Sol­id Bio is hit by an­oth­er set­back as ini­tial biop­sies spot­light a flop for Duchenne MD

Sol­id Bio­sciences has had an­oth­er set­back.

The biotech an­nounced this morn­ing that its dose-as­cend­ing Phase I/II study of its lead gene ther­a­py for Duchenne mus­cu­lar dy­s­tro­phy flopped, send­ing the com­pa­ny in­to over­drive to hus­tle a high­er dose in­to the clin­ic.

Ilan Gan­ot

The com­pa­ny an­nounced Thurs­day morn­ing that a 3-month biop­sy of a hand­ful of pa­tients “showed low lev­els of mi­crody­s­trophin pro­tein ex­pres­sion.” In 2 of 3 pa­tients, pro­tein ex­pres­sion was un­de­tectable by west­ern blot analy­sis. In the third pa­tient the dy­s­trophin ex­pres­sion hit on­ly 5% by west­ern blot analy­sis, while an­a­lysts and the com­pa­ny were look­ing for 10% or bet­ter.

The com­pa­ny’s shares im­plod­ed, plung­ing 68% by the close. Shares of Sarep­ta, which has the on­ly cus­tom ther­a­py on the mar­ket, jumped about 7% and then slid in­to the red.

Giv­en the safe­ty is­sues that the ther­a­py has al­ready run in­to, Leerink’s Joseph Schwartz ques­tioned the com­pa­ny’s abil­i­ty to pow­er up an ef­fec­tive dose with­out threat­en­ing pa­tients.

Our the­sis that in­vestors should fo­cus not on­ly on the quan­ti­ty of mi­crody­s­trophin ex­pres­sion but al­so on the qual­i­ty of the ex­pressed pro­tein ap­pears to be at sig­nif­i­cant risk based up­on the in­creas­ing­ly un­cer­tain abil­i­ty of SGT-001 (Duchenne mus­cu­lar dy­s­tro­phy/DMD) to be safe­ly dose-es­ca­lat­ed to a lev­el which is suf­fi­cient to achieve com­pet­i­tive mi­crody­s­trophin lev­els. We be­lieve it is pru­dent to wait and see if SLDB can achieve ad­e­quate lev­els of ex­pres­sion in a safe man­ner be­fore con­sid­er­ing whether the mi­crody­s­trophin pro­tein that is ex­pressed by SGT-001 is dif­fer­en­ti­at­ed from that of SRPT and PFE (Bam­boo).

CEO Ilan Gan­ot quick­ly spot­light­ed the com­pa­ny’s cash re­serves, a com­mon strat­e­gy for dis­tressed com­pa­nies.

He not­ed: “This strat­e­gy is fur­ther sup­port­ed by our scal­able man­u­fac­tur­ing process, from which we have suf­fi­cient drug prod­uct avail­able to dose es­ca­late with­out de­lay. We have the fi­nan­cial re­sources to ex­e­cute on our plan and look for­ward to com­mu­ni­cat­ing ad­di­tion­al da­ta lat­er this year.”

Gan­ot — a for­mer JP Mor­gan in­vest­ment banker — has made much of the fact that he’s a Duchenne MD dad out to find a gene ther­a­py that could cure the lethal, rare dis­ease. By in­tro­duc­ing a syn­thet­ic dy­s­trophin trans­gene con­struct, called mi­crody­s­trophin, via a vi­ral vec­tor, the com­pa­ny has en­cour­aged hopes it can do what Sarep­ta and oth­ers have been grop­ing for with one de­ci­sive in­ter­ven­tion. And he had at­tract­ed some heavy­weight back­ers, in­clud­ing RA Cap­i­tal and their col­leagues at Bain.

The com­pa­ny ran in­to ear­ly trou­ble, though.

The very first pa­tient to be treat­ed with SGT-001 ex­pe­ri­enced a se­ri­ous ad­verse event, trig­ger­ing alarm bells af­ter in­ves­ti­ga­tors saw a “de­crease in platelet count fol­lowed by a re­duc­tion in red blood cell count, tran­sient re­nal im­pair­ment and ev­i­dence of com­ple­ment ac­ti­va­tion.” That trig­gered a clin­i­cal hold that last­ed sev­er­al months.

It wasn’t the first brush with trou­ble.

In the lead up to its IPO Gan­ot ne­glect­ed to tell in­vestors about an ini­tial clin­i­cal hold on the pro­gram, post­ing that news just ahead of the list­ing. The biotech was al­so forced to note that gene ther­a­py pi­o­neer James Wil­son from Penn had re­signed from their sci­en­tif­ic ad­vi­so­ry board due to ris­ing safe­ty con­cerns re­lat­ed to high dos­ing us­ing the vec­tor he had de­vel­oped.

FDA chief Stephen Hahn on Capitol Hill earlier this week (Getty Images)

As FDA’s work­load buck­les un­der the strain, Trump again ac­cus­es the agency of a po­lit­i­cal hit job

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Mi­no­ryx and Sper­o­genix ink an ex­clu­sive li­cense agree­ment to de­vel­op and com­mer­cial­ize lerigli­ta­zone in Chi­na

September 23, 2020 – Hong Kong, Beijing, Shanghai (China) and Mataró, Barcelona (Spain)  

Minoryx will receive an upfront and milestone payments of up to $78 million, as well as double digit royalties on annual net sales 

Sperogenix will receive exclusive rights to develop and commercialize leriglitazone for the treatment of X-linked adrenoleukodystrophy (X-ALD), a rare life-threatening neurological condition

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The leading anti-tau antibody has failed its first Phase II testing, casting a shadow on a popular target (just trailing amyloid beta) for Alzheimer’s disease.

Roche and AC Immune are quick to acknowledge disappointment in the topline readout, which suggested that semorinemab did not reduce cognitive decline among patients with early Alzheimer’s disease, who are either just starting to have symptoms or have mild manifestations.

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Vas Narasimhan (AP Images)

Still held down by clin­i­cal hold, No­var­tis' Zol­gens­ma falls fur­ther be­hind Bio­gen and Roche as FDA asks for a new piv­otal study

Last October, the FDA slowed down Novartis’ quest to extend its gene therapy to older spinal muscular atrophy patients by slapping a partial hold on intrathecal administration. Almost a year later, the hold is still there, and regulators are adding another hurdle required for regulatory submission: a new pivotal confirmatory study.

The new requirement — which departs significantly from Novartis’ prior expectations — will likely stretch the path to registration beyond 2021, when analysts were expecting a BLA submission. That could mean more time for Biogen to reap Spinraza revenues and Roche to ramp up sales of Evrysdi in the absence of a rival.

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Scoop: ARCH’s Bob Nelsen is back­ing an mR­NA up­start that promis­es to up­end the en­tire man­u­fac­tur­ing side of the glob­al busi­ness

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Right now, he says, he has a working “GMP-in-a-box” prototype for a new company he’s building — after launching 3 public companies — which plans to spread this contained, precise manufacturing tech around the world with a set of partners. He’s raised $60 million, recruited some prominent experts. And not coincidentally, he’s going semi-public with this just as a small group of pioneers appears to be on the threshold of ushering in the world’s first mRNA vaccines to fight a worldwide pandemic.

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Samit Hirawat (Bristol Myers Squibb)

Af­ter bruis­ing re­jec­tion, blue­bird and Bris­tol My­ers Squibb land ide-cel pri­or­i­ty re­view. But will it mat­ter for the CVR?

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The acceptance comes five months after the two companies weres slammed with a surprise refuse-to-file that threatened to foreclose the CVR entirely. Today’s acceptance sets the FDA decision date for March 27, 2021 – or precisely 4 days before the CVR deadline of March 31. Given the breakthrough designation and strong pivotal data — 81.5% response rate, 35.2% complete response rate — priority review was largely expected.

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The win­dow is wide open as four more biotechs join the go-go IPO class of 2020

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The biggest offering comes from PMV Pharma, an oncology biotech focusing on p53 mutations, which raised $211.8 million after pricing shares at $18 apiece. Prelude Therapeutics, developing PRMT5 inhibitors for rare cancers, was next with a $158 million raise, pricing shares at $19 each. Graybug Vision raised $90 million after pricing at $16 per share for its wet AMD candidates, and breast cancer biotech Greenwich Lifesciences brought up the rear with a small, $7 million raise after pricing shares at $5.75.

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Testing two dose levels either as a single dose or in a two-dose schedule spaced by 56 days in, the scientists from Janssen, the J&J subsidiary developing its vaccine, reported that the low dose induced a similar immune response as the high dose. The interim Phase I/IIa results were posted in a preprint on medRxiv.

Daniel O'Day, Gilead CEO (Kevin Dietsch/UPI/Bloomberg via Getty Images)

Play-by-play of Gilead­'s $21B Im­munomedics buy­out de­tails a fren­zied push — and mints a new biotech bil­lion­aire

Immunomedics had not really been looking for a buyout when the year began. Excited by its BLA for Trodelvy, submitted to the FDA in late 2019, executive chairman Behzad Aghazadeh started off looking for potential licensing deals and zeroed in on four potential partners, including Gilead, following January’s JP Morgan Healthcare Conference in San Francisco. Such talks advanced throughout the year, with discussions advancing to the second round in mid-August.

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