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.

The Fac­tors Dri­ving a Rapid Evo­lu­tion of Gene & Cell Ther­a­py and CAR-T Clin­i­cal Re­search in APAC

APAC is the fastest growing region globally for cell & gene therapy trials representing more than a third of all cell & gene studies globally, with China leading in the region. 

APAC is the leading location globally for CAR-T trials with China attracting ~60% of all CAR-T trials globally between 2015-2022. The number of CAR-T trials initiated by Western companies has rapidly increased in recent years (current CAGR of about 60%), with multiple targets being explored including CD19, CD20, CD22, BCMA, CD30, CD123, CD33, CD38, and CD138.

The End­points 11; blue­bird's $3M gene ther­a­py; Bio­gen tout new neu­ro da­ta; Harsh re­views for can­cer drugs; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

Reading about John Carroll’s pick of biotech’s most promising startups has become a treasured tradition. If you ever get curious about previous classes of the Endpoints 11, you can find all of them (plus a number of our other regular specials) here.

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EMA warns of short­ages of two Boehringer heart drugs due to a spike in de­mand

The EMA is putting EU member states on alert over the shortage of two drugs that counter heart attacks due to an uptick in demand.

On Friday, the EMA sent out a warning that two Boehringer Ingelheim drugs are experiencing a shortage: Actilyse and Metalyse. The drugs are used as emergency treatments for adults experiencing acute myocardial infarction, or a heart attack, by dissolving blood clots that have formed in the blood vessels.

The End­points 11: The top pri­vate biotechs in pur­suit of new drugs. Push­ing the en­ve­lope with pow­er­ful new tech­nolo­gies

Right around the beginning of the year, we got a close-up look at what happens after a boom ripples through biotech. The crash of life sciences stocks in Q1 was heard around the world.

In the months since, we’ve seen the natural Darwinian down cycle take effect. Reverse mergers made a comeback, with more burned out shells to go public at a time IPOs and road shows are out of favor. And no doubt some of the more recent arrivals on the investing side of the business are finding greener pastures.

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An­oth­er Cipla site lands a Form 483 over clean­ing is­sues and QC con­trols

A Cipla drug manufacturing site in India has once again landed in the crosshairs of FDA inspectors.

The facility in question is Cipla’s drug manufacturing facility in the village of Verna, in the state of Goa in India’s southwest. In a sign that foreign inspections might ramp up again, the FDA’s visit from Aug. 16 to Aug. 22 uncovered six observations.

The 11-page report noted that environmental monitoring at the site did not properly ensure that microbial contaminants were not making any impact in the aseptic filling areas. It also found that procedures meant to stop microbial contamination were not adequately conducted in aseptic areas of the facility.

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Solicitor General Elizabeth Prelogar

Should SCO­TUS hear Am­gen's Repatha case? So­lic­i­tor gen­er­al says no

Back in April, Amgen said it was encouraged by the solicitor general’s anticipated review of its Supreme Court petition to rehear a Repatha patent case. They’re likely much less optimistic about the outcome now.

Solicitor General Elizabeth Prelogar wrote in a recent 27-page brief that Amgen’s arguments “lack merit and further review is not warranted.”

The case traces back to a suit filed in 2014 against Sanofi and Regeneron’s Praluent, which ended up beating Amgen’s PCSK9 blockbuster Repatha to market by a month just a year later.

Klick Health gath­ers biotech and phar­ma lu­mi­nar­ies to dis­cuss in­dus­try in­no­va­tions, in­vest­ments and fu­ture

At Klick Health’s first Ideas Exchange conference with biotech and pharma industry insiders since before the pandemic began, it was no surprise many conversations included Covid topics. Yet while vaccines and treatments were discussed, so too were the effects on drug development, federal responses, health inequities — and what to do now and next.

George Yancopoulos, chief scientist and cofounder of Regeneron, opened the conference responding to a question from Acorda CEO Ron Cohen about the spotlight on the industry during Covid and some of the “flak” biopharma has taken in the past.

FDA's out­side ex­perts vote in fa­vor of Fer­ring's fe­cal trans­plant for C. dif­fi­cile, set­ting the stage for Seres

FDA’s outside advisors voted in favor of Ferring Pharmaceuticals’ RBX2660, an experimental poop-based drug implant that the company says would be the first microbiota-based live biotherapeutic to receive an FDA green light.

That was a point repeatedly discussed during the Vaccines and Related Biological Products Advisory Committee, or VRBPAC, meeting Thursday when evaluating Ferring’s fecal microbiota transplant, or FMT, for reducing the recurrence of Clostridioides difficile infection in adults who have received antibiotics. Multiple members brought up the need for a regulated product amid a landscape of unregulated FMTs already happening in clinical care.

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Vas Narasimhan, Novartis CEO (Simon Dawson/Bloomberg via Getty Images)

No­var­tis un­veils 'US-first' strat­e­gy ahead of San­doz spin­off

Weeks after announcing the spinoff of generics arm Sandoz, Vas Narasimhan paints a picture of the new, slimmer Novartis — with a “US-first mindset,” he said at an investor event on Thursday.

The CEO unveiled ambitious plans to become a top-five player in the US by 2027 at Novartis’ “Meet the Management” event in Basel, Switzerland, which means ramping up clinical trials in the states and “building capability and talent, among other things.” The company’s also shooting for a top-three ranking in China.

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