Alnylam’s next chapter: a conversation with Yvonne Greenstreet

New CEO looks beyond rare diseases, says culture important in navigating tough waters

With six months under her belt as CEO of Alnylam, Yvonne Greenstreet is planning to build the company’s pipeline beyond rare diseases where it marked its success so far, recognizing there are both biology and executional risks in doing so.

On The BioCentury Show, Greenstreet expanded on the priorities for Alnylam Pharmaceuticals Inc. (NASDAQ:ALNY) and how she is steering the company through its next phase, including through the difficult downmarket.

Greenstreet joined Alnylam in 2016 as chief operating officer, added the title of president in 2020, and became CEO at the start of this year on the departure of founding CEO John Maraganore.

She inherited a rich pipeline, four marketed products and a strategy dubbed P5X25, announced at the start of 2021, to become a top-five biotech by market cap in the next five years. Alnylam’s market cap sat at about $17.2 billion after Wednesday’s close.

Greenstreet told The BioCentury Show that though the siRNA platform has been largely de-risked — Alnylam’s fifth product, Amvuttra vutrisiran, was approved in June — it is still “certainly not turnkey” to  generate new therapies.

“Each program has its specific opportunities and challenges,” said Greenstreet, but the company has so far had a 65% success rate going from IND to positive Phase III. 

Whether Alnylam can retain that rate is a question, as it broadens beyond rare diseases. That’s a key part of the company’s future, with programs in prevalent diseases such as hypertension, Alzheimer’s disease, and others, but Greenstreet notes in those diseases “the genetics isn’t always as tightly linked.”

Going into targets in the CNS, muscle, heart and kidney will mean continuing to invest in the platform, for example by multiplexing siRNAs to address two or three targets with a single approach.

The ambition is to “make a difference at a population level,” said Greenstreet. “We think this is actually one of the next catalysts for the company.”

Greenstreet also said Alnylam’s 2020 deal with Blackstone Life Sciences has given it a healthy financial position to help weather the “biotech winter.” That deal involved a $1 billion royalty and commercial milestone purchase around Leqvio inclisiran, plus up to $150 million in development funding for two other cardiometabolic products, a $100 million purchase of Alnylam common stock, and a loan of up to $750 million.

She said smaller companies need to continue to find partnerships and creative financings to get them through the crunch.

But culture is also key, said Greenstreet, and CEOs need to be able to set a clear strategy, pivot when needed, and inspire. “I encourage CEOs to think about how culture can be a differentiator for them,” she said. “At the end of the day, we’re a people-based business, and I don’t think that’s going to change. My primary job in this role is enabling people who work at Alnylam to bring their best selves to work.”