Lead compound: SNF472

SNF472 FOR TREATMENT OF CALCIPHYLAXIS

Status: single Phase 3 pivotal study underway.

Sanifit is developing its lead candidate, SNF472, as a potential treatment for calciphylaxis, a rare disease related to progressive cardiovascular calcification (CVC). Calciphylaxis occurs most frequently in patients with chronic kidney disease (CKD), particularly those with end-stage kidney disease (ESKD) who are undergoing dialysis. Although less common, calciphylaxis also occurs in patients without CKD. The rationale for developing SNF472 for calciphylaxis is based on its capacity to block CVC progression.

CKD, a progressive and long-term condition where the kidneys do not work effectively, is a large and growing problem among aging populations. Once the disease has progressed to ESRD, kidney failure is permanent and irreversible, and the patient requires renal replacement therapy through dialysis or a renal transplant.

The metabolic and hormonal abnormalities in ESKD lead to a chronic state of inflammation, malnutrition, disordered mineral metabolism, anemia, and electrolyte disturbances. These conditions cause calcium deposits to form in the cardiovascular system of patients with ESKD, which can lead to cardiovascular diseases.

Calciphylaxis is a severe form of CVC in which the calcium deposits block small blood vessels in skin and fat tissue. These blockages cause the development of intensely painful and debilitating chronic skin lesions. Calciphylaxis is a devastating rare disease that affects 1-4% of dialysis patients and has a 1-year mortality rate of 55%.

Infections and other wound-related complications are leading causes of morbidity and hospitalization in patients with calciphylaxis. Patients are usually treated with pain medications and wound management but there are no approved therapies to address the underlying cause of the disease. SNF472 inhibits pathological CVC and has the potential to offer an innovative solution for this devastating condition.

Sanifit has obtained orphan drug status from the FDA and EMA for SNF472 as an investigational treatment for calciphylaxis. In an open-label Phase 2 study of calciphylaxis, improvements in wound healing, pain, and wound-related quality of life were observed after 12 weeks of SNF472 therapy. Sanifit successfully completed end-of-phase 2 regulatory interactions with the FDA and EMA and a placebo-controlled Phase 3 study is underway.

 

SNF472: NOVEL MECHANISM OF ACTION

SNF472 is a selective calcification inhibitor with a novel mechanism of action. SNF472 inhibits the development and progression of ectopic calcifications by binding to the growth sites of hydroxyapatite (HAP) crystals, the main component of calcification deposits, and in doing so blocks the formation and growth of HAP crystals in blood vessels, preventing CVC.

CaLIPSO: PHASE 2b STUDY IN DIALYSIS PATIENTS ASSESSED THE EFFECT OF SNF472 IN REDUCING CVC PROGRESSION

Status: Results announced in November 2019.

Sanifit conducted the Phase 2b CaLIPSO study in dialysis patients as a mechanistic proof of concept to evaluate the effect of SNF472 in reducing CVC progression by inhibiting HAP crystallization in blood vessels. SNF472 significantly reduced progression of CVC, the primary endpoint, in patients with ESKD receiving hemodialysis. SNF472 treated patients had coronary artery calcium volume score progression of 11% from baseline to week 52 versus 20% in patients receiving placebo (p=0.016). SNF472 was well tolerated and adverse events were similar for the SNF472 treated patients compared to those receiving placebo. For more information please refer to:  clinicaltrials.gov/ct2/show/NCT02966028?term=sanifit&rank=1.

HAP crystallization is the final common pathway of CVC-related diseases, such as calciphylaxis. CVC occurs at an accelerated rate in ESKD patients on dialysis and leads to other calcification-related diseases, like Peripheral Arterial Disease (PAD-ESKD) PAD-ESKD is driven by progressive calcification of peripheral arteries that supply blood to the legs, contributing to narrowing and hardening of these vessels and high mortality and morbidity. Symptoms include claudication (cramping leg pain while walking), weak peripheral pulses, cyanosis (bluish discoloration of skin and mucosa), ulceration, and reduced ability to walk. There are more than 3 million ESRD patients on dialysis, with 15 20% of them suffering from PAD.