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.

Regeneron CEO Leonard Schleifer speaks at a meeting with President Donald Trump, members of the Coronavirus Task Force, and pharmaceutical executives in the Cabinet Room of the White House (AP Photo/Andrew Harnik)

OWS shifts spot­light to drugs to fight Covid-19, hand­ing Re­gen­eron $450M to be­gin large scale man­u­fac­tur­ing in the US

The US government is on a spending spree. And after committing billions to vaccines defense operations are now doling out more of the big bucks through Operation Warp Speed to back a rapid flip of a drug into the market to stop Covid-19 from ravaging patients — possibly inside of 2 months.

The beneficiary this morning is Regeneron, the big biotech engaged in a frenzied race to develop an antibody cocktail called REGN-COV2 that just started a late-stage program to prove its worth in fighting the virus. BARDA and the Department of Defense are awarding Regeneron a $450 million contract to cover bulk delivery of the cocktail starting as early as late summer, with money added for fill/finish and storage activities.

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Donald and Melania Trump watch the smoke of fireworks from the South Lawn of the White House on July 4, 2020 (via Getty)

Which drug de­vel­op­ers of­fer Trump a quick, game-chang­ing ‘so­lu­tion’ as the pan­dem­ic roars back? Eli Lil­ly and Ab­Cellera look to break out of the pack

We are unleashing our nation’s scientific brilliance and will likely have a therapeutic and/or vaccine solution long before the end of the year.

— Donald Trump, July 4

Next week administration officials plan to promote a new study they say shows promising results on therapeutics, the officials said. They wouldn’t describe the study in any further detail because, they said, its disclosure would be “market-moving.”

— NBC News, July 3

Something’s cooking. And it’s not just July 4 leftovers involving stale buns and uneaten hot dogs.

Over the long weekend observers picked up signs that the focus in the Trump administration may swiftly shift from the bright spotlight on vaccines being promised this fall, around the time of the election, to include drugs that could possibly keep patients out of the hospital and take the political sting out of the soaring Covid-19 numbers causing embarrassment in states that swiftly reopened — as Trump cheered along.

So far, Gilead has been the chief beneficiary of the drive on drugs, swiftly offering enough early data to get remdesivir an emergency authorization and into the hands of the US government. But their drug, while helpful in cutting stays, is known for a limited, modest effect. And that won’t tamp down on the hurricane of criticism that’s been tearing at the White House, and buffeting the president’s most stalwart core defenders as the economy suffers.

We’ve had positive early-stage vaccine data, most recently from Pfizer and BioNTech, playing catchup on an mRNA race led by Moderna — where every little sign of potential trouble is magnified into a lethal threat, just as every advance excites a frenzy of support. But that race still has months to play out, with more Phase I data due ahead of the mid-stage numbers looming ahead. A vaccine may not be available in large enough quantities until well into 2021, which is still wildly ambitious.

So what about a drug solution?

Trump’s initial support for a panacea focused on hydroxychloroquine. But that fizzled in the face of data underscoring its ineffectiveness — killing trials that aren’t likely to be restarted because of a recent population-based study offering some support. And there are a number of existing drugs being repurposed to see how they help hospitalized patients.

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RA Cap­i­tal dou­bles down on Sid­dhartha Mukher­jee's vi­sion for a new cell en­gi­neer­ing ap­proach, lead­ing Vor's $110M Se­ries B

Vor Biopharma is muscling up.

CEO Robert Ang, who was reluctant to divulge the headcount when discussing his move from Neon Therapeutics to Vor last August, readily offered that the team has grown from 6 to 50 in less than a year. The biotech is moving to a larger office on Cambridge Parkway Drive in weeks, giving it more space to complete the IND-enabling work and manufacturing scale-up — conducted by a CDMO partner — in preparation for clinical trials planned for the first half of 2021.

In­vestors give ail­ing Unum a lease on life and a whole new suite of ex­per­i­men­tal can­cer drugs

Investors, it seems, are willing to give Unum Therapeutics one last shot — or at least one last shot to a company of that name.

The ailing cancer biotech, beset by a series of clinical holds and multiple failed lead programs, announced today that they’ve acquired Kiq LLC and that investors are putting in $104 million to advance Kiq’s pipeline of kinase inhibitors. Unum shareholders will now own only 16.2% of the company and CEO Chuck Wilson indicated that the cell therapies the biotech has worked on since its founding may be on their way out, saying Unum will “explore strategic options” for those products.

Covid-19 roundup: Left out no longer, No­vavax se­cures largest Warp Speed deal yet: $1.6B

It looks like Novavax won’t be left out of Operation Warp Speed after all.

A month after the Gaithersburg, MD biotech saw its shares tumble when it was left off the first reported list of finalists for the White House’s Covid-19 vaccine accelerator, HHS and the Department of Defense have announced a $1.6 billion deal to scale up their Covid-19 candidate. It is the largest deal HHS has announced yet, eclipsing the $1.2 billion deal the administration reached with AstraZeneca in May.

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Bill Haney, Dragonfly CEO (Dave Pedley/Getty Images for SXSW)

A boom­ing Drag­on­fly is tak­ing its TriN­KETs to Copen­hagen as the lat­est Bris­tol My­ers pact spurs ex­pan­sion plans — out­side the US

Bristol Myers Squibb is making a habit out of collaborating with the crew at Dragonfly, adding their 3rd deal in a series that now will take them into newly charted R&D territory. And the fast-growing team at the Cambridge-based biotech is adding a facility in Copenhagen for its next growth spurt, where the government is making it easy to recruit scientists internationally as the U.S. throttles back.

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Cel­lec­tis slammed af­ter pa­tient dies and FDA slaps a hold on their tri­al for an off-the-shelf CAR-T for mul­ti­ple myelo­ma

Cellectis was slammed after the market close on Monday as the biotech reported that the FDA demanded it hit the brakes on their MELANI-01 trial for their off-the-shelf cell therapy UCARTCS1A after one of the patients in the study died of treatment-related cardiac arrest.

The multiple myeloma patient had previously been treated unsuccessfully with various therapies, noted the biotech, and had been given dose level two (DL2) of their allogeneic CAR-T.

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Jean-Paul Clozel, Idorsia CEO (Patrick Straub/Keystone via AP Images)

Sec­ond PhI­II study for Idor­si­a's sleep drug re­turns pos­i­tive re­sults, but al­so rais­es new ques­tions

Following a successful Phase III study in April showcasing the safety and potential of its new sleep drug, Idorsia posted some mixed news in the second Phase III study, but that won’t stop a planned filing aimed at regulatory approval.

The drug, a dual orexin receptor antagonist (DORA) called daridorexant, was found to significantly improve sleep maintenance and subjective total sleep time in 25 mg doses, replicating results from the first Phase III study. However, improvements in sleep onset and daytime functioning narrowly missed statistical significance, despite numerical consistency with the April study.

UP­DAT­ED: Im­munomedics spells out PFS ben­e­fit of Trodelvy in mTNBC, hunt­ing a full OK just weeks af­ter ac­cel­er­at­ed ap­proval

By the time the FDA finally granted an accelerated OK for Immunomedics’ Trodelvy, we already got a very strong hint that their confirmatory Phase III study in metastatic triple-negative breast cancer was a success.

That’s because the independent data safety monitoring committee recommended that the trial be stopped early. But just what pointed them to the conclusion was still unclear.

“We do not know the totality of their decision other than it’s pretty evident that the primary endpoint was met; otherwise they could not request to halt the study,” Behzad Aghazadeh, the executive chairman, told Endpoints News at the time.