Eric Shaff, Seres CEO

'By no means are we de­terred': Seres' stock spi­rals af­ter PhII mi­cro­bio­me fail in ul­cer­a­tive col­i­tis

Al­most five years af­ter Seres Ther­a­peu­tics slammed in­to a Phase II fail­ure with its lead can­di­date, the mi­cro­bio­me pi­o­neer is re­port­ing an­oth­er mas­sive flop in ul­cer­a­tive col­i­tis. But like the last time, the com­pa­ny isn’t throw­ing in the tow­el just yet.

Pa­tients who took SER-287 — a con­sor­tia of bac­te­ria found in the gas­troin­testi­nal tracts of healthy in­di­vid­u­als — showed no dif­fer­ence in clin­i­cal re­mis­sion com­pared to those giv­en a place­bo, Seres said of the Phase IIb tri­al. The news sent the biotech’s shares $MCRB spi­ral­ing more than 50% on Thurs­day morn­ing, pric­ing in at just un­der $10 apiece.

As a re­sult, Seres is clos­ing the open la­bel and main­te­nance por­tions of the study — but that doesn’t mean the drug is dead.

“Pi­o­neer­ing a new space is sel­dom a straight line from point A to point B,” CEO Er­ic Shaff told End­points News. “We’ve been here be­fore as a team and as a com­pa­ny, and we’re dis­ap­point­ed, but by no means are we de­terred.”

Shaff com­pared the fail­ure to the com­pa­ny’s lead can­di­date, SER-109, which flopped in a Phase II tri­al for C. dif­fi­cile in­fec­tion back in 2016 and di­min­ished in­vestor in­ter­est in the field for years af­ter­ward. But af­ter bid­ding adieu to for­mer CEO and Mer­ck vet Roger Pomer­antz, the com­pa­ny sol­diered on, claim­ing pos­i­tive topline Phase III re­sults last sum­mer. Nestlé Health Sci­ence put down $175 mil­lion up­front ear­li­er this month to co-com­mer­cial­ize the can­di­date, and has promised Seres an­oth­er $125 mil­lion if the FDA fol­lows through with an ap­proval.

“Af­ter our Phase IIb study re­sults in SER-109 for re­cur­rent C diff., we were in a sit­u­a­tion where we had a sur­pris­ing and dis­ap­point­ing re­sult,” Shaff said. “We went through a rig­or­ous sci­en­tif­i­cal­ly ob­jec­tive analy­sis, and ul­ti­mate­ly, at the end of that we came up with ad­just­ments that we thought could im­prove our prob­a­bil­i­ty of suc­cess.”

Lisa von Moltke

CMO Lisa von Moltke says mi­cro­bio­me analy­ses for SER-287 should be ready in the sec­ond half of 2021.

“I can’t tell you where that analy­sis will go, but we cer­tain­ly do feel that that type of ap­proach is ap­pro­pri­ate here,” Shaff said.

The Phase IIb tri­al, dubbed ECO-RE­SET, en­rolled 203 UC pa­tients who re­ceived ei­ther a full in­duc­tion or step-down in­duc­tion dose of SER-287, or a place­bo. Pa­tients in the full in­duc­tion dose co­hort saw an ab­solute clin­i­cal re­mis­sion rate of 10.3%, com­pared to 10.6% for the step-down dose and 11.6% for the place­bo group.

Those on the drug al­so showed no dif­fer­ences in en­do­scop­ic im­prove­ment, en­do­scop­ic re­mis­sion, or symp­to­matic re­mis­sion, Seres said.

Back in March, Seres an­nounced its part­nered pro­gram with the Park­er In­sti­tute for Can­cer Im­munother­a­py in metasta­t­ic melanoma was be­ing shelved due to “chal­lenges” pre­sent­ed by run­ning the study dur­ing the pan­dem­ic.

When asked dur­ing a call with in­vestors whether the pan­dem­ic had any ef­fect on the SER-287 tri­al re­sults, von Moltke re­spond­ed, “Based on the topline da­ta we’ve seen so far, it looks like the ex­e­cu­tion was re­al­ly smooth through­out, and we’ll be look­ing of course for any kind of pat­tern as we dig deep­er in­to it, but I think we were quite pleased with the way the sites and the clin­i­cal team ex­e­cut­ed, and we’re quite thank­ful for their ef­forts.”

In the mean­time, the com­pa­ny seems to be shift­ing its fo­cus to SER-301, its Phase 1b can­di­date for UC. SER-301 is al­so made up of a con­sor­tia of healthy bac­te­ria — but it’s cul­ti­vat­ed in a lab, un­like SER-287, which is donor-de­rived.

“It re­al­ly is fo­cused,” Shaff said. “It al­lows us to think about the or­gan­isms that we know have the most ben­e­fi­cial ef­fects for dis­ease, in­clud­ing an­ti-in­flam­ma­to­ry prop­er­ties (and) pro­mot­ing gut bar­ri­er in­tegri­ty.”

The com­pa­ny has not an­nounced when it will read out those Phase Ib re­sults, but Shaff says the com­pa­ny will con­sid­er mak­ing ad­just­ments to the tri­al based on re­sults from the mi­cro­bio­me analy­sis of the SER-287 study.

“As al­ways, what we’ll do is fol­low the da­ta,” he said.

Adap­tive De­sign Meth­ods Of­fer Rapid, Seam­less Tran­si­tion Be­tween Study Phas­es in Rare Can­cer Tri­als

Rare cancers account for 22 percent of cancer diagnoses worldwide, yet there is no universally accepted definition for a “rare” cancer. Moreover, with the evolution of genomics and associated changes in categorizing tumors, some common cancers are now characterized into groups of rare cancers, each with a unique implication for patient management and therapy.

Adaptive designs, which allow for prospectively planned modifications to study design based on accumulating data from subjects in the trial, can be used to optimize rare oncology trials (see Figure 1). Adaptive design studies may include multiple cohorts and multiple tumor types. In addition, numerous adaptation methods may be used in a single trial and may facilitate a more rapid, seamless transition between study phases.

UK re-in­ves­ti­gates Pfiz­er's eye-pop­ping price goug­ing on an epilep­sy drug

When a drugmaker raises the price of a drug in the US by more than 2,000% overnight, and without any particular reason for that increase, nothing typically happens to the company. No fines, no court orders, just business as usual.

Martin Shkreli’s decades-old anti-parasitic drug Daraprim was the perfect example — massive price spike on an old drug, lots of media attention, public outcry, Congressional committees dragging his former company through multiple hearings, and at the end of it? Nothing happened to the price or the company (until generic competition came).

Marianne De Backer (L) and Jeff Hatfield

Bay­er nabs star biotech Vi­vid­ion with a $2B buy­out and an ‘arms-length’ pact, pulling a part­ner out of the IPO con­ga line

Vividion is canceling that IPO it filed. Instead of following the industry-wide migration to Nasdaq, the biotech that has captured considerable attention for its still-preclinical work finding cryptic pockets to bind to on proteins is going to work for Bayer now.

The pharma giant is putting out word today that it has bought out Vividion for $1.5 billion in cash and another half-billion dollars in milestones.

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Josh Hoffman, outgoing Zymergen CEO (Zymergen)

UP­DAT­ED: Syn­bio uni­corn Zymer­gen jet­ti­sons found­ing CEO, cuts guid­ance as cus­tomers re­port lead prod­uct does­n't work

Zymergen, just months off a $500 million IPO that put the synthetic bio firm in rarified air, has now ejected its founding CEO and downgraded its revenue forecasts after customers reported its lead film product doesn’t work as advertised, the company said Tuesday afternoon.

CEO Josh Hoffman will leave his role and sacrifice his board seat immediately in favor of Jay Flatley, the former CEO of Illumina who will take the lead role on an interim basis as the company conducts a search for its next leader.

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Tadataka Yamada (Photographer: Kiyoshi Ota/Bloomberg via Getty Images)

Sci­ence pi­o­neer, phar­ma re­search chief, glob­al health ad­vo­cate and biotech en­tre­pre­neur Tadata­ka ‘Tachi’ Ya­ma­da has died

Tadataka Yamada, a towering physician-scientist who made his name in academia before transforming drug development at GlaxoSmithKline and developing vaccines for malaria and meningitis at the Gates Foundation, died unexpectedly of natural causes at his home in Seattle Wednesday morning.

He was 76. Frazier Healthcare Partners’ David Socks confirmed his death.

Known widely by the mononym “Tachi,” Yamada had a globetrotting career and arrived in industry relatively late in life. A 2004 Independent article noted GSK had asked Yamada to stay on beyond his approaching 60th birthday, the company’s usual retirement age. Yamada would continue working for the next 17 years, steering the Gates Foundation’s global health division for 6 years, funding Jim Wilson’s gene therapy work when few would touch it, launching Takeda Vaccines and co-founding a series of high-profile biotechs.

Thomas Lingelbach, Valneva CEO

A small vac­cine de­vel­op­er fa­vored by the UK gov­ern­ment in Covid-19 touts a PhI­II first in chikun­gun­ya

Before Valneva garnered the favor of the UK government as a potential supplier of Covid-19 vaccines, the French biotech prided itself on being the first company to bring a chikungunya vaccine into Phase III.

It now has positive pivotal results to back up the breakthrough therapy designation the FDA granted just weeks ago.

There are currently no approved jabs to prevent chikungunya virus infection despite decades of R&D efforts, a fact that underscores just how arduous traditional vaccine development can be, particularly for neglected tropical disease. In a absence of a major commercial market, the US government and NGOs such as CEPI have deployed various grants and incentives to spur on a small crew of academics and industry players, with Merck, via its acquisition of Themis, claiming a spot in that race.

Zymergen co-founders Zach Serber, Josh Hoffman, and Jed Dean (Zymergen via website)

Zymer­gen's sud­den im­plo­sion shocked biotech. A lin­ger­ing loan could make things even worse

As former synbio unicorn Zymergen picks up the pieces from its spectacular implosion Tuesday, an outstanding loan from Perceptive Advisors — the only blue-chip biotech crossover investor to touch Zymergen’s fundraising efforts — could make the situation worse, according to public documents.

In December 2019, more than a year before Zymergen filed for what would eventually become a $500 million IPO, the “biofacturing” firm signed a $100 million credit facility with Perceptive to help supplement the nearly $700 million the company had raised across four VC rounds.

Lan Huang, BeyondSpring CEO

Shares of Be­yond­Spring sky­rock­et on new, pos­i­tive can­cer drug tri­al re­sults

Sometimes results come along that shock even a biotech’s believers.

On Wednesday, BeyondSpring, a small New York biotech with an offbeat approach to immunotherapy, announced its lead drug significantly extended non-small cell lung cancer patients’ lives in a large trial. Although the company did not release the exact survival data, it said that nearly twice as many patients were alive after two years on the drug arm than on the standard-of-care arm.

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Pfiz­er puts the pres­sure on Eli Lil­ly's JAK in­hibitor Olu­mi­ant with new da­ta in alope­cia area­ta

As Eli Lilly looks to secure a win for its blockbuster Olumiant in alopecia areata, going where no JAK inhibitor has gone before, Pfizer is coming up from behind with Phase IIb/III results suggesting its own candidate can help regrow hair lost due to the autoimmune disease.

On Wednesday, Pfizer unveiled topline results from the ALLEGRO trial, which enrolled 718 patients 12 years and older with alopecia areata, a condition that can cause sudden, severe and patchy hair loss. While the patients’ episodes of alopecia areata varied in length, they all had one thing in common: They had lost at least half the hair on their scalps.