Ralph Mechoulam. EPM via YouTube

Start­up EPM launch­es, high off cannabi­noid acid in­no­va­tion

When Sue Sis­ley opened the first bag of her Wash­ing­ton-li­censed weed, she knew some­thing was wrong. It came with the verisimil­i­tude of gov­ern­ment cheese, a bu­reau­crat­ic knock-off that nei­ther looked nor smelled like the re­al thing.

“It was this green pow­der with lit­tle sticks and leaves,” Sis­ley, head of the Scotts­dale Re­search Group, told End­points News ear­li­er this month.”So di­lut­ed.”

Sue Sis­ley

Two years ago, Sis­ley gained ap­proval for a PhII study on the ef­fects of mar­i­jua­na on vet­er­ans with PTSD. Since the 1960s, though, the DEA has on­ly al­lowed one lab in the coun­try, at the Uni­ver­si­ty of Mis­sis­sip­pi, to grow mar­i­jua­na. That meant that when Sis­ley and oth­er re­searchers be­gan some of the first mod­ern stud­ies on med­ical mar­i­jua­na, they were forced to use a prod­uct that looks more like oregano than weed. Al­so, it ap­peared to be moldy.

It was just one of sev­er­al prob­lems that have plagued cannabis re­search and kept the drug in­dus­try from fol­low­ing the stri­dent changes in the na­tion­al view of a once-taboo drug. More broad­ly, re­search in­to mar­i­jua­na and de­riv­a­tives such as cannabi­noids has suf­fered from a lack of pre­ci­sion: The un­der­ly­ing prob­lem be­hind the gov­ern­ment weed is that weed doesn’t come with a stan­dard dose of THC, or stan­dard­ized at all, as you’d want for a drug tri­al. And cannabi­noids might have more pre­ci­sion, but they’re plant ex­tracts — not the chem­i­cal com­pounds the FDA and drug com­pa­nies want for clin­i­cal tri­als.

Which is why Raphael Me­choulam, the 88-year-old Is­raeli “grand­fa­ther” of cannabis re­search, was so ex­cit­ed about the launch of the start­up EPM yes­ter­day and the sig­na­ture tech­nol­o­gy he helped pro­duce: The dis­til­la­tion, sta­bi­liza­tion and in­dus­tri­al-lev­el pro­duc­tion of cannabi­noid acids, the po­tent mol­e­cules that give rise to the plant’s psy­chotrop­ic ef­fects and that, com­pa­ny founders say, could move soon to the clin­ic.

“Here we have a new fam­i­ly of cannabi­noid that are prob­a­bly par­al­lel or even bet­ter than CBD it­self,” he told End­points.

Reshef Swisa

Me­choulam and CEO Reshef Swisa are care­ful to dis­tance them­selves from the plant and re­search done di­rect­ly on its con­sump­tion. But at its root, the point of the new mol­e­cules is to un­lock for the clin­ic the leaf and oil based ef­fects ad­vo­cates have boast­ed about for years and that orig­i­nal­ly drove Me­choulam to start study­ing mar­i­jua­na in the ear­ly 1960s, when as a young re­searcher at the Re­hovot-based Weiz­man In­sti­tute, he man­aged to con­vince a lo­cal po­lice of­fi­cer to il­le­gal­ly hand him five ki­los of Lebanese hashish and then prompt­ly car­ried the pun­gent par­cel from the sta­tion to his lab on a crowd­ed bus of pas­sen­gers ask­ing “What the hell is this smell?”

Me­choulam’s re­search then was to dis­till the ac­tive in­gre­di­ent in mar­i­jua­na, THC. This new sci­ence goes a cou­ple steps fur­ther, iso­lat­ing and sta­bi­liz­ing the acids that give rise to cannabi­noids in the first place.

The prob­lem with look­ing in­to these acids has al­ways been that while they ap­pear on the plant alive, they dis­ap­pear off the plant it­self as it be­gins to dry. This earned them the movie-style moniker “the mys­tery com­pounds,” Swisa told End­points. You could smoke weed your whole life with­out en­coun­ter­ing them.

But by tak­ing the acid from the plant and us­ing a par­tic­u­lar es­ter, EPM re­searchers were able to sta­bi­lize it, cre­at­ing a po­tent com­pound they can take in­to the lab as you would ibupro­fen. Swisa said they’ve spo­ken with the FDA, and their prod­uct would be treat­ed not as cannabis, with­out all its at­ten­dant rules and stig­mas, but as any oth­er drug in de­vel­op­ment.

“You can look at this com­pound as in­spired by cannabis,” Swisa said. “But it is a se­mi-syn­thet­ic com­pound.”

The im­pli­ca­tions are about as man­i­fold as the wild promise med­i­c­i­nal weed has some­times held, and on­ly tri­als will tell what in­di­ca­tions bear fruit. EPM has done re­search on hu­man cells and rats in­to the com­pounds’ ef­fect on IBD, skin dis­eases and meta­bol­ic dis­eases, find­ing sim­i­lar rates of ef­fec­tive­ness to steroids and oth­er drugs with­out the steep side ef­fects those drugs can bring. They hope to move in­to the clin­ic on a cou­ple in­di­ca­tions soon.

But the crux is that this puts the drug in a form — dis­crete, patentable and con­sis­tent — that makes them at­trac­tive to phar­ma, Swisa said. They hope to li­cense their prod­uct out to oth­er phar­ma­ceu­ti­cal com­pa­nies, and he not­ed that there was en­thu­si­as­tic in­ter­est when they pre­sent­ed the re­sults Mon­day in LA — but then again, they were pre­sent­ing at a cannabis con­fer­ence.

“Peo­ple chas­ing our re­searchers; peo­ple fol­low­ing them; peo­ple com­ing to ask what can be done; peo­ple com­ing to our booths, ask­ing ques­tions, see­ing what we can do and how we can col­lab­o­rate,” he said. “The in­ter­est is big.”

The field is in­deed hot right now de­spite on­go­ing con­cerns from some re­searchers, in­clud­ing Me­choulam, that the pub­lic is em­brac­ing CBD be­fore it’s been prop­er­ly test­ed. Re­sults from Sis­ley’s tri­al are forth­com­ing; oth­er tri­als are un­der­way or al­ready back with pos­i­tive re­sults and sci­en­tists are now mak­ing ef­forts to bio­engi­neer THC through CRISPR. This morn­ing, the EU OK’d a cannabis-based epilep­sy drug al­ready ap­proved by the FDA.

But for a re­searcher who’s been in the game as long as Me­choulam, there still aren’t enough clin­i­cal tri­als and there’s a bit­ter­sweet tinge to some of these new pro­nounce­ments. Me­choulam’s lab con­duct­ed a small clin­i­cal tri­al on CBD and epilep­sy in 1980, find­ing it all but elim­i­nat­ed seizures in 4 of 8 pa­tients and curbed them in three hours. But it was decades be­fore any­one took up that work.

“This was a pity,” Me­choulam said. “We could have saved thou­sands of pa­tients, in par­tic­u­lar chil­dren.”

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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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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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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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.

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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