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.

2023 Spot­light on the Fu­ture of Drug De­vel­op­ment for Small and Mid-Sized Biotechs

In the context of today’s global economic environment, there is an increasing need to work smarter, faster and leaner across all facets of the life sciences industry.  This is particularly true for small and mid-sized biotech companies, many of which are facing declining valuations and competing for increasingly limited funding to propel their science forward.  It is important to recognize that within this framework, many of these smaller companies already find themselves resource-challenged to design and manage clinical studies themselves because they don’t have large teams or in-house experts in navigating the various aspects of the drug development journey. This can be particularly challenging for the most complex and difficult to treat diseases where no previous pathway exists and patients are urgently awaiting breakthroughs.

Christian Itin, Autolus CEO (UKBIO19)

Au­to­lus tips its hand, bags $220M as CAR-T show­down with Gilead looms

The first batch of pivotal data on Autolus Therapeutics’ CAR-T is in, and execs are ready to plot a path to market.

With an overall remission rate of 70% at the interim analysis featuring 50 patients, the results set the stage for a BLA filing by the end of 2023, said CEO Christian Itin.

Perhaps more importantly — given that Autolus’ drug, obe-cel, is going after an indication that Gilead’s Tecartus is already approved for — the biotech highlighted “encouraging safety data” in the trial, with a low percentage of patients experiencing severe immune responses.

Dipal Doshi, Entrada Therapeutics CEO

Ver­tex just found the next big ‘trans­for­ma­tive’ thing for the pipeline — at a biotech just down the street

Back in the summer of 2019, when I was covering Vertex’s executive chairman Jeff Leiden’s plans for the pipeline, I picked up on a distinct focus on myotonic dystrophy Type I, or DM1 — one of what Leiden called “two diseases (with DMD) we’re interested in and we continue to look for those assets.”

Today, Leiden’s successor at the helm of Vertex, CEO Reshma Kewalramani, is plunking down $250 million in cash to go the extra mile on DM1. The lion’s share of that is for the upfront, with a small reserve for equity in a deal that lines Vertex up with a neighbor in Seaport that has been rather quietly going at both of Vertex’s early disease targets with preclinical assets.

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Rami Elghandour, Arcellx CEO

Up­dat­ed: Gilead, Ar­cel­lx team up on an­ti-BC­MA CAR-T as biotech touts a 100% re­sponse rate at #ASH22

Gilead and Kite are plunking down big cash to get into the anti-BCMA CAR-T game.

The pair will shell out $225 million in cash upfront and $100 million in equity to Arcellx, Kite announced Friday morning, to develop the biotech’s lead CAR-T program together. Kite will handle commercialization and co-development with Arcellx, and profits in the US will be split 50-50.

Concurrent with the deal, Arcellx revealed its latest cut of data for the program known as CART-ddBCMA, ahead of a full presentation at this weekend’s ASH conference — a 100% response rate among patients getting the therapy. Investors jumped at the dual announcements, sending Arcellx shares $ACLX up more than 25% in Friday’s morning session.

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WIB22: Am­ber Salz­man had few op­tions when her son was di­ag­nosed with a rare ge­net­ic dis­ease. So she cre­at­ed a bet­ter one

This profile is part of Endpoints News’ 2022 special report about Women in Biopharma R&D. You can read the full report here.

Amber Salzman’s life changed on a cold, damp day in Paris over tiny plastic cups of lukewarm tea.

She was meeting with Patrick Aubourg, a French neurologist studying adrenoleukodystrophy, or ALD, a rare genetic condition that causes rapid neurological decline in young boys. It’s a sinister disease that often leads to disability or death within just a few years. Salzman’s nephew was diagnosed at just 6 or 7 years old, and died at the age of 12.

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Ahead of ad­comm, FDA rais­es un­cer­tain­ties on ben­e­fit-risk pro­file of Cy­to­ki­net­ic­s' po­ten­tial heart drug

The FDA’s Cardiovascular and Renal Drugs Advisory Committee will meet next Tuesday to discuss whether Cytokinetics’ potential heart drug can safely reduce the risk of cardiovascular death and heart failure in patients with symptomatic chronic heart failure with reduced ejection fraction.

The drug, known as omecamtiv mecarbil and in development for more than 15 years, has seen mixed results, with a first Phase III readout from November 2020 hitting the primary endpoint of reducing the odds of hospitalization or other urgent care for heart failure by 8%. But it also missed a key secondary endpoint analysts had pegged as key to breaking into the market.

Ab­b­Vie slapped with age dis­crim­i­na­tion law­suit, fol­low­ing oth­er phar­mas

Add AbbVie to the list of pharma companies currently facing age discrimination allegations.

Pennsylvania resident Thomas Hesch filed suit against AbbVie on Wednesday, accusing the company of passing him over for promotions in favor of younger candidates.

Despite 30 years of pharma experience, “Hesch has consistently seen younger, less qualified employees promoted over him,” the complaint states.

Scoop: Gilead ter­mi­nates ear­ly-stage FLT3 tri­al in sol­id tu­mors

Gilead chopped a Phase Ib dose escalation study in recent days, with an update to the federal trials database saying the premature termination followed an “internal safety assessment.”

The IV-administered FLT3 agonist, dubbed GS-3583, was being tested as a monotherapy in 13 patients with advanced solid tumors. The goal of the trial was to find out what dose to test in a Phase II, or maximum tolerated dose.

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Susan Galbraith, AstraZeneca EVP, oncology R&D, at EUBIO22 (Rachel Kiki for Endpoints News)

As­traZeneca’s Su­san Gal­braith high­lights twin wins for the can­cer drug pipeline at SABCS, as oral SERD ex­cels

It’s a good time to be the head of R&D for oncology at AstraZeneca. And no one gets that quite like Susan Galbraith.

Today, Galbraith is at the San Antonio Breast Cancer Symposium, highlighting the data on two key drugs in the cancer pipeline: mid-stage results for its oral SERD camizestrant among patients after one line of therapy, and the AKT drug capivasertib, wrapping the Phase III. Both fall neatly into the range of successes, beating out fulvestrant in hormone receptor-positive, HER2-negative breast cancer.

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