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Mestag’s pipeline consists of antibody therapies based on fibroblast-immune interactions as a treatment for cancer and inflammatory diseases. Image credit: Sergiy Palamarchuk / Shutterstock. MSD ( Merck & Co) has signed a license and collaboration agreement with Mestag Therapeutics to develop new fibroblast therapies for inflammatory diseases – a deal potentially worth $1.9bn The companies did not disclose the particulars of the deal, noting that the agreement allows MSD the option to get exclusive development and marketing licences to “a prespecified number of potential targets.” The UK-based biotech in return will receive an upfront payment, and access fees and will be in line to receive option fees and “downstream payments”. Fibroblasts form the connective tissue and are responsible for synthesising extracellular matrix components and collagen, the structural framework of the body. They also play an important role in wound healing, inflammation, and tissue repair. Mestag’s pipeline consists of antibody therapies based on fibroblast-immune interactions as a treatment for cancer and inflammatory diseases. The company’s lead candidate, MST-0300, is a bispecific antibody. The therapy targets lymphotoxin beta receptor (LTBR) in the tumour on co-engagement of fibroblast activation protein (FAP), a tumour-specific marker expressed by cancer-associated fibroblasts, to induce the formation of tertiary lymphoid structures (TLSs) in solid tumours. The presence of these TLSs can be predictive of improved patient outcomes and better therapeutic response. Mestag plans to file an investigational new drug (IND) application in the second half of 2025. Another preclinical candidate in the company’s pipeline is M402, a stromal checkpoint agonist antibody. The therapy is designed to inhibit specific immune cell populations, including myeloid cells. Mestag states that M402 has the “potential to benefit patients across inflammatory diseases including rheumatoid arthritis, lupus, Sjogren’s, graft-versus-host disease and others.” See Also: Clinical Dose Companies in Contract Manufacturing for the Pharmaceutical Industry Innovent and ASK Pharm to commercialise limertinib for lung cancer MSD has been steadily investing in expanding its antibody therapies pipeline. In August, the company acquired Curon Biopharmaceutical , a Chinese biopharmaceutical company specialising in developing bispecific antibodies. The deal is worth approximately $1.3bn in upfront and milestone-based payments. Mestag had previously collaborated with Johnson & Johnson (J&J) in 2021. The licensing agreement allowed J&J the option of an exclusive license to develop and commercialise up to two therapies for the treatment of inflammatory disease.

- Innovate UK, part of UK Research and Innovation, is investing £10 million in innovation projects to advance next-generation immunotherapies for cancer, of which £1.5 million has been awarded to Mestag - Bispecific antibody MST-0300 is a first-of-its-kind approach designed to conditionally induce tertiary lymphoid structures (TLS) in solid tumors, an exciting new therapeutic strategy with potential to revolutionize cancer treatment Aug. 28, 2024 -- Mestag Therapeutics (“Mestag”), a biotech company harnessing new insights into fibroblast-immune interactions, today announced that it has been awarded a “Transforming Cancer Therapeutics” grant from Innovate UK’s Cancer Therapeutics program of £1.5 million ($1.9 million) to accelerate the development of its MST-0300 antibody. MST-0300 is a first-in-class bispecific antibody designed to induce TLS in solid tumors in a highly specific and localized fashion. The presence of TLS in tumors has recently emerged as being strongly correlated with improved outcomes for cancer patients across multiple tumor types. TLS are believed to enable improved immune cell access to the tumor and drive local immune cell education, leading to a powerful orchestrated anti-tumor response. Mestag data in hard-to-treat cancer models, recently presented at the 2024 American Association of Cancer Research conference, demonstrate potent anti-tumor effects. Susan Hill, PhD, Chief Executive Officer of Mestag Therapeutics, said, “We are honored to have been selected as a recipient for this highly competitive translational award. The presence of TLS in tumors is emerging as a key driver of improved treatment outcomes in cancer patients, and our MST-0300 program, designed to induce the formation of TLS in tumors, holds important therapeutic promise. Leveraging the dynamic UK biotech ecosystem, Innovate UK funding will enable us to advance MST-0300 rapidly to solid tumor patients who urgently need new treatment options.” MST-0300 is a first-in-class bispecific antibody that co-engages fibroblast activated protein (FAP) and lymphotoxin beta receptor (LTBR) to conditionally activate LTBR and induce tertiary lymphoid structures (TLS) in the tumor. TLS are aggregates of immune cells that can form in tumor tissue as part of our bodies’ natural anti-cancer mechanisms, and drive powerful immune responses by recruiting, educating, and activating new anti-tumor T- and B-cells. Fibroblast populations play a key role in the induction and maintenance of TLS. TLS in tumors are strongly predictive of both improved patient outcomes across solid tumor types and better response to therapy. Mestag recently presented in vivo preclinical data which showed potent monotherapy efficacy, as well as tumor regression in combination with tumor antigen or a checkpoint inhibitor. Innovate UK, part of UK Research and Innovation (UKRI), is the UK’s innovation agency. It works to create a better future by inspiring, involving and investing in businesses developing life-changing innovations. Its mission is to help companies to grow through their development and commercialisation of new products, processes and services, supported by an outstanding innovation ecosystem that is agile, inclusive and easy to navigate. Mestag harnesses new insights into fibroblast-immune interactions to develop impactful treatments for patients with cancer and inflammatory diseases. We are progressing a pipeline of sophisticated first-in-class antibodies designed to direct and drive the immune system using known and emerging fibroblast-immune biology for a distinctly differentiated class of therapeutics. Our pipeline includes a bispecific antibody MST-0300, which leverages a new understanding of tertiary lymphoid structures (TLS) in solid tumors and their role in driving improved patient outcomes; the M402 program, targeting a stromal checkpoint to dampen down the activation of specific immune cell subsets in inflammatory disease; and earlier programs in discovery stage. Separately, in a collaboration with Janssen Biotech, Inc., a Johnson & Johnson company, we are also identifying novel targets for future therapies.“ Our founding investigators comprise global experts in inflammatory disease, cancer, computational biology and fibroblast biology from the University of Oxford, Brigham & Women’s Hospital, Harvard Medical School and Cold Spring Harbor Laboratory. We are supported by leading life science investors SV Health Investors, Johnson & Johnson Innovation – JJDC, Inc., Forbion, GV (formerly Google Ventures) and Northpond Ventures. Mestag is headquartered in Cambridge, UK, and in 2021 was recognized on the Fierce 15 list of innovative biotechnology companies. The content above comes from the network. if any infringement, please contact us to modify.

– NKTR-0165 Demonstrates Selective Enhancement of Treg Cell Function Through Novel Agonistic Mechanism – – IND-Enabling Studies Underway for NKTR-0165 with First-in-Human Studies Planned in First Half of 2025 - SAN FRANCISCO, June 12, 2024 /PRNewswire/ -- Nektar Therapeutics (Nasdaq: NKTR) today announced the presentation of a poster highlighting new preclinical data on NKTR-0165 at the European Alliance of Associations for Rheumatology (EULAR) 2024 Congress. NKTR-0165 is a novel, first-in-class tumor necrosis factor receptor 2 (TNFR2) agonist and bivalent antibody designed to selectively stimulate TNFR2 receptor activity, without modulation of the TNFR1 signaling. TNFR2 signaling has been shown to be an important gatekeeper of inflammation and its absence or deficit is associated with a broad range of autoimmune diseases. TNFR2 is highly expressed on Tregs, neuronal cells and endothelial cells and has been shown to potentiate the suppressive effects and overall functional properties of regulatory T cells (Tregs). "The preclinical data presented at EULAR show that NKTR-0165 is a unique antibody that selectively binds to TNFR2 on Tregs to enhance its immunosuppressive activities, and could potentially become a first-in-class treatment for various autoimmune diseases, including ulcerative colitis and vitiligo," said Jonathan Zalevsky, Ph.D., Senior Vice President and Chief Research & Development Officer at Nektar. "By selectively binding to TNFR2, NKTR-0165 upregulates expression of proteins that are critical to Treg proliferation and function. Animal models show that NKTR-0165 reduces inflammation through the selective enhancement of Treg cell function via TNFR2 agonism. These data demonstrate a unique and differentiated profile for this bivalent antibody in the field of TNFR2 agonists." The poster presentation is available for download at . Key details and takeaways from the presentation are as follows: Abstract 3174: "A Novel Therapeutically Active Anti-TNFR2 Agonistic Antibody Promotes Treg Proliferation and Induction of Treg Functional Markers", Miyazaki, et al. NKTR-0165 shows selective TNFR2 binding and receptor agonism in human Tregs, with minimal binding and signaling activity in other TNFR2-expressing immune cells in vitro and in vivo. NKTR-0165 agonistic activity enhances Treg lineage stabilization and upregulates expression of proteins involved in Treg proliferation and function. NKTR-0165 demonstrates therapeutic efficacy in a KLH-induced delayed type hypersensitivity (DTH) model in human TNFR2 knock-in mice. About Nektar Therapeutics Nektar Therapeutics is a clinical-stage biotechnology company focused on developing treatments that address the underlying immunological dysfunction in autoimmune and chronic inflammatory diseases. Nektar's lead product candidate, rezpegaldesleukin (REZPEG, or NKTR-358), is a novel, first-in-class regulatory T cell stimulator being evaluated in two Phase 2b clinical trials, one in atopic dermatitis and one in alopecia areata. Our pipeline also includes a preclinical candidate NKTR-0165, which is a bivalent tumor necrosis factor receptor type II agonist antibody. Nektar, together with various partners, is also evaluating NKTR-255, an investigational IL-15 receptor agonist designed to boost the immune system's natural ability to fight cancer, in several ongoing clinical trials. Nektar is headquartered in San Francisco, California. For further information, visit and follow us on LinkedIn. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements which can be identified by words such as: "could," "design," "develop," "potential" and similar references to future periods. Examples of forward-looking statements include, among others, statements we make regarding the therapeutic potential of NKTR-0165 and rezpegaldesleukin, observations from early data emerging from preclinical research of NKTR-0165, the potential of the technology incorporated into our drug candidates, and the future development plans for NKTR-0165 and rezpegaldesleukin. 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-0165 and rezpegaldesleukin are based on preclinical and clinical findings and observations and are subject to change as research and development continue; (ii) NKTR-0165 and rezpegaldesleukin 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 is in clinical development and NTKR-0165 is in preclinical 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 health epidemics, 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 Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on May 10, 2024. 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