Rachel Haurwitz, Caribou president and CEO

Along­side tiny da­ta drop, Cari­bou plans dose es­ca­la­tion for its first off-the-shelf CAR-T tri­al

In May, Cari­bou Bio­sciences shared im­pres­sive ear­ly da­ta on its first tri­al for an off-the-shelf CAR-T ther­a­py, dis­clos­ing that four of five pa­tients suf­fer­ing from B cell non-Hodgkin’s lym­phoma had a com­plete re­sponse.

With its EHA pre­sen­ta­tion com­ing up Sat­ur­day, the Jen­nifer Doud­na-found­ed biotech has un­wrapped more da­ta on its lead can­di­date. As of May, the biotech has re­sults from one more pa­tient in its Phase I tri­al — a sixth pa­tient who had an ini­tial com­plete re­sponse, but saw their can­cer progress three months af­ter re­ceiv­ing the CAR-T in­fu­sion.

Two oth­er pa­tients in the tri­al al­so reached com­plete re­sponse un­til the can­cer pro­gressed at six months af­ter treat­ment. On the oth­er hand, one pa­tient in the tri­al has had on­go­ing com­plete re­sponse for twelve months.

Num­bers-wise, that puts Cari­bou’s an­ti-CD19 CAR-T ther­a­py at six of six pa­tients re­spond­ing to the treat­ment and two of five with com­plete re­sponse at the six-month mark.

When asked about dura­bil­i­ty, Cari­bou pres­i­dent and CEO Rachel Hau­r­witz told End­points News: “We’re en­cour­aged that at this point we see a 40% 6-month CR rate — I think that’s quite promis­ing. I rec­og­nize this is a small num­ber of pa­tients and ear­ly da­ta, so [dura­bil­i­ty] is ob­vi­ous­ly some­thing we are con­tin­u­ing to keep an eye on.

“It’s al­so why we’re dose-es­ca­lat­ing to dose lev­el two with a spe­cif­ic fo­cus on dura­bil­i­ty,” Hau­r­witz con­tin­ued.

In­vestors did not feel the same way. Cari­bou’s stock $CR­BU had been trad­ing up around 30% since the first news dropped in May, though all in all it has dropped more than 40% since the Berke­ley, CA-based biotech went pub­lic in Ju­ly. In re­ac­tion to this up­dat­ed da­ta, Cari­bou was trad­ing down over 16% be­fore the mar­kets opened. Soon af­ter the mar­kets opened, Cari­bou fell be­low where it was pri­or to the May an­nounce­ment, down 34% from one day ago.

SVB an­a­lysts had a less re­ac­tionary view, main­tain­ing that Cari­bou’s can­di­date was “ear­ly but com­pet­i­tive, though de­bate rages on dura­bil­i­ty.” SVB’s Mani Foroohar and Rick Bi­enkows­ki wrote:

Ques­tions around ex­pan­sion/PK ki­net­ics con­tin­ue to sim­mer be­neath the sur­face, but our view is that this up­date shows enough ev­i­dence of clin­i­cal ef­fi­ca­cy with a mod­est ab­solute dose yield­ing a small tail of per­sis­tent cells.

Mov­ing for­ward, the biotech will test a sec­ond dose lev­el that has twice the num­ber of CAR-T cells as the first.

Safe­ty-wise, four of the six pa­tients suf­fered from grade 3 ad­verse events, with three in­stances of low white blood cell counts, one of neu­trope­nia and one of ICANS.

Un­like au­tol­o­gous CAR-T ther­a­pies avail­able now, al­lo­gene­ic CAR-T ther­a­pies don’t have to be made with the T cells of each in­di­vid­ual pa­tient. In a cli­mate where doc­tors have to weigh which pa­tients get per­son­al­ized CAR-T ther­a­py and which don’t, as re­port­ed by STAT News, an off-the-shelf can­cer treat­ment would be a colos­sal break­through.

A host of oth­er biotechs are work­ing on off-the-shelf CAR-T ther­a­pies. On Wednes­day, Pre­ci­sion Bio­Sciences an­nounced in­ter­im Phase I/II re­sults on its an­ti-CD19 ther­a­py that fea­tured se­ri­ous safe­ty con­cerns and four pa­tient deaths. While Pre­ci­sion said it is head­ed to the FDA lat­er this year and aims to be­come the first al­lo­gene­ic CAR-T ap­proved, one an­a­lyst called the biotech’s pipeline “lack­lus­ter.”

Fol­low­ing a three-month clin­i­cal hold, Al­lo­gene restart­ed clin­i­cal tri­als for its off-the-shelf CAR-Ts in Jan­u­ary of this year. The biotech has a Phase II tri­al in re­lapsed/re­frac­to­ry large B cell lym­phoma planned for this year.

Ac­cord­ing to Cari­bou, what makes its ther­a­py dif­fer­ent is its ad­di­tion­al PD-1 knock­out, which is meant to make the treat­ment last longer. It al­so us­es a CRISPR sys­tem known as chRD­NA, pro­nounced as “chardon­nay,” which is sup­posed to be more spe­cif­ic and pre­vent un­want­ed mu­ta­tions — the con­cern that re­sult­ed in Al­lo­gene’s clin­i­cal hold.

The chRD­NA method us­es DNA-RNA hy­brid guides to di­rect the nu­cle­ase, the DNA cut­ter, to its lo­ca­tion, where­as ear­li­er ver­sions of CRISPR fea­tured RNA-on­ly guides. “It’s the in­clu­sion of DNA in the guides that dra­mat­i­cal­ly im­proves the speci­fici­ty of genome edit­ing,” Hau­r­witz said.

Cari­bou could en­roll up to 50 pa­tients on its ANTLER Phase I tri­al, though the biotech said it is not dis­clos­ing the cur­rent num­ber of pa­tients it has en­rolled. Hau­r­witz said vague­ly that the biotech will dis­close ad­di­tion­al tri­al da­ta be­fore the end of the year.

This ar­ti­cle has been up­dat­ed with ad­di­tion­al in­for­ma­tion on the tri­al and stock and an­a­lyst re­ac­tions, as well as to clar­i­fy when Cari­bou went pub­lic.

Scoop: Boehringer qui­et­ly shut­ters a PhII for one of its top drugs — now un­der re­view

Boehringer Ingelheim has quietly shut down a small Phase II study for one of its lead drugs.

The private pharma player confirmed to Endpoints News that it had shuttered a study testing spesolimab as a therapy for Crohn’s patients suffering from bowel obstructions.

A spokesperson for the company tells Endpoints:

Taking into consideration the current therapeutic landscape and ongoing clinical development programs, Boehringer Ingelheim decided to discontinue our program in Crohn’s disease. It is important to note that this decision is not based on any safety findings in the clinical trials.

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Deborah Dunsire, Lundbeck CEO

Af­ter a 5-year re­peat PhI­II so­journ, Lund­beck and Ot­su­ka say they're fi­nal­ly ready to pur­sue OK to use Rex­ul­ti against Alzheimer's ag­i­ta­tion

Five years after Lundbeck and their longtime collaborators at Otsuka turned up a mixed set of Phase III data for Rexulti as a treatment for Alzheimer’s dementia-related agitation, they’ve come through with a new pivotal trial success they believe will finally put them on the road to an approval at the FDA. And if they’re right, some analysts believe they’re a short step away from adding more than $500 million in annual sales for the drug, already approved in depression and schizophrenia.

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Chris Anzalone, Arrowhead CEO

Take­da, Ar­row­head spot­light da­ta from small tri­al show­ing RNAi works in a rare liv­er con­di­tion

Almost two years after Takeda wagered $300 million cash to partner with Arrowhead on an RNAi therapy for a rare disease, the companies are spelling out Phase II data that they believe put them one step closer to their big dreams.

In a small, open label study involving only 16 patients who had liver disease associated with alpha-1 antitrypsin deficiency (AATD), Arrowhead’s candidate — fazirsiran, previously ARO-AAT — spurred substantial reductions in accumulated mutant AAT protein in the liver, a hallmark of the condition. Investigators also tracked improvements in symptoms, with seven out of 12 who received the high, 200 mg dose seeing regression of liver fibrosis.

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No stranger to gene ther­a­py woes, Astel­las runs in­to an­oth­er safe­ty-re­lat­ed clin­i­cal hold

Astellas Pharma, which has been at the forefront of uncovering the risks associated with gene therapies delivered by adeno-associated viruses, must take another safety alarm head-on.

The FDA has slapped a clinical hold on Astellas’ Phase I/II trial of a gene therapy candidate for late-onset Pompe disease, after investigators flagged a serious case of peripheral sensory neuropathy.

It marks the latest in a streak of setbacks Astellas has encountered since making a splashy entry into the gene therapy space with its $3 billion buyout of Audentes. But the lead program, AT132 for the treatment of X-linked myotubular myopathy (XLMTM), had to be halted more than once after a total of four patients died in the trial — and the scientific community still doesn’t have all the answers of what caused the deaths.

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Alex­ion puts €65M for­ward to strength­en its po­si­tion on the Emer­ald Isle

Ireland has been on a roll in 2022, with several large pharma companies announcing multimillion-euro projects. Now AstraZeneca’s rare disease outfit Alexion is looking to get in on the action.

Alexion on Friday announced a €65 million ($68.8 million) investment in new and enhanced capabilities across two sites in the country, including at College Park in the Dublin suburb of Blanchardstown and the Monksland Industrial Park in the central Irish town of Athlone, according to the Industrial Development Agency of Ireland.

State bat­tles over mifepri­s­tone ac­cess could tie the FDA to any post-Roe cross­roads

As more than a dozen states are now readying so-called “trigger” laws to kick into effect immediate abortion bans following the overturning of Roe v. Wade on Friday, these laws, in the works for more than a decade in some states, will likely kick off even more legal battles as states seek to restrict the use of prescription drug-based abortions.

Since Friday’s SCOTUS opinion to overturn Americans’ constitutional right to an abortion after almost 50 years, reproductive rights lawyers at Planned Parenthood and other organizations have already challenged these trigger laws in Utah and Louisiana. According to the Guttmacher Institute, other states with trigger laws that could take effect include Arkansas, Idaho, Kentucky, Mississippi, Missouri, North Dakota, Oklahoma, South Dakota, Tennessee, Texas, and Wyoming.

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A Mer­ck part­ner is sucked in­to the fi­nan­cial quag­mire as key lender calls in a note

Another biotech standing on shaky financial legs has fallen victim to the bears.

Merck partner 4D Pharma has reported that a key lender, Oxford Finance, shoved the UK company into administration after calling in a $14 million loan they couldn’t immediately make good on. Trading in their stock was halted with a market cap that had fallen to a mere £30 million.

“Despite the very difficult prevailing market conditions,” 4D reported on Friday, the biotech had been making progress on finding some new financing and turned to Oxford with an alternative late on Thursday and then again Friday morning.

Members of the G7 from left to right: Prime Minister of Italy Mario Draghi, European Commission President Ursula von der Leyen, President Joe Biden, German Chancellor Olaf Scholz, British Prime Minister Boris Johnson, Canadian Prime Minister Justin Trudeau, Prime Minister of Japan Fumio Kishida, French President Emmanuel Macron and European Council President Charles Michel (AP Photo/Susan Walsh)

Biden and G7 na­tions of­fer funds for vac­cine and med­ical prod­uct man­u­fac­tur­ing project in Sene­gal

Amidst recently broader vaccine manufacturing initiatives from the EU and European companies, the G7 summit in the mountains of Bavaria has brought about some positive news for closing vaccine and medical product manufacturing gaps around the globe.

According to a statement from the White House, the G7 leaders have formally launched the partnership for global infrastructure, PGII. The effort will aim to mobilize hundreds of billions of dollars to deliver infrastructure projects in several sectors including the medical and pharmaceutical manufacturing space.

Fed­er­al judge de­nies Bris­tol My­er­s' at­tempt to avoid Cel­gene share­hold­er law­suit

Some Celgene shareholders aren’t happy with how Bristol Myers Squibb’s takeover went down.

On Friday, a New York federal judge ruled that they have a case against the pharma giant, denying a request to dismiss allegations that it purposely slow-rolled Breyanzi’s approval to avoid paying out $6.4 billion in contingent value rights (CVR).

When Bristol Myers put down $74 billion to scoop up Celgene back in 2019, liso-cel — the CAR-T lymphoma treatment now marketed as Breyanzi — was supposedly one of the centerpieces of the deal. After going back and forth on negotiations for about six months, BMS put $6.4 billion into a CVR agreement that required an FDA approval for Zeposia, Breyanzi and Abecma, each by an established date.