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.”

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

Hal Barron, Endpoints UKBIO20 (Jeff Rumans)

'Al­tos was re­al­ly a once-in-a-life­time op­por­tu­ni­ty': Hal Bar­ron re­flects on his big move

By all accounts, Hal Barron had one of the best jobs in Big Pharma R&D. He made more than $11 million in 2020, once again reaping more than his boss, Emma Walmsley, who always championed him at every opportunity. And he oversaw a global R&D effort that struck a variety of big-dollar deals for oncology, neurodegeneration and more.

Sure, the critics never let up about what they saw as a rather uninspiring late-stage pipeline, where the rubber hits the road in the Big Pharma world’s hunt for the next big near-term blockbuster, but the in-house reviews were stellar. And Barron was firmly focused on bringing up the success rate in clinical trials, holding out for the big rewards of moving the dial from an average 10% success rate to 20%.

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Executive Director of the EMA Emer Cooke (AP Photo/Geert Vanden Wijngaert)

Eu­ro­pean Par­lia­ment signs off on strength­en­ing drug reg­u­la­tor's abil­i­ty to tack­le short­ages

The European Parliament on Thursday endorsed a plan to increase the powers of the European Medicines Agency, which will be better equipped to monitor and mitigate shortages of drugs and medical devices.

By a vote of 655 to 31, parliament signed off on a provisional agreement reached with the European Council from last October, in which the EMA will create two shortage steering groups (one for drugs, the other for devices), a new European Shortages Monitoring Platform to facilitate data collection and increase transparency, and on funding for the work of the steering groups, task force, working parties and expert panels that are to be established.

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Kenneth Galbraith, incoming Zymeworks CEO

Zymeworks re­places half its C-suite, aims to lay off 25% of to­tal work­force as new CEO takes over

New Zymeworks CEO Kenneth Galbraith is aiming to hit the ground running when his tenure officially begins next month, but he’ll be doing so with a much different looking team.

In a lengthy press release outlining the biotech’s 2022 goals, Galbraith said Zymeworks will be laying off at least 25% of its staff over the course of the year. Half of its C-suite will also be replaced immediately as Galbraith looks to remake the company in his image after Ali Tehrani, Zymeworks’ founder and CEO since 2003, stepped down two weeks ago.

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Crit­ics push back on Alzheimer’s As­so­ci­a­tion ad blitz to get Medicare to change its Aduhelm rul­ing: 'Dead wrong'

The latest Alzheimer’s Association advertising campaign encourages people to fight.

Not against the disease or for more research or treatments, but against the Centers for Medicare and Medicaid Services. More specifically, CMS’ recent reimbursement decision to only pay for Biogen and Eisai’s controversial Alzheimer’s drug Aduhelm for patients in clinical trials.

With CMS’ preliminary decision now in a 30-day comment period, patient advocates’ goal is to convince CMS to reverse its decision with a marketing blitz and public pressure.

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Dan O'Day, Gilead CEO (Jim Watson/AFP via Getty Images)

Fail­ing to con­firm clin­i­cal ben­e­fit, Gilead pulls 2 ac­cel­er­at­ed ap­proval in­di­ca­tions for can­cer drug

Gilead recently decided to pull two indications for its cancer drug Zydelig — in relapsed follicular B-cell non-Hodgkin lymphoma (FL) and relapsed small lymphocytic leukemia (SLL) — after failing to complete the confirmatory trials required as part of the accelerated approvals from 2014.

“As the treatment landscape for FL and SLL has evolved, enrollment into the confirmatory study has been an ongoing challenge,” Gilead said in a statement, noting it formally notified the FDA of its decision to voluntarily withdraw these indications.

Richard Pazdur (via AACR)

Time lim­its on ac­cel­er­at­ed ap­provals? FDA's on­col­o­gy chief Rick Paz­dur eyes po­ten­tial re­forms via in­ter­na­tion­al ap­proach­es

The spotlight on the accelerated approval pathway continues to shine bright, with the FDA’s top oncology official writing in an opinion that the pathway may be strengthened with bits and pieces of what other regulators in Europe and elsewhere have done with their expedited approval pathways, such as adding expiration dates for these faster approvals to ensure they confirm clinical benefit in a timely manner.

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Covid-19 roundup: HHS may strug­gle to ab­sorb Op­er­a­tion Warp Speed; Eu­rope has no plans for a fourth vac­cine dose

Operation Warp Speed, perhaps the greatest achievement of the former Trump administration, promptly delivered Covid-19 vaccine supplies nationwide when they became available, thanks to collaborations between HHS and the Department of Defense, while helping to fund and aid the manufacture of billions of doses.

But since the Biden administration took over a year ago, acting FDA commissioner Janet Woodcock transitioned out of her role as the therapeutics lead in Warp Speed, which has been converted into a new operation without the fancy name (now known as the “HHS-DOD COVID-19 Countermeasures Acceleration Group”), and as of the start of 2022, the Department of Defense is no longer helping HHS on the program.

Flori­da man con­vict­ed of fal­si­fy­ing clin­i­cal tri­al re­sults sen­tenced to over 2 years in prison

A Florida man who falsified medical records in connection to clinical trials was sentenced to 30 months in prison in federal court Thursday.

Daniel Tejeda, 35, of Clewiston, was also ordered to pay $2.1 million in restitution. Tejeda was a project manager and study manager for the CRO Tellus Clinical Research, and made it appear that subjects were participating in trials when they weren’t. Two other research workers from Florida were sentenced in the same case in August for 46 and 30 months, respectively.