Cirius Therapeutics Announces Positive Data for MPC Inhibitor 0602K Alone and in Combination with Tirzepatide

• MPC-inhibitor 0602K shows significant preservation of lean mass & increased muscle function combined with tirzepatide in pre-clinical DIO models
• 0602K shows profound beneficial transformation of adipose tissue in multiple ways & novel potential synergy with tirzepatide
• Both 0602K+tirzepatide and tirzepatide alone produced very similar rapid and substantial weight loss
• Pilot clinical study also shows 0602K by itself drives dramatic beneficial changes in muscle composition and metabolic function in patients with obesity & T2D
• Mitochondrial reprogramming with 0602K may add to benefits of GLP-1 weight loss with synergies in muscle & adipose tissues
• Data to be presented Sunday at ADA Scientific Sessions

GRAND RAPIDS, Mich., June 20, 2025 /PRNewswire/ -- Cirius Therapeutics, Inc., a developer of innovative therapies for patients suffering from diseases caused by insulin resistance, including obesity/overweight and type 2 diabetes (T2D), today announced positive results from the first preclinical diet-induced obesity (DIO) studies demonstrating the potential benefits of combining 0602K and tirzepatide for patients with obesity / overweight, as well as from a pilot clinical study. Detailed data is being presented as a late-breaking poster at the American Diabetes Association's (ADA) 85th Scientific Sessions as well as a short oral presentation available online as part of the conference. 

"We have been advocating for the potential benefits of combining an insulin sensitizer with the latest incretin therapies, especially to more fully resolving the underlying metabolic dysfunctions in obesity, type 2 diabetes and other cardio-renal-metabolic diseases," said Dr. Ralph DeFronzo, MD, co-author and Professor of Medicine at the University of Texas Health Science Center at San Antonio. Dr. DeFronzo continued, "First generation insulin sensitizer pioglitazone has given us strong hints of the possibilities. Now, this very exciting preclinical data combining next generation insulin sensitizer 0602K with a state-of-the-art GLP-1/GIP receptor agonist, tirzepatide, further supports the enormous potential. The pilot clinical data further suggests 0602K has similar effects on body composition and metabolism in patients with obesity, and that combining the highly complementary mechanisms of 0602K and tirzepatide should drive benefits for patients beyond those already gained via weight loss."

Collaborators at the Dasman Diabetes Institute in Kuwait and St. Louis University conducted parallel, independent DIO studies producing highly consistent results:

• Both 0602K+tirzepatide and tirzepatide alone produced very similar rapid and substantial weight loss through as long as 6 weeks treatment.
  
  
• 0602K + tirzepatide reduced the loss of lean mass and muscle typically seen with tirzepatide alone.
  
  
• Even more significantly, adding 0602K to tirzepatide increased both muscle strength and metabolic (mitochondrial) function by +50% each vs. tirzepatide alone. Adding 0602K to tirzepatide restored muscle strength/exercise capacity nearly to that of lean controls and increased mitochondrial abundance (number of mitochondria per muscle cell) by 50% over both lean controls and tirzepatide alone.
  
  
• 0602K + tirzepatide produced multi-faceted remodeling of adipose (fat) tissue, including reduced visceral-to-subcutaneous adipose tissue ratio (VAT:SAT), increased brown adipose tissue, and a synergistic transformation in subcutaneous adipose tissue (SAT) phenotype transformation.
  
  
• In SAT, 0602K and tirzepatide each produced marked decreases in adipocyte (fat cell) size, with the combination decreasing adipocyte size dramatically more than either alone. Smaller adipocytes are believed to be associated with several metabolic benefits, including an increase in numbers of "beige" adipocytes. Beige adipocytes actively consume stored fats and characteristically express uncoupling protein 1 (UCP-1), which aids in burning those fat calories. While both 0602K and tirzepatide increased UCP-1 protein in SAT by 2-3-fold over untreated high fat diet controls, the combination increased UCP1 ~7-fold with ~15% of cells UCP-1-positive.

Separately, collaborators at the University of Texas Health Science Center at San Antonio conducted a small (n=3) pilot mechanistic clinical study of 0602K effects on muscle composition and metabolic function. In patients with obesity & T2D. assessed at baseline and after taking 250mg 0602K daily for 3 months:

• 0602K decreased intramyocellular lipid (fat inside muscle cells) by ~50%
  
  
• Increased muscle metabolic function (insulin-mediated glucose disposal) by ~50%
  
  
• Reduced HbA1c from an average of 8.33% at baseline to 6.97%.

"These results support that targeting MPC with 0602K reprograms mitochondrial metabolism, not only reversing insulin resistance but also driving broad multi-organ benefits. Particularly important is 0602K synergy with GLP-1 receptor agonists we're describing here," remarked Dr. Jerry Colca, PhD, Cirius Chief Scientific Officer. Dr. Colca added, "0602K has previously been shown effective for T2D and MASH in Phase 2 clinical studies and without the side effect concerns that hung over earlier insulin sensitizers. These results highlight the need to explore the benefits of this combination particularly in patients with obesity / overweight."

Cirius and several of the academic collaborators involved in the study will be available at the ADA poster (1982-LB) from 12:30-1:30 PM CDT this Sunday, June 22.

Presentation Details:

• Title: 1982-LB - MPC-Directed Insulin Sensitizer MSDC-0602K Combines with Tirzepatide to Maintain Muscle Mass/Function and Restructure Adipose Tissue [Board No. 1982]
  
  
• Authors: M. Abu-Farha, J. Abubaker, F. Almulla – Dasman Diabetes Institute
  M. Abdul-Ghani, L. Norton, R.A. DeFronzo – University of Texas Health Sciences Center at San Antonio
  J.R. Colca – Cirius Therapeutics
  K.S. McCommis – St. Louis University
  
  
• Date & Time: Sunday, June 22, at 12:30 AM CT (poster will be up throughout meeting)
  
  
• Location: Poster Hall (Hall F1)

About Cirius
Cirius is a clinical-stage pharmaceutical company focusing on mitochondrial pyruvate carrier (MPC), addressing the metabolic dysfunction that causes insulin resistance and the organ pathologies associated with type 2 diabetes (T2D) and obesity/overweight. Its lead product candidate, 0602K (azemiglitazone potassium), is a potential best-in-class novel small molecule being developed as a once-daily oral therapy designed to selectively inhibit the mitochondrial target MPC, which plays a central role in selecting mitochondrial energy substrates. MPC inhibition reprograms mitochondrial metabolism, reducing insulin resistance in cells and driving metabolic benefits in organs throughout the body. This markedly improves glycemic control in T2D, body composition in obesity, liver function and fibrosis in metabolic dysfunction-associated steatohepatitis (MASH), and outcomes in cardiometabolic disorders.

About 0602K
0602K has completed 7 US clinical trials including a 52-week placebo-controlled Phase 2b study in 392 subjects with MASH with and without T2D, and a 28-day placebo-controlled Phase 2a study in 129 subjects with T2D. In those clinical studies it markedly lowered HbA1c and insulin levels, and reduced liver injury and MASH – including on top of existing GLP-1 therapy. A pilot clinical study showed 0602K markedly both reduces fat in muscle and increases muscle metabolic function in patients with obesity & T2D. Preclinical studies also demonstrate increased lean muscle mass, strength and metabolic function, together with metabolically beneficial shifts in adipose tissue phenotype ("bad fat" to "good fat"), both alone and on top of GLP-1 and GLP-1/GIP agonists. In combination with GLP-1/GIP dual agonist tirzepatide, the transformation of subcutaneous adipose tissue includes dramatic reduction in adipocyte size and synergistic increase in "beiging." Selectively targeting MPC – while avoiding PPAR-γ activation – 0602K harnesses the real-world proven efficacy of 1^st generation insulin sensitizers, such as pioglitazone, but without their side effect concerns.

Directly correcting a major underlying pathophysiology of chronic metabolic disease, 0602K has the potential to become a cornerstone of therapy. Coupling this potent pharmacology with that of the GLP-1s could particularly benefit patients with T2D, obesity/overweight and other cardiometabolic diseases.

www.CiriusTx.com

SOURCE Cirius Therapeutics