Charles Nichols, LSU School of Medicine

Could psy­che­delics tack­le the obe­si­ty cri­sis? A long­time re­searcher in the field says his lat­est mouse study sug­gests po­ten­tial

Psy­che­delics have ex­pe­ri­enced a re­nais­sance in re­cent years amid a tor­rent of pre­clin­i­cal and clin­i­cal re­search sug­gest­ing it might pro­vide a path to treat mood dis­or­ders con­ven­tion­al reme­dies have on­ly scraped at. Now a pre­clin­i­cal tri­al from a young biotech sug­gests at least one psy­che­del­ic com­pound has ef­fects be­yond the mind, and — if you be­lieve the still very, very ear­ly hype — could pro­vide the first sin­gle rem­e­dy for some of the main com­pli­ca­tions of obe­si­ty.

A study in mice fund­ed by Eleu­sis and pub­lished in Sci­en­tif­ic Re­ports found a long-known drug called (R)-DOI could be used to treat car­dio­vas­cu­lar dis­ease, re­duc­ing in­flam­ma­tion in the aor­ta, de­creas­ing over­all and HDL cho­les­terol lev­els, and po­ten­tial­ly curb­ing di­a­betes by in­creas­ing glu­cose tol­er­ance.

Lead au­thor Charles Nichols says di­a­betes and high cho­les­terol, though of­ten re­sults of the same un­der­ly­ing con­di­tion, re­quire sep­a­rate drugs and a re­strict­ed di­et.

“This mod­el that treats car­dio­vas­cu­lar dis­ease and meta­bol­ic dis­ease — it’s all-en­com­pass­ing,” Nichols, a pro­fes­sor of phar­ma­col­o­gy at LSU, told End­points News. “Trans­lat­ed in­to the clin­ic in hu­mans, it would be as if some­one was obese, had di­a­betes, had high cho­les­terol, and was able to take a low dose of this drug at a sub-be­hav­ioral lev­el and re­al­ly treat sev­er­al dif­fer­ent as­pects of the com­pli­ca­tions of be­ing obese.”

They’re bold words, though al­most mut­ed in a psy­che­del­ic field brim­ming with hype. Re­searchers have called the re­sults of some psy­chi­atric stud­ies “mind-blow­ing” as clin­i­cal tri­als hint at the pow­er of psilo­cy­bin (the chem­i­cal in mag­ic mush­rooms) to al­le­vi­ate de­pres­sion and MD­MA to re­lieve PTSD.

David Nichols Pur­due

The no­tion that the same class of drugs might have oth­er phys­i­o­log­i­cal and specif­i­cal­ly an­ti-in­flam­ma­to­ry ef­fects is new­er. Nichols, the son of long­time psy­che­del­ic re­search pro­po­nent David Nichols, un­der­stands the rhetoric can get rosy but points out that the tri­al was tar­get­ed. They test­ed DOI in oth­er types of tis­sue and when it had lit­tle ef­fect, fo­cused on vas­cu­lar in­di­ca­tions.

“This is not a com­plete panacea,” said Nichols, who ear­li­er tout­ed his an­i­mal stud­ies in­di­cat­ing DOI’s po­ten­tial in asth­ma.

Nichols dis­cov­ered that sero­tonin 5-HT2A re­cep­tor ag­o­nists, fol­low­ing a well-un­der­stood path­way psy­che­delics act on, can re­duce in­flam­ma­tion by ac­ci­dent in his LSU lab in 2008. Lat­er, he got a cold call from Shlo­mi Raz, a for­mer Wall Street ex­ec­u­tive who went on to get a mas­ter’s in psy­chol­o­gy at NYU.

Eleu­sis launched in 2013 with a mis­sion, Raz told End­points, of ex­plor­ing the broad pos­si­bil­i­ties for these ag­o­nists, with their work so far rang­ing from a tri­al on the ef­fects of ‘mi­cro-dos­ing’ LSD on time per­cep­tion to fil­ing a patent for the treat­ment of Alzheimer’s with LSD. Nichols has pub­lished sev­er­al pre­vi­ous stud­ies on psy­che­delics and an­ti-in­flam­ma­to­ries, but this was no­table in its abil­i­ty to on­ramp in­to clin­i­cal tri­als.

Raz be­lieves what is com­mon­ly called psy­che­delics have a broad ar­ray of im­pacts be­yond their “psy­che­del­ic” func­tion. He says he has peer-re­viewed re­search com­ing soon that will help bol­ster that claim, and that the cen­tral ques­tion is how to un­lock those ef­fects with­out trig­ger­ing the psy­cho­log­i­cal im­pact.

“If you think of it as an ice­berg,” Raz said, “maybe the tip of the ice­berg is the psy­chi­atrics and the part be­low the sur­face is not psy­chi­atric.”

The vas­cu­lar study showed phys­i­o­log­i­cal with­out any psy­cho­log­i­cal ef­fects (mice giv­en a psy­che­del­ic can some­times show be­hav­ior con­sis­tent with psy­chosis). The re­searchers fat­tened up mice on the “West­ern di­et” for four months and at in­ter­vals ad­min­is­tered DOI to one group and saline to a con­trol.

They found that vas­cu­lar in­flam­ma­tion was low­er in the DOI, as they an­tic­i­pat­ed. They hadn’t an­tic­i­pat­ed that cho­les­terol would be down and glu­cose tol­er­ance up, and they’re still not sure why.

Nichols, though, said the study was trans­lat­able to a clin­i­cal tri­al, and he was hope­ful there would be a drug with­in 10 to 20 years. Reg­u­la­tion, more than the sci­ence, was the bar­ri­er. Raz was mum about what’s next, both in terms of oth­er ap­pli­ca­tions and in busi­ness mod­el, but he left one clue:

“I can tell you it’s not a pill,” he said, “at first.”

No­var­tis reshuf­fles its wild cards; Tough sell for Bio­gen? Googling pro­teins; Ken Fra­zier's new gig; 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.

If you enjoy the People section in this report, you may also want to check out Peer Review, my colleagues Alex Hoffman and Kathy Wong’s comprehensive compilation of comings and goings in biopharma.

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Demis Hassabis, DeepMind CEO (Qianlong/Imaginechina via AP Images)

Google's Deep­Mind opens its pro­tein data­base to sci­ence — po­ten­tial­ly crack­ing drug R&D wide open

Nearly a year ago, Google’s AI outfit DeepMind announced they had cracked one of the oldest problems in biology: predicting a protein’s structure from its sequence alone. Now they’ve turned that software on nearly every human protein and hundreds of thousands of additional proteins from organisms important to medical research, such as fruit flies, mice and malaria parasite.

The new database of roughly 350,000 protein sequences and structures represents a potentially monumental achievement for the life sciences, one that could hasten new biological insights and the development of new drugs. DeepMind said it will be free and accessible to all researchers and companies.

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Vas Narasimhan, Novartis CEO (Jason Alden/Bloomberg via Getty Images)

No­var­tis dis­cards one of its ‘wild card’ drugs af­ter it flops in key study. But it takes one more for the hand

Always remember just how risky it is to gamble big on small studies.

A little more than 4 years ago, Novartis reportedly put up a package worth up to $1 billion for the dry eye drug ECF843 after a small biotech called Lubris put it through its paces in a tiny study of 40 moderate to severe patients, tracking some statistically significant markers of efficacy.

By last fall, the program had risen up to become one of CEO Vas Narasimhan’s top “wild card” programs in line for a potential breakthrough year in 2021. These drugs were all considered high-risk, high-reward efforts. And in this case, risk won.

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6 top drug­mak­ers of­fer per­spec­tives on FDA's new co­vari­ates in RCTs guid­ance

Back in May, the FDA revised and expanded a 2019 draft guidance that spells out how to adjust for covariates in the statistical analysis of randomized controlled trials.

Building on the ICH’s E9 guideline on the statistical principles for clinical trials, the 3-page draft was transformed into an 8-page draft, with more detailed recommendations on linear and nonlinear models to analyze the efficacy endpoints in RCTs.

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In­side Bio­gen's scram­ble to sell Aduhelm: Pro­ject 'Javelin' and pres­sure to ID as many pa­tients as pos­si­ble

In anticipation of Aduhelm’s approval for Alzheimer’s in June, Biogen employees were directed to identify and guarantee treatment centers would administer the drug through a program called “Javelin,” a senior Biogen employee told Endpoints News.

The program identified about 800 centers for use, he said, and Biogen now pays for the use of bioassays to identify beta amyloid in potential patients having undergone a lumbar puncture procedure, the employee said — and one center preparing to administer the drug confirmed its participation in the bioassay program.

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EMA re­jects FDA-ap­proved Parkin­son's drug, signs off on Mod­er­na vac­cine use in ado­les­cents ahead of FDA

The European Medicines Agency on Friday rejected Kyowa Kirin’s Parkinson’s disease drug Nouryant (istradefylline), which the US FDA approved in 2019 under the brand name Nourianz.

EMA said it considered that the results of the clinical studies used to support the application “were inconsistent and did not satisfactorily show that Nouryant was effective at reducing the ‘off’ time. Only four out of the eight studies showed a reduction in ‘off’ time, and the effect did not increase with an increased dose of Nouryant.”

Laurent Fischer, Adverum CEO

Ad­verum faces murky fu­ture af­ter re­view turns up deep­er safe­ty is­sues for gene ther­a­py

Three months after revealing that a patient lost significant vision in one eye after receiving its experimental gene therapy, Adverum announced it found the safety issues were more widespread: Five of 12 patients who received a high dose of the therapy saw “similar clinically-relevant events.”

Three required surgery on their treated eye. And all 12 are being recommended “aggressive immunomodulatory treatments” to prevent further injury.

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Mol­e­c­u­lar Di­ag­nos­tics Can Trans­form Can­cer Care. Let’s Make It Hap­pen.

Like so many people around the world, my life has been profoundly shaped by cancer. Those personal experiences, along with a deep love of clinical laboratory science and a passion to apply the power of genomics in medicine, motivated me to launch a company that would improve cancer care through better diagnostics. Thirteen years later, I am proud that we are delivering more accurate information at multiple points along the patient journey, with a focus on eight of the 10 cancers that are most commonly diagnosed in the United States.

FDA lev­els clin­i­cal hold on Ma­gen­ta's sec­ond lead drug, ask­ing for an ad­di­tion­al bioas­say be­fore it gets to hu­mans

Earlier this summer, Magenta Therapeutics was forced to say goodbye to its head of R&D at a pivotal time as the biotech read out data for its lead stem cell conditioning hopeful. Just weeks later, the company’s second drug is facing a clinical hold from the FDA as the agency demands more info on how the candidate works in humans.

Magenta will be required to submit an additional bioassay to help determine the best path forward on dose escalation for the biotech’s Phase I/II study of MGTA-117, an antibody-drug conjugate used to deplete hematopoietic stem cells prior to a transplant of HSC-based gene therapy, the biotech said Wednesday.

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