Aprea AB

The Challenge

Cancers develop and spread due to malfunction of the cells' normal growth control mechanisms. One such growth mechanism is the p53 tumor suppressor gene. De-activation of p53 results in uncontrolled growth of the cell that may lead to cancer development. Moreover, de-activation of p53 is also strongly associated with resistance to chemotherapy. Mutations of the p53 gene occur in around 50 % of tumors and can be found in almost all known human cancer indications. Therefore, normalization of the function of p53 is a very attractive approach to cancer therapy and to help overcome resistance to existing cancer chemotherapeutics.

Aprea's Solution

Restoration of p53 function should eliminate tumor cells by apoptosis. Aprea has identified small molecules that reactivate p53. The company's first candidate drug, APR-246, has been shown to induce cell death in many cancer cell lines with varying p53 status. Promising therapeutic effects on tumors taken directly from patients and on human tumors transplanted to mice have also been demonstrated. 

A first Phase I/II safety study in cancer patients has been completed. The study demonstrated good tolerability at intended therapeutic doses of APR-246. A continuation of the study was recently started with the aim to evaluate safety and pharmacokinetics further and to establish the optimum dose as well as duration of exposure.

Aprea has also developed analogs of APR-246 that can be given by the oral route.

Competitive Advantages

APR-246 activates the function of p53 whether it is apparently normal or mutated and thus triggers programmed cell death in tumor cells. This function appears to be a unique characteristic of APR-246.  The drug has shown potential to be effective on many tumor types on its own, and to be used to overcome resistance to conventional chemotherapies.

The Market

Oncology is still an area with large unmet medical needs and the general ageing of the population means that morbidity and mortality figures are expected to rise over the next few years. Each year 6.5 million people are diagnosed with cancer and over four million people die worldwide as a result¹.