Press Release:

CYTOCHROMA ANNOUNCES DATA PRESENTATIONS AT AMERICAN SOCIETY OF NEPHROLOGY’S 43RD ANNUAL MEETING AND SCIENTIFIC EXPOSITION

Markham, Ontario, Canada — November 18, 2010 — Cytochroma today announced that data on several of its product candidates will be presented at the American Society of Nephrology’s 43rd Annual Meeting and Scientific Exposition (ASN) in Denver, Colorado taking place from November 18-21, 2010. These data relate to clinical results on CTAP101 Capsules and CTAP201 Injection, as well as research results on Cytochroma’s upstream compounds targeting cytochrome P-450 24 (CYP24), the enzyme responsible for catabolism of vitamin D.

“Cytochroma’s clinical and non-clinical teams continue to achieve important research advances that validate our focus on vitamin D, CYP24 and secondary hyperparathyroidism,” stated P. Martin Petkovich, Chief Scientific Officer. “With existing vitamin D treatments limited by mediocre efficacy and dose-limiting side effects, our therapeutic approach of using vitamin D, yet mitigating the impact of CYP24, may result in superior treatment of secondary hyperparathyroidism in chronic kidney disease patients.”

ASN abstracts can be viewed online at www.asn-online.org. Summaries of Cytochroma’s abstracts appear below.

Presentation Title: Pharmacodynamic and Pharmacokinetic Profiles of CTAP101 Capsules and Intravenous Calcifediol for Secondary Hyperparathyroidism in Stage 3 or 4 CKD
Abstract: TH-PO185 Poster Presentation
Lead Author: Joel Z. Melnick, MD
Date and Time: November 18, 10:00 AM - 2:30 PM

Current therapies are ineffective in normalizing low serum vitamin D pro-hormone (25D) and high intact parathyroid hormone (iPTH) levels in CKD patients. Cytochroma evaluated CTAP101 Capsules in a Phase I/II randomized open label single-dose study in which 27 subjects with vitamin D insufficiency and serum iPTH above K/DOQI targets were dosed with CTAP101 (450 or 900 mcg) or IV 25D3 (450 mcg). Despite rapid and higher increases in mean 25D3 and 1,25D3 (vitamin D hormone) in the IV arm versus the CTAP101 arms, the IV arm did not result in a reduction of mean iPTH. In contrast, CTAP101 dosed at 900 mcg achieved gradual increases of 25D3 to target, but also reduced iPTH at 24 hrs by a mean of 19% from baseline. No confirmed hypercalcemia was observed in any treatment group and no SAEs were reported. The rapid increase in 1,25D3 after bolus administration of 25D3 may have triggered excessive expression of CYP24 in the parathyroid glands, leading to local hormone resistance and limited iPTH suppression. These findings demonstrate that the mechanism to lower iPTH may be more complex than simply driving up serum 25D3 levels, and that the gradual increase in 25D3 achieved through CTAP101 Capsules may be an important new method in treating CKD patients with vitamin D insufficiency and elevated PTH.

Presentation Title: Dose Comparison Study of CTAP201 Injection and Doxercalciferol (Hectorol®) Injection in Hemodialysis Patients with Secondary Hyperparathyroidism
Abstract: TH-PO208 Poster Presentation
Lead Author: Joel Z. Melnick, MD
Date and Time: November 18, 10:00 AM - 2:30 PM

In a Phase I open label pharmacokinetic cross-over study, Cytochroma compared CTAP201 Injection to doxercalciferol (DOX) injection in 24 hemodialysis patients with secondary hyperparathyroidism. Subjects were enrolled sequentially into two dose groups and were randomized to receive single doses of CTAP201 and DOX, separated by a two-week wash-out. Mean total exposures to 1,25D2 from CTAP201 were comparable to that following twice the dose of DOX. CTAP201 Injection achieved comparable % reductions in iPTH with significantly lower serum calcium and a trend toward lower phosphorus levels.

Presentation Title: Novel Synthetic Prohormonal Forms of Vitamin D for Use in the Treatment of Secondary Hyperparathyroidism Associated with CKD
Abstract: TH-PO187 Poster Presentation
Lead Author: Christian Helvig, PhD
Date and Time: November 18, 10:00 AM - 2:30 PM

CTA192 is a novel synthetic vitamin D prohormone developed by Cytochroma which resists catabolism by CYP24 when activated by the kidney enzyme CYP27B1. In a cell line expressing CYP27B1, CTA192 induced vitamin D receptor transcriptional activity at a level approximately 5-10% of that observed with the activated parent compound. However, when CTA192 was administered over a two-week period (six doses) in a pre-clinical adenine model of CKD, the compound was equally effective in lowering blood PTH levels as its parent compound at doses only five to six fold higher. In contrast to its parent, CTA192 did not raise serum calcium or FGF23 levels. These studies indicate that synthetic vitamin D prohormones requiring CYP27B1 for activation, such as CTA192, may offer safety advantages over current hormone replacement therapies which frequently cause hypercalcemia.

Presentation Title: The Use of Inhibitors of CYP24 To Control Secondary Hyperparathyroidism in an Adenine Induced Rat Model of CKD
Abstract: F-FC199 Oral Presentation
Lead Author: Martin P. Petkovich, PhD
Date and Time: November 19, 5:18 PM - 5:30 PM

Cytochroma recently reported evidence that CYP24 is increased in CKD and may be at least partly responsible for declining vitamin D status and end organ resistance to exogenous vitamin D treatment. Several of Cytochroma’s compounds, which specifically inhibit CYP24, were evaluated in a pre-clinical adenine model of CKD. In single or repeat dose studies with these inhibitor compounds, efficient reductions in elevated parathyroid hormone were achieved without significant increases in blood calcium levels. These studies demonstrated that blocking CYP24 activity effectively facilitated:
1) the activity of existing vitamin D hormone in target tissues and/or;
2) the production of vitamin D hormone by blocking catabolism of existing vitamin D pro-hormone substrate.

These studies demonstrate that CYP24 may be a promising therapeutic target for the treatment of secondary hyperparathyroidism associated with CKD.

About Chronic Kidney Disease

CKD is a condition characterized by a progressive decline in the function of the kidney, which is normally responsible for excreting waste and excess water from the body, and for regulating various hormones. 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 Vitamin D Insufficiency

Vitamin D insufficiency is a condition in which the body has low blood 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 secondary hyperparathyroidism (SHPT) and resultant debilitating bone diseases.  Mounting evidence continues to link vitamin D insufficiency with progression of CKD, cardiovascular morbidity, and increased mortality.

About Secondary Hyperparathyroidism (SHPT)

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 and phosphorus to be released from bone into the blood, leading to elevated serum calcium and phosphorus, softening of the bones (osteomalacia) and calcification of vascular tissues.  SHPT affects 40-60% of patients with moderate CKD and approximately 90% of patients with severe CKD.

About CYP24

CYP24 is a cytochrome P450 24-hydroxylase also known as the “vitamin D catabolic enzyme” because it acts only on vitamin D and its metabolites, hormones and analogs. Intracellular expression of CYP24 regulates tissue response to vitamin D therapies. In healthy individuals, CYP24 has a protective role: its expression rapidly increases in proportion to intracellular levels of vitamin D hormone, thereby preventing potential toxicity. Abnormally elevated CYP24 in certain disease states, including CKD, is associated with vitamin D insufficiency and with resistance to vitamin D therapies.

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 SHPT associated with 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 product candidates in clinical development for CKD patients: CTA018 Injection and CTAP201 Injection are being developed for the treatment of SHPT in stage 5 CKD, while CTAP101 Capsules are being developed for the treatment of vitamin D insufficiency and associated SHPT in stage 3 and 4 CKD. Cytochroma also has a portfolio of compounds that inhibit CYP24 in early stage development.

For information contact:

Investors:
Gordon Ngan
Executive Director, Corporate Development
Tel: +1 (905) 479-5306 ext. 333
gngan@cytochroma.com

Media:
Robert Stanislaro (FD)
Tel: +1 (212) 850-5657
robert.stanislaro@fd.com

< go back >