Sevelamer Hydrochloride

R1 Therapeutics launched Tuesday with $77.5 million in hand and a lead asset called AP306 that it believes will improve outcomes for chronic kidney disease (CKD) patients by controlling hyperphosphataemia via a new mechanism. Rather than depending on the burdensome binder drugs patients have used for years, the California-based biotech aims to block phosphate absorption directly in the gut.It also announced a partnership with Alebund Pharmaceuticals to license global rights to AP306 outside China. Although exact terms of the deal weren't disclosed, Alebund said that it is eligible to receive milestone payments of up to low triple-digit millions of US dollars, as well as tiered sales royalties in the low double-digit percentage range. Alebund added that it also holds "a substantial non-dilutive equity interest in R1."AP306, also known as EOS789, is designed to inhibit all three phosphate transporters — NaPi-IIb, PiT-1 and PiT-2 — blocking phosphate uptake in the gut. It was discovered by Chugai Pharmaceutical and licensed to Alebund in 2021 for an undisclosed upfront payment and potential milestones.Current phosphate binders have been the standard of care for 60 years, but are limited by low binding capacity, high pill burden and poor gastrointestinal (GI) tolerability. More recently, Ardelyx's Xphozah (tenapanor) was approved by the FDA to lower serum phosphorus in CKD patients on dialysis as an add-on therapy that targets the NHE3 sodium transporter, though R1 says managing hyperphosphataemia continues to be an area of high unmet need."By blocking the active transport of phosphate through three different phosphate transporters in the GI tract, initial clinical studies suggest AP306 has the potential to deliver superior efficacy with substantially lower pill burden compared to current phosphate binder therapies," said R1 CEO Krishna Polu, adding the experimental drug, if successful, "should redefine the class of phosphate lowering therapies."Advancing to Phase IIbIn a Phase IIa study in dialysis patients, AP306 met its primary endpoint, reducing serum phosphate by 2.51 mg/dL from baseline at 12 weeks in haemodialysis patients with hyperphosphataemia, compared with a 1.08 mg/dL reduction for Sanofi's phosphate binder Renagel/Renvela (sevelamer). The study also suggested AP306 was safe and well tolerated, with a markedly lower dose burden than standard binders, which often require patients to take up to nine to 15 pills a day, R1 says on its website.A Phase IIb study of AP306 as monotherapy for hyperphosphatemia in patients with CKD is slated to start later this year in the US and China, with Alebund serving as a collaborative development partner on the drug.The oversubscribed series A financing was co-led by Abingworth, F-Prime and DaVita Venture Group, with participation from Curie.Bio, SymBiosis and US Renal Care.