Interview: CellCentric Prostate Cancer Drug Promises Much
Executive Summary
The Cambridge-based company's CEO Will West tells Scrip that CCS1477 has shown a lot of potential for patients with late-stage prostate cancer who are resistant to second-line anti-androgen drugs like Zytiga and Xtandi and the $26m it has just raised will help fund development of the epigenetic therapy up to Phase IIb.
Having investigated around 60 potential epigenetic-related drug targets, the UK's CellCentric Ltd. believes it has found one that is a first-in-class candidate for treatment-resistant prostate cancer and is heading to the clinic with $26m in new funds.
The Cambridge-headquartered privately held biotech has raised all the cash from one of its existing backers - Morningside Venture Investments – to finance clinical testing of CCS1477, an inhibitor of the twin histone acetyl transferase proteins p300 and CBP. In an interview with Scrip, CellCentric CEO Will West said that the treatment significantly lowers the key drivers of late-stage prostate cancer - the androgen receptor (AR) and AR-splice variants (AR-SV) and c-Myc – and reducing AR-SV in particular is believed to address resistance to the existing second-generation blockbuster anti-androgen treatments, namelyJohnson & Johnson's Zytiga (abiraterone) and Pfizer Inc./Astellas Pharma Inc.'s Xtandi (enzalutamide), as well as J&J's Erleada (apalutamide).
West said that while formed back in 2004, CellCentric has shifted more recently from being "a knowledge epigenetics-based business" to a developer which decided that "we are going to choose a target and go for it." About 60 were explored and the company worked diligently on six of them, selling one - based on an arginine methyltransferase target - to Takeda Pharmaceutical Co. Ltd.. (Also see "Takeda licenses epigenetic programme from CellCentric" - Scrip, 23 Feb, 2010.)
Since 2013, it has been focused on just one target and trials of CCS1477 will start next month at the Royal Marsden Hospital in London. The plan is for CellCentric to take the drug through to Phase IIb but West told Scrip he was "slightly surprised" at the level of interest seen from prospective partners already.
He added that once the company shows efficacy and tolerability in trials, "it will get quite interesting, but we are not in a panic" to be bought or look at an initial public offering. West went on to praise Morningside, which it chose as the sole investor for this particular financing, adding that "they have been incredibly patient" and there is no time frame for an exit.
In terms of the market for the compound, he said that the company had done a lot of modeling and believed some 80,000 patients could benefit. Noting that the oncology space is highly competitive and complicated, West said that the situation with CCS1477 was quite special in that "you know exactly where you are positioned. It's crystal clear, if you fail on second-generational anti-hormonals, our drug will be there," if all goes well in the clinic.
CCS1477 is to be evaluated both as monotherapy and in combinations and potentially as a replacement for Zytiga and Xtandi. West added that "the stars have aligned on the p300/CBP dual target from a biology perspective in terms of understanding the mechanism of action and then how that translates to treat a clinical population. Clinicians have said 'we are looking for something that solves this' and we said 'well we've got that'."
Also, in the west, he noted that lots of patients have been lucky enough to have access to the aforementioned big-selling anti-androgen treatments, "so it is unusual to have a large but discreet population you can slot straight into without either displacing or muddying up things with existing treatments," and doing so with a potential first-in-class compound.
CellCentric is focused on one asset but is exploring its possibilities in indications other than prostate cancer where p300/CBP inhibition could be beneficial. Data presented at the recent American Association of Cancer Research meeting in Chicago highlighted the potential of CCS1477 in a range of cancers and West noted that by the end of the year, a hematology program would be launched with a specific focus on acute myeloid leukemia and multiple myeloma.
Further down the line, CellCentric is looking to test CCS1477 in bladder and lung cancers, where there is a high prevalence of tumors that have a mutation in either p300 or CBP. The company, which originally spun out of the University of Cambridge, is a tight unit with only five employees but collaborates with 12 key consultants globally, including Johann De Bono at the Royal Marsden and Martin Page, former head of global oncology research at J&J.