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.”

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.

Dipal Doshi, Entrada Therapeutics CEO

Ver­tex just found the next big ‘trans­for­ma­tive’ thing for the pipeline — at a biotech just down the street

Back in the summer of 2019, when I was covering Vertex’s executive chairman Jeff Leiden’s plans for the pipeline, I picked up on a distinct focus on myotonic dystrophy Type I, or DM1 — one of what Leiden called “two diseases (with DMD) we’re interested in and we continue to look for those assets.”

Today, Leiden’s successor at the helm of Vertex, CEO Reshma Kewalramani, is plunking down $250 million in cash to go the extra mile on DM1. The lion’s share of that is for the upfront, with a small reserve for equity in a deal that lines Vertex up with a neighbor in Seaport that has been rather quietly going at both of Vertex’s early disease targets with preclinical assets.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Christian Itin, Autolus CEO (UKBIO19)

Au­to­lus tips its hand, bags $220M as CAR-T show­down with Gilead looms

The first batch of pivotal data on Autolus Therapeutics’ CAR-T is in, and execs are ready to plot a path to market.

With an overall remission rate of 70% at the interim analysis featuring 50 patients, the results set the stage for a BLA filing by the end of 2023, said CEO Christian Itin.

Perhaps more importantly — given that Autolus’ drug, obe-cel, is going after an indication that Gilead’s Tecartus is already approved for — the biotech highlighted “encouraging safety data” in the trial, with a low percentage of patients experiencing severe immune responses.

WIB22: Am­ber Salz­man had few op­tions when her son was di­ag­nosed with a rare ge­net­ic dis­ease. So she cre­at­ed a bet­ter one

This profile is part of Endpoints News’ 2022 special report about Women in Biopharma R&D. You can read the full report here.

Amber Salzman’s life changed on a cold, damp day in Paris over tiny plastic cups of lukewarm tea.

She was meeting with Patrick Aubourg, a French neurologist studying adrenoleukodystrophy, or ALD, a rare genetic condition that causes rapid neurological decline in young boys. It’s a sinister disease that often leads to disability or death within just a few years. Salzman’s nephew was diagnosed at just 6 or 7 years old, and died at the age of 12.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 154,300+ biopharma pros reading Endpoints daily — and it's free.

Ahead of ad­comm, FDA rais­es un­cer­tain­ties on ben­e­fit-risk pro­file of Cy­to­ki­net­ic­s' po­ten­tial heart drug

The FDA’s Cardiovascular and Renal Drugs Advisory Committee will meet next Tuesday to discuss whether Cytokinetics’ potential heart drug can safely reduce the risk of cardiovascular death and heart failure in patients with symptomatic chronic heart failure with reduced ejection fraction.

The drug, known as omecamtiv mecarbil and in development for more than 15 years, has seen mixed results, with a first Phase III readout from November 2020 hitting the primary endpoint of reducing the odds of hospitalization or other urgent care for heart failure by 8%. But it also missed a key secondary endpoint analysts had pegged as key to breaking into the market.

Ab­b­Vie slapped with age dis­crim­i­na­tion law­suit, fol­low­ing oth­er phar­mas

Add AbbVie to the list of pharma companies currently facing age discrimination allegations.

Pennsylvania resident Thomas Hesch filed suit against AbbVie on Wednesday, accusing the company of passing him over for promotions in favor of younger candidates.

Despite 30 years of pharma experience, “Hesch has consistently seen younger, less qualified employees promoted over him,” the complaint states.

Rami Elghandour, Arcellx CEO

Up­dat­ed: Gilead, Ar­cel­lx team up on an­ti-BC­MA CAR-T as biotech touts a 100% re­sponse rate at #ASH22

Gilead and Kite are plunking down big cash to get into the anti-BCMA CAR-T game.

The pair will shell out $225 million in cash upfront and $100 million in equity to Arcellx, Kite announced Friday morning, to develop the biotech’s lead CAR-T program together. Kite will handle commercialization and co-development with Arcellx, and profits in the US will be split 50-50.

Concurrent with the deal, Arcellx revealed its latest cut of data for the program known as CART-ddBCMA, ahead of a full presentation at this weekend’s ASH conference — a 100% response rate among patients getting the therapy. Investors jumped at the dual announcements, sending Arcellx shares $ACLX up more than 25% in Friday’s morning session.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 154,300+ biopharma pros reading Endpoints daily — and it's free.

WIB22: Lead­ing NK cell re­searcher re­flects on roots in Iran, the UK and Texas

This profile is part of Endpoints News’ 2022 special report about Women in Biopharma R&D. You can read the full report here.

In a small but widely-cited 11-person study published in NEJM in 2020, seven patients saw signs of their cancer completely go away after getting a new therapy made from natural killer cells. The study was one of the earliest to provide clinical proof that the experimental treatment method had promise.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 154,300+ biopharma pros reading Endpoints daily — and it's free.

Philip Astley-Sparke, Replimune CEO

Replimune looks to rope in $225M on the back of melanoma da­ta

The Massachusetts-based, oncolytic virus biotech Replimune is feeling bullish now that it has lifted the cover on data for its lead product.

Replimune said Thursday it looks to nab about $225 million from a public offering after giving a snapshot of some initial data from its IGNYTE clinical study earlier this week. The trial is investigating RP1 in combination with Opdivo, for patients with melanoma and who did not have a response when being treated with a PD-1.