Aprea Banks $51m Series B To Tackle 'Holy Grail' Of Oncology
This article was originally published in Scrip
Aprea AB, which is targeting the "holy grail" of anticancer research – the p53 tumor suppressor protein – and has the former head of oncology drug discovery of Bristol-Myers Squibb as its executive chair, has raised SEK 437m ($51m) in a series B financing.
The transaction sees former majority shareholder Karolinska Development drop its stake from 62% to around 19% via the conversion of SEK 60m of outstanding loans.
The deal marks a year since Karolinska Development's CEO Jim Van heusden took over the top job and was given the task of changing its strategy in a bid to change its fortunes.
He has been busy spinning out portfolio companies such as Pharmanest and XSpray Microparticles to sharpen Karolinska's focus, and also attract outside investment into the companies it retains.
"I'm very happy. This absolutely fits in with the grand plan of getting outside sophisticated investors on board," Van heusden told Scrip. Karolinska previously had a go-it-alone strategy that had not served it well. "It was very important to regain trust and credibility. This [deal] shows the value in our more focused strategy."
Aprea's new investor syndicate includes Versant Ventures and 5AM Ventures from the US, with participation by Sectoral Asset Management (Canada), and also included HealthCap (Sweden) as the local lead.
"Bringing in US investors will be very helpful in building the company and attracting top management," said Van heusden.
But Aprea already has a big name on the management team, with seasoned executive (and former BMS man) Bernd Seizinger as its executive chair.
Seizinger describes p53 as the "holy grail" of oncology, as more than 50% of tumors have a mutation in the p53 gene. Mutant p53 is often associated with resistance to anticancer drugs and poor overall survival, representing a major unmet medical need in the treatment of cancer. "However p53 is not your typical tumor suppressor gene." Rather than being completely deleted, most p53 mutations are associated with smaller "point mutations" that seem to lead to a conformational change in the p53 protein. Some of these mutations may be reactivated under certain conditions such as temperature change. "Even the wild-type p53 protein may switch back and forth from active to inactive."
Aprea's lead program APR-246 re-activates mutant p53 protein to its wild-type (normal) conformation and tumor suppressor function, thereby re-activating its anti-tumor activity.
Seizinger has a "two decade long history with p53" and admits to being "skeptical" about Aprea's prospects when he initially joined its board three years ago. According to Seizinger, BMS and other large pharma peers have attempted to find small molecules that could reactivate mutant p53. "We didn't succeed," he said.
He asked "lots of questions" when he joined Aprea and lots of mechanism based experiments were conducted in the intervening years. "About a year ago, I was excited enough to take on the role of executive chair."
Aprea is investigating APR-246 in a Phase Ib/II clinical study in high-grade serous ovarian cancer: the Phase Ib part of the study is completing shortly and the randomized Phase II part is expected to start within the first half of this year. Additionally, the company is planning to conduct exploratory trials in other cancer indications, including both solid and hematological tumors, and to establish a presence in the US.
The Phase II trial will have progression free survival as its endpoint, the same endpoint that will be pursued in Phase III, noted Seizinger. The trial will include sites in the US and Europe.
"We are financed through to 2019 and we expect to have Phase II proof of concept data in ovarian cancer as well as data from additional exploratory trials." Seizinger is particularly excited about the potential of APR-246 in acute myeloid leukemia (AML) and esophageal cancer.
His preference is for a trade sale of Aprea following Phase II data, or possibly an IPO on Nasdaq. "Neither would have been feasible if we had remained a parochial Swedish company," he concluded. "We will of course remain a Swedish company and further expand in Stockholm, particularly in clinical development, but strategically the US expansion is very important."