New biotech Exalys, seek­ing to pre­vent post­op­er­a­tive delir­i­um, launch­es with $15 mil­lion in Se­ries A

An old group of for­mer col­leagues will be re­unit­ing to lead a new biotech ven­ture aimed at cul­ti­vat­ing a port­fo­lio to treat neu­roin­flam­ma­to­ry dis­or­ders.

Led by Rick Orr, who ran the biotech Ad­ynxx, the group is launch­ing the start­up Exalys on Thurs­day with $15 mil­lion in Se­ries A fund­ing from ven­ture firms Catalys Pa­cif­ic and Do­main As­so­ci­ates. The nascent com­pa­ny’s first project will fo­cus on pre­vent­ing post­op­er­a­tive delir­i­um, li­cens­ing a plat­form of EP4 re­cep­tors from Japan­ese phar­ma Ei­sai.

“We’re work­ing with a team that has done this mul­ti­ple times, par­tic­u­lar­ly with as­sets that were sourced out of Japan,” Orr told End­points News. “All the pieces are in place — you’ve got the tech­nol­o­gy and you’ve got the team.”

In ad­di­tion to Orr, who will serve as pres­i­dent and CEO, Exalys’ board will be head­ed by Den­nis Podle­sak and joined by Eckard We­ber. The three have pre­vi­ous­ly col­lab­o­rat­ed with Do­main on Penin­su­la Phar­ma­ceu­ti­cals, Cerexa, Cal­ixa and Corthera.

EP4s es­sen­tial­ly dri­ve the im­mune sys­tem’s re­sponse com­ing out of surgery, Orr said. Im­mune cells re­lease cy­tokines that dis­rupt the brain bar­ri­er in surgery, which can lead to post­op­er­a­tive delir­i­um af­ter­wards. EP4 is piv­otal in the se­cre­tion of those cy­tokines, and block­ing the im­mune re­sponse dur­ing sur­gi­cal pro­ce­dures can pre­vent pa­tients from con­tract­ing the con­di­tion.

There is noth­ing on the mar­ket that can cur­rent­ly pre­vent post­op­er­a­tive delir­i­um, and though there are lim­it­ed med­i­cines that can treat the con­di­tion, few are both safe and ef­fec­tive, Orr said. By re­search­ing and ul­ti­mate­ly de­vel­op­ing EP4 an­tag­o­nists, Exalys hopes this ini­tial tar­get in­di­ca­tion can pro­vide a foun­da­tion for the com­pa­ny mov­ing for­ward.

“It’s not the on­ly re­sponse,” Orr said of post­op­er­a­tive delir­i­um, “but cer­tain­ly there are oth­er neu­roin­flam­ma­to­ry dis­eases that can be tar­get­ed through EP4 an­tag­o­nists. So we’re start­ing with post­op­er­a­tive delir­i­um giv­en that it’s such an un­met med­ical need, but with the port­fo­lio we cur­rent­ly have we’ll be look­ing to ad­dress oth­er neu­roin­flam­ma­to­ry dis­or­ders.”

Orr en­vi­sions an even­tu­al pro­ce­dure look­ing some­thing like this: A pa­tient at high risk for post­op­er­a­tive delir­i­um — gen­er­al­ly in­di­vid­u­als old­er than 65 — is prepped for surgery and is ad­min­is­tered anes­the­sia. In ad­di­tion to the typ­i­cal pre-op drugs, the pa­tient is al­so giv­en the hy­po­thet­i­cal Exalys drug, pre­emp­tive­ly in­hibit­ing the body’s EP4 re­sponse. Dur­ing the surgery, the EP4 an­tag­o­nists do their work, and once the surgery has end­ed, the at-risk in­di­vid­u­als will be safe from the dis­or­der.

Not on­ly would such can­di­dates di­min­ish neg­a­tive im­pacts on the pa­tients, but they al­so have the po­ten­tial to ease the bur­den on the health­care sys­tem. Those who suf­fer from post­op­er­a­tive delir­i­um of­ten re­quire ex­tend­ed hos­pi­tal stays, adding up to an es­ti­mat­ed $150 bil­lion in costs per year, Orr said.

“It’s pret­ty marked in the im­pact it has on the pa­tient as well as the fam­i­ly,” Orr said. “Tru­ly the pa­tient al­most be­comes un­rec­og­niz­able, just in terms of change in be­hav­ior and change in cog­ni­tion. That does lead to pro­longed hos­pi­tal­iza­tions, but there are oth­er as­pects that, prob­a­bly from the pa­tient’s per­spec­tive, are even more dra­mat­ic than just the longer time in the hos­pi­tal.”

Those al­ready suf­fer­ing from oth­er neu­ro­log­i­cal dis­eases, such as Alzheimer’s or de­men­tia, may have their con­di­tions ex­ac­er­bat­ed by post­op­er­a­tive delir­i­um, Orr added.

The cur­rent plan, Orr said, is to start clin­i­cal de­vel­op­ment us­ing the Se­ries A fund­ing, and if every­thing stays on track, Exalys will ap­ply for an IND for the post­op­er­a­tive delir­i­um can­di­date in the sec­ond half of 2021. Exalys is look­ing at two oth­er EP4 an­tag­o­nist can­di­dates, but those are far­ther down the road.

What oth­er po­ten­tial can­di­dates end up treat­ing, Orr doesn’t know yet, but the biotech will con­tin­ue fo­cus­ing on neu­roin­flam­ma­tion. Exalys doesn’t aim to start with a prob­lem it wants to fix and work to­ward that, but rather con­tin­ue test­ing the EP4 an­tag­o­nists and go in the di­rec­tion of the most promis­ing da­ta.

It’s part of the com­pa­ny’s phi­los­o­phy of “fol­low­ing where the sci­ence leads you,” Orr said.

Cell and Gene Con­tract Man­u­fac­tur­ers Must Em­brace Dig­i­ti­za­tion

The Cell and Gene Industry is growing at a staggering 30% CAGR and is estimated to reach $14B by 20251. A number of cell, gene and stem cell therapy sponsors currently have novel drug substances and products and many rely on Contract Development Manufacturing Organizations (CDMO) to produce them with adherence to stringent regulatory cGMP conditions. Cell and gene manufacturing for both autologous (one to one) and allogenic (one to many) treatments face difficult issues such as: a complex supply chain, variability on patient and cellular level, cell expansion count and a tight scheduling of lot disposition process. This complexity affects quality, compliance and accountability in the entire vein-to-vein process for critically ill patients.

Phase III read­outs spell dis­as­ter for Genen­tech’s lead IBD drug

Roche had big plans for etrolizumab. Eyeing a hyper-competitive IBD and Crohn’s market where they have not historically been a player, the company rolled out 8 different Phase III trials, testing the antibody for two different uses across a range of different patient groups.

On Monday, Roche released results for 4 of those studies, and they mark a decided setback for both the Swiss pharma and their biotech sub Genentech, potentially spelling an end to a drug they put over half-a-decade and millions of dollars behind.

Vi­da Ven­tures co-leads Dyne's $115M megaround for next-gen oli­go ther­a­pies aimed square­ly at mus­cles

Dyne Therapeutics started out last April with a modest $50 million to mine targeted muscle disease therapies from its in-house conjugate technology. The biotech has now convinced more investors that it’s got gems on its hands, closing $115 million in fresh financing to push its next-gen oligonucleotide drugs into the clinic.

Vida Ventures and Surveyor Capital led the round, joined by a group of other new backers including Wellington Management Company, Logos Capital and Franklin Templeton.

DFC CEO Adam Boehler and Kodak CEO Jim Continenza (Kodak)

Covid-19 roundup: Cure­Vac beefs up its uni­corn IPO dreams as bil­lion­aire own­er takes this Covid-19 mR­NA play­er on a forced march to Nas­daq; Ko­dak's $765M deal is put on hold

When CureVac initially jotted down $100 million for its IPO raise a couple of weeks ago, it seemed small. The German mRNA player, after all, had jumped into a Covid-19 race that swelled the sails of Moderna and BioNTech by tens of billions. And after raising $640 million in a slate of deals, $100 million in a hot market like this seemed like a pittance in the bigger scheme of things.

Today, we got a look at a figure that probably comes closer to the game-changing number the top execs probably have in mind. Selling 15.3 million shares at the high end of their $14 to $16 range would net a $243 million bounty. Majority owner Dietmar Hopp is putting in another €100 million, bringing the total to around $350 million. And what are the chances they want to do even better than that?

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Eric Shaff (Seres)

UP­DAT­ED: Af­ter a 4-year so­journ, strug­gling mi­cro­bio­me pi­o­neer Seres claims a break­out PhI­II come­back. And shares re­spond in fren­zied spike

Almost exactly 4 years ago, Seres Therapeutics $MCRB experienced one of those soul-crunching failures that can raise big questions about a biotech’s future. Out front in their pursuit of a gut punch to C. difficile infection (CDI), the Phase II test was a flat failure, and investors wiped out a billion dollars of equity value that never returned in the years that followed.

Seres, though, pressed ahead, changing out CEOs a year ago — bidding Merck vet Roger Pomerantz farewell from the C suite — and pushing through a Phase III, hoping that amping up the dosage would make the key difference. And this morning, they unveiled a claim that they had aced the Phase III and positioned themselves for a run at a landmark FDA OK.

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Michel Vounatsos, Biogen CEO (via YouTube)

UP­DAT­ED: Bio­gen scores a pri­or­i­ty re­view for its Alzheimer's drug ad­u­canum­ab, mov­ing one gi­ant leap for­ward in its con­tro­ver­sial quest

Biogen scored a big win at the FDA today as regulators accepted their application for the controversial Alzheimer’s drug aducanumab and gave it a priority review.

The PDUFA date is March 7, 2021.

Significantly, Biogen says it did not use its priority review voucher to win special treatment at the FDA. The agency handed that out gratis.

That’s the ideal scenario Biogen was looking for as disappointed analysts wondered aloud about the delayed application earlier in the year.

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Eli Lil­ly teams with Pieris on HER2+ tu­mors; Op­di­vo + Yer­voy best chemo in mesothe­lioma

Despite the FDA putting a partial clinical hold on its lead program only a few weeks ago, Boston-based Pieris Pharmaceuticals is plowing forward with a new collaboration.

Pieris will work with Eli Lilly to further advance studies on PRS-343, a 4-1BB/HER2 bispecific for HER2-positive tumors, in combination with the latter’s ramucirumab and paclitaxel for the second-line treatment of patients with HER2-positive gastric cancer in a single-arm, Phase II study.

In­novent and Eli Lil­ly chal­lenge Mer­ck­'s mega-block­buster Keytru­da in non-small cell lung can­cer field

China-based Innovent Biologics and its multinational ally Eli Lilly shared Phase III evidence that their PD-1 inhibitor combo can delay the progression of nonsquamous non-small cell lung cancer.

But the drugmakers will face stiff competition in China from Merck’s Keytruda, the ruling PD-1 which is already approved to treat both squamous and nonsquamous NSCLC and boasts positive overall survival rates.

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Anap­tys­Bio's etokimab pro­vides more dis­ap­point­ing re­sults, rais­ing ques­tions about com­pound's fu­ture

The lead program for AnaptysBio’s in-house pipeline has hit another setback.

Etokimab, an IL-33 inhibitor, did not achieve statistically significant improvement in a Phase II trial for patients suffering from chronic rhinosinusitis with nasal polyps. Researchers measured the individuals’ bilateral nasal polyps score and sino-nasal outcome test, finding that neither improved upon a placebo after both four- and eight-week time markers, though they did demonstrate improvement over baseline levels of the examinations.