Not content with getting the first lupus drug to market in the form of the blockbuster Benlysta more than a decade ago, GSK is handing over $300 million in upfront cash for a clinical-stage T-cell engager it believes could target patients who aren’t benefiting from current treatments.
The candidate in question is CMG1A46, a dual CD19- and CD20-targeted T cell engager that Chimagen Biosciences is currently evaluating in phase 1 trials for leukemia and lymphoma. However, GSK has spied potential in focusing the asset on systemic lupus erythematosus (SLE) and lupus nephritis with potential to expand to other B-cell-driven autoimmune diseases and related conditions.
Alongside the initial fee, GSK could also pay out up to $550 million in biobucks to China-based Chimagen.
As an IgG-like molecule with high affinity for CD19- and CD20-positive B cells but a low affinity for CD3, GSK’s hope is that CMG1A46 could lower the toxicities that are often associated with T-cell engagers. Preclinical studies have already shown “rapid, deep B cell depletion both in the bloodstream and in tissues which could lead to more durable responses in patients,” GSK pointed out.
If successful, it means the British Big Pharma would have a fresh lupus offering for patients who suffer from severe forms of the disease that don’t respond to existing treatments.
“Through our work in systemic lupus erythematosus and lupus nephritis, we increasingly understand the underlying drivers of B cell-driven diseases,” GSK Chief Scientific Officer Tony Wood, Ph.D., said in an Oct. 29 release. “As a novel therapeutic option directed at deep B cell depletion, CMG1A46 offers exciting potential which we are pleased to take forward to address unmet need in lupus and related autoimmune conditions.”
There are several types of lupus, with SLE being the most common. The condition is caused by an autoimmune disease in which the immune system attacks its own tissues, causing widespread inflammation and tissue damage. Organ damage can occur in up to 48% of people living with lupus, most within five years of diagnosis, with lupus flares also upping the risk of organ damage.
GSK was the first to market when its BLyS-specific inhibitor Benlysta was approved by the FDA in 2011. It has since become a blockbuster medicine, while AstraZeneca’s more recent challenger Saphnelo, a type 1 interferon blocker, has struggled to catch up in terms of sales since getting the green light in 2021.
The lupus landscape could be set to change further as a result of already-approved drugs in the form of AbbVie’s blockbuster JAK inhibitor Rinvoq, which is in phase 3 testing for SLE, and Bristol Myers Squibb’s TYK2 inhibitor Sotyktu, which presented positive data in SLE at the start of the year.
There are also other investigational contenders in the form of UCB Pharma’s anti-CD40L drug dapirolizumab pegol and Idorsia’s S1P1 receptor modulator cenerimod.