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.

Endpoints News

Sign up to read this article for free.

Get free access to a limited number of articles, plus choose newsletters to get straight to your inbox.