Kalypsys has an emerging, wholly owned product pipeline, derived from platform technology, and comprised of differentiated candidates addressing large and well-established therapeutic needs. The Saturation Discovery approach enables the rapid interrogation and validation of new targets and provides for continual replenishment of the Kalypsys pipeline. For its proprietary pipeline of novel small molecule product candidates, Kalypsys is currently focused on the therapeutic areas of pain/inflammation and metabolic disease.
PAIN AND INFLAMMATION
Topical iNOS Inhibitor
Kalypsys is developing molecules targeting iNOS, a member of the nitric oxide synthase (NOS) family of enzymes. The NOS family consists of three related enzymes (iNOS, eNOS and nNOS), each functioning in distinct physiological processes. Nitric oxide (NO) generation via the inducible nitric oxide synthase (iNOS) pathway has been implicated in the pathophysiology of pain and inflammation.
Our lead molecule in this area is KD7040, a potent, topically administered, inhibitor of iNOS with greater than 200-fold and 2000-fold selectivity over nNOS and eNOS, respectively. KD7040 demonstrates robust reduction of tactile allodynia in rodent models of pain, including the Chung model (peripheral neuropathy), the Bennett chronic constrictive injury model, and the capsaicin model of central sensitization. GLP safety pharmacology and toxicology studies have defined a favorable profile for clinic development. A Phase IIa clinical proof of concept trial in patients with post herpetic neuralgia was completed in late 2008.
METABOLIC DISEASE
Peroxisome Proliferator-Activated Receptor δ (PPAR δ) Agonist
PPARδ play a significant role in the control of lipid and energy homeostasis. Until recently, PPARα and PPARγ agonists were prominently used to treat hypertriglyceridemia and diabetes respectively and collectively achieved over $7.5 billion in sales in 2006. Recent safety concerns have significantly reduced the use of PPARα and γ agonists. Kalypsys has interrogated all PPAR subtypes in parallel using Saturation Discovery to provide a clear and early understanding of the potential for PPAR selectivity and the rationale for targeting PPAR δ. PPAR δ agonists were found to have significant efficacy in non-clinical models of aspects of metabolic syndrome, without the associated toxicities of PPARα and PPARγ agonists.
Our lead molecule in this program, KD3010, is a potent and selective oral PPAR δ agonist with diabetes and non-alcoholic steatohepatitis as the two lead indications. Data from relevant non-clinical models demonstrate that KD3010 treatment results in significant reduction of central adiposity, atherogenic lipid profiles, and improved glucose utilization associated with insulin sensitivity. Data from GLP safety pharmacology and toxicology studies have defined a favorable safety profile for entry in to the clinic. No hepatic, cardiac or muscle toxicities were observed in the Phase I human clinical studies of KD3010, and it is ready to enter Phase II clinical trials. Back to Top