Mass cloning for neu­ro re­search? Chi­nese sci­en­tists re­port birth of five gene-edit­ed mon­keys

Re­mem­ber when Chi­nese re­searchers an­nounced the birth of the first mon­keys cre­at­ed by so­mat­ic cell nu­clear trans­fer? Ex­act­ly a year lat­er, the same team is re­port­ing a sec­ond break­through — cloning five gene-edit­ed mon­keys in an ef­fort to over­come pre­vi­ous con­cerns about the costs and ef­fi­cien­cy in us­ing cloned mon­keys for med­ical re­search.

“It can be said that this re­search means the tech­nol­o­gy for cloning gene-edit­ed mon­keys has made the leap from the­o­ry to prac­tice,” sci­en­tists from the Chi­nese Acad­e­my of Sci­ences In­sti­tute of Neu­ro­science in Shang­hai write in a blog­post for Chi­nese me­dia Sina.

Car­ry­ing a ge­net­ic al­ter­ation that pre­dis­pos­es them to dys­reg­u­la­tion of the cir­ca­di­an rhythm, the five mon­keys are ex­pect­ed to shed light on dis­ease mech­a­nisms and of­fer ther­a­peu­tic test­ing ground for neu­rode­gen­er­a­tion. In dis­eases such as Alzheimer’s and Parkin­son’s, mice mod­els have proven woe­ful­ly in­ad­e­quate in terms of pre­dict­ing hu­man re­ac­tions to drugs, cre­at­ing a big hur­dle in pre­clin­i­cal ex­per­i­ments for new ther­a­pies.

Like Zhong Zhong and Hua Hua, the iden­ti­cal long-tailed macaques in the spot­light last Jan­u­ary, the new mon­keys — now three to six months old — were cloned in a process that in­volves tak­ing the nu­cle­us of a dif­fer­en­ti­at­ed cell from one an­i­mal and in­fus­ing it in­to an emp­ty egg cell from an­oth­er. An elec­tric cur­rent trig­gers the egg to de­vel­op in­to an ear­ly em­bryo and the re­sult­ing fe­tus, grown in a sur­ro­gate, would be a repli­ca of the an­i­mal that do­nat­ed the nu­cle­us.

In their case, the donor was an abort­ed mon­key fe­tus. While adult cells were al­so test­ed in a sep­a­rate co­hort of the tri­al, both ba­bies born in that group were short-lived and one had ab­nor­mal body de­vel­op­ment.

This time around, re­searchers think they have cracked the code for “batch pro­duc­ing” iden­ti­cal mon­keys that all pos­sess a de­sired trait, state-owned Xin­hua re­port­ed, cit­ing a pa­per from Chi­nese jour­nal Na­tion­al Sci­ence Re­view. Specif­i­cal­ly, they knocked out BMAL1, a “clock gene” re­spon­si­ble for pro­duc­ing a “clock pro­tein,” in the donor mon­key.

No­tably, the suc­cess rate of cloning is still the same as in ear­li­er ex­per­i­ments at around 1% — a pos­i­tive sign, the sci­en­tists say, con­sid­er­ing the added com­plex­i­ties of us­ing adult cells and tweak­ing DNA.

Re­searchers have ob­served signs of sleep dis­or­ders, anx­i­ety and be­hav­iors in these mon­keys that are sug­ges­tive of schiz­o­phre­nia, they added in the blog­post.

They al­so told Xin­hua that the pro­gram “ad­hered to in­ter­na­tion­al ethics stan­dards and recog­ni­tion,” with sup­port and su­per­vi­sion from the in­sti­tute’s ethics pan­el.

Im­age: Five cloned mon­keys. SCI­ENCE CHI­NA PRESS

BiTE® Plat­form and the Evo­lu­tion To­ward Off-The-Shelf Im­muno-On­col­o­gy Ap­proach­es

Despite rapid advances in the field of immuno-oncology that have transformed the cancer treatment landscape, many cancer patients are still left behind.1,2 Not every person has access to innovative therapies designed specifically to treat his or her disease. Many currently available immuno-oncology-based approaches and chemotherapies have brought long-term benefits to some patients — but many patients still need other therapeutic options.3

Pfiz­er’s Doug Gior­dano has $500M — and some ad­vice — to of­fer a cer­tain breed of 'break­through' biotech

So let’s say you’re running a cutting-edge, clinical-stage biotech, probably public, but not necessarily so, which could see some big advantages teaming up with some marquee researchers, picking up say $50 million to $75 million dollars in a non-threatening minority equity investment that could take you to the next level.

Doug Giordano might have some thoughts on how that could work out.

The SVP of business development at the pharma giant has helped forge a new fund called the Pfizer Breakthrough Growth Initiative. And he has $500 million of Pfizer’s money to put behind 7 to 10 — or so — biotech stocks that fit that general description.

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Hill­house re­casts spot­light on Chi­na's biotech scene with $160M round for Shang­hai-based an­ti­body mak­er

Almost two years after first buying into Genor Biopharma’s pipeline of cancer and autoimmune therapies, Hillhouse Capital has led a $160 million cash injection to push the late-stage assets over the finish line while continuing to fund both internal R&D and dealmaking.

The Series B has landed right around the time Genor would have listed on the Hong Kong stock exchange, according to plans reported by Bloomberg late last year. Insiders had said that the company was looking to raise about $200 million.

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Fangliang Zhang (Imaginechina via AP Images)

The big mon­ey: Poised to make drug R&D his­to­ry, a Chi­na biotech un­veils uni­corn rac­ing am­bi­tions in a bid to raise $350M-plus on Nas­daq

Almost exactly three years after Shanghai-based Legend came out of nowhere to steal the show at ASCO with jaw-dropping data on their BCMA-targeted CAR-T for multiple myeloma, the little player with Big Pharma connections is taking a giant step toward making it big on Wall Street. And this time they want to seal the deal on a global rep after staking out a unicorn valuation in what’s turned out to be a bull market for biotech IPOs — in the middle of a pandemic.

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Gilead re­leas­es an­oth­er round of murky remde­sivir re­sults

A month after the NIH declared the first trial on remdesivir in Covid-19 a success, Gilead is out with new results on their antiviral. But although the study met one of its primary endpoints, the data are likely to only add to a growing debate over how effective the drug actually is.

In a Phase III trial, patients given a 5-day dose of remdesivir were 65% more likely to show “clinical improvement” compared to an arm given standard-of-care. The trial, though, gave little indication for whether the drug had an impact on key endpoints such as survival or time-to-recovery. And in a surprising twist, a 10-day dosing arm of remdesivir didn’t lead to a statistically significant improvement over standard of care.

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Stephen Isaacs, Aduro president and CEO (Aduro)

Once a high fly­er, a stag­ger­ing Aduro is auc­tion­ing off most of the pipeline as CEO Stephen Isaacs hands off the shell to new own­ers

After a drumbeat of failure, setbacks and reorganizations over the last few years, Aduro CEO Stephen Isaacs is handing over his largely gutted-out shell of a public company to another biotech company and putting up some questionable assets in a going-out-of-business sale.

Isaacs —who forged a string of high-profile Big Pharma deals along the way — has wrapped a 13-year run at the biotech with one program for kidney disease going to the new owners at Chinook Therapeutics. A host of once-heralded assets like their STING agonist program partnered with Novartis (which dumped their work on ADU-S100 after looking over weak clinical results), the Lilly-allied cGAS-STING inhibitor program and the anti-CD27 program out-licensed to Merck will all be posted for auction under a strategic review process.

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No­var­tis chips in $10M for IPO-bound part­ner Pli­ant; Tenax shares soar on heart drug da­ta

Novartis is coming in with $10 million to help support the looming IPO of a partner. Pliant Therapeutics posted a new filing with the SEC showing that Novartis is buying the shares at $15, the mid-point of the range. It’s adding several million shares to the offering, bringing the total to around $135 million. Biotech companies have been enjoying quite a run on virtual Wall Street, with investors boosting new offerings to some big hauls.

Bris­tol My­ers Squib­b's just-launched MS drug Zeposia makes the cut in key ul­cer­a­tive col­i­tis tri­al

In March, Zeposia became the third oral S1P modulator to secure US approval for multiple sclerosis. Now, the drug has succeeded in a key ulcerative colitis study.

The immunomodulator, akin to others in its class, controls lymphocyte trafficking by limiting the white blood cells to the lymphatic system, in the lymph nodes, and thwarting their ability to jam up lymph nodes — precluding their ability to penetrate the bloodstream and the central nervous system.

Federico Mingozzi (Spark)

Spark touts an­i­mal da­ta for a so­lu­tion to AAV gene ther­a­py's an­ti­body prob­lem

Among all the limitations of using an adeno-associated virus as a vector to deliver a gene — still the most established modality in gene therapy given years of trial and error and finally success — the presence of neutralizing antibodies, whether pre-existing or induced, looms large.

“When I think about the immune responses in AAV, I try to sort of layer them,” Federico Mingozzi, the CSO at Spark Therapeutics, told Endpoints News. “The antibody is the first layer. It’s the first block that you find when you’re trying to do gene transfer.”