Big Pharma Quartet Puts $30M Behind Aileron’s P53 Peptide Drug

11/18/13Follow @benthefidler

Aileron Therapeutics decided long ago to design a stapled peptide drug that just might be able to protect one of cancer biology’s most tantalizing, yet untouchable targets—the tumor suppressor protein known as p53. Now, the Cambridge, MA-based startup’s investors have armed it with $30 million to see if it’s on to something.

Aileron has pulled in a $30 million Series E round of equity financing from all of its existing investors, which include Apple Tree Partners, Excel Venture Management, and the VC arms of four pharmaceutical giants: Roche (Roche Venture Fund), Novartis (Novartis Venture Funds), Eli Lilly (Lilly Ventures), and GlaxoSmithKline (SR One). The round was “substantially oversubscribed,” according to Aileron president and CEO Joseph Yanchik.

Aileron has now raised just under $100 million since its inception in 2005. And the cash is primarily being used to push the company’s high-risk, high-reward cancer drug candidate, ALRN-6924, through an ambitious, first clinical trial in the middle of 2014 that’ll be designed to make it clear whether Aileron has a chance against one of hardest targets in cancer biology.

Aileron envisions running a roughly 100-patient Phase I trial testing ALRN-6924 in patients with solid and liquid tumors, and a variety of different cancers, to see if it can find which tumor types respond the best to its drug while assessing its safety in humans. With the cash it now has on hand, Aileron also has enough breathing room to pick out those responders and add an additional trial arm—more of a Phase 2 type of study—that focuses specifically on them and the type of results the drug can produce. Aileron is still designing the trial, however, so the structure is up in the air.

“We are going into the trial to try to get an early answer, and an early look, not only at the potential range of applications, but to also demonstrate that we are, in fact, modulating this incredibly important target,” Yanchik says.

Aileron also plans to expand its clinical team and roughly double the size of its 20 or so employee workforce to help with the effort.

As I wrote back in August, ALRN-6924 is an optimized version of a drug candidate Aileron developed to attempt to protect p53, something pharmaceutical companies have unsuccessfully tried to do for more than two decades. P53 is bound to the DNA in the nucleus and has been nicknamed the “Guardian of the Genome,” because it is the cell’s first line of defense. It keeps cell division is check, senses whether anything is wrong, and orders the cell to commit suicide if it is. That’s the job of a tumor suppressor.

P53, however, is deactivated in every type of cancer. When it’s shut down, either by being mutated, or repressed by another gene, cells begin rapidly replicating, and liquid or solid tumors are formed. Its potential broad usage is what makes it so attractive to drugmakers, which have poured millions into finding a way to stop this process from happening.

As is often the case, however, this is much easier said than done. Antibodies hit targets on the surface of cells, so they can’t make it to the proper site in the nucleus of the cell. And small-molecules aren’t big enough to rip apart the protein-protein interaction that causes p53 to shut down.

Aileron is betting that one of its “stapled” peptides—protein fragments that are chemically stapled to one another—can succeed where other attempts have failed by being specially configured to simultaneously hit proteins made by two genes, MDM2 and MDMX, that deactivate p53. Given the past failures industry players have had trying to shield p53, and to this point, the lack of clinical proof that stapled peptides truly work, it’s a tall order. But the potential payoff is so big that Aileron has made this drug candidate its top priority. Though another experimental drug for rare endocrine disorders (ALRN-5281) has already passed a Phase I trial, it is now the 1B to the p53 drug’s 1A.

“An oncology drug of this importance clearly starts to move itself front and center,” Yanchik. “[But] as we show the data from [ALRN-5281], I think a close second is ok. Really we are now starting to establish that the stapled peptide platform is going to yield some very important drugs and create an entirely different avenue of drug development.”

ALRN-6924 is the latest version of a drug Aileron developed and then put into a $1.1 billion partnership with Roche in 2010. Roche, however, recently pulled back its p53 research when it closed its Nutley, NJ R&D hub. So Aileron reacquired rights to the drug this past year, according to Yanchik. Roche, of course, is still an equity holder in Aileron.

Ben Fidler is Xconomy's Deputy Biotechnology Editor. You can e-mail him at bfidler@xconomy.com Follow @benthefidler

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