Human nephron organoid study shows reduced cyst expansion, supporting further investigation of HTD1801 in autosomal dominant polycystic kidney disease

人肾单位类器官研究显示囊肿扩张减少，支持进一步调查HTD1801在常染色体显性多囊肾病中的作用

HighTide Therapeutics, Inc., an innovative biopharmaceutical company specializing in the development of multifunctional, multi-targeted therapies for cardiovascular–kidney–metabolic (CKM) diseases, today presented new preclinical findings for HTD1801 in autosomal dominant polycystic kidney disease (ADPKD) at Kidney Week 2026, the 59th Annual Meeting of the American Society of Nephrology (ASN), in Denver, US.

HighTide Therapeutics, Inc. 是一家专注于开发针对心血管-肾脏-代谢（CKM）疾病的多功能、多靶点疗法的创新生物制药公司，今日在美国丹佛举行的美国肾脏病学会（ASN）第59届年度会议“Kidney Week 2026”上，公布了其候选药物 HTD1801 在常染色体显性多囊肾病（ADPKD）中的最新临床前研究结果。

The findings demonstrate potent inhibitory activity of HTD1801 against cyst expansion in ADPKD..

研究结果证实，HTD1801 对常染色体显性多囊肾病（ADPKD）的囊肿扩张具有强效抑制活性。

ADPKD is the most common inherited kidney disorder, characterized by progressive cyst formation and kidney failure by age 60 in approximately 50% of patients. Although existing treatments are available to slow disease progression in certain patients, safety risks and eligibility limitations leave substantial unmet medical needs in ADPKD..

常染色体显性多囊肾病（ADPKD）是最常见的遗传性肾脏疾病，其特征为进行性囊肿形成，约50%的患者在60岁时发展为肾衰竭。尽管现有治疗方法可延缓某些患者的疾病进展，但安全性风险和适用人群限制使得ADPKD领域仍存在巨大的未满足医疗需求。

HTD1801 targets the AMPK–NLRP3 axis by activating AMPK, suppressing cAMP-driven epithelial cyst proliferation while inhibiting NLRP3 to mitigate renal inflammation and fibrotic remodeling, thereby potentially targeting key pathological processes in ADPKD.

HTD1801 通过激活 AMPK，抑制 cAMP 驱动的上皮性囊肿增殖，同时抑制 NLRP3 以减轻肾脏炎症和纤维化重塑，从而靶向作用于常染色体显性多囊肾病（ADPKD）的关键病理过程。

In this study, the effect of HTD1801 on forskolin (FSK)-induced cyst expansion was evaluated in PKD1−/− human iPSC-derived nephron organoids, with metformin and tolvaptan as reference comparators.

在本研究中，以二甲双胍和托伐普坦作为参照对照，评估了HTD1801对福司柯林（FSK）诱导的PKD1−/−人诱导多能干细胞衍生肾单位类器官囊肿扩张的影响。

The results showed that HTD1801 significantly reduced the median cystic area fraction to 10.70%, compared with 20.40% in the FSK model control group. Meanwhile, organoids with a low cystic burden (<20%) increased from 46.9% in the model control group to 97.3%, while organoids with a high cystic burden (≥30%) decreased from 8.2% to 0%..

结果显示，与FSK模型对照组的中位囊性面积分数20.40%相比，HTD1801将其显著降低至10.70%。同时，低囊性负担（<20%）的类器官比例从模型对照组的46.9%增加至97.3%，而高囊性负担（≥30%）的类器官比例则从8.2%下降至0%。

By comparison, metformin reduced the median cystic area fraction to 13.12%, while tolvaptan did not alter cyst burden, as this model does not respond to tolvaptan.

相比之下，二甲双胍将中位囊性面积分数降低至13.12%，而托伐普坦并未改变囊肿负荷，因为该模型对托伐普坦无反应。

These findings further expand the potential multidimensional renal benefits of HTD1801. Previous studies have demonstrated the potential of HTD1801 to improve metabolic abnormality-associated renal impairment. HTD1801 effectively suppresses cyst expansion in PKD1-mutant human nephron organoids, validating its dual effects of AMPK activation and NLRP3 inhibition in ADPKD pathogenesis..

这些发现进一步拓展了HTD1801在肾脏方面的潜在多维获益。既往研究已证实HTD1801在改善代谢异常相关肾损伤方面的潜力。HTD1801能有效抑制PKD1突变人肾单位类器官中的囊肿扩张，从而验证其在常染色体显性多囊肾病（ADPKD）发病机制中激活AMPK和抑制NLRP3的双重作用。

These preclinical findings provide a strong rationale for further clinical investigation of HTD1801 to explore its potential as a disease-modifying therapy for ADPKD. They further highlight the therapeutic potential of HTD1801 for patients with ADPKD and other chronic kidney diseases (CKD), particularly those currently underserved by existing treatment options..

这些临床前发现为HTD1801的进一步临床研究提供了充分依据，以探索其作为常染色体显性多囊肾病（ADPKD）疾病修饰疗法的潜力。它们还凸显了HTD1801对于ADPKD及其他慢性肾脏病（CKD）患者的治疗潜力，尤其是对于那些现有治疗手段尚无法满足需求的患者群体。