Lead compound: SNF472

SNF472 FOR TREATMENT OF CALCIPHYLAXIS

Status: in preparation for Phase 3 pivotal study.

Sanifit is developing its lead candidate, SNF472, as a potential treatment for calciphylaxis, a rare disease related to progressive cardiovascular calcification (CVC). Calciphylaxis is a rare disorder that occurs most frequently in patients with chronic kidney disease (CKD), particularly those with end-stage renal disease (ESRD) 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 ESRD lead to a chronic state of inflammation, malnutrition, disordered mineral metabolism, anaemia, and electrolyte disturbances. These conditions cause calcium deposits to form in the cardiovascular system of patients with ESRD, which can lead to CVD.

Calciphylaxis is a severe form of cardiovascular calcification 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 which 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 has successfully completed end-of-phase 2 regulatory interactions with the FDA and EMA and preparations for placebo-controlled Phase 3 study are 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 TO ASSESS THE EFFECT OF SNF472 IN REDUCING CVC PROGRESSION

Status: fully recruited. Results in Q4 2019.

For more information please refer to:  clinicaltrials.gov/ct2/show/NCT02966028?term=sanifit&rank=1.

Sanifit is conducting 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.

HAP crystallization is the final common pathway of CVC-related diseases, such as calciphylaxis. CVC occurs at an accelerated rate in ESRD patients on dialysis and leads to other calcification-related diseases, which represent future opportunities:

  • Peripheral Arterial Disease (PAD): PAD is an accelerated CVC in the femoral 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.
  • Cardiovascular Disease (CVD): Accelerated CVC in the coronary arteries, heart valves, and aorta leads to a number of complications including the development of cardiac dysfunction and failure, with an increased likelihood of arrhythmia and sudden cardiac death. The annual cardiovascular event rate in ESRD patients on dialysis is around 20%. Approximately 80% of the 3+ million dialysis patients worldwide are affected by CVD. In addition, the annual mortality rate of dialysis patients is approximately 17%, with approximately 40% of those deaths caused by cardiovascular events. There are no approved treatments for CVD in dialysis. There is therefore a significant unmet need for a novel therapy to reduce the progression of CVC and lower the burden of morbidity and mortality in these patients.