Kidney Week

Abstract: TH-PO1190

Evidence of Kidney Benefit with HTD1801 in Patients with Mild Renal Impairment

Session Information

• Late-Breaking Research Posters
  November 06, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

• Surmont, Filip Ame, Shenzhen HighTide Biopharmaceutical Ltd, Shenzhen, Guangdong, China

Filip Ame Surmont, DrMed, ScD, ScM

• Gao, Leili, Peking University People's Hospital, Beijing, China

Leili Gao, PhD

• Liu, Kui, Shenzhen HighTide Biopharmaceutical Ltd, Shenzhen, Guangdong, China

Kui Liu, MD

• Liberman, Alexander, Hightide Therapeutics, Inc., San Diego, California, United States

Alexander Liberman, PhD

• Macconell, Leigh, Hightide Therapeutics, Inc., San Diego, California, United States

Leigh Macconell, PhD

• Yu, Meng, Shenzhen HighTide Biopharmaceutical Ltd, Shenzhen, Guangdong, China

Meng Yu

• Liu, Liping, Shenzhen HighTide Biopharmaceutical Ltd, Shenzhen, Guangdong, China

Liping Liu, PhD, MBA

• Ji, Linong, Peking University People's Hospital, Beijing, China

Linong Ji, MD

Group or Team Name

• On behalf of the SYMPHONY Investigators.

Background

Chronic kidney disease (CKD) progresses from initial glomerular hyperfiltration to irreversible eGFR decline, driven by inflammation leading to tubulointerstitial fibrosis. Current therapies fail to reverse the decline of eGFR. HTD1801, a first-in-class NME, is an anti-inflammatory metabolic modulator that activates AMPK and inhibits NLRP3. It warrants investigation in patients with and without T2D, from early eGFR decline through advanced stages of CKD.

Methods

Data from two randomized, double-blind, placebo-controlled Phase 3 studies of HTD1801 in patients with T2D (Symphony 1 & 2) were pooled (N=956). The primary endpoint was change in HbA1c at Week 24. Key entry criteria: T2DM, HbA1c 7.0%-10.5%, FPG ≤13.9 mmol/L, and eGFR >60 ml/min/1.73m². Hyperfiltration was defined as baseline eGFR ≥120 ml/min/1.73m². Mild renal impairment was defined as baseline eGFR 60-90 ml/min/1.73m².

Results

In patients with mild renal impairment (n=123), a significant increase in eGFR from baseline was observed following the initiation of HTD1801 (Fig 1) compared with placebo (5.30 vs 0.35 ml/min/1.73m², p<0.05) resulting in a positive eGFR slope with a difference in annual eGFR slope of 9.81 ml/min/1.73m²/year (p<0.01). In patients with hyperfiltration (n=85), eGFR was reduced following the initiation of HTD1801 compared with placebo (-2.83 vs -0.28 ml/min/1.73m²). HTD1801 treatment demonstrated no clinically relevant effects on blood pressure, serum sodium, or serum potassium.

Conclusion

These data provide the first clinical evidence that a therapy may benefit patients with CKD by improving the eGFR trajectory and recovering kidney function from the earliest stages of CKD, distinguishing HTD1801from existing therapies. The findings suggest a potential disease-modifying effect, indicating that HTD1801 may improve the eGFR trajectory.

Funding

• Commercial Support – HighTide Therapeutics

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.202552fxp7aj