Nektar Therapeutics

Please stand by. Your conference call will begin momentarily. Once again, please remain on the line. Your conference call will begin momentarily. Thank you. Thank you. Thank you. Thank you. Good day and thank you for standing by. Welcome to the Nexra Therapeutics fourth quarter 2021 financial results conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star and then one on your telephone. Please be advised that today's conference may be recorded. If you require any further assistance, please press star and then zero. I would now like to hand the conference over to your speaker today. Jennifer Ruddick, Head of Corporate Affairs. Please go ahead.

Jennifer Ruddick Thank you, Crystal, and good afternoon, everyone. Thank you for joining us today. With us on the call are Howard Robin, our President and CEO, Gil Laboucherie, our COO and CFO, Dr. Jonathan Zaleski, our Chief of Research and Development, and Dr. Dimitri Naughton, our Chief Medical Officer. On today's call, we expect to make forward-looking statements regarding our business, including clinical trial enrollments and clinical trial results, timing and plans for future clinical trials, timing and plans for future clinical data presentations, the therapeutic potential of our drug candidates, outcomes and plans for health authority regulatory actions and decisions, financial guidance, and certain other statements regarding the future of our business. Because these forward-looking statements relate to the future, they are subject to inherent uncertainties and risks that are difficult to predict, and many of which are outside of our control. Our actual results may differ materially from these statements Important risks and uncertainties are set forth in the Form 10-Q that we filed on November 5th, 2021, which is available at sec.gov. We undertake no obligation to update any of these forward-looking statements, whether as a result of new information, future developments, or otherwise. A webcast of this call will be available on the investor relations page of Nectar's website at Nectar.com. Before turning the call over to Howard, I'd like to remind you that since we're calling in from different locations, I will moderate the Q&A session for our team so we can avoid technical issues during the session. We appreciate your patience during this time. With that said, I would like to hand the call over to our president and CEO, Howard Robin. Howard?

Thanks, Jennifer. Thank you all for joining us today. 2021 was highlighted by advancement and execution across many areas of our business, and we continue to establish Nectar's leadership position in the development of cytokine therapeutics for the treatment of cancer and autoimmune disease. And we are excitedly awaiting three late-stage registrational study readouts in the first half of this year from our FEMPEG program. If successful, these studies will put us on a path to regulatory approvals and global commercialization in multiple large frontline cancer settings in melanoma, renal cell carcinoma, and bladder cancer. Our organization is preparing for potential regulatory filings and the commercialization of FEMPEG And moreover, with a breakthrough designation in first-line melanoma, we believe that positive phase three data will enable us to expedite the U.S. regulatory filing for BEMPEG in this setting. And this means we could potentially make BEMPEG available to cancer patients beginning in the latter part of this year or early 2023. Beyond the three studies reading out in the first half of this year, we have several additional registrational studies underway with nivolumab in the adjuvant setting of melanoma and the periadjuvant setting of bladder cancer, and with pembrolizumab in first-line head and neck cancer. A broad global registrational program for BEMPEG was designed to capture the most significant cancer types where we believe BEMPEG in combination with a checkpoint inhibitor has the potential to demonstrate significant clinical benefit for a large number of patients. Current sales of checkpoint inhibitors in these settings are in excess of $6 billion, and we believe we have positioned BEMPEG as a first-in-class IL-2 therapeutic with a development strategy to establish BEMPEG in first-line settings targeting a large number of patients. BEMPEG is the only IL-2 agent in development that possesses three key differentiated attributes in one therapeutic candidate. So first, BEMPEG is designed to allow preferential signaling to the beta gamma portion of the IL-2 pathway with some retained transient binding to the alpha receptor, which is necessary for T-cell priming in the lymph nodes. Second, we leveraged full-lymph IL-2 to avoid treatment challenges that could arise in the mutain structures. And third, MPEG has a prodrug design, which allows us to maintain sustained pathway signaling and mitigate the toxicities associated with high-dose IL-2 and achieve an antibody-like dosing schedule that could be combined easily with a checkpoint inhibitor regimen. These attributes in our first-line registrational clinical program are important competitive advantages and make the development path in these indications very difficult for all other IL-2 programs being pursued by others that are in much earlier stages of research and development. As a leader in cytokine therapeutic development, our next program, Nectar 255, targets the IL-15 pathway, enabling us to stimulate the immune system with natural killer cell proliferation, which we believe has broad therapeutic potential, not just in solid tumors, but also in liquid tumors. And Jay Z will share our progress with that program later in the call. In the area of autoimmune disease, our NECTAR-358 program, partnered with Eli Lilly, is also advancing very rapidly. We're pursuing significant settings for Nectar 358, lupus, ulcerative colitis, and ectopic dermatitis, where sales of current agents range from $12 to $15 billion. So this key program has very significant value to Nectar. And our agreement with Lilly has significant double-digit royalties in the mid-teens and low-20s. And we have the option to co-promote as well. With the broad manufacturing process, the mechanism of Nectar 358 and its potential in a number of autoimmune and inflammatory conditions, we're truly excited about how large the opportunity could be. Nectar 358 is designed to be a monotherapy biologic therapeutic that is administered subcutaneously to treat a range of autoimmune conditions. In December, we were pleased to see our partner Eli Lilly announce at their annual investor meeting the first proof of concept data for Nectar 358 in the setting of ectopic dermatitis. These data underscore the great promise that Lilly and Nectar see in this potential resolution therapeutic. Lilly now has three phase two studies announced for the development program for Nectar 358 in lupus, ulcerative colitis, and ectopic dermatitis, with a fourth phase two study planned as well. Nectar 358 is the clear leader in capitalizing on the novel T regulatory cell top biology with respect to both our scope and our stage of development. And again, Jaydee will spend some time later in the call highlighting the tremendous progress we've made in 2021 for NECTA-358. Now, as this is front of mind for many of you, I'll spend some time now on BEMPEG, which is being developed in combination with checkpoint inhibitors, nivolumab and prembrolizumab. As I mentioned earlier, three studies are on track for top-line data readouts in the first half of this year, beginning first with the Phase III melanoma data, followed by renal cell carcinoma, and then bladder cancer data. Positive results from these studies would support a series of regulatory registrational filings for BEMPEG plus NEVO, followed by commercial launches for the doublet regimen, beginning as early as late 2022 or early 2023. NECDA will lead all distribution, pricing, and market access activities for BEMPEG, Nectar and BMS will share in promotional activities. We look forward to working closely with BMS as we advance towards regulatory filings and launch. And as a reminder, Nectar will book all revenue for BEMPEG and retain 65% of the profit. We estimate the patent protection for the BEMPEG combination with an anti-PD-1 antibody extends to at least February 2035. As I stated at the J.P. Morgan conference in January, BMS and Nectar have guided to top-line results from the Phase III melanoma study before the end of April, and we expect shortly thereafter to have the results from the two studies Nectar is running in renal cell carcinoma and bladder cancer. BMS and Nectar are not providing any additional detail on the timing of these top-line data. As in most late-stage studies conducted in partnership, our companies plan to make a joint announcement. As a reminder, and as we've previously stated, we expect to report top line results for the first two co-primary endpoints of ORR and PFS. With positive PFS results from the melanoma study, we plan to submit regulatory approval filings virtually simultaneously in both U.S. and Europe. The potential European approval and country launches would, of course, follow potential U.S. approval and launch as the process for European regulatory review and approval is typically longer. Now, as a reminder, Nectar is entitled to receive a total of up to $1.4 billion in milestones for BEMPEC filings and first commercial sales following approvals, and Gil will provide more granularity on the timing and triggers for these milestones in a moment when he reviews our 2022 financial guidance. As I mentioned earlier, Jaydee will discuss the Nectar 255 program later in the call, but I'd like to highlight a few key accomplishments for this program in 2021. So first, we generated some important early data in combination with cetuximab and solid tumors in the early dose escalation work in our Phase I clinical study of Nectar-255, and this led to an exciting new collaboration for Nectar-255 with Merck KGA and Pfizer. The collaboration will combine Nectar-255 with Avilamab as part of Merck's Phase II javelin bladder medley umbrella trial. Merck will sponsor and conduct the study, and we will provide supply of Nectar 255. It is a relatively large Phase II comparative study, which has an Avelimab comparator arm and will evaluate treatment in the maintenance setting of bladder cancer, which is a label unique to Avelimab. We're highly encouraged that Merck shares our enthusiasm for Nectar-255 and its potential to combine with a velumab, which has shown an ADCC mechanism in preclinical studies. Also, we recently presented data at ASH highlighting the potential role for Nectar-255 to serve as a CAR-T potentiator, with Nectar-255 eliciting a several-fold increase over baseline CAR-T cells even a year past the patient's CAR-T regimen. We're excited to announce today that we just received FDA clearance for the IND related to a study to evaluate Nectar 255 in the setting of CAR T therapies, specifically CD19 CAR T. The study will be initiated as an investigator-sponsored study at the Fred Hutchinson Cancer Center. From an operational perspective, we have an exceptionally strong balance sheet and ended the year with approximately $800 million in cash This cash position, together with the support of our strategic collaborations and potential for up to $1.4 billion in regulatory filings and first commercial sales milestones, or BEDPEG, provides us with a strong financial foundation to execute our robust development strategy. And with that, I'd like to turn the call over to our Chief Medical Officer, Dr. Dimitri Knighton, to continue. Thank you. Dimitri?