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.

Roger Perlmutter. Merck via webcast

'Our lega­cy mat­ter­s': Mer­ck maps out Keytru­da king­dom while spot­light­ing ad­vances in vac­cines, hos­pi­tal care

“You can for the mo­ment stop tak­ing notes. You can put down your pens and your pad. I have no slides. I have no sub­stan­tive da­ta. I have no pitch.”

So be­gan Roger Perl­mut­ter’s brief ap­pear­ance on­stage at Mer­ck’s first in­vestor day in five years, where he dived in­to the com­pa­ny’s his­to­ry dat­ing back to 1933. The first em­ploy­ees at Mer­ck Re­search Lab­o­ra­to­ries, hand­picked by founder George W. Mer­ck, were crit­i­cal to Mer­ck’s abil­i­ty to achieve clin­i­cal and com­mer­cial suc­cess.

Eli Casdin, Casdin Capital

Eli Cas­din backs Codex­is' plat­form tech with $50M eq­ui­ty buy

About a month af­ter Codex­is notched a deal with No­var­tis $NVS, the Cal­i­for­nia com­pa­ny $CDXS on Thurs­day said long-time in­vestor Cas­din Cap­i­tal is putting up $50 mil­lion in a pri­vate place­ment, which puts the New York-based in­vest­ment firm in con­trol of more than 5% of the pro­tein en­gi­neer­ing play­er’s stock.

Eli Cas­din start­ed his epony­mous in­vest­ment firm in 2012 and dates his re­la­tion­ship with Codex­is back to at least a decade. About three years ago, Cas­din Cap­i­tal be­gan in­vest­ing in the in­dus­tri­al biotech com­pa­ny, af­ter it piv­ot­ed its fo­cus to the life sci­ences — un­der the aus­pices of new chief John Nicols — away from the en­er­gy in­dus­try.

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.
Endpoints News

Basic subscription required

Unlock this story instantly and join 53,100+ biopharma pros reading Endpoints daily — and it's free.

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:

Endpoints News

Basic subscription required

Unlock this story instantly and join 53,100+ biopharma pros reading Endpoints daily — and it's free.

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.

In­vestors pony up $476M for the lat­est round of biotech IPOs to hit the Street

Three biotechs — and a genome se­quenc­ing play­er — have caught the lat­est tide to the Gold Coast of IPOs, round­ing out the first half of 2019 with 23 new drug de­vel­op­ers mak­ing it on Nas­daq.

Most of these com­pa­nies filed their IPOs al­most si­mul­ta­ne­ous­ly, though we’re still wait­ing on word of fel­low class­mate Bridge­Bio’s pric­ing af­ter CEO Neil Ku­mar set the terms at $14 to $16 a share on Mon­day in search of a $240 mil­lion (or so) wind­fall. If he’s suc­cess­ful, that would take the one-week haul past the $700 mil­lion mark, a fresh sign that in­vestors’ en­thu­si­asm for new­ly coined pub­lic biotechs hasn’t cooled.

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.

Robert Forrester, Verastem

Ve­rastem CEO For­rester steps to the ex­it as the board hunts com­mer­cial-savvy ex­ec for the be­lea­guered biotech

Robert For­rester is step­ping down as CEO of Ve­rastem On­col­o­gy $VSTM just 8 months af­ter the com­pa­ny nabbed an ap­proval for du­velis­ib, a PI3K drug with a sto­ried past — and what ap­pears as not much of a fu­ture.

The biotech put out word this morn­ing that For­rester will take an ad­vi­so­ry role with Ve­rastem while COO Dan Pa­ter­son steps up to take charge of the lead­er­ship team and the board looks around for a new CEO.

Ken Frazier appears before the Senate Committee on Finance for a hearing on prescription drug pricing on Capitol Hill in Washington, DC, February 26, 2019. Chris Kleponis for CNP via AP Images

Who’s next in line to suc­ceed Ken Fra­zier as CEO of the Keytru­da-blessed Mer­ck?

When Merck waved off a looming forced retirement for Ken Frazier last September, the board cited flexibility in CEO transition as a key factor in the decision. Having Frazier — who’s also chairman of the company — around beyond his 65th birthday in 2019 would ensure they install the best person at the best time, they said.

The board has evidently begun that process with a clear preference for internal candidates, sources told Bloomberg. CFO Robert Davis, chief marketing officer Michael Nally, and chief commercial officer Frank Clyburn are all in the running, according to an insider.

Endpoints News

Basic subscription required

Unlock this story instantly and join 53,100+ biopharma pros reading Endpoints daily — and it's free.