Unicycive Therapeutics Announces the Publication of Preclinical Data on Synergies Between Oxylanthanum Carbonate and Tenapanor in American Society of Nephrology Journal Kidney360
Unicycive Therapeutics (UNCY) has published preclinical data in the ASN journal Kidney360 demonstrating synergistic benefits of combining oxylanthanum carbonate (OLC) with tenapanor for phosphate management. The study showed that the combination therapy achieved a 41.3% reduction in urinary phosphate excretion compared to vehicle, significantly outperforming both individual treatments.
Key results showed tenapanor alone achieved a 12.5% reduction, while OLC monotherapy demonstrated a 17.7% reduction in phosphate excretion. The combination proved statistically significant (p=0.009 for 0.75% OLC + tenapanor). This research is particularly relevant as approximately 75% of dialysis patients fail to meet serum phosphate targets set by KDIGO guidelines. The study suggests OLC's low pill burden and palatable formulation, combined with tenapanor, could improve patient adherence and clinical outcomes in hyperphosphatemia treatment.
Unicycive Therapeutics (UNCY) ha pubblicato dati preclinici nella rivista ASN Kidney360 che dimostrano i benefici sinergici della combinazione di carbonato di ossilantano (OLC) con tenapanor per la gestione del fosfato. Lo studio ha mostrato che la terapia combinata ha raggiunto una riduzione del 41,3% dell'escrezione urinaria di fosfato rispetto al veicolo, superando significativamente entrambi i trattamenti singoli.
I risultati chiave hanno mostrato che il tenapanor da solo ha raggiunto una riduzione del 12,5%, mentre la monoterapia OLC ha dimostrato una riduzione del 17,7% nell'escrezione di fosfato. La combinazione si è rivelata statisticamente significativa (p=0.009 per 0.75% OLC + tenapanor). Questa ricerca è particolarmente rilevante poiché circa il 75% dei pazienti in dialisi non riesce a raggiungere gli obiettivi di fosfato sierico stabiliti dalle linee guida KDIGO. Lo studio suggerisce che il basso carico di pillole e la formulazione gradevole dell'OLC, combinati con il tenapanor, potrebbero migliorare l'aderenza dei pazienti e i risultati clinici nel trattamento dell'iperfosfatemia.
Unicycive Therapeutics (UNCY) ha publicado datos preclínicos en la revista ASN Kidney360 que demuestran los beneficios sinérgicos de combinar carbonato de oxilantano (OLC) con tenapanor para la gestión del fosfato. El estudio mostró que la terapia combinada logró una reducción del 41,3% en la excreción urinaria de fosfato en comparación con el vehículo, superando significativamente ambos tratamientos individuales.
Los resultados clave mostraron que el tenapanor solo logró una reducción del 12,5%, mientras que la monoterapia OLC demostró una reducción del 17,7% en la excreción de fosfato. La combinación resultó estadísticamente significativa (p=0.009 para 0.75% OLC + tenapanor). Esta investigación es particularmente relevante ya que aproximadamente el 75% de los pacientes en diálisis no logra alcanzar los objetivos de fosfato sérico establecidos por las directrices de KDIGO. El estudio sugiere que la baja carga de píldoras y la formulación agradable de OLC, combinadas con tenapanor, podrían mejorar la adherencia de los pacientes y los resultados clínicos en el tratamiento de la hiperfosfatemia.
유니사이브 테라퓨틱스 (UNCY)는 ASN 저널 Kidney360에 옥실란타늄 탄산염(OLC)과 테나파노르를 결합한 인산염 관리의 시너지 효과에 대한 전임상 데이터를 발표했습니다. 연구에 따르면, 이 조합 요법은 차량에 비해 41.3% 감소한 요분 인산염 배출량을 달성하여 개별 치료법보다 훨씬 우수한 성과를 보였습니다.
주요 결과에 따르면 테나파노르 단독으로는 12.5% 감소를 달성했으며, OLC 단독 치료는 인산염 배출에서 17.7% 감소를 보였습니다. 이 조합은 통계적으로 유의미한 결과(p=0.009, 0.75% OLC + 테나파노르)를 나타냈습니다. 이 연구는 약 75%의 투석 환자가 KDIGO 지침에서 설정한 혈청 인산염 목표를 충족하지 못하는 만큼 특히 중요합니다. 연구는 OLC의 낮은 복용 부담과 기호성을 높인 제형이 테나파노르와 결합할 경우, 환자의 복약 순응도 및 임상 결과 개선에 기여할 수 있음을 시사합니다.
Unicycive Therapeutics (UNCY) a publié des données précliniques dans la revue ASN Kidney360 démontrant les avantages synergiques de la combinaison du carbonate d'oxylanthane (OLC) avec le ténapanor pour la gestion du phosphate. L'étude a montré que la thérapie combinée a atteint une réduction de 41,3% de l'excrétion urinaire de phosphate par rapport au véhicule, surpassant significativement les deux traitements individuels.
Les résultats clés ont montré que le ténapanor seul a atteint une réduction de 12,5%, tandis que la monothérapie OLC a démontré une réduction de 17,7% de l'excrétion de phosphate. La combinaison s'est avérée statistiquement significative (p=0,009 pour 0,75% OLC + ténapanor). Cette recherche est particulièrement pertinente car environ 75% des patients sous dialyse ne parviennent pas à atteindre les objectifs de phosphate sérique fixés par les directives KDIGO. L'étude suggère que la faible charge de pilules et la formulation agréable de l'OLC, combinées au ténapanor, pourraient améliorer l'adhérence des patients et les résultats cliniques dans le traitement de l'hyperphosphatémie.
Unicycive Therapeutics (UNCY) hat präklinische Daten in der ASN-Zeitschrift Kidney360 veröffentlicht, die synergistische Vorteile der Kombination von Oxylanthanumcarbonat (OLC) mit Tenapanor zur Phosphatverwaltung zeigen. Die Studie zeigte, dass die Kombinationstherapie eine 41,3%ige Reduktion der urinären Phosphatausscheidung im Vergleich zum Vehikel erreichte und beide Einzelbehandlungen signifikant übertraf.
Wichtige Ergebnisse zeigten, dass Tenapanor allein eine Reduktion von 12,5% erreichte, während die OLC-Monotherapie eine Reduktion von 17,7% in der Phosphatausscheidung zeigte. Die Kombination erwies sich als statistisch signifikant (p=0,009 für 0,75% OLC + Tenapanor). Diese Forschung ist besonders relevant, da etwa 75% der Dialysepatienten die von den KDIGO-Richtlinien festgelegten Serumphosphatziele nicht erreichen. Die Studie legt nahe, dass die geringe Pillenlast und die schmackhafte Formulierung von OLC in Kombination mit Tenapanor die Patientenadhärenz und die klinischen Ergebnisse bei der Behandlung von Hyperphosphatämie verbessern könnten.
- Preclinical data showed significant 41.3% reduction in phosphate excretion with combination therapy
- Statistically significant synergistic effects demonstrated (p=0.009)
- OLC offers advantages of low pill burden and better palatability, potentially improving patient adherence
- Further clinical studies required to validate effectiveness in patients
- Results are only preclinical, not yet proven in human trials
Insights
The publication in Kidney360 represents a significant milestone in addressing one of nephrology's most persistent challenges - phosphate management in dialysis patients. The preclinical data reveals a compelling synergistic effect between OLC and tenapanor, achieving a 41.3% reduction in urinary phosphate excretion - substantially higher than either agent alone.
The significance extends beyond the impressive numbers. Current phosphate binders often fail due to poor adherence, largely attributed to high pill burden and palatability issues. OLC's improved formulation, combined with tenapanor's unique mechanism of action as an NHE3 inhibitor, could address these fundamental challenges. This dual-mechanism approach is particularly noteworthy as it targets phosphate absorption through complementary pathways, potentially offering better outcomes with improved tolerability.
However, it's important to note that while preclinical data is promising, the path to clinical validation remains critical. The p-values of 0.009 and 0.010 for different OLC combinations with tenapanor demonstrate strong statistical significance, but human trials will need to confirm these benefits in real-world settings. The market opportunity is substantial, considering that 75% of dialysis patients currently fail to meet KDIGO guidelines for phosphate control.
The synergistic effect observed could be particularly valuable for patients who are either unresponsive to current treatments or struggle with compliance. If these results translate to clinical settings, this combination therapy could represent a significant advance in hyperphosphatemia management, potentially improving both treatment efficacy and patient quality of life.
Combination therapy with oxylanthanum carbonate plus tenapanor led to greater reductions in urinary phosphate excretion than either drug alone
LOS ALTOS, Calif., Feb. 20, 2025 (GLOBE NEWSWIRE) -- Unicycive Therapeutics, Inc. (Nasdaq: UNCY), a clinical-stage biotechnology company developing therapies for patients with kidney disease, today announced the publication of preclinical data describing the benefits of combination treatment of oxylanthanum carbonate (OLC) and tenapanor on phosphate management in the American Society of Nephrology (ASN) journal, Kidney360.
The publication, entitled “Combination Oxylanthanum Carbonate and Tenapanor Lowers Urinary Phosphate Excretion in Rats,” examines the potential synergistic benefits of a combination of OLC, a phosphate binder, with tenapanor, a sodium/hydrogen exchanger 3 (NHE3) inhibitor, on urinary phosphate excretion. Data demonstrated sizeable reductions in urinary phosphate excretion (a proxy for intestinal phosphate absorption) in response to both OLC monotherapy and the combination of OLC with tenapanor.
“With approximately
“We're excited by these preclinical data showing a synergistic treatment effect from the combination of OLC and tenapanor. OLC, with its low pill burden and more palatable formulation, could complement tenapanor, significantly enhancing patient adherence and clinical outcomes,” said Shalabh Gupta, MD, Chief Executive Officer of Unicycive. “Further studies in patients with end-stage kidney disease and hyperphosphatemia will be required to understand the most effective and best tolerated OLC-containing regimens, as we aim to improve long-term control of hyperphosphatemia and prevent its myriad complications.”
Key Findings:
- Treatment with tenapanor alone (0.15 mg/kg) led to
12.5% lower mean urinary phosphate excretion compared to the vehicle in rats fed a high phosphorus diet. - A pooled analysis of monotherapy with OLC (
0.75% ,1.5% , and3% ) demonstrated a17.7% reduction in urinary phosphate excretion compared to vehicle. - Treatment with tenapanor in combination with OLC demonstrated a more pronounced
41.3% reduction in urinary phosphate excretion compared to vehicle. - The combination of OLC and tenapanor was synergistic and statistically significant (p=0.009 for
0.75% OLC + tenapanor and p=0.010 for1.5% OLC + tenapanor).
About Oxylanthanum Carbonate (OLC)
Oxylanthanum carbonate is a next-generation lanthanum-based phosphate binding agent utilizing proprietary nanoparticle technology being developed for the treatment of hyperphosphatemia in patients with chronic kidney disease (CKD). OLC has over forty issued and granted patents globally. Its potential best-in-class profile may have meaningful patient adherence benefits over currently available treatment options as it requires a lower pill burden for patients in terms of number and size of pills per dose that are swallowed instead of chewed. Based on a survey conducted in 2022, Nephrologists stated that the greatest unmet need in the treatment of hyperphosphatemia with phosphate binders is a lower pill burden and better patient compliance.1 The global market opportunity for treating hyperphosphatemia is projected to be in excess of
Unicycive is seeking FDA approval of OLC via the 505(b)(2) regulatory pathway. The NDA submission package is based on data from three clinical studies (a Phase 1 study in healthy volunteers, a bioequivalence study in healthy volunteers, and a tolerability study of OLC in CKD patients on dialysis), multiple preclinical studies, and the chemistry, manufacturing and controls (CMC) data. OLC is protected by a strong global patent portfolio including issued patents on composition of matter with exclusivity until 2031, and with the potential for patent term extension until 2035.
About Hyperphosphatemia
Hyperphosphatemia is a serious medical condition that occurs in nearly all patients with End Stage Renal Disease (ESRD). If left untreated, hyperphosphatemia leads to secondary hyperparathyroidism (SHPT), which then results in renal osteodystrophy (a condition similar to osteoporosis and associated with significant bone disease, fractures and bone pain); cardiovascular disease with associated hardening of arteries and atherosclerosis (due to deposition of excess calcium-phosphorus complexes in soft tissue). Importantly, hyperphosphatemia is independently associated with increased mortality for patients with chronic kidney disease on dialysis. Based on available clinical data to date, over
Dialysis patients are already at an increased risk for cardiovascular disease (because of underlying diseases such as diabetes and hypertension), and hyperphosphatemia further exacerbates this. Treatment of hyperphosphatemia is aimed at lowering serum phosphate levels via two means: (1) restricting dietary phosphorus intake; and (2) using, on a daily basis, and with each meal, oral phosphate binding drugs that facilitate fecal elimination of dietary phosphate rather than its absorption from the gastrointestinal tract into the bloodstream.
About Unicycive Therapeutics
Unicycive Therapeutics is a biotechnology company developing novel treatments for kidney diseases. Unicycive’s lead drug candidate, oxylanthanum carbonate (OLC), is a novel investigational phosphate binding agent being developed for the treatment of hyperphosphatemia in chronic kidney disease patients on dialysis. Positive pivotal trial results were reported in June 2024 for OLC, and a New Drug Application (NDA) is under review by the U.S. Food and Drug Administration (FDA) with a Prescription Drug User Fee Act (PDUFA) Target Action Date of June 28, 2025. OLC is protected by a strong global patent portfolio including an issued patent on composition of matter with exclusivity until 2031, and with the potential patent term extension until 2035 after OLC approval. Unicycive’s second asset, UNI-494, is a patent-protected new chemical entity in clinical development for the treatment of conditions related to acute kidney injury. UNI-494 has successfully completed a Phase 1 trial. For more information, please visit Unicycive.com and follow us on LinkedIn, X, and YouTube.
Forward-looking statements
Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified using words such as "anticipate," "believe," "forecast," "estimated" and "intend" or other similar terms or expressions that concern Unicycive's expectations, strategy, plans or intentions. These forward-looking statements are based on Unicycive's current expectations and actual results could differ materially. There are several factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, clinical trials involve a lengthy and expensive process with an uncertain outcome, and results of earlier studies and trials may not be predictive of future trial results; our clinical trials may be suspended or discontinued due to unexpected side effects or other safety risks that could preclude approval of our product candidates; risks related to business interruptions, which could seriously harm our financial condition and increase our costs and expenses; dependence on key personnel; substantial competition; uncertainties of patent protection and litigation; dependence upon third parties; and risks related to failure to obtain FDA clearances or approvals and noncompliance with FDA regulations. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: the uncertainties related to market conditions and other factors described more fully in the section entitled ‘Risk Factors’ in Unicycive’s Annual Report on Form 10-K for the year ended December 31, 2023, and other periodic reports filed with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Unicycive specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise.
1Reason Research, LLC 2022 survey. Results here.
2 Fortune Business InsightsTM, Hyperphosphatemia Treatment Market, 2023-2030
3 US-DOPPS Practice Monitor, May 2021; http://www.dopps.org/DPM
4 Block GA, Klassen PS, Lazarus JM, Ofsthun N, Lowrie EG, Chertow GM. Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol. 2004 Aug;15(8):2208-18. doi: 10.1097/01.ASN.0000133041.27682.A2. PMID: 15284307.
Investor Contacts:
Kevin Gardner
LifeSci Advisors
kgardner@lifesciadvisors.com
Chris Calabrese
LifeSci Advisors
ccalabrese@lifesciadvisors.com
Media Contact:
Rachel Visi
Real Chemistry
redery@realchemistry.com
SOURCE: Unicycive Therapeutics, Inc.
FAQ
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