Kidney Week

Abstract: TH-PO0118

Novel CD39 Recombinant Enzyme Regulating Inflammation, Thrombosis, and Organ Function in AKI and Sepsis

Session Information

• AKI: Mechanisms - 1
  November 06, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 103 AKI: Mechanisms

Authors

• Warncke, Max, Novartis Institutes for BioMedical Research Basel, Basel, BS, Switzerland

Max Warncke

• Lafont, Armelle, Novartis Institutes for BioMedical Research Basel, Basel, BS, Switzerland

Armelle Lafont

• Boehler, Vincent, Novartis Institutes for BioMedical Research Basel, Basel, BS, Switzerland

Vincent Boehler

• Li, Jianping, Novartis Institutes for BioMedical Research Basel, Basel, BS, Switzerland

Jianping Li, MD, PhD

• De Rosny, Charlotte, Novartis Institutes for BioMedical Research Basel, Basel, BS, Switzerland

Charlotte De Rosny

• Cattini, Alexander, Novartis Institutes for BioMedical Research Basel, Basel, BS, Switzerland

Alexander Cattini

• Welzenbach, Karl, Novartis Institutes for BioMedical Research Basel, Basel, BS, Switzerland

Karl Welzenbach, PhD

• Klein, Laurent, Novartis Institutes for BioMedical Research Basel, Basel, BS, Switzerland

Laurent Klein

• Pfister, Sabina, Novartis Institutes for BioMedical Research Basel, Basel, BS, Switzerland

Sabina Pfister

• Yang, Ming, Novartis Institutes for BioMedical Research Basel, Basel, BS, Switzerland

Ming Yang, PhD

• Ebersbach, Hilmar, ImmunOs Therapeutics AG, Schlieren, ZH, Switzerland

Hilmar Ebersbach

• Muller, Alban, Novartis Institutes for BioMedical Research Basel, Basel, BS, Switzerland

Alban Muller, MSc

• Sindelar, Miriam, Novartis Institutes for BioMedical Research Basel, Basel, BS, Switzerland

Miriam Sindelar, MSc, PhD

• Urban, Beatrice, Novartis Institutes for BioMedical Research Basel, Basel, BS, Switzerland

Beatrice Urban

• Calonder, Claudio, Novartis Institutes for BioMedical Research Basel, Basel, BS, Switzerland

Claudio Calonder, MSc, PhD

• Stempinski, Heike, Novartis Institutes for BioMedical Research Basel, Basel, BS, Switzerland

Heike Stempinski, MSc

• Flandre, Thierry Dany, Novartis Institutes for BioMedical Research Basel, Basel, BS, Switzerland

Thierry Dany Flandre, MSc, PhD, DVM

• Cochin de Billy, Benjamin, Novartis Institutes for BioMedical Research Basel, Basel, BS, Switzerland

Benjamin Cochin de Billy, MSc

• Darribat, Katy, Novartis Institutes for BioMedical Research Basel, Basel, BS, Switzerland

Katy Darribat

• Wieczorek, Grazyna, Novartis Institutes for BioMedical Research Basel, Basel, BS, Switzerland

Grazyna Wieczorek, DVM

• Junge, Guido, Novartis Institutes for BioMedical Research Basel, Basel, BS, Switzerland

Guido Junge, MD, PhD

Background

TIN816 is a novel recombinant CD39 enzyme that was investigated in preclinical models of acute kidney injury (AKI) and sepsis to decrease inflammation, thrombosis, and restore renal function.

Methods

The effect of TIN816 was assessed in ischemia/reperfusion (I/R)–induced AKI mice models by evaluating factors including neutrophil extravasation, tubular necrosis, and renal function (through serum creatinine levels). In the cecal ligation and puncture (CLP)–induced sepsis models, the effect of TIN816 was assessed using parameters such as mortality, markers of organ damage, and bacterial load.

Results

In an ischemia/reperfusion–induced AKI model with elevated extracellular adenosine triphosphate (eATP) levels, in vivo administration of TIN816 resulted in the conversion of eATP to extracellular adenosine monophosphate as observed in the urine, reduced tissue damage and inflammation, consequently protecting kidney function. Similarly, TIN816 administration in models of highly severe sepsis and sepsis-induced AKI conferred protection from multiorgan injury (kidneys, liver, and lungs) and inflammation, demonstrated by significant improvements in clinical scoring and survival rates. Besides tissue-protective effects, TIN816 improved in vitro bacterial clearance in the presence of adenosine triphosphate, and correspondingly significantly reduced colony-forming units in the bloodstream and peritoneum of the sepsis animal model. The protective effect of TIN816 was dose dependent and correlated with normalization of transcriptomic and metabolomic changes in the blood, urine, and tissues of the affected organs induced by AKI and sepsis in both models.

Conclusion

TIN816 demonstrated protective effects in models of AKI induced by I/R injury and sepsis induced by CLP. Currently, a phase 2b (NCT05996835) trial is evaluating TIN816 in sepsis-induced AKI.

Funding

• Commercial Support – Novartis

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.20258zakhrk3