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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Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

Jacob Van Naarden (Eli Lilly)

Ex­clu­sives: Eli Lil­ly out to crash the megablock­buster PD-(L)1 par­ty with 'dis­rup­tive' pric­ing; re­veals can­cer biotech buy­out

It’s taken 7 years, but Eli Lilly is promising to finally start hammering the small and affluent PD-(L)1 club with a “disruptive” pricing strategy for their checkpoint therapy allied with China’s Innovent.

Lilly in-licensed global rights to sintilimab a year ago, building on the China alliance they have with Innovent. That cost the pharma giant $200 million in cash upfront, which they plan to capitalize on now with a long-awaited plan to bust up the high-price market in lung cancer and other cancers that have created a market worth tens of billions of dollars.

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David Meek, new Mirati CEO (Marlene Awaad/Bloomberg via Getty Images)

Fresh off Fer­Gene's melt­down, David Meek takes over at Mi­rati with lead KRAS drug rac­ing to an ap­proval

In the insular world of biotech, a spectacular failure can sometimes stay on any executive’s record for a long time. But for David Meek, the man at the helm of FerGene’s recent implosion, two questionable exits made way for what could be an excellent rebound.

Meek, most recently FerGene’s CEO and a past head at Ipsen, has become CEO at Mirati Therapeutics, taking the reins from founding CEO Charles Baum, who will step over into the role of president and head of R&D, according to a release.

FDA hands ac­cel­er­at­ed nod to Seagen, Gen­mab's so­lo ADC in cer­vi­cal can­cer, but com­bo stud­ies look even more promis­ing

Biopharma’s resident antibody-drug conjugate expert Seagen has scored a clutch of oncology approvals in recent years, finding gold in what are known as “third-gen” ADCs. Now, another of their partnered conjugates is ready for prime time.

The FDA on Monday handed an accelerated approval to Seagen and Genmab’s Tivdak (tisotumab vedotin-tftv, or “TV”) in second-line patients with recurrent or metastatic cervical cancer who previously progressed after chemotherapy rather than PD-(L)1 systemic therapy, the companies said in a release.

Volker Wagner (L) and Jeff Legos

As Bay­er, No­var­tis stack up their ra­dio­phar­ma­ceu­ti­cal da­ta at #ES­MO21, a key de­bate takes shape

Ten years ago, a small Norwegian biotech by the name of Algeta showed up at ESMO — then the European Multidisciplinary Cancer Conference 2011 — and declared that its Bayer-partnered targeted radionuclide therapy, radium-223 chloride, boosted the overall survival of castration-resistant prostate cancer patients with symptomatic bone metastases.

In a Phase III study dubbed ALSYMPCA, patients who were treated with radium-223 chloride lived a median of 14 months compared to 11.2 months. The FDA would stamp an approval on it based on those data two years later, after Bayer snapped up Algeta and christened the drug Xofigo.

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The biggest ques­tions fac­ing gene ther­a­py, the XLMTM com­mu­ni­ty, and Astel­las af­ter fourth pa­tient death

After three patients died last year in an Astellas gene therapy trial, the company halted the study and began figuring out how to safely get the program back on track. They would, executives eventually explained, cut the dose by more than half and institute a battery of other measures to try to prevent the same thing from happening again.

Then tragically, Astellas announced this week that the first patient to receive the new regimen had died, just weeks after administration.

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Dave Lennon, former president of Novartis Gene Therapies

Zol­gens­ma patent spat brews be­tween No­var­tis and Re­genxbio as top No­var­tis gene ther­a­py ex­ec de­parts

Regenxbio, a small licensor of gene therapy viral vectors spun out from the University of Pennsylvania, is now finding itself in the middle of some major league patent fights.

In addition to a patent suit with Sarepta Therapeutics from last September, Novartis, is now trying to push its smaller partner out of the way. The Swiss biopharma licensed Regenxbio’s AAV9 vector for its $2.1 million spinal muscular atrophy therapy Zolgensma.

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Rafaèle Tordjman (Jeito Capital)

Con­ti­nu­ity and di­ver­si­ty: Rafaèle Tord­j­man's women-led VC firm tops out first fund at $630M

For a first-time fund, Jeito Capital talks a lot about continuity.

Rafaèle Tordjman had spotlighted that concept ever since she started building the firm in 2018, promising to go the extra mile(s) with biotech entrepreneurs while pushing them to reach patients faster.

Coincidentally, the lack of continuity was one of the sore spots listed in a report about the European healthcare sector published that same year by the European Investment Bank — whose fund is one of the LPs, alongside the American pension fund Teacher Retirement System of Texas and Singapore’s Temasek, to help Jeito close its first fund at $630 million (€534 million). As previously reported, Sanofi had chimed in €50 million, marking its first investment in a French life sciences fund.

Mi­rati tri­umphs again in KRAS-mu­tat­ed lung can­cer with a close­ly watched FDA fil­ing now in the cards

After a busy weekend at #ESMO21, which included a big readout for its KRAS drug adagrasib in colon cancer, Mirati Therapeutics is ready to keep the pressure on competitor Amgen with lung cancer data that will undergird an upcoming filing.

In topline results from a Phase II cohort of its KRYSTAL-1 study, adagrasib posted a response rate of 43% in second-line-or-later patients with metastatic non-small cell lung cancer containing a KRAS-G12C mutation, Mirati said Monday.