Nektar Therapeutics to Present Rezpegaldesleukin Data at EADV 2024

Nektar Therapeutics recently unveiled new findings about rezpegaldesleukin (REZPEG) at the 2024 European Academy of Dermatology and Venereology (EADV) Congress. The innovative drug demonstrated a distinct proteomic profile in patients suffering from atopic dermatitis (AD). According to Jonathan Zalevsky, Ph.D., the company's Senior Vice President and Chief Research & Development Officer, REZPEG showcased its unique action mechanism by activating immunoregulatory pathways, particularly affecting the protein levels of interleukin-10 (IL-10), a significant anti-inflammatory cytokine. This was accompanied by reductions in specific cytokines and chemokines that often exhibit elevated levels in AD patients, such as IL-15, CCL22, CX3CL1, and IL-19.

REZPEG is a pioneering regulatory T (Treg) cell stimulator designed to address the immune system's imbalance seen in autoimmune and chronic inflammatory conditions. It primarily targets the IL-2 receptor complex, focusing on stimulating the proliferation of Treg cells. These cells play a crucial role in maintaining immune homeostasis without activating cytotoxic CD8+ T and CD4+ T cells, which are responsible for driving autoimmune responses. Presently, REZPEG is being scrutinized through two Phase 2b trials—one focusing on moderate-to-severe AD and another on severe to very severe alopecia areata (AA). Nektar anticipates that key data from these studies will be available in the first and middle halves of 2025, respectively.

Spyridon Gkalpakiotis, M.D., Ph.D., MBA, a primary investigator in the Phase 2b AD study, emphasized the progress in treating atopic dermatitis. Despite advances, some patients remain unresponsive to current biologics and small molecule treatments, highlighting the need for new therapies like REZPEG that offer immunoregulatory benefits rather than merely suppressing the immune system.

Key points from the EADV Congress presentations included an abstract on the serum proteomic biomarker analysis of REZPEG in AD patients. Using the Olink proteomics platform, this study measured soluble serum protein levels at different intervals, revealing that REZPEG modulated Treg pathways and influenced processes like lymphocyte immune homeostasis, MHC expression, cellular migration, and adhesion.

Another abstract detailed a Phase 2b trial evaluating REZPEG's efficacy and safety in adults with moderate-to-severe AD. This trial is recruiting biologic and JAK-inhibitor naïve patients and aims to reduce the Eczema Area and Severity Index (EASI) score from baseline. Secondary endpoints include improvements in the Investigator's Global Assessment (IGA) AD score and total body surface area (BSA).

A third abstract presented a Phase 2b study assessing REZPEG's impact on severe to very severe alopecia areata. This trial also enrolls JAK-inhibitor naïve patients and measures changes in the Severity Alopecia Tool (SALT) score from baseline as its primary endpoint. Secondary endpoints include additional changes in SALT scores at various time points and patient-reported outcomes.

Autoimmune and inflammatory diseases often result from the immune system's erroneous attack on healthy cells due to a failure in self-tolerance mechanisms. REZPEG aims to correct this imbalance by stimulating Treg cells, thus potentially offering a new therapeutic avenue for numerous autoimmune and inflammatory conditions. It is being developed as a self-administered injection and remains fully owned by Nektar Therapeutics.

Nektar Therapeutics, headquartered in San Francisco, is spearheading the development of treatments that address immunological dysfunctions in autoimmune and chronic inflammatory diseases. Their lead candidate, rezpegaldesleukin (NKTR-358), is under evaluation in two significant Phase 2b trials. The company's pipeline also includes other promising candidates, such as a bivalent tumor necrosis factor receptor type II agonist antibody (NKTR-0165) and an IL-15 receptor agonist (NKTR-255) aimed at enhancing the immune system's cancer-fighting capabilities.