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.

The FDA’s Oncology Center of Excellence has been a bright spot within the agency in terms of speeding new treatments to patients. That flexibility was on full display this morning as FDA released new draft guidance spelling out exactly how oncology drug developers can fulfill both the accelerated and full approval’s requirements with just a single randomized controlled trial.

While Congress recently passed legislation that will allow FDA to require confirmatory trials to be recruiting and ongoing prior to granting an accelerated approval, the agency is now making clear that the initial trial used to win the AA, if designed appropriately, can also serve as the trial for converting the accelerated approval into a full approval.

US regulators cleared an ultra-rare drug from Pharming Group, by way of Novartis, on Friday afternoon.

The Dutch biotech said the FDA greenlit leniolisib for an immunodeficiency disease known as activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome, or APDS. People 12 years and older can receive the oral drug, to be marketed as Joenja, beginning early next month, Pharming said, five days ahead of the decision deadline set by the FDA as part of a priority review.

A California judge will allow a plaintiff in a state court case to introduce expert testimony connecting a potential carcinogen in former blockbuster medicine Zantac to cancer.

The order was handed down on Thursday from state judge Evelio Grillo, who is now allowing both parties to introduce expert testimony in an upcoming trial after what’s known as a Sargon hearing, where a judge determines the admissibility of expert witnesses and expert opinions.