Af­ter a PhII cat­a­stro­phe wiped out a bil­lion dol­lars in mar­ket cap, Seres is look­ing for a do-over

Seres CEO Roger Pomer­antz

Last sum­mer, shares of Seres Ther­a­peu­tics $MCRB were shred­ded by a failed Phase II study for their lead mi­cro­bio­me drug pro­gram, wip­ing out a bil­lion dol­lars of mar­ket cap.

The set­back not on­ly raised se­ri­ous ques­tions about Seres and its ex­per­tise in the field, as the most ad­vanced mi­cro­bio­me study in the in­dus­try it al­so cast a pall over the whole field of mi­cro­bio­me R&D, the use of teem­ing mul­ti­tudes of bac­te­ria in the gut to fix what ails you.

Seres’ first tar­get was a tough one. The biotech tack­led re­cur­rent Clostrid­i­um dif­fi­cile in­fec­tion, but fell far short of sta­tis­ti­cal sig­nif­i­cance when com­pared to a place­bo. And the stock has yet to re­cov­er.

But now Seres wants a do-over, tak­ing what it learned from what went wrong and ap­ply­ing it in a new study, once they have a chance to re­view their plans for this drug with the FDA.

“We don’t think we screwed up the tri­al de­sign,” says CEO Roger Pomer­antz, an ex­pe­ri­enced Mer­ck vet who made the switch to biotech, in re­sponse to my first query. “We did learn things in a new field not in­tu­itive­ly ob­vi­ous or the sci­ence had been there 2.5 years ago.” And the re­view in­volved look­ing through every­thing, from CMC to phar­ma­co­dy­nam­ics and phar­ma­co­ki­net­ics, mi­cro­bio­me analy­sis and more.

One key mis­take, says Pomer­antz, was choos­ing the wrong di­ag­nos­tic test. Most of the pa­tients were cho­sen us­ing a poly­merase chain re­ac­tion test, he says, which doesn’t ac­tu­al­ly tell you if the C. dif­fi­cile cy­to­tox­in genes found by the test are pro­duc­ing dis­ease-caus­ing cy­to­tox­ins.

Switch­ing to sam­ples of pa­tients who chose to join the open la­bel ex­ten­sion study, few­er than half of the to­tal of 72 who were en­rolled, the cy­to­tox­in test found that on­ly 44% of the pa­tients who test­ed pos­i­tive with the PCR test al­so test­ed pos­i­tive with the cy­to­tox­in test.

In­ves­ti­ga­tors con­clud­ed that the test re­sults could have been sim­ply screwed up through the use of the wrong test, al­so skew­ing the num­ber of re­cur­rences tracked in the two drug arms. That could be fixed by switch­ing to the cy­to­tox­in test, which they plan to do in the new tri­al.

They al­so found that the dose used was clear­ly “sub­op­ti­mal,” sug­gest­ing a bet­ter dos­ing would have pro­duced much bet­ter re­sults.

But it’s not nec­es­sar­i­ly easy to make that ar­gu­ment at the FDA. Do-overs are not un­com­mon in bio­phar­ma, but they are ex­treme­ly high-risk af­fairs that of­ten do not work out the way they’re planned.

The PCR test that they de­cid­ed to use on the first go is al­so en­dorsed by the Mayo Clin­ic — which has par­tic­i­pat­ed in the tri­al work for Seres — as “high­ly ac­cu­rate.” The cy­to­tox­in test is more cum­ber­some, ac­cord­ing to the clin­ic, takes longer and is some­times paired with an en­zyme im­munoas­say test for ac­cu­ra­cy. Pomer­antz, though, says there have been sev­er­al new pa­pers just this year that high­light the is­sues they ex­pe­ri­enced with the PCR test.

In ad­di­tion, Seres ac­knowl­edges that there was a sig­nif­i­cant­ly high­er rate of se­ri­ous ad­verse events in the drug group, 15% ver­sus 10.3% in the place­bo arm — though the in­ves­ti­ga­tors did not con­sid­er the SAEs drug re­lat­ed.

But Pomer­antz is sat­is­fied that when you break new ground in drug R&D, as Seres is try­ing to do, there will be a con­sid­er­able amount of tri­al and er­ror in the process.

“We re­al­ly are open­ing a new field in med­i­cine,” says the R&D vet. But Seres al­so has a break­through drug des­ig­na­tion with the FDA, which gives the biotech ready ac­cess to reg­u­la­tors. At this point, he adds, it’s too ear­ly to tell ex­act­ly how the agency will re­spond to the pitch. And he isn’t say­ing now what the ob­jec­tive is go­ing to be.

The big ques­tion for Seres is whether the FDA will look over its find­ing and ask for a new Phase II to clear the hur­dle that now ex­ists, or if it will al­low the de­vel­op­er to shape this in­to a piv­otal study that would po­si­tion them to ap­ply for mar­ket­ing ap­proval, if it proves suc­cess­ful. I asked. Pomer­antz, though, just isn’t go­ing there right now.

“I don’t like to get ahead with the FDA,” says the CEO.

But one way or the oth­er the come­back cam­paign is about to take it’s next big step. There’s a lot rid­ing on it.

Scoop: Boehringer qui­et­ly shut­ters a PhII for one of its top drugs — now un­der re­view

Boehringer Ingelheim has quietly shut down a small Phase II study for one of its lead drugs.

The private pharma player confirmed to Endpoints News that it had shuttered a study testing spesolimab as a therapy for Crohn’s patients suffering from bowel obstructions.

A spokesperson for the company tells Endpoints:

Taking into consideration the current therapeutic landscape and ongoing clinical development programs, Boehringer Ingelheim decided to discontinue our program in Crohn’s disease. It is important to note that this decision is not based on any safety findings in the clinical trials.

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Almost two years after Takeda wagered $300 million cash to partner with Arrowhead on an RNAi therapy for a rare disease, the companies are spelling out Phase II data that they believe put them one step closer to their big dreams.

In a small, open label study involving only 16 patients who had liver disease associated with alpha-1 antitrypsin deficiency (AATD), Arrowhead’s candidate — fazirsiran, previously ARO-AAT — spurred substantial reductions in accumulated mutant AAT protein in the liver, a hallmark of the condition. Investigators also tracked improvements in symptoms, with seven out of 12 who received the high, 200 mg dose seeing regression of liver fibrosis.

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Ireland has been on a roll in 2022, with several large pharma companies announcing multimillion-euro projects. Now AstraZeneca’s rare disease outfit Alexion is looking to get in on the action.

Alexion on Friday announced a €65 million ($68.8 million) investment in new and enhanced capabilities across two sites in the country, including at College Park in the Dublin suburb of Blanchardstown and the Monksland Industrial Park in the central Irish town of Athlone, according to the Industrial Development Agency of Ireland.

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Since Friday’s SCOTUS opinion to overturn Americans’ constitutional right to an abortion after almost 50 years, reproductive rights lawyers at Planned Parenthood and other organizations have already challenged these trigger laws in Utah and Louisiana. According to the Guttmacher Institute, other states with trigger laws that could take effect include Arkansas, Idaho, Kentucky, Mississippi, Missouri, North Dakota, Oklahoma, South Dakota, Tennessee, Texas, and Wyoming.

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Merck partner 4D Pharma has reported that a key lender, Oxford Finance, shoved the UK company into administration after calling in a $14 million loan they couldn’t immediately make good on. Trading in their stock was halted with a market cap that had fallen to a mere £30 million.

“Despite the very difficult prevailing market conditions,” 4D reported on Friday, the biotech had been making progress on finding some new financing and turned to Oxford with an alternative late on Thursday and then again Friday morning.

Members of the G7 from left to right: Prime Minister of Italy Mario Draghi, European Commission President Ursula von der Leyen, President Joe Biden, German Chancellor Olaf Scholz, British Prime Minister Boris Johnson, Canadian Prime Minister Justin Trudeau, Prime Minister of Japan Fumio Kishida, French President Emmanuel Macron and European Council President Charles Michel (AP Photo/Susan Walsh)

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According to a statement from the White House, the G7 leaders have formally launched the partnership for global infrastructure, PGII. The effort will aim to mobilize hundreds of billions of dollars to deliver infrastructure projects in several sectors including the medical and pharmaceutical manufacturing space.

Fed­er­al judge de­nies Bris­tol My­er­s' at­tempt to avoid Cel­gene share­hold­er law­suit

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On Friday, a New York federal judge ruled that they have a case against the pharma giant, denying a request to dismiss allegations that it purposely slow-rolled Breyanzi’s approval to avoid paying out $6.4 billion in contingent value rights (CVR).

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San Francisco-based Nuvation Bio announced early Monday the FDA placed a partial clinical hold on a Phase I dose-escalation study of NUV-422, its CDK inhibitor program for certain types of solid tumors. The trial began enrolling patients in December 2020, and, according to Nuvation, researchers were in the middle of exploring dose escalation and defining the maximum dose tolerable in patients.