~ In PATH-1 and PATH-2 upacicalcet met primary and key secondary endpoints of reducing parathyroid hormone (PTH) in patients with end-stage kidney disease and Secondary Hyperparathyroidism (SHPT) on hemodialysis

~ Upacicalcet also reduced FGF23 and markers of bone turnover in the trial population ~

~ The pivotal data were simultaneously published in the Journal of the American Society of Nephrology ~

RALEIGH, N.C., Oct. 23, 2026 /PRNewswire/ — Pathalys Pharma, Inc., a private, US-based biopharmaceutical company committed to supporting the unique needs of patients with chronic kidney disease (CKD), today presented data demonstrating the company’s investigational calcimimetic, upacicalcet, met the primary endpoint and prespecified secondary endpoints in two pivotal Phase 3 studies, PATH-1 and PATH-2, that evaluated the safety and efficacy of upacicalcet in patients with secondary hyperparathyroidism (SHPT) and end-stage kidney disease receiving hemodialysis (HD).^1,2

Upacicalcet is an investigational product candidate and has not been approved by the U.S. Food and Drug Administration.

Results were presented during scientific sessions at the American Society of Nephrology (ASN) Kidney Week 2026 in Denver, CO and simultaneously published in the Journal of the American Society of Nephrology (JASN).

In its featured oral presentation, “Efficacy and Safety of Upacicalcet in Hemodialysis Patients with Secondary Hyperparathyroidism (SHPT): Two Randomized Clinical Trials (RCTs)”, the company reported upacicalcet met the primary endpoint of the proportion of participants achieving ≥30% reductions of intact parathyroid hormone (iPTH) compared with placebo during the efficacy assessment period (EAP). Consistent with the 2017 KDIGO guideline update the PATH trials estimated the effect of upacicalcet under a controlled background-treatment protocol that limited changes in supplemental calcium and active vitamin D sterols.^3,4

Upacicalcet also met the prespecified secondary endpoints of the proportion of participants achieving ≥50% reductions iPTH and the proportion of participants achieving iPTH of 150-300 pg/mL, which is the target range established by the National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (K/DOQI).⁵

“Clinicians caring for patients with CKD undergoing dialysis face a multitude of complex challenges, including the management of SHPT. Persistent elevations in parathyroid hormone may contribute to serious complications, including fractures, vascular calcification, and cardiovascular disease, which may place patients at increased risk of hospitalization and death,” said Jessica Kendrick, MD, MPH, Professor, Division of Renal Diseases and Hypertension, Department of Medicine at the University of Colorado Anschutz and Primary Investigator of the studies. “As clinicians work to address the many interconnected challenges that patients face, there remains a need for new treatment options and approaches that can help advance the management of SHPT.”

PATH-1 and PATH-2 efficacy results during the efficacy assessment period* (EAP) (Weeks 22-27)

*Baseline iPTH was defined as the mean of all active screening and pre-dose Day 1 iPTH values. Under the primary composite estimand, participants who died, permanently discontinued treatment for any reason, or received prohibited calcimimetics were counted as nonresponders regardless of observed iPTH values.

In both studies, upacicalcet was generally well tolerated. The rates of serious adverse events (SAEs) were similar for upacicalcet and placebo. The rates of gastrointestinal adverse events (AEs) – the most common of which were diarrhea and nausea – were similar for upacicalcet and placebo. The most frequent AE was asymptomatic hypocalcemia (23% for upacicalcet vs. 8% for placebo in PATH-1; 19% vs. 11%, respectively, in PATH-2). Symptomatic hypocalcemia with upacicalcet was observed in 0.8% (2/239) of participants in PATH-1 and 2% (6/271) of participants in PATH-2, vs. 0.0% for placebo in both studies.³

“Nearly half a million people in the United States receive hemodialysis, and with SHPT affecting nearly all patients with kidney failure receiving maintenance dialysis, the need for new and approved treatment approaches is both significant and urgent,” said Bastian Dehmel, MD, Chief Medical Officer of Pathalys Pharma. “At Pathalys, we believe every person living with CKD deserves access to innovation that addresses the key challenges they face. Our commitment to advancing new treatment options for SHPT reflects our broader mission to help address the unmet needs in CKD.

Separately at Kidney Week 2026, Pathalys presented additional data from PATH-1 and PATH-2 in the poster, “CKD-MBD Biomarker Profile in HD Patients With SHPT Treated With Upacicalcet: Biomarker Results From the Phase 3 PATH-1 and PATH-2 Trials.” The results suggested upacicalcet produced improvements across the full CKD-MBD (chronic kidney disease–mineral and bone disorder) profile, including reductions in iPTH and whole PTH (wPTH); reductions in C-terminal and intact FGF23, a risk marker for cardiovascular events and mortality in this patient population; and three markers of bone turnover.⁶

Upacicalcet is an investigational small molecule calcimimetic that acts as a positive allosteric modulator.⁷ It is thought to activate CaSR in the presence of extracellular calcium, with little agonist activity when calcium falls below the physiologic range.⁸

About PATH-1 and PATH-2
PATH-1 (NCT05832931) and PATH-2 (NCT05836220) were identical, randomized, double-blind, placebo-controlled trials comparing the safety and efficacy of intravenous (IV) upacicalcet (PLS240) with placebo in patients with secondary hyperparathyroidism (SHPT) and end-stage renal disease receiving hemodialysis. Consistent with the 2017 KDIGO guideline update, the PATH trials estimated the effect of upacicalcet under a controlled background-treatment protocol that limited changes in supplemental calcium and active vitamin D sterols.

PATH-1 and PATH-2 randomized 359 and 409 participants, respectively, in a 2:1 ratio to receive either upacicalcet or placebo following each hemodialysis session for 27 weeks. For participants randomized to receive upacicalcet, dose titration occurred over the first 19 weeks: participants received an initial upacicalcet dose of either 25 or 50 mcg, depending on cCa (corrected serum calcium) levels, then were eligible for dose increases every three weeks through Week 19 to 50, 100, 150, 200, 250 and 300 mcg, in stepwise fashion, if cCa≥8.3 mg/dL and PTH>300 pg/mL. Participants then remained on a stable dose of upacicalcet for Weeks 20-27, with Weeks 22-27 constituting the efficacy assessment period (EAP).

After completing the double-blind phase of the studies, all participants had the opportunity to enroll in the open-label extension to receive upacicalcet three times per week for a maximum of 26 weeks.

About Pathalys
Pathalys is a private, U.S.-based biopharmaceutical company committed to supporting the unique needs of patients living with chronic kidney disease (CKD). An initial area of focus is pursuing advancements in the treatment of secondary hyperparathyroidism (SHPT), a common complication for the approximately 486,000 patients in the U.S. with CKD undergoing hemodialysis.

Pathalys is developing upacicalcet, a calcimimetic for the treatment of SHPT. SHPT develops as the body struggles to maintain healthy calcium, phosphorus and parathyroid hormone levels when kidney function is lost.

Founded in 2021, Pathalys was built to be a biopharmaceutical company focused on innovation to meet the needs of patients living with CKD.

Learn more at PATHALYS.com and follow us on LinkedIn.

¹ Parathyroid Hormone (PTH) Attenuation Trial in Hemodialysis-1 (PATH-1). ClinicalTrials.gov. Accessed August 12, 2026. https://clinicaltrials.gov/study/NCT05832931.
² Parathyroid Hormone (PTH) Attenuation Trial in Hemodialysis-2 (PATH-2). ClinicalTrials.gov. Accessed August 12, 2026. https://clinicaltrials.gov/study/NCT05836220
³ Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update Work Group. KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl (2011). 2017;7(1):1-59. doi: 10.1016/j.kisu.2017.04.001
⁴ Pathalys. Data on file. 2026.
⁵ National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis. 2003;42(4 Suppl 3):S1-S201.
⁶ ASN Kidney Week 2026. CKD-MBD Biomarker Profile in Patients on Hemodialysis with SHPT Treated with Upacicalcet: Biomarker Results from the Phase 3 PATH-1 and PATH-2 Trials. Poster FR-PO0299.
⁷ Sato H, et al. Mol Pharmacol. 2022;102(4):183-195.
⁸ Goto M, et al. Eur J Pharmacol. 2023;956:175936.

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SOURCE Pathalys Pharma