Anthony Marucci, Celldex CEO

Aim­ing to re­bound from blun­ders years ago, Celldex touts a Phase Ib win with sights set on Xo­lair

Fol­low­ing mul­ti­ple high-pro­file mis­steps sev­er­al years ago, the folks over at Celldex Ther­a­peu­tics be­gan chart­ing a path to re­demp­tion that would take on Roche and No­var­tis’ block­buster Xo­lair fran­chise. That path got a boost Fri­day with a da­ta read­out the com­pa­ny says po­si­tions it well against the phar­ma gi­ants.

Celldex re­port­ed re­sults from a Phase Ib study for their mon­o­clon­al an­ti­body CDX-0159 to treat two con­di­tions that cause se­vere and de­bil­i­tat­ing hives. The Hamp­ton, NJ-based biotech said that among 19 pa­tients who re­ceived a full dose of the an­ti­body, 18 achieved a com­plete re­sponse and the 19th saw a par­tial re­sponse.

That stands in stark con­trast to some of the re­sponse rates Celldex says pa­tients see on Xo­lair, which fall around the 40% to 50% range. Those with such con­di­tions al­so need to take mul­ti­ple dos­es of Xo­lair, while Celldex’s da­ta come from pa­tients tak­ing on­ly one dose of CDX-0159, CEO An­tho­ny Maruc­ci em­pha­sized.

“We’ve been an­ti­body de­vel­op­ers for a long time, both in on­col­o­gy and non-on­col­o­gy as­sets,” Maruc­ci told End­points News. “Look­ing at this tar­get and where we be­lieved it worked, nat­u­ral­ly the sci­ence took us to in­flam­ma­tion. That’s not to say we’ve aban­doned on­col­o­gy … but this tar­get and the way we de­signed the mol­e­cule, to re­duce in­fu­sion re­ac­tions and im­prove its half life, the da­ta in our minds [are] spec­tac­u­lar even in the ear­ly stages.”

In the wake of the an­nounce­ment, Celldex $CLDX shares were up 45% ahead of the bell Mon­day morn­ing.

The dis­eases in ques­tion are two forms of chron­ic in­ducible ur­ticaria. The first, called symp­to­matic der­mo­graphism, makes up more than half of cas­es. Pa­tients can de­vel­op se­vere hives in re­sponse to lit­tle stim­u­la­tion on the skin, such as putting on socks. The sec­ond con­di­tion, known as “cold ur­ticaria,” makes up 16% of cas­es and caus­es hives out­breaks when skin is ex­posed be­low cer­tain tem­per­a­tures.

With­in the Phase Ib study, nine of the 19 pa­tients had symp­to­matic der­mo­graphism while the oth­er 10 suf­fered from cold ur­ticaria. Eight of the nine SD pa­tients achieved com­plete re­sponse, in­clud­ing three who had pre­vi­ous­ly been treat­ed with Xo­lair, and all 10 with ColdU met their com­plete re­sponse.

On top of the re­sponse rates, Celldex said the treat­ments proved high­ly durable. The SD pa­tients main­tained their re­spons­es at a me­di­an of 57 days, and those with ColdU main­tained the dis­ease state for a me­di­an of 77 days.

CDX-0159 works by tar­get­ing mast cells by bind­ing the re­cep­tor ty­ro­sine ki­nase KIT. Mast cells me­di­ate in­flam­ma­to­ry re­spons­es in the body and KIT sig­nal­ing con­trols mast cell dif­fer­en­ti­a­tion. As such, Celldex’s the­o­ry in­volves tamp­ing down on KIT in or­der to de­plete the mast cells in the skin.

Celldex is con­tin­u­ing to study the drug in oth­er forms of ur­ticarias, in­clud­ing hives trig­gered by sweat­ing in warm tem­per­a­tures or from ex­er­cise, as well as ur­ticarias that re­sult in spon­ta­neous hive out­breaks. Both of these datasets in the on­go­ing Phase Ib tri­al are ex­pect­ed in the first half of 2022.

Should every­thing turn out hunky do­ry, the pro­gram would mark a sharp turn­around for a biotech that culled mul­ti­ple late-stage as­sets from its pipeline af­ter Phase III fail­ures. In 2016, a can­cer vac­cine pro­gram flopped a glioblas­toma study, and 2018 brought a Phase IIb dis­as­ter in breast can­cer — a miss that re­sult­ed in Celldex lay­ing off about 40% of its work­force.

But now Celldex is en­gag­ing in a full court press to get CDX-0159 to pa­tients, and Maruc­ci hopes the com­pa­ny can ex­pand the pro­gram in­to oth­er dis­eases where mast cells are im­pli­cat­ed. Celldex isn’t say­ing much yet, but re­searchers are look­ing at oth­er in­di­ca­tions in the res­pi­ra­to­ry, al­ler­gic, oph­thalmic and GI ar­eas.

Tak­ing a bite out of the Xo­lair pie is prov­ing to be an op­por­tu­ni­ty Celldex sim­ply can’t pass up, Maruc­ci said. Xo­lair net­ted about $3.3 bil­lion in sales be­tween Roche and No­var­tis in 2020 and con­tin­ued to see growth in 2021’s first quar­ter, and an­a­lysts es­ti­mate that about $1.5 bil­lion of that to­tal comes from the spon­ta­neous form of the dis­ease.

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).

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.

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.

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.