Bempegaldesleukin

Sanofi’s work with engineered cytokines has stumbled in the clinic, but the company isn’t throwing in the towel yet on such therapies, which hold potential for treating autoimmune diseases and cancer. The French pharmaceutical giant is now partnering with a clinical-stage startup whose technologies for engineering these protein therapies could avoid limitations that have stymied some research efforts. Per deal terms announced Monday, Sanofi is paying Synthekine $40 million up front. Depending on the progress of the research, Menlo Park, California-based Synthekine will be eligible for an unspecified sum in milestone payments. Cytokines are signaling proteins that modulate immune responses. While these proteins are already in our bodies, leveraging them for therapeutic effect presents challenges. A cytokine’s effects can vary on different types of cells or even on the same cell types. Cytokine therapies can also spark broad responses that have toxic effects. The Sanofi partnership is focused on one particular cytokine called interleukin-10, or IL-10. While this cytokine has drawn research interest for potential immunosuppressive applications, dose-limiting toxicity has been a problem. Synthekine’s version of IL-10 is engineered to dial out the protein’s immunostimulatory effects, which the company says separates the drug’s therapeutic efficacy from potential toxic effects. The inflammatory disease targets for the partnered research were not disclosed. But the deal calls for Synthekine and Sanofi to work together up to a defined but undisclosed point of preclinical development. After that, Sanofi will take responsibility for developing the IL-10 therapeutic candidates. The companies said the collaboration will focus on using Synthekine’s technologies to optimize IL-10 with the goal of developing drugs that are more selective to their targets while offering a wider therapeutic index, the dose range that balances safety and efficacy. “We look forward to working with Synthekine, a leader in targeted cytokine engineering with outstanding technologies and scientific team,” John Bertin, global head of inflammation and immunology research at Sanofi, said in a prepared statement. “IL-10 plays a key role in immune regulation, and this collaboration aimed at developing precisely tailored IL-10 therapies reaffirms our commitment to deliver the next wave of novel therapies to treat inflammatory diseases.” Sanofi previously placed a big bet on cytokines when it acquired engineered cytokines developer Synthorx for $2.5 billion in 2019. Synthorx’s lead program was an IL-2 therapy in development for cancers and autoimmune diseases. In 2022, Sanofi disclosed Phase 2 results showing this cytokine therapy did not achieve the desired efficacy. No safety issues were reported for the therapy, which now bears the name pegenzileukin. But the disappointing results led the company to return the therapy to early-stage testing to sort out what it described as dosing issues. Sanofi aims to develop this therapy for treating solid tumors. Lack of efficacy was also cited in the disappointing clinical trial outcomes for bempegaldesleukin, an IL-2 therapy that Nektar Therapeutics was developing in partnership with Bristol Myers Squibb. In 2022, this therapy ran into successive failures, first in a Phase 3 test in melanoma and then two Phase 2 trials in kidney and bladder cancers. The mid-stage failures led to the end of the alliance, which began in 2018 with a $1.8 billion financial commitment from BMS. Synthekine has another big pharma research partner. In 2021, Merck and Synthekine struck up an alliance on the development of cytokine drugs for two autoimmune and inflammation targets that remain undisclosed. The sum of the upfront payment was also not disclosed, but Merck is providing Synthekine with research funding and the startup could earn up to $525 million in milestone payments. Synthekine’s internal pipeline is led by an IL-12 therapy currently in Phase 1 testing for cancer. The startup last raised money in 2023, a $100 million Series C round of financing.

SAN FRANCISCO, Nov. 7, 2023 /PRNewswire/ -- Nektar Therapeutics (Nasdaq: NKTR) today reported financial results for the third quarter ended September 30, 2023. Cash and investments in marketable securities at September 30, 2023, were $372.7 million as compared to $505.0 million at December 31, 2022. Nektar's cash and marketable securities are expected to support strategic development activities and operations into the middle of 2026. "We've made significant progress across our pipeline, including initiating a Phase 2b atopic dermatitis study in October and completing plans to start a Phase 2b alopecia areata study in early 2024," said Howard W. Robin, President and CEO of Nektar. "These two studies position us for important and transformative data readouts for rezpegaldesleukin in the first half of 2025. In September, we signed a new clinical study collaboration with cell therapy leader, Cellular Biomedicine Group, who will evaluate NKTR-255 in combination with CBMG's tumor-infiltrating lymphocyte therapy in advanced non-small cell lung cancer. This study is an example of the potential of NKTR-255 in combination with a range of cell therapies in liquid and solid tumors. Finally, we will end this year in a strong financial position with at least $320 million in cash and investments which provides us with a cash runway into the middle of 2026." Summary of Financial Results Revenue in the third quarter of 2023 was $24.1 million as compared to $23.6 million in the third quarter of 2022. Revenue for the first nine months of 2023 was $66.2 million as compared to $70.0 million in the first nine months of 2022. Total operating costs and expenses in the third quarter of 2023 were $69.0 million as compared to $77.9 million in the third quarter of 2022. Total operating costs and expenses in the first nine months of 2023 were $296.4 million as compared to $393.7 million in the first nine months of 2022. The reduction in operating costs and expenses for both the third quarter and the first nine months of 2023 were due to decreases in research and development expenses, general and administrative expense and restructuring, impairment and costs of terminated program. For the first nine months of 2023, these decreases were partially offset by $76.5 million in non-cash goodwill impairment. R&D expense in the third quarter of 2023 was $24.1 million as compared to $33.6 million for the third quarter of 2022. For the first nine months of 2023, R&D expense was $84.2 million as compared to $183.6 million in the first nine months of 2022. R&D expense decreased for both the third quarter and first nine months of 2023 due to the wind down of the bempegaldesleukin program. G&A expense was $21.1 million in the third quarter of 2023 as compared to $22.5 million in the third quarter of 2022. For the first nine months of 2023, G&A expense was $60.1 million as compared to $70.4 million in the first nine months of 2022. G&A expense decreased for both the third quarter and first nine months of 2023 due to the wind down of the bempegaldesleukin program. Restructuring, impairment and costs of terminated program were $11.4 million in the third quarter of 2023 as compared to $16.8 million in the third quarter of 2022. The amount for the third quarter of 2023 includes $10.2 million in non-cash lease and equipment impairment charges, $0.7 million for the wind down of the bempegaldesleukin program and $0.5 million in severance. The amount for the third quarter of 2022 includes $8.5 million for the wind down of the bempegaldesleukin program, $5.0 million for contract termination and other restructuring costs, $2.1 million in severance and $1.2 million in non-cash lease impairment charges. For the first nine months of 2023, restructuring, impairment and costs of terminated program were $49.1 million. This amount includes $36.6 million in non-cash lease and equipment impairment charges, $8.0 million in severance and $3.6 million for the wind down of the bempegaldesleukin program. For the first nine months of 2022, restructuring, impairment and costs of terminated program were $124.4 million. This amount includes $58.5 million in non-cash lease and equipment impairment charges, $29.8 million in severance, $28.9 million for the wind down of the bempegaldesleukin program and $7.1 million in contract termination and other restructuring costs. Net loss for the third quarter of 2023 was $45.8 million or $0.24 basic and diluted loss per share as compared to a net loss of $59.0 million or $0.31 basic and diluted loss per share in the third quarter of 2022. Net loss in the first nine months of 2023 was $234.0 million or $1.23 basic and diluted loss per share as compared to a net loss of $308.5 million or $1.65 basic and diluted loss per share in the first nine months of 2022. Excluding the $10.2 million in non-cash impairment charges, net loss, on a non-GAAP basis, for the third quarter of 2023 was $35.7 million or $0.19 basic and diluted loss per share. Excluding the $113.1 million in non-cash goodwill and other impairment charges, net loss, on a non-GAAP basis, for the first nine months of 2023 was $120.8 million or $0.64 basic and diluted loss per share. Third Quarter 2023 and Recent Business Updates In September 2023, Nektar announced a clinical study collaboration with Cellular Biomedicine Group Inc. (CBMG) to evaluate NKTR-255 in combination with C-TIL051 in advanced non-small cell lung cancer (NSCLC) patients that are relapsed or refractory to anti-PD-1 therapy. Under the collaboration, CBMG will add NKTR-255 to its ongoing Phase 1 clinical trial being conducted at Duke Cancer Institute. Enrollment for this trial is ongoing. In October 2023, Nektar presented final data from the Phase 1b study of rezpegaldesleukin in patients with atopic dermatitis at the 2023 European Academy of Dermatology and Venereology (EADV) Congress. Patients with moderate-to-severe AD that were treated with rezpegaldesleukin showed dose-dependent improvements in Eczema Area and Severity Index (EASI), Validated Investigator Global Assessment (vIGA), Body Surface Area (BSA), and Itch Numeric Rating Scale (NRS) over 12 weeks of treatment compared to placebo, which were sustained post-treatment over an additional 36 weeks. At the highest studied dose, the proportion of Daily Life Quality Index (DLQI) responders was 75% and the proportion of Patient Oriented Eczema Measure (POEM) responders was 65% at week 12. rezpegaldesleukin was well tolerated with no patients in the rezpegaldesleukin groups experiencing severe, serious, or fatal adverse events, and no anti-rezpegaldesleukin antibodies were detected. In October 2023, Nektar initiated a Phase 2b study of rezpegaldesleukin in patients with atopic dermatitis. Conference Call to Discuss Third Quarter 2023 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 7, 2023. This press release and 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 8, 2023. 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. About Nektar Therapeutics Nektar Therapeutics is a biopharmaceutical company with a robust, wholly owned R&D pipeline of investigational medicines in immunology and oncology as well as a portfolio of approved partnered medicines. Nektar is headquartered in San Francisco, California, with additional manufacturing 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," "could," "develop," "potential," "advance" and similar references to future periods. Examples of forward-looking statements include, among others, statements regarding the therapeutic potential of, and future development plans for, rezpegaldesleukin and NKTR-255. 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 and NKTR-255 are based on preclinical and clinical findings and observations and are subject to change as research and development continue; (ii) rezpegaldesleukin and NKTR-255 are investigational agents and continued research and development for these drug candidates is subject to substantial risks, including negative safety and efficacy findings in future clinical studies (notwithstanding positive findings in earlier preclinical and clinical studies); (iii) rezpegaldesleukin and NKTR-255 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 cost savings we expect from our 2022 corporate restructuring and reorganization plan or our 2023 cost restructuring plan and we may undertake additional restructuring and cost-saving activities in the future, (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 Annual Report on Form 10-Q filed with the Securities and Exchange Commission on August 9, 2023. 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 Investors: Vivian Wu of Nektar Therapeutics 628-895-0661 For Media: David Rosen of Argot Partners (212) 600-1902 [email protected] SOURCE Nektar Therapeutics