Sarep­ta shares yo-yo in the red on an­oth­er glimpse of stel­lar re­sults for Duchenne MD gene ther­a­py — what gives?

There’s just no telling what a stock will do — even when you stack the deck in your fa­vor.

Tonight Sarep­ta $SRPT came out with a GREAT piece of news. Adding to the stel­lar, but very ear­ly glimpse of pos­i­tive da­ta for their gene ther­a­py for Duchenne mus­cu­lar dy­s­tro­phy, the biotech up­dat­ed their da­ta with a set of new num­bers that would ap­pear to add to the over­all glow of the pro­gram.


And then its stock took a dive, falling close to 10% in a mat­ter of min­utes af­ter the de­layed re­lease hit the wires. Then it bounced back, on­ly a few points in the red. What gives?

Is this sell the news? And why would that be? Shorts cov­er­ing their po­si­tions? Sev­er­al in­s­ta-re­ac­tions in the Twit­ter­verse sus­pect­ed that the fourth pa­tient did too well, see­ing a 182% in­crease in dy­s­trophin, the much-want­ed el­e­ment that cre­ates hav­oc for pa­tients, whose mus­cles waste and die with­out it.

As mea­sured by West­ern blot, pa­tient 4 showed ro­bust lev­els of mi­cro-dy­s­trophin, with a mean of 182.7% com­pared to nor­mal uti­liz­ing Sarep­ta’s method, or 222% com­pared to nor­mal pur­suant to Na­tion­wide Chil­dren’s quan­tifi­ca­tion of Sarep­ta’s method that ad­justs for fat and fi­brot­ic tis­sue.

Was that too much? Or too vari­able?

Baird’s Bri­an Sko­r­ney, a strong Sarep­ta bull, heard the dis­tur­bance in the force, but isn’t about to crum­ble now.

We ex­pect to de­bate con­cerns over noisy CK da­ta and im­pli­ca­tions of over­ex­pres­sion but see these as very mi­nor points on an oth­er­wise very im­pres­sive da­ta set and re­it­er­ate our Out­per­form.

I asked Sko­r­ney — one of the more thought­ful an­a­lysts in the bunch — about the red num­bers. His re­ply:

I think the ini­tial neg­a­tive re­ac­tion is due to the high ex­pres­sion lev­els that are rem­i­nis­cent of the con­cerns around vari­abil­i­ty with Bio­Marin’s Fac­tor VI­II pro­gram and some re­bound in CK lev­els in the first three pa­tients. I don’t re­al­ly ex­pect any af­ter­hours down move to be sus­tained to­mor­row though.

Sev­er­al an­a­lysts and re­porters help­ful­ly pro­vid­ed the em­bar­goed thumbs up, with quotes. Yet there, but for the grace of the biotech Gods, go I. I was tipped to the re­lease… but nev­er ac­tu­al­ly got it as of­fered.

Again, an­oth­er mys­tery for those of us who cov­er the field.

On the face of it, Sarep­ta would seem to have every­thing go­ing in its fa­vor. The gene ther­a­py is pro­vid­ing the nec­es­sary ev­i­dence of a sol­id bio­mark­er re­sponse. Even some signs in the sin­gle arm study — with­out the com­par­i­son da­ta that would help prove that it makes a dif­fer­ence  — that it’s help­ing pa­tients im­prove phys­i­cal­ly.

And this is a ter­ri­ble dis­ease. An ac­tu­al cure would be a god­send.

Sarep­ta has an un­for­tu­nate his­to­ry when it comes to his­tor­i­cal com­par­isons, though, which raised sig­nif­i­cant doubts in the agency that eteplirsen works.

Any­way, be­fore the post-mar­ket trad­ing closed Wednes­day evening, the stock had edged back in­to the green, so the de­fend­ers of the faith had held the line, briefly. By mid-morn­ing Thurs­day, the stock was back in the red again.

I’ll wait for some ad­di­tion­al com­men­tary. In the mean­time, caveat emp­tor.

You’re on your own, as al­ways.

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

Graphic: Kathy Wong for Endpoints News

What kind of biotech start­up wins a $3B syn­di­cate, woos a gallery of mar­quee sci­en­tists and re­cruits GSK's Hal Bar­ron as CEO in a stun­ner? Let Rick Klaus­ner ex­plain

It started with a question about a lifetime’s dream on a walk with tech investor Yuri Milner.

At the beginning of the great pandemic, former NCI chief and inveterate biotech entrepreneur Rick Klausner and the Facebook billionaire would traipse Los Altos Hills in Silicon Valley Saturday mornings and talk about ideas.

Milner’s question on one of those mornings on foot: “What do you want to do?”

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FDA+ roundup: FDA's neu­ro­science deputy de­parts amid on­go­ing Aduhelm in­ves­ti­ga­tions; Califf on the ropes?

Amid increased scrutiny into the close ties between FDA and Biogen prior to the controversial accelerated approval of Aduhelm, the deputy director of the FDA’s office of neuroscience has called it quits after more than two decades at the agency.

Eric Bastings will now take over as VP of development strategy at Ionis Pharmaceuticals, the company said Wednesday, where he will provide senior clinical and regulatory leadership in support of Ionis’ pipeline.

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Sec­ondary patents prove to be key in biosim­i­lar block­ing strate­gies, re­searchers find

While the US biosimilars industry has generally been a disappointment since its inception, with FDA approving 33 biosimilars since 2015, just a fraction of those have immediately followed their approvals with launches. And more than a handful of biosimilars for two of the biggest blockbusters of all time — AbbVie’s Humira and Amgen’s Enbrel — remain approved by FDA but still have not launched because of legal settlements.

Hal Barron (GSK via YouTube)

GSK R&D chief Hal Bar­ron jumps ship to run a $3B biotech start­up, Tony Wood tapped to re­place him

In a stunning switch, GlaxoSmithKline put out word early Wednesday that R&D chief Hal Barron is exiting the company after 4 years — a relatively brief run for the man chosen by CEO Emma Walmsley in late 2017 to turn around the slow-footed pharma giant.

Barron is being replaced by Tony Wood, a close associate of Barron’s who’s taking one of the top jobs in Big Pharma R&D. He’ll be closer to home, though, for GSK. Barron has been running a UK and Philadelphia-based research organization from his perch in San Francisco.

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Chamath Palihapitiya and Pablo Legorreta

Bil­lion­aires Chamath Pal­i­hapi­tiya and Pablo Legor­re­ta hatch an $825M SPAC for cell ther­a­py biotech

Three years after Royalty Pharma chief Pablo Legorreta led a group of investors to buy up a pair of biotechs and create a new startup called ProKidney, the biotech is jumping straight into an $825 million public shell created by SPAC king and tech billionaire Chamath Palihapitiya.

ProKidney was founded 6 years ago but really got going at the beginning of 2019 with the $62 million acquisition of inRegen, which was working on an autologous — from the patient — cell therapy for kidney disease. After extracting kidney cells from patients, researchers expand the cells in the lab and then inject them back into patients, aiming to restore the kidneys of patients suffering from CKD.

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CBO: Medicare ne­go­ti­a­tions will ham­per drug de­vel­op­ment more than pre­vi­ous­ly thought

As President Biden’s Build Back Better Act — and, with it, potentially the Democrats’ last shot at major drug pricing reforms in the foreseeable future — remains on life support, the Congressional Budget Office isn’t helping their case.

The CBO last week released a new slide deck, outlining an update to its model on how Medicare negotiations might take a bite out of new drugs making it to market. The new model estimates a 10% long-term reduction in the number of new drugs, whereas a previous CBO report from August estimated that 8% fewer new drugs will enter the market over 30 years.

Joshua Brumm, Dyne Therapeutics CEO

FDA or­ders DMD tri­al halt, rais­ing ques­tions about a whole class of promis­ing drugs

Dyne Therapeutics’ stock took a nasty hit this morning after the biotech put out word that the FDA had slapped a clinical hold on their top program for Duchenne muscular dystrophy. And now speculation is bouncing around Biotwitter that there could be a class effect at work here that would implicate other drug developers in the freeze.

Dyne execs didn’t have a whole lot to say about why the FDA sidelined their IND for DYNE-251 in DMD while “requesting additional clinical and non-clinical information for” the drug.

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CEO Lex Rovner (64x Bio)

A George Church spin­out fight­ing the vi­ral vec­tor bot­tle­neck in cell and gene ther­a­py lands $55M

A synthetic biology company spun out of George Church’s lab is set to tackle the gene therapy manufacturing bottleneck, and it just landed $55 million in a Series A financing round to do so.

64x Bio comes out of the Harvard Department of Genetics. CEO Lex Rovner and her team — which right now, sits around 10 people — are looking to tackle a key hurdle for major companies: manufacturing cell and gene therapies.