Ker­ris­dale’s Sahm Ad­ran­gi leads a bru­tal new biotech short at­tack as tri­al re­sults loom

Ker­ris­dale Cap­i­tal’s Sahm Ad­ran­gi has called a cou­ple of re­cent biotech dis­as­ters in ad­vance. Just two months ago his pre­dic­tion that Bavar­i­an Nordic’s can­cer vac­cine would flunk a long-run­ning study proved ac­cu­rate, and that came right on the heels of Sage’s ug­ly mis­fire on SRSE demon­strat­ing that the drug was no bet­ter than a place­bo in get­ting a re­sponse.

Sahm Ad­ran­gi

Now the in­flu­en­tial hedge fund man­ag­er has got a new biotech in his sights, and this morn­ing he’s pulling the trig­ger on an­oth­er short at­tack, blast­ing the com­pa­ny’s lead drug as an ab­solute fail­ure in the mak­ing.

The biotech is Prothena $PR­TA and the drug is NEOD001, an AL amy­loi­do­sis drug which fig­ures promi­nent­ly in a mar­ket cap that has swelled well past the $2 bil­lion mark.

Ac­cord­ing to Ker­ris­dale an­a­lysts, the Phase I/II study for this drug failed to show any promise. Point­ing to ex­pert — though un­named — fig­ures in the field, the da­ta from the loom­ing Phase IIb and Phase III stud­ies will prove the drug’s worth­less­ness be­yond any doubt.

“It’s clear that this has no chance of suc­cess,” Ad­ran­gi tells me. “Both stud­ies are go­ing to flop.”

Any ex­pec­ta­tions of suc­cess, they add, are built on ran­dom re­spons­es for the NT-proB­NP bio­mark­er that are like­ly to hap­pen at any time in any case.

To be sure, Ker­ris­dale’s mis­sion is clear here — and it’s al­so con­tro­ver­sial in a mar­ket that of­ten sin­gles out shorts for crit­i­cism. Hav­ing pre­dict­ed a cat­a­stro­phe in the clin­ic, it’s now bet­ting that Prothena’s shares will tank, and if it does they stand to prof­it enor­mous­ly. But in a field where anony­mous short at­tacks are a dime a dozen, Ker­ris­dale’s Ad­ran­gi goes pub­lic with his gam­bles, and the rea­sons why he’s gone on the of­fen­sive. They rep­re­sent the po­lar op­po­site of the sell-side notes, which of­ten gain wide­spread at­ten­tion for rosy sce­nar­ios.

Prothena’s shares dropped 8% on the re­port this morn­ing.

I’ve queried Prothena ex­ecs for a re­sponse as Ker­ris­dale’s re­port hit Wednes­day morn­ing.

Ker­ris­dale’s short re­ports — they al­so go long on oc­ca­sion — are typ­i­cal­ly harsh and Prothena is no ex­cep­tion. Some key points:

  • “Prothena’s “best re­sponse” is an un­in­for­ma­tive mea­sure that sub­sti­tutes vari­ance for ef­fi­ca­cy, and Prothena pro­vides this in lieu of mean­ing­ful da­ta be­cause NEOD001 does not work.” The re­port cites one pa­tient who had to drop out of the study af­ter a dan­ger­ous de­vel­op­ment, but was still count­ed as a suc­cess. And Ker­ris­dale ac­cus­es Prothena of hid­ing bad da­ta.
  • “Prothena’s car­diac best re­sponse rate is mere­ly a byprod­uct of well-doc­u­ment­ed nat­ur­al vari­ance, and we be­lieve there is no chance of NEOD001 pro­duc­ing sta­tis­ti­cal­ly sig­nif­i­cant re­sults in its cur­rent Phase 2b and Phase 3 tri­als.”
  • There was no dose re­sponse rate tracked and no way the drug can beat the re­spons­es seen in a con­trol arm.
  • The sci­ence is bad. “The pro­teins and amy­loid struc­tures vary be­tween pa­tients and even among amy­loid de­posits with­in a sin­gle pa­tient far too much for a sin­gle cryp­tic epi­tope to work with any con­sis­ten­cy.”

And they even go af­ter Neil Wood­ford, a backer who has al­so in­vest­ed in North­west Bio­ther­a­peu­tics, now trad­ing as a pen­ny stock.

Prothena re­cent­ly wrote off a pso­ri­a­sis drug af­ter a dis­ap­point­ing Phase Ib, blunt­ly call­ing the da­ta a dis­ap­point­ment. But Ad­ran­gi and his an­a­lyst say they had no choice in the mat­ter, call­ing it im­pos­si­ble to mask.

Ker­ris­dale takes no pris­on­ers dur­ing these at­tacks.

BY­OD Best Prac­tices: How Mo­bile De­vice Strat­e­gy Leads to More Pa­tient-Cen­tric Clin­i­cal Tri­als

Some of the most time- and cost-consuming components of clinical research center on gathering, analyzing, and reporting data. To improve efficiency, many clinical trial sponsors have shifted to electronic clinical outcome assessments (eCOA), including electronic patient-reported outcome (ePRO) tools.

In most cases, patients enter data using apps installed on provisioned devices. At a time when 81% of Americans own a smartphone, why not use the device they rely on every day?

Image: Shutterstock

Eli Lil­ly asks FDA to re­voke EUA for Covid-19 treat­ment

Eli Lilly on Friday requested that the FDA revoke the emergency authorization for its Covid-19 drug bamlanivimab, which is no longer as effective as a combo therapy because of a rise in coronavirus variants across the US.

“With the growing prevalence of variants in the U.S. that bamlanivimab alone may not fully neutralize, and with sufficient supply of etesevimab, we believe now is the right time to complete our planned transition and focus on the administration of these two neutralizing antibodies together,” Daniel Skovronsky, Lilly’s CSO, said in a statement.

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As­traZeneca-Alex­ion merg­er slides through FTC re­view af­ter sup­posed M&A crack­down pos­es no bar­ri­ers

The AstraZeneca-Alexion megamerger received a good sign Friday, despite warning signs of the tides turning against large M&A pharma deals.

US regulators at the FTC have cleared the acquisition for approval, AstraZeneca announced, all but signing off on the deal to go through once it officially closes in the third quarter. AstraZeneca originally said it was planning to buy out Alexion back in December for $39 billion.

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J&J faces CDC ad­vi­so­ry com­mit­tee again next week to weigh Covid-19 vac­cine risks

The CDC’s Advisory Committee on Immunization Practices punted earlier this week on deciding whether or not to recommend lifting a pause on the administration of J&J’s Covid-19 vaccine, but the committee will meet again in an emergency session next Friday to discuss the safety issues further.

The timing of the meeting likely means that the J&J vaccine will not return to the US market before the end of next week as the FDA looks to work hand-in-hand with the CDC to ensure the benefits of the vaccine still outweigh the risks for all age groups.

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David Stack, Pacira Biosciences CEO

In high­ly un­usu­al move, Paci­ra sues med­ical jour­nal for li­bel over its non-opi­oid painkiller

A New Jersey biotech whose only approved drug is used as a painkiller after surgeries is suing a scientific journal, its editors and a handful of authors for libel after the publication printed numerous papers and editorials that the company says discredited the drug.

Pacira Biosciences filed the complaint against the American Society of Anesthesiologists in the US District Court for New Jersey on Wednesday afternoon. A February issue of the group’s journal Anesthesiology printed three articles and other content full of “bias” that “seriously disparaged” the drug Exparel, Pacira claimed.

Osman Kibar (Samumed, now Biosplice)

Os­man Kibar lays down his hand at Sa­mumed, step­ping away from CEO role as his once-her­ald­ed an­ti-ag­ing biotech re­brands

Samumed made quite the entrance back in 2016, when it launched with some anti-aging programs and a whopping $12 billion valuation. That level of fanfare was nowhere to be found on Thursday, when the company added another $120 million to its coffers and quietly changed its name to Biosplice Therapeutics.

Why the sudden rebrand?

“We did that for obvious reasons,” CFO and CBO Erich Horsley told Endpoints News. “The name Biosplice echoes our science much more than Samumed does.”

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Ex­clu­sive in­ter­view: Pe­ter Marks on why full Covid-19 vac­cine ap­provals could be just months away

Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, took time out of his busy schedule last Friday to discuss with Endpoints News all things related to his work regulating vaccines and the pandemic.

Marks, who quietly coined the name “Operation Warp Speed” before deciding to stick with his work regulating vaccines at the FDA rather than join the Trump-era program, has been the face of vaccine regulation for the FDA throughout the pandemic, and is usually spotted in Zoom meetings seated in front of his wife’s paintings.

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Near­ly a year af­ter Au­den­tes' gene ther­a­py deaths, the tri­al con­tin­ues. What hap­pened re­mains a mys­tery

Natalie Holles was five months into her tenure as Audentes CEO and working to smooth out a $3 billion merger when the world crashed in.

Holles and her team received word on the morning of May 5 that, hours before, a patient died in a trial for their lead gene therapy. They went into triage mode, alerting the FDA, calling trial investigators to begin to understand what happened, and, the next day, writing a letter to alert the patient community so they would be the first to know. “We wanted to be as forthright and transparent as possible,” Holles told me late last month.

The brief letter noted two other patients also suffered severe reactions after receiving a high dose of the therapy and were undergoing treatment. One died a month and a half later, at which point news of the deaths became public, jolting an emergent gene therapy field and raising questions about the safety of the high doses Audentes and others were now using. The third patient died in August.

“It was deeply saddening,” Holles said. “But I was — we were — resolute and determined to understand what happened and learn from it and get back on track.”

Eleven months have now passed since the first death and the therapy, a potential cure for a rare and fatal muscle-wasting disease called X-linked myotubular myopathy, is back on track, the FDA having cleared the company to resume dosing at a lower level. Audentes itself is no more; last month, Japanese pharma giant Astellas announced it had completed working out the kinks of the $3 billion merger and had restructured and rebranded the subsidiary as Astellas Gene Therapies. Holles, having successfully steered both efforts, departed.

Still, questions about precisely what led to the deaths of the 3 boys still linger. Trial investigators released key details about the case last August and December, pointing to a biological landmine that Audentes could not have seen coming — a moment of profound medical misfortune. In an emerging field that’s promised cures for devastating diseases but also seen its share of safety setbacks, the cases provided a cautionary tale.

Audentes “contributed in a positive way by giving a painful but important example for others to look at and learn from,” Terry Flotte, dean of the UMass School of Medicine and editor of the journal Human Gene Therapy, told me. “I can’t see anything they did wrong.”

Yet some researchers say they’re still waiting on Astellas to release more data. The company has yet to publish a full paper detailing what happened, nor have they indicated that they will. In the meantime, it remains unclear what triggered the events and how to prevent them in the future.

“Since Audentes was the first one and we don’t have additional information, we’re kind of in a holding pattern, flying around, waiting to figure out how to land our vehicles,” said Jude Samulski, professor of pharmacology at UNC’s Gene Therapy Center and CSO of the gene therapy biotech AskBio, now a subsidiary of Bayer.

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Pascal Soriot (AstraZeneca via YouTube)

Af­ter be­ing goad­ed to sell the com­pa­ny, Alex­ion's CEO set some am­bi­tious new goals for in­vestors. Then Pas­cal So­ri­ot came call­ing

Back in the spring of 2020, Alexion $ALXN CEO Ludwig Hantson was under considerable pressure to perform and had been for months. Elliott Advisers had been applying some high public heat on the biotech’s numbers. And in reaching out to some major stockholders, one thread of advice came through loud and clear: Sell the company or do something dramatic to change the narrative.

In the words of the rather dry SEC filing that offers a detailed backgrounder on the buyout deal, Alexion stated: ‘During the summer and fall of 2020, Alexion also continued to engage with its stockholders, and in these interactions, several stockholders encouraged the company to explore strategic alternatives.’

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