimen. Now, some centers, as well as some investigators, use such a text map as a single agent as well. So, due to the variety of different uses, we also saw an opportunity to combine with such a text map as a single agent in combination with 255 to improve upon the benefit a single agent has.
And should we C N T rugs and it's one of the main reasons why I was so excited that we're now in the face to be those range finding study with Lily.
A study began you know just a couple of months ago in the summertime and it's currently enrolling patients in a second phase two study is around the corner as well and I'm sorry to colitis, an additional ones will follow next year.
Thanks George.
Thank you and then the interest of time, we kindly ask that you. Please let me guess I'll just have one question at this time.
And our next question comes from the <unk> from the Zoo how your line is open.
Good afternoon, everyone. This is Alex on for a debate. Thanks for taking my question and I apologize. If this was addressed already but quick question of non small cell lung cancer and Pentech combo with Pembroke I'm, assuming you show positive data here and the upcoming Readouts, what would be the strategy I'm going forward and would there.
Wei: And again, it's in the 15% range in terms of single agent activity in colorectal cancer in a later stage setting. And were we to be successful there, it leaves room for us to move into an earlier stage setting where it's in combination with chemotherapy as well. So I think now... It's because both head and neck and colorectal cancer offer opportunities to leverage the monoclonal antibody, ADCC, MOA, and has well-established standard care in use in a later-life setting. And with the efficacy bar that leaves tremendous room for improvement, those were the reasons we kind of picked this indication and picked the text map as a combination partner to start out with. Now, if we generate the proof of concept with the text map in head and neck cancer or in colorectal cancer, that would allow us to move forward after demonstrating this proof of concept based on this MOA to expand the combination to other ADCC-based monoclonal antibodies in cellular tumors, as well as the generation data in heme allow us to move forward in heme legacies as well.
Would be an opportunity to pursue kind of an accelerated pathway.
Approval.
Thanks, I like the way I'll ask you to comment again briefly I'm not sure Yeah I <unk>.
<unk> <unk> <unk> <unk> <unk> <unk>, it's a great idea, that's certainly something that we would be willing to interesting explore with a <unk> now T. Historically and the first line setting they're not being an example off on October approval based on just a a response rate.
Certainly not with exception, but I find like a T K as such as Chris on it. So now so D. So it's something that we will have to explore with a health forties and it really depends on your bill passed my stuff off the data with January <unk>.
Thank you.
Our next question comes from our Linda Lee Some Canaccord your line is open.
Perfect and what's your line is on mute.
Hi, guys. Thanks for taking my question, sorry about that Uhm I'm 358, given the potentially Friday portability.
T Reg mechanism at your cable yesterday I'm kind of curious.
About how you guys children that.
The first two indications and.
To it's for others as well thank you.
Speaker: And to build upon that, and I think 2.5 really has huge potential and will improve upon the current standard of care, which is the wide use of ADCC monoclonal antibodies that cover so many different tumors. Thanks for the question. Thank you. And our next question comes from George Farmer from BMO Capital Markets. Your line is open.
Thanks, and Linda JC I'm gonna have to answer that okay Yep higher Linda Great question. So about the indications for for T. Rag. So there's definitely very large realm of auto immune indications and chronic inflammatory diseases, where you can consider the T Rex <unk>.
And and it kind of sort of breaks apart and some of the different parts of Biology's. So one of the key reasons why we focused on S. L. A is the first indication is that is a disease that has a very clear characteristic dysfunction in the T red compartment.
George Farmer: Hi, good afternoon; thanks for taking my questions. Wei, can you please comment a bit on what the bar for success would be in Propel? 30 patients that are basically going to be distributed among different PD-L1 subgroups, you know; are you expecting to see any differences there? I know 30 patients is a good number to hit, but it's spread across all these different subgroups. It might get a little thin per subgroup. And then, Jay-Z, I know there was some discussion about this yesterday, but could you talk about it?
So those patients have especially as they get more severe than the disease progression. They have both a drop in to brag levels and then the T. Rags that are recovered from those patients are far less oppressive they're much less functionally active now.
Now if you also remember David talked about T Follicular help herself yesterday.
She rags antagonize, though so the T follicular help herself or the main T cells to drive the Germinal center reaction, which leads to antibody production, which an auto immune diseases is really you know detrimental because at least the auto antibody production.
Speaker: The significance of the CLASS EA score and how that relates to SLEDI in lupus and how we can think about the two different... Thanks for where you want to go. Sure. Yeah, I'll take the first part of the question. Yeah. Thanks for that great question.
And in those same patients that have a drop in T. Rex they have an expansion of people that can I help herself. So that was one of the the very strong reasons why some of those early studies and you know in the earliest cases of treating you know lupus patients with little child, who specifically to reduce the T rag increase in there.
Wei: So it's something we've thought a lot about because of that. The registration goal decision is an important decision for the development of any drug. For BEMPEC in particular, and for the PROPEL study, as you well know, the current standard of care really segments that population in the first-line metastatic non-small-cell lung cancer population into three subgroups, and that's less than 1% of PDR expression, 1-49, and then we have either early-phase data or resolution data that we can use to benchmark against the historical numbers that Pembrolizumab has in each of these So first of all, looking at the population, of less than 1%, Temporal LISMAP, a single agent based on their early phase data, really had a response rate of 7 to 8%, so really in the single digit range, in the 5 to 10% range. And that's what we should expect, right?
Patients led to some of the very encouraging results set up the record in that sound. Good replicated in multiple studies, but look logo style too you know you can really only two so much of a T. Reg normalization, so really with an extra 358, we can reach our far higher levels too.
<unk> and sustain those levels for much longer periods of time that is possible with mono style too cause.
So that's why this is a key leaving on vacation for us.
The second indication as alternative colitis, and and actually this is very interesting because you see is also another disease. That's highly done to be characterized by two rug biology and this is biology at the got access where you have a lot of T Rex function associated with the laminar another car.
Signs of compartments, where you're regulating pathologic T cell responses and that disease and and unlike a disease like Lucas, which has auto antibodies <unk>.
<unk> like you see has much less but it is underlying chronic information with pathogenic T cells and here, we know the T. Rags can restore those pathogenic to solve responses. It's also very notable norlander. The the the earliest discovery of the Fox P. Three cell to solve it was originally.
Speaker: So that's the benchmark for that population. For the one to 49%, the response rate is typically hovering around 17% or so from past trials, specifically Kino 42. And so we're really looking at a benchmark for Pembrolizumab in that population of patients of one to 49, ranging about 15 to 20% of response rates. And then finally, the benchmark for the 6% above PD-L1 expression subgroup, looking at data from... Keynote 24 as well as 42, we're looking at numbers that are really in the 40 to 50% range. So that's the baseline response rate for monotherapy pampylosis. So I think to your point, you know, because of these subgroups, we have, when we do generate the 30 plus patient worth of data, we would be looking at the data by segmenting it into each of these subgroups.
Coin to suppress Harold later learned to be a T. Rag actually came from studies an E E E, which is the mouse model.
Of.
D C. So it was a very very.
Gordon related and also can be us as well. So it's very very very nice correlation the links to that and then beyond these to these indications.
We're also evaluating with Eli Lilly a number of other indications in the collaboration that we struck with Lilly Lilly will be running for phase two studies of which the first one is started in a second one that just recently announced just yesterday and getting covered today, you see and said.
There'll be two other studies that are starting uhm and we'll see more of those coming next year, we'll be sampling different indications so it'll be different than the first two and we're really be focusing and all of the places where T rug biology and intervention with 358, we would expect scientists to have a very strong.
The fact that controlling the disease.
Thank you.
Speaker: And this would help us to really understand fully how our drug works and also help us to design our registration. So I think we'll be, now there's a recent study for a doublet of Pembrol plus Bantec. Pitting that against temporalist monotherapy will be limited to, The 1% above population because temporal mono is not approved in less than that 1%. However, I think that less than 1% data generating from Propel will be extremely informative because I think IL-2, being known as a proven inflammatory cytokine, is expected to inflame the tumor, as we have shown in our early phase data from PICC-L2 on treatment biopsies, for instance, in our bladder cancer we were able to demonstrate that 7 out of 10 patients who previously was PD-L1 negative, meaning PD-L1 expression less than 1%, were able to convert to be PD-L1 positive after treatment, just one cycle treatment of BANPAC.
Thank you. Our next question comes from J I'll send some Oppenheimer. Your line is open.
Oh, hi, Thanks for taking my question and congrats on that 358 update yesterday.
I had a question about let's see.
Seems like a dose dependent increase in N K cells and I was wondering how you would interpret those findings. Thank you.
Do you think that's gonna take that.
Yep, Yeah. Thanks, J further questions. So so we do observe low level increases in in in case L. And we only really observe that at the highest dose level tested 24 microgram per kilogram dose level.
No. It's also important to note that will be presented yesterday was we dove into the N K subset.
And so they're they're you know several but the two primary types that occur in you know in humans are the C. V 56 Bright C. D 16, dim subset. These are the ones that cannot participate in a D. C. C. They cannot bind to F C. Because they lack the C V 16 receptor.
And then there's the C V 56, <unk> the 16 bright.
<unk> the 16 them.
Speaker: And so I think this is where we really hope to be able to see similar phenomena in non-small-cell lung cancer in the PROPEL study, and hence, while Pembro Monotherapy is approved in a broad spectrum of patients, I think probably the subgroup that will be most informative to us will be the less than 1%, as well as the 1 to 48, 1 to 49%, because, number one, those benchmarks are known.
Uhm, sorry, the 56, and 16 bright or the majority of the N K cells in the body. They're also the ones that are the most hyperactive and may cause that's the C. D 16, so they buy F. C. An antibody was hector's and what you saw in our presentation at least very little changed in that compartment, where we have the <unk>.
Georgia change the 56 bright 16.
And actually a lot of scientists consider those to be like regulatory N K cells and why they're coin that way is because we don't disagree killer cytokines or inflammatory cytokines in response to stimulus so they're they're almost the kind of salad does the opposite function that.
Speaker: Number two is those benchmark are actually fairly low such that if we demonstrate a significant improvement of say a doubling of the response, then we know that the BMPAC as a molecule has truly followed through with MOA as we have seen in other tumor types of inflaming the tumor, especially in the PD-L1 low-expressing or the non-expressing tumors to really engage and inflame the tumor, allowing it to be sensitive to a checkpoint inhibitor such as Tempolizumab. So, we'd be definitely looking at the data in a very nuanced way, dissecting out each subgroup and interpreting them separately and looking for really robust signals that will allow us to have confidence that we have a combination of BMPAC plus Tempol that can simply improve upon the benefit that Tempolizumab monotherapy is delivering to patients in first-line non-small cell lung cancer. Thanks. And, Jay-Z, you want to take the CLASI versus SLEDI question? Yeah. Hey, George.
You have the traditional main case I'll do.
So that's one important component that's why we presented that day to day to show the delineation and that this is really a subset specific effect.
The other important point is that what we learn is very consistent with what's been known and studied with the use of dial too.
<unk> <unk>.
Many historical uses so we've always seen that that 56 bright excuse me 16 them subset is much more sensitive to I O two than the other in case upset.
And we've also seen the same NK cells elevated multiple studies of logo style too and not just the studies from debit classrooms lab, even John correct studies.
And chronograph person posted these patients. We also saw an expansion of NK cells only has a 56 bright upset and they really haven't been to any sequela.
So it's something that will be following you know and all of our studies cause obviously in phase two will be going too much longer treatment duration and so we'll be studying that very very closely but so far it doesn't look like that seems to have any clinically negative significant smelt.
Speaker: Thanks for the question. So, you asked about the CLASI versus SLEDI, kind of how they're related. And so, to start off with, the CLASI is a score that specifically zeros in on the cutaneous manifestations of the lupus disease, so really looking at the skin.
Thank you.
And our next question comes from all Choi found Goldman Sachs. Your line is open.
Hi, This is Karen Jenkins on for Paul I was hoping you could talk a little bit about your strategy. In melanoma. You think you are going to have potentially a combination and add you then but also two separate combinations and that is all right now, but I was just hoping you could talk a little bit more about how do you think about all of those kind of in the same education.
Speaker: It's not directly linked to the SRI or the SLEDI, but we always use CLASI along with those other instruments because we use them to characterize lupus patients. But there is one important difference. And remember, lupus patients are characterized by their secondary organ involved. This lead eye, as well as bilag, they both take into account the additional accessory tissue. And since these are multi-component scales, you get scoring ranging from the presence or absence of autoantibodies to the presence or absence of secondary organ involvement. For example, if you have cutaneous lupus, that will contribute to the SLEDI score.
Yeah, Thanks for <unk> way I'm Gonna ask you to comment.
Thanks.
Sure Yeah. It's Q, maybe can you elaborate what do you mean by two different combinations an medicine haddock.
And pack next week. So I was just hoping pending obviously positive data then how would you think about development and and what kind of how those two combinations work together in that market.
<unk>, sorry, I didn't catch the first part of what you were saying.
With the city did as an actor 262, and then <unk>.
Your ongoing then paid first of all I live in metastatic melanoma, how are you thinking about that.
Right right. So yeah. So the 262, it's right now he patient population being address is in the post I owe setting so relax apraxia trial versus deep and tech placebo combination that is sweeping to bought the first time that attack melanoma. So the.
Speaker: So there is a level of Now, we really focused in on it because we know that there is really good, long-standing biology about Tregs and Treg action, particularly in the skin. And you know that with Lily, we are currently in the process of two phase 1b studies that focus on dermal application, right? So there we're treating patients in one study with atopic dermatitis. In another study, we're treating patients with psoriasis.
I think so the thinking there is truly in the first time setting we're trying to improve upon the the standard of care, which is need Boulevard single agent, you'll downtown on top of that by introducing combination doublet <unk>.
<unk> plus the full amount and really displacing evil I saw a standard of care not setting now off the patient with salad I O therapy, and the first time setting whether it be checkpoint heavier or nine a P. Two one plus a <unk> for a combination.
Speaker: And even if you remember from David's presentation yesterday, he showed that low-dose IL-2 showed quite a bit of efficacy in patients with psoriasis and other skin diseases, because he showed that large table of phenotypes of patients treated in transreg studies. So really, we're both extremely excited and encouraged that we saw a dose-dependent reduction in Class E. The effect was really quite pronounced, like, as you saw, one patient that was enrolled in the study had pretty severe skin involvement with a 22 score baseline. That patient had a 17-point reduction in their CLASS-E score over the course of treatment.
Those are the patients being really being addressed with he two combinations that are currently reveal study. That's 262 program. You two combinations are to 262 molecule, which is a <unk> receptor seven eight in combination with hunt and Peck or the second combination it's a triplet.
262, plus <unk> plus can you pull a map so that's a triple combination and either combinations will be designed to address a patient who have progressed on a checklist inhibitor and the first time studying whether the addition of a total lockers hepker uhm agonist, which.
Speaker: That patient was enrolled at the highest dose level of Nektar 358. So it's a very encouraging piece of information, and it's very, very consistent with the dose-dependent relationship we see in Tregs. And it's one of the main reasons why we're so excited that we're now in the Phase 2B dose range-finding study with Lilly. That study began just a couple of months ago in the summertime, and it's currently enrolling patients. And a second Phase 2 study is around the corner as well for ulcerative colitis, and additional ones will follow next year. Thanks, George.
Would ignite D. A maiden name and a cheap cause so far I think if you think about whether you're talking about <unk>, four where you're talking about.
A P D one agent or you're talking about a band Tech agent, which is I O two targeting T cells.
All of these are really trying to harness the bodies adaptive immunity in the fight against cancer and to 262 agent and any told Doctor separation is truly <unk>. The other side really quite a trigger immune response, alright trying to trigger adopting U T. Two deactivation.
Speaker: Thank you. And in the interest of time, we kindly ask that you please limit yourselves to one question at this time. And our next question comes from Desai Yang from Mizuho. Your line is open.
Alex: Hi, good afternoon, everyone. This is Alex from DFAT. Thanks for taking the question, and apologies if this was addressed already. But quick question on non-small cell lung cancer and the PEMPEC combo with PEMBRO. Assuming you show positive data here in the upcoming readouts, what would be the strategy going forward? And would there be an opportunity to pursue kind of an accelerated path?
<unk> mood, he first so and and I think there's been some data with other pull doctors Harper agents that seem to indicate that's a viable strategy to really weak 19 in response and really to pull in the adopting a cute by first.
Gauging activating <unk> to these interest you in rejection pull up your separate hockey's, so and I can call. What our strategy is truly unique <unk> is really plugged it 262 or <unk> strategy is being done by others as well we have the unique opportunity to add.
Speaker: Thanks, Alex. Wei, I'll ask you to comment again briefly on that. Sure. Yeah. I think it's a great idea.
Wei: It's certainly something that we would be willing to interest and explore with the health priorities. Now, historically, in the first-line setting, there has not been an example of accelerated approval based on just a response rate, certainly not – with exceptions of like a TCAG, such as for the CRRS-NOTNIP. So, now, so it's something that we will have to explore with the health priorities, and it really depends on the robustness of the data we generate from Propel. Thank you. And our next question comes from Arlinda Lee from Canaccord. Your line is open. Please check that your line is now on mute.
And I owe two agents like Bam peg to livvie additional provide the H boost tobacco <unk> community. So it really you get intense night, all fun off the immune response.
That that's associated with a checkpoint <unk> like an equal amount and you get a Darwin has been on the one hand with a <unk> such as 262, so really trying to claim that humor end of your response by activating the nitty gritty and on the other hand, he also adding an aging like M. P.
Arlinda Lee: Hi guys, thanks for taking my question. Sorry about that.
Speaker: On 358. Given the potentially broad applicability of, and yesterday, I'm kind of curious about how you guys. Foundation, is, Thanks, Erlinda. Jay-Z, I'm going to ask you to answer that.
<unk>, which really enhances adapting me immunity. So so with with this combination. It's I think it's one of the unique combinations that that <unk> <unk> really do that really leverages trying to I T. T immune response in a I L. We've actually practice setting by accident.
Jay-Z: Thank you. Yeah. Hi Erlinda.
Speaker: Great question. So, about the indications for TRAG. So, there's definitely a very large realm of autoimmune indications and chronic inflammatory diseases where you can consider the TRAG mechanism. And it kind of sort of breaks apart in some of the different pathobiology.
<unk> adapted as far as the <unk>.
I hope that helps you to answer your question.
Thank you and that does conclude our question and answer session for today's conference and I'd like to find the call back over it's all Howard Robin for any closing Vermont.
Well. Thank you everyone for joining US today, you know like the first snake are incredible employees for their continued hard working tireless efforts. During these challenging times their dedication to advancing are clinical studies.
Jay-Z: So one of the key reasons why we focused on SLE as the first indication is that it's a disease that has a very clear and characteristic dysfunction in the TRAG compartment. So those patients have, especially as they get more severe in the disease progression, they have both a drop in Treg levels, and then the Tregs that are recovered from those patients are far less suppressive. So they're much less functionally active. Now, if you also remember, David talked about T follicular helper cells yesterday. Tregs antagonize those cells, and T-follicular helper cells are the main T-cells that drive the germinal center reaction, which leads to antibody production, which in autoimmune diseases is really detrimental because it leads to autoantibody production.
Keeping our business on track makes me, especially proud.
As I stated earlier, we're well positioned with a strong balance sheet.
Drink portfolio and you know oncology.
Programs and we thank our shareholders for their ongoing support and look forward to continuing to provide you with updates on our progress and please join us at our analyst event on November 11th and lastly, we sincerely hope that you and your family you stay safe and healthy throughout the coming months. So thank you very much.
For joining us today.
Ladies and gentlemen. This concludes today's conference. Thank you for your participation and you may now disconnect everyone have a wonderful day.
Jay-Z: And in those same patients that have a drop in Tregs, they have an expansion of T-follicular helpers. So, that was one of the very strong reasons why some of those early studies, you know, in the earliest cases of treating lupus patients with low-dose IL-2 specifically to reduce the TRAG increase in those patients led to some of the very encouraging results that have been reported. And that's now been replicated in multiple studies. But with low-dose IL-2, you can really only achieve so much of TRAG normalization. So, really, with Nectar 358 we can reach far, far higher levels of TRAG elevation and sustain those levels for much longer periods of time than is possible with low-dose IL-2. And that's why this is a key lead indication for us.
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Jay-Z: The second indication is ulcerative colitis, and actually, this is very interesting because UC is also another disease that's highly known to be characterized by Treg biology. And this is biology at the gut axis, where you have a lot of Treg function associated with the lamina and other kinds of compartments where you're regulating pathologic T cell responses in that disease. And unlike a disease like lupus, which has autoantibodies, a disease like UC has much less, but it has underlying chronic inflammation with pathogenic T-cells.
Jay-Z: And here we know that T-regs can restore those pathogenic T-cell responses. It's also very notable, Arlinda, that the earliest discovery of the FOXP3 cell, the cell that was originally coined a T-suppressor cell but later learned to be a T-reg, actually came from studies in EAE, which is the mouse model of UC. So it's a very, very important related, and also TNBS as well. So it's a very, very, very nice correlation that links to that. And then beyond these two indications, we're also evaluating with Eli Lilly a number of other indications. In the collaboration that we struck with Lilly, Lilly will be running four Phase II studies, of which the first one has started, and the second one was just recently announced, just yesterday, and again covered today with UC.
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Jay-Z: And so there'll be two other studies that are starting, and we'll see more of those coming next year. We'll be sampling different indications, so they will be different than these first two, and we'll really be focusing on all of the places where Treg biology and intervention with 358 would be expected scientifically to have a very strong effect in controlling the disease. Thank you. Thank you. Our next question comes from Jay Olson from Oppenheimer. Your line is open.
Jay Olson: Oh, hi. Thanks for taking my question, and congrats on the 358 update yesterday. I had a question about what seems like a dose-dependent increase in NK cells, and I was wondering how you would interpret those findings. Thank you. J.C., I'll ask you to take... Yeah, thanks, Jay, for the question.
J.C.: So, we do observe low-level increases in NK cells, and we only really observe that at the highest dose level tested, 24 micrograms per kilogram dose level. Now, it's also important to note that what we presented yesterday was we dove into the NK subsets. And so, there are several, but the two primary types that occur in humans are the CD56 bright and CD16 dim subsets.
Speaker: These are the ones that cannot participate in ADCC. They cannot bind to FC because they lack the CD16 receptor. And then there's the CD56 dim, and the CD16 bright.
Speaker: And the 16 DIMM, sorry, the 56 DIMM, 16 BRITE are the majority of the NK cells in the body. They're also the ones that are the most hyperactive, and they possess the CD16, so they bind to F-suite and antibody receptors. And what you saw in our presentation is that we saw very little change in that compartment, but we saw the majority of change in the 56 BRITE, and 16 DIMM. And actually, a lot of scientists consider those to be like regulatory NK cells. And why they're coined that way is because they don't secrete killer cytokines or inflammatory cytokines in response to stimuli.
Speaker: So they're almost the kind of cell that does the opposite function that you have the traditional in case I'll do. So that's one important component. That's why we presented that data, Jay, to show the delineation and that this is really a subset-specific effect. The other important point is that what we learned is very consistent with what's been known and studied with the use of IL-2 throughout, you know, many historical uses. So we've always seen that the VAT-56 BRITE CD16 DIMM subset is much more sensitive to IL-2 than the other NK subset. And we've also seen those same NK cells elevated in multiple studies of low-dose IL-2, and not just the studies from David Klatsman's lab, but even John Kuret's studies in chronic graft-versus-host disease patients.
Speaker: We also saw an expansion of NK cells, only the 56-brite subset, and they really haven't led to any sequela. So it's something that we'll be following, you know, in all of our studies, because obviously, in Phase II, we'll be going to a much longer treatment duration. And so we'll be studying that very, very closely, but so far, it doesn't look like that seems to have any clinically negative significance at all. Thank you. And our next question comes from Paul Choi from Goldman Sachs. Your line is open.
Paul Choi: Hi, this is Corinne Jenkins on for Paul. I was hoping you could talk a little bit about your strategy for treating melanoma. I think you're going to potentially have a combination in adjuvant, but also two separate combinations in metastatic melanoma. And I was just hoping you could talk a little bit more about how you think about all of those kinds of in the same indication. Yes. Thanks, Corinne. Wei, I'm going to ask you to comment on this.
Corinne Jenkins: Thanks. Sure. Yes. Can you maybe elaborate on what you mean by two different combinations in metastatic? Ben Pegg next week.
Speaker: So just hoping, pending obviously positive data, but how would you think about development and how those two combinations work together in that market? Sorry, I didn't catch the first part of what you were saying. With the SIDSI data for Nektar 262 and BIMPEG, plus your ongoing BIMPEG studies and metastatic melanoma, how are you thinking about that? Right, right. So, yeah.
Wei: So, the 262, right now, the patient population being addressed is in the post-IO setting. So, relaxotractory to IO versus the BEMPEC plus NEBO combination that is really being developed in the first line, which is melanoma. So, I think the thinking there is really in the first line setting, we're trying to improve upon the standard care, which is NEBO as a single agent, build on top of that by introducing a combination doublet of BEMPEC plus NEBO and really replacing NEBO as a standard of care in that setting. Now, after the patient who has failed IO therapy in the first line setting, whether it be checkpoint inhibitor or APD That's the 262 program. The two combinations are the 262 molecule, which is a total X-receptor 7.8 in combination with BEMPEC, or the second combination, the triplet of 262 plus BEMPEC plus NEBO-LOMAP. So, that's a triple combination.
[music].
Speaker: And either combination is really designed to address a patient who has progressed on a checkpoint inhibitor in the first line setting, whether the addition of a total X-receptor agonist, which would ignite innate immunity. So far, I think, if you think about whether you're talking about CTLA-4 or you're talking about a PD-1 agent, or you're talking about a BMPAC agent, which is All of these are really trying to harness the body's adaptive immunity in the fight against cancer. And the 262 agent and any total active separation is really on the other side, really trying to trigger a new response, trying to trigger adaptive immunity through the activation of innate immunity first. So, and I think there's been some data with other total active receptor agents that seem to indicate that's a viable strategy to really reignite the immune response and really pull in the adaptive immunity by first engaging and activating DNA immunity through these intratumor injections of total active receptor activity. So, and I think what our strategy is really unique in is that, well, the 262 or total active discovery strategy is being done by others as well.
Wei: We have the unique opportunity to add IL-2 agents like BAMPEG to really provide that additional boost to that community. So really, you get an enhancement of the immune response that's associated with a checkpoint inhibitor like nivolumab. And you get a double enhancement on the one hand with a tolexis agonist such as 262, so really trying to inflame the tumor and the immune response by activating innate immunity. And on the other hand, you also add an agent like NPEG, which really enhances the adaptive immunity. So with this combination, I think it's one of the unique combinations that only Nektar can really do that really leverages trying to activate the immune response in an IL-relaxed refractory setting by activating both the adaptive as well as the innate immune response.
[music].
Howard W. Robin: I hope that helps to answer your question. Thank you. And that does conclude our question and answer session for today's conference. I'd now like to turn the call back over to Howard Robin for any closing remarks.
Howard W. Robin: Well, thank you, everyone, for joining us today. I'd like to first thank our incredible staff for their continued hard work and tireless efforts during these challenging times. Their dedication to advancing our clinical studies while keeping our business on track makes me especially proud. As I stated earlier, we're well-positioned with a strong balance sheet, a maturing portfolio of immuno-oncology and immunology programs, and we thank our shareholders for their ongoing support and look forward to continuing to provide you with updates on our progress. And please join us at our analyst event on November 11th. And lastly, we sincerely hope that you and your family stay safe and healthy throughout the coming months. So, thank you very much for joining us. Ladies and gentlemen, this concludes today's conference.
Howard W. Robin: Thank you for your participation and you may now disconnect everyone. Have a wonderful day, ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ??