In­side Ver­tex 3.0: Can Resh­ma Ke­wal­ra­mani re­peat one of biotech's biggest suc­cess sto­ries 'a­gain and again and again'?

This was not how Reshma Kewalramani imagined spending her first day as Vertex CEO. The 47-year-old nephrologist should’ve been in a spacious window office on the 14th floor of the biotech’s glassy Boston Seaport headquarters, three rooms down from where she had spent the last three years. There should have been family photos on the desk, scientists buzzing in the labs beneath, and, feet away, executives she knew and trusted, briefing her on potential cures for sickle cell disease and diabetes.

Instead, on that bone-chillingly cold day last spring, she was at a makeshift desk in the dimly lit basement of her home outside Boston, a bivouac chosen because it was closest to the Wifi router. Her closest companion was Ferris Bueller’s smug face on the wall and she spent the day jumping from Zoom call to Zoom call, worried less about making new drugs than making sure her employees were safe and that the global supply chain didn’t leave a cystic fibrosis patient without access to the Vertex pills that had changed their life. It was April 1, 2020.

“These are not what I thought would be the two of the highest priorities,” she tells me. “The safety of our people? You take it for granted.”

The pandemic hit Vertex at the worst possible time. Over the last decade, CEO Jeffrey Leiden, a jovial but shrewd and commanding figure, had pushed the development of those CF drugs, turning the most common fatal genetic disease in US and Europe into, for 90% of patients, a treatable condition. In the process, they had gone from a $6 billion to a $60 billion company and won the rare collective awe of the business, medical and patient communities. “I scream it from the rooftops,” says Bob Coughlin, former CEO of industry group MassBio, whose 19-year-old son has CF. “He’s a whole new person, I’m filled with more gratitude than I’ve ever had in my whole damn life.”

Now, just as Leiden passed the torch, the entire world was collapsing. It was a trial by wildfire for Kewalramani, who had already been an unlikely choice as CEO. The heads of large biotechs are almost exclusively businesspeople, executives whose chief job is to sell the drugs the company has already developed and find other companies to acquire. If they have MDs, they also have an MBA or 20 years of experience in sales. All, historically, have been men.

Kewalramani was a clear-eyed, affable physician who had trained at Boston’s most prestigious hospitals and spent 12 years running trials at Amgen, but she had little experience on the business side of biotech. For the prior three years, leading Vertex’s medical team, she stood opposite the executive committee at key moments, explaining results from trials she designed and ran in sickle cell and cystic fibrosis.

She came from the medical side, which was unique,” says Terry McGuire, founder and general partner of the Boston-based biotech VC Polaris Partners. “It speaks to their desire to really focus on what’s going on in the clinic and for patients.” Indeed, Vertex had only considered physician-scientists for the role. They had big plans for the role — for what they called Vertex 3.0. Although they had become known as the CF company, for years, Leiden told anyone who would listen that he didn’t just want to transform one disease: He planned to use the lavish proceeds from those pills to cure CF completely and either cure or defang an Infernal Council of famous ailments: Sickle cell disease, diabetes, muscular dystrophy and pain, among others.

It was as ambitious a plan as a biotech had ever put forward, spanning medical disciplines from hematology to nephrology and technologies from old-fashioned pills to new forms of CRISPR gene editing, and they needed someone with unimpeachable scientific chops to carry it out. If Kewalramani and her team can, they will change the face of medicine: Not just for one rare disease but several, and a few not so rare ones as well. They could also set off the same string of rancorous global debates that have followed Vertex’s CF drugs, as the company charged more than what many countries said they could pay. Kewalramani, while striking a less abrasive tone than her predecessor, has pledged to keep the same pricing strategy moving forward.

“We’re going to do what we did in CF,” Kewalramani tells me, echoing a promise she makes repeatedly. “Again and again and again.” But first they would have to deal with Covid-19.

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In­side Track: Be­hind the Scenes of a Ma­jor Biotech SPAC

Dr. David Hung and Michelle Doig are no strangers to the SPAC phenomenon. As Founder and CEO of Nuvation Bio, a biotech company tackling some of the greatest unmet needs in oncology, Dr. Hung recently took the company public in one of this year’s biggest SPAC related deals. And as Partner at Omega Funds, Doig not only led and syndicated Nuvation Bio’s Series A, but is now also President of the newly formed, Omega-sponsored, Omega Alpha SPAC (Nasdaq: OMEG; oversubscribed $138m IPO priced January 6, 2021).

Janet Woodcock, acting FDA commissioner (Al Drago/Bloomberg via Getty Images)

New Alzheimer's drug ap­proval fall­out: Pub­lic Cit­i­zen seeks re­moval of FDA's Wood­cock, Cavaz­zoni and Dunn

As Capitol Hill begins to wake up to the financial and scientific mess behind the FDA’s approval of Biogen’s new controversial Alzheimer’s drug Aduhelm, nonprofit watchdog Public Citizen is now calling for the top three FDA officials who are responsible to be removed from their positions.

In a letter to HHS Secretary Xavier Becerra on Wednesday, the group highlighted the “litany of flaws” in the FDA’s approval of the new drug, including the “unprecedented, inappropriately close” collaboration between the FDA and Biogen in the analysis of key trial data, basing approval on an unvalidated surrogate endpoint, not following the advice of its expert advisory committee (3 members of which have since resigned), and the wide label that the agency granted.

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In a first, Re­gen­eron's an­ti­body cock­tail re­duces deaths for a sub­group of hos­pi­tal­ized Covid-19 pa­tients

Scientists have come up with the first evidence that Regeneron’s antibody cocktail, which has so far only been authorized for the outpatient setting, may reduce deaths of hospitalized Covid-19 patients — albeit only a subset.

The combination of casirivimab and imdevimab is the subject of the latest data cut from RECOVERY, the large-scale UK-based trial testing a variety of potential treatments. In total, 9,785 patients hospitalized with Covid-19 were enrolled in this arm of the study and were randomly assigned to receive either usual care plus the intravenous combo or usual care alone.

Barry Greene, Sage CEO

UP­DAT­ED: Sage's sec­ond chance at de­pres­sion hits the PhI­II pri­ma­ry, but ques­tions re­main over dura­bil­i­ty, side ef­fects

Looking to make a comeback after a big Phase III flop, Sage Therapeutics revealed data they believe could change the entire depression treatment landscape, given the vast array of failures in the field. But some results are spooking investors, sending Sage $SAGE shares down early Tuesday.

First, the primary: Sage and Biogen reported Phase III data for once-daily zuranolone Tuesday morning, saying the experimental drug hit its primary endpoint by spurring a statistically significant change from baseline in the 17-item Hamilton Rating Scale for Depression total score. After 15 days, patients in the drug arm saw an average change of -14.1 points, compared to -12.3 on placebo.

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Bio­gen sig­nals a big PhI­II fail­ure as the lead gene ther­a­py in their $800M Night­star buy­out goes down in flames

That $800 million buyout of Nightstar has turned into a bust for Biogen as the lead therapy in the deal failed a pivotal study, signaling a severe setback for the biotech’s ambitions in gene therapies.

The big biotech put out the word after the market closed on Monday that the gene therapy they picked up in the deal for a degenerative blindness called choroideremia failed the Phase III study, just a month after their #2 drug in the deal also flopped in a mid-stage study.

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As Covid-19 shifts the world's at­ten­tion to biotech, Noubar Afeyan's Flag­ship builds $3.4B fund to fu­el new in­ven­tions. Here's the plan

A little more than a year ago, Flagship Pioneering rolled out a monster fund with $1.1 billion in it to bankroll the platform companies they were creating inside their own labs. But it turns out, that was just the prelude to a much, much larger raise, as both current investors — who’ve been reaping the rewards of some booming biotech stocks — join in with new investors betting on more in the years to come.

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CEO Harith Rajagopalan (Fractyl)

Af­ter a decade in the type 2 di­a­betes game, Fractyl Lab­o­ra­to­ries recharges with a fresh $100M and a new name

Harith Rajagopalan compared the way type 2 diabetes is managed to sticking your fingers in a dam that’s leaking from a number of places.

You can take drugs to lower your blood sugar, cholesterol, or blood pressure, but you’re not addressing what he says is the core issue — the metabolic abnormality that causes the disease.

“We’re so busy plugging the holes in the dam, we don’t have time to see that the whole infrastructure is at risk,” he said. “That infrastructure is a full-body systemic metabolic abnormality called metabolic syndrome, that we’re ignoring while we’re so busy trying to treat all of the individual symptoms of the condition.”

Michel Sade­lain puts his name and new cell en­gi­neer­ing tech be­hind 'ag­nos­tic' CAR-T start­up chas­ing epi­ge­net­ic anti­gens

It felt natural for Alain Maiore and Sebastian Amigorena to bring in Michel Sadelain as a co-founder of Mnemo Therapeutics. A CAR-T pioneer, Sadelain had been involved as an advisor since the early days — enthusiastic about Amigorena’s work in a genetic knockout that could enhance T cell memory and a new class of potential targets he’s discovered — and could introduce some well-known technologies to the toolbox. So they got the initial cash from Sofinnova Partners to plant roots in Paris and New York in early 2019; within a few months, they began to see more clearly just what the antigen discovery platform might unlock.

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Stephen Hahn (AP Images)

UP­DAT­ED: Ex-FDA com­mish Stephen Hahn joins Flag­ship, a ven­ture group that spawned Covid-19 vac­cine mak­er Mod­er­na

That revolving door between the FDA and industry is spinning even faster than usual.

Former FDA commissioner Stephen Hahn is joining Flagship Pioneering, the venture outfit that founded Moderna — which raced its way to an FDA EUA for a Covid-19 vaccine that is making billions of dollars– as the new CMO of its Preemptive Medicine and Health Security initiative.

Flagship confirmed the hire — first reported in The Washington Post — in a statement out late Monday.

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