BioWorld International Correspondent

PARIS - Cerep SA reported encouraging, but mixed, results from a proof-of-concept Phase I/II trial of a cancer drug developed by its subsidiary, Cerenis, which is being tested in refractory or relapsing acute myeloid leukemia (AML).

The drug, CER 227185, is being tested in a multicenter trial on 13 patients, and results for the first 10 show that three had increased survival. Their survival rates were between 250 days and more than a year, against a mean average of 75 days.

However, while describing the results as "very encouraging" in view of the poor prognosis profile for the patients, Cerep, of Paris, said that the particular drug presents "several drawbacks." In effect, there was a "series of adverse drug reactions," which were "most probably linked to its interaction with its main pharmacological target in its initial non-cancer indication." It also has a "narrow therapeutic window."

As a result, Cerenis will discontinue development of the drug in favor of other similar compounds with improved profiles.

CER 227185 is designed to stimulate tumor reversion, a natural event in which tumor cells spontaneously revert to a non-malignant phenotype with a low occurrence rate. Cerenis pioneered the deciphering of the molecular mechanisms of tumor reversion, which it described as a cellular reprogramming process leading to the suppression of tumorigenicity, and identified the key steps in the process.

In particular, it discovered the translationally controlled tumor protein (TCTP) as a key molecular target, and went on to identify small molecules that stimulate the tumor reversion process through the inhibition of TCTP.

Cerenis used those results to test drugs that already were on the market in indications besides cancer and identified CER 227185 as a TCTP inhibitor. It demonstrated that the compound exerted an antitumor effect on multiple cancer cell lines from various origins and on primary cancer cells from patients.

On the basis of those results, it embarked on the Phase I/II trial of CER 227185 in AML. The test showed that the intracellular level of TCTP in blood cells decreased and that the drug had the expected biological effect on the target, acting in humans as a TCTP inhibitor at the doses administered.

Cerep expects the final results to establish proof of concept for that class of drugs and to validate the cancer drug discovery strategy of its subsidiary. Cerenis has several other TCTP inhibitors in its pipeline and plans to build a portfolio of cancer drug candidates acting through tumor reversion.

The first of those compounds is CER 233790, which is a metabolite of CER 227185. It displays the same therapeutic potential but is expected to have fewer side effects in humans due to its reduced interaction with the primary target of CER 227185 and because of the reduced likelihood of drug-drug interaction due to the absence of CYP2D6 interaction. Cerenis expects to complete preclinical development of CER 233790 and file an investigational new drug application in several cancer indications within the next 18 months.