Nektar Therapeutics (Nasdaq: NKTR), a clinical-stage biotechnology company headquartered in San Francisco, announced an academic research collaboration with the University of California, San Francisco and Stephen L. Hauser, M.D., to evaluate NKTR-0165 — the company’s preclinical tumor necrosis factor receptor 2 (TNFR2) agonist antibody — in models of multiple sclerosis. The collaboration pairs Nektar’s first-in-class molecule with one of the field’s most recognized neuroimmunologists, whose work on B cell biology in MS led to multiple approved therapies and earned the 2025 Breakthrough Prize in Life Sciences.

Financial terms were not disclosed. The arrangement is structured as a non-commercial academic collaboration rather than a traditional licensing or co-development deal. UCSF will conduct and fund all research activities. Nektar will supply NKTR-0165 and will retain all rights to its programs under the collaboration.

NKTR-0165 is a novel antibody designed to selectively activate TNFR2, a receptor expressed on regulatory T cells, endothelial cells, and neuronal cells. TNFR2 signaling plays a role in immune regulation, neuroprotection, and tissue repair — functions that are distinct from, and in many cases opposite to, signaling through the related TNFR1 receptor, which tends to drive inflammation and cell death.

This receptor-level distinction is central to the program’s rationale. Broad TNF inhibitors such as adalimumab, infliximab, and etanercept have categorically failed in MS. Clinical trials of pan-TNF blockers in demyelinating disease worsened outcomes, a result now understood to stem from the simultaneous suppression of TNFR2’s protective signaling alongside TNFR1’s inflammatory signaling. NKTR-0165 is designed to activate TNFR2 without engaging TNFR1, a selectivity profile that is hypothesized could unlock the protective arm of TNF biology while avoiding the inflammatory arm.

The molecule is currently in IND-enabling studies. Nektar has stated that it is being developed to address autoimmune and CNS disorders including multiple sclerosis, vitiligo, and ulcerative colitis.

Stephen Hauser and UCSF Neurology

The collaboration will be led by Dr. Hauser and his postdoctoral researcher Dr. Chaitrali Saha at the UCSF Weill Institute for Neurosciences. The research will explore whether TNFR2 agonism can reduce neurodegeneration and promote neuroprotection and cell repair when neurons are exposed to patient-derived B cells.

As Director of the UCSF Weill Institute for Neurosciences, Dr. Hauser has spent decades establishing the role of B cells in MS pathogenesis — work that led directly to the development of anti-CD20 therapies such as ocrelizumab (Roche/Genentech), now a standard-of-care treatment across relapsing and primary progressive forms of the disease. His research transformed the understanding of MS from a predominantly T cell-mediated disease to one in which B cells play a central pathogenic role.

The use of patient-derived B cell models in the collaboration is consistent with this body of work and positions the research to generate disease-relevant preclinical data. Jonathan Zalevsky, Nektar’s Chief Research and Development Officer, described the collaboration as an opportunity to “explore the role of TNFR2 agonism in several models of MS” alongside a “renowned and pioneering researcher in the field.”

Dr. Hauser stated that the research initiative aims to “evaluate the potential neuroprotective effect associated with the agonism of this receptor for treating both MS and other neurological conditions.”

Nektar pipeline

NKTR-0165 sits within a broader TNFR2-focused pipeline at Nektar. The company is also developing NKTR-0166, a bivalent bispecific antibody that pairs a TNFR2 agonist epitope with an antagonist epitope validated in rheumatology. NKTR-0166 is being developed for rheumatic disorders and leverages learnings from the NKTR-0165 program.

Nektar’s lead clinical-stage asset is rezpegaldesleukin (NKTR-358), a regulatory T cell stimulator in Phase IIb trials for atopic dermatitis and alopecia areata, and in a Phase II trial for Type 1 diabetes mellitus. The company’s oncology pipeline includes NKTR-255, an IL-15 receptor agonist being evaluated in multiple clinical trials with various partners.