Chas­ing a 'mas­ter mod­u­la­tor' in the en­do­cannabi­noid sys­tem, biotech up­start promis­es to shake up neu­ropsy­chi­atric treat­ments

For two years in the ear­ly 2000s, new dis­cov­er­ies and bud­ding en­thu­si­asm around the en­doge­nous cannabi­noid sys­tem — so named be­cause it’s re­spon­si­ble for the ef­fects of cannabis in the hu­man body — cul­mi­nat­ed in a mar­ket­ed drug: Sanofi’s Acom­plia.

An­drea Chic­ca

The first drug to specif­i­cal­ly tar­get the cannabi­noid re­cep­tor CB1, it was ul­ti­mate­ly with­drawn from the EU and Brazil due to find­ings that it may cause sui­ci­dal thoughts de­spite be­ing ef­fec­tive in treat­ing obe­si­ty. The FDA nev­er ap­proved it.

“For some years the com­pa­nies be­came a bit re­luc­tant to touch the re­cep­tor be­cause of this po­ten­tial ef­fect,” said An­drea Chic­ca, then a post­doc study­ing can­cer bi­ol­o­gy.

But the pen­du­lum has swung back again, ac­cord­ing to Chic­ca — whose biotech start­up, Synen­dos, has just gath­ered $21.85 mil­lion (CHF$20 mil­lion) to prove its suite of se­lec­tive en­do­cannabi­noid re­up­take in­hibitors can of­fer a brand new way to treat neu­ropsy­chi­atric dis­or­ders.

Chic­ca, a long­time re­searcher at the Uni­ver­si­ty of Bern, is CEO, CSO and, for now, the on­ly full-time em­ploy­ee of the biotech start­up.

Jürg Gertsch

The idea draws from a decade of ba­sic sci­ence work by him­self and Jürg Gertsch, chas­ing pro­teins known as en­do­cannabi­noid trans­porters. Even­tu­al­ly, they re­al­ized that the com­pounds they were gen­er­at­ing to block cannabi­noid re­up­take for ex­per­i­men­tal use could have po­ten­tial as hu­man med­i­cines, and de­vised a sec­ond gen­er­a­tion of what they called SERIs.

With­out giv­ing away the pre­cise tar­get, Chic­ca not­ed that what they’re go­ing af­ter sits up­stream to the clas­sic neu­ro­trans­mit­ters: sero­tonin, glu­ta­mate, GA­BA and oth­ers.

In oth­er words, it’s a “mas­ter mod­u­la­tor” that be­comes dys­reg­u­lat­ed in CNS dis­or­ders and trig­gers a cas­cade to the down­stream sig­nal­ing.

While Chic­ca ac­knowl­edges the op­ti­mism around psy­che­del­ic drugs, their in­trin­sic risks mean pa­tients must be treat­ed in very spe­cif­ic hos­pi­tal set­tings un­der tight con­trol of doc­tors.

“So they can­not re­al­ly be­come pills to be giv­en to a pa­tient that they can take at home for months,” he said.

Si­mon Rus­sell

Even cannabis, which is much less risky, is as­so­ci­at­ed with side ef­fects like cog­ni­tive, learn­ing and mem­o­ry is­sues. Synen­dos’ small mol­e­cules are de­signed to side­step those ex­act prob­lems while re­tain­ing the an­ti-stress func­tion. They can al­so pen­e­trate the brain, at least in an­i­mal mod­els — a nice plus for a com­pound Synen­dos is po­si­tion­ing for large in­di­ca­tions like post-trau­mat­ic stress dis­or­der, anx­i­ety, com­pul­sive be­hav­ior and even de­pres­sion.

“We aim not to ac­ti­vate the sys­tem from out­side, but re­store the en­doge­nous cannabi­noid sys­tem,” Chic­ca said. “So by in­creas­ing the lev­el of the en­doge­nous mol­e­cules that are al­ready present in our body, we don’t need to add any­thing.”

If suc­cess­ful — and this is no guar­an­tee in an area akin to a mine­field for drug de­vel­op­ers — Chic­ca sees Synen­dos ex­pand­ing to oth­er ar­eas such as neu­roin­flam­ma­tion.

The Se­ries A should grow the team and take the com­pa­ny through ini­tial, healthy vol­un­teers test­ing fol­lowed by a proof-of-con­cept in a yet-to-be-an­nounced in­di­ca­tion that links anx­i­ety, stress and mood re­lat­ed dis­or­ders. It’s al­so the first fi­nanc­ing Synen­dos has raised since spin­ning out of the Uni­ver­si­ty of Bern and the re­search con­sor­tium NC­CR Tran­sCure, as Chic­ca and Gertsch had been re­ly­ing on non-di­lu­tive fund­ing while work­ing with Base­Launch.

Si­mon Rus­sell, an en­tre­pre­neur-in-res­i­dence at the Basel-based ac­cel­er­a­tor and in­cu­ba­tor who has a full time job as CBO of Ome­icos Ther­a­peu­tics, joined the duo as a co-founder and board mem­ber.

Kur­ma Part­ners and Sun­stone Life Sci­ence Ven­tures led the round, with par­tic­i­pa­tion from BERN­I­NA BioIn­vest, Schroder Ad­veq, High-Tech Grün­der­fonds, Licht­stein­er Foun­da­tion, Es­sen­tial In­vest­ments, Zürcher Kan­ton­al­bank and pri­vate in­vestors.

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His­toric drug pric­ing re­forms pass; Pfiz­er ac­quires GBT; The long search for non-opi­oid pain drugs; 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.

The Endpoints Weekly has officially crossed the 60,000 mark on subscribers — thanks to all of your support. As the editorial team grows, we’ve been able to do a lot more, with many of those on display this week. Be sure to check out Lei Lei Wu’s deep dive on pain R&D. If you missed it, you may also rewatch her companion panel here.

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Gold for adults, sil­ver for in­fants: Pfiz­er's Pre­vnar 2.0 head­ed to FDA months af­ter Mer­ck­'s green light

Pfizer was first to the finish line for the next-gen pneumococcal vaccine in adults, but Merck beat its rival with a jab for children in June.

Now, two months after Merck’s 15-valent Vaxneuvance won the FDA stamp of approval for kids, Pfizer is out with some late-stage data on its 20-valent shot for infants.

Known as Prevnar 20 for adults, Pfizer’s 20vPnC will head to the FDA by the end of this year for an approval request in infants, the Big Pharma said Friday morning. Discussions with the FDA will occur first and more late-stage pediatric trials are expected to read out soon, informing the regulatory pathway in other countries and regions.

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Seagen interim CEO Roger Dansey and Daiichi Sankyo CEO Sunao Manabe

Paving the way for Mer­ck­'s buy­out, Seagen los­es ar­bi­tra­tion dis­pute with Dai­ichi over ADC tech

As Seagen awaits a final buyout offer from Merck that could be in the territory of $40 billion, Seagen revealed Friday afternoon that it lost an arbitration dispute with Daiichi Sankyo relating to the companies’ 2008 collaboration around the use of antibody-drug conjugate (ADC) technology.

But that loss likely won’t matter much when it comes to Merck’s deal.

After breaking off its pact with Daiichi in mid-2015, the two companies battled over “linker” tech — a chemical bridge between an ADC’s antibody component and the cytotoxic payload — that Seagen claims Daiichi would improve upon and implement in its current generation of ADCs.

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Tony Coles, Cerevel CEO

Cerev­el takes the pub­lic of­fer­ing route, with a twist — rais­ing big mon­ey thanks to ri­val da­ta

As public biotechs seek to climb out of the bear market, a popular strategy to raise cash has been through public offerings on the heels of positive data. But one proposed raise Wednesday appeared to take advantage not of a company’s own data, but those from a competitor.

Cerevel Therapeutics plans to raise $250 million in a public offering and another $250 million in debt, the biotech announced Wednesday afternoon, even though it did not report any news on its pipeline. However, the move comes days after rival Karuna Therapeutics touted positive Phase III data in schizophrenia, a field where Cerevel is pursuing a similar program.

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House pass­es his­toric drug pric­ing re­forms, lin­ing up decades-in-the-mak­ing win for Biden and De­moc­rats

The US House of Representatives today voted along party lines (all Dems voted for it), 220-207 to pass new, wide-ranging legislation that will allow Medicare drug price negotiations for the first time ever, and cap seniors’ drug expenses to $2,000 per year and seniors’ insulin costs at $35 per month.

Setting up a major victory for President Joe Biden, representatives returned from their summer recess to pass the Inflation Reduction Act, even as many noted the bill would only modestly reduce inflation.

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Senate Finance Committee Chair Ron Wyden (D-OR) (Francis Chung/E&E News/POLITICO via AP Images)

Sen­ate Fi­nance chair con­tin­ues his in­ves­ti­ga­tion in­to phar­ma tax­es with re­quests for Am­gen

Amgen is the latest pharma company to appear on the radar of Senate Finance Committee Chair Ron Wyden (D-OR), who is investigating the way pharma companies are using subsidiaries in low- or zero-tax countries to lower their tax bills.

Like its peers Merck, AbbVie and Bristol Myers Squibb, Wyden notes how Amgen uses its Puerto Rico operations to consistently pay tax rates that are substantially lower than the U.S. corporate tax rate of 21%, with an effective tax rate of 10.7% in 2020 and 12.1% in 2021.

FDA ap­proves sec­ond in­di­ca­tion for As­traZeneca and Dai­ichi's En­her­tu in less than a week

AstraZeneca and Daiichi Sankyo’s antibody-drug conjugate Enhertu scored its second approval in less than a week, this time for a subset of lung cancer patients.

Enhertu received accelerated approval on Thursday to treat adults with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, and who have already received a prior systemic therapy.

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J&J to re­move talc prod­ucts from shelves world­wide, re­plac­ing with corn­starch-based port­fo­lio

After controversially spinning out its talc liabilities and filing for bankruptcy in an attempt to settle 38,000 lawsuits, Johnson & Johnson is now changing up the formula for its baby powder products.

J&J is beginning the transition to an all cornstarch-based baby powder portfolio, the pharma giant announced on Thursday — just months after a federal judge ruled in favor of its “Texas two-step” bankruptcy to settle allegations that its talc products contained asbestos and caused cancer. An appeals court has since agreed to revisit that case.