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.”

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

Covid-19 vac­cine boost­ers earn big thumbs up, but Mod­er­na draws ire over world sup­ply; What's next for Mer­ck’s Covid pill?; The C-suite view on biotech; 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.

You may remember that at the beginning of this year, Endpoints News set a goal to go broader and deeper. We are still working towards that, and are excited to share that Beth Snyder Bulik will be joining us on Monday to cover all things pharma marketing. You can sign up for her weekly Endpoints MarketingRx newsletter in your reader profile.

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No­var­tis de­vel­op­ment chief John Tsai: 'We go deep in the new plat­form­s'

During our recent European Biopharma Summit, I talked with Novartis development chief John Tsai about his experiences over the 3-plus years he’s been at the pharma giant. You can read the transcript below or listen to the exchange in the link above.

John Carroll: I followed your career for quite some time. You’ve had more than 20 years in big pharma R&D and you’ve obviously seen quite a lot. I really was curious about what it was like for you three and a half years ago when you took over as R&D chief at Novartis. Obviously a big move, a lot of changes. You went to work for the former R&D chief of Novartis, Vas Narasimhan, who had his own track record there. So what was the biggest adjustment when you went into this position?

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Amit Etkin, Alto Neuroscience CEO (Alto via Vimeo)

A star Stan­ford pro­fes­sor leaves his lab for a start­up out to re­make psy­chi­a­try

About five years ago, Amit Etkin had a breakthrough.

The Stanford neurologist, a soft-spoken demi-prodigy who became a professor while still a resident, had been obsessed for a decade with how to better define psychiatric disorders. Drugs for depression or bipolar disorder didn’t work for many patients with the conditions, and he suspected the reason was how traditional diagnoses didn’t actually get at the heart of what was going on in a patient’s brain.

Roche's Tecen­triq cross­es the fin­ish line first in ad­ju­vant lung can­cer, po­ten­tial­ly kick­ing off gold rush

While falling behind the biggest PD-(L)1 drugs in terms of sales, Roche has looked to carve out a space for its Tecentriq with a growing expertise in lung cancer. The drug will now take an early lead in the sought-after adjuvant setting — but competitors are on the way.

The FDA on Friday approved Tecentriq as an adjuvant therapy for patients with Stage II-IIIA non small cell lung cancer with PD-(L)1 scores greater than or equal to 1, making it the first drug of its kind approved in an early setting that covers around 40% of all NSCLC patients.

Susan Galbraith, Executive VP, Oncology R&D, AstraZeneca

As­traZeneca on­col­o­gy R&D chief Su­san Gal­braith: 'Y­ou're go­ing to need or­thog­o­nal com­bi­na­tion­s'

 

Earlier in the week we broadcast our 4th annual European Biopharma Summit with a great lineup of top execs. One of the one-on-one conversations I set up was with Susan Galbraith, the oncology research chief at AstraZeneca. In a wide-ranging discussion, Galbraith reviewed the cancer drug pipeline and key trends influencing development work at the pharma giant. You can watch the video, above, or stick with the script below. — JC

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Tillman Gerngross, Adagio CEO

Q&A: Till­man Gern­gross ex­plains why his Covid mAb will have an edge over an al­ready crowd­ed field

If anyone knows about monoclonal antibodies, it’s serial entrepreneur, Adimab CEO, and Dartmouth professor of bioengineering Tillman Gerngross.

Even the name of Gerngross’ new antibody startup Adagio Therapeutics is meant to reflect his vision behind the development of his Covid-19 mAb: slowly, he said, explaining that “everyone else, whether it’s Regeneron, Lilly, or AstraZeneca, Vir, they all valued speed over everything.”

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Susan Galbraith speaking at Endpoints News' virtual EUBIO21 summit

Imfinzi/treme­li­mum­ab com­bo scores As­traZeneca an­oth­er OS win — this time in liv­er can­cer

Is the tide turning on AstraZeneca’s battered PD-L1/CTLA4 combo?

A single priming dose of the experimental tremelimumab, followed by Imfinzi every four weeks, beat Nexavar (sorafenib) in helping a group of liver cancer patients live longer in a Phase III study, the company reported, meeting the primary endpoint.

Specifically, the two drugs extended overall survival for patients with unresectable hepatocellular carcinoma who had not received prior systemic therapy and were not eligible for localized treatment.

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FDA's vac­cine ad­comm unan­i­mous­ly sup­ports Mod­er­na's boost­er in same pop­u­la­tions as Pfiz­er's boost­er

The FDA’s vaccine advisory committee on Thursday voted 19-0 in support of expanding Moderna’s Covid-19 vaccine EUA for booster doses for certain high-risk individuals. FDA is expected to authorize the Moderna booster shortly.

Similarly to the Pfizer booster shot, Moderna’s will likely be authorized for those older than 65, adults at high risk of severe Covid-19, and adults whose frequent institutional or occupational exposure to SARS-CoV-2 puts them at high risk of serious complications of Covid-19. But unlike the Pfizer adcomm, where FDA had to scramble to get the committee to vote in favor of a booster, this committee was unanimous with the Moderna shot.