AP-306 / Roche, Alebund, R1 Therapeutics - LARVOL DELTA

Cholestatic Liver Disease Secondary to Novel ABCB4 and ABCC2 Mutations Responds to Ursodiol and Fenofibrate Therapy (ACG 2026) - "After 12 months of therapy, laboratory parameters improved to TB 0.7, AST 59, ALT 117, and AP 306. UDCA is a bile acid and works by increasing the solubility of bile contents. Fenofibrate through its activation of peroxisome proliferator-activated receptor alpha (PPARa) has been shown to increase the transcription of ABCB4."

Cholestasis • Fibrosis • Hepatology • Immunology • Inflammation • Liver Failure • ABCB1 • ABCB4 • ABCC2 • ER • PPARA

AP306-HP-02: A Study to Evaluate Safety, Tolerability and Efficacy of AP306 at Fixed Doses in Dialysis Participants With Hyperphosphatemia (clinicaltrials.gov) - P2 | N=168 | Recruiting | Sponsor: R1 Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Kidney Disease • Metabolic Disorders • Nephrology • Renal Disease

AP306-HP-02: A Study to Evaluate Safety, Tolerability and Efficacy of AP306 at Fixed Doses in Dialysis Participants With Hyperphosphatemia (clinicaltrials.gov) - P2 | N=168 | Not yet recruiting | Sponsor: R1 Therapeutics | Trial completion date: Dec 2025 ➔ Mar 2027 | Trial primary completion date: Nov 2025 ➔ Feb 2027

Trial completion date • Trial primary completion date • Chronic Kidney Disease • Metabolic Disorders • Nephrology • Renal Disease

Novel therapeutic approaches for phosphate regulation. (PubMed, Curr Opin Nephrol Hypertens) - "Combining phosphate binders with agents that inhibit paracellular and transcellular intestinal phosphate absorption may improve the treatment of hyperphosphatemia while reducing pill burden in CKD. Defining optimal serum phosphate targets and the mortality benefits of phosphate lowering is essential to minimize treatment-related adverse effects."

Journal • Chronic Kidney Disease • Metabolic Disorders • Nephrology • Renal Disease

A Phase 2 Trial to Evaluate Serum Phosphate Lowering Effect of a Pan-phosphate Transporter Inhibitor AP306 in Dialysis Patients with Hyperphosphatemia (ERA-EDTA 2024) - P2 | "AP306 (formerly known as EOS789) is an oral pan-inhibitor of phosphate transporters, including NaPi-2b, PiT-1, and PiT-2, which is designed to block the active uptake of phosphate through the gastrointestinal tract...The patients undergoing stable hemodialysis were randomized in a 1:1 ratio to receive AP306 or the active comparator, sevelamer carbonate, if their serum phosphorus was between 5.5 and 9.0 mg/dL after a wash-out period... AP306 monotherapy significantly reduced serum phosphorus with clinical significance and substantially improved the control rate in hemodialysis patients with hyperphosphatemia. AP306 was safe and well-tolerated."

Clinical • Late-breaking abstract • P2 data • Chronic Kidney Disease • Dermatology • Gastroenterology • Gastrointestinal Disorder • Immunology • Metabolic Disorders • Nephrology • Renal Disease • SLC34A2

Effects of EOS789, a novel pan-phosphate transporter inhibitor, on phosphate metabolism : Comparison with a conventional phosphate binder. (PubMed, J Med Invest) - "EOS789 has differing regulatory effects on Pi metabolism compared to LC. The properties of EOS789 may compensate for the limitations of LC therapy. The combined or selective use of EOS789 and conventional Pi binders may allow tighter control of hyperphosphatemia. J. Med. Invest. 70 : 260-270, February, 2023."

Journal • Metabolic Disorders • Nephrology • Renal Disease • SLC34A2

EOS789, pan-phosphate transporter inhibitor, ameliorates the progression of kidney injury in anti-GBM-induced glomerulonephritis rats. (PubMed, Pharmacol Res Perspect) - "These results indicate that EOS789 prevented glomerular crescent formation caused by mesangial fibrosis by ameliorating hyperphosphatemia. In conclusion, EOS789 would not only be useful against hyperphosphatemia but may also have the potential to relieve mesangial proliferative glomerulonephritis with crescent formation."

Journal • Preclinical • Chronic Kidney Disease • Fibrosis • Glomerulonephritis • Immunology • Lupus Nephritis • Metabolic Disorders • Nephrology • Orthopedics • Renal Disease

Past, Present, and Future of Phosphate Management. (PubMed, Kidney Int Rep) - "These include EOS789, which acts on the transcellular pathway, and tenapanor, which targets the dominant paracellular pathway. As observational evidence has established a strong association between phosphorus concentration and clinical outcomes, such as mortality, phosphate is an important target for improving the health of patients with CKD and end-stage kidney disease (ESKD)."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Gastrointestinal Disorder • Metabolic Disorders • Nephrology • Renal Disease • FGF23

EOS789, a broad-spectrum inhibitor of phosphate transport, is safe with an indication of efficacy in a Phase 1b randomized cross-over trial in hemodialysis patients. (PubMed, Kidney Int) - "Importantly, the use of P as a sensitive and direct measure of intestinal phosphate absorption allows specific testing of drug efficacy. The effectiveness of EOS789 needs to be evaluated in future Phase 2 and Phase 3 studies."

Clinical • Journal • P1 data • Metabolic Disorders • Nephrology • Renal Disease • SLC34A2

EOS789, a novel pan-phosphate transporter inhibitor, is effective for the treatment of chronic kidney disease-mineral bone disorder. (PubMed, Kidney Int) - "Additionally, EOS789 treatment also ameliorated kidney deterioration in rats with progressive kidney injury, probably due to the strict phosphate control. Thus, EOS789 has potent efficacy against hyperphosphatemia and its complications and could provide a significant benefit to patients who are ineffectively treated with phosphate binders."

Journal • Chronic Kidney Disease • Nephrology • Orthopedics • Renal Disease • FGF • FGF23

EOS789, a Novel Pan-Inhibitor of NaPi-IIb/PiT-1/PiT-2, Decreased Intestinal Phosphate Absorption in Hemodialysis Patients Measured by Sensitive and Direct Method Using 33P: A Phase 1b Clinical Trial (KIDNEY WEEK 2019) - "The second compared EOS789 100 mg vs EOS789 100 mg + 1600 mg sevelamer carbonate tid with meals. There was a significant decrease in intestinal P absorption at EOS789 100 mg tid. Importantly, 33P is a sensitive and direct measure of intestinal absorption, and is a superior method to serum P that is confounded by dialysis P clearance and bone remodeling."

Clinical • P1 data

EOS789, a Novel Pan-Inhibitor of NaPi-IIb/PiT-1/PiT-2, Suppressed Intestinal Phosphate Absorption in Healthy Subjects: A Phase 1 Clinical Trial (KIDNEY WEEK 2019) - "The safety, tolerability, and efficacy of EOS789 in patients with hyperphosphatemia will be further investigated in future clinical trials. Funding Commercial Support"

Clinical • P1 data