Karolinska Development will exchange its shares in Oncopeptides for Industrifonden’s in Aprea. Karolinska Development and Industrifonden have been majority shareholders in Aprea and Oncopeptides, both cancer drug development companies, for several years. During this time, both companies have reached Phase I/II stage of clinical development.
The exchange gives Karolinska Development control of 69.4% of Aprea. It owned 43.4% of Oncopeptides and 41.1% of Aprea prior to the transaction. The transaction also includes a provision that will give Karolinska Development a 5% share of any revenue Industrifonden receives from its holdings of Oncopeptides up to a maximum of SEK 80 million. Likewise, Industrifonden will receive a 5% share of any revenue Karolinska Development receives from its holding of Aprea up to a maximum of SEK 80 million.
Oncopeptides is developing prodrugs of chemotherapeutic agents already approved for the treatment of cancer. These prodrugs are designed to be activated by enzymes that are overexpressed in tumor cells, which results in the selective delivery of the active moiety to tumor cells.
The company’s lead product, J1, is a prodrug of melphalan that consists of a dipeptide bound to melphalan. Once inside the cytoplasm, the aminopeptidase N enzyme activates J1 by cleaving the dipeptide from melphalan, thereby releasing free melphalan into the cytoplasm. Since J1 is transported across cell membranes much more efficiently than melphalan and aminopeptidase N is frequently overexpressed in tumor cells, the release of free melphalan from J1 occurs selectively in cancer cells.
Because of the mechanism of the prodrug activation, treatment with J1 results in a 10–20-fold higher intracellular concentration of melphalan in tumor cells than direct treatment with equal doses of melphalan, while the J1 toxicity profile is comparable to melphalan. J1 is currently in a Phase I/II clinical trial.
Aprea develops target-specific drugs for the treatment of cancer with nonfunctional p53. Aprea’s first investigational product, APR-246, has been granted orphan drug designation in the EU for APR-246, for the treatment of acute myeloid leukemia. It has been tested in a Phase I/II study in patients with refractory hematological malignancies or prostate carcinoma. The results show that the compound is safe at predicted therapeutic plasma levels.
The open-labeled, dose-escalating trial included 22 patients at seven clinics in Sweden. It was designed to reveal the highest feasible dose of APR-246 (primary endpoint) after two hours IV-infusions for up to four consecutive days.
APR-246 was reportedly found to induces apoptosis in p53 dysfunctional chemoresistant cancer cells. It demonstrated cancer cell specificity in primary cells from patients and synergistic or additive effects with different types of conventional chemotherapy. The company believes it is a promising option for combination treatment without adding to the burden of serious side effects.
"We believe that both Aprea and Oncopeptides have medical and hence commercial potential,” says Torbjörn Bjerke, CEO of Karolinska Development. “By doing this ownership exchange we will be able to focus on Aprea’s continued clinical development, and at the same time this transaction allows each party to benefit from the future success in the other’s investment.”