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.

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

David Meek, new Mirati CEO (Marlene Awaad/Bloomberg via Getty Images)

Fresh off Fer­Gene's melt­down, David Meek takes over at Mi­rati with lead KRAS drug rac­ing to an ap­proval

In the insular world of biotech, a spectacular failure can sometimes stay on any executive’s record for a long time. But for David Meek, the man at the helm of FerGene’s recent implosion, two questionable exits made way for what could be an excellent rebound.

Meek, most recently FerGene’s CEO and a past head at Ipsen, has become CEO at Mirati Therapeutics, taking the reins from founding CEO Charles Baum, who will step over into the role of president and head of R&D, according to a release.

Jacob Van Naarden (Eli Lilly)

Ex­clu­sives: Eli Lil­ly out to crash the megablock­buster PD-(L)1 par­ty with 'dis­rup­tive' pric­ing; re­veals can­cer biotech buy­out

It’s taken 7 years, but Eli Lilly is promising to finally start hammering the small and affluent PD-(L)1 club with a “disruptive” pricing strategy for their checkpoint therapy allied with China’s Innovent.

Lilly in-licensed global rights to sintilimab a year ago, building on the China alliance they have with Innovent. That cost the pharma giant $200 million in cash upfront, which they plan to capitalize on now with a long-awaited plan to bust up the high-price market in lung cancer and other cancers that have created a market worth tens of billions of dollars.

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Volker Wagner (L) and Jeff Legos

As Bay­er, No­var­tis stack up their ra­dio­phar­ma­ceu­ti­cal da­ta at #ES­MO21, a key de­bate takes shape

Ten years ago, a small Norwegian biotech by the name of Algeta showed up at ESMO — then the European Multidisciplinary Cancer Conference 2011 — and declared that its Bayer-partnered targeted radionuclide therapy, radium-223 chloride, boosted the overall survival of castration-resistant prostate cancer patients with symptomatic bone metastases.

In a Phase III study dubbed ALSYMPCA, patients who were treated with radium-223 chloride lived a median of 14 months compared to 11.2 months. The FDA would stamp an approval on it based on those data two years later, after Bayer snapped up Algeta and christened the drug Xofigo.

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Mi­rati tri­umphs again in KRAS-mu­tat­ed lung can­cer with a close­ly watched FDA fil­ing now in the cards

After a busy weekend at #ESMO21, which included a big readout for its KRAS drug adagrasib in colon cancer, Mirati Therapeutics is ready to keep the pressure on competitor Amgen with lung cancer data that will undergird an upcoming filing.

In topline results from a Phase II cohort of its KRYSTAL-1 study, adagrasib posted a response rate of 43% in second-line-or-later patients with metastatic non-small cell lung cancer containing a KRAS-G12C mutation, Mirati said Monday.

Jay Bradner (Jeff Rumans for Endpoints News)

Div­ing deep­er in­to in­her­it­ed reti­nal dis­or­ders, No­var­tis gob­bles up an­oth­er bite-sized op­to­ge­net­ics biotech

Right about a year ago, a Novartis team led by Jay Bradner and Cynthia Grosskreutz at NIBR swooped in to scoop up a Cambridge, MA-based opthalmology gene therapy company called Vedere. Their focus was on a rather narrow market niche: inherited retinal dystrophies that include a wide range of genetic retinal disorders marked by the loss of photoreceptor cells and progressive vision loss.

But that was just the first deal that whet their appetite.

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FDA hands ac­cel­er­at­ed nod to Seagen, Gen­mab's so­lo ADC in cer­vi­cal can­cer, but com­bo stud­ies look even more promis­ing

Biopharma’s resident antibody-drug conjugate expert Seagen has scored a clutch of oncology approvals in recent years, finding gold in what are known as “third-gen” ADCs. Now, another of their partnered conjugates is ready for prime time.

The FDA on Monday handed an accelerated approval to Seagen and Genmab’s Tivdak (tisotumab vedotin-tftv, or “TV”) in second-line patients with recurrent or metastatic cervical cancer who previously progressed after chemotherapy rather than PD-(L)1 systemic therapy, the companies said in a release.

Mi­rati's KRAS drug looks like the ear­ly fa­vorite in colon can­cer with new da­ta, putting the pres­sure square on Am­gen

With Amgen already providing proof-of-concept for KRAS inhibitors with its sotorasib, Mirati Therapeutics is piecing together a follow-up effort in lung cancer with data it thinks are superior. But in colon cancer, where solo sotorasib has turned in a dud, Mirati may now have a strong case for superiority.

Mirati’s adagrasib, dosed solo or in combination with chemotherapy cetuximab, showed numerically higher response rates than sotorasib solo and as part of a combination study in a similar patient population also revealed this week at #ESMO21. Mirati’s data were presented as part of a cohort update from the Phase II KRYSTAL-1 study testing adagrasib in a range of solid tumors harboring the KRAS-G12C mutation.

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Ex­elix­is pulls a sur­prise win in thy­roid can­cer just days ahead of fi­nal Cabome­tyx read­out

Exelixis added a thyroid cancer indication to its super-seller Cabometyx’s label on Friday — months before the FDA was expected to make a decision, and days before the company was set to unveil the final data at #ESMO21.

At a median follow-up of 10.1 months, differentiated thyroid cancer patients treated with Cabometyx (cabozantinib) lived a median of 11 months without their disease worsening, compared to just 1.9 months for patients given a placebo, Exelixis said on Monday.