It’s a good week to be working on drugs targeting STAT6. Kymera Therapeutics Inc.’s, KT-621, the first oral STAT6 degrader candidate to enter the clinic, surpassed expectations with impressive safety, pharmacokinetic and biomarker data from a phase I trial, while potential fast-followers from Nurix Therapeutics Inc. and Recludix Pharma Inc. advanced via respective partnerships with Sanofi SA.
Sanofi SA has exercised its option to exclusively license Nurix Therapeutics Inc.’s STAT6 program, including the drug development candidate NX-3911, an oral, highly selective STAT6 degrader.
Recludix Pharma Inc. has nominated a lead development candidate, REX-8756, an oral, selective and reversible small-molecule inhibitor of STAT6, and completed GLP toxicology studies for the compound. REX-8756 has potential for patients with type 2 immune-related inflammatory diseases.
Teva Pharmaceutical Industries Ltd. has commenced IND-enabling studies with BD-9, a dual-specific multibody targeting thymic stromal lymphopoietin (TSLP) and interleukin-13 (IL-13). By simultaneously blocking two key drivers of TH2-driven inflammation, BD-9 has the potential to improve outcomes for patients with conditions such as atopic dermatitis and asthma.
Rheumatoid arthritis, atopic dermatitis, ulcerative colitis and several other inflammatory diseases involve hyperactivation of JAK-STAT signaling, in which the kinase JAK binds and phosphorylates the transcription factor STAT, which then turns on gene expression.
CC chemokine receptor 6 (CCR6) is a G-protein coupled receptor involved in guiding immune cells through the body and the hallmark receptor for T helper 17 (Th17) cells, and is also expressed in other immune cell populations, such as B cells and innate lymphoid cells, among others.
With a promising IL-36 inhibitor for atopic dermatitis (AD, or eczema) at the phase II stage, Turn Therapeutics Inc. has gained $75 million in post-public commitments and meanwhile is pursuing a grassroots strategy to keep the coffers in balance.
The sparsity of mid-to-late stage prospects in atopic dermatitis (AD, or eczema) – which has proved an especially challenging indication – plus some newsmaking fizzles in the space have caused developers to probe new targets with particular intensity. Most popular approaches thus far involve IL-4, IL-13, thymic stromal lymphopoietin and JAK. Developers have stumbled for varying reasons such as high placebo response rates, safety or lack of clinical proof of concept. Among the potential AD rescuers is Nektar Therapeutics Inc. with rezpegaldesleukin (rezpeg), which takes aim at IL-2.
At this week’s American Chemical Society Spring meeting, Galderma SA reported the discovery of novel, oral and selective macrocyclic inhibitors of protein kinase C θ (PKCθ) for the potential treatment of atopic dermatitis (AD) and psoriasis.
