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.”

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

So — that pig-to-hu­man trans­plant; Po­ten­tial di­a­betes cure reach­es pa­tient; Ac­cused MIT sci­en­tist lash­es back; 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.

We’re incredibly excited to welcome Beth Bulik, seasoned pharma marketing reporter, to the team. You can find much of her work in our new Marketing channel — and in her weekly newsletter, Endpoints PharmaRx, which will launch in early November. Add it to your subscriptions here.

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NYU surgeon transplants an engineered pig kidney into the outside of a brain-dead patient (Joe Carrotta/NYU Langone Health)

No, sci­en­tists are not any clos­er to pig-to-hu­man trans­plants than they were last week

Steve Holtzman was awoken by a 1 a.m. call from a doctor at Duke University asking if he could put some pigs on a plane and fly them from Ohio to North Carolina that day. A motorcyclist had gotten into a horrific crash, the doctor explained. He believed the pigs’ livers, sutured onto the patient’s skin like an external filter, might be able to tide the young man over until a donor liver became available.

UP­DAT­ED: Agenus calls out FDA for play­ing fa­vorites with Mer­ck, pulls cer­vi­cal can­cer BLA at agen­cy's re­quest

While criticizing the FDA for what may be some favoritism towards Merck, Agenus on Friday officially pulled its accelerated BLA for its anti-PD-1 inhibitor balstilimab as a potential second-line treatment for cervical cancer because of the recent full approval for Merck’s Keytruda in the same indication.

The company said the BLA, which was due for an FDA decision by Dec. 16, was withdrawn “when the window for accelerated approval of balstilimab closed,” thanks to the conversion of Keytruda’s accelerated approval to a full approval four months prior to its PDUFA date.

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How to col­lect and sub­mit RWD to win ap­proval for a new drug in­di­ca­tion: FDA spells it out in a long-await­ed guid­ance

Real-world data are messy. There can be differences in the standards used to collect different types of data, differences in terminologies and curation strategies, and even in the way data are exchanged.

While acknowledging this somewhat controlled chaos, the FDA is now explaining how biopharma companies can submit study data derived from real-world data (RWD) sources in applicable regulatory submissions, including new drug indications.

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David Livingston (Credit: Michael Sazel for CeMM)

Renowned Dana-Far­ber sci­en­tist, men­tor and bio­phar­ma ad­vi­sor David Liv­ingston has died

David Livingston, the Dana-Farber/Harvard Med scientist who helped shine a light on some of the key molecular drivers of breast and ovarian cancer, died unexpectedly last Sunday.

One of the senior leaders at Dana-Farber during his nearly half century of work there, Livingston was credited with shedding light on the genes that regulate cell growth, with insights into inherited BRCA1 and BRCA2 mutations that helped lay the scientific foundation for targeted therapies and earlier detection that have transformed the field.

No­vo CEO Lars Fruer­gaard Jør­gensen on R&D risk, the deal strat­e­gy and tar­gets for gen­der di­ver­si­ty


I kicked off our European R&D summit last week with a conversation involving Novo Nordisk CEO Lars Fruergaard Jørgensen. Novo is aiming to launch a new era of obesity management with a new approval for semaglutide. And Jørgensen had a lot to say about what comes next in R&D, how they manage risk and gender diversity targets at the trendsetting European pharma giant.

John Carroll: I’m here with Lars Jørgensen, the CEO of Novo Nordisk. Lars, it’s been a really interesting year so far with Novo Nordisk, right? You’ve projected a new era of growing sales. You’ve been able to expand on the GLP-1 franchise that was already well established in diabetes now going into obesity. And I think a tremendous number of people are really interested in how that’s working out. You have forecast a growing amount of sales. We don’t know specifically how that might play out. I know a lot of the analysts have different ideas, how those numbers might play out, but that we are in fact embarking on a new era for Novo Nordisk in terms of what the company’s capable of doing and what it’s able to do and what it wants to do. And I wanted to start off by asking you about obesity in particular. Semaglutide has been approved in the United States for obesity. It’s an area of R&D that’s been very troubled for decades. There have been weight loss drugs that have come along. They’ve attracted a lot of attention, but they haven’t actually ever gained traction in the market. My first question is what’s different this time about obesity? What is different about this drug and why do you expect it to work now whereas previous drugs haven’t?

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René Russo, Xilio CEO (Alicia Petitti for Xilio)

Xilio Ther­a­peu­tics goes pub­lic as bio­phar­ma IPOs rum­ble for­ward in Q4

It’s been a busy fall on Wall Street — and this week, we’ve got another biotech going public after Ventyx yesterday.

Massachusetts solid-tumor biotech Xilio Therapeutics made its public debut today, joining 149 other biotechs that have gone public so far this year.

Back on October 1st, Xilio filed its S-1 with the SEC to make its IPO debut for $100 million — the next step in financing after completing a $95 million Series C back in February.

Luc Boblet, Egle Therapeutics CEO

A new Treg play­er emerges with $46M and back­ing from Take­da

In recent years, the chorus of biotechs and Big Pharma backers targeting regulatory T cells — also known as “Tregs” — for cancer and autoimmune diseases has only grown louder.

The newest voice is from Egle Therapeutics, which sang out a $46.4 million Series A round on Friday led by LSP and Bpifrance through their InnoBio 2 fund. Takeda’s venture arm also chipped in, about a year after the pharma struck a research pact with the Paris-based upstart.

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