Remogliflozin - Etabonate
Remogliflozin Etabonate (“Remo”) is a unique selective sodium glucose co-transporter (SGLT) 2 small molecule inhibitor. Remo has demonstrated robust insulin-independent lowering or HbA1c and weight in patients with type 2 diabetes by inhibiting reabsorption of glucose in the kidney. After positive results in a phase 3 clinical study, Remo was approved by the Indian DCGI and commercially launched in June 2019 for the treatment of type 2 diabetes in India. In September 2019, a fixed dose combination of Remo with metformin was approved for commercial sale by the DCGI. Remogliflozin is marketed as Remo and Remozen, and in combination with metformin as Remo-m and Remozen-m by Avolynt collaborator Glenmark Pharmaceuticals.
AVO-3235 is in phase 2 development for the treatment of Post Bariatric Hypoglycemia (“PBH”). PBH is a rare disease associated with bariatric surgery. There are currently no therapeutics approved for the treatment of PBH.
PBH is a form of reactive hypoglycemia that usually presents 6 months to 4 years post-bariatric surgery and is caused by a hyperinsulinemic response (uncontrolled spike in insulin) that occurs after a meal. Concurrent with the hypoglycemia, additional symptoms can include those associated with neuroglycopenia such as shakiness, hunger, dizziness, confusion, sweating and loss of consciousness which can dangerously impair normal day-to-day activities and can be life-threatening. In clinical studies, AVO-3235 has been shown to substantially delay and reduce postprandial spikes in plasma insulin.
AVO-3235 is an NCE that has been dosed in over 500 patients in 8 clinical studies and has been demonstrated to be safe and well tolerated.
AVO-1681 is in development for the treatment of Primary Sclerosing Cholangitis (PSC) and Primary Biliary Cholangitis (PBC). PSC and PBC are rare diseases of the liver. There are currently no marketed therapeutics that have been approved for the treatment of PSC. There are two approved treatments for PBC, however there remains significant unmet medical need in this patient population.
Primary sclerosing cholangitis is a chronic liver disease characterized by a progressive course of cholestasis with inflammation and fibrosis of the intrahepatic and extrahepatic bile ducts. The etiology of PSC is not well understood. PSC is generally a progressive disease that eventually culminates in cirrhosis with complications (e.g., portal hypertension, end-stage liver disease, hepatic failure). The median length of survival from diagnosis to death is approximately 12 years. Liver transplantation is the only treatment modality that appears to change the prognosis. Survival prospects are more dismal for those who are symptomatic at diagnosis.
Primary biliary cholangitis is a chronic liver disease characterized by a progressive course of cholestasis with inflammation and fibrosis of the intrahepatic bile ducts. The etiology of this disease is not well understood; PBC primarily affects women. PBC is a slow progressing disease that may culminate in cirrhosis and ultimately liver failure. There is no cure for PBC but two FDA approved treatment options are available, however they have limited patient response and significant side effects. Liver transplantation is considered when medical treatment no longer sufficiently controls the disease.
AVO-1681 has been dosed in multiple clinical studies and has been demonstrated to be safe and well tolerated. AVO-1681 was orally dosed in a mouse model (TIA mice) of bowel and liver disease. Compared to control, AVO-1681-treated mice had significantly less (p=0.01) progression of liver and biliary disease, as measured by a composite inflammation score. In parallel, a reduction of fibrosis was also observed in AVO‑1681-treated mice versus control mice; although the study duration was not sufficient to measure statistical significance. Other nonclinical studies of AVO-1681 have demonstrated statistically significant improvements in liver function such as reduced alanine aminotransferase (ALT) and aspartate aminotransferase (AST), reduced liver weight and reduced liver fat content. In addition, AVO‑1681 also reduced expression of pro-inflammatory cytokines, and reduced markers of oxidative stress in liver and serum. Clinical studies have also shown that treatment with AVO-1681 improves liver-related parameters including inflammation, oxidative stress and insulin resistance. Furthermore, post-hoc analysis of changes in ALT, showed that subjects with elevated ALT had statistically significant reductions after 12 weeks of AVO-1681 treatment versus placebo; indicating improved liver function.