Interferon gamma biosimilar(Livzon Pharmaceutical Group, Inc.)

NKTR-288 upregulated MHC Class I and PD-L1 expression on tumors, enhancing anti-tumor activity when combined with anti-PD-1 or anti-PD-L1 antibodies SAN FRANCISCO, Nov. 10, 2022 /PRNewswire/ -- Nektar Therapeutics (Nasdaq: NKTR) today announced the first presentation of preclinical data for NKTR-288 at the 2022 Society for Immunotherapy of Cancer (SITC) Annual Meeting. NKTR-288 is a novel polyethylene glycol (PEG)-conjugate of interferon gamma (IFN-γ), designed to modify binding of IFN-γ to its substrates and optimize the duration of IFN-γ signaling. IFN-γ is a cytokine that induces cellular antigen presentation and enhances tumor antigen-specific cytotoxic T cell response, and may have applications in a number of therapeutic areas, including oncology and infectious diseases, among others. The presentation today showed the sustained pharmacological properties of NKTR-288 relative to native cytokine, including durable exposure and induction of the well characterized interferon gamma response. These data support further evaluation of NKTR-288 as a monotherapy or in combination with checkpoint inhibitors in the clinical setting. "The results presented at SITC clearly demonstrate that NKTR-288 has differentiated pharmacokinetic and pharmacodynamic properties compared to native IFN-γ, leading to durable in vivo anti-tumor activity in preclinical models," said Jonathan Zalevsky, Ph.D., Senior Vice President and Chief Research & Development Officer at Nektar. "Particularly promising were data that show NKTR-288 upregulates PD-L1 expression in tumor tissue, supporting potential combination therapy with checkpoint inhibitors by enhancing checkpoint blockade efficacy in low-MHC Class I 'cold' tumor models. It highlights the potential of NKTR-288 to augment currently available PD-1 or PD-L1 treatment strategies and possibly broaden the responsive patient population." Also presented at SITC by Nektar's partner, Merck KGaA, is a trials in progress poster of the Phase 2 JAVELIN Bladder Medley study (NCT05327530). The ongoing clinical trial includes evaluation of BAVENCIO® (avelumab), Merck's anti-PD-L1 therapy, in combination with NKTR-255, Nektar's IL-15 receptor agonist designed to increase the proliferation and survival of natural killer (NK) cells and memory CD8+ T cells to enhance anti-tumor immunity. Merck KGaA is running this study and is on track to generate comparative progression-free survival (PFS) data for this study by the end of 2024. Key details and takeaways from the presentation are as follows: Abstract 1086: "NKTR-288, a PEGylated Interferon Gamma Drug Candidate for the Treatment of Cancer", Hamel, D., et al. NKTR-288 demonstrated reduced affinity to both IFN-γ receptor and heparin, decreasing target mediated drug disposition (TMDD) and increasing bioavailability compared to native IFN-γ. Induced sustained upregulation of major histocompatibility complex class I (MHC Class I) expression in fast-growing, low-MHC Class I "cold" syngeneic tumor models, as well as T cell-mediated anti-tumor activity, alone and in combination with checkpoint inhibitors. NKTR-288 also upregulated PD-L1 expression in tumor tissue as a monotherapy, while significant anti-tumor activity was observed when combined with anti-PD-1 or anti-PD-L1 antibodies. Well tolerated at pharmacologically active doses in preclinical models well below maximum tolerated dose (1 mg/kg). These results support the development of NKTR-288, a novel, optimized IFN-γ pathway agonist, to treat cancer as a monotherapy or in combination with PD-1/PD-L1 therapy. Details of the Trials in Progress poster presentation are as follows: Abstract 665: "JAVELIN Bladder Medley: a phase 2 trial of avelumab in combination with other antitumor drugs as first-line maintenance therapy for advanced urothelial carcinoma", Hoffman-Censits, J., et al. The objective of the phase 2, multicenter, randomized, open-label parallel-arm JAVELIN Bladder Medley umbrella trial (NCT05327530) is to assess the safety and efficacy of avelumab in combination with other antitumor agents, including NKTR-255, as first-line (1L) maintenance treatment for patients with advanced urothelial carcinoma (UC). When completed, the ongoing JAVELIN Bladder Medley study will show whether 1L maintenance treatment with avelumab-based combinations can improve PFS vs avelumab alone and report the safety and tolerability of the combination regimens. Details of the data presentations at SITC are available on the Science section of Nektar's website at . About NKTR-288 NKTR-288 is a PEG-conjugate of the protein, IFN-γ, a cytokine that induces cellular antigen presentation and has great potential in cancer treatment through enhancement of tumor antigen specific cytotoxic T cell response. NKTR-288 was designed utilizing a site-specific conjugation approach to modify binding of IFN-γ with one of its substrates, and overall, to optimize the duration of IFN-γ signaling. This program has applications in a number of therapeutic indications including oncology as well as in infectious disease and others. About NKTR-255 NKTR-255 is a biologic that targets the IL-15 pathway in order to activate the body's innate and adaptive immunity. Through optimal engagement of the IL-15 receptor complex, NKTR-255 is designed to enhance functional NK cell populations and formation of long-term immunological memory, which may lead to sustained and durable anti-tumor immune response. Preclinical findings suggest NKTR-255 has the potential to synergistically combine with antibody-dependent cellular cytotoxicity molecules as well as to enhance CAR-T therapies. Nektar has initiated a Phase 1 dose escalation and expansion clinical study of NKTR-255 in adults with relapsed or refractory non-Hodgkin lymphoma or multiple myeloma, as well as a Phase 1/2 clinical study of NKTR-255 in patients with relapsed or refractory head and neck squamous cell carcinoma or colorectal cancer. Nektar is also continuing its oncology clinical collaboration with Merck KGaA and Pfizer Inc. to evaluate the maintenance regimen of NKTR-255 in combination with avelumab, a PD-L1 inhibitor, in patients with locally advanced or metastatic urothelial carcinoma in the Phase 2 JAVELIN Bladder Medley study. Nektar is also currently designing a Nektar-sponsored Phase 2/3 study combining NKTR-255 with approved CAR-T cell therapies in diffuse large B-cell lymphoma, which it aims to initiate in the first quarter of 2023. About Nektar Therapeutics Nektar Therapeutics is a biopharmaceutical company with a robust, wholly owned R&D pipeline of investigational medicines in oncology and immunology as well as a portfolio of approved partnered medicines. Nektar is headquartered in San Francisco, California, with additional operations in Huntsville, Alabama. Further information about the company and its drug development programs and capabilities may be found online at . Nektar Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements which can be identified by words such as: "will," "may," "demonstrate," "potential," "designed," "initiate," "generate" and similar references to future periods. Examples of forward-looking statements include, among others, statements we make regarding the therapeutic potential of, and future development plans for NKTR-288, NKTR 255 and our other drug candidates in research programs, the prospects and plans for our collaborations with other companies, and the timing of the initiation of clinical studies and the data readouts for our drug candidates. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based only on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, anticipated events and trends, the economy and other future conditions. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict and many of which are outside of our control. Our actual results may differ materially from those indicated in the forward-looking statements. Therefore, you should not rely on any of these forward-looking statements. Important factors that could cause our actual results to differ materially from those indicated in the forward-looking statements include, among others: (i) our statements regarding the therapeutic potential of NKTR-288, NKTR-255 and our other drug candidates are based on preclinical and clinical findings and observations and are subject to change as research and development continue; (ii) NKTR-288, NKTR-255 and our other drug candidates are investigational agents and continued research and development for these drug candidates is subject to substantial risks, including negative safety and efficacy findings in ongoing clinical studies (notwithstanding positive findings in earlier preclinical and clinical studies); (iii) NKTR-288, NKTR-255 and our other drug candidates are in various stages of clinical development and the risk of failure is high and can unexpectedly occur at any stage prior to regulatory approval; (iv) the timing of the commencement or end of clinical trials and the availability of clinical data may be delayed or unsuccessful due to challenges caused by the COVID-19 pandemic, regulatory delays, slower than anticipated patient enrollment, manufacturing challenges, changing standards of care, evolving regulatory requirements, clinical trial design, clinical outcomes, competitive factors, or delay or failure in ultimately obtaining regulatory approval in one or more important markets; (v) we may not achieve the expected costs savings we expect from our corporate restructuring and reorganization, (vi) patents may not issue from our patent applications for our drug candidates, patents that have issued may not be enforceable, or additional intellectual property licenses from third parties may be required; and (vii) certain other important risks and uncertainties set forth in our Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on November 4, 2022. Any forward-looking statement made by us in this press release is based only on information currently available to us and speaks only as of the date on which it is made. We undertake no obligation to update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise. Contact: For Media: David Rosen of Argot Partners (212) 600-1902 david.rosen@argotpartners.com For Investors: Vivian Wu of Nektar Therapeutics 628-895-0661 Company Codes: NASDAQ-NMS:NKTR

SAN FRANCISCO, Nov. 3, 2022 /PRNewswire/ -- Nektar Therapeutics (Nasdaq: NKTR) today reported financial results for the third quarter ended September 30, 2022. Cash and investments in marketable securities on September 30, 2022, were approximately $546.4 million as compared to $628.2 million at the end of the second quarter of 2022. Our cash and marketable securities are expected to support our strategic development activities and operations through the middle of 2025. "In the third quarter, we made progress advancing our biologics pipeline in oncology and immunology," said Howard W. Robin, President and CEO of Nektar. "With our partner, Eli Lilly, we presented positive proof-of-concept data for NKTR-358 in atopic dermatitis which demonstrate the potential for this first-in-class Treg stimulator to emerge as a differentiated therapy for patients with serious inflammatory conditions. In the first half of 2023, we expect Lilly to report topline data from the Phase 2 study of NKTR-358 in lupus as well as initiate a Phase 2 study in atopic dermatitis." "In addition, we are also advancing NKTR-255 in large B-cell lymphoma, with plans to launch a comparative study in combination with approved autologous CD19 CAR-T therapies," continued Robin. "NKTR-255 targets the IL-15 pathway and we have conducted and published extensive preclinical studies showing that IL-15 can potentiate these approved cell therapies by expanding and extending the persistence of CAR-T cells. Finally, we are planning presentations at both SITC and ASH for both our preclinical and clinical programs that will showcase the strength of our science and lay the foundation for continued pipeline progress." Summary of Financial Results Revenue, which primarily includes non-cash royalty revenue, in the third quarter of 2022 was $23.6 million as compared to $24.9 million in the third quarter of 2021. Revenue for the first nine months of 2022 was $70.0 million as compared to $76.9 million in the first nine months of 2021. Revenue was lower compared to 2021 as a result of a decrease in non-cash royalty revenue. Total operating costs and expenses in the third quarter of 2022 were $77.9 million as compared to $138.5 million in the third quarter of 2021. Total operating costs and expenses in the first nine months of 2022 were $393.7 million as compared to $410.1 million in the first nine months of 2021. Operating costs and expenses for the first nine months of 2022 include $124.3 million in restructuring, impairment and other costs of terminated program. R&D expense in the third quarter of 2022 was $33.6 million as compared to $103.7 million for the third quarter of 2021. For the first nine months of 2022, R&D expense was $183.6 million as compared to $300.7 million in the first nine months of 2021. R&D expense decreased for both the third quarter and the first nine months of 2022 primarily due to the wind down of the bempegaldesleukin program. G&A expense was $22.5 million in the third quarter of 2022 and $29.5 million in the third quarter of 2021. For the first nine months of 2022, G&A expense was $70.4 million as compared to $90.7 million in the first nine months of 2021. G&A expense decreased for both the third quarter and the first nine months of 2022 primarily due to the wind down of the bempegaldesleukin program. Restructuring, impairment and other costs of terminated program was $16.8 million in the third quarter of 2022 and $124.3 million in the first nine months of 2022. The year-to-date amount includes $58.5 million in non-cash lease and equipment impairment charges, $29.8 million in employee severance expense and $28.9 million for clinical trial and related employee compensation costs for the wind down of the bempegaldesleukin program, as well as $7.1 million in other restructuring costs. Net loss for the third quarter of 2022 was $59.0 million or $0.31 basic and diluted loss per share as compared to a net loss of $129.7 million or $0.70 basic and diluted loss per share in the third quarter of 2021. Net loss in the first nine months of 2022 was $308.5 million or $1.65 basic and diluted loss per share as compared to a net loss of $378.2 million or $2.07 basic and diluted loss per share in the first nine months of 2021. Third Quarter 2022 and Recent Business Highlights: In September 2022, Nektar presented data from two Phase 1b proof-of-concept studies of rezpegaldesleukin in patients with atopic dermatitis (AD) and plaque psoriasis at the 2022 European Academy of Dermatology and Venereology (EADV) Congress. Data from both studies showed rezpegaldesleukin's ability to stimulate Tregs to target an immune system imbalance resulting in an improvement of disease activity in patients. Particularly in AD patients, dose-dependent improvements in key efficacy measures including EASI and vIGA-AD scores were observed for an additional 36 weeks following the 12-week treatment period. In August 2022, Nektar announced the publication of preclinical data for NKTR-255 in Blood Advances, the open-access journal of the American Society of Hematology. The data highlighted the effects of NKTR-255 on natural killer cell function and proliferation in multiple myeloma (MM), supporting the clinical development of NKTR-255 and further evaluation of the novel immunotherapeutic approach in MM, alone or in combination with monoclonal antibodies or potentially with other immunomodulatory drugs. Nektar also announced upcoming presentations at the following scientific congresses: The Society for Immunotherapy of Cancer (SITC) Annual Meeting November 8-12, 2022 (In person and virtual) Poster presentation: "NKTR-288, a polymer-conjugated interferon gamma mutein for the treatment of solid tumors", Hamel, D., et al. Poster presentation (Trials in Progress): "JAVELIN Bladder Medley: a phase 2 trial of avelumab in combination with other antitumor drugs as first-line maintenance therapy for advanced urothelial carcinoma", Hoffman-Censits, J., et al. (collaborator presentation with Merck KGaA) 2022 American Society of Hematology (ASH) Annual Meeting December 10-13, 2022 (In person and virtual) Poster presentation: "Safety, Tolerability, PK/PD and Preliminary Efficacy of NKTR-255, a Novel IL-15 Receptor Agonist, in Patients with Relapsed/Refractory Hematologic Malignancies", Patel K., et al. Poster presentation (Trials in Progress): "A Phase 2/3, Randomized, Double Blind, Placebo-Controlled, Multicenter Study of NKTR-255 Vs Placebo Following CD-19 Directed CAR-T Therapy in Patients with Relapsed/Refractory Large B-Cell Lymphoma", Perales M., et al. Conference Call to Discuss Third Quarter 2022 Financial Results Nektar management will host a conference call to review the results beginning at 5:00 p.m. Eastern Time/2:00 p.m. Pacific Time, November 3, 2022. This press release and a live audio-only webcast of the conference call can be accessed through a link that is posted on the home page and Investors section of the Nektar website: . The web broadcast of the conference call will be available for replay through December 3, 2022. To access the conference call, please pre-register at Nektar Earnings Call Registration. All registrants will receive dial-in information and a PIN allowing them to access the live call. In the event that any non-GAAP financial measure is discussed on the conference call that is not described in this press release, or explained on the conference call, related information will be made available on the Investors section of the Nektar website as soon as practical after the conclusion of the conference call. About Nektar Therapeutics Nektar Therapeutics is a biopharmaceutical company with a robust, wholly owned R&D pipeline of investigational medicines in oncology and immunology as well as a portfolio of approved partnered medicines. Nektar is headquartered in San Francisco, California, with additional operations in Huntsville, Alabama. Further information about the company and its drug development programs and capabilities may be found online at . Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements which can be identified by words such as: "will," "may," "expect," "potential," "advance," "initiate" and similar references to future periods. Examples of forward-looking statements include, among others, statements we make regarding the therapeutic potential of, and future development plans for rezpegaldesleukin (previously referred to as NKTR-358), NKTR-255 and our other drug candidates in research programs, the prospects and plans for our collaborations with other companies, the timing of the initiation of clinical studies and the data readouts for our drug candidates, and our expectations (including our expected charges and cost savings) following our corporate restructuring, reorganization and workforce reduction, and our expected working capital and our cash runway. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based only on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, anticipated events and trends, the economy and other future conditions. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict and many of which are outside of our control. Our actual results may differ materially from those indicated in the forward-looking statements. Therefore, you should not rely on any of these forward-looking statements. Important factors that could cause our actual results to differ materially from those indicated in the forward-looking statements include, among others: (i) our statements regarding the therapeutic potential of rezpegaldesleukin, NKTR-255 and our other drug candidates are based on preclinical and clinical findings and observations and are subject to change as research and development continue; (ii) rezpegaldesleukin, NKTR-255 and our other drug candidates are investigational agents and continued research and development for these drug candidates is subject to substantial risks, including negative safety and efficacy findings in ongoing clinical studies (notwithstanding positive findings in earlier preclinical and clinical studies); (iii) rezpegaldesleukin, NKTR-255 and our other drug candidates are in various stages of clinical development and the risk of failure is high and can unexpectedly occur at any stage prior to regulatory approval; (iv) the timing of the commencement or end of clinical trials and the availability of clinical data may be delayed or unsuccessful due to challenges caused by the COVID-19 pandemic, regulatory delays, slower than anticipated patient enrollment, manufacturing challenges, changing standards of care, evolving regulatory requirements, clinical trial design, clinical outcomes, competitive factors, or delay or failure in ultimately obtaining regulatory approval in one or more important markets; (v) we may not achieve the expected costs savings we expect from the restructuring and reorganization, (vi) patents may not issue from our patent applications for our drug candidates, patents that have issued may not be enforceable, or additional intellectual property licenses from third parties may be required; and (vii) certain other important risks and uncertainties set forth in our Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on August 5, 2022. Any forward-looking statement made by us in this press release is based only on information currently available to us and speaks only as of the date on which it is made. We undertake no obligation to update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise. Contact: Vivian Wu of Nektar Therapeutics 628-895-0661 SOURCE Nektar Therapeutics