Michael Amoroso, Precision BioSciences CEO

UP­DAT­ED: With eyes on first al­lo­gene­ic CAR-T ap­proval, Pre­ci­sion touts 100% re­sponse in 's­mall niche' pop­u­la­tion

Pre­ci­sion Bio­Sciences has grand reg­u­la­to­ry am­bi­tions for its lead pro­gram: first al­lo­gene­ic CAR-T ther­a­py on the mar­ket, but the biotech will have to shore up safe­ty con­cerns of its drug as four deaths were re­port­ed in a Phase I/IIa tri­al.

En route to meet­ing with the FDA lat­er this year on po­ten­tial reg­is­tra­tion strat­e­gy, the North Car­oli­na biotech is out with new in­ter­im Phase I/IIa clin­i­cal da­ta on its prized pos­ses­sion, dubbed PB­CAR0191. The an­ti-CD19 can­di­date is be­ing test­ed in pa­tients with re­lapsed or re­frac­to­ry ag­gres­sive lym­phomas.

All 11 evalu­able CAR-T re­lapsed pa­tients re­spond­ed to the ther­a­py as of a May 31 da­ta cut­off, the biotech said Wednes­day morn­ing. Eight of the 11 pa­tients had a com­plete re­sponse at day 28. The da­ta come from six pa­tients on dose lev­el 3 and an­oth­er six in a co­hort added this year at dose lev­el 4. One of the 12 pa­tients died at day 23 due to “sus­pect­ed flu­dara­bine-as­so­ci­at­ed neu­ro­tox­i­c­i­ty,” the biotech said.

The tri­al saw mul­ti­ple Grade 5 events with four pa­tient deaths. In one of the two co­horts, there were two deaths “re­lat­ed to in­fec­tions and sus­pect­ed flu­dara­bine as­so­ci­at­ed neu­ro­tox­i­c­i­ty.” In the oth­er co­hort, two deaths were al­so re­lat­ed to the “sus­pect­ed” flu-as­so­ci­at­ed neu­ro­tox­i­c­i­ty.

“Is this a small niche of pa­tients? Why fo­cus on the re­lapsed CAR-T pop­u­la­tion? The short­est an­swer I can pro­vide is pa­tients need this ur­gent­ly and the time has nev­er been more pre­car­i­ous,” CEO Michael Amoroso said on an in­vestor call. “The CAR-T re­lapsed pop­u­la­tion is ex­pect­ed to grow four- to five-fold over the next few years.”

Three of six evalu­able pa­tients re­spond­ed for at least six months, and six of the 11 pa­tients were still re­spond­ing as of the cut­off date. Sev­en of 10 evalu­able pa­tients had a pro­gres­sion free sur­vival of at least two months, the biotech said.

Pre­ci­sion ex­pects to start con­ver­sa­tions with the FDA in the third quar­ter and gen­er­ate da­ta on an­oth­er “three, four or five pa­tients,” Amoroso said on the in­vestor call. The com­pa­ny’s stock $DTIL was up about 9.5% be­fore the open­ing bell Wednes­day morn­ing.

Where­as au­tol­o­gous CAR-T ther­a­pies take cells di­rect­ly from the pa­tient, Pre­ci­sion’s ther­a­py takes T cells from donors and us­es gene edit­ing to mod­i­fy them. Au­tol­o­gous CAR-T ther­a­pies have racked up mul­ti­ple ap­provals in re­cent years — Gilead and Kite’s Yescar­ta and Tecar­tus, No­var­tis’ Kym­ri­ah, Bris­tol My­ers Squibb’s Breyanzi and Leg­end-J&J’s Carvyk­ti — but al­lo­gene­ic CAR-T has not se­cured reg­u­la­to­ry vic­to­ry yet.

Amoroso was Kite’s chief com­mer­cial of­fi­cer dur­ing the ear­ly days of the Yescar­ta mar­ket roll­out and joined Pre­ci­sion last au­tumn.

“Over­all, we view Pre­ci­sion’s pipeline up­dates as lack­lus­ter among the al­lo­gene­ic CAR-T land­scape,” William Blair an­a­lysts wrote in a note af­ter the biotech’s pipeline up­date. “In our view, Pre­ci­sion’s dif­fer­en­ti­a­tion in on­ly pre­vi­ous re­lapsed au­tol­o­gous CAR-T pa­tient pop­u­la­tion is a po­ten­tial­ly lim­it­ed share of the NHL mar­ket with its lead PCAR0191 pro­gram; how­ev­er, the ex­act mech­a­nis­tic ra­tio­nal for why its prod­uct serves this pop­u­la­tion bet­ter than oth­ers in this space is un­clear.”

Fur­ther down the pipeline, Pre­ci­sion’s sec­ond gen­er­a­tion an­ti-CD19 al­lo­gene­ic CAR-T is ex­pect­ed to re­sume dos­ing in the third quar­ter. The com­pa­ny pre­vi­ous­ly paused dos­ing to op­ti­mize man­u­fac­tur­ing in the first quar­ter. New clin­i­cal tri­al ma­te­r­i­al is slat­ed to be re­leased soon so the dose lev­el 2 group can be­gin, the biotech said.

And the com­pa­ny is al­so at­tempt­ing to com­pete against Carvyk­ti, a re­cent­ly ap­proved CAR-T for pa­tients with re­lapsed or re­frac­to­ry mul­ti­ple myelo­ma. Pre­ci­sion is bet­ting it can best the biotech-Big Phar­ma duo by com­bin­ing its al­lo­gene­ic CAR-T, named PB­CAR269A, with Spring­Works Ther­a­peu­tics’ nirogace­s­tat. A Phase I/IIa study is mov­ing in­to dose lev­el 3.

The fo­cus on hu­man ther­a­pies comes af­ter a spin­out of a food and agri­cul­ture busi­ness, named Elo Life Sys­tems, at the end of 2021.

This sto­ry has been up­dat­ed with an­a­lyst com­ment. 

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.