Tadataka Yamada (Photographer: Kiyoshi Ota/Bloomberg via Getty Images)

Sci­ence pi­o­neer, phar­ma re­search chief, glob­al health ad­vo­cate and biotech en­tre­pre­neur Tadata­ka ‘Tachi’ Ya­ma­da has died

Tadata­ka Ya­ma­da, a tow­er­ing physi­cian-sci­en­tist who made his name in acad­e­mia be­fore trans­form­ing drug de­vel­op­ment at Glax­o­SmithK­line and de­vel­op­ing vac­cines for malar­ia and menin­gi­tis at the Gates Foun­da­tion, died un­ex­pect­ed­ly of nat­ur­al caus­es at his home in Seat­tle Wednes­day morn­ing.

He was 76. Fra­zier Health­care Part­ners’ David Socks con­firmed his death.

Known wide­ly by the mononym “Tachi,” Ya­ma­da had a glo­be­trot­ting ca­reer and ar­rived in in­dus­try rel­a­tive­ly late in life. A 2004 In­de­pen­dent ar­ti­cle not­ed GSK had asked Ya­ma­da to stay on be­yond his ap­proach­ing 60th birth­day, the com­pa­ny’s usu­al re­tire­ment age. Ya­ma­da would con­tin­ue work­ing for the next 17 years, steer­ing the Gates Foun­da­tion’s glob­al health di­vi­sion for 6 years, fund­ing Jim Wil­son’s gene ther­a­py work when few would touch it, launch­ing Take­da Vac­cines and co-found­ing a se­ries of high-pro­file biotechs.

Trib­utes to Ya­ma­da poured out Thurs­day night from a wide range of promi­nent fig­ures from for­mer Pres­i­dent Bill Clin­ton to Al­ny­lam CEO John Maraganore, re­flect­ing on Ya­ma­da’s work as a soft-spo­ken men­tor, his in­flu­ence across biotech R&D and fas­tid­i­ous, un­spar­ing de­fense of pub­lic health.

“Dr. Tachi Ya­ma­da was an ex­tra­or­di­nary sci­en­tist and leader who used his bril­liant mind and kind, good heart to im­prove the lives of mil­lions of peo­ple,” Clin­ton, who worked with Ya­ma­da at the HIV-fo­cused Clin­ton Health Ac­cess Ini­tia­tive, said in a state­ment. “Tachi brought a world of ex­pe­ri­ence, knowl­edge, and good judge­ment to CHAI. He in­spired us all to help more peo­ple and save more lives.”

Nim­bus CEO Jeb Keiper called him a “ti­tan of R&D.” Pe­ter Hotez, the promi­nent vac­ci­nol­o­gist for ne­glect­ed trop­i­cal dis­ease, said “he had a great vi­sion for glob­al health, and will be great­ly missed.”

Pe­ter A. Singer, spe­cial ad­vi­sor to WHO chief Tedros Ad­hanom Ghe­breye­sus, shared an ex­cerpt from his book re­call­ing Ya­ma­da’s ear­ly days as pres­i­dent of glob­al health at the Gates Foun­da­tion, where he pushed sci­en­tists to pro­duce tan­gi­ble re­sults from the “Grand Chal­lenges” strat­e­gy, an ef­fort to back new so­lu­tions to glob­al crises like HIV or tu­ber­cu­lo­sis.

“This high­ly fo­cused man was clear­ly chang­ing the grand chal­lenges strat­e­gy from straight dis­cov­er to ‘show me the goods,'” Singer wrote.

Born in Japan, Ya­ma­da was sent by his fa­ther to board­ing school in An­dover, Mass­a­chu­setts and stud­ied at Stan­ford be­fore land­ing at NYU for med­ical school. The US Army Med­ical Re­search In­sti­tute of In­fec­tious Dis­eases at Fort De­t­rick, MD gave him a lab af­ter he fin­ished res­i­den­cy and, though he lat­er said he had known lit­tle about how to even do re­search, he be­gan learn­ing pro­tein chem­istry and try­ing to un­der­stand the role of small pep­tides in the body.

Af­ter a fel­low­ship, he end­ed up at the Uni­ver­si­ty of Michi­gan, re­cruit­ed by Bill Kel­ley, the same chair­man of med­i­cine who re­cruit­ed Jef­frey Lei­den, Gary Nabel and a se­ries of oth­er sci­en­tists who be­came promi­nent in acad­e­mia and biotech. He soon be­came head of gas­troen­terol­o­gy and stayed for 13 years, ris­ing to be­come the school’s chair­man of med­i­cine, un­til a head­hunter called on be­half of a drug­mak­er then known as Beecham SmithK­line.

Ya­ma­da had turned down nu­mer­ous of­fers to be a vice pres­i­dent of this or that, but he soon be­came en­thralled with the in­tel­lec­tu­al chal­lenge of mak­ing med­i­cines: How much could go wrong, and the supreme pay­off when things went right.

Af­ter SmithK­line merged with Glaxo to form GSK in 2001, Ya­ma­da rose to chair­man of R&D and be­came fa­mous for over­haul­ing the way the com­pa­ny de­vel­oped drugs. To pre­vent bu­reau­crat­ic bloat, he stripped the phar­ma down in­to small­er labs — 400-per­son max — that would op­er­ate with the mind­set, com­mit­ment and hus­tle of biotech star­tups, de­vel­op­ing mol­e­cules from dis­cov­ery to clin­i­cal test­ing. The num­ber of com­pounds in GSK’s pipeline soon dou­bled.

He al­so earned a name for hold­ing phar­ma to a high­er stan­dard. Af­ter the merg­er, GSK, one of the world’s lead­ing sell­ers of HIV meds, sued Nel­son Man­dela and the South African gov­ern­ment over how the coun­try priced the HIV drugs. “‘That shocked and em­bar­rassed me and made me won­der what I was do­ing in the com­pa­ny,” Ya­ma­da told JCI. “I told the board of di­rec­tors I thought we should ac­tu­al­ly be mak­ing med­i­cines for peo­ple who need them.”

He con­vinced them to set up a lab­o­ra­to­ry to fo­cus on vac­cines for ma­jor pub­lic health crises, such as tu­ber­cu­lo­sis and malar­ia. That work was fund­ed in part by the Gates Foun­da­tion, which in 2006 of­fered Ya­ma­da a po­si­tion as pres­i­dent of glob­al health. There, he helped de­vel­op and de­ploy the MenAfriVac, a 50-cent-per-dose menin­gi­tis vac­cine that could be wide­ly de­ployed across Africa.

In 2013, Take­da brought Ya­ma­da back to in­dus­try as CSO and CMO. He promised to in­ject a sense of “ur­gency” in the drug­mak­er, long a lag­gard be­hind the big phar­mas. He helped de­vel­op the ul­cer­a­tive col­i­tis drug En­tyvio and per­son­al­ly over­saw the launch of Take­da Vac­cines, a di­vi­sion that is now help­ing man­u­fac­ture No­vavax’s Covid-19 shot and near­ing com­ple­tion of the sec­ond-ever vac­cine for dengue fever, a long-ne­glect­ed mos­qui­to-borne virus.

In his lat­er ca­reer, he be­came a ven­ture part­ner at Fra­zier Health­care Part­ners and co-found­ed a se­ries of com­pa­nies, in­clud­ing the GI spe­cial­ist Phath­om and the vac­cine play­er Hill­e­Vax, both Take­da spin­outs.

Per­haps most no­tably, he teamed up with Wil­son, whom he had first men­tored at the Uni­ver­si­ty of Michi­gan. Af­ter Jesse Gelsinger’s death in 1999, few in in­dus­try or acad­e­mia want­ed to work with Wil­son or with any­thing hav­ing to do with gene ther­a­py.

Ya­ma­da, though, felt that Wil­son and oth­er re­searchers had been un­fair­ly de­mo­nized. “I hate that kind of thing,” he lat­er said, and lob­bied skep­tics at GSK to fund Wil­son with just un­der $30 mil­lion over the next decade. The mon­ey helped keep Wil­son’s lab alive as they de­vel­oped new tech­nol­o­gy that al­lowed gene ther­a­py to be de­liv­ered far more safe­ly, help­ing bring about a re­birth in the field and the US’ sec­ond-ever ap­proved gene ther­a­py, Zol­gens­ma, for a rare and once-fa­tal ge­net­ic dis­ease.

In the last 3 years, the pair found­ed 2 com­pa­nies, Pas­sage Bio and G2Bio, to ad­vance those ef­forts fur­ther. Pas­sage now has 2 ther­a­pies in the clin­ic, with 5 more in de­vel­op­ment. G2Bio is try­ing to ad­vance gene ther­a­pies for larg­er, more com­mon and com­plex dis­eases.

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

Lat­est news on Pfiz­er's $3B+ JAK1 win; Pacts over M&A at #JPM22; 2021 by the num­bers; Bio­gen's Aduhelm reck­on­ing; The sto­ry of sotro­vimab; and more

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For those of you who attended #JPM22 in any shape or form, we hope you had a fruitful time. Regardless of how you spent the past hectic week, may your weekend be just what you need it to be.

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