French can­cer-fo­cused mi­cro­bio­me play­er is flush with €18M Se­ries B in­jec­tion

Last year, the death of an im­muno-com­pro­mised el­der­ly pa­tient in a fe­cal mi­cro­bio­ta trans­plan­ta­tion tri­al — due to a do­na­tion that con­tained a rare type of E. coli bac­te­ria — sent shiv­ers across the field. The in­ci­dent marred an oth­er­wise ex­plod­ing field of drug de­vel­op­ment that backed re­plen­ish­ing the gut with good bac­te­ria as a safe and ef­fec­tive means to for­ti­fy the im­mune sys­tem to fight dis­ease.

Hervé Affa­gard

For France’s MaaT Phar­ma, an on­col­o­gy-fo­cused mi­cro­bio­me com­pa­ny, the set­back was al­most re­as­sur­ing.

“Bot­tom line is if they would have used our prod­uct, this pa­tient would not have died,” chief Hervé Affa­gard said in an in­ter­view with End­points News, sug­gest­ing that MaaT’s rig­or­ous test­ing stan­dards in­clude the screen­ing of drug-re­sis­tant bac­te­ria that would have pre­clud­ed the use of the rogue do­na­tion.

On Wednes­day the com­pa­ny — whose lead ex­per­i­men­tal prod­uct is an en­e­ma for­mu­la­tion de­signed to help pa­tients with acute graft-ver­sus-host dis­ease that have un­der­gone stem cell trans­plan­ta­tion — scored €18 mil­lion in Se­ries B fi­nanc­ing as it works on prov­ing its met­tle in a field crowd­ed with com­peti­tors fo­cused on a raft of dis­eases.

Mi­cro­bio­me-based ther­a­peu­tics to­day is a fe­cund field for drug de­vel­op­ers — big and small — cap­i­tal­iz­ing on sci­ence that sug­gests flush­ing ‘good’ gut bac­te­ria in­to the sys­tem can treat a pletho­ra of con­di­tions — from C. diff in­fec­tions to obe­si­ty — us­ing dif­fer­ent ther­a­peu­tic modal­i­ties, some of which are de­signed to side­step the “ick” fac­tor as­so­ci­at­ed with tra­di­tion­al stool trans­fer or fe­cal mi­cro­bio­ta trans­plan­ta­tion (FMT).

The con­cept of FMT was orig­i­nal­ly doc­u­ment­ed in Chi­na and has been used in the Unit­ed States since the 1950s with lit­tle reg­u­la­to­ry scruti­ny. In the last decade, the FDA sanc­tioned the use of FMT as a last re­sort mea­sure for re­cur­rent C. diff, but the agency con­tin­ues to con­sid­er it an in­ves­ti­ga­tion­al treat­ment. Glob­al­ly, hun­dreds of tri­als are now un­der­way test­ing the po­ten­tial of FMT for pa­tients suf­fer­ing from var­i­ous ill­ness­es, from autism to can­cer.

A few years ago, the spec­tac­u­lar fail­ure of Seres Ther­a­peu­tics’ sem­i­nal ef­fort in­to de­vel­op­ing a “crap­sule” — donor-de­rived processed fe­cal ma­te­r­i­al en­cap­su­lat­ed in a pill — de­railed an emerg­ing field work­ing to har­ness the in­sights gained from gut mi­cro­bio­ta to de­vel­op drugs. How­ev­er, the suc­cess of fe­cal trans­plant ther­a­pies to treat stub­born­ly re­cur­rent C. diff in­fec­tions has gained trac­tion, at­tract­ing a buck­et of biobucks and even in­spir­ing the takeover of a key play­er, Re­bi­otix.

MaaT Phar­ma prides it­self on its metic­u­lous process of donor screen­ing, qual­i­ty con­trol and di­ver­si­ty of bac­te­ria in its prod­uct — which like many oth­ers is for­mu­lat­ed us­ing fe­ces from healthy donors.

The Ly­on-based com­pa­ny’s lead for­mu­la­tion — MaaT013 — is cur­rent­ly in a mid-stage study in GvHD pa­tients. Da­ta from this tri­al are ex­pect­ed by the end of the year.

“It’s a kind of an im­muno-restora­tion, in­stead of im­muno­sup­pres­sion,” Affa­gard said of MaaT013, not­ing that all the drugs that have been de­vel­oped so far for GvHD pa­tients are im­muno­sup­pres­sive.

Late last year, MaaT re­port­ed en­cour­ag­ing MaaT013 da­ta from 8 pa­tients whose GvHD per­sist­ed de­spite up to five pre­vi­ous sys­temic treat­ments as part of a com­pas­sion­ate use pro­gram in hos­pi­tals. Each pa­tient ex­pe­ri­enced at least a par­tial re­sponse af­ter re­ceiv­ing MaaT013, while 3 out of 8 pa­tients at­tained a com­plete re­sponse, the com­pa­ny said.

“So we know our project is work­ing,” Affa­gard said. “Those pa­tients they’re re­ceiv­ing chemother­a­py, stem cell trans­plan­ta­tion…their mi­cro­bio­me was de­stroyed many times dur­ing their jour­ney.”

Next-gen­er­a­tion se­quenc­ing plat­forms and ad­vanced bioin­for­mat­ics ap­proach­es have stim­u­lat­ed re­search eval­u­at­ing the role of the gut mi­cro­bio­me in can­cer. In 2019, a con­sor­tium of ex­perts con­vened to dis­cuss the ev­i­dence un­der­ly­ing the as­so­ci­a­tion and found that while there are plau­si­ble mech­a­nisms and sup­port­ive ev­i­dence from in vit­ro, murine and cross-sec­tion­al hu­man stud­ies —di­rect ev­i­dence from large lon­gi­tu­di­nal co­hort stud­ies is lack­ing. In ef­fect, the role of the hu­man mi­cro­bio­me in the cause and sub­se­quent de­vel­op­ment of can­cer re­mains un­proven, the pan­el con­clud­ed, al­though a ma­jor­i­ty of pan­elists nev­er­the­less agreed with the hy­poth­e­sis.

MaaT is go­ing to use the fresh in­jec­tion of funds to prove its bet on the as­so­ci­a­tion. The mon­ey will be used for the on­go­ing Phase II en­e­ma study, as well as a cap­sule for­mu­la­tion that is set to be test­ed in a tri­al this year. The com­pa­ny is al­so ex­plor­ing the po­ten­tial of “restor­ing a bal­anced mi­cro­bio­me” to im­prove the clin­i­cal out­comes of check­point in­hibitors, with plans for a com­bi­na­tion tri­al in sol­id tu­mors.

The Se­ries B round in­clud­ed the par­tic­i­pa­tion of US in­vestor Sym­Bio­sis as well as sup­port from MaaT’s ex­ist­ing in­vestors Sev­en­ture Part­ners, Crédit Mutuel In­no­va­tion and Biocodex.

What Will it Take to Re­al­ize the Promise and Po­ten­tial of Im­mune Cell Ther­a­pies?

What does it take to get to the finish line with a new cancer therapy – fast? With approvals in place and hundreds of immune cell therapy candidates in the pipeline, the global industry is poised to create a fundamental shift in cancer treatments towards precision medicine. At the same time, unique challenges associated with cell and process complexity present manufacturing bottlenecks that delay speed to market and heighten cost of goods sold (COGS) — these hurdles must be overcome to make precision treatments an option for every cancer patient. This series of articles highlights some of the key manufacturing challenges associated with the production of cell-based cancer therapies as well as the solutions needed to transcend them. Automation, process knowledge, scalability, and assured supply of high-quality starting material and reagents are all critical to realizing the full potential of CAR-based therapies and sustaining the momentum achieved in recent years. The articles will highlight leading-edge technologies that incorporate these features to integrate across workflows, accelerate timelines and reduce COGS – along with how these approaches are enabling the biopharmaceutical industry to cross the finish line faster with new treatment options for patients in need.

The biggest ques­tions fac­ing gene ther­a­py, the XLMTM com­mu­ni­ty, and Astel­las af­ter fourth pa­tient death

After three patients died last year in an Astellas gene therapy trial, the company halted the study and began figuring out how to safely get the program back on track. They would, executives eventually explained, cut the dose by more than half and institute a battery of other measures to try to prevent the same thing from happening again.

Then tragically, Astellas announced this week that the first patient to receive the new regimen had died, just weeks after administration.

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Lat­est news: It’s a no on uni­ver­sal boost­ers; Pa­tient death stuns gene ther­a­py field; In­side Tril­li­um’s $2.3B turn­around; and more

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Next week is shaping up to be a busy one, as our editor-in-chief John Carroll and managing editor Kyle Blankenship lead back-to-back discussions with a great group of experts to discuss the weekend news and trends. John will be spending 30 minutes with Jake Van Naarden, the CEO of Lilly Oncology, and Kyle has a brilliant panel lined up: Harvard’s Cigall Kadoch, Susan Galbraith, the new head of cancer R&D at AstraZeneca, Roy Baynes at Merck, and James Christensen at Mirati. Don’t miss out on the action — sign up here.

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Mi­rati's KRAS drug looks like the fa­vorite in colon can­cer with new da­ta, putting the pres­sure square on Am­gen

With Amgen already providing proof-of-concept for KRAS inhibitors with its sotorasib, Mirati Therapeutics is piecing together a follow-up effort in lung cancer with data it thinks are superior. But in colon cancer, where solo sotorasib has turned in a dud, Mirati may now have a strong case for superiority.

Mirati’s adagrasib, dosed solo or in combination with chemotherapy cetuximab, showed response rates grater than sotorasib solo  and as part of combination study in a similar patient population also revealed this week at #ESMO21. Mirati’s data were presented as part of a cohort update from the Phase II KRYSTAL-1 study testing adagrasib in a range of solid tumors harboring the KRAS-G12C mutation.

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President Biden and Pfizer CEO Albert Bourla (Patrick Semansky/AP Images)

Chaot­ic ad­comm sees Pfiz­er/BioN­Tech boost­ers re­ject­ed for gen­er­al pop­u­la­tion, but rec­om­mend­ed for old­er and high-risk pop­u­la­tions

With just days before President Joe Biden’s Covid-19 booster rollout is set to go into effect, an FDA advisory committee appeared on the verge of not recommending boosters for anyone in the US before a last-minute change of wording laid the groundwork for older adults to have access to a third dose.

The FDA’s adcomm on Vaccines and Related Biological Products (VRBPAC) roundly rejected Pfizer/BioNTech booster shots for all individuals older than 16 by a 16-2 vote Friday afternoon. Soon after, however, the agency posed committee members a new question limiting booster use to the 65-and-older population and individuals at high risk of disease due to occupational exposure or comorbidities.

The best of the rest: High­lights from the be­low-the-fold pre­sen­ta­tions at #ES­MO21

This year’s ESMO Congress has had a major focus on Big Pharma drugs — most notably candidates from Merck and AstraZeneca — but there have also been updates from smaller biotechs with data looking to challenge the big-name drugmakers.

Today, we’re highlighting some of the data releases that flew under the radar at #ESMO21 — whether from early-stage drugs looking to make a mark or older stalwarts with interesting follow-up data.

As­traZeneca, Dai­ichi Sanky­o's ADC En­her­tu blows away Roche's Kad­cy­la in sec­ond-line ad­vanced breast can­cer

AstraZeneca and Japanese drugmaker Daiichi Sankyo think they’ve struck gold with their next-gen ADC drug Enhertu, which has shown some striking data in late-stage breast cancer trials and early solid tumor tests. Getting into earlier patients is now the goal, starting with Enhertu’s complete walkover of a Roche drug in second-line breast cancer revealed Saturday.

Enhertu cut the risk of disease progression or death by a whopping 72% (p=<0.0001) compared with Roche’s ADC Kadcyla in second-line unresectable and/or metastatic HER2-positive breast cancer patients who had previously undergone treatment with a Herceptin-chemo combo, according to interim data from the Phase III DESTINY-Breast03 head-to-head study presented at this weekend’s #ESMO21.

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Merck Research Laboratories CMO Roy Baynes

Mer­ck­'s Keytru­da un­corks full da­ta on lat­est ad­ju­vant win — this time in melanoma — adding bricks to ear­ly can­cer wall

In recent months, the battle for PD-(L)1 dominance has spilled over into early cancer with Merck’s Keytruda and Bristol Myers Squibb’s Opdivo all alone on the front lines. Keytruda now has another shell in its bandolier, and it could spell a quick approval.

Keytruda cut the risk of relapse or death by 35% over placebo (p=0.00658) in high-risk, stage 2 melanoma patients who had previously undergone surgery to remove their tumors, according to full data from the Phase III KEYNOTE-716 presented Saturday at #ESMO21.

Mer­ck flesh­es out Keytru­da win in first-line cer­vi­cal can­cer, adding more fire­pow­er to its ear­ly can­cer push

Merck has worked hard to bring its I/O blockbuster Keytruda into earlier and earlier lines of therapy, and now the wonder drug appears poised to make a quick entry into early advanced cervical cancer.

A combination of Keytruda and chemotherapy with or without Roche’s Avastin cut the risk of death by 33% over chemo with or without Avastin (p=<0.001) in first-line patients with persistent, recurrent or metastatic cervical cancer, according to full data from the Phase III KEYNOTE-826 study presented Saturday at #ESMO21.