Psy­che­del­ic re­search gains mo­men­tum, as ear­ly tri­al sug­gests mi­cro-dos­ing LSD is safe

Psy­che­delics have been long ne­glect­ed as the sub­ject of vig­or­ous sci­en­tif­ic re­search af­ter gov­ern­ments brand­ed them as il­le­gal he­do­nis­tic com­pounds with no ther­a­peu­tic po­ten­tial. But in re­cent years, de­spite tricky reg­u­la­tions, a resur­gence of in­ter­est from re­searchers has cul­mi­nat­ed in an FDA ap­proved ke­t­a­mine-de­rived de­pres­sion treat­ment, clin­i­cal tri­als test­ing the po­ten­tial of psilo­cy­bin in ‘mag­ic mush­rooms,’ and the set­ting up of a psy­che­del­ic re­search cen­ter at Johns Hop­kins.

The col­or­less, odor­less and taste­less drug, ly­ser­gic acid di­ethy­lamide (LSD) — or acid, as it is fond­ly known — is part of this re­search re­nais­sance. On Wednes­day, a small pri­vate­ly held com­pa­ny — Eleu­sis Ben­e­fit Cor­po­ra­tion — un­veiled da­ta from an ear­ly study in healthy old­er vol­un­teers that test­ed its mi­cro-dos­ing ap­proach with LSD. And if it all goes ac­cord­ing to plan — nev­er a sure thing in biotech — they’ve got plans to tar­get Alzheimer’s with the ap­proach.

Neilo­u­far Fam­i­ly

In the study, 48 vol­un­teers (mean age = 62.9 years) re­ceived ei­ther 5 μg, 10 μg, or 20 μg of LSD, or place­bo  — ad­min­is­tered in wa­ter — every four days in six ses­sions. Over­all, the LSD was well tol­er­at­ed, and the fre­quen­cy of ad­verse events was no high­er than the place­bo, the com­pa­ny said, while claim­ing this is the first ever pub­li­ca­tion of clin­i­cal study da­ta on mi­cro-dosed LSD.

PK da­ta showed that the half-life of the LSD dos­es was short. “So at 12 hours post-dose, there was no drug in the blood at any of the dos­es,” Neilo­u­far Fam­i­ly, the tri­al’s lead in­ves­ti­ga­tor, told End­points News. “And there al­so wasn’t any drug in the blood at base­line on the sixth dose.”

The da­ta sup­port fur­ther clin­i­cal de­vel­op­ment of LSD, whose psy­choac­tiv­i­ty is un­der­stood to be me­di­at­ed pri­mar­i­ly through the 5-HT2A re­cep­tor, Eleu­sis said. The com­pa­ny even plans to de­vel­op the drug to treat and pre­vent Alzheimer’s dis­ease, a field lit­tered with fail­ure and a pauci­ty of promis­ing ther­a­peu­tics in the late-stage pipeline.

But the brim­ming en­thu­si­asm comes with a healthy dose of skep­ti­cism. Crit­ics wor­ry that the bur­geon­ing psy­che­del­ic re­search could in­cen­tivize un­bri­dled use of non-phar­ma­ceu­ti­cal ver­sions of these drugs and that clin­i­cal tri­al da­ta could be cloud­ed by the fact that place­bo-con­trolled stud­ies are not nec­es­sar­i­ly dou­ble-blind­ed, be­cause it is far too easy to de­ter­mine which group of pa­tients have been giv­en a place­bo.

“The one thing that we did ex­pect — but is still re­mark­able — is the high place­bo re­sponse,” Fam­i­ly said. “Peo­ple were re­port­ing per­cep­tions of psy­choac­tive ef­fects, when lat­er on we found out they were on place­bo…but in any case, any per­cep­tions of psy­choac­tive ef­fects were very mild and they sub­sided by the end of the day, both in the ac­tive dose groups and the place­bo groups.”

Eleu­sis has a plan to hedge its Alzheimer’s bet, and to deal with the pesky prob­lem of di­ver­sion.

Be­fore div­ing in­to a Phase II ef­fi­ca­cy study in Alzheimer’s, the com­pa­ny is plan­ning an ear­ly-stage study with a com­pound — a “not-so-psy­che­del­ic” psy­che­del­ic sero­tonin 5-HT2A ag­o­nist — in oph­thal­mol­o­gy. At the mo­ment, the eye drug is at the pre­clin­i­cal stage of de­vel­op­ment.

Shlo­mi Raz

The Phase I tri­al, which is ex­pect­ed to kick off in ear­ly 2021, will pro­vide a key mech­a­nis­tic in­sight in­to how psy­che­delics could pre­vent neu­rode­gen­er­a­tion as­so­ci­at­ed with in­flam­ma­tion, Eleu­sis chief Shlo­mi Raz told End­points.

“The eye is a win­dow to the soul but al­so to the brain,” he said.”The reti­na, in par­tic­u­lar, gives us a very neat way of as­sess­ing how psy­che­delics could po­ten­tial­ly man­age neu­ro­pro­tec­tion, neu­roin­flam­ma­tion and pro­vides us a cost-ef­fec­tive proof-of-con­cept be­fore go­ing in­to — by all mea­sures —what seems to be the most ex­pen­sive type of clin­i­cal tri­al around, which is in Alzheimer’s dis­ease.”

The hope is to de­vel­op an LSD com­pound for ther­a­peu­tic use that can be used in the out­pa­tient set­ting, but psy­choac­tiv­i­ty is a risk that must be mon­i­tored, he said. The com­pa­ny says it is de­vel­op­ing a non­in­va­sive safe­ty mon­i­tor­ing tech­nol­o­gy that will be used in its clin­i­cal tri­als, and if the com­pound is ap­proved, for pa­tient use.

“In all cas­es, there’s a cal­cu­lus of safe­ty, ver­sus un­met need, and clin­i­cal util­i­ty,” he said.  “I think in the case of Alzheimer’s dis­ease, should we demon­strate that LSD in fact, is ef­fec­tive in slow­ing or halt­ing the pro­gres­sion of the dis­ease, then I think that there’s a clear jus­ti­fi­ca­tion for tak­ing that risk.”

Inside FDA HQ (File photo)

The FDA just ap­proved the third Duchenne MD drug. And reg­u­la­tors still don’t know if any of them work

Last year Sarepta hit center stage with the FDA’s controversial reversal of its CRL for the company’s second Duchenne muscular dystrophy drug — after the biotech was ambushed by agency insiders ready to reject a second pitch based on the same disease biomarker used for the first approval for eteplirsen, without actual data on the efficacy of the drug.

On Wednesday the FDA approved the third Duchenne MD drug, based on the same biomarker. And regulators were ready to act yet again despite the lack of efficacy data.

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Cell and Gene Con­tract Man­u­fac­tur­ers Must Em­brace Dig­i­ti­za­tion

The Cell and Gene Industry is growing at a staggering 30% CAGR and is estimated to reach $14B by 20251. A number of cell, gene and stem cell therapy sponsors currently have novel drug substances and products and many rely on Contract Development Manufacturing Organizations (CDMO) to produce them with adherence to stringent regulatory cGMP conditions. Cell and gene manufacturing for both autologous (one to one) and allogenic (one to many) treatments face difficult issues such as: a complex supply chain, variability on patient and cellular level, cell expansion count and a tight scheduling of lot disposition process. This complexity affects quality, compliance and accountability in the entire vein-to-vein process for critically ill patients.

Franz-Werner Haas, CureVac CEO

UP­DAT­ED: On the heels of a snap $1B raise, Cure­Vac out­lines plans to seek emer­gency OK for their Covid-19 vac­cine in a mat­ter of months

CureVac is going from being one of the quietest players in the race to develop a new vaccine to fight the worst public health crisis in a century to a challenger for the multibillion-dollar market that awaits the first vaccines to make it over the finish line. Typically low-key at a time of brash comments and incredibly ambitious development timelines from the leaders, CureVac now is jumping straight into the spotlight.

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US gov­ern­ment re­port­ed­ly be­gins prepar­ing for Covid-19 chal­lenge tri­als. Are they eth­i­cal?

Controversial human challenge trials for potential Covid-19 vaccines reportedly have a new booster — the US government.

Scientists working for the government have begun manufacturing a strain of the novel coronavirus that could be used in such studies, Reuters reported Friday morning. The trials would enroll healthy volunteers to be vaccinated and then intentionally infected with a weakened coronavirus.

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Trevor Martin (Mammoth)

Eye­ing in-vi­vo edit­ing, Mam­moth li­cens­es Jen­nifer Doud­na’s new CRISPR en­zyme

Last month, Jennifer Doudna revealed in Science a new, “hyper-compact” CRISPR enzyme that was half the size of traditional CRISPR enzymes and could, she suspected, offer a new, more versatile tool for gene editing.

Now, the University of California-Berkeley has licensed that enzyme, known as Casφ, exclusively to a biotech startup she and two former students set up three years ago: Mammoth Biosciences. It’s the second new CRISPR protein Mammoth has licensed from Doudna’s lab, after they licensed Cas14 in 2019.

Sanofi vet Kather­ine Bowdish named CEO of PIC Ther­a­peu­tics; As the world Terns: Liv­er dis­ease biotech makes ex­ec­u­tive changes

PIC Therapeutics hasn’t raised much money, yet. But the fledgling biotech has attracted a high-profile player to the helm.

The Boston-based biotech has handed the reins to Katherine Bowdish as its president and CEO. Bowdish will also join the board of directors of PIC. Bowdish joins from Sanofi where she served as VP and head of R&D strategy, as well as helping launch and lead Sanofi Sunrise, a venture investment and partnering vehicle at Sanofi. Before that, Bowdish held several exec roles at Permeon Biologics, Anaphore, Alexion Pharmaceuticals and Prolifaron (acquired by Alexion).

Clockwise from left: Canaccord Genuity principal Michelle Gilson, Canaccord Genuity CSO Brian Mueller and BioMarin CSO Hank Fuchs (Canaccord Genuity webcast)

Bio­Marin CSO diss­es ri­vals for the he­mo­phil­ia A gene ther­a­py crown: Way be­hind, fac­ing big re­cruit­ment chal­lenges and at best a .6 on the gen-one scale

The leader in the race to a hemophilia A gene therapy does not like to be compared unfavorably to the competition. And when their top execs do the comparing, don’t look for any modesty — BioMarin, they say, owns the lead.

As Factor VIII expression wanes over time, quite a few analysts have raised questions about the kind of future BioMarin’s gene therapy — a supposed once-and-done treatment — faces if it stops working. But just 7 days away from their PDUFA date, with high odds of success, the top execs clearly feel that they are way out front, while promising their rivals will discover there’s a tough slog ahead trying to pursue trials where large numbers of patients are ineligible for new therapies.

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Cal­lid­i­tas bets up to $102M on a biotech buy­out, snag­ging a once-failed PBC drug

After spending years developing its oral formulation of the corticosteroid budesonide, Sweden’s Calliditas now has its sights set on the primary biliary cholangitis field.

The company will buy out France-based Genkyotex, and it’s willing to bet up to €87 million ($102 million) that Genkyotex’s failed Phase II drug, GKT831, will do better in late-stage trials.

Under the current agreement, Calliditas $CALT will initially pay €20.3 million in cash for 62.7% of Genkyotex (or €2.80 a piece for 7,236,515 shares) in early October, then circle back for the rest of Genkyotex’s shares under the same terms. If nothing changes, the whole buyout will cost Calliditas €32.3 million, plus up to  €55 million in contingent rights.

James Wilson, WuXi Global Forum at JPM20

FDA puts up a red light for Pas­sage Bio’s first gene ther­a­py pro­gram, de­lay­ing a pro­gram from James Wilson's group at Penn

Gene therapy pioneer James Wilson spearheaded animal studies demonstrating the potential of new treatments injected directly into the brain, looking to jumpstart a once-and-done fix for an extraordinarily rare disease called GM1 gangliosidosis in infants. His team at the University of Pennsylvania published their work on monkeys and handed it over to Passage Bio, a Wilson-inspired startup building a pipeline of gene therapies — with an IND for PBGM01 to lead the way.

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