Stewart Campbell, Axial Therapeutics

Treat­ing autism through the gut? Ax­i­al Ther­a­peu­tics re­fu­els on its ex­plo­ration of the gut-brain ax­is

If Stew­art Camp­bell had said five years ago that you could treat con­di­tions of the brain through the gut, you prob­a­bly would have thought he was crazy — or at least that’s what he likes to say.

Since then, a crop of biotechs ex­plor­ing the gut-brain ax­is has got­ten the at­ten­tion of some well-known in­vestors. Camp­bell’s Ax­i­al Ther­a­peu­tics is now the lat­est, un­veil­ing a $37.25 mil­lion Se­ries C round on Wednes­day morn­ing that brings the com­pa­ny’s to­tal raise to just over $90 mil­lion.

The ex­tra cash will be used to con­duct a Phase II tri­al of the com­pa­ny’s lead pro­gram, a gut-re­strict­ed mol­e­c­u­lar ther­a­py for ir­ri­tabil­i­ty in chil­dren with autism called AB-2004.

David Don­abe­di­an

Ax­i­al’s sci­ence traces back to a plat­form that pro­fes­sor Sarkis Maz­man­ian had brew­ing in his lab sev­er­al years ago at Cal­tech. His team pub­lished re­search from an­i­mal stud­ies that es­tab­lished a link be­tween the pop­u­la­tion of tiny mi­crobes in your body and the course of autism spec­trum dis­or­ders. In 2016, he and the Long­wood Fund’s David Don­abe­di­an spun that re­search in­to a com­pa­ny, which Don­abe­di­an ran un­til hand­ing the reins to Camp­bell ear­li­er this year.

AB-2004’s mech­a­nism of ac­tion be­gins with mi­crobes in the gut that di­gest pro­tein down to their com­po­nent amino acids, which are fur­ther di­gest­ed in­to some­thing called small mol­e­cule metabo­lites. A cer­tain class of these metabo­lites are then ab­sorbed by the blood and can trav­el to the brain, Camp­bell ex­plained. There, sci­en­tists have shown that the metabo­lites can al­ter the de­vel­op­ment of cer­tain brain cells — in par­tic­u­lar, cells that pro­duce myelin.

If you think of an elec­tri­cal wire, there’s usu­al­ly a plas­tic coat­ing to in­su­late the wire and keep it from short-cir­cuit­ing, Camp­bell said. That’s what myelin is for neu­rons. When cells that pro­duce myelin are pre­vent­ed from ma­tur­ing prop­er­ly, Ax­i­al be­lieves be­hav­ior is af­fect­ed, like dan­ger sens­ing or fear con­di­tion­ing.

“That’s the way we con­nect all those dots from the gut mi­crobes all the way to be­hav­ior,” he said.

AB-2004 is de­signed to pass through the gut, pick­ing up metabo­lites al­most like a sponge, then pass through the stool, low­er­ing metabo­lite lev­els in the gut, and there­fore in the brain. It’s an oral med­ica­tion that would need to be tak­en three times per day with food (though Camp­bell says they’re work­ing on for­mu­la­tions that could be tak­en twice or even once per day). The com­pa­ny re­cent­ly read out Phase Ia/IIb da­ta that showed the can­di­date was safe, and that it re­duced sev­er­al key GI neu­roac­tive mi­cro­bial metabo­lites in the plas­ma and urine.

“We think it has got a strong safe­ty pro­file, be­cause we don’t need to get it in the body or in­to the brain at all in or­der for it to work,” Camp­bell said.

Ax­i­al is plan­ning on launch­ing a Phase II tri­al soon, which should read out in 2023, Camp­bell said. They’ve al­so got pre­clin­i­cal pro­grams in Parkin­son’s dis­ease and on­col­o­gy in the works.

When asked if an IPO is in the fu­ture, Camp­bell re­spond­ed with a chuck­le: “No idea.”

“We’re so fo­cused right now on just get­ting this ex­e­cu­tion to­ward our mile­stones and (mov­ing) our pro­grams ahead,” he added.

Aus­tralian VC firm On­eVen­tures led Ax­i­al’s lat­est round along with the Uni­ver­si­ty of Tokyo In­no­va­tion Plat­form Com­pa­ny. The Autism Im­pact Fund, Corun­dum Sys­tems Bi­ol­o­gy, the Long­wood Fund, Sev­en­ture Part­ners, Tai­ho Ven­tures, and Do­main As­so­ci­ates al­so chimed in.

Ax­i­al is one of sev­er­al mi­cro­bio­me com­pa­nies ex­plor­ing the gut-brain ax­is, in­clud­ing Kally­ope, which land­ed a $112 mil­lion Se­ries C round last year. No­vo Nordisk has dipped its feet, ink­ing a part­ner­ship with Kally­ope in obe­si­ty and di­a­betes back in 2018.

“Autism and Parkin­son’s are the tip of the ice­berg for us,” Camp­bell said. “This is a very dif­fer­ent way and we hope this is re­al­ly like a phase shift in how we think about neu­ro­log­i­cal dis­or­ders.”

Has the mo­ment fi­nal­ly ar­rived for val­ue-based health­care?

RBC Capital Markets’ Healthcare Technology Analyst, Sean Dodge, spotlights a new breed of tech-enabled providers who are rapidly transforming the way clinicians deliver healthcare, and explores the key question: can this accelerating revolution overturn the US healthcare system?

Key points

Tech-enabled healthcare providers are poised to help the US transition to value, not volume, as the basis for reward.
The move to value-based care has policy momentum, but is risky and complex for clinicians.
Outsourced tech specialists are emerging to provide the required expertise, while healthcare and tech are also converging through M&A.
Value-based care remains in its early stages, but the transition is accelerating and represents a huge addressable market.

Alaa Halawaa, executive director at Mubadala’s US venture group

The ven­ture crew at Mubadala are up­ping their biotech cre­ation game, tak­ing care­ful aim at a new fron­tier in drug de­vel­op­ment

It started with a cup of coffee and a slow burning desire to go early and long in the biotech creation business.

Wrapping up a 15-year discovery stint at Genentech back in the summer of 2021, Rami Hannoush was treated to a caffeine-fueled review of the latest work UCSF’s Jim Wells had been doing on protein degradation — one of the hottest fields in drug development.

“Jim and I have known each other for the past 15 years through Genentech collaborations. We met over coffee, and he was telling me about this concept of the company that he was thinking of,” says Hannoush. “And I got immediately intrigued by it because I knew that this could open up a big space in terms of adding a new modality in drug discovery that is desperately needed in pharma.”

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Flare Therapeutics biochemists Yong Li (L) and Valerie Vivat

A $123M Flare will get Third Rock on­col­o­gy biotech in­to the clin­ic this year

Flare Therapeutics will start its first human trial this year with an investigational urothelial cancer drug after pulling together a $123 million Series B from Big Pharmas, VCs and its incubator, Third Rock Ventures.

Launched in 2021 on the idea that a biotech could finally succeed at drugging the much-sought-after but stubborn transcription factor, Flare Therapeutics said Wednesday it is now primed for the clinic after closing its large financing haul earlier this year. The raise is a relatively stark figure in a tough startup financing environment but further buoys the upbeat signals coming out of other Third Rock biotechs in recent weeks, including the $200 million CARGO Therapeutics and $100 million Rapport Therapeutics rounds.

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Rohan Palekar, 89bio CEO

89bio’s PhII da­ta add to quick suc­ces­sion of NASH read­outs as field seeks turn­around

89bio said its drug was better than placebo at lessening fibrosis without worsening nonalcoholic steatohepatitis, or NASH, in two of three dose groups.

The San Francisco biotech said it thinks the Phase IIb data pave the way for a potential Phase III, following in the footsteps of another biotech in its drug class, Akero Therapeutics. To fund a late-stage study, CEO Rohan Palekar told Endpoints News 89bio “would need to raise additional capital,” with the company having about $188 million at the end of last year.

Roche and Lil­ly team up to de­vel­op blood test to de­tect ear­ly signs of Alzheimer's

Eli Lilly is teaming up with Roche to help develop a blood test to detect early signs of Alzheimer’s disease and determine whether a patient should go for further confirmatory testing.

Roche’s Elecsys Amyloid Plasma Panel (EAPP) measures pTau 181 protein assay and APOE E4 assay in human blood plasma – elevations in pTau 181 are present in the early stages of Alzheimer’s, while the presence of APO E4 is the most common genetic risk factor for the disease.

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Francesco Marincola, newly-appointed Sonata Therapeutics CSO

Kite's head of re­search leaves for Flag­ship start­up Sonata

Another leader is departing Kite Pharma, and will to spend the “last part” of his career exploring how cancer evades the immune system.

Kite’s senior VP and global head of cell therapy research Francesco Marincola left the Gilead CAR-T unit last week for Sonata Therapeutics. Flagship last May unveiled the startup, which was pieced together from two fledgling biotechs Inzen and Cygnal Therapeutics. As CSO, Marincola will lead Sonata’s push to reprogram cancer cells to make them more immunogenic.

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FDA in­di­cates will­ing­ness to ap­prove Bio­gen ALS drug de­spite failed PhI­II study

Ahead of Wednesday’s advisory committee hearing to discuss Biogen’s ALS drug tofersen, the FDA appeared open to approving the drug, newly released briefing documents show.

Citing the need for flexibility in a devastating disease like ALS, regulators signaled a willingness to consider greenlighting tofersen based on its effect on a certain protein associated with ALS despite a failed pivotal trial. The documents come after regulatory flexibility was part of the same rationale the agency expressed when approving an ALS drug last September from Amylyx Pharmaceuticals, indicating the FDA’s openness to approving new treatments for the disease.

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Josep Bassaganya-Riera, NImmune Biopharma

Ex­clu­sive: Af­ter get­ting his drug back, Lan­dos founder as­sem­bles new start­up for the big PhI­II test

By the time Josep Bassaganya-Riera stepped down as founding CEO of Landos Biopharma in 2021, the company had racked up Phase II data for its top autoimmune program, completed what he called a positive end-of-Phase-II meeting with the FDA and plans to launch pivotal Phase III trials.

Since then, though, the new leaders at Landos have reshuffled their plans for the drug, omilancor, first announcing they will run a Phase IIb ahead of a Phase III and eventually shelving it altogether.

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NIH re­jects an­oth­er at­tempt to 'march-in' on Astel­las' prostate can­cer drug over ex­ces­sive price

The National Institutes of Health has again declined to use so-called “march-in” rights to lower the price of Astellas and Pfizer’s prostate cancer drug Xtandi despite being invented at UCLA with grants from the US Army and NIH.

“Given the remaining patent life and the lengthy administrative process involved for a march-in proceeding, NIH does not believe that use of the march-in authority would be an effective means of lowering the price of the drug,” NIH told prostate cancer patients Robert Sachs and Clare Love, in a letter shared with Endpoints News. The institutes’ analyses found Xtandi “to be widely available to the public,” an indication that there was not a pressing need for the US to act.