Af­ter big 2016 set­back, field of mi­cro­bio­me-based drugs gets in­jec­tion of promise with pos­i­tive sig­nal from Re­bi­otix piv­otal study

Sev­er­al years ago, as com­pa­nies cap­i­tal­iz­ing on sci­ence that sug­gests flush­ing ‘good’ gut bac­te­ria in­to the sys­tem can treat a pletho­ra of con­di­tions — from C. diff in­fec­tions to obe­si­ty — be­gan to gain trac­tion, the op­por­tu­ni­ties to har­ness the mi­cro­bio­me gar­nered fever­ish promise and gen­er­ous fund­ing. Then, in 2016, Seres Ther­a­peu­tics’ fail­ure in a mid-stage tri­al eval­u­at­ing its “crap­sule” — donor-de­rived processed fe­cal ma­te­r­i­al en­cap­su­lat­ed in a pill — de­railed the emerg­ing field, rel­e­gat­ing the mi­cro­bio­me from hero to ze­ro sta­tus.

The mon­ey has since be­gun to trick­le back in, but the ex­pec­ta­tions are now more down to earth. A num­ber of sig­nif­i­cant da­ta read­outs from key play­ers this year are ex­pect­ed to gen­er­ate con­crete ev­i­dence that the ecosys­tem of gut bac­te­ria has a cru­cial role to play in health. On Wednes­day, Re­bi­otix of­fered the first glimpse of pos­i­tive da­ta from its on­go­ing late-stage study.

The com­pa­ny’s poop-de­rived frozen for­mu­la­tion, RBX2660, which is de­liv­ered in­to pa­tients via an en­e­ma, is be­ing de­vel­oped to re­duce re­cur­rent in­fec­tions of C. diff, a stub­born in­fec­tion that has grown re­sis­tant to ex­ist­ing an­tibi­otics and kills more than 29,000 Amer­i­cans each year.

Lee Jones Re­bi­otix

The 270 pa­tient place­bo-con­trolled study has met the main goal — the pro­por­tion of pa­tients with treat­ment suc­cess with RBX2660 to pre­vent re­cur­rent C. diff with­in 8 weeks ver­sus place­bo, but the full dataset is still to come, the com­pa­ny said, with­out dis­clos­ing any specifics.

“It has been a long time com­ing through a num­ber of ob­sta­cles to be able to pro­vide the da­ta that demon­strates that this is a ther­a­peu­tic op­tion for pa­tients and can be de­vel­oped as a drug prod­uct and can meet the re­quire­ments,” said Lee Jones, chief, and founder of Re­bi­otix, in an in­ter­view.

“It sig­nals to the field that this is re­al.”

Re­bi­otix, found­ed in 2011, was swal­lowed by Swiss drug­mak­er Fer­ring Phar­ma­ceu­ti­cals in 2018.

Per Falk Fer­ring

“I spent the bet­ter part of 34 years ei­ther as a grad stu­dent or as a sci­en­tist or as an in­vestor in this game, so I know how it has evolved,” said Fer­ring’s CSO Per Falk in an in­ter­view. “And this is clear­ly the clos­est we have ever got­ten to see a re­al ap­pli­ca­tion of the knowl­edge that has been build­ing for so long.”

The field of mi­cro­bio­me-based ther­a­peu­tics has grown to be a fe­cund field for drug de­vel­op­ers — big and small — us­ing dif­fer­ent ther­a­peu­tic modal­i­ties, some of which are de­signed to side­step the “ick” fac­tor as­so­ci­at­ed with tra­di­tion­al stool trans­fer or FMT.

The in­ter­ven­tion re­quires a stool sam­ple to be screened, liq­ue­fied, and de­liv­ered to the colon by nasal or rec­tal tube. Pa­tients must ei­ther find their own donor, ob­tain vi­able stool from a li­censed health care provider, or turn to a stool bank, such as Open­Bio­me. Few­er than 3% of the pop­u­la­tion qual­i­fy as healthy donors, ac­cord­ing to the Fe­cal Trans­plant Foun­da­tion.

Orig­i­nal­ly pi­o­neered in Chi­na, FMT has been used in the Unit­ed States for years now as a way to com­bat re­cur­rent C.diff, as the per­pe­trat­ing bac­te­ria have mu­tat­ed to in­creas­ing­ly ren­der tra­di­tion­al an­tibi­otics ob­so­lete. How­ev­er, the FDA con­sid­ers the in­ter­ven­tion an in­ves­ti­ga­tion­al treat­ment with an un­proven safe­ty and ef­fi­ca­cy pro­file. In 2013, the US reg­u­la­tor im­ple­ment­ed a pol­i­cy of “en­force­ment dis­cre­tion” in re­la­tion to FMT for treat­ment-re­frac­to­ry C. diff: While de­vel­op­ers are work­ing on ad­vanc­ing prod­ucts un­der an IND, physi­cians can use FMT prod­ucts af­ter se­cur­ing rea­son­able con­sent from pa­tients.

Jones has been a vo­cal crit­ic of the en­force­ment dis­cre­tion pol­i­cy, sug­gest­ing that the FDA has in a way gen­er­at­ed a path­way for pa­tients and doc­tors to con­duct stool trans­fers, with­out the req­ui­site safe­ty and over­sight. In ad­di­tion, she said, the pol­i­cy has slowed the process of tri­al en­roll­ment for com­pa­nies like Re­bi­otix and oth­ers in the field.

“What it (en­force­ment dis­cre­tion) did was it changed the re­fer­ral pat­terns,” she said. “It set the whole field back be­cause no­body re­al­ly knows now how those prod­ucts work, or if they were safe … I would say there was a five­fold de­crease in en­roll­ment rates through the course of our pro­grams based on the en­force­ment dis­cre­tion is­sues. We would have had a safe prod­uct out to the for pa­tient use well be­fore the time­frame that we’re talk­ing about now.”

Oth­ers in the field, such as Finch Ther­a­peu­tics CEO Mark Smith (who helped co-found Open­Bio­me) have as­sert­ed that while en­roll­ment in place­bo-con­trolled stud­ies is dif­fi­cult when pa­tients have open-la­bel ac­cess to FMT, it is still fea­si­ble, point­ing out many pa­tients do not even qual­i­fy for clin­i­cal tri­al en­roll­ment due to co­mor­bidi­ties or be­cause they have no ac­cess to sites.

Re­bi­otix’s full late-stage dataset is ex­pect­ed by this fall, but the coro­n­avirus pan­dem­ic has put some­what of a ques­tion mark on that time­line, Lee said.

“Un­for­tu­nate­ly, C. diff keeps go­ing on and in fact, with the ad­vent of a lot of peo­ple head­ing in­to the ICU, we ex­pect to see an uptick in this,” she said of the on­go­ing Phase III study. “So for those sites that are still ac­cept­ing pa­tients, and they’re still do­ing the clin­i­cal pro­gram. What’s dif­fi­cult is that a lot of clin­i­cal peo­ple are ground­ed in terms of trav­el­ing to the site … and so ac­cess to the clin­i­cal sites to do da­ta mon­i­tor­ing is tricky at this point in time.”

Safe­ty con­cerns

While drug de­vel­op­ers such as Re­bi­otix, Finch and Seres con­tin­ue on with their quest to de­vel­op drugs from bugs us­ing do­nat­ed stool, since last sum­mer, a hand­ful of safe­ty is­sues re­lat­ed to the raw ma­te­r­i­al have caused a stir.

Last year, the death of an im­muno-com­pro­mised 73-year old pa­tient in an FMT tri­al con­duct­ed by Mass­a­chu­setts Gen­er­al Hos­pi­tal (MGH) struck a chord with re­searchers, af­ter post-mortem test­ing re­vealed the stool do­na­tion used con­tained a rare type of E. coli bac­te­ria. The in­ci­dent shed light on the non-stan­dard­ized meth­ods dif­fer­ent re­searchers have been em­ploy­ing in or­der to screen and pu­ri­fy the stool used in such tri­als.

Mak­ing mat­ters worse, the FDA is­sued a safe­ty alert in March af­ter E. coli-taint­ed stool from the wide­ly used non-prof­it stool bank Open­Bio­me made six pa­tients sick, four of whom were hos­pi­tal­ized. Two oth­er FMT re­cip­i­ents whose trans­plants com­prised Open­Bio­me’s prod­uct al­so died. Weeks lat­er, the FDA is­sued an­oth­er safe­ty alert high­light­ing the risk of po­ten­tial trans­mis­sion of the new coro­n­avirus from fe­cal mat­ter de­rived from donors used in FMT and said that ad­di­tion­al safe­ty mea­sures are nec­es­sary.

Com­pa­nies in the field are now high­light­ing these in­ci­dents as an­oth­er rea­son to wait for their prod­ucts, which may still be har­nessed from the same raw ma­te­r­i­al, but must un­der­go the same rig­or­ous safe­ty and ef­fi­ca­cy test­ing as any oth­er chem­i­cal or bi­o­log­ic ther­a­py does be­fore hit­ting the mar­ket.

What these FDA alerts show is that with FMT, there will al­ways be an is­sue that must be chased, said Seres’ chief tech­nol­o­gy of­fi­cer John Aunins in a pre­vi­ous in­ter­view. “You didn’t test pre­vi­ous agents, or you use the test that wasn’t sen­si­tive enough or a pathogen emerges and you don’t have a test for it,” he said. “So it’s, it’s just an in­her­ent sit­u­a­tion with that kind of a prod­uct.”

Jones echoed the sen­ti­ment, say­ing she be­lieves the com­pa­ny’s pro­vi­sions for safe­ty will hold it in good stead. “We haven’t had the same is­sues that they’ve (Open­Bio­me) had in terms of safe­ty,” she said.

IDC: Life Sci­ences Firms Must Em­brace Dig­i­tal Trans­for­ma­tion Now

Pre-pandemic, the life sciences industry had settled into a pattern. The average drug took 12 years and $2.9 billion to bring to market, and it was an acceptable mode of operations, according to Nimita Limaye, Research Vice President for Life Sciences R&D Strategy and Technology at IDC.

COVID-19 changed that, and served as a proof-of-concept for how technology can truly help life sciences companies succeed and grow, Limaye said. She recently spoke about industry trends at Egnyte’s Life Sciences Summit 2022. You should watch the entire session, free and on-demand, but here’s a brief recap of why she’s urging life sciences companies to embrace digital transformation.

Tom Barnes, Orna Therapeutics CEO

UP­DAT­ED: 'We have failed to fail': Mer­ck gam­bles $250M cash on a next-gen ap­proach to mR­NA — af­ter punt­ing its big al­liance with Mod­er­na

Merck went in deep on its collaboration with Moderna on new mRNA programs, and dropped them all over time, including their RSV partnership. But after writing off what turned out as one of the most successful infectious disease players in the business, Merck is coming in this morning with a new preclinical alliance — this time embracing a biotech that hopes to eventually outdo the famously successful mRNA in a new run at vaccines and therapeutics.

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Bayer's first DTC ad campaign for chronic kidney disease drug Kerendia spells out its benefits

Bay­er aims to sim­pli­fy the com­plex­i­ties of CKD with an ABC-themed ad cam­paign

Do you know the ABCs of CKD in T2D? Bayer’s first ad campaign for Kerendia tackles the complexity of chronic kidney disease with a play on the acronym (CKD) and its connection to type 2 diabetes (T2D).

Kerendia was approved last year as the first and only non-steroidal mineralocorticoid receptor antagonist to treat CKD in people with type 2 diabetes.

In the TV commercial launched this week, A is for awareness, B is for belief and C is for cardiovascular, explained in the ad as awareness of the connection between type 2 and kidney disease, belief that something can be done about it, and cardiovascular events that may be reduced with treatment.

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James Mock, incoming CFO at Moderna

Mod­er­na taps new CFO from PerkinElmer af­ter for­mer one-day CFO oust­ed

When Moderna hired a new CFO last year,  it didn’t expect to see him gone after only one day. Today the biotech named his — likely much more vetted — replacement.

The mRNA company put out word early Wednesday that after the untimely departure of then brand-new CFO Jorge Gomez, it has now found a replacement in James Mock, the soon-to-be former CFO at diagnostics and analytics company PerkinElmer.

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Etleva Kadilli, director of UNICEF’s supply division

GSK lands first-ever UNICEF con­tract for malar­ia vac­cine worth $170M

GSK has landed a new first from UNICEF the first-ever contract for malaria vaccines, worth up to $170 million for 18 million vaccine doses distributed over the next three years.

The vaccine, known as Mosquirix or RTS,S, won WHO’s backing last October after a controversial start, but UNICEF said these doses will potentially save thousands of lives every year.

“We hope this is just the beginning,” Etleva Kadilli, director of UNICEF’s supply division, said. “Continued innovation is needed to develop new and next-generation vaccines to increase available supply, and enable a healthier vaccine market. This is a giant step forward in our collective efforts to save children’s lives and reduce the burden of malaria as part of wider malaria prevention and control programmes.”

Kate Haviland, Blueprint Medicines CEO

Blue­print met all its end­points in bid for ex­pand­ed Ay­vak­it la­bel — but stock trends low­er any­way

Blueprint Medicines announced this morning that the second part of its study on Ayvakit in non-advanced systemic mastocytosis (SM) — a rare disease in which a type of white blood cells known as mast cells builds up — met all endpoints, but the biopharma left key questions unanswered.

In 212 patients, with 141 in the treatment arm and 71 in the control arm, patients who got Ayvakit saw an average 15.6-point decrease in their symptom scores compared to a 9.2-point decrease in the placebo arm at 24 weeks. In an extension study, those on Ayvakit saw their symptom scores drop by 20.2 points by week 48.

Paul Perreault, CSL Behring CEO

CSL CEO Paul Per­reault de­ter­mined to grow plas­ma col­lec­tion af­ter full-year sales dip

As the ink dries on CSL’s $11.7 billion Vifor buyout, the company posted a dip in profits, due in part to a drop in plasma donations amid the pandemic.

However, CEO Paul Perreault assured investors and analysts on the full-year call that the team has left “no stone unturned” when assessing options to grow plasma volumes. The chief executive also spelled out positive results for the company’s monoclonal antibody garadacimab in hereditary angioedema (HAE), though he isn’t revealing the exact numbers just yet.

Paul Hudson, Sanofi CEO (Eric Piermont/AFP via Getty Images)

Up­dat­ed: Hit by an­oth­er PhI­II flop, Sanofi culls breast can­cer drug — sound­ing alarm for the class

Sanofi is officially giving up on its oral SERD.

The French drugmaker put out word Wednesday morning that it will discontinue the global development program of amcenestrant, the selective estrogen receptor degrader once billed as a top late-stage prospect. Having already failed a Phase II monotherapy test earlier this year, a combo with the drug also missed the bar in a second trial for breast cancer, triggering the decision to drop the whole program.

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Joe Jonas (Photo by Anthony Behar/Sipa USA)(Sipa via AP Images)

So­lo Jonas broth­er car­ries Merz's new tune in Botox ri­val cam­paign

As the lyrics of his band’s 2019 pop-rock single suggest, Joe Jonas is only human — and that means even he gets frown lines. The 33-year-old singer-songwriter is Merz’s newest celebrity brand partner for its Botox rival Xeomin, as medical aesthetics brands target a younger audience.

Merz kicked off its “Beauty on Your Terms” campaign on Tuesday, featuring the Jonas brother in a video ad for its double-filtered anti-wrinkle injection Xeomin.

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