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.”

At the In­flec­tion Point for the Next Gen­er­a­tion of Can­cer Im­munother­a­py

While oncology researchers have long pursued the potential of cellular immunotherapies for the treatment of cancer, it was unclear whether these therapies would ever reach patients due to the complexity of manufacturing and costs of development. Fortunately, the recent successful development and regulatory approval of chimeric antigen receptor-engineered T (CAR-T) cells have demonstrated the significant benefit of these therapies to patients.

Stéphane Bancel, Moderna CEO

'This is not go­ing to be good': Mod­er­na CEO Ban­cel warns of a 'ma­te­r­i­al drop' in vac­cine ef­fi­ca­cy as Omi­cron spreads

Even as public health officials remain guarded about their comments on the likelihood Omicron will escape the reach of the currently approved Covid-19 vaccines, there’s growing scientific consensus that we’re facing a variant that threatens to overwhelm the vaccine barricades that have been erected.

Stéphane Bancel, the CEO of Moderna, one of the leading mRNA players whose quick vault into the markets with a highly effective vaccine created an instant multibillion-dollar market, added his voice to the rising chorus early Tuesday. According to Bancel, there will be a significant drop in efficacy when the average immune system is confronted by Omicron. The only question now is: How much?

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Philip Dormitzer, new GSK global head of vaccines R&D

Glax­o­SmithK­line poach­es Pfiz­er's vi­ral vac­cines lead in rush to cap­i­tal­ize on fu­ture of mR­NA

GlaxoSmithKline has appointed Philip Dormitzer, formerly chief scientific officer of Pfizer’s viral vaccines unit, as its newest global head of vaccines R&D, looking to leverage one of the leading minds behind Pfizer and BioNTech’s RNA collaboration that led to Covid-19 jab Comirnaty, the British drug giant said Tuesday.

Dormitzer had been with Pfizer for a little more than six years, joining up after a seven-year stint with Novartis, where he reached the role of US head of research and head of global virology for the company’s vaccines and diagnostics unit.

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In­tro­duc­ing End­points Stu­dio, a new way to ad­ver­tise with End­points-craft­ed brand­ing cam­paigns

Since our start in 2016, Endpoints has grown fast while executing our mission to cover biopharma’s most critical developments for industry pros worldwide. As readership has grown, our advertising business has too. Endpoints advertising partners support the mission and engage their desired audiences through announcements on our email and web platforms, brand recognition in our event coverage and sponsorships of Endpoints daily and weekly reports.

With on­ly burns to show in gene ther­a­py, Astel­las inks deal with AAV spe­cial­ist Dyno in push for a bet­ter cap­sid

On the hunt for a better AAV capsid for gene therapy, Eric Kelsic’s Dyno Therapeutics has set itself apart with its focus on machine learning to help speed discovery. Now, Japanese drugmaker Astellas — fresh off a slate of gene therapy burns — is taking a bet on Dyno as it looks to the future.

Astellas and Dyno will work together as part of an R&D pact to develop next-gen AAV vectors for gene therapy using Dyno’s CapsidMap platform directed at skeletal and cardiac muscle, the companies said Wednesday. Under the terms of the deal, Dyno will design AAV capsids for gene therapy, while Astellas will be responsible for conducting preclinical, clinical and commercialization activities for gene therapy product candidates using the capsids.

As first Omi­cron case in US crops up, re­searchers won­der: which an­ti­bod­ies, vac­cines will hold up?

As Covid-19 drug and vaccine developers race to figure out which of their products might be hampered by the new variant, the CDC on Wednesday afternoon announced the first confirmed case of the Omicron variant (B.1.1.529) in the US, found in San Francisco.

The unidentified individual was a traveler who returned from South Africa on Nov. 22, 2021, was fully vaccinated, and had mild symptoms that the CDC described as improving. All close contacts have been contacted and have tested negative, the centers said.

As lead drug runs in­to a wall, De­ci­phera slims down its pipeline, puts 140 jobs on the chop­ping block

Barely a month after disappointing data shattered hopes for a major label expansion for the GI tumor drug Qinlock, Deciphera is making a major pivot — scrapping development plans for that drug and discarding another while it hunkers down and focuses on two remaining drugs in the pipeline.

As a result, 140 of its staffers will be laid off.

The restructuring, which claims the equivalent of 35% of its total workforce, will take place across all departments including commercial, R&D as well as general and administrative support functions, Deciphera said, as it looks to streamline Qinlock-related commercial operations in the US while concentrating only on a “select number of key European markets.”

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Mod­er­na los­es lat­est bat­tle in key vac­cine de­liv­ery patent fight as fed­er­al ap­peal falls flat

The US Court of Appeals for the Federal Circuit on Wednesday rejected Moderna’s attempt to overturn key patents related to the delivery vehicle for its Covid-19 vaccine after the biotech sought to preempt a potentially risky infringement lawsuit.

For years, Moderna has been battling a tiny Pennsylvania biotech known as Arbutus over patents for a technology required to deliver its mRNA drugs and vaccines, known as lipid nanoparticles or LNP. Moderna is concerned there’s a substantial risk that Arbutus will assert the ’069 patent in an infringement suit targeting Moderna’s Covid-19 vaccine, particularly as Arbutus has boasted of its patent protection and refused to grant a covenant not to sue Moderna.

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Lan Huang, BeyondSpring CEO

Months af­ter shock­ing in­vestors with lung can­cer win, Be­yond­Spring's lead drug hits road­block at the FDA

BeyondSpring shocked investors in early August after its once-marginal lead drug suddenly showed a lot of promise in a common form of lung cancer. With hopes high, the FDA has now slammed the door on that drug in another indication — does that spell bad news for BeyondSpring’s Cinderella story?

The FDA issued BeyondSpring a complete response letter for its plinabulin in combination with granulocyte colony-stimulating factor (G-CSF) for the prevention of chemotherapy-induced neutropenia, effectively shutting down the drug’s immediate chances at a marketing approval, the biotech said Wednesday.

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