Psy­che­del­ic drug re­search breaks out of deep freeze as re­searchers head for the clin­ic with am­bi­tious tri­al plans

David Nichols en­tered grad­u­ate school in 1969 with dreams of crack­ing LSD. He was a child of the 60s, his friends drop­ping tabs and go­ing on about the vi­sions they saw – the big bang, god, in­fin­i­ty pro­ject­ed – and how it changed them in ways on­ly ma­jor life events could. Nichols was go­ing to fig­ure out how it all worked.

David Nichols Pur­due

And then in 1970, Con­gress passed the Con­trolled Sub­stance Act. LSD, which the gov­ern­ment had stud­ied ex­ten­sive­ly for two decades, be­came a Sched­ule I drug. The dol­lars washed up. For 30 years, psy­che­delics be­came all but un­touch­able for clin­i­cal tri­als.

“The Con­trolled Sub­stances Act was passed, and I thought, ‘Oh, well there goes that [idea],” Nichols told End­point News.

Now half a cen­tu­ry lat­er, Johns Hop­kins Med­i­cine is open­ing up the na­tion’s first ma­jor cen­ter for psy­che­del­ic re­search, a $17 mil­lion, pri­vate­ly-backed bet that re­flects a 20-year-long sea change in how psy­che­del­ic re­search is viewed by clin­i­cians and the promise the drugs have shown in treat­ing a host of psy­chi­atric dis­or­ders. The Cen­ter for Psy­che­del­ic and Con­scious­ness Re­search at Johns Hop­kins Med­i­cine will al­so ex­plore the drugs’ im­pact on cre­ativ­i­ty and well-be­ing.

“Oh, it’s huge,” says Nichols, who as a pro­fes­sor at Pur­due Uni­ver­si­ty be­came one of the on­ly psy­che­del­ic re­searchers (he fo­cused on an­i­mals) and one of the top ad­vo­cates for re­open­ing clin­i­cal tri­als dur­ing the three-plus decades the drugs were al­most en­tire­ly mar­gin­al­ized. “Where mon­ey has been the ob­sta­cle, now mon­ey is no longer the prob­lem.”

Af­ter years in the side­lines, psy­che­delics  be­gan­to creep back in­to the phar­ma­ceu­ti­cal imag­i­na­tion in 2000, when Johns Hop­kins ob­tained ap­proval to ad­min­is­ter psy­che­delics to healthy hu­man sub­jects.

Sci­en­tists at a hand­ful of promi­nent in­sti­tu­tions have since en­tered the field, con­duct­ing tri­als on how psy­che­delics can treat long-in­tractable dis­or­ders – some­times with dra­mat­ic suc­cess: psilo­cy­bin (the chem­i­cal found in mag­ic mush­rooms) for ad­dic­tion and a slew of ail­ments, LSD for de­pres­sion, MD­MA for PTSD.

Ear­ly re­sults have ap­peared as a panacea to psy­chi­atric pa­tients who have gone years on SS­RIs and oth­er treat­ments with­out sig­nif­i­cant im­prove­ment and opened the door to a string of star­tups seek­ing to ad­vance and cap­i­tal­ize on the emerg­ing mar­ket. Re­searchers tout­ed the re­sults of one pair of NYU and Hop­kins stud­ies on psilo­cy­bin to treat “ex­is­ten­tial dread” in can­cer pa­tients as “mind-blow­ing,”

“I think we’re look­ing at a par­a­digm shift,” says Nichols, who found­ed the Heffter Re­search In­sti­tute in 1993 to ad­vo­cate for and even­tu­al­ly fund clin­i­cal tri­als. “I think it’ll be a rev­o­lu­tion­ary change for peo­ple who suf­fer from these dis­or­ders. We didn’t have any­thing that worked un­til now.”

Re­searchers char­ac­ter­ized the cen­ter as a sign of how main­stream the field has be­come and an an­nounce­ment that will on­ly le­git­imize it fur­ther.

But im­me­di­ate­ly, the mon­ey will fu­el sev­er­al clin­i­cal tri­als at Hop­kins – in­clud­ing those for opi­oid ad­dic­tion, Alzheimer’s dis­ease, PTSD and co-oc­cur­ring mood and al­co­hol prob­lems – equip­ping sci­en­tists with funds that re­main scarce for psy­che­del­ic re­search.

Al­most all psy­che­delics are still Sched­ule I drugs, mean­ing of­fi­cial­ly they have “no cur­rent­ly ac­cept­ed med­ical use” and the NIH will not fund stud­ies on them. The prob­lem has plagued the field since its resur­gence.

Al­bert Gar­cia Johns Hop­kins

“Usu­al­ly sci­ence is a lot of beg­ging for mon­ey,” Al­bert Gar­cia, who will lead the Hop­kins Alzheimer’s study, told End­points News, “and this means we won’t have to do that for a cou­ple years at least.”

The fu­ture be­yond clin­i­cal tri­als re­mains murky, though, and the ex­u­ber­ance of some re­searchers and ad­vo­cates has led to push­back by crit­ics of the sci­ence (psy­che­del­ic stud­ies are nec­es­sar­i­ly not dou­ble-blind) and those, in­clud­ing health writer and pro­po­nent of psy­che­del­ic re­search Michael Pol­lan, who say ad­vo­cates for mag­ic mush­room de­crim­i­nal­iza­tion send a mes­sage that the drugs are not dan­ger­ous.

“This is not some sort of mag­ic bul­let that will be solv­ing all these men­tal health prob­lems,” Gar­cia said.

In March, the FDA ap­proved its first psy­che­del­ic drug: Es­ke­t­a­mine for treat­ing de­pres­sion. And in 2017 and 2018, the agency grant­ed break­through sta­tus to an MD­MA pro­to­col for treat­ing PTSD and to UK start­up Com­pass Path­ways’ psilo­cy­bin pro­to­col for treat­ing de­pres­sion. But there’s been lit­tle in­di­ca­tion of change to the un­der­ly­ing fed­er­al law.

Sim­i­lar ques­tions re­main about pre­cise­ly how these drugs would come to mar­ket, es­pe­cial­ly as the field has caught the eye of in­vestors in Sil­i­con Val­ley and Eu­rope. The list of Hop­kins donors in­cludes TOMS founder Blake My­coskie and pop­u­lar en­tre­pre­neur Tim Fer­riss but oth­er in­vestors have fun­neled mon­ey in­to pri­vate, for-prof­it ven­tures like Com­pass and ATAI.

In­g­mar Gor­man

“Scal­ing and ac­ces­si­bil­i­ty of treat­ments are ques­tions on every­one’s mind at the mo­ment,” In­g­mar Gor­man, di­rec­tor of the Psy­che­del­ic Ed­u­ca­tion and Con­tin­u­ing Care Pro­gram at the Cen­ter for Op­ti­mal Liv­ing and co-prin­ci­pal in­ves­ti­ga­tor on a stage III MD­MA study for treat­ing PTSD, told End­points News in an email.

Psy­che­delics such as psilo­cy­bin won’t op­er­ate on the pill-a-day for­mu­la that dom­i­nates most cur­rent psy­chi­atrics. Rather, a pa­tient would go in a few times per year to re­ceive dos­es in a con­trolled en­vi­ron­ment with med­ical pro­fes­sion­als. It’s un­clear yet what the costs would be, though Nichols and oth­ers are op­ti­mistic wide­spread knowl­edge of how to man­u­fac­ture psilo­cy­bin, for in­stance, will make it dif­fi­cult to patent and keep prices down.

Eka­te­ri­na Malievska­ia Com­pass

Last year, Com­pass Path­ways made head­lines af­ter in­sid­ers ac­cused them in Quartz of try­ing to form a mo­nop­oly on the glob­al sup­ply of psilo­cy­bin. They de­nied the charges but said se­cur­ing a large sup­ply was es­sen­tial to their busi­ness mod­el of in­te­grat­ing their ther­a­pies sys­tems.

They told End­points they weren’t a psy­che­del­ic com­pa­ny, but sim­ply look­ing for the best ways to tack­le men­tal health prob­lems.

“Right now, I don’t see any­thing more promis­ing than re­search in psy­che­delics,” says CIO and co-founder Eka­te­ri­na Malievska­ia. “But things can change.”

2023 Spot­light on the Fu­ture of Drug De­vel­op­ment for Small and Mid-Sized Biotechs

In the context of today’s global economic environment, there is an increasing need to work smarter, faster and leaner across all facets of the life sciences industry.  This is particularly true for small and mid-sized biotech companies, many of which are facing declining valuations and competing for increasingly limited funding to propel their science forward.  It is important to recognize that within this framework, many of these smaller companies already find themselves resource-challenged to design and manage clinical studies themselves because they don’t have large teams or in-house experts in navigating the various aspects of the drug development journey. This can be particularly challenging for the most complex and difficult to treat diseases where no previous pathway exists and patients are urgently awaiting breakthroughs.

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Since losing a controversial court case over orphan drug exclusivity last year, the FDA’s Office of Orphan Products Development has remained entirely silent on orphan exclusivity for any product approved since last November, leaving many sponsors in limbo on what to expect.

That silence means that for more than 70 orphan-designated indications for more than 60 products, OOPD has issued no public determination on the seven-year orphan exclusivity in the Orange Book, and no new listings of orphan exclusivity appear in OOPD’s searchable database, as highlighted recently by George O’Brien, a partner in Mayer Brown’s Washington, DC office.

Albert Bourla, Pfizer CEO (Efren Landaos/Sipa USA/Sipa via AP Images)

Pfiz­er makes an­oth­er bil­lion-dol­lar in­vest­ment in Eu­rope and ex­pands again in Michi­gan

Pfizer is continuing its run of manufacturing site expansions with two new large investments in the US and Europe.

The New York-based pharma giant’s site in Kalamazoo, MI, has seen a lot of attention over the past year. As a major piece of the manufacturing network for Covid-19 vaccines and antivirals, Pfizer is gearing up to place more money into the site. Pfizer announced it will place $750 million into the facility, mainly to establish “modular aseptic processing” (MAP) production and create around 300 jobs at the site.

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Vas Narasimhan, Novartis CEO (Thibault Camus/AP Images, Pool)

No­var­tis bol­sters Plu­vic­to's case in prostate can­cer with PhI­II re­sults

The prognosis is poor for metastatic castration-resistant prostate cancer (mCRPC) patients. Novartis wants to change that by making its recently approved Pluvicto available to patients earlier in their course of treatment.

The Swiss pharma giant unveiled Phase III results Monday suggesting that Pluvicto was able to halt disease progression in certain prostate cancer patients when administered after androgen-receptor pathway inhibitor (ARPI) therapy, but without prior taxane-based chemotherapy. The drug is currently approved for patients after they’ve received both ARPI and chemo.

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Nkarta CEO Paul Hastings at Endpoints' #BIO22 panel (J.T. MacMillan Photography for Endpoints News)

Nkar­ta un­der­scores safe­ty of CAR-NK, boasts ear­ly re­spons­es

The first generation of personalized CAR-T therapies made big waves in the treatment of lymphoma for their stunning efficacy. Nkarta is hoping its off-the-shelf natural killer cell approach will stand out on safety — while keeping some of those impressive numbers on responses.

In a new update from its Phase I dose escalation study, the South San Francisco-based biotech reported that seven out of 10 patients treated with the highest doses of its NK cell therapy, NKX019, achieved a complete response, translating to a complete response rate of 70%.

Pfiz­er-backed Me­di­ar Ther­a­peu­tics ropes in an­oth­er Big Phar­ma in­vestor

A biotech centered on treating fibrosis — born out of Mass General and Brigham and Women’s Hospital — has received a financial boost.

According to an SEC filing, the company has raised $31,761,186 in its latest funding round, which includes 17 investors. The filing lists six names attached to the company, including Meredith Fisher, a partner at Mass General Brigham Ventures and Mediar’s acting CEO.

Sekar Kathiresan, Verve Therapeutics CEO

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We now know why Verve’s lead candidate was placed on hold last month by US regulators.

In an SEC filing, Verve laid out the FDA’s conditions for lifting the hold on its lead therapy, VERVE-101. That includes submitting preclinical data about potency differences in human versus non-human cells, risks of gene editing germline cells, and off-target analyses in non-hepatocyte cell types.

The FDA also wants clinical data from the ongoing Heart-1 trial, and to modify the trial protocol in the US to add additional contraceptive measures and increase the length of a staggering interval between the dosing of participants.

Illustration: Assistant Editor Kathy Wong for Endpoints News

As mon­ey pours in­to dig­i­tal ther­a­peu­tics, in­sur­ance cov­er­age crawls



Talk therapy didn’t help Lily with attention deficit hyperactivity disorder, or ADHD. But a video game did.

As the 10-year-old zooms through icy waters and targets flying creatures on the snow-capped planet Frigidus, she builds attention skills, thanks to Akili Interactive Labs’ video game EndeavorRx. She’s now less anxious and scattered, allowing her to stay on a low dose of ADHD medication, according to her mom Violet Vu.

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Rick Modi, Affinia Therapeutics CEO

Ver­tex-part­nered gene ther­a­py biotech Affinia scraps IPO plans

Affinia Therapeutics has ditched its plans to go public in a relatively closed-door market that has not favored Nasdaq debuts for the drug development industry most of this year. A pandemic surge in 2020 and 2021 opened the doors for many preclinical startups, which caught Affinia’s attention and gave the gene therapy biotech confidence in the beginning days of 2022 to send in its S-1.

But on Friday, Affinia threw in the S-1 towel and concluded now is not the time to step onto Wall Street. The biotech has put out few public announcements since the spring of this year. Endpoints News picked the startup as one of its 11 biotechs to watch last year.

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