First patients dosed in Phase 2 trials of Argo’s complement therapy BW-40202
Treatment is being tested in PNH and immunoglobulin A nephropathy
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The first patient has been dosed in Argo Biopharmaceutical’s Phase 2 clinical trial of BW-40202 for paroxysmal nocturnal hemoglobinuria (PNH), one of two new Phase 2 studies testing the investigational therapy.
The Phase 2 studies follow a Phase 1 trial (NCT06917482) initiated last year to assess BW-40202’s safety, tolerability, and pharmacological properties in healthy adults. The company did not provide additional details on the Phase 2 trial designs, such as enrollment goals or dosing schedules.
According to the company, the first patient has also been dosed in a separate Phase 2 trial of BW-40202 in people with immunoglobulin A nephropathy (IgAN), a chronic kidney disease marked by immune protein deposits in the kidneys. Both PNH and IgAN involve dysregulation or overactivation of the complement system, a part of the immune system.
BW-40202 targets complement factor B
“Dosing the first patient in both of these [Phase 2] trials marks an important step forward in Argo’s mission to develop more efficacious treatment options for patients suffering from complement-mediated diseases,” Dongxu Shu, PhD, co-founder and CEO of Argo, said in a company press release. “Complement pathway biology is highly complex and we believe a potent and durable siRNA therapeutic has the potential to make a meaningful difference for patients.”
PNH is caused by acquired mutations in blood-forming stem cells. These mutations can leave red blood cells without certain protective proteins, making them vulnerable to destruction by the complement system, a part of the immune system that helps fight infections. This red blood cell destruction, called hemolysis, can lead to dark or reddish urine due to hemoglobin released from destroyed red blood cells, low blood cell counts, fatigue, blood clots, and other symptoms.
BW-40202 is a small-interfering RNA (siRNA) molecule that blocks the production of complement factor B (CFB), a protein needed to activate part of the complement alternative pathway, a branch of the complement system. By reducing CFB, BW-40202 is expected to help slow this pathway.
It works by binding to and causing the destruction of CFB messenger RNA, or mRNA, the intermediate molecule derived from DNA that guides protein production. By lowering CFB levels, BW-40202 is expected to reduce complement-driven red blood cell destruction in PNH and may help ease disease symptoms. It is given by subcutaneous, or under-the-skin, injections and targets the liver, where complement proteins are mostly produced.
In preclinical studies, BW-40202 demonstrated a favorable safety profile and led to durable reductions in blood CFB levels and inhibition of complement alternative pathway activity.
Last year, the company launched the Phase 1 trial, which started dosing participants at a clinical site in Australia. The study also obtained approval from the regulatory agency in China, enabling expansion into Chinese clinical sites. Participants were divided into five groups, each receiving a single dose of BW-40202 at one of five ascending doses, or a placebo.
