Prothena care­ful­ly ex­plains why it's killing a pso­ri­a­sis drug af­ter PhIb

Sarah Noon­berg

Prothena is cut­ting its loss­es on one of its key drug de­vel­op­ment pro­grams af­ter con­clud­ing their ther­a­py failed to pass muster in a Phase Ib study of pso­ri­a­sis.

PRX003 hit its mark — CD146 — on Th17 cells, as they ex­pect­ed. But re­searchers didn’t see the kind of phar­ma­co­dy­nam­ic ef­fect they were look­ing for. So there will be no Phase II to come in ei­ther pso­ri­a­sis or atopic der­mati­tis, two ail­ments which have seen con­sid­er­able progress re­cent­ly from new­ly ap­proved ther­a­pies.

To their cred­it, ex­ecs at Dublin-based Prothena $PR­TA were un­sen­ti­men­tal in their eval­u­a­tion of the re­sults. And for a small study with 33 pa­tients di­vid­ed be­tween a va­ri­ety of dos­es and a place­bo arm, Prothena gath­ered con­sid­er­able knowl­edge from the study.

The biotech’s stock dipped 6% on the news in af­ter-mar­ket trad­ing.

This seg­ment is worth read­ing:

Across all PRX003 dose lev­els in the Phase 1b MAD study, no clin­i­cal­ly rel­e­vant or sta­tis­ti­cal­ly sig­nif­i­cant ben­e­fit on PASI 75 re­sponse was ob­served. At week 12, 29 per­cent of PRX003-treat­ed pa­tients (2 out of 7) in the 1 mg/kg dose co­hort achieved a PASI 75 re­sponse  (p=0.2 rel­a­tive to place­bo), and no pa­tients in the 3 mg/kg, 10 mg/kg or 30 mg/kg dose co­horts achieved a PASI 75 re­sponse. Eval­u­a­tion of Th17 cell mi­gra­tion re­vealed in­suf­fi­cient de­creas­es in Th17 cell in­fil­tra­tion in­to tis­sue. Ad­di­tion­al­ly, as mea­sured from skin biop­sies there were no clin­i­cal­ly mean­ing­ful or dose-de­pen­dent changes in RNA tran­script lev­els of genes as­so­ci­at­ed with Th17-me­di­at­ed in­flam­ma­tion, in­clud­ing IL-17A, IL-17F, IL-6, TN­Fα, and IFNγ. De­spite mod­est ev­i­dence of a clin­i­cal ef­fect on PASI 75 re­sponse at the low­est dose lev­el, there was no re­la­tion­ship be­tween dose lev­els, RNA tran­script lev­els or oth­er mark­ers of in­flam­ma­to­ry ac­tiv­i­ty that pro­vid­ed ev­i­dence of a mean­ing­ful ther­a­peu­tic ef­fect. Col­lec­tive­ly, these da­ta demon­strat­ed that near-com­plete down­reg­u­la­tion of CD146 is in­suf­fi­cient to in­hib­it Th17 cell in­fil­tra­tion and as­so­ci­at­ed in­flam­ma­tion to the de­gree nec­es­sary to achieve mean­ing­ful clin­i­cal ben­e­fit in pa­tients with pso­ri­a­sis.

CEO Gene Kin­ney says the fo­cus now is on NEOD001 (Phase IIb and Phase III), PRX002 (Phase I) and PRX004 (ex­pect­ed to en­ter Phase I by mid-2018).

CEO Gene Kin­ney

“While we ob­served oc­cu­pan­cy and down­reg­u­la­tion of CD146 fol­low­ing ad­min­is­tra­tion of PRX003 con­sis­tent with our pre­vi­ous Phase 1a SAD study, the clin­i­cal re­sults in this study did not meet our pre-spec­i­fied cri­te­ria for ev­i­dence of a well-de­fined re­la­tion­ship be­tween bi­o­log­i­cal ac­tiv­i­ty and mean­ing­ful clin­i­cal ef­fects re­quired to ad­vance PRX003 in­to mid-stage clin­i­cal de­vel­op­ment for pso­ri­a­sis or pso­ri­at­ic arthri­tis as pre­vi­ous­ly planned,” said Sarah Noon­berg, chief med­ical of­fi­cer of Prothena. “More­over, these re­sults in­di­cate the need for a deep­er un­der­stand­ing of CD146 mod­u­la­tion in the treat­ment of com­plex dis­ease states. We want to thank the pa­tients, clin­i­cians and site co­or­di­na­tors who have helped us ex­e­cute this thor­ough study.”

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.

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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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.

Leen Kawas, Athira CEO (Athira)

Can a small biotech suc­cess­ful­ly tack­le an Ever­est climb like Alzheimer’s? Athi­ra has $85M and some in­flu­en­tial back­ers ready to give it a shot

There haven’t been a lot of big venture rounds for biotech companies looking to run a Phase II study in Alzheimer’s.

The field has been a disaster over the past decade. Amyloid didn’t pan out as a target — going down in a litany of Phase III failures — and is now making its last stand at Biogen. Tau is a comer, but when you look around and all you see is destruction, the idea of backing a startup trying to find complex cocktails to swing the course of this devilishly complicated memory-wasting disease would daunt the pluckiest investors.

GSK presents case to ex­pand use of its lu­pus drug in pa­tients with kid­ney dis­ease, but the field is evolv­ing. How long will the mo­nop­oly last?

In 2011, GlaxoSmithKline’s Benlysta became the first biologic to win approval for lupus patients. Nine years on, the British drugmaker has unveiled detailed positive results from a study testing the drug in lupus patients with associated kidney disease — a post-marketing requirement from the initial FDA approval.

Lupus is a drug developer’s nightmare. In the last six decades, there has been just one FDA approval (Benlysta), with the field resembling a graveyard in recent years with a string of failures including UCB and Biogen’s late-stage flop, as well as defeats in Xencor and Sanofi’s programs. One of the main reasons the success has eluded researchers is because lupus, akin to cancer, is not just one disease — it really is a disease of many diseases, noted Al Roy, executive director of Lupus Clinical Investigators Network, an initiative of New York-based Lupus Research Alliance that claims it is the world’s leading private funder of lupus research, in an interview.

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.

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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