Nektar Therapeutics

Ladies and gentlemen, thank you for standing by, and welcome to the Nectar Therapeutics Second Quarter 2020 Financial Results Conference Call. At this time, all participants' lines are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press star and then 1 on your telephone. Please be advised that today's conference may be recorded. If you require any further assistance, please press star and then 0. I would now like to hand the conference over to your speaker today, Ms. Jennifer Ruddock, Head of Corporate Affairs. Ma'am, you may begin. Thank you, Crystal.

Good afternoon, everyone, and thank you for joining us today. With us are Howard Robin, our President and CEO, Gil Libursary, our COO and CFO, Dr. Jonathan Zalevsky, our Chief of Research and Development, and Dr. Wei Lin, our Head of Development. On today's call, we expect to make forward-looking statements regarding our business. including clinical trial enrollment and clinical trial results, timing and plans for future clinical trials, timing and plans for future clinical data presentations, the therapeutic potential of our drug candidates, 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 inherent uncertainties and risks that are difficult to predict, and many of which are outside of our control. Important risks and uncertainties are set forth in our Form 10-Q that we filed on May 8, 2020, which is available at sec.gov. We undertake no obligation to update any of these forward-looking statements, whether as a result of new information, future developments, or otherwise. A webcast of this call will be available on the IR page at NECTAR's website at NECTAR.com. Before turning the call over to Howard, I'd like to comment on a small housekeeping item. Due to the continued shelter-in-place restrictions in San Francisco, each of us are, again, calling in from different locations. So in order to facilitate a smooth call flow, I will moderate the Q&A session for our team so we can avoid technical issues during the session. We appreciate your patience as we work to ensure that there are no technology disruptions for those who are listening. With that said, I will hand the call over to our President and CEO, Howard Robin. Howard?

Thank you, Jennifer, and thank you to everyone for joining us on the call today. I'd like to start the call by reviewing the ways in which we've successfully led our business, as well as our accomplishments during the second quarter and year to date. For all of us located in the many areas that we operate our business and our clinical trials, we continue to face a complex environment caused by COVID-19. Our key focus has been to navigate this dynamic situation with minimal disruption to our business. And as a result of these efforts, we've seen continued progress in the advancement of our registrational and earlier stage clinical trials, as well as the continuation of our research and manufacturing activities in spite of the challenges posed by the COVID-19 pandemic. We ended the second quarter in a position of exceptional strength. We have built a robust pipeline in oncology and immunology, with multiple registrational and earlier stage clinical trials underway. And we ended the second quarter in a strong financial position with $1.2 billion in cash and investments and no debt on our balance sheet. During this time, we've adapted our practices to allow us to both protect the health of our employees and continue essential operations at our locations, such as research and manufacturing laboratory-based activities, which are essential to our business. We've also worked tirelessly with our trial investigators and their teams to ensure that they can continue to provide superior care and uninterrupted access to study treatment to patients fighting cancer in our clinical trials. Finally, we've been diligently working to ensure that the conduct of our clinical trials is minimally impacted by the evolving situation and that the integrity and quality of data being collected from these studies are maintained and tracked appropriately. Wei will review these items in more detail later in the call. With these things in mind, we made great progress on a number of fronts during the second quarter, including continuing to enroll new patients in our clinical studies in order to meet our enrollment timelines, while at the same time providing effective oversight of trial conduct and support to our trial sites. We've worked closely with our pharmaceutical partners on this front as well, and I will provide more updates on this in a moment, We've experienced no supply interruptions for manufacturing and our continued preparations for commercial supply of BEMPEG remain on track. Many of you continue to ask about our assessment of current clinical trial timelines or impacts to any of our clinical studies related to COVID, and I'll provide a review of the current timelines for our studies today. We have been tracking timelines for all of our studies very closely during a fluid and uncertain time, and we will need to continually assess these timelines as well as assess any impact to patients in our clinical studies throughout this year. This quarter, we continue to laser focus on oversight and advancement of the five registrational studies for BEMTAG plus NEVO in the BMS Nectar Joint Development Program. These are the first-line metastatic melanoma study, the first-line bladder cancer study, the first-line renal cell carcinoma study, the muscle invasive bladder cancer study, and the adjuvant melanoma study. In addition to these registrational trials, we're also advancing nicely in the PROPEL study of BEMPEG plus PEMBRO, the NECTAR-262 REVEAL study with BEMPEG, and finally, the NECTAR-255 study in hematological malignancies. First, starting with adjuvant melanoma. We're particularly pleased to announce today that NECTAR achieved their goal to start this Phase III study of BEMPEG plus nivolumab, which plans to enroll 950 patients. Our team was able to initiate this trial in early Q3, which was ahead of our original schedule, with the first patients in the study entering screening just last week. This is an important study that builds on our breakthrough designation achieved with a doublet in metastatic melanoma. In Q2, we recognized a new $25 million milestone payment from BMS related to this study start. I'm very proud of our team and the progress and execution on this front. With respect to the first-line metastatic melanoma study, which is being run by our partner BMS, starting in July, BMS has successfully restarted enrollment activities for this study in many countries. They also have a plan to bring on more sites to this study in order to make up for the lost time related to the COVID pause. At their recent analyst event, BMS indicated that the first data from the melanoma study would be expected in Q4 of 21 or Q1 of 22, and this is relatively consistent with our assessment of the situation, which we provided last quarter, that we expected enrollment delays related to COVID could push timelines out by as long as six months. While we are all disappointed in the timeline delay relative to COVID-19, we're very pleased to see that BMS is actively bringing back enrollment activities which were paused as a result of the pandemic and that they are working to meet these revised timelines for this very important study. Many of you have listened to the BMS analyst call this morning and where they highlighted BEMPAG as an important next-generational late-stage medicine in IO that has achieved proof of concept in their development pipeline. With respect to the first-line bladder cancer study, we expect to be on track to reach our enrollment goal late this summer. As a reminder, the primary endpoints in this study are ORR, and duration of response by independent review for patients with under 10 CPS score. Depending upon how long we follow patients for duration of response, we're projecting a timeline to achieve top line results for this study in the second half of 21, consistent with our prior guidance. For the first line renal cell carcinoma study, we remain on track for our projections for enrollment with this study, which means we also expect to potentially achieve the first interim analysis on the primary endpoint of overall survival in the first quarter of 22, consistent with our prior guidance. For the first-line muscle-invasive bladder cancer study, which is being run by BMS, this study is enrolling approximately 540 patients who will receive BEMPEG plus NEVO or NEVO for a 12-month treatment period following surgery. This study is actively recruiting patients, and more sites are being initiated throughout the year. As this study is longer, we expect first data readouts to be in 2024. With respect to earlier stage studies of BEM-PAG and the BMS Infectory Development Program, BMS is also planning to start an additional study of BEM-PAG plus NEVO in combination with a TKI in patients in the first line renal cell carcinoma setting. This study builds on the registrational study in RCC that we're running of the doublet of BEM-PAG plus NEVO versus a TKI. With respect to first line non-small cell lung cancer, as you know, Nectar has been running the PROPEL study of BEMPEG plus PEMBRO as a separate independent study from the BMS development program with the goal of moving forward with a registrational strategy in non-small cell lung cancer that combines BEMPEG with the existing and preferred standard of care, which is PEMBRO-Lizumab. The development of regulatory pathway for BEMPEG plus NEVO is very challenging given the volumab's lack of a single agent label in first line non-small cell lung cancer. BMS has recently informed us that they will not start the phase two study in first line non-small cell lung cancer with BEMPEG plus NEVO. That was outlined in our amended agreement. Thus, in line with this agreement, Nectar no longer has any exclusivity obligations related to advancing registrational or other trials in non-small cell lung cancer with BMS. With pembrolizumab firmly established as the preferred standard of care, we are now in a position to move quickly on a strategy for a registrational trial in first-line non-small cell lung cancer with PEMBRO upon successful outcomes with a Propel study. The Propel study is actively enrolling patients in line with our timeline objectives, although last quarter we mentioned that the COVID situation delayed initiation for some investigator sites in Europe for Propel. We were able to successfully bring several new European sites online during the second quarter, and these sites are now actively enrolling patients. will expect to be on track to generate initial safety as well as preliminary ORR data for between 10 and 20 patients with a minimum of two scans on treatment from both the dose escalation and non-small cell lung cancer cohorts of this study by the end of this year or first quarter 21. Our phase 1-2 reveal study of Nectar 262 is also on track. We're in the expansion phase of this study which is evaluating simultaneous dosing of the recommended Phase II dose of Nectar 262 administered in combination with BEMPEG, either with or without nivolumab, in up to 24 relapsed and refractory melanoma patients. As we stated last quarter, we observed high levels of TLR activation in the tumor microenvironment during the sequential dosing of Nectar 262 and BEMPEG, and we're able to characterize safety for Nectar 262. These data are being submitted for presentation at the CITSE Congress this November, and support our advancement into the relapse and refractory melanoma patient population post-IO treatments with this program. For NECTAR-255, our IL-15 agonist program and our next cytokine therapy and clinical development, we are actively enrolling patients into the first in human clinical study of NECTAR-255 in patients with hematological malignancies which began late last year. Our goal is to complete the dose escalation monotherapy portion of this study by the end of this year. Of course, meeting this goal will depend on how many dose cohorts we need to enroll before achieving the maximum tolerated dose. As a reminder, this study is evaluating Nectar 255 first as a monotherapy in dose escalation, after which we will expand into several arms that will evaluate Nectar 255 as a monotherapy at the recommended phase two dose, and also evaluate Nectar-255 in combination with Aritumumab in multiple myeloma and with Rituximab in non-Hodgkin's lymphoma. We have already observed target engagements of the IL-15 pathway starting from the first dose level studied and we are very excited to submit these preliminary data for presentation at this year's CIPSI conference. There has been an increasing interest in natural killer cell therapies and we are taking a comprehensive approach to developing NECTAR-255 in several cancer settings. In addition to the studies ongoing in heme malignancies, we're also planning to initiate a study of NECTAR-255 in patients with solid tumors before the end of this year. And Jaydee will talk more about this study in a moment. Moving on to our partner Eli Lilly and NECTAR-358, our Treg Simulatory Program. We recently presented data at the ULAR Congress from the Phase 1B study of Nectar 358 in patients with mild to moderate lupus. These exciting data led to the Phase 2 study, which is also being run by Lilly, in patients with moderate to severe lupus. And I'm excited to announce that Lilly began initiating clinical sites in late July and screening patients in this study just this week. Jaydee will, again, talk more about this study later in the call. In addition, the Phase 1 multiple-dose study in psoriasis and ectopic dermatitis being conducted by Lilly are enrolling patients again after a three-month pause in response to the COVID-19 situation. Finally, we are planning to present additional data on Nectar 358 from the Phase 1B study at the 2020 American College of Rheumatology Congress, also known as ACR, which occurs in early November. So we're all looking forward to sharing new data on Nectar 358 with you folks. Finally, Lilly plans to start another Phase II study in an additional autoimmune disease in the second half of this year. We are very pleased with Lilly's continued commitment to Nectar 358, as well as their broad plans for its development, which reflect the potential of this truly novel mechanism to play an important role in the treatment of a wide range of autoimmune diseases. Before I hand the call to Wei, I'd like to mention an additional data presentation for BEMPEG that we're planning this year. First, for the melanoma cohort from PIVOT-02, as many of you know, last year we obtained an FDA breakthrough therapy designation for BEMPEG plus NEVO in patients with metastatic melanoma based upon the positive data from the PIVOT-02 study, including a high resist complete response rate of 34%, with 42% of patients experiencing complete regression of their resist target meetings. As we stated on our last call, at the 21-month median follow-up point for patients in this cohort, we had still not achieved median PFS. We continue to see deepening of response for these patients and are very excited to submit updated data from the melanoma cohort with an even later data cut closer to this year's 50-2020 meeting. We also plan to present some initial landmark survival data. As we've stated in the past, we are very excited about the potential of this doublet combination for melanoma patients. So for this year's CITSE Congress, our plans are to present data from three Nectar programs. Updated data from the first-line metastatic melanoma cohort, as I just stated, data from the first patients in the Nectar 255 study in hematological malignancies, and data from the dose escalation phase of the Nectar 262 study. And with that, I'd like to turn Nicole over to Wei to review in more detail the Bentec Development Program.