Special report 2024: Meet 20 women breaking new ground in biopharma R&D

Ded­i­cat­ed to the mem­o­ry of Na­tal­ie Grover, who co-cre­at­ed the Women in Bio­phar­ma R&D spe­cial re­port while she was a re­porter at End­points from 2018-2020. Na­tal­ie passed away ear­li­er this year, but part of her lega­cy lives on through this project.

When Na­tal­ie Grover and Am­ber Tong launched End­points News’ Women in Bio­phar­ma R&D re­port in 2019, they set a few key ground rules.

They de­cid­ed to give equal air­time to hon­orees’ R&D ac­com­plish­ments and their ex­pe­ri­ence as women lead­ers; to not shy away from hard ques­tions; and to try their best to bring these women the recog­ni­tion they de­serve. Na­tal­ie’s in­dig­na­tion at gen­der in­equal­i­ty, her pas­sion­ate be­lief in change, and her love of a good sto­ry set the tone for what has be­come a beloved an­nu­al tra­di­tion.

We have now cel­e­brat­ed more than 120 women break­ing bound­aries in bio­phar­ma R&D. Na­tal­ie and Am­ber’s vi­sion has trans­formed in­to a news­room-wide ef­fort in­volv­ing more than 17 re­porters and ed­i­tors. We’re pleased to in­tro­duce you to 20 women dri­ving change in 2024. Thank you for con­tin­u­ing the tra­di­tion with us. — Am­ber Tong and Nicole De­Feud­is

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An­naliesa An­der­son: Go­ing from bac­te­ria to vac­cines, An­naliesa An­der­son shep­herds Pfiz­er in­to RSV com­pe­ti­tion

An­naliesa An­der­son helped steer Pfiz­er’s RSV vac­cine ef­forts, set­ting the com­pa­ny up for suc­cess in a bur­geon­ing mar­ket that’s caught a lot of at­ten­tion. But she ac­tu­al­ly got her start in bac­te­ria, not virus­es.

Grow­ing up in Eng­land, An­der­son said there wasn’t much to do dur­ing sum­mers off from school. But as a 12-year-old at her cousin’s house, she watched a TV show de­scrib­ing how peo­ple could use yeast to make hu­man growth hor­mone and it just hooked her.

“I just thought that was the coolest thing,” An­der­son said. “The fact that peo­ple think about bugs and or­gan­isms as things that are bad, but you could ac­tu­al­ly make them do things that were good. That was my first kind of, ‘Oh, this looks like some­thing I’m in­ter­est­ed in.’”

While yeast is tech­ni­cal­ly a fun­gus, the TV pro­gram start­ed An­der­son on a path down learn­ing about the ins and outs of mi­cro­bi­ol­o­gy. Her sense of di­rec­tion led to, even­tu­al­ly, be­com­ing the head of vac­cine R&D at Pfiz­er, whose RSV shot Abrys­vo ex­ceed­ed sales ex­pec­ta­tions in 2023 with $890 mil­lion in its first sea­son.

Orig­i­nal­ly in­ter­est­ed in how bac­te­ria and oth­er mi­croor­gan­isms could help pre­vent pol­lu­tion, An­der­son shift­ed to bio­med­ical re­search while do­ing her PhD, look­ing in­to how bac­te­ria can make mol­e­cules that in­ter­act with oth­er bac­te­ria. The re­search helped lead to her first job at Mer­ck, where she ran a lab tasked with find­ing new ways of mak­ing drugs from bac­te­ria.

As she con­tin­ued work­ing with bac­te­ria, how­ev­er, she be­gan de­vel­op­ing more in­ter­est in the bi­ol­o­gy of drug dis­cov­ery.

“What I no­ticed was, you’re there in your lab, mak­ing all these new mol­e­cules. But your mol­e­cule’s on­ly in­ter­est­ing if it fits with a bi­o­log­i­cal pur­pose,” An­der­son said.

Soon, An­der­son was asked to join Mer­ck’s vac­cines or­ga­ni­za­tion and found it a nat­ur­al pair­ing. Even though she didn’t know much about vac­cines at the time, her col­leagues need­ed her ex­per­tise to un­der­stand how bac­te­ria were caus­ing cer­tain in­fec­tions. She said the ex­pe­ri­ence of point­ing the team to the right tar­get anti­gen helped her re­al­ize she en­joyed be­ing able to ap­ply her knowl­edge to a more hands-on en­vi­ron­ment.

“It fit more with my sense of cu­rios­i­ty and prob­lem solv­ing, be­cause ul­ti­mate­ly, what is sci­ence?” An­der­son said. “It’s solv­ing prob­lems, and that’s what I like to do.”

An­der­son stayed at Mer­ck for near­ly 10 years, main­ly in the ear­ly-phase space, be­fore mov­ing to Pfiz­er, where she worked on the Pre­vnar pneu­mo­coc­cal, menin­gi­tis B and C. dif­fi­cile vac­cines. She didn’t move to virus­es un­til the Covid-19 pan­dem­ic.

When her boss who had re­cruit­ed her to Pfiz­er, Kathrin Jansen, an­nounced her re­tire­ment, An­der­son in­her­it­ed the vac­cines lead­er­ship po­si­tion and be­gan over­see­ing RSV work. Fol­low­ing its strong first sea­son, Abrys­vo is ex­pect­ed to con­tin­ue to com­pete with GSK’s Arexvy and Mod­er­na’s mResvia as the com­pa­nies look to ex­pand their la­bels in­to younger pop­u­la­tions and for use dur­ing preg­nan­cy.

When it comes to im­prov­ing gen­der bal­ance in the work­place, An­der­son said the strug­gles bio­phar­ma faces are sim­i­lar to most oth­er in­dus­tries. She be­gan to no­tice it more, es­pe­cial­ly as she con­tin­ued as­cend­ing through the ranks, not­ing that at uni­ver­si­ties, the gen­der split in bi­o­log­i­cal sci­ence de­grees is rough­ly 50-50. The same is true for many en­try-lev­el jobs at Pfiz­er, she said.

But her biggest piece of ad­vice for women who want to pur­sue ca­reers in bio­phar­ma is to not let oth­er peo­ple de­fine who you are.

“Most peo­ple, es­pe­cial­ly women, of­ten bring more to the ta­ble than they re­al­ize. And so I think that that’s an im­por­tant les­son,” An­der­son said. — Max Gel­man

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Al­li­son Au­gust: Co­manche Bio CMO eyes long-await­ed treat­ment for preg­nan­cy con­di­tion

Al­li­son Au­gust knew she want­ed to make a dif­fer­ence.

“I grew up in a house­hold where the ethos was you had a re­spon­si­bil­i­ty in re­pair­ing the world a lit­tle,” she said.

Au­gust car­ried that mot­to with her, from 20 years in gy­ne­col­o­gy and ob­stet­rics to her work on Mod­er­na’s Phase 3 tri­als for a Covid-19 vac­cine dur­ing the glob­al pan­dem­ic. Yet through­out her vast and var­ied ca­reer, one con­di­tion kept crop­ping up: preeclamp­sia, a form of high blood pres­sure in preg­nant women that can lead to pre­ma­ture birth.

Her in­ter­est was sparked dur­ing her med­ical stud­ies at the Uni­ver­si­ty of Chica­go. The school build­ing has five plaques for physi­cians in women’s health. Four are filled, but the fifth is left blank and is ded­i­cat­ed to a fu­ture sci­en­tist who de­vel­ops a cure for preeclamp­sia.

Dur­ing her work as a gy­ne­col­o­gist, Au­gust rou­tine­ly di­ag­nosed women, in some cas­es who were 30 weeks preg­nant or ear­li­er.

“Ob­stet­rics and gy­ne­col­o­gy has been a field where there has been po­ten­tial­ly less true in­no­va­tion,” Au­gust said. “If you look at the way that preeclamp­tic pa­tients are man­aged to­day, as com­pared with 100 years ago, it re­al­ly hasn’t changed.”

Fast for­ward two decades, and she is now ful­ly fo­cused on de­vel­op­ing a treat­ment for preterm preeclamp­sia in her role at Co­manche Bio­phar­ma.

The com­pa­ny won the FDA’s fast track des­ig­na­tion last Au­gust for its Phase 1 lead can­di­date, an siR­NA in­ves­ti­ga­tion­al drug in­ject­ed in­to pa­tients.

“That’s re­al­ly what drew me to Co­manche, is that we know that there are sev­er­al ap­proved siR­NA-based ther­a­peu­tics. But part of what’s unique here is that this as­set is tar­get­ed and specif­i­cal­ly de­liv­ered to the pla­cen­ta,” Au­gust said.

Au­gust al­so hopes Co­manche will be a tem­plate and a mod­el for how clin­i­cal stud­ies should be con­duct­ed in preg­nant women. She said re­searchers should be mind­ful of the preg­nant in­di­vid­ual as well as the fe­tus.

It’s a ma­jor un­met need, Au­gust said. Glob­al­ly, preeclamp­sia caus­es around 80,000 ma­ter­nal and more than 500,000 fe­tal and new­born deaths each year. Mor­tal­i­ty rates due to preeclamp­sia in ma­ter­nal women are ris­ing in the US, she said, in part due to ris­ing rates of gen­er­al hy­per­ten­sion and di­a­betes, which can go hand in hand with preeclamp­sia.

Au­gust de­scribes her work as a “full cir­cle” mo­ment af­ter start­ing her ca­reer as an ob­ste­tri­cian gy­ne­col­o­gist.

“There’s no short­age of is­sues that need to be ad­dressed. It re­al­ly needs to be root­ed in that ba­sic sci­ence. I think that’s what dif­fer­en­ti­ates Co­manche; they get how pow­er­ful this po­ten­tial­ly can be,” she said. — An­na Brown

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Sharon Barr: As­traZeneca’s bio­phar­ma head on ap­ply­ing lessons from rare dis­ease to chron­ic dis­ease

Sharon Barr al­ways want­ed her sci­ence to lead to new med­i­cines.

She kicked off her ca­reer as a post­doc­tor­al fel­low in mol­e­c­u­lar phar­ma­col­o­gy at Stan­ford Uni­ver­si­ty, but lat­er re­al­ized that she might be able to reach her goal faster in the phar­ma­ceu­ti­cal in­dus­try.

“The time­line would be very com­pressed,” she told End­points News.

In 2005, Barr land­ed her “dream job” as a re­search sci­en­tist at the biotech com­pa­ny OSI Phar­ma­ceu­ti­cals, which had an EGFR ki­nase in­hibitor on the mar­ket for non-small cell lung can­cer dubbed Tarce­va. The com­pa­ny didn’t know where to take the drug next, and it was up to Barr and a hand­ful of oth­er sci­en­tists to form a trans­la­tion­al re­search team and find out.

Dur­ing this pe­ri­od, Barr said she was learn­ing about how drugs are cre­at­ed, what ques­tions have to be asked and an­swered dur­ing their de­vel­op­ment, and the un­knowns that re­main once they’re in the clin­ic. Astel­las ac­quired OSI in 2010, and Barr re­mained at the com­pa­ny’s on­col­o­gy unit for al­most a decade.

Then, in 2013, she found her­self at a “ca­reer junc­ture,” with sev­er­al job op­por­tu­ni­ties in on­col­o­gy and one in a com­plete­ly dif­fer­ent area: rare dis­eases.

“I thought, ‘If I go work in rare dis­ease, I’m go­ing to have to learn new modal­i­ties, build a new net­work, learn new path­ways, com­plete­ly re­boot my un­der­stand­ing of bi­ol­o­gy,’” Barr said. “That sounds re­al­ly hard, so I think I want to do it.”

Barr joined Alex­ion Phar­ma­ceu­ti­cals in Ju­ly of that year, start­ing off as a di­rec­tor in trans­la­tion­al med­i­cine and cy­cling through var­i­ous roles over a pe­ri­od of eight years. There, she gained a deep­er un­der­stand­ing of how to tai­lor R&D to the needs of spe­cif­ic dis­ease com­mu­ni­ties af­ter meet­ing pa­tients with fi­brodys­pla­sia os­si­f­i­cans pro­gres­si­va, a de­bil­i­tat­ing neu­ro­mus­cu­lar con­di­tion in which mus­cle tis­sue and con­nec­tive tis­sue grad­u­al­ly os­si­fy to bone.

“They might care more about up­per body strength than they do about the six-minute walk test, be­cause they want to be able to feed them­selves more than they want to be able to walk down­stairs,” Barr said. “It changed the way I think about cre­at­ing new med­i­cines.”

In 2021, As­traZeneca snapped up Alex­ion for $39 bil­lion, and Barr was head­ing up the UK drug­mak­er’s bio­phar­ma­ceu­ti­cals R&D unit just two years lat­er. Now, she ap­plies the learn­ings from rare dis­eases to much larg­er, more chron­ic con­di­tions, span­ning ther­a­peu­tic ar­eas from car­diometa­bol­ic to im­munol­o­gy. She is one mem­ber of a team of se­nior ex­ec­u­tives who re­port to CEO Pas­cal So­ri­ot, along­side ex­ec­u­tive vice pres­i­dent of on­col­o­gy R&D Su­san Gal­braith.

At As­traZeneca, Barr is keen on ex­pand­ing the com­pa­ny’s ca­pa­bil­i­ties in im­munol­o­gy with the help of its $1 bil­lion ac­qui­si­tion of Chi­na-US cell ther­a­py com­pa­ny Gra­cell Biotech­nolo­gies. The deal brought in a BC­MA- and CD19-tar­get­ing CAR-T ther­a­py called AZD-0120. In an in­ves­ti­ga­tor-ini­ti­at­ed lu­pus tri­al, the can­di­date achieved “ex­treme­ly” promis­ing Sys­temic Lu­pus Ery­the­mato­sus Dis­ease Ac­tiv­i­ty In­dex scores, re­turn­ing pa­tients’ scores to base­line, she said.

Barr is al­so “su­per-ex­cit­ed” about an up­com­ing car­diomy­opa­thy read­out for the com­pa­ny’s Io­n­is-part­nered lig­and-con­ju­gat­ed an­ti­sense oligonu­cleotide drug Wain­ua, which is ap­proved for polyneu­ropa­thy as­so­ci­at­ed with hered­i­tary transthyretin-me­di­at­ed amy­loi­do­sis.

“We have the chance to of­fer pa­tients a med­i­cine that changes the out­come of their dis­ease, and I’m thrilled to pieces about that,” she said. — Ay­isha Shar­ma

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Jo­han­na Ben­dell: Pick­ing drugs for can­cer pa­tients of the fu­ture

In her years as a prac­tic­ing on­col­o­gist and clin­i­cal tri­al in­ves­ti­ga­tor, Jo­han­na Ben­dell has seen and cared for thou­sands of pa­tients. But these days, she push­es her­self to think of ones she has nev­er met.

“Who’s the can­cer pa­tient of the fu­ture? I say this to my folks all the time, es­pe­cial­ly in dis­cov­ery,” she said. “Be­cause when we start in dis­cov­ery, we’re go­ing to make a mol­e­cule for pa­tients 10 years from now.”

Dis­cov­ery was a new area for Ben­dell when she joined Roche in 2021. Be­fore join­ing the com­pa­ny to head up on­col­o­gy for its phar­ma re­search and ear­ly de­vel­op­ment group, or pRED, Ben­dell spent 13 years at Sarah Can­non Re­search In­sti­tute in Ten­nessee, where she led hun­dreds of clin­i­cal tri­als while think­ing of new ways to de­sign them and bring them to pa­tients.

She be­lieves that the ex­pe­ri­ence of be­ing in the room with pa­tients gave her a unique per­spec­tive as she spear­head­ed a strat­e­gy re­vamp at one of the world’s largest can­cer drug­mak­ers — with the goal of di­ver­si­fy­ing the ear­ly-stage port­fo­lio but al­so fo­cus­ing on ar­eas pRED is best po­si­tioned in.

When Ben­dell first ar­rived at Roche, for in­stance, can­cer im­munother­a­pies took up 80% to 90% of the pipeline fol­low­ing the check­point boom. To­day, she counts a 50/50 split be­tween im­munother­a­pies and what she calls “can­cer cell de­pen­den­cies” — treat­ments that hit can­cers in vul­ner­a­ble spots such as tran­scrip­tion fac­tors and through syn­thet­ic lethal­i­ty.

Build­ing on Roche’s his­toric ex­per­tise on T cell bis­pecifics, her team is “ag­gres­sive­ly chas­ing down” a com­bi­na­tion of the CD20-di­rect­ed drug glofi­ta­m­ab with a tar­get­ed co-stim­u­la­tor that showed ear­ly promise as an off-the-shelf re­place­ment for CAR-T ther­a­py. The group is al­so ex­plor­ing new ex­tra­cel­lu­lar can­cer cell sur­face tar­gets, which could bol­ster the de­vel­op­ment of an­ti­body-drug con­ju­gates and ra­di­oli­gands down the road, she said.

Those changes she spear­head­ed at pRED co­in­cid­ed with a broad­er pri­or­i­ti­za­tion ex­er­cise at Roche, in­clud­ing a sep­a­rate de­ci­sion by Ben­dell’s coun­ter­parts at gRED — the R&D unit at Roche’s Genen­tech — to dis­solve its can­cer im­munol­o­gy group and in­te­grate it in­to the larg­er on­col­o­gy unit.

While stop­ping the de­vel­op­ment of mol­e­cules is al­ways a tough de­ci­sion, Ben­dell con­sid­ers them nec­es­sary to max­i­mize pa­tient im­pact. That pur­suit for ef­fi­cien­cy, af­ter all, was what pushed her to move from acad­e­mia to a com­mu­ni­ty-based re­search cen­ter be­fore join­ing phar­ma.

Be­ing ef­fi­cient, though, doesn’t mean nev­er slow­ing down. Ben­dell re­calls be­ing scared of tak­ing three months off when she was preg­nant with her sec­ond child. It was Sarah Can­non’s pres­i­dent, Skip Bur­ris, who re­as­sured her that ma­ter­ni­ty leave will be “a blink in your pro­fes­sion­al time­line.”

“That al­ways made me feel so safe,” she said. At pRED, she is now a spon­sor for the women’s net­work. “To be able to now say that to oth­er women in the or­ga­ni­za­tion, ‘We’re go­ing to be there. We’re go­ing to help you through it […] that’s great.”

There will al­ways be more to do with Roche’s push for R&D ex­cel­lence. For Ben­dell, that means al­so re­flect­ing on how var­i­ous groups are op­er­at­ing to­geth­er. In on­col­o­gy, she cham­pi­ons “seam­less” drug de­vel­op­ment by en­sur­ing that her team of 280 in dis­cov­ery and ear­ly clin­i­cal de­vel­op­ment is in reg­u­lar con­ver­sa­tion with those in late-stage de­vel­op­ment. The for­mer needs to know who the pa­tients are and what op­tions they al­ready have, es­pe­cial­ly in a rapid­ly chang­ing field; the lat­ter could ben­e­fit from un­der­stand­ing how the sci­ence is evolv­ing and what could be pos­si­ble.

“Be­ing able to trans­late those two lan­guages to each oth­er [is] go­ing to be key to com­ing up with what’s next and what’s best,” she said. — Am­ber Tong

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Kristi­na Burow: ARCH man­ag­ing di­rec­tor en­joys ‘every sin­gle minute’ of build­ing the blue­print for biotechs

Be­hind one of the biggest names in biotech start­up in­vest­ing of the past quar­ter-cen­tu­ry is Kristi­na Burow, a man­ag­ing di­rec­tor at ARCH Ven­ture Part­ners, a firm that’s seem­ing­ly at­tached to near­ly every large bet in the fick­le world of drug de­vel­op­ment.

The for­mer UC Berke­ley swim­mer quick­ly found her lane once en­ter­ing the bio­phar­ma field, first work­ing at the Ge­nomics In­sti­tute at the No­var­tis Re­search Foun­da­tion, then mov­ing over to the Swiss gi­ant’s ven­ture fund in San Diego around the turn of the mil­len­ni­um. A few years lat­er, she took a role at ARCH, an in­vest­ment ap­pa­ra­tus in op­er­a­tion since its late-’80s found­ing in Chica­go.

“This will sur­prise no one who knows Bob Nelsen, but I had an open in­vi­ta­tion to hang out and do cool shit at ARCH. So that’s what I did,” Burow told End­points News. She moved to Chica­go, worked for ARCH while get­ting her MBA and then opened up the firm’s of­fice in San Fran­cis­co, where she stayed un­til the pan­dem­ic.

Burow has played a role in the firm’s go-big-or-go-home bets on in­fec­tious dis­ease at Vir Biotech­nol­o­gy (that com­pa­ny is shape-shift­ing now), in neu­ro­science at Neumo­ra Ther­a­peu­tics (ex­pect a cru­cial Phase 3 read­out for a new type of ma­jor de­pres­sion drug in the com­ing quar­ters) and now in obe­si­ty at Met­sera (a part­ner­ship with for­mer Med­i­cines Com­pa­ny ex­ec­u­tives).

Her im­print is al­so found in the dark genome at Rome Ther­a­peu­tics, in RNA med­i­cines at Or­bital Ther­a­peu­tics, in mi­to­chon­dr­i­al bi­ol­o­gy at Pret­zel Ther­a­peu­tics and in on­col­o­gy at Bound­less Bio, which was part of a small co­hort of biotech star­tups to go pub­lic ear­li­er this year.

The list goes on. She said each new build starts with three key ques­tions: What’s the mis­sion? Who’s go­ing to lead the dai­ly grind? And what’s the like­li­hood of suc­cess? Each of those come with a laun­dry list of sub­ques­tions.

When she en­tered the biotech in­vest­ing world near­ly 30 years ago, the pace of com­pa­ny cre­ation paled in com­par­i­son to to­day’s mo­men­tum, at least at ARCH, which has some of the in­dus­try’s biggest pock­ets.

“Every com­pa­ny seemed to take 15 years to build, and now I think the biotech in­dus­try has got­ten much faster at tak­ing in­no­va­tion, putting it on the train tracks and cre­at­ing ther­a­peu­tics that dri­ve pa­tient out­comes but al­so tend to dri­ve merg­ers and ac­qui­si­tions and IPO out­comes,” Burow said.

That longevi­ty gives Burow lit­tle to no pause when think­ing about the state of the biotech fi­nanc­ing scene over the past few years. She and the ARCH team have seen it again and again.

“We are not let­ting the ex­ter­nal en­vi­ron­ment dic­tate what types of com­pa­nies we’re go­ing to build or what types of sci­ence or en­tre­pre­neurs we’re go­ing to back,” she said.

And cre­at­ing biotech star­tups might not be as hard as help­ing start new Montes­sori schools in San Fran­cis­co, which the moth­er of three has al­so done.

“They’re very sim­i­lar. There is a lot of reg­u­la­tion in preschools in San Fran­cis­co. I can tell you that,” Burow said with a chuck­le. “It re­quires a lot of cap­i­tal, so there are some very dis­tinct sim­i­lar­i­ties. And it all comes down to the teacher, which is like the CEO.”

Set­ting up schools and form­ing the blue­print for biotechs: It’s all one big ex­per­i­ment. And Burow said she has “en­joyed every sin­gle minute.” — Kyle LaHu­cik

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An­na Win­dle and Karin Conde-Knape: We­govy work from the US to the glob­al stage

Karin Conde-Knape and An­na Win­dle watched No­vo Nordisk’s weight loss drug We­govy take off from two dif­fer­ent per­spec­tives: Conde-Knape from a glob­al drug dis­cov­ery role, and Win­dle from a clin­i­cal de­vel­op­ment and reg­u­la­to­ry fo­cus in North Amer­i­ca.

Now they’re in­ter­est­ed in what the drug can do out­side of weight loss and di­a­betes.

Win­dle joined No­vo Nordisk in 2011 in med­ical af­fairs, rough­ly six years be­fore semaglu­tide won its first ap­proval in di­a­betes as Ozem­pic. The com­pa­ny was al­ready de­vel­op­ing the GLP-1 re­cep­tor ag­o­nist at the time, and up­on re­view­ing the da­ta, the team re­al­ized they had some­thing “pret­ty amaz­ing.”

Semaglu­tide was ap­proved in 2017 as Ozem­pic for di­a­betes. In 2021, it be­came the first drug ap­proved for chron­ic weight man­age­ment, a land­mark mo­ment for the obe­si­ty field. The treat­ment, mar­ket­ed as We­govy, gen­er­at­ed more than $915 mil­lion in 2022, its first full year on the mar­ket.

“But I would say prob­a­bly the big turn­ing point was es­sen­tial­ly when we ac­tu­al­ly got the read­outs of the car­dio­vas­cu­lar da­ta,” Win­dle said.

In the SE­LECT tri­al, We­govy re­duced pa­tients’ risk of ma­jor ad­verse car­dio­vas­cu­lar events by 20% com­pared to place­bo, lead­ing to a la­bel ex­pan­sion in March.

“I was so proud of us, ac­tu­al­ly, for that tri­al,” Win­dle said. “Peo­ple were leav­ing the obe­si­ty field, and No­vo de­cid­ed that we would com­mit to it and we would stay in it.”

Win­dle’s cur­rent role in­volves lead­ing clin­i­cal de­vel­op­ment for North Amer­i­ca across all ther­a­peu­tic ar­eas, as well as lead­ing reg­u­la­to­ry in­ter­ac­tions with the FDA. Her team spends a lot of time un­der­stand­ing what pa­tients’ un­met needs are — and plan­ning semaglu­tide’s next steps.

The drug is in clin­i­cal tri­als for a va­ri­ety of con­di­tions, in­clud­ing Alzheimer’s and a liv­er dis­ease called MASH.

As se­nior vice pres­i­dent of glob­al drug dis­cov­ery, Conde-Knape al­so thinks about “con­tin­u­ing to build the jour­ney around GLP-1.”

Conde-Knape joined No­vo in 2018, first fo­cused on car­dio­vas­cu­lar and liv­er dis­eases and then even­tu­al­ly di­a­betes and kid­ney dis­ease as well as build­ing a trans­la­tion­al team. She said it was clear ear­ly on that the GLP-1 mech­a­nism had “the po­ten­tial to de­liv­er more.”

Look­ing to the fu­ture, Conde-Knape sees a sat­u­rat­ed GLP-1 space, in­clud­ing dou­ble and triple ag­o­nists, sim­i­lar to the PDL-1 space for can­cer. She sees the next gen­er­a­tion of mol­e­cules as “quite crit­i­cal,” as well as con­sid­er­ing sub­groups of pa­tients in the obe­si­ty com­mu­ni­ty who have co­mor­bidi­ties.

“What else do you bring in the un­der­stand­ing of dis­ease and bi­ol­o­gy so that you can ac­tu­al­ly im­pact mul­ti­ple or­gans that go be­yond weight loss? That is, for me, what is go­ing to be the change,” she said. —  Kather­ine Lewin

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Su­san Gal­braith: How As­traZeneca’s on­col­o­gy head chart­ed a path in pre­ci­sion med­i­cine

Su­san Gal­braith fell in­to on­col­o­gy by chance.

As a ju­nior doc­tor, she had want­ed to spe­cial­ize in car­di­ol­o­gy, but end­ed up on a ro­ta­tion that in­clud­ed on­col­o­gy at Ad­den­brooke’s Hos­pi­tal in the UK. She found her­self en­joy­ing the long-term con­tact with can­cer pa­tients and their fam­i­lies, and nur­tured a grow­ing in­ter­est in the mech­a­nisms be­hind can­cer and its treat­ment.

At the turn of the cen­tu­ry, Gal­braith fol­lowed that in­ter­est even fur­ther and pur­sued a PhD fo­cused on a vas­cu­lar-tar­get­ing agent for can­cer owned by a small biotech com­pa­ny. The com­pound was lat­er li­censed by Bris­tol My­ers Squibb, with a job op­por­tu­ni­ty at the US drug­mak­er fol­low­ing soon af­ter.

“It came at a con­ve­nient time in my ca­reer — I’d al­ways been in­ter­est­ed in work­ing in a dif­fer­ent coun­try for a pe­ri­od of time and it was just be­fore I would have been ap­ply­ing for con­sul­tant roles in the NHS,” she told End­points News.

With her hus­band and two young chil­dren in tow, Gal­braith made the trip across the At­lantic, on­ly to learn two weeks af­ter her ar­rival that Bris­tol My­ers had killed the drug.

“That was a les­son about burn­ing bridges,” she said. “I had no choice but to make it work at that point.”

Af­ter chat­ting with staff at Bris­tol My­ers’ dis­cov­ery lab, Gal­braith be­came in­ter­est­ed in the then-nascent field of im­munother­a­py. While at­tend­ing a small con­fer­ence in New York, she came across a pre­sen­ta­tion on Phase 1 da­ta for a mon­o­clon­al an­ti­body drug tar­get­ing CT­LA-4. Im­pressed by the re­sults, she ini­ti­at­ed the in-li­cens­ing of that drug by Bris­tol My­ers.

Now bet­ter known by its brand name Yer­voy, the drug gen­er­at­ed $1.38 bil­lion in sales last year.

“I prob­a­bly wouldn’t have been so fo­cused on the po­ten­tial of im­muno-on­col­o­gy if they hadn’t killed the drug I’d orig­i­nal­ly worked on,” Gal­braith said. “It’s like one door clos­es and an­oth­er opens, but you’ve got to be will­ing to take the risk and walk through that door.”

Nine years in­to her time at Bris­tol My­ers in the US, Gal­braith got a call from As­traZeneca. “It was prob­a­bly the on­ly job back in the UK that I would have been in­ter­est­ed in do­ing, with a com­pa­ny that had its dis­cov­ery and ear­ly de­vel­op­ment group fo­cused there,” she said.

When Gal­braith joined As­traZeneca in 2010, its PARP in­hibitor ola­parib was at a cross­roads. The com­pa­ny had re­for­mu­lat­ed the drug from a cap­sule to a tablet, but was strug­gling to achieve bioe­quiv­a­lence. Ola­parib had al­so com­plet­ed a Phase 2 test in sec­ond-line plat­inum-sen­si­tive re­lapsed ovar­i­an can­cer, show­ing im­proved pro­gres­sion-free sur­vival, but there was “not yet a trend to over­all sur­vival,” Gal­braith said.

Gal­braith, how­ev­er, no­ticed a “re­mark­ably large” ef­fect size in a sub­set of pa­tients with BR­CA mu­ta­tions. “We’re not even sure we’ve got a for­mu­la­tion that could go for­ward, and we’re want­i­ng to spend more mon­ey to test bio­mark­ers in this tri­al — some­body told me that I was propos­ing to throw good mon­ey af­ter bad,” she said.

But with the sup­port of Pas­cal So­ri­ot, who was named CEO in 2012, Gal­braith man­aged to se­cure the funds to look fur­ther in­to ola­parib’s po­ten­tial. The drug’s ap­proval in 2014 was a “turn­ing point” for As­traZeneca’s on­col­o­gy group and helped dri­ve a change in its phi­los­o­phy. Now mar­ket­ed as Lyn­parza, ola­parib made $2.81 bil­lion in sales last year.

Gal­braith is now one mem­ber of a team of se­nior ex­ec­u­tives who re­port to So­ri­ot, along­side ex­ec­u­tive vice pres­i­dent of bio­phar­ma­ceu­ti­cals R&D Sharon Barr.

In re­cent years, As­traZeneca has made a point of di­ver­si­fy­ing its on­col­o­gy pipeline. In De­cem­ber, the drug­mak­er en­tered the CAR-T field with a $1 bil­lion deal to ac­quire Chi­na-US cell ther­a­py com­pa­ny Gra­cell Biotech­nolo­gies. In March, it struck a deal for $2 bil­lion up­front to buy Fu­sion Phar­ma­ceu­ti­cals, join­ing the in­creas­ing­ly pop­u­lar ra­dio­phar­ma­ceu­ti­cals field. These deals added to on­go­ing work on an­ti­body-drug con­ju­gates in col­lab­o­ra­tion with Japan’s Dai­ichi Sankyo.

While some have ques­tioned whether the com­pa­ny is spread­ing it­self too thin, Gal­braith said there’s a method to the ap­proach. “The idea is we’ve got to have a di­verse set of mech­a­nisms that we can put to­geth­er in ef­fec­tive com­bi­na­tions,” she said.

For in­stance, ra­dio con­ju­gates could sup­ple­ment or re­place some parts of the way ra­dio­ther­a­py is giv­en, while cell ther­a­pies could help broad­en the po­ten­tial reach of im­munother­a­pies to ar­eas where im­mune check­point in­hibitors on their own haven’t been as ef­fec­tive, Gal­braith said.

That all comes along with the com­pa­ny’s ef­forts to boost ear­ly screen­ing and di­ag­no­sis of can­cer with the help of tools such as AI, and with its ex­pan­sion in­to the dig­i­tal health space. It builds on the lessons she learned at Bris­tol My­ers — be­ing re­cep­tive to oth­er doors open­ing in case one clos­es.

“I think we have some­thing that’s dif­fer­en­ti­at­ed from what many com­pa­nies are of­fer­ing,” Gal­braith said. — Ay­isha Shar­ma

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Qui­ta High­smith: Genen­tech’s first chief di­ver­si­ty of­fi­cer on be­ing a ‘change­mak­er’

Qui­ta High­smith was putting to­geth­er a sum­mit in 2017 for Genen­tech em­ploy­ees to learn from pa­tients who had par­tic­i­pat­ed in the com­pa­ny’s clin­i­cal re­search.

But she was hav­ing a hard time find­ing Black or His­pan­ic pa­tients to en­gage, be­cause their rep­re­sen­ta­tion was so dis­pro­por­tion­ate.

The episode drove High­smith and a co-work­er to found the Ad­vanc­ing In­clu­sive Re­search ini­tia­tive at Genen­tech to re­cruit more rep­re­sen­ta­tive pop­u­la­tions in­to clin­i­cal re­search. Af­ter nar­row­ing down lo­ca­tions spe­cif­ic to cer­tain dis­eases and re­search ar­eas such as on­col­o­gy, she would pick cities like Mem­phis, San An­to­nio, Los An­ge­les and oth­ers where the com­mu­ni­ty around them has a pop­u­la­tion that’s rep­re­sen­ta­tive of those most af­fect­ed by each con­di­tion.

Un­der the ini­tia­tive, Genen­tech’s par­tic­i­pat­ing on­col­o­gy sites en­rolled 89% more Black and His­pan­ic pa­tients than oth­er sites on the same stud­ies, the biotech said. Genen­tech al­so launched what it says was the first tri­al to as­sess dis­ease ac­tiv­i­ty and bio­mark­ers in Black and His­pan­ic pa­tients with re­laps­ing mul­ti­ple scle­ro­sis, and sub­mit­ted 20 di­ver­si­ty ac­tion plans out of a to­tal of 76 plans turned in to the FDA across the bio­phar­ma in­dus­try last year.

It was the per­fect segue in­to her cur­rent role as Genen­tech’s first chief di­ver­si­ty of­fi­cer in the 48-year his­to­ry of the biotech. High­smith reached out to HB­CUs to fund school­ing for un­der­priv­i­leged stu­dents who want to pur­sue PhDs to be­come sci­en­tists. She pushed for di­ver­si­ty in Genen­tech’s sup­pli­ers, seek­ing out busi­ness­es owned by vet­er­ans, in­di­vid­u­als with dis­abil­i­ties or women.

It’s re­ward­ing but tough to have to wear so many hats in her role, High­smith said.

“Just to be a chief di­ver­si­ty of­fi­cer, here’s what you are: You are a change­mak­er, you are an ad­vo­cate, you are an ad­vi­sor, you are an ed­u­ca­tor, you’re a truth teller, you bring in the da­ta,” she said. “And last­ly, you are a ther­a­pist to the en­tire com­pa­ny be­cause every­body wants to talk about their is­sues.” — Ngai Ye­ung

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Ju­la In­rig: Tra­vere’s CMO re­flects on the im­por­tance of col­lab­o­ra­tion

When Tra­vere Ther­a­peu­tics’ chief med­ical of­fi­cer Ju­la In­rig came aboard in late 2016 to help de­vel­op and guide two rare dis­ease kid­ney tri­als, she brought tons of ex­pe­ri­ence with her, hav­ing al­ready run more than 50 clin­i­cal tri­als across dozens of coun­tries.

That ex­ten­sive ex­pe­ri­ence has led her to stress the im­por­tance of col­lab­o­ra­tion.

“Col­lab­o­ra­tion has been the biggest key dri­ver to change and suc­cess,” In­rig told End­points News. “It of­ten takes many years to move the field for­ward as it takes a vil­lage, and many stake­hold­ers work in si­los.”

She of­fered one col­lab­o­ra­tive ex­am­ple with the Kid­ney Health Ini­tia­tive, which is a part­ner­ship in­volv­ing the FDA, the Amer­i­can So­ci­ety of Nephrol­o­gy, aca­d­e­mics and in­dus­try that de­fined end­points for dis­eases such as IGA nephropa­thy, a kid­ney dis­or­der.

Ten years ago, there were no FDA-ap­proved drugs for IGA nephropa­thy, “and now we have three new FDA-ap­proved ther­a­pies (in­clud­ing one we got ap­proved) and 10+ in de­vel­op­ment,” In­rig, a for­mer glob­al head of the Re­nal Cen­ter of Ex­cel­lence at IQVIA, not­ed.

Re­gard­ing her ex­pe­ri­ence as a woman in a male-dom­i­nant biotech world, In­rig said things have changed, par­tic­u­lar­ly in the last five years as com­pa­nies look to more di­ver­si­ty.

“I was very in­ten­tion­al in where I worked, and I try to com­mit to gen­der eq­ui­ty and al­so work­ing to en­sure the next gen­er­a­tion has a sim­i­lar ex­pe­ri­ence to me. That means men­tor­ing and giv­ing time to pro­fes­sion­al so­ci­eties which fo­cus on gen­der equal­i­ty,” she said.

As far as ad­vice for women who are de­bat­ing whether to move in­to the bio­phar­ma in­dus­try, In­rig said, “Do your re­search, make sure you are well in­formed at all lev­els about who you are work­ing for (the sci­ence, the cor­po­rate pri­or­i­ties, the cul­ture), and who your peers are as you will be in the trench­es with them! Cul­ture is crit­i­cal and can make or break you.”

On the ben­e­fits of mov­ing from acad­e­mia to in­dus­try, In­rig added that acad­e­mia “can be very siloed and the abil­i­ty to make an im­pact can some­times be lim­it­ed to n=1 or n=100,” where­as work­ing on a col­lec­tive goal such as a new drug ap­proval “can be per­son­al­ly re­ward­ing and im­pact­ful on a much larg­er scale,” she said. — Zachary Bren­nan

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Iya Khalil: Bring­ing the on­col­o­gy play­book — pow­ered by AI — to fu­el Mer­ck’s pipeline

Iya Khalil has a dif­fer­ent per­spec­tive than most on Mer­ck’s re­cent $10.8 bil­lion pur­chase of Prometheus Bio­sciences.

For many Wall Street an­a­lysts and in­vestors, the deal looks like a move to re­place rev­enue from Keytru­da with a po­ten­tial im­munol­o­gy block­buster in a TL1A block­er now called MK-7240.

But for Khalil, who joined Mer­ck in 2023 as vice pres­i­dent and head of da­ta, AI, and genome sci­ences, that TL1A pro­gram is just one ex­am­ple of an even big­ger trend defin­ing Mer­ck’s fu­ture. Khalil’s team is build­ing dis­ease foun­da­tion mod­els, hop­ing to un­cov­er new ther­a­peu­tic tar­gets as well as find­ing pre­ci­sion bio­mark­ers to help learn which pa­tients are most like­ly to re­spond to a drug.

Pa­tients who en­roll in Mer­ck’s late-stage stud­ies for MK-7240 will al­so have a mix of ge­net­ic and -omics pro­fil­ing, both pre-treat­ment and post-treat­ment. All those da­ta are fed in­to AI mod­els her team is build­ing to mod­el and sim­u­late dis­eases. The goal is these foun­da­tion mod­els could then be fine-tuned to sim­u­late spe­cif­ic sce­nar­ios to help re­searchers make de­ci­sions on what dis­ease or types of pa­tients may be most like­ly to ben­e­fit from a drug.

Khalil has been work­ing in the com­pu­ta­tion­al bi­ol­o­gy space since 2000, when she co-found­ed a start­up called GNS (re­cent­ly named Aitia). Af­ter two decades there, she left to run an AI lab at No­var­tis be­fore jump­ing to Mer­ck last year.

“We are in build mode,” Khalil said. “As far as I can tell, it looks very promis­ing.”

Khalil’s team of over 100 peo­ple is help­ing turn am­bi­tious ideas like foun­da­tion mod­els of bi­ol­o­gy in­to re­al­i­ty across Mer­ck’s re­search in im­munol­o­gy, neu­ro­science, on­col­o­gy and car­diometa­bol­ic dis­ease.

“We’re at a point where we can now do this,” she said. “It was pro­hib­i­tive a while back” for rea­sons like the qual­i­ty of the bi­o­log­i­cal da­ta and chal­lenges in cap­tur­ing this da­ta while main­tain­ing the tri­al’s in­tegri­ty. “We’re at the con­ver­gence of 2024, where these things can tru­ly come to­geth­er.”

The work is ear­ly, but Khalil said there are mul­ti­ple rea­sons to be­lieve now is the op­por­tune time for these mod­els to be suc­cess­ful. Pa­tient da­ta have be­come cheap­er and more de­tailed. New AI mod­els al­low bet­ter ways for com­put­ers to process dif­fer­ent types of bi­o­log­i­cal da­ta. And com­pute pow­er has got­ten sig­nif­i­cant­ly bet­ter, al­low­ing these mod­els to be trained.

“In­stead of learn­ing the lan­guage of words with Chat­G­PT, can it learn the lan­guage of ge­net­ics, ge­nomics, pro­teomics, imag­ing and how that im­pacts a cell phe­no­type?” Khalil said. “It’s a mas­sive ef­fort, both in terms of the da­ta we’re col­lect­ing and gen­er­at­ing to train them, as well as the com­pute pow­er.” — An­drew Dunn

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There­sa LaVallee: When the ninth PD-1 al­so marked a his­toric first

There­sa LaVallee is used to run­ning projects that every­body says couldn’t be done — or wouldn’t think to do.

She was the first trans­la­tion­al med­i­cine em­ploy­ee at As­traZeneca’s Med­Im­mune, watch­ing them take on the bold chal­lenge of de­vel­op­ing an an­ti­body for RSV and ex­plor­ing check­point in­hi­bi­tion be­fore im­muno-on­col­o­gy took off. A cou­ple of ex­ec­u­tive jobs lat­er, she moved across the coun­try to join “this wacky idea” that was the Park­er In­sti­tute for Can­cer Im­munother­a­py, where she led col­lab­o­ra­tive re­search projects to run ex­per­i­ments that phar­ma com­pa­nies wouldn’t.

“A cou­ple of peo­ple asked me if I was hav­ing a life cri­sis,” she said.

So when Co­herus Bio­Sciences, a com­pa­ny most­ly known for its biosim­i­lars, called about steer­ing a made-in-Chi­na PD-1 drug to a his­toric FDA ap­proval in the mid­dle of a pan­dem­ic, she took the op­por­tu­ni­ty.

When LaVallee first joined Co­herus, the per­cep­tion was that the agency had an open-arms at­ti­tude to­ward drugs test­ed and de­vel­oped ex­clu­sive­ly in Chi­na. But soon af­ter, the agency made clear — through a re­jec­tion of Eli Lil­ly and In­novent’s drug — that Chi­na-on­ly da­ta are not go­ing to cut it.

But even with some con­fu­sion about the FDA’s view­point on Chi­na-on­ly da­ta, and af­ter a man­u­fac­tur­ing-re­lat­ed re­jec­tion, it hap­pened: In Oc­to­ber 2023, Cal­i­for­nia-based Co­herus and its part­ner Jun­shi brought the ninth PD-(L)1 in­hibitor on­to the US mar­ket. The FDA green­lit tori­pal­imab — a par­tic­u­lar­ly im­pres­sive feat for her “lit­tle tee­ny” reg­u­la­to­ry team of six.

“Get­ting tori­pal­imab ap­proved was by far the biggest hur­dle — the hard­est thing I’ve ever done,” said LaVallee, who’s now chief de­vel­op­ment of­fi­cer at the biotech. “Peo­ple re­al­ly didn’t be­lieve it was go­ing to hap­pen.”

Co­herus and Jun­shi man­aged to pull off the ex­cep­tion that proved the rule by fo­cus­ing on na­sopha­ryn­geal car­ci­no­ma, a can­cer type that’s par­tic­u­lar­ly preva­lent in East Asian pop­u­la­tions and rare in the US.

They were al­so suc­cess­ful be­cause they were able to find so­lu­tions when Chi­na im­posed se­vere trav­el re­stric­tions re­lat­ed to Covid, phys­i­cal­ly bar­ring FDA in­spec­tors from reach­ing the con­tract re­search or man­u­fac­tur­ing sites in­volved in pro­duc­ing the drug. By 2023, those in­spec­tions were the on­ly thing hold­ing up the ap­proval.

“We looked at some very cre­ative ap­proach­es col­lab­o­rat­ing with oth­er com­pa­nies that were in sim­i­lar sit­u­a­tions,” LaVallee said, in­clud­ing ask­ing the FDA to con­sid­er set­ting up a “bub­ble” for per­son­nel, like in the Olympics.

It didn’t come to that, and Chi­na even­tu­al­ly lift­ed all re­stric­tions. And that “al­most was a big­ger prob­lem,” she said, be­cause the FDA now had an en­tire back­log to go through. But with her con­stant con­tact with the agency or even luck — LaVallee her­self wasn’t quite sure which end­ed up the de­cid­ing fac­tor — the drug end­ed up be­ing the FDA’s sec­ond in­spec­tion once the agency en­tered Chi­na.

With a PD-1 back­bone in its port­fo­lio, Co­herus is ex­plor­ing part­ner­ships to fund com­bi­na­tion stud­ies while test­ing oth­er ear­ly-stage can­di­dates as it looks to es­tab­lish it­self in im­muno-on­col­o­gy. The com­pa­ny is still open to work­ing with Chi­nese biotechs with sci­en­tif­ic mer­its — it will just have to be vig­i­lant about the evolv­ing geopo­lit­i­cal con­cerns.

“We are mov­ing the man­u­fac­tur­ing of tori­pal­imab to the Unit­ed States,” LaVallee said. “I don’t want to have to wor­ry about trav­el­ing to Chi­na again.” — Am­ber Tong

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Jeanne Lor­ing: Af­ter years of pi­o­neer­ing stem cell work, a no­table re­searcher push­es for a break­through

Jeanne Lor­ing, who has been called the god­moth­er of stem cells, is watch­ing her decades­long re­search reach a piv­otal junc­ture.

Her tenac­i­ty pro­duced, per­haps most no­tably, a po­ten­tial Parkin­son’s treat­ment that start­ed a clin­i­cal tri­al ear­li­er this year. The mile­stone fol­lows years of set­backs in the stem cell field, and more broad­ly, Parkin­son’s drug de­vel­op­ment.

“A plan I put in place a long time ago is work­ing,” said Lor­ing, found­ing di­rec­tor of the Cen­ter for Re­gen­er­a­tive Med­i­cine at Scripps Re­search.

Her work with stem cells has run the gamut and ex­tend­ed to ar­eas that might seem more sci­ence fic­tion than re­al­i­ty: from re­viv­ing the north­ern white rhi­noc­er­os pop­u­la­tion to study­ing cells in space. Her pur­suits were the sub­ject of an in-depth End­points News pro­file last year.

Lor­ing’s next big fron­tier: po­ten­tial­ly treat­ing brain con­di­tions.

She co-found­ed As­pen Bio­sciences in 2018 and helped raise $220 mil­lion to try a per­son­al­ized ap­proach to Parkin­son’s. The com­pa­ny cre­ates ther­a­pies us­ing a pa­tient’s own cells, which is known as an au­tol­o­gous ther­a­py.

The clin­i­cal tri­al is look­ing to see if, once in­ject­ed, these cells can ma­ture in­to dopamine-pro­duc­ing neu­rons. In pa­tients with Parkin­son’s, neu­rons die, caus­ing stiff­ness, tremors and anx­i­ety, among oth­er symp­toms.

Pa­tients cur­rent­ly have lim­it­ed op­tions. Long­time Parkin­son’s treat­ment lev­odopa has lim­it­ed ef­fects and wears off over time.

A com­peti­tor, Blue­Rock Ther­a­peu­tics, is in clin­i­cal tri­als with a sim­i­lar ther­a­py, but one that’s based on donor cells. To pre­vent the body from re­ject­ing the med­i­cine, pa­tients must take im­muno­sup­pres­sive drugs that can weak­en the body’s de­fens­es.

Be­cause of As­pen’s per­son­al­ized ap­proach, the in­dus­try is close­ly watch­ing its clin­i­cal tri­al. But Lor­ing doesn’t see it as an ei­ther/or. In June, Lor­ing and co-au­thors wrote in the jour­nal Stem Cells that com­pe­ti­tion shouldn’t take prece­dence over col­lab­o­ra­tion — one of her key philoso­phies.

As­pen, Blue­Rock and oth­er or­ga­ni­za­tions are part of a glob­al part­ner­ship called G-Force PD to share da­ta on stem cell ther­a­pies.

“This field is too chal­leng­ing for com­pe­ti­tion to be the main goal; there are so many peo­ple suf­fer­ing from Parkin­son’s dis­ease that there should be room for mul­ti­ple ap­proach­es to suc­ceed,” Lor­ing and oth­ers wrote in the pa­per.

Mul­ti­ple com­pa­nies pur­su­ing stem cell treat­ment for Parkin­son’s seemed like a far-off pos­si­bil­i­ty ear­ly in Lor­ing’s ca­reer. At that time, she ran in­to dif­fi­cul­ties putting stem cells to work be­cause she strug­gled to get fund­ing. Her ad­vice to women en­coun­ter­ing sim­i­lar bar­ri­ers?

“When fun­ders say ‘no,’ ask them why, and then have them ex­plain it, and then tell them why they’re wrong,” Lor­ing said. But, she cau­tioned, not every in­vestor wel­comes such di­rect­ness.

“The path I’ve tak­en has prob­a­bly alien­at­ed just as many peo­ple as I’ve won over be­cause I’m very straight­for­ward,” she said.

Nonethe­less, she’s learned how to speak the lan­guage of both acad­e­mia and in­dus­try, mov­ing back and forth be­tween the two realms through­out her ca­reer.

“You re­al­ly do have to change the way you talk to peo­ple, the way you in­ter­act with peo­ple, and re­mark­ably, it has been a lot of fun,” Lor­ing said. — Jared Whit­lock

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Jirong Lu: The pro­tein bio­chemist be­hind Lil­ly’s biggest an­ti­body drugs

There’s a lot of be­hind-the-scenes work that goes in­to turn­ing a promis­ing an­ti­body in­to a bona fide drug can­di­date. Jirong Lu is the chemist re­spon­si­ble for fine-tun­ing some of Eli Lil­ly’s biggest an­ti­body med­i­cines, in­clud­ing the pso­ri­a­sis drug Taltz and the re­cent­ly-ap­proved Alzheimer’s dis­ease ther­a­py Kisun­la.

Lu grew up in rur­al Chi­na, where time spent out­doors fos­tered an ap­pre­ci­a­tion for na­ture and a strong cu­rios­i­ty. Her par­ents nev­er went to col­lege, but a young high school chem­istry teacher ig­nit­ed her in­ter­est in the cen­tral sci­ence, which she then stud­ied at Sichuan Uni­ver­si­ty.

Lat­er, as she was wrap­ping up her post­doc­tor­al re­search on pro­teins at the Uni­ver­si­ty of Wash­ing­ton in 1997, Lil­ly be­gan hir­ing sci­en­tists for a new biotech­nol­o­gy re­search unit. When Lu saw an ad­ver­tise­ment for the In­di­anapo­lis drug­mak­er’s ini­tia­tive while flip­ping through a sci­ence mag­a­zine, she im­me­di­ate­ly knew it was “like a dream job.”

This was a big turn­ing point for Lil­ly, best known then for mak­ing in­sulin and Prozac. Pro­tein ther­a­pies were cut­ting-edge sci­ence, and Lu loved the group’s mantra that “your body doesn’t make the pro­tein to be used as a ther­a­peu­tic,” she said. Nat­ur­al pro­teins need­ed to be en­gi­neered and op­ti­mized to do their job. It was chem­istry, but with mol­e­cules whose size and com­plex­i­ty dwarfed the com­pounds found in pills.

Lu be­came fast friends with bi­ol­o­gist Ling Liu, an­oth­er new­com­er to Lil­ly who al­so stud­ied at Sichuan Uni­ver­si­ty. The duo worked on a mys­te­ri­ous im­mune pro­tein now known as IL-17. Liu dis­cov­ered that it caused in­flam­ma­tion, and Lu cre­at­ed an an­ti­body that could block it.

Mak­ing an­ti­bod­ies was still a la­bo­ri­ous task in the ear­ly 2000s. Lu had to im­mu­nize mice with the IL-17 pro­tein, col­lect their an­ti­bod­ies, test them to find the best ones, re­work the mouse an­ti­bod­ies to make them look like hu­man ones, and then op­ti­mize those mol­e­cules to make sure they were sol­u­ble and sta­ble. All told, it could take three to five years, Lu said.

When an­ti­body op­ti­miza­tion fails, pro­grams are of­ten canned be­fore in­vestors ever hear about them. And when they suc­ceed, the fo­cus quick­ly shifts to clin­i­cal tests. The vi­tal work that sci­en­tists like Lu do rarely reach­es the pub­lic lime­light.

The IL-17 an­ti­body was ini­tial­ly test­ed in rheuma­toid arthri­tis, with lack­lus­ter re­sults, but its abil­i­ty to clear skin plaques in peo­ple with pso­ri­a­sis was dra­mat­ic. The an­ti­body was first ap­proved in 2016 and is now mar­ket­ed as Taltz. It’s among Lil­ly’s biggest sell­ers, earn­ing the com­pa­ny more than $2.7 bil­lion last year.

Lu al­so played a key role in mul­ti­ple Alzheimer’s pro­grams, plant­i­ng the seeds for Lil­ly’s even­tu­al suc­cess af­ter sev­er­al fail­ures.

It all start­ed when Lil­ly neu­ro­sci­en­tist Ron De­Mat­tos iden­ti­fied a par­tic­u­lar part of the in­fa­mous amy­loid plaques that he want­ed to tar­get. An­ti­body en­gi­neer Ying Tang worked nights and week­ends to find an an­ti­body that could do the job. Af­ter iden­ti­fy­ing a promis­ing lead, Lu steered a full-blown ef­fort to im­prove its affin­i­ty. Hu­man­iz­ing the an­ti­body was tricky, and ini­tial­ly re­sult­ed in a weak­er mol­e­cule that was quick­ly cleared from the body. But ad­di­tion­al chem­i­cal tweaks saved the drug.

That an­ti­body, called do­nanemab, is now sold as Kisun­la. It’s un­clear if it will be the big block­buster that Lil­ly and oth­ers al­ways imag­ined an Alzheimer’s drug would be. But Lil­ly al­ready has se­quels in the works. Remter­ne­tug, an­oth­er amy­loid-bust­ing an­ti­body that Lu helped de­sign, is giv­en as a sim­ple in­jec­tion rather than a lengthy in­fu­sion. It’s be­ing test­ed in Phase 3 tri­als now.

More re­cent­ly, Lu has helped push Lil­ly’s “10-year jour­ney” to de­sign an­ti­body and pro­tein ther­a­pies that pen­e­trate the blood-brain bar­ri­er, the pro­tec­tive shield that keeps most drugs out of the brain — in­clud­ing most of do­nanemab. Lil­ly hasn’t talked much about this ef­fort pub­licly, but Lu said the com­pa­ny is work­ing to­ward test­ing it in the clin­ic.

Over the past few years, Lu has stepped back from the lab bench and tak­en on man­age­ment roles at the com­pa­ny to guide its an­ti­body and pro­tein drug strate­gies. She al­so de­votes a lot of time men­tor­ing the next gen­er­a­tion of sci­en­tists.

“I have re­al­ly ben­e­fit­ed from hav­ing great men­tors at Lil­ly,” she said. “So I’m very pas­sion­ate about try­ing to pay back, to give oth­er sci­en­tists that op­por­tu­ni­ty.” — Ryan Cross

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Mar­i­ann Mic­si­nai-Bal­an: Mov­ing from Wall Street to phar­ma to bring AI in­to R&D

Grow­ing up east of the Iron Cur­tain in Hun­gary, Mar­i­ann Mic­si­nai-Bal­an has al­ways been com­fort­able with blend­ing cul­tures, lan­guages and ideas. That has led her to the cut­ting edge of R&D in phar­ma, tasked with bring­ing ar­ti­fi­cial in­tel­li­gence tech­nol­o­gy to a lega­cy drug-mak­ing gi­ant.

Be­fore join­ing Bris­tol My­ers Squibb in 2020, where she is now head of da­ta sci­ence, Mic­si­nai-Bal­an worked on Wall Street at Lehman Broth­ers and in the tech world at a start­up then called Green­plum Soft­ware.

She’s picked up a few de­grees along the way, in­clud­ing mas­ter’s de­grees in com­pu­ta­tion­al bi­ol­o­gy, eco­nom­ics, in­ter­na­tion­al stud­ies and in­ter­na­tion­al re­la­tions. She al­so earned a PhD in com­pu­ta­tion­al bi­ol­o­gy and is now com­plet­ing an ex­ec­u­tive MBA pro­gram.

That eclec­tic aca­d­e­m­ic jour­ney in­clud­ed an elec­tive class in sta­tis­ti­cal ge­nomics, which got her hooked on bio­phar­ma.

“I’ve tak­en the long, non­tra­di­tion­al route to bio­phar­ma that end­ed up giv­ing me a pret­ty good wealth of ex­pe­ri­ence and an adap­tive, flex­i­ble mind­set,” Mic­si­nai-Bal­an said.

That jour­ney across dis­ci­plines has shaped her per­spec­tive on bring­ing da­ta sci­ence and com­put­er sci­ence in­to the drug R&D world. Her team at Bris­tol My­ers isn’t fo­cused on ap­ply­ing AI to one par­tic­u­lar R&D task, but rather think­ing across the en­tire process. For in­stance, she said ear­ly dis­cov­ery in­sights can be in­te­grat­ed in­to lat­er-stage de­vel­op­ment plans.

Da­ta sci­ence is a team sport, Mic­si­nai-Bal­an said, em­pha­siz­ing the im­por­tance of get­ting buy-in across the com­pa­ny and work­ing to­geth­er, rather than op­er­at­ing as a siloed group. Mic­si­nai-Bal­an’s team al­so has some di­ver­si­ty that is of­ten lack­ing in AI cir­cles. Two-thirds of her in­terns were women this year, she said, as are over a quar­ter of per­ma­nent team mem­bers. The team has a wide range of back­grounds, from as­tro­physics to com­pu­ta­tion­al bi­ol­o­gy to math­e­mat­ics and more.

Mic­si­nai-Bal­an said she ad­vis­es her in­terns to stop doubt­ing them­selves. As her own ca­reer shows, in mov­ing from Wall Street to the tech start­up world to a drug-mak­ing gi­ant, some pro­fes­sion­al bound­aries on what’s doable are self-im­posed, she said.

“Don’t be afraid of fail­ing, be­cause if you don’t ex­plore, you close your chances of fig­ur­ing out, ‘Hey, this might be a route,’” she said. — An­drew Dunn

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Theo Ross: From med school to phar­ma, em­pa­thy is the through line of Ross’ ca­reer

Grow­ing up, Theo Ross says she had “no in­ter­est in sci­ence.” In­stead, she want­ed to be a con­cert vi­o­lin­ist or maybe a stand-up com­ic. She dropped out of high school, went to mu­sic school and chased her dreams.

Then she heard her broth­er, a renowned cel­list, play in a recital. She came to a painful­ly clear re­al­iza­tion: “‘Oh my God, I can nev­er be this per­son, and this is who I want to be,’” she thought to her­self. “So I quit.”

Decades lat­er, scores of pa­tients can be grate­ful that Ross put down the vi­o­lin for the lab coat. Ross, an aca­d­e­m­ic and on­col­o­gist at heart, has for­ayed in­to in­dus­try for the lat­est chap­ter of her ca­reer. She’s now the vice pres­i­dent of ear­ly on­col­o­gy re­search & de­vel­op­ment at Ab­b­Vie af­ter pri­or ex­ec­u­tive stints at Am­gen and Mer­ck.

Af­ter switch­ing from mu­sic to med­i­cine, Ross land­ed at Brigham and Women’s Hos­pi­tal, where she worked un­der the tute­lage of Mar­shall Wolf, the in­ter­nal med­i­cine res­i­den­cy di­rec­tor. Wolf is col­lo­qui­al­ly known as the “dean of med­ical res­i­den­cy pro­gram di­rec­tors” and helped train more than 2,000 doc­tors, in­clud­ing more than 1,000 who be­came full-time pro­fes­sors at lead­ing med­ical in­sti­tu­tions.

Ross said that Wolf on­ly al­lowed two peo­ple in the res­i­den­cy pro­gram from Har­vard. The rest had to come from med­ical schools around the coun­try.

“He was a guy who be­lieved in di­ver­si­ty be­fore peo­ple be­lieved in di­ver­si­ty,” she said.

Wolf was at Ross’ wed­ding. And he stepped up for her in the clin­ic when she had to deal with a fam­i­ly emer­gency. His em­pa­thy be­came a blue­print for Ross who, de­spite her as­cen­sion, con­tin­ues to see pa­tients pe­ri­od­i­cal­ly, main­ly for fam­i­ly or friends. She’s dri­ven by the fact that just tak­ing a mo­ment out of her day to give some med­ical ad­vice could ex­tend some­one’s life.

The em­pa­thy — and the pow­er of di­ver­si­ty — came to the fore­front while Ross worked at the Uni­ver­si­ty of Michi­gan. When her soon-to-be-hired lab man­ag­er told her she was preg­nant, Ross didn’t bat an eye. On­ly up­on re­flec­tion did she re­al­ize how nov­el that may have been to some­one like that lab man­ag­er who was con­cerned about tak­ing ma­ter­ni­ty leave in a field where men dom­i­nate lead­er­ship roles.

Ross next moved from Michi­gan to UT-South­west­ern, where she led the Can­cer Ge­net­ics Pro­gram and had a lab of her own. She in­ves­ti­gat­ed how cer­tain genes im­pact­ed pa­tients’ risk for can­cer, in­clud­ing the re­la­tion­ship be­tween BR­CA1 and leukemia. In one of the ear­ly it­er­a­tions of Ross’ lab, she went by “Snoop Dog,” be­cause she was so hy­per-vig­i­lant of what every­one was work­ing on that she’d check her re­searchers’ lab note­books at night. When they’d come back to work the next day, Ross would be armed with ques­tions.

“I learned that I was a mi­cro­man­ag­er, and I need­ed to work on that, and I have been work­ing on it ever since,” she con­ced­ed.

Years lat­er, a con­ver­sa­tion with Roger Perl­mut­ter, the for­mer head of Mer­ck Re­search Labs, in­spired her jump to phar­ma. He of­fered her a job work­ing in trans­la­tion­al med­i­cine — a sweet spot for physi­cian-sci­en­tists — and Ross felt it was an op­por­tu­ni­ty she “had to take.” She spent al­most two years at Mer­ck be­fore jump­ing to Am­gen for a year.

In No­vem­ber 2022, Ross joined Ab­b­Vie as the VP of on­col­o­gy ear­ly R&D, veer­ing the com­pa­ny to­ward sol­id tu­mors with the ac­qui­si­tion of Im­muno­Gen. She’s al­so been able to hire new lead­ers on her team and “clean up” some of the ear­ly port­fo­lio. Ross said she’s not con­cerned about mov­ing quick­ly.

“We want to get our drugs to pa­tients soon­er,” she said. “And if we waste time on some­thing that’s not work­ing out, or it’s tox­ic or it’s not ef­fi­ca­cious, that’s bad for pa­tients.” — Max Bay­er

Ed­i­tor’s Note: An Ab­b­Vie spokesper­son clar­i­fied that Ab­b­Vie had been work­ing on sol­id tu­mors be­fore the Im­muno­Gen ac­qui­si­tion.

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Luisa Salter-Cid: Phar­ma vet­er­an builds out Flag­ship’s in-house pipeline of new med­i­cines

For three and a half years, Luisa Salter-Cid has been build­ing out Flag­ship Pi­o­neer­ing’s in-house pipeline of new med­i­cines.

She leads the sci­en­tif­ic charge at Pi­o­neer­ing Med­i­cines, where she brings to­geth­er the R&D en­gines of the Boston-area in­cu­ba­tor’s 40-plus star­tups and cor­rals three big part­ners: No­vo Nordisk, Pfiz­er and the Cys­tic Fi­bro­sis Foun­da­tion.

Salter-Cid is fa­mil­iar with bridg­ing teams. Af­ter work­ing at the hu­man genome re­search com­pa­ny Genset in the ear­ly 2000s, she moved to La Jol­la Phar­ma­ceu­ti­cal and then spent about a dozen years at Bris­tol My­ers Squibb. While at the large phar­ma, she helped in­te­grate the Medarex team (which gave them what would be­come Yer­voy), and even­tu­al­ly moved up to head of im­muno-on­col­o­gy small mol­e­cule work and sci­en­tif­ic lead on Bris­tol My­ers’ deal­mak­ing.

“BMS at that time was prob­a­bly one of the best drug dis­cov­ery com­pa­nies,” Salter-Cid said. She is par­tic­u­lar­ly fond of the com­pa­ny’s TYK2 work, which led to the plaque pso­ri­a­sis pill So­tyk­tu.

“One day we were told by high man­age­ment, ‘Well, the IL-23 an­ti­bod­ies are al­ready out there, so you need to come up with a small mol­e­cule that does the same thing,’” she re­called.

She then went to Gos­samer Bio for a few years be­fore land­ing at Pi­o­neer­ing Med­i­cines in ear­ly 2021. Her team is work­ing on ex­per­i­men­tal drugs for MASH, obe­si­ty, cys­tic fi­bro­sis and oth­er ar­eas be­ing kept un­der wraps. She hopes to give cys­tic fi­bro­sis pa­tients bet­ter treat­ments, as there’s “still a lot of draw­backs from the cur­rent ther­a­pies,” she said.

Salter-Cid en­joys over­see­ing a broad port­fo­lio that goes be­yond her long­time fo­cus on im­munol­o­gy.

“You can­not avoid meta­bol­ics these days,” she said.

Car­dio­vas­cu­lar has al­so be­come an area of in­ter­est for her late­ly. It’s prob­a­bly the most dif­fer­ent from im­munol­o­gy, she said.

“It re­al­ly blows my mind a lit­tle bit, to be hon­est. I like my cells in a Petri dish that we can put to­geth­er and see stuff hap­pen­ing. That’s not go­ing to hap­pen in car­dio­vas­cu­lar,” Salter-Cid said with a laugh. — Kyle LaHu­cik

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Nia Tat­sis: Ver­tex’s chief reg­u­la­to­ry of­fi­cer on how FDA is evolv­ing

Nia Tat­sis has been with Ver­tex Phar­ma­ceu­ti­cals for sev­en years and was pro­mot­ed to chief reg­u­la­to­ry and qual­i­ty of­fi­cer in 2019. Tat­sis is al­so a board mem­ber at car­dio­vas­cu­lar dis­ease gene edit­ing com­pa­ny Verve Ther­a­peu­tics. She was born in Athens, Greece, but im­mi­grat­ed with her fam­i­ly to the US out­side of Philadel­phia when she was a year old.

This in­ter­view has been edit­ed sub­stan­tial­ly for length and clar­i­ty.

Lei Lei Wu: Part of your job in­volves work­ing with the FDA, so I’m cu­ri­ous what your thoughts are on how the FDA is chang­ing.

Nia Tat­sis: There’s CDER [Cen­ter for Drug Eval­u­a­tion and Re­search] and there’s CBER [Cen­ter for Bi­o­log­ics Eval­u­a­tion and Re­search]. CDER al­ways felt, when I start­ed, like the most reg­i­ment­ed. They knew ex­act­ly how they want­ed things done, and what they want­ed. CBER, when I start­ed at vac­cine [at Wyeth], they were open to just meet­ing with us a lot.

CBER now is a dif­fer­ent beast al­to­geth­er. Now, as we’ve all moved in­to bi­o­log­ics, they have to learn sci­ence very quick­ly. They have to make some re­al­ly big de­ci­sions in the ab­sence of hav­ing the abil­i­ty to sit down with us and go through it, as much as I used to have the plea­sure of do­ing, 10, 15, 20 years ago.

They’ve be­come much more like CDER. It’s a lit­tle bit more reg­i­ment­ed.

Wu: You re­cent­ly joined Verve’s board. How did that con­ver­sa­tion come about, and what are your per­son­al thoughts on what Verve is work­ing on? I feel like peo­ple have very dif­fer­ent opin­ions on do­ing gene edit­ing for a very com­mon dis­ease.

Tat­sis: Be­fore I joined [Ver­tex], I did the an­ti-PC­SK9 that Sanofi was de­vel­op­ing with Re­gen­eron — Pralu­ent. I re­mem­ber sit­ting and talk­ing and lis­ten­ing to the pa­tients that came through the ad­vi­so­ry com­mit­tee [for Pralu­ent], and these folks have heart at­tacks. Those folks who have hy­per­c­ho­les­terolemia, many don’t know they have it. It’s a silent dis­ease. And it’s a re­al­ly im­por­tant dis­ease.

I spoke to a re­cruiter like you nor­mal­ly do. Verve was one of the com­pa­nies that kept com­ing up.

For the rare dis­eases that we’ve been work­ing on, maybe it’s an eas­i­er way to think about CRISPR gene ther­a­py. But sci­ence is go­ing to evolve. And the way it’s go­ing to evolve is it’s not al­ways go­ing to be a small mol­e­cule, it’s not al­ways go­ing to be a pill, and maybe a one-and-done is the way to go.

I think Verve has the right idea. I think their sci­ence is amaz­ing­ly strong. I think their lead­er­ship is strong. Do you know Sek [Kathire­san]?

Wu: I’ve met him a cou­ple times.

Tat­sis: I think if you spend 10 min­utes talk­ing to Sek, you’re con­vert­ed. It’s be­cause of the pas­sion he feels for what he’s do­ing and the deep knowl­edge that he has. So it wasn’t a hard de­ci­sion at all.

Wu: What is your per­spec­tive on how the po­si­tion of women in the in­dus­try has evolved or changed, if at all, since you’ve joined?

Tat­sis: It’s evolved. First, I would say, Ver­tex does it so well: Resh­ma [Ke­wal­ra­mani] be­ing the CEO. Be­fore she was the CEO, she was promi­nent­ly do­ing amaz­ing work. [For­mer CEO] Jeff [Lei­den] be­fore Resh­ma was com­mit­ted to en­sur­ing that women are well-rep­re­sent­ed. If you look at our ex­ec­u­tive team, or if you look at our board, I think you’d see that.

But there are dif­fer­ent ways dif­fer­ent com­pa­nies think about it.

One of the rea­sons I want­ed to come to Ver­tex … There were women in lead­er­ship and every­one was treat­ed pret­ty equal­ly. I didn’t feel like I was a woman in­ter­view­ing for a job. I just felt like I was an­oth­er can­di­date — that re­al­ly mat­tered. I don’t know that I al­ways felt that way at oth­er places. There wasn’t any­thing overt, but I felt like here it was not even a dis­cus­sion.

I don’t know that oth­er com­pa­nies have evolved. I’m not there. But if you look across se­nior lead­ers — if I look at Sanofi, and I’m not say­ing it in a bad way, I don’t know who they have now, but when I was there — there re­al­ly weren’t se­nior lead­ers who were women. There were a few.

Here, you can’t help but no­tice that we have a lot of strong and im­por­tant women who have a lot to say and are re­al­ly mak­ing changes. I get to learn watch­ing them, and hope­ful­ly some­one learns watch­ing me. — Lei Lei Wu

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Becky Taub: How a ‘go­ing-away present’ led to the first ap­proval for a vex­ing liv­er dis­ease

Sci­en­tists and clin­i­cians didn’t quite un­der­stand the sever­i­ty of a liv­er dis­ease called non­al­co­holic steato­hep­ati­tis (NASH) more than 20 years ago. But even then, Becky Taub knew it would be an im­por­tant dis­ease to treat.

Up to 5% of Amer­i­cans are es­ti­mat­ed to have NASH, a dis­ease al­so re­ferred to as meta­bol­ic dys­func­tion-as­so­ci­at­ed steato­hep­ati­tis (MASH) that can progress to se­vere scar­ring or cir­rho­sis of the liv­er. For years, the stan­dard of care was di­et and ex­er­cise. Taub led a team of sci­en­tists at Madri­gal Phar­ma­ceu­ti­cals to the field’s first drug ap­proval in March, a cru­cial mile­stone for pa­tients.

The sto­ry starts with a shelved Roche can­di­date, an in­op­por­tune job of­fer and a valu­able “go­ing-away present.”

Taub left a po­si­tion at the Uni­ver­si­ty of Penn­syl­va­nia in 2000 to pur­sue a ca­reer in the phar­ma­ceu­ti­cal in­dus­try. She land­ed at Roche in 2004, where resme­tirom was dis­cov­ered as a po­ten­tial meta­bol­ic can­di­date for clin­i­cal de­vel­op­ment. But sci­en­tists had al­ready writ­ten it off be­cause when they dosed an­i­mals, they didn’t see very high lev­els of the mol­e­cule cir­cu­lat­ing in the blood.

“When I looked at it, I said, ‘Well, maybe that’s be­cause it’s go­ing to the liv­er,’” Taub said. “We had in the back of our minds that there was a fat­ty liv­er dis­ease and it might be good for that.”

They al­so hy­poth­e­sized that it would be good at low­er­ing cho­les­terol and oth­er lipids that cause heart dis­ease. Taub and her team re­vis­it­ed the can­di­date, work­ing on it for four years un­til Roche re­or­ga­nized. The new job Roche had for Taub was in Basel, Switzer­land, which she said “wasn’t some­thing I want­ed to do at the time.”

So for “not much mon­ey,” she li­censed resme­tirom and re­lat­ed mol­e­cules and even­tu­al­ly found­ed Madri­gal in Sep­tem­ber 2011.

“I called it a go­ing-away present,” Taub jokes.

Mean­while, sci­en­tists chipped away at the vex­ing liv­er dis­ease. In­ter­cept Phar­ma­ceu­ti­cals’ pi­o­neer­ing obeti­cholic acid stirred up a surge of in­ter­est around NASH in the in­vestor and med­ical com­mu­ni­ties, but the ther­a­py was re­ject­ed by the FDA last year over safe­ty is­sues.

Bill Si­bold, now Madri­gal’s CEO, would go on to call NASH a “ver­i­ta­ble grave­yard of drug de­vel­op­ment.” There was lit­tle recog­ni­tion for the dis­ease and no des­ig­nat­ed reg­u­la­to­ry path.

“The hard­est things were ear­ly on,” Taub said. “We had a cer­tain amount of mon­ey that was com­ing from a sin­gle fund, and you have to make that go a long way.”

When Madri­gal was first found­ed, Taub was es­sen­tial­ly both CEO and chief med­ical of­fi­cer. The com­pa­ny was still fo­cused on resme­tirom’s lipid-low­er­ing ef­fects at the time. Madri­gal of­fi­cial­ly piv­ot­ed to NASH in 2014, when it had non­clin­i­cal, clin­i­cal and tox­i­col­o­gy da­ta to sup­port a Phase 2 tri­al in NASH.

Resme­tirom was ap­proved in March as Rezd­if­fra. Madri­gal said on its most re­cent earn­ings call that it’s “mak­ing great progress” on the launch. Jef­feries an­a­lysts pre­dict­ed in March that Rezd­if­fra sales could reach $3.4 bil­lion across the US and Eu­rope. The fo­cus now is ex­pan­sion.

“A lot of our pre­scribers are not aware of NASH and I think that that’s a big chal­lenge,” Taub said.

Look­ing back, Taub said she was al­ways “su­per-in­ter­est­ed in NASH,” even be­fore the in­dus­try knew much about the dis­ease. “It was a good di­rec­tion for me.” — Nicole De­Feud­is

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Michelle Wern­er: Her son was di­ag­nosed with Duchenne. That changed every­thing

It was a PE teacher at a school in Stock­holm who sug­gest­ed that Michelle Wern­er and her hus­band bring their son to see a doc­tor once they moved back to the US.

Wern­er, then an ex­ec­u­tive at As­traZeneca, was mov­ing with her fam­i­ly to Mary­land to take a new post head­ing the com­pa­ny’s hema­tol­ogy fran­chise. It was De­cem­ber 2019, and Wern­er’s son Caf­frey, 9 at the time, was get­ting up off the floor in an un­usu­al way. They now know that’s called the Gow­er ma­neu­ver — a re­sult of mus­cle weak­ness and of­ten a sign of Duchenne mus­cu­lar dy­s­tro­phy. In Wash­ing­ton, DC, the fam­i­ly went to Chil­dren’s Na­tion­al Hos­pi­tal.

“Right away, when we were in that ap­point­ment with the neu­rol­o­gist, she said, ‘I can tell you right now, Caf­frey has mus­cu­lar dy­s­tro­phy,’” Wern­er said. She re­flect­ed back to the be­gin­ning of her son’s life, when he start­ed miss­ing gross mo­tor skill mile­stones like rolling over and sit­ting at around six months old. At the time, he was di­ag­nosed with hy­po­to­nia, or low mus­cle tone, but doc­tors said he would even­tu­al­ly catch up with his peers.

On Caf­frey’s 10th birth­day, ge­net­ic test re­sults con­firmed he had Duchenne mus­cu­lar dy­s­tro­phy. Wern­er, hav­ing worked in the phar­ma in­dus­try for two decades, im­me­di­ate­ly went search­ing for clin­i­cal tri­als of in­ves­ti­ga­tion­al ther­a­pies for Duchenne.

“Caf­frey was el­i­gi­ble for ze­ro of these clin­i­cal tri­als be­cause he had the wrong mu­ta­tion, or he was too old al­ready at 10 years old, or he was too am­bu­la­to­ry,” she said. “It was an im­pos­si­ble idea to me that there was re­al­ly noth­ing that was be­ing done or could be done for my kid, and as some­body who has re­al­ly ded­i­cat­ed their ca­reer to try­ing to ad­dress some very, very chal­leng­ing dis­eases.”

Wern­er and her hus­band fell in­to what she calls a “black hole pe­ri­od” for a few months. “You re­al­ize that every­thing that you thought about your kids’ fu­ture, your fam­i­ly’s fu­ture, might not be re­al any­more, and that we might be fac­ing a com­plete­ly dif­fer­ent re­al­i­ty as a re­sult of this di­ag­no­sis,” she said.

It’s now been more than four years since Caf­frey’s di­ag­no­sis. Com­bat­ing rare dis­ease has be­come both Wern­er’s per­son­al mis­sion and her ca­reer.

In 2022, she be­came a CEO-part­ner at Flag­ship Pi­o­neer­ing, the ven­ture firm be­hind Mod­er­na, to lead a start­up fo­cused on har­ness­ing trans­fer RNA, or tR­NA for short. Known as All­tr­na, the com­pa­ny’s chas­ing a holy grail ther­a­py that can be used across a host of rare dis­eases to re­store func­tion­al pro­tein pro­duc­tion. The com­pa­ny isn’t work­ing specif­i­cal­ly on Duchenne. All­tr­na’s still in the ear­ly phas­es and has not yet said when it will have an ex­per­i­men­tal treat­ment ready for hu­man stud­ies.

“In the 20 years that I’d ded­i­cat­ed to drug de­vel­op­ment so far, it had all been fo­cused on on­col­o­gy,” Wern­er said. “I want­ed to spend the next 20 years of my ca­reer fo­cus­ing on rare dis­eases.”

For Caf­frey, Wern­er’s fam­i­ly has been pur­su­ing an n-of-1 treat­ment with Cure Rare Dis­ease, a non-prof­it start­ed by Rich Hor­gan, whose broth­er had Duchenne, to de­vel­op new treat­ments for rare and ul­tra-rare dis­eases. For a treat­ment for Caf­frey’s Duchenne mu­ta­tion, re­search in mice is be­ing con­duct­ed with Sick­Kids in Toron­to.

When the first Duchenne gene ther­a­py from Sarep­ta Ther­a­peu­tics was grant­ed a broad la­bel by the FDA in June (and not with­out con­tro­ver­sy), Wern­er’s fam­i­ly had a de­ci­sion to make. Caf­frey’s mu­ta­tion of Duchenne en­ables him to pro­duce 1% to 2% of dy­s­trophin on his own, which may be why he was di­ag­nosed lat­er than what’s typ­i­cal for Duchenne, Wern­er said, and there are no an­swers around how nat­ur­al dy­s­trophin and mi­crody­s­trophin — which is what is made with the gene ther­a­py — in­ter­act.

Caf­frey, who re­cent­ly start­ed high school, al­so weighed in on the fi­nal de­ci­sion, say­ing he did not want the gene ther­a­py now. And af­ter con­sult­ing with ex­perts, Wern­er con­clud­ed that the fam­i­ly should not pur­sue Sarep­ta’s gene ther­a­py Ele­v­idys for Caf­frey. “There is no right an­swer. There is maybe no wrong an­swer. There is on­ly any per­son’s in­di­vid­ual an­swer, and we just have to get com­fort­able with that,” Wern­er said.

Mean­while in her day job at All­tr­na, Wern­er hopes to in­ject the ur­gency she feels as a rare dis­ease par­ent in­to her team.

“We need to take a ‘many dis­eases at a time’ strat­e­gy if we are go­ing to be able to help as many pa­tients as pos­si­ble,” Wern­er said. “Oth­er­wise, so many of these dis­eases would have no in­no­va­tion what­so­ev­er, be­cause on­ly a hand­ful of them that are maybe the most preva­lent would get the at­ten­tion of, for ex­am­ple, the phar­ma com­pa­nies that I had been work­ing with in my ca­reer up un­til that point.

“There are over 6,000 rare ge­net­ic dis­eases, and when we’re try­ing to tack­le 6,000 dis­eases, one dis­ease at a time, it will take thou­sands of years for us to make a dent in all of them,” she said. “This is some­thing that I re­al­ized as a par­ent: the im­por­tance of time and mak­ing progress as quick­ly as pos­si­ble is crit­i­cal, be­cause pa­tients re­al­ly do not have time to wait. It’s a race against the clock.” — Lei Lei Wu