Alnylam’s CEO Is Ready to Take Over From a Biotech Legend

(Bloomberg) -- Yvonne Greenstreet was sitting on a plane at Boston Logan International Airport waiting to take off in 2018 when U.S. regulators approved Alnylam Pharmaceuticals Inc.’s first drug, Onpattro. The chief operating officer grabbed her carry-on from the overhead bin, ran off the plane and bolted to the office so she could celebrate the accomplishment with her colleagues. 

Now Greenstreet will be leading many of those same colleagues as Alnylam’s new chief executive officer, and she has a tough task ahead of her. On Jan. 1 she took the reins from John Maraganore, who led Alnylam since its 2002 inception and became a legend in the biotech industry. 

Under Maraganore, Alnylam turned RNA interference -- a Nobel Prize-winning technology that silences disease-causing genes -- from an idea into four approved drugs. It will be up to Greenstreet to realize Alnylam’s grander ambitions: developing treatments for more common conditions such as hypertension and diabetes, becoming a top-five biotech and ultimately turning a profit. Wall Street, not known for its patience, will be watching.

“Nothing against Yvonne, because she has an incredible background, but John’s an incredibly tough act to follow,” said Stifel analyst Paul Matteis. 

On Sunday, Alnylam said in a statement that preliminary sales for Onpattro last year were $475 million, up 55% from $306.1 million in 2020. More than 2,050 patients are receiving the drug worldwide, the company said. Alnylam executives will discuss selected preliminary financial results at the JPMorgan Healthcare Conference on Monday. 

Taking Alnylam to the next level was exactly what Greenstreet says she was hired to do. 

“What I and all of us need to do is execute,” she said in an interview. 

Greenstreet, 59, decided she wanted to become a doctor at age 9. She grew up in Ghana and went to medical school in the U.K., where she practiced until she entered the pharmaceutical industry. The career change allowed her to combine her passion for science, medicine and business. 

After spending almost two decades at GlaxoSmithKline Plc, Greenstreet moved to Pfizer Inc. She then left Big Pharma entirely in 2013 to start her own consulting practice. But six years ago, Maraganore invited Greenstreet to dinner at Sorellina, an upscale Italian restaurant in Boston. There, he offered her the COO job. Eager to get closer to the cutting edge of innovation, she accepted.

“I felt liberated by the opportunity to really focus on what it is that’s important that we do in our industry: bringing medicines forward and figuring out the best way of doing that and having the courage to do that,” Greenstreet said. 

Big Plans

Since joining Alnylam in 2016 , Greenstreet has experienced the highs and lows of biotech. During her first week on the job, the company halted a program after data showed patients receiving its experimental drug were more likely to die than those in the placebo group in a late-stage trial. On the positive side, she has witnessed the approval of Onpattro and three other drugs -- and may celebrate another this spring.

In 2020, Maraganore promoted Greenstreet to president when longtime executive Barry Greene left the company. A year later, Maraganore and Greenstreet unveiled their plan to expand Alnylam’s reach and become one of the five largest biotech companies as measured by market capitalization. Alnylam currently ranks 10th in the XBI, the SPDR S&P Biotech exchange-traded fund of industry stocks, with a market value of about $18 billion.

Later that year, Maraganore again invited Greenstreet to Sorellina. This time, he asked if she were interested in succeeding him as CEO. She said yes.  

The new chief executive says she’s “absolutely committed” to the strategy she and her predecessor laid out last year. As co-architect of the company’s five-year plan, she said it would be “bizarre” for her to come in and do something different. 

That’s exactly what investors want to hear, said Matteis and RBC Capital Markets analyst Luca Issi. The surprising news of Maraganore’s impending departure on Oct. 28 sent Alnylam’s stock sliding 15%, but the shares recovered and ended up rising 31% in 2021.

“A lot of times CEOs are brought on to stir the pot and make changes to the strategic vision,” Issi said. “That’s not the case here. People are really looking for continuity.”

Major Test

Alnylam’s vision hinges on expanding into diseases that afflict millions of people, including Alzheimer’s disease. Its current drugs are approved for conditions such as rare liver and kidney diseases.

One major test will come this year. The company is studying Onpattro for use in ATTR amyloidosis with cardiomyopathy, a disorder where deposits of abnormal protein weaken the heart, limiting its pumping ability. Onpattro is currently approved to treat nerve damage from the disease. Adding the heart indication would increase the potential market for Onpattro by five or 10 times, Issi said. 

Investors are nervous about the trial, titled APOLLO-B, because the primary endpoint is the same six-minute walk test that hampered a study from BridgeBio Pharma Inc., a biotech developing a different approach for ATTR amyloidosis with cardiomyopathy, Issi said. BridgeBio’s late-stage trial failed because patients in the placebo group didn’t worsen as much as in previous studies. 

Alnylam is “extremely confident” in the design and execution of its study, Greenstreet said. The company has been rigorous in diagnosing patients to include them in the study. It has vigilantly trained trial sites how to conduct the test, she said. 

The company plans to launch a next-generation version of Onpattro in April pending approval from the Food and Drug Administration. By year-end, Alnylam also expects to share proof-of-concept data for its experimental treatment for Alzheimer’s disease. It also plans to reveal results from a study of zilebesiran for hypertension and topline results from a trial of ALN-HSD, under development for nonalcoholic fatty liver disease. 

Gene Editing

Beyond Alnylam, Greenstreet pays close attention to gene editing. It’s a space that threatens to disrupt her company’s technology because, if successful, it could fix the genetic errors that Alnylam’s medicines treat. 

“Watching the progress of gene-editing companies is fascinating and looks, to me, very much how Alnylam looked maybe 10 years ago where there’s a lot of hope and promise, and I think excitement,” she said. 

Alnylam still needs to prove it can still grow sales and eventually become profitable. Wall Street analysts expect Alnylam to lose $5.61 a share, adjusted, and post sales of of $815.4 million for 2021, according to Bloomberg consensus estimates. 

There’s also the possibility that a company like Novartis AG will acquire Alnylam. Greenstreet said the company is focused on its strategy while recognizing it has a fiduciary duty to its shareholders. Novartis and Alnylam on Thursday said they’ll work together on developing a treatment to regrow liver cells, which, if successful, could replace the need for liver transplants. 

And then there’s the pandemic. Greenstreet will need to steer the company while Covid-19 again thwarts in-person interactions. The longer the virus continues to disrupt business, the more she worries about maintaining the culture that she says makes Alnylam so special. 

She was scheduled to make her debut as CEO in San Francisco at the JPMorgan conference this week. She’ll now present virtually, making her case to replace the leader she recognizes as “iconic’ on the screens of investors instead of the podium.

“We’re only at the beginning of what we can do,” Greenstreet said. “We’ve just scratched the surface of this technology, and I’m so excited to see where we can take it next.”

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