Our R&D Pipeline

Phase II Ready Small Molecule: MCHR1 Antagonist CSTI-100 for Nonalcoholic Steatohepatitis (NASH) and Prader-Willi Syndrome (PWS)

  • NASH affects about 16 million Americans and is set to become one of the next epidemic-level chronic diseases. It's set to surpass hepatitis as the biggest reason for liver transplants by 2020. There is no approved treatment for NASH yet.
  • Multi-factorial treatment for all hallmark symptoms in rodent models - reductions in key liver inflammatory, fibrosis and injury biomarkers; reductions in liver fat (triglycerides and non-esterified fatty acids) and cholesterol; improvements in liver histology; fat-selective weight loss due to reduction in food intake; improvements in glucose tolerance and insulin sensitivity; better efficacy vs two other agents that have shown efficacy in clinical trials of NASH.
  • Safe and well tolerated in Phase I clinical studies, oral t1/2 of 26 h.
  • PWS is a rare genetic disorder that results in hyperphagia, early-onset life-threatening obesity, anxiety, and excessive day time sleepiness for which there are no approved therapeutic options. Hyperphagia and anxiety are cited as the highest priority symptoms of PWS from a caregiver perspective.
  • The preclinical and clinical pharmacological profile of CSTI-100 is well positioned to address appetite suppression. In phase I studies of CSTI-100, healthy, overweight volunteers had up to a 47% suppression of hunger on a visual analog scale after 14 days of dosing suggesting the potential to treat hyperphagia in PWS patients. The blockade of MCHR1 results in anxiolytic effects in various rodent models. These additional attributes of MCHR1 antagonism is anticipated to be beneficial to address increased anxiety observed in PWS patients.
  • Phase II ready asset: Triple Reuptake Inhibitor CSTI-500 for Prader-Willi Syndrome (PWS)

  • Appropriately balanced “triple pharmacology” is expected to address the hallmark symptoms of Prader-Willi syndrome, particularly the hyperphagia, behavioral issues, and sleep disorder
  • Weight loss and reduction of appetite observed in Phase I
  • High serotonin transporter (SERT), low-mid norepinephrine (NET), and dose-dependent dopamine transporter (DAT) occupancy
  • Human CNS receptor occupancy studies completed to confirm target engagement and guide Phase II dosing
  • Potential for highly differentiated treatment for multiple other CNS indications: depression, binge-eating disorder, ADHD, excessive day time sleepiness
  • CSTI-300: Novel targeting of the 5-HT3 Receptor to Treat Diarrhea-predominant Irritable Bowel Syndrome (IBS-D) and IBS with alternating constipation and diarrhea (IBS-M).

  • Irritable Bowel Syndrome (IBS) is a major functional disorder affecting 12% of adults with considerable economic burden (>$25 billion)
  • There is currently no effective treatment widely available
  • CSTI-300 is a 5-HT3 receptor partial agonist, expected to deliver such best-in-class treatment
  • Represents a new clinical approach; designed to avoid the side effects associated with maximal 5-HT3 receptor inhibition (i.e. severe constipation, ischemic colitis)
  • Excellent efficacy in translational preclinical models
  • Excellent drug properties and safety profile
  • Please contact info@consynance.com for a non-confidential deck