Staff Writer

Aileron Therapeutics Inc. raised $7 million to move from proof of concept toward clinical development of products based on its stapled peptide technology platform.

The technology is designed to allow peptides to penetrate cells, where they are directed at intracellular protein-protein interaction targets. The platform potentially has broad applications, with the lead program targeting the Bcl-2 protein for cancer indications.

"There have been quite a few efforts in the area of developing peptides as drugs," said Joseph Yanchik III, president and CEO of Aileron. "But none has succeeded for intracellular targets.

"The fact that a stapled peptide actually gets into the cell is the first thing that makes it unique," Yanchik told BioWorld Today. "Then its ability to hit various targets within the cell makes it even more distinct from any previous stabilizing technology. There have been other techniques and approaches to stabilize peptides in an attempt to turn them into drugs. Some have done a fine job in stabilizing them, but they don't act like a drug; they don't do what they need to do in the cell."

The company began in early 2005 to evaluate various technologies to form around, and had turned its focus to the stapled peptide technology by the second quarter of 2005. "It was something we thought had a fantastic chance to work, something to build a company around solely," Yanchik said.

In 2006, Aileron gained exclusive, worldwide rights in all application from inventors at Harvard University and the Dana-Farber Cancer Institute.

Aileron said the technology is the "first and only" process that allows peptides to penetrate cells in a sequence-independent manner.

Founding investor Apple Tree Partners had provided about $3 million in seed funding over time. Investors in the new $7 million financing, which the company refers to as its Series B round, included Apple Tree and the Novartis Venture Fund.

The only target disclosed so far is Bcl-2, a member of a family of proteins involved in the control of cell death. The idea with the technology is to selectively restore the cell-death, or apoptotic, process in cancer cells.

Biologics can't access the target, and small molecules have a hard a time controlling the protein-protein interactions, said Huw Nash, vice president of corporate development at Aileron. "What got us excited about the technology was these peptides with the chemical stapling applied to them were able to be injected into mouse models and show significant reductions of cancers.

"The mechanism we were able to induce with these peptides is essentially restoring the activation function of this process," Nash told BioWorld Today. He said others are trying to control the cell-death process by blocking the protein interactions with small molecules. "The other way, unique to peptides, is that we are able to activate the process."

Nash described the peptide staple as an optimized chemical bridge that stabilizes the biologically active confirmation of peptides and protects them from degradation inside the body, as well as facilitating their entry into cells. The staple does not alter the natural specificity of the peptide, he said.

Yanchik said the apoptosis-restoring mechanism is showing good results in a range of both solid and liquid cancers.

The company is not disclosing other target areas, but said there are a number of intracellular protein-protein interaction targets that could be addressed with a similar activating function using other sequences.

Some discussion of other therapeutic areas of interest is being held until the publication of promising data, which is expected in the near term, Yanchik said.

The company plans to have established proof of concept in multiple cancer models by this summer. Yanchik said trials in humans could begin within two years. "This technology is being noticed, and we are being contacted by many of the top pharmaceutical companies," he said.

Aileron's plan is to "enter into a couple of select partnerships in the near term to help us broaden our understanding of the technology and the platform," Yanchik said, although the company is not disclosing specifics on the types of deals it is looking for. "We are actively listening to ideas," he said.

Aileron now has three full-time employees, along with about a dozen consultants working in various areas of drug development. With the new funding, it plans to convert some of those consultant roles into company positions.

The Aileron name comes from the French word for "little wing," the stabilizing flaps on airplanes. That is analogous to the stapling technology, Yanchik said, which is designed to stabilize the peptide and guide it to the target.