Cytochroma announces new findings regarding the role of CYP24 in chronic kidney disease

Research presented at the V International Symposium "Advances in Bone and Mineral Disorders in CKD" -

MARKHAM, ON, March 19 /CNW/ - Cytochroma today announced new research findings demonstrating the increased expression of CYP24 in a preclinical model of chronic kidney disease (CKD). These findings suggest that abnormally increased expression of CYP24, the cytochrome P450 enzyme specific for catabolizing vitamin D, may be a key consideration in the management of secondary hyperparathyroidism (SHPT) in CKD.

Further, they highlight the potential benefit of CTA018, the Company's novel vitamin D hormone analog designed to simultaneously activate the vitamin D signaling pathway and inhibit CYP24. CTA018 Injection is currently in Phase II clinical trials. The new CYP24 data and Phase I study results for CTA018 Injection are being presented in oral presentations by Dr. Martin Petkovich, Chief Scientific Officer, and Dr. Joel Melnick, Vice President, Clinical Research and Development, at the V International Symposium "Advances in Bone and Mineral Disorders in CKD", which is taking place March 19-20 in Oviedo, Spain. Dr. Petkovich commented, "Cytochroma's research has provided significant new insights into the potential role of CYP24 in the etiology and treatment of SHPT. Our latest data suggest that the widespread existence of vitamin D insufficiency and resultant morbidities in CKD patients may originate from increased expression of CYP24. Vitamin D hormone analogs designed to inhibit CYP24 represent a promising new approach to the treatment of SHPT associated with CKD."

CYP24-Mediated Vitamin D Catabolism in a Preclinical Model of CKD

The new research reported by Cytochroma demonstrates that normal animals have low levels of CYP24 in the kidney, indicating that this enzyme is down-regulated to conserve vitamin D stores in the body. In contrast, uremic (renal-impaired) animals have markedly elevated levels of CYP24 in the kidney, indicating abnormal CYP24 regulation in CKD. Chronically elevated levels of CYP24 cause vitamin D insufficiency and reduce the effectiveness of vitamin D therapies by catabolizing the administered drugs. Cytochroma's findings suggest that elevated levels of CYP24 need to be managed in CKD patients to optimize the treatment of SHPT with vitamin D hormone replacement therapy.

Phase I Clinical Evaluation of CTA018 Injection

Cytochroma is developing an intravenous formulation of CTA018 as a new vitamin D hormone replacement therapy for SHPT in CKD. In a Phase I study, CTA018 Injection was well tolerated and produced clinically meaningful improvement in SHPT after less than two weeks of dosing. The study had an open label, placebo-controlled, and randomized design in which CTA018 Injection was administered to 20 healthy volunteers. In the first part of the study, the safety of CTA018 Injection was evaluated after single doses of up to 180 mcg. In the second part of the study, two different doses of CTA018 (90 and 180 mcg/injection) were administered every other day for 10 days. Key safety evaluations included the monitoring of subjects for abnormal serum and urine biochemistries and for adverse events. No clinically relevant side effects, including elevations in serum calcium or phosphorus, were observed that were related to CTA018 Injection. Cytochroma has granted Mitsubishi Tanabe Pharma Corporation (MTPC) exclusive rights to CTA018 in the U.S. and Asia. The companies have a co-development and co-promotion partnership in the U.S., whereas in Asia, MTPC has sole responsibility for development and commercialization in exchange for royalties.

About CTA018 Injection

CTA018 Injection is the first compound in a new class of vitamin D hormone analogs having a novel dual mechanism of action. The product is designed to activate the vitamin D signaling pathway as well as inhibit CYP24, the intracellular cytochrome P450 enzyme which catabolizes vitamin D and its hormones. CTA018 is being developed for the treatment of SHPT and is protected under patents and patent applications exclusively licensed to Cytochroma from the Johns Hopkins University.

About Chronic Kidney Disease

CKD is a condition characterized by progressive deterioration of the kidney, the organ responsible for excreting waste and excess water from the body as well as regulating vitamin D hormone production. CKD is classified in five different stages - mild (stage 1) to severe (stage 5) disease - as measured by the kidney's glomerular filtration rate. According to the National Kidney Foundation, CKD afflicts over 26 million people in the United States, including more than eight million patients with moderate (stages 3 and 4) and severe (stage 5) forms of CKD. In stage 5 CKD, kidney function is minimal to absent, and patients require regular dialysis or a kidney transplant for survival.

About Secondary Hyperparathyroidism

SHPT is a condition commonly associated with CKD in which the parathyroid glands secrete excessive amounts of parathyroid hormone (PTH). Excess PTH secretion arises as a result of impaired kidneys that are unable to produce sufficient quantities of vitamin D hormones to maintain a state of balance (homeostasis) between calcium and phosphorus in the body. Prolonged elevation of PTH causes excessive calcium to be released from bone into the blood, leading to softening of the bones (i.e. osteomalacia) and calcification of vascular tissues. SHPT affects 40-60% of patients with moderate CKD and approximately 90% of patients with severe CKD.

About Vitamin D Insufficiency

Vitamin D insufficiency is a condition in which the body has insufficient serum levels of vitamin D prohormones, collectively known as 25-hydroxyvitamin D. An estimated 70-90% of CKD patients have vitamin D insufficiency, which can lead to SHPT and resultant debilitating bone diseases. Mounting evidence continues to link vitamin D insufficiency with progression of CKD, cardiovascular events, and increased mortality.

About Cytochroma

Cytochroma is a clinical stage specialty pharmaceutical company focused on developing and commercializing proprietary products to treat and prevent the clinical consequences of vitamin D insufficiency and secondary hyperparathyroidism (SHPT) associated with chronic kidney disease (CKD). The Company specializes in developing new vitamin D therapies which are designed to safely and effectively treat patients with stage 3, 4 or 5 CKD. Cytochroma has three lead product candidates in development for CKD patients: CTA018 Injection and CTAP201 Injection are being developed for the treatment of SHPT, while CTAP101 Capsules are being developed for the treatment of vitamin D insufficiency. In addition, Cytochroma is developing novel therapies to treat hyperphosphatemia in CKD patients. For more information about Cytochroma, please visit www.cytochroma.com<http://www.cytochroma.com>.

 

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/For further information: Investors: Gordon Ngan, Executive Director, Corporate Development, Tel: (905) 479-5306 ext. 333, gngan@cytochroma.; Media: Robert Stanislaro, FD, Tel: (212) 850-5657, robert.stanislaro@fd.com

Posted: March 2009

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