Take­da tees up $420M deal for celi­ac an­ti­dote, con­tin­u­ing R&D re­fo­cus

Some­time in the 1st cen­tu­ry AD, a pa­tient pre­sent­ed to Arataeus look­ing like a vari­cose ghost. He was “ema­ci­at­ed and at­ro­phied, pale, fee­ble and in­ca­pable of per­form­ing any of his ac­cus­tomed works,” the Greek physi­cian wrote, with hol­low tem­ples and huge veins run­ning all over his body.

A dys­func­tion­al di­ges­tive sys­tem, Arataeus con­clud­ed – an im­bal­ance he at­trib­uted to a “heat” de­fi­cien­cy in a sys­tem he and oth­er Greeks re­gard­ed as func­tion­ing sim­i­lar­ly to an oven – and coined a term: coeli­ac dis­ease, af­ter the Greek word for ab­domen.

Arataeus pre­scribed rest and fast­ing – to re­store the heat – and for 2,000 years lit­tle changed for the au­toim­mune dis­ease. Samuel Gee, the 19th-cen­tu­ry physi­cian who re­vived sci­en­tif­ic study of the con­di­tion, fig­ured di­et was the an­swer; he just didn’t know which one. A ba­nana-based di­et, said one doc­tor in 1924, and that caught on for decades. On­ly in the lat­ter half of the cen­tu­ry was celi­ac’s au­toim­mune na­ture un­cov­ered and with it the pre­scrip­tion for most pa­tients: Stay away from gluten, the chem­i­cal be­hind bread’s chewi­ness.

But re­searchers didn’t stop look­ing for some­thing that could bet­ter as­suage and pre­vent the dys­func­tion that all but killed Arataeus’s pa­tient ze­ro. And now Take­da thinks they have a can­di­date. Im­pressed with a part­ner’s new Phase IIa da­ta, the phar­ma gi­ant is putting near­ly half a bil­lion be­hind the idea.

Take­da will li­cense CNP-101/TAK-101 from COUR Phar­ma­ceu­ti­cals for $420 mil­lion in mile­stones, plus roy­al­ties. Take­da ex­er­cised their op­tion from a 2015 deal on the same day COUR un­veiled Phase IIa da­ta show­ing celi­ac pa­tients re­ceiv­ing the drug saw an in­di­ca­tor for au­toim­mune re­sponse fall dra­mat­i­cal­ly.

John Pui­sis

“It’s tough to al­ways say cure but, you know, dis­ease-mod­i­fy­ing,” COUR CEO John Pui­sis told End­points News. “I can’t make the [cure] claim from a reg­u­la­to­ry stand­point but I think there’s some­thing re­al­ly here.”

Pui­sis has grand plans for his com­pa­ny’s nanopar­ti­cle plat­form and views to­day’s re­sults as con­fir­ma­tion for a tech­nol­o­gy he hopes to bring to oth­er au­toim­mune dis­or­ders. For Take­da, the re­sults are an im­por­tant win as the com­pa­ny con­tin­ues to stream­line R&D in the wake of the Shire deal, fo­cus­ing on key ar­eas such as gas­troen­terol­o­gy.

The Japan­ese gi­ant will be en­ter­ing a crowd­ed space, as just in the past three months mul­ti­ple large play­ers have signed deals to ad­dress celi­ac’s root caus­es. Most no­tably in Sep­tem­ber, Anokion bought out Kanyos Bio and its anti­gen-spe­cif­ic treat­ment, while Glax­o­SmithK­line pur­chased a biotech with a dif­fer­ent ap­proach.

Es­sen­tial­ly, COUR used their nanopar­ti­cle plat­form to trick the body in­to be­liev­ing that gliadin, the gluten com­po­nent that trig­gers the au­toim­mune re­sponse, is a nat­ur­al bod­i­ly anti­gen: friend, not foe. They en­cased gliadin in a biodegrad­able poly­mer small­er than a mi­cron and sent it whirling Al­ice in Won­der­land style through the body – ush­ered by mono­cyte “sen­tinels” down in­to the spleen and liv­ers, where anti­gen-pre­sent­ing T cells en­cod­ed it as non-harm­ful.

“Some­where along the line — whether it’s ge­net­ics or virus or a com­bi­na­tion – the im­mune sys­tem went hay­wire and start­ed at­tack­ing these peo­ple’s small in­tes­tine when they di­gest­ed gluten,” Pui­sis said. “And what we had to do is re­pro­gram that.”

COUR gave two small groups CNP-101 or a con­trol on days 1 and 8 and then ad­min­is­tered gluten for two weeks days. Six days af­ter the gluten dos­es, COUR test­ed pa­tients for in­ter­fer­on-gam­ma spot form­ing units – a bio­mark­er mea­sur­ing the au­toim­mune re­sponse – and found 17.57 in the con­trol group and 2.10 in the treat­ment group. A sec­ondary end­point mea­sur­ing the anatom­i­cal au­toim­mune re­sponse, duo­de­nal vil­lus height to crypt depth ra­tio, al­so showed “ex­pect­ed, sig­nif­i­cant re­duc­tion.”

Pui­sis told End­points they al­so asked pa­tients about symp­toms, but the sur­vey da­ta were not an­nounced.

Af­ter 6 dropouts for gluten-re­lat­ed symp­toms, there were 28 pa­tients in to­tal.

Pui­sis, who ear­ly on re­ject­ed in­vestor pres­sure to fo­cus the com­pa­ny on one in­di­ca­tion, spoke of the re­sults with lofti­er am­bi­tion than treat­ing one dis­ease. He and the pro­mo­tion­al ma­te­ri­als tout­ed the Phase IIa as the first tri­al to “demon­strate in­duc­tion of anti­gen-spe­cif­ic im­mune tol­er­ance in any au­toim­mune dis­ease.” In oth­er words, the first case of a com­pa­ny con­vinc­ing the au­toim­mune pa­tient’s body not to at­tack it­self, at least us­ing this method.

The main non-di­et treat­ment for celi­ac is im­mune sup­pres­sants that can have sig­nif­i­cant side ef­fects, and more broad­ly the man­age­ment for au­toim­mune dis­eases has been whole-body ap­proach­es that treat symp­toms with­out ad­dress­ing the root cause, such as in­sulin for di­a­betes. But faced with di­min­ish­ing re­turns on those ther­a­pies, re­searchers have re­cent­ly turned to­ward ways of snub­bing out or pre­vent­ing the un­der­ly­ing is­sue.

Last year, for in­stance, Vi­en­na Uni­ver­si­ty of Tech­nol­o­gy re­searchers dis­played an an­ti­body tech­nol­o­gy that would latch on­to and neu­tral­ize in­com­ing gliadin anti­gens.

“The prob­lem is that clas­si­cal im­mune in­ter­ven­tion has re­lied al­most ex­clu­sive­ly on broad act­ing agents, which, al­though they have shown ther­a­peu­tic ben­e­fits, are not spe­cif­ic for the dis­ease and of­ten in­crease the risk of in­fec­tions and ma­lig­nan­cies,” No­var­tis’s José Car­balli­do and Parvus Ther­a­peu­tics’ Pere San­ta­maria wrote in an is­sue of the Jour­nal of Ex­per­i­men­tal Med­i­cine in Jan­u­ary, be­fore run­ning through some new de­vel­op­ments, in­clud­ing elim­i­nat­ing ma­ture hematopoi­et­ic cells to start a com­plete im­mune re­set. “A far less ag­gres­sive and more amenable choice to pro­mote im­mune tol­er­ance in­volves tar­get­ing the ex­ist­ing pe­riph­er­al ef­fec­tor and/or mem­o­ry au­tore­ac­tive T cell com­part­ments us­ing anti­gen-based ap­proach­es.”

Take­da will next ini­ti­ate a dose-rang­ing study, while COUR looks to de­vel­op their mul­ti­ple scle­ro­sis and peanut al­ler­gy drugs. Pui­sis said they be­gan with celi­ac be­cause the dis­ease it­self was rel­a­tive­ly well-un­der­stood – but that’s all the more rea­sons why the next ap­pli­ca­tions may be that much hard­er to pro­duce.

Fangliang Zhang, AP Images

UP­DAT­ED: Leg­end fetch­es $424 mil­lion, emerges as biggest win­ner yet in pan­dem­ic IPO boom as shares soar

Amid a flurry of splashy pandemic IPOs, a J&J-partnered Chinese biotech has emerged with one of the largest public raises in biotech history.

Legend Biotech, the Nanjing-based CAR-T developer, has raised $424 million on NASDAQ. The biotech had originally filed for a still-hefty $350 million, based on a range of $18-$20, but managed to fetch $23 per share, allowing them to well-eclipse the massive raises from companies like Allogene, Juno, Galapagos, though they’ll still fall a few dollars short of Moderna’s record-setting $600 million raise from 2018.

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As it hap­pened: A bid­ding war for an an­tibi­ot­ic mak­er in a mar­ket that has rav­aged its peers

In a bewildering twist to the long-suffering market for antibiotics — there has actually been a bidding war for an antibiotic company: Tetraphase.

It all started back in March, when the maker of Xerava (an FDA approved therapy for complicated intra-abdominal infections) said it had received an offer from AcelRx for an all-stock deal valued at $14.4 million.

The offer was well-timed. Xerava was approved in 2018, four years after Tetraphase posted its first batch of pivotal trial data, and sales were nowhere near where they needed to be in order for the company to keep its head above water.

José Basel­ga finds promise in new class of RNA-mod­i­fy­ing can­cer tar­gets, lock­ing in 3 pre­clin­i­cal pro­grams with $55M

Having dived early into some of the RNA breakthroughs of the last decades — betting on Moderna’s mRNA tech and teaming up with Silence on the siRNA front — AstraZeneca is jumping into a new arena: going after proteins that modify RNA.

Their partner of choice is Accent Therapeutics, which is receiving $55 million in upfront payment to steer a selected preclinical program through to the end of Phase I. After AstraZeneca takes over, the Lexington, MA-based startup has the option to co-develop and co-commercialize in the US — and collect up to $1.1 billion in milestones in the long run. The deal also covers two other potential drug candidates.

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Por­tion of Neil Wood­ford’s re­main­ing in­vest­ments, in­clud­ing Nanopore, sold off for $284 mil­lion

It’s been precisely one year and one day since Neil Woodford froze his once-vaunted fund, and while a global pandemic has recently shielded him from the torrent of headlines, the fallout continues.

Today, the California-based patent licensing firm Acacia Research acquired the fund’s shares for 19 healthcare and biotech companies for $284 million.  Those companies include shares for public and private companies and count some of Woodford’s most prominent bio-bets, such as Theravance Biopharma, Oxford Nanopore and Mereo Biopharma, according to Sky News, which first reported the sale. It won’t include shares for BenevelontAI, the machine learning biotech once valued at $2 billion.

Drug man­u­fac­tur­ing gi­ant Lon­za taps Roche/phar­ma ‘rein­ven­tion’ vet as its new CEO

Lonza chairman Albert Baehny took his time headhunting a new CEO for the company, making it absolutely clear he wanted a Big Pharma or biotech CEO with a good long track record in the business for the top spot. In the end, he went with the gold standard, turning to Roche’s ranks to recruit Pierre-Alain Ruffieux for the job.

Ruffieux, a member of the pharma leadership team at Roche, spent close to 5 years at the company. But like a small army of manufacturing execs, he gained much of his experience at the other Big Pharma in Basel, remaining at Novartis for 12 years before expanding his horizons.

Covid-19 roundup: Ab­b­Vie jumps in­to Covid-19 an­ti­body hunt; As­traZeneca shoots for 2B dos­es of Ox­ford vac­cine — with $750M from CEPI, Gavi

Another Big Pharma is entering the Covid-19 antibody hunt.

AbbVie has announced a collaboration with the Netherlands’ Utrecht University and Erasmus Medical Center and the Chinese-Dutch biotech Harbour Biomed to develop a neutralizing antibody that can treat Covid-19. The antibody, called 47D11, was discovered by AbbVie’s three partners, and AbbVie will support early preclinical work, while preparing for later preclinical and clinical development. Researchers described the antibody in Nature Communications last month.

President Donald Trump (left) and Moncef Slaoui, head of Operation Warp Speed (Alex Brandon, AP Images)

UP­DAT­ED: White House names fi­nal­ists for Op­er­a­tion Warp Speed — with 5 ex­pect­ed names and one no­table omis­sion

A month after word first broke of the Trump Administration’s plan to rapidly accelerate the development and production of a Covid-19 vaccine, the White House has selected the five vaccine candidates they consider most likely to succeed, The New York Times reported.

Most of the names in the plan, known as Operation Warp Speed, will come as little surprise to those who have watched the last four months of vaccine developments: Moderna, which was the first vaccine to reach humans and is now the furthest along of any US effort; J&J, which has not gone into trials but received around $500 million in funding from BARDA earlier this year; the joint AstraZeneca-Oxford venture which was granted $1.2 billion from BARDA two weeks ago; Pfizer, which has been working with the mRNA biotech BioNTech; and Merck, which just entered the race and expects to put their two vaccine candidates into humans later this year.

Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

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Pfiz­er’s Doug Gior­dano has $500M — and some ad­vice — to of­fer a cer­tain breed of 'break­through' biotech

So let’s say you’re running a cutting-edge, clinical-stage biotech, probably public, but not necessarily so, which could see some big advantages teaming up with some marquee researchers, picking up say $50 million to $75 million dollars in a non-threatening minority equity investment that could take you to the next level.

Doug Giordano might have some thoughts on how that could work out.

The SVP of business development at the pharma giant has helped forge a new fund called the Pfizer Breakthrough Growth Initiative. And he has $500 million of Pfizer’s money to put behind 7 to 10 — or so — biotech stocks that fit that general description.

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