At the cen­ter of a glob­al tem­pest, Jiankui He de­fends edit­ing the genes of 2 new­borns

HONG KONG — Fac­ing a storm of crit­i­cism from some of the med­ical world’s best known ex­perts and un­der in­ves­ti­ga­tion by Chi­nese of­fi­cials for pro­duc­ing the world’s first gene-edit­ed ba­bies in a self-fund­ed ex­per­i­ment that has spurred head­lines around the world, Jiankui He took to the cen­ter stage of a promi­nent sci­en­tif­ic con­fer­ence in Hong Kong to de­fend his work.

Calm­ly and clear­ly, He out­lined his project us­ing CRISPR to dis­able a key gene in or­der to con­fer im­mu­ni­ty to HIV for the new­borns — who were ex­posed to the threat by an HIV-pos­i­tive par­ent — and of­fered an apol­o­gy as the news that he had al­tered em­bryos “leaked un­ex­pect­ed­ly” be­fore he could present it at a sci­en­tif­ic venue.

But the sci­en­tist al­so in­sist­ed he was proud of what he’s done for the fam­i­ly, adding that he’s al­so sub­mit­ted the study to a sci­en­tif­ic jour­nal for re­view — which might clear up some of the lin­ger­ing ques­tions that came up af­ter he ap­peared in front of a packed hall Wednes­day.

“The first ques­tion was whether CCR5 is an un­met med­ical need,” He told the crowd in the Q&A part of the pre­sen­ta­tion. “I ac­tu­al­ly be­lieve that this is not just for this case, but for mil­lions of chil­dren. They need this pro­tec­tion. HIV vac­cine is not avail­able. I per­son­al­ly ex­pe­ri­ence with some peo­ple in AIDS where 30% of a vil­lage peo­ple are in­fect­ed. They even have to give their chil­dren to rel­a­tives and un­cles to raise just to pre­vent po­ten­tial trans­mis­sion. For this spe­cif­ic case, I feel proud. I feel proud­est, be­cause they had lost hope for life.”

The sci­en­tist not­ed that it would be il­le­gal to re­veal the iden­ti­ties of the fa­ther of Lu­lu and Nana, the twins at the cen­ter of the con­tro­ver­sial tri­al. Born a few weeks ago to an HIV-pos­i­tive fa­ther and HIV-neg­a­tive moth­er, their genomes were al­tered by CRISPR-Cas9 while they were still em­bryos such that the CCR5 gene was dis­abled or short­ened.

Ap­pear­ing at the Sec­ond In­ter­na­tion­al Sum­mit on Hu­man Genome Edit­ing, He de­tailed the var­i­ous rounds of se­quenc­ing, can­cer gene blood test, and pre-im­plan­ta­tion ge­net­ic di­ag­no­sis he con­duct­ed be­fore, dur­ing and af­ter the preg­nan­cy — all paid for by him­self. All 59 of He’s pre­sen­ta­tion slides can be found on this Google dri­ve.

No­tably, one off-tar­get ef­fect was de­tect­ed in “the meg-based in­ter­genic re­gion far from oth­er genes, with no cod­ing RNA and no tran­scrip­tion fac­tor by their sides,” he said.

“The vol­un­teers were in­formed of the risk posed by this one ex­ist­ing off-tar­get, and they de­cid­ed to im­plant,” he added, re­fer­ring to the par­ents of Lu­lu and Nana whom he de­scribed a cou­ple of times as “very well ed­u­cat­ed.” By the 19th week of ges­ta­tion, the off-tar­get was no longer ob­served, ac­cord­ing to He.

He al­so re­vealed that there was one oth­er “po­ten­tial preg­nan­cy,” al­though the tri­al — in­volv­ing sev­en cou­ples to­tal — has been halt­ed in light of the cur­rent sit­u­a­tion. When pressed, He said 30 blas­to­cysts were de­vel­oped, 70% of which were edit­ed, but didn’t pro­vide fur­ther de­tails on the full scope of the study.

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Amid the swath of in­quiries di­rect­ed at He, three lines of ques­tions cap­tured` the most in­tense in­ter­est of the sci­en­tists present: trans­paren­cy, med­ical need and the choice of gene.

The first ques­tion has to do with se­cre­cy and lack of feed­back from fel­low aca­d­e­mics. While He main­tained he en­gaged with both sci­en­tists and ethi­cists about his tri­al (with UC Berke­ley re­searcher Mark De­Witt con­firm­ing to STAT  he knew of the plan and ad­vised He against it) on­ly four peo­ple re­viewed the in­formed con­sent form pro­vid­ed to pa­tients.

That would be unimag­in­able in the US, where hun­dreds of re­view­ers would like­ly be in­volved for a tri­al like this, com­ment­ed Stan­ford Med­i­cine pro­fes­sor Matt Por­teus af­ter the event. Por­teus was one of two pan­elists charged with ask­ing He ques­tions on stage be­fore open­ing up to the floor.

“In gen­er­al peo­ple talk about their plans years in ad­vance: Here’s what we plan to do, here’s why,” Por­teus said. “I don’t think he’s talked or lis­tened to enough peo­ple about this,” adding that as a par­tic­i­pant at some of the pre­vi­ous con­fer­ences He spoke at, there was no hint the Chi­nese re­searcher was plan­ning to jus­ti­fy a hu­man clin­i­cal tri­al based on the da­ta pre­sent­ed.

Sec­ond­ly, there were con­cerns over whether the whole ef­fort was worth­while. David Bal­ti­more, chair of the sum­mit, said point blank in his brief re­mark: “I per­son­al­ly don’t think it was med­ical­ly nec­es­sary” — a com­ment echoed by CRISPR pi­o­neer David Liu, who point­ed out sperm wash­ing could be suf­fi­cient for gen­er­at­ing un­in­fect­ed em­bryos.

In re­sponse, He said the key here is not just giv­ing birth to un­in­fect­ed ba­bies but en­sur­ing pro­tec­tion against HIV in the fu­ture, giv­en that no HIV vac­cine is cur­rent­ly avail­able.

The third ma­jor ques­tion has to with the un­der­stand­ing of CCR5, as it’s been sug­gest­ed that de­fi­cien­cy of the gene may make peo­ple vul­ner­a­ble to oth­er in­fec­tions like West Nile and in­fluen­za virus­es and have ef­fects on the im­mune sys­tem and cog­ni­tion.

He said ear­ly in his talk that CCR5 is “one of the most stud­ied vari­a­tions, and it’s one of the most well un­der­stood genes.” Vol­un­teers were aware of some of the risks, he added, and more ver­i­fi­ca­tion is need­ed for new­er re­search on the gene.

He’s plan is to fol­low up with the twin girls for at least 10 phys­i­cal ex­am­i­na­tions un­til they are 18, at which point it would be up to them whether they would like to con­tin­ue to be mon­i­tored. It is un­clear, how­ev­er, whether he will be able to do so as he’s un­der in­ves­ti­ga­tion by the lo­cal health com­mis­sions and be­ing dis­tanced by the in­sti­tu­tions he used to be af­fil­i­at­ed with.

The South­ern Uni­ver­si­ty of Sci­ence and Tech­nol­o­gy, which He said did not know about his plan, re­leased a state­ment say­ing the pro­fes­sor had been sus­pend­ed with­out pay since Feb­ru­ary. The Har­Moni­Care Shen­zhen Women and Chil­dren’s Hos­pi­tal — where He sup­pos­ed­ly con­duct­ed the IVF pro­ce­dures — de­nied in­volve­ment and said it has asked the po­lice to in­ves­ti­gate.

His last ques­tion:

“If this was go­ing to be your ba­by, would you have gone ahead with this?

“That’s a good ques­tion. If it was my ba­by, with the same sit­u­a­tion, yes I would try first.”

Top: Jiankui He. Bot­tom left to right: Robin Lovell-Badge, Jiankui He, and Matt Por­teus. AM­BER TONG, END­POINTS NEWS

In starved an­tibi­ot­ic field, Melin­ta soars as FDA grants speedy drug re­view

Such is the state of af­fairs in an­tibi­ot­ic land that the FDA agree­ing to pri­or­i­ty re­view an ap­pli­ca­tion to ex­pand the use of an an­tibi­ot­ic can rock­et up a stock more than two-fold.

On Wednes­day, Melin­ta Ther­a­peu­tics said its ap­proved an­tibi­ot­ic Baxdela had been grant­ed pri­or­i­ty re­view for use in com­mu­ni­ty-ac­quired bac­te­r­i­al pneu­mo­nia (CAPB). The FDA is ex­pect­ed to make its de­ci­sion by Oc­to­ber 24. Shares of the Con­necti­cut drug­mak­er $ML­NT cat­a­pult­ed, clos­ing up near­ly 224% at $6.41.

Brent Saunders at an Endpoints News event in 2017 — File photo

An­a­lyst call with Al­ler­gan ex­ecs stokes an­tic­i­pa­tion of a plan to split the com­pa­ny in ‘a month or two’

So what’s up at Al­ler­gan?

Ear­li­er this week the ubiq­ui­tous Ever­core ISI an­a­lyst Umer Raf­fat was on the line with com­pa­ny ex­ec­u­tives to probe in­to the lat­est on the num­bers as well as CEO Brent Saun­ders’ re­cent de­c­la­ra­tion that he’d be do­ing some­thing de­fin­i­tive to help long-suf­fer­ing in­vestors who have watched their shares dwin­dle in val­ue.

He came away with the im­pres­sion that a sig­nif­i­cant com­pa­ny split is on the way. And not on some dis­tant time hori­zon.

The top 10 block­buster drugs in the late-stage pipeline — Eval­u­ate adds 6 new ther­a­pies to heavy-hit­ter list

Vertex comes in for a substantial amount of criticism for its no-holds-barred tactical approach toward wresting the price it wants for its commercial drugs in Europe. But the flip side of that coin is a highly admired R&D and commercial operation that regularly wins kudos from analysts for their ability to engineer greater cash flow from the breakthrough drugs they create.

Both aspects needed for success in this business are on display in the program backing Vertex’s triple for cystic fibrosis. VX-659/VX-445 + Tezacaftor + Ivacaftor — it’s been whittled down to 445 now — was singled out by Evaluate Pharma as the late-stage therapy most likely to win the crown for drug sales in 5 years, with a projected peak revenue forecast of $4.3 billion.

The latest annual list, which you can see here in their latest world preview, includes a roster of some of the most closely watched development programs in biopharma. And Evaluate has added 6 must-watch experimental drugs to the top 10 as drugs fail or go on to a first approval. With apologies to the list maker, I revamped this to rank the top 10 by projected 2024 sales, instead of Evaluate's net present value rankings.

It's how we roll at Endpoints News.

Here is a quick summary of the rest of the top 10:

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How small- to mid-sized biotechs can adopt pa­tient cen­tric­i­ty in their on­col­o­gy tri­als

By Lucy Clos­sick Thom­son, Se­nior Di­rec­tor of On­col­o­gy Pro­ject Man­age­ment, Icon

Clin­i­cal tri­als in on­col­o­gy can be cost­ly and chal­leng­ing to man­age. One fac­tor that could re­duce costs and re­duce bar­ri­ers is har­ness­ing the pa­tient voice in tri­al de­sign to help ac­cel­er­ate pa­tient en­roll­ment. Now is the time to adopt pa­tient-cen­tric strate­gies that not on­ly fo­cus on pa­tient needs, but al­so can main­tain cost ef­fi­cien­cy.

John Reed at JPM 2019. Jeff Rumans for Endpoints News

Sanofi's John Reed con­tin­ues to re­or­ga­nize R&D, cut­ting 466 jobs while boost­ing can­cer, gene ther­a­py re­search

The R&D reorganization inside Sanofi is continuing, more than a year after the pharma giant brought in John Reed to head the research arm of the Paris-based company.
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John Chiminski, Catalent CEO - File Photo

'It's a growth play': Catal­ent ac­quires Bris­tol-My­er­s' Eu­ro­pean launch pad, ex­pand­ing glob­al CD­MO ops

Catalent is staying on the growth track.

Just two months after committing $1.2 billion to pick up Paragon and take a deep dive into the sizzling hot gene therapy manufacturing sector, the CDMO is bouncing right back with a deal to buy out Bristol-Myers’ central launchpad for new therapies in Europe, acquiring a complex in Anagni, Italy, southwest of Rome, that will significantly expand its capacity on the continent.

There are no terms being offered, but this is no small deal. The Anagni campus employs some 700 staffers, and Catalent is planning to go right in — once the deal closes late this year — with a blueprint to build up the operations further as they expand on oral solid, biologics, and sterile product manufacturing and packaging.

This is an uncommon deal, Catalent CEO John Chiminski tells me. But it offers a shortcut for rapid growth that cuts years out of developing a green fields project. That’s time Catalent doesn’t have as the industry undergoes unprecedented expansion around the world.

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Arc­turus ex­pands col­lab­o­ra­tion, adding $30M cash; Ku­ra shoots for $100M raise

→  Rare dis­ease play­er Ul­tragenyx $RARE is ex­pand­ing its al­liance with Arc­turus $ARCT, pay­ing $24 mil­lion for eq­ui­ty and an­oth­er $6 mil­lion in an up­front as the two part­ners ex­pand their col­lab­o­ra­tion to in­clude up to 12 tar­gets. “This ex­pand­ed col­lab­o­ra­tion fur­ther so­lid­i­fies our mR­NA plat­form by adding ad­di­tion­al tar­gets and ex­pand­ing our abil­i­ty to po­ten­tial­ly treat more dis­eases,” said Emil Kakkis, the CEO at Ul­tragenyx. “We are pleased with the progress of our on­go­ing col­lab­o­ra­tion. Our most ad­vanced mR­NA pro­gram, UX053 for the treat­ment of Glyco­gen Stor­age Dis­ease Type III, is ex­pect­ed to move in­to the clin­ic next year, and we look for­ward to fur­ther build­ing up­on the ini­tial suc­cess of this part­ner­ship.”

UP­DAT­ED: Chica­go biotech ar­gues blue­bird, Third Rock 'killed' its ri­val, pi­o­neer­ing tha­lassemia gene ther­a­py in law­suit

Blue­bird bio $BLUE chief Nick Leschly court­ed con­tro­ver­sy last week when he re­vealed the com­pa­ny’s be­ta tha­lassemia treat­ment will car­ry a jaw-drop­ping $1.8 mil­lion price tag over a 5-year pe­ri­od in Eu­rope — mak­ing it the plan­et’s sec­ond most ex­pen­sive ther­a­py be­hind No­var­tis’ $NVS fresh­ly ap­proved spinal mus­cu­lar at­ro­phy ther­a­py, Zol­gens­ma, at $2.1 mil­lion. A Chica­go biotech, mean­while, has been fum­ing at the side­lines. In a law­suit filed ear­li­er this month, Er­rant Gene Ther­a­peu­tics al­leged that blue­bird and ven­ture cap­i­tal group Third Rock un­law­ful­ly prised a vi­ral vec­tor, de­vel­oped in part­ner­ship with the Memo­r­i­al Sloan Ket­ter­ing Can­cer Cen­ter (MSK), from its grasp, and thwart­ed the de­vel­op­ment of its sem­i­nal gene ther­a­py.

Neil Woodford. Woodford Investment Management via YouTube

Wood­ford braces po­lit­i­cal storm as UK fi­nan­cial reg­u­la­tors scru­ti­nize fund sus­pen­sion

The shock of Neil Wood­ford’s de­ci­sion to block with­drawals for his flag­ship fund is still rip­pling through the rest of his port­fo­lio — and be­yond. Un­der po­lit­i­cal pres­sure, UK fi­nan­cial reg­u­la­tors are now tak­ing a hard look while in­vestors con­tin­ue to flee.

In a re­sponse let­ter to an MP, the Fi­nan­cial Con­duct Au­thor­i­ty re­vealed that it’s opened an in­ves­ti­ga­tion in­to the sus­pen­sion fol­low­ing months of en­gage­ment with Link Fund So­lu­tions, which tech­ni­cal­ly del­e­gat­ed Wood­ford’s firm to man­age its funds.