John Maraganore, Alnylam CEO (Scott Eisen/Bloomberg via Getty Images)

'I want to be a grand­dad': Why John Maraganore left and where he (and Al­ny­lam) are go­ing

John Maraganore knew that peo­ple would be sur­prised when Al­ny­lam an­nounced his de­par­ture this morn­ing af­ter 19 years as CEO of the com­pa­ny. But he said it shouldn’t come as too much of a shock.

“Nine­teen years as a CEO lead­ing Al­ny­lam has been the great­est joy of my life, but 19 years has been a long time,” he said in an in­ter­view Thurs­day morn­ing. That’s “be­ing in the 24/7 op­er­a­tional mode of run­ning a com­pa­ny for 19 years.”

Maraganore, 59, start­ed as CEO when Phillip Sharp and a hand­ful of sci­en­tists and in­vestors de­cid­ed to launch a new com­pa­ny around RNAi, a new tech­nol­o­gy for si­lenc­ing genes that would go on to win the No­bel Prize. He re­mained CEO as the com­pa­ny faced tech­no­log­i­cal hur­dles, laid off em­ploy­ees, and lost the in­ter­est of in­vestors and large phar­mas.

But be­gin­ning about a decade ago, Maraganore out­lined a se­ries of five-year plans that, by 2018, re­sult­ed in the first ap­proved RNAi drug. An­oth­er ap­proval fol­lowed each suc­ces­sive year, and a fourth is like­ly to come in 2022.

In the process, he won a rare de­gree of trust from the once skep­ti­cal in­vestors, which ex­plains why the stock $AL­NY dropped 12.5% on news of Maraganore’s de­pa­ture, a $3 bil­lion swing for the big biotech.

So Maraganore will like­ly have his share of of­fers, though he’ll prob­a­bly turn many down. His CEO days are done, he said: Too much time, too much en­er­gy, too much com­mit­ment.

“My wife would punch me in the gut,” he said.

In­stead, he’ll drift for the ven­ture world, he said, even if he nev­er ful­ly joins any one firm. He be­lieves the hey­day of bio­med­ical in­no­va­tion is just be­gin­ning and he wants to ad­vise new com­pa­nies at the fore­front.

“It’s like a grand­fa­ther, right?  You get the ben­e­fit of lov­ing your grand­chil­dren, but not hav­ing to take care of them all the time,” Maraganore said. “I want to be a grand­dad.”

Yvonne Green­street

He leaves the keys to Al­ny­lam with Yvonne Green­street, who joined the biotech in 2016 af­ter stints at Pfiz­er and GSK and who was pro­mot­ed last year to pres­i­dent and COO.

Green­street, al­so 59, will be re­spon­si­ble for ex­e­cut­ing Al­ny­lam’s lat­est five-year plan. Un­veiled be­fore last year’s JPM, it promised to leave as a top five biotech by mar­ket cap by 2025, with six drugs on the mar­ket, 20 mol­e­cules in the clin­ic, and 500,000 pa­tients tak­ing RNAi ther­a­peu­tics glob­al­ly.

The new move won’t change that plan, Green­street said. Al­ny­lam had been ear­mark­ing her as a suc­ces­sor for “a bit of time,” Maraganore said, and she helped craft the lat­est plan.

Ex­e­cut­ing will re­quire com­pet­ing with oth­er new modal­i­ties. RNAi was one of the on­ly ge­net­ic tech­nolo­gies avail­able when Al­ny­lam was found­ed, along­side an­ti­sense. Now, thanks in part to some of the in­no­va­tions the com­pa­ny helped pi­o­neer, there are more than a half dozen, in­clud­ing mR­NA, gene ther­a­py, gene edit­ing.

This year, In­tel­lia, one of the first CRISPR com­pa­nies, showed proof-of-con­cept for a one-time treat­ment for amy­loi­do­sis, threat­en­ing Al­ny­lam’s biggest rev­enue gen­er­a­tor: On­pat­tro, an amy­loi­do­sis treat­ment that has to be giv­en every three weeks. The com­pa­ny’s next big drug is a new amy­loi­do­sis treat­ment that has to be giv­en quar­ter­ly.

Green­street and Maraganore are con­fi­dent, though, that Al­ny­lam will re­main com­pet­i­tive in any dis­ease that in­volves knock­ing down a gene. They’re work­ing on med­i­cines with even longer du­ra­tions, re­search­ing ways to de­liv­er in­to the ner­vous sys­tem with Re­gen­eron, and be­gin­ning to push their own drugs in more com­mon dis­or­ders.

“I’m go­ing to con­tin­ue ex­e­cut­ing with­out los­ing any mo­men­tum,” Green­street said in an in­ter­view. “We’ve on­ly just re­al­ly start­ed see­ing the pos­si­ble is well be able to de­liv­er to pa­tients with RNAi.”

Has the mo­ment fi­nal­ly ar­rived for val­ue-based health­care?

RBC Capital Markets’ Healthcare Technology Analyst, Sean Dodge, spotlights a new breed of tech-enabled providers who are rapidly transforming the way clinicians deliver healthcare, and explores the key question: can this accelerating revolution overturn the US healthcare system?

Key points

Tech-enabled healthcare providers are poised to help the US transition to value, not volume, as the basis for reward.
The move to value-based care has policy momentum, but is risky and complex for clinicians.
Outsourced tech specialists are emerging to provide the required expertise, while healthcare and tech are also converging through M&A.
Value-based care remains in its early stages, but the transition is accelerating and represents a huge addressable market.

FDA ad­vi­sors unan­i­mous­ly rec­om­mend ac­cel­er­at­ed ap­proval for Bio­gen's ALS drug

A panel of outside advisors to the FDA unanimously recommended that the agency grant accelerated approval to Biogen’s ALS drug tofersen despite the drug failing the primary goal of its Phase III study, an endorsement that could pave a path forward for the treatment.

By a 9-0 vote, members of the Peripheral and Central Nervous System Drugs Advisory Committee said there was sufficient evidence that tofersen’s effect on a certain protein associated with ALS is reasonably likely to predict a benefit for patients. But panelists stopped short of advocating for a full approval, voting 3-5 against (with one abstention) and largely citing the failed pivotal study.

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Alaa Halawa, executive director at Mubadala’s US venture group

The ven­ture crew at Mubadala are up­ping their biotech cre­ation game, tak­ing care­ful aim at a new fron­tier in drug de­vel­op­ment

It started with a cup of coffee and a slow burning desire to go early and long in the biotech creation business.

Wrapping up a 15-year discovery stint at Genentech back in the summer of 2021, Rami Hannoush was treated to a caffeine-fueled review of the latest work UCSF’s Jim Wells had been doing on protein degradation — one of the hottest fields in drug development.

“Jim and I have known each other for the past 15 years through Genentech collaborations. We met over coffee, and he was telling me about this concept of the company that he was thinking of,” says Hannoush. “And I got immediately intrigued by it because I knew that this could open up a big space in terms of adding a new modality in drug discovery that is desperately needed in pharma.”

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Genen­tech to stop com­mer­cial man­u­fac­tur­ing at Cal­i­for­nia head­quar­ters

Genentech is halting commercial manufacturing at its California headquarters — and laying off several hundred employees.

The move is the result of a decision Genentech made in 2007 to relocate manufacturing operations from its South San Francisco headquarters location to other facilities or move the work to CDMOs, said Andi Goddard, Genentech’s SVP of quality and compliance for pharmaceutical technical operations, in an interview with Endpoints News. Genentech has made changes in capabilities and invested more in technology, so it doesn’t need as many large-scale manufacturing facilities as it did in the past, she said.

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Sanofi, Re­gen­eron boast PhI­II win with Dupix­ent in COPD, clear­ing first bar for ex­pan­sion

Dupixent, the blockbuster anti-inflammatory drug from Sanofi and Regeneron, has cleared a high-stakes Phase III study in chronic obstructive pulmonary disease, the companies announced Thursday morning.

If they hold up in a second, identical trial, the data pave the way for Dupixent to become the first biologic to treat patients whose COPD remains uncontrolled despite being on maximal standard-of-care inhaled therapy — the patient population studied in the pivotal program. The companies had spotlighted this as a key readout as they look to expand the Dupixent franchise and explore its full potential.

Chat­G­PT with phar­ma da­ta de­buts for med­ical meet­ings, be­gin­ning with AACR

What do you get when you combine ChatGPT generative AI technology with specific pharma and clinical datasets? A time-saving tool that can answer questions about medical conference abstracts and clinical findings in seconds in one new application from ZoomRx called FermaGPT.

ZoomRx is debuting a public version of its generative AI product specifically for medical conferences beginning this week for the upcoming American Association for Cancer Research (AACR) annual meeting that runs April 14-19.

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'Band­ing to­geth­er': 50 fe­male biotech ex­ec­u­tives lay out plans for board di­ver­si­ty, new com­pa­nies and men­tor­ing founders

Earlier this month, during the Silicon Valley Bank meltdown, Angie You recalled the speed with which female biotech CEOs were helping each other connect with bankers, get their wires through and assuage concerns during a financial implosion.

This past weekend, 50 of about 125 women who are part of that Slack group and a broader coalition self-dubbed the Biotech Sisterhood met in person in Cancun for the second rendition of an annual summit connecting female biotech CEOs. The attendance list doubled that of the inaugural gathering in Arizona 12 months ago.

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Who are the women break­ing bar­ri­ers in drug de­vel­op­ment? Nom­i­nate them for End­points' an­nu­al re­port

Today, we’re opening nominations for our fifth annual Women in Biopharma R&D special report.

Over the last four years, we’ve honored 80 women whose extraordinary accomplishments have changed the game in biopharma R&D. We’re looking for big thinkers, scientists, executives and other enterprising women who are breaking barriers in drug development and inspiring the next generation of leaders.

Francesco Marincola, newly-appointed Sonata Therapeutics CSO

Kite's head of re­search leaves for Flag­ship start­up Sonata

Another leader is departing Kite Pharma, and will to spend the “last part” of his career exploring how cancer evades the immune system.

Kite’s senior VP and global head of cell therapy research Francesco Marincola left the Gilead CAR-T unit last week for Sonata Therapeutics. Flagship last May unveiled the startup, which was pieced together from two fledgling biotechs Inzen and Cygnal Therapeutics. As CSO, Marincola will lead Sonata’s push to reprogram cancer cells to make them more immunogenic.

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