Henry Klassen (UC Irvine via YouTube)

Can prog­en­i­tor cells go fur­ther than gene ther­a­py in reti­nal dis­or­ders? A biotech's an­swer shines in PhI­Ib

By the time the FDA ap­proved Lux­tur­na — the pi­o­neer­ing gene ther­a­py for an in­her­it­ed reti­nal dis­ease — Hen­ry Klassen had been re­search­ing and treat­ing the group of dis­eases known as re­tini­tis pig­men­tosa for more than 20 years.

Spark Ther­a­peu­tics’ suc­cess there had not just in­spired a $4.3 bil­lion takeover by Roche, it had al­so em­bold­ened oth­er biotechs pur­su­ing a ther­a­py that would de­liv­er one of the genes tied to dif­fer­ent vari­a­tions of the dis­or­der. Night­star Ther­a­peu­tics sub­se­quent­ly scored its own buy­out with Bio­gen, and MeiraGTx re­cent­ly post­ed ear­ly but “ex­cit­ing da­ta” on its J&J-part­nered pro­gram.

But Klassen went a dif­fer­ent way.

Catch­ing on the stem cell craze right at the turn of the mil­len­ni­um, he took in­spi­ra­tion from sci­en­tists who trans­plant­ed neur­al prog­en­i­tor cells in­to the reti­na and de­vel­oped a method to grow reti­nal prog­en­i­tor cells in­stead as a ther­a­py. Start­ing out as the di­rec­tor of stem cell re­search at the Chil­dren’s Hos­pi­tal of Or­ange Coun­ty, he con­tin­ued the work at the Uni­ver­si­ty of Cal­i­for­nia, Irvine, even­tu­al­ly spin­ning out a biotech dubbed jCyte in 2012.

Paul Bres­ge

Over the week­end jCyte re­port­ed pos­i­tive Phase IIb re­sults from what they call one of the largest stud­ies ever con­duct­ed in RP, sug­gest­ing that pa­tients on the treat­ment saw im­proved func­tion­al vi­sion com­pared to the place­bo group.

“The cred­it to the gene ther­a­pies is that they’re ac­tive­ly try­ing to fix the gene un­der­ly­ing the prob­lem. That’s very com­mend­able, and we’re not do­ing that,” Klassen told End­points News. “But our treat­ment as it stands should have im­pact across a va­ri­ety of dif­fer­ent geno­types.”

The study en­rolled a to­tal of 84 pa­tients, of whom 74 were in­clud­ed for the fi­nal analy­sis. For each pa­tient on the pri­ma­ry end­point of best cor­rect­ed vi­su­al acu­ity (mea­sured with glass­es on), the mean change from base­line to month 12 for the sham, low dose and high dose arms were +2.81, +2.96, and +7.43 let­ters, re­spec­tive­ly.

In a post hoc analy­sis for a tar­get sub­group, the dif­fer­ence was even more promi­nent: +1.85, -0.15, and +16.27 let­ters, re­spec­tive­ly.

There was one se­ri­ous ad­verse event in the low dose arm, but jCyte said the grade 3 oc­u­lar hy­per­ten­sion re­solved with treat­ment and oth­er side ef­fects were gen­er­al­ly mi­nor.

CEO Paul Bres­ge not­ed that the tar­get sub­group analy­sis was in­tend­ed to ham­mer out the cri­te­ria they might use to re­cruit pa­tients in­to Phase III — which would like­ly have a sim­i­lar de­sign and use the same pri­ma­ry end­point of BC­VA, the “gold stan­dard in the con­text of FDA.” The late-stage tri­al is slat­ed for 2021.

“We did en­roll a very wide pa­tient pop­u­la­tion in­to our Phase IIb, in­clud­ing pa­tients that had vi­sion any­where from 20/80 to 20/800, just to learn which pa­tients would po­ten­tial­ly be the best re­spon­ders,” he said.

The tar­get sub­group is char­ac­ter­ized by hav­ing re­li­able fix­a­tion on the study eye, and a study eye that does not have sig­nif­i­cant­ly worse BC­VA (≤15 let­ters) than the fel­low eye.

He added that in­ves­ti­ga­tors al­so ob­served en­cour­ag­ing re­sults with the sec­ondary end­points such as low light mo­bil­i­ty, con­trast sen­si­tiv­i­ty ki­net­ic vi­su­al fields and a vi­sion func­tion ques­tion­naire, al­though the da­ta weren’t dis­closed.

“Typ­i­cal­ly peo­ple think about the dis­ease as a nar­row­ing of this pe­riph­er­al vi­sion in a very nice gran­u­lar way, but that’s ac­tu­al­ly not what hap­pens,” he said about the vi­su­al fields find­ing. “What hap­pens in the dis­ease is that pa­tients lose like is­lands of vi­sion. So what we’re do­ing in our tests is ac­tu­al­ly mea­sur­ing […] is­lands that the pa­tients have at base­line, and then what we’re see­ing af­ter treat­ment is that the is­lands are ex­pand­ing. It’s sim­i­lar to the way that one would track, let’s say a tu­mor, in on­col­o­gy of course we’re look­ing for the op­po­site ef­fect. We’re look­ing for the is­lands of vi­sion to ex­pand.”

The ther­a­py works pri­mar­i­ly by pre­serv­ing pho­tore­cep­tors, Klassen posits, not by gen­er­at­ing new ones. But what he thinks is hap­pen­ing is that pho­tore­cep­tors are re­gen­er­at­ing the out­er seg­ment — if pho­tore­cep­tors are ra­dios, these would be the an­ten­na — there­by re­gain­ing some func­tion.

That could po­si­tion it as a treat­ment for a dif­fer­ent stage of the dis­ease than Spark’s or Night­star’s. Klassen, who’s al­so re­search­ing reti­nal re­con­struc­tion us­ing stem cells, is hap­py to not view it through the com­pet­i­tive lens.

“If you look in­to the fu­ture, one could imag­ine that gene ther­a­pies will be most ef­fec­tive very ear­ly in the course of a dis­ease be­fore pho­tore­cep­tors are lost,” he said. “Then as pho­tore­cep­tors be­gin to be lost any­way, if that hap­pens, then a ther­a­py like ours would be­come ex­treme­ly valu­able. And if ours starts to lose pow­er late in the course of a dis­ease, maybe cell trans­plan­ta­tion un­der the reti­na could have a role.”

In his­toric Covid-19 ad­comm, vac­cine ex­perts de­bate a sea of ques­tions — but of­fer no clear an­swers

The most widely anticipated and perhaps most widely watched meeting in the FDA’s 113-year history ended late Thursday night with a score of questions and very few answers.

For nearly 9 hours, 18 different outside experts listened to public health agencies and foundations present how the United States’ Covid-19 vaccine program developed through October, and they debated where it should go from there: Were companies testing the right metrics in their massive trials? How long should they track patients before declaring a vaccine safe or effective? Should a vaccine, once authorized, be given to the volunteers in the placebo arm of a trial?

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Ul­tragenyx in­jects $40M to grab Solid's mi­crody­s­trophin trans­gene — while side­step­ping the AAV9 vec­tor that stirred up safe­ty fears

Since before Ilan Ganot started Solid Bio to develop a gene therapy for kids like his son, who has Duchenne muscular dystrophy, Ultragenyx CEO Emil Kakkis has been watching and advising the former investment banker as he navigated the deep waters of drug development.

Just as Solid is getting back up on its feet after a yearlong clinical hold, Kakkis has decided to jump in for a formal alliance.

With a $40 million upfront, Ultragenyx is grabbing 14.45% of Solid’s shares $SLDB and the rights to its microdystrophin construct for use in combination with AAV8 vectors. Solid’s lead program, which utilizes AAV9, remains unaffected. The company also retains rights to other applications of its transgene.

A top drug pro­gram at Bay­er clears a high bar for CKD — open­ing the door to an FDA pitch

Over the past 4 years, Bayer has been steering a major trial through a pivotal program to see if their drug finerenone could slow down the pace of chronic kidney disease in patients suffering from both CKD as well as Type 2 diabetes.

Today, their team jumped on a virtual meeting hosted by the American Society of Nephrology to offer a solid set of pivotal data to demonstrate that the drug can delay dialysis or a kidney replacement as well as cardio disease, while also adding some worrying signs of hyperkalemia among the patients taking the drug. And they’re hustling it straight to regulators in search of an approval for kidney disease and cardio patients — one of the toughest challenges in the book, as demonstrated by repeated past failures.

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Michel Vounatsos, Biogen CEO (via YouTube)

UP­DAT­ED: Bio­gen spot­lights a pair of painful pipeline set­backs as ad­u­canum­ab show­down looms at the FDA

Biogen has flagged a pair of setbacks in the pipeline, spotlighting the final failure for a one-time top MS prospect while scrapping a gene therapy for SMA after the IND was put on hold due to toxicity.

Both failures will raise the stakes even higher on aducanumab, the Alzheimer’s drug that Biogen is betting the ranch on, determined to pursue an FDA OK despite significant skepticism they can make it with mixed results and a reliance on post hoc data mining. And the failures are being reported as Biogen was forced to cut its profit forecast for 2020 as a generic rival started to erode their big franchise drug.

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Biond­Vax stock im­plodes af­ter a big PhI­II gam­ble for its uni­ver­sal flu vac­cine fails

After flying high on Wall Street for the last few months of a pandemic, BiondVax’s stock and dreams of getting approval for its universal flu vaccine hit the windshield.

The Jerusalem-based biotech announced on Friday that its only clinical candidate, M-001, failed both primary and secondary endpoints in a Phase III study. There was no statistically significant difference in reduction of flu illness and severity between the vaccine and placebo groups, according to the company. The vaccine did prove safe, if ineffective, BiondVax said.

Pascal Soriot, AstraZeneca CEO (Zach Gibson/Bloomberg via Getty Images)

UP­DAT­ED: FDA gives As­traZeneca the thumbs-up to restart PhI­II Covid-19 vac­cine tri­als, and J&J is prepar­ing to re­sume its study

Several countries had restarted their portions of AstraZeneca’s global Phase III Covid-19 vaccine trial after the study was paused worldwide in early September, but the US notably stayed on the sidelines — until now. Friday afternoon the pharma giant announced the all clear from US regulators. And on top of that, J&J announced Friday evening that it’s preparing to resume its own Phase III vaccine trial.

Bo Cumbo, AavantiBio CEO (file photo)

Bo Cum­bo jumps from the top com­mer­cial post at Sarep­ta to the helm of a gene ther­a­py start­up with some in­flu­en­tial back­ers, big plans and $107M

After a 7-year stretch building the commercial team at Sarepta, longtime drug salesman Bo Cumbo is jumping to the entrepreneurial side of the business, taking the helm of a startup that’s got several deep-pocket investors. And he’s not just bringing his experience in selling drugs.

He tells me that when he told Sarepta CEO Doug Ingram about it, his boss got excited about the venture and opted to jump in with a $15 million investment from Sarepta to add to the launch money, alongside 3 of the busiest investors in biotech.

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Adam Koppel and Jeffrey Schwartz, Bain

Bain ex­ecs Adam Kop­pel and Jef­frey Schwartz line up $125M for their first blank check deal as Wall Street con­tin­ues to em­brace biotech

Adam Koppel and Jeffrey Schwartz have jumped into the blank check game, raising $125 million for a stock listing in search of a company.

Their SPAC, BCLS Acquisition Corp, raised $125 million this week, with a line on $25 million more as it scouts for a biotech in search of money and a place on Wall Street.

The two principals at Bain Life Sciences have been on a romp since they set up the Bain operation 4 years ago. Their S-1 spells out a track record of 22 deals totaling $650 million for the life sciences group, which led to 9 IPOs.

Covid-19 roundup: An mR­NA play­er gets a boost out of the lat­est round of an­i­mal da­ta; Phase­Bio pulls the plug on treat­ment tri­al

The big tell for CureVac $CVAC is coming up with a looming early-stage readout on their mRNA Covid-19 vaccine in the clinic. But for now they’ll make do with an upbeat assessment on the preclinical animal data they used to get into the clinic.

Researchers for the German biotech say they got the high antibody titers and T cell activation they were looking for, lining up a hamster challenge to demonstrate — in a simple model — that the vaccine could protect the furry creatures. Like the other mRNA vaccines, the drug sends instructions to spur cells to decorate themselves with the distinctive spike on the virus to elicit an immune response.