ENT-03: A Novel Drug for Obesity and Type 2 Diabetes

ENT-03 is a centrally-acting endogenous steroidal molecule (spermine-bile acid) that regulates whole-body responsiveness to insulin, energy homeostasis and body weight.

  • Potent inhibitor of PTP1b, an established Obesity and Type 2 Diabetes target

  • Rapidly induces weight loss, normalizes glucose and restores insulin senstitivity

  • May be used as monotherapy or in combination with GLP-1’s

  • Administered subcutaneously weekly

  • Preserves lean muscle mass in comparison to GLP-1s

  • Sustained effect weight loss and glucose control after therapy cessation

Obesity

  • Lead program targeting obesity, a $131B projected U.S. market by 2028, impacting nearly 60% of American adults

Diabetes

  • Over 36 million Americans now live with diabetes and the numbers continue to increase
  • Despite new highly efficacious drugs ~50% of diabetic individuals do not reach target goals and are at risk for debilitating and expensive long-term complications – new approaches still needed
  • Current recommendations support the use of multiple drugs in combination to achieve target levels of glucose; +60% are on combination therapy
  • No currently approved therapies directly improve insulin sensitivity. ENT-03 and ENT-21 aim to change that

MASH 

  • MASH (fatty liver disease) affects 9–15 million U.S. adults; ENT-03 and ENT-21 have demonstrated reversal of MASH pathology in preclinical studies

Offers Differentiation And Its Own Market vs. Incretin Class

  • Superior Tolerability – No nausea; better tolerated than GLP-1s.
  • Sustained Weight Loss – No rebound effect post-treatment, unlike GLP-1a.
  • Preserves Lean Mass – Suitable for older adults with sarcopenia, unlike GLP-1s.
  • Greater Versatility – Effective as monotherapy, adjunct, or maintenance therapy.
  • Enhanced Weight Loss Potential – Additive effect when combined with semaglutide.
  • Fast-Acting & Dose-Proportional – No need for a gradual dose escalation, unlike GLP-1s.
  • Robust Metabolic Benefits – Improves insulin sensitivity and reverses hepatic steatosis.
  • New MOA – Acts centrally on PTP1b in hypothalamic nuclei to regulate energy metabolism.