R1 Therapeutics has randomized the first patient in its global phase 2b study of AP306, a first‑in‑class pan phosphate transporter inhibitor being developed as a monotherapy for hyperphosphatemia in chronic kidney disease patients on dialysis.
The multi‑centre, randomized, double‑blind, placebo‑controlled trial will assess safety, tolerability and serum phosphate lowering across six fixed‑dose regimens over eight weeks.
Around 168 patients will be enrolled at sites in the US and China through R1’s partnership with Alebund Pharmaceuticals.
Hyperphosphatemia is a near‑universal complication in advanced chronic kidney disease and is linked to cardiovascular disease, bone disease and mortality. More than 70% of US dialysis patients fail to achieve normal phosphate levels, despite phosphate binders remaining the standard of care for 60 years.
L. Mary Smith, Co‑Founder and Chief Operating Officer of R1 Therapeutics, said: “Randomizing the first patient is a significant milestone for R1 and reflects the rapid pace at which our team and partners are moving.”
She added: “We founded R1 to address a problem that has lacked therapeutic innovation for decades. Patients on dialysis face a heavy daily pill burden yet still struggle to keep their phosphate in range, and AP306 was designed to change that. Advancing it into phase 2b alongside our partner Alebund is a meaningful step forward, and we’re focused on generating the data needed to bring AP306 to patients.”
AP306 is the only agent that blocks the ‘active’ transport of phosphate, targeting three transporters in the gut.
The phase 2b study builds on positive phase 2a data published in Kidney International Reports, which showed significant reductions in serum phosphate with good safety and tolerability. Topline results are expected in the first half of 2027.
Glenn M. Chertow, Chair of R1’s Scientific Advisory Board, explained: “Hyperphosphatemia is among the most stubborn challenges we face in the day‑to‑day management of patients receiving maintenance dialysis, and is associated with mortality, cardiovascular events, and fracture.”
He continued: “AP306 targets the absorption of phosphate through inhibition of three active transporters in the gut, providing a unique mechanism of action that could complement or potentially replace the use of commonly prescribed phosphate binders, agents that have been used for decades with only modest success.
“It is exciting to see this study begin, and I look forward to the insights it will provide on AP306’s potential to lower serum phosphate across a range of doses.”
AP306 was originally discovered by Chugai Pharmaceutical and later licensed to Alebund Pharmaceuticals.
