Two years af­ter a wrench­ing set­back, Pro­tag­o­nist touts a slice of da­ta and sets sights on piv­otal tri­al in a sur­pris­ing place: the blood

In 2018, the floor fell out be­neath Pro­tag­o­nist Ther­a­peu­tics. Months ahead of an ex­pect­ed read­out, the com­pa­ny’s first ma­jor tri­al, a Phase IIb test­ing their lead drug in ul­cer­a­tive col­i­tis,  failed a fu­til­i­ty analy­sis. In­vestors sold off en masse. Pro­tag­o­nist searched for an­swers.

Two years lat­er, CEO Di­nesh Pa­tel main­tains the drug had ef­fi­ca­cy – point­ing to a blind­ed re-read con­duct­ed lat­er that year – but the com­pa­ny has moved on. Now, armed with the re­sults from a small proof-of-con­cept, they are ready­ing to put their re­sources be­hind a new lead pro­gram and an­oth­er at­tempt at a piv­otal tri­al in an en­tire­ly dif­fer­ent dis­ease.

Di­nesh Pa­tel

”We couldn’t have asked for bet­ter da­ta,” Pa­tel told End­points News. 

The drug is an ar­ti­fi­cial pro­tein called PTG–300. Un­like the drug in the 2018 tri­al or a com­pound li­censed in 2017 to J&J, PTG-300 is de­signed to treat blood dis­or­ders. Since Au­gust, the com­pa­ny has been test­ing it in a se­ries of tiny proof-of-con­cept tri­als to see how well it works in dif­fer­ent dis­eases, in­clud­ing be­ta tha­lassemia, hered­i­tary he­mochro­mato­sis and myelodys­plas­tic syn­dromes.

The lat­est study, an­nounced to­day, is in peo­ple with poly­cythemia ve­ra, a chron­ic blood can­cer in which pa­tients pro­duce an over­abun­dance of red blood cells. Com­pli­ca­tions can range from itch­i­ness to blood clots. Nor­mal­ly, pa­tients are treat­ed with phle­botomies every few weeks or months.  The prob­lem, though, is that their red blood cell counts can rise in-be­tween and con­tin­u­al­ly re­mov­ing a per­son’s blood is not with­out con­se­quence. It can lead to weak­ness and iron de­fi­cien­cy, among oth­er com­pli­ca­tions.

In the part of the tri­al that is now evalu­able, in­ves­ti­ga­tors gave dif­fer­ent dos­es of PTG-300 to 7 dif­fer­ent pa­tients who had at least three phle­botomies in the 24 weeks pri­or. Six pa­tients did not need a phle­boto­my over the 4 to 28 weeks they took it. A 7th had an un­in­tend­ed in­ter­rup­tion to his dos­ing, re­ceived a sin­gle phle­boto­my and con­tin­ued ther­a­py.

Lead in­ves­ti­ga­tor Ron Hoff­man, called it a po­ten­tial “par­a­digm shift.” Un­like phle­botomies or the oth­er drugs used to treat the dis­ease, it could al­low pa­tients to main­tain good red blood cell counts over long stretch­es with­out se­vere side ef­fects.

”What has been done for 100 years is that pa­tients un­der­go blood let­ting es­sen­tial­ly,” Hoff­man told End­points. “We didn’t an­tic­i­pate us­ing this kind of ap­proach. It’s re­al­ly pret­ty cool ac­tu­al­ly, I’m ex­cit­ed.”

The drug mim­ics the ef­fect of hep­cidin, a nat­ur­al hor­mone that reg­u­lates iron lev­els. Be­cause the body needs iron to pro­duce red blood cells, lim­it­ing those lev­els can in the­o­ry lim­it over­pro­duc­tion in these pa­tients.

The re­sults con­vinced Pro­tag­o­nist to pick their lead in­di­ca­tion ahead of sched­ule, Pa­tel said. They will now ex­pand their cur­rent study from a goal of 30 pa­tients to 50 pa­tients and they plan to start a piv­otal tri­al next year. That will move it sig­nif­i­cant­ly ahead of their re­main­ing ir­ri­ta­ble bow­el dis­ease as­set, PTG-943. De­vel­op­ment of that drug has been pushed back sig­nif­i­cant­ly dur­ing the Covid-19 pan­dem­ic; be­cause it tar­gets IL-23, it could make pa­tients more sus­cep­ti­ble to in­fec­tion.

“These are im­muno-sup­pres­sive agents at the end of the day,” Pa­tel said of PTG–973. “Ba­si­cal­ly, for now the fo­cus is on blood dis­or­ders.”

It’s a marked shift for Pa­tel and Pro­tag­o­nist. The com­pa­ny spent a decade build­ing its pep­tide-based plat­form, and its ear­li­est as­sets were for IBD. They raised in­vestors con­fi­dence around PTG–100 and quick­ly brought it in­to a Phase IIb study. J&J of­fered $990 mil­lion in a deal cen­tered on a sec­ond IBD drug, PTG-200. These drugs ap­pealed par­tic­u­lar­ly be­cause they were oral, un­like the in­jecta­bles that have dom­i­nat­ed the in­flam­ma­to­ry dis­or­ders mar­ket.

The J&J drug is still in the clin­ic, but in March of 2018, Pro­tag­o­nist an­nounced that PTG-100 failed a fu­til­i­ty analy­sis; an in­de­pen­dent re­view board de­ter­mined it had no chance of beat­ing place­bo. The stock fell 58%, from $20.43 to $8.59, rough­ly where it sits to­day.

PTG-100 has since been re­tired, but Pa­tel claimed the re­view de­ci­sion was ac­tu­al­ly wrong. The com­pa­ny not­ed a high place­bo re­sponse in the ini­tial as­sess­ment and sent it for a blind­ed re­view to a third par­ty and CRO’s sub­con­trac­tor, who de­ter­mined some of the ini­tial en­do­scopes had been ini­tial­ly mis­read and the tri­al should have con­tin­ued.

“With­in two days we fig­ured out the en­doscopy read­outs were er­rant,” he said. “The out­come should not have been fu­tile.”

The com­pa­ny went back to the FDA with the third par­ty re­view, Pa­tel said, but the FDA said they had to start a new tri­al. By that point, though, the com­pa­ny had al­ready come up with PTG-943, which they be­lieved worked bet­ter and was wis­er to ad­vance if they were go­ing to start a new tri­al.

Now with Covid-19 push­ing back IBD fur­ther, blood dis­or­ders have be­come the com­pa­ny’s main strat­e­gy, de­spite hav­ing on­ly a tiny, open-la­bel da­ta set. Pa­tel is con­fi­dent, though, that it can be a fruit­ful one. He said there was a clear reg­u­la­to­ry path with a 150-per­son tri­al, good ef­fects in those pa­tients, and a sig­nif­i­cant po­ten­tial mar­ket.

“It fits all of the three cat­e­go­ry: strong da­ta, a good reg­u­la­to­ry path for­ward, and a very large com­mer­cial op­por­tu­ni­ty,” he said. “So that’s where Pro­tag­o­nist will be fo­cused.

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The cell and gene therapies (CGT) sector offers unprecedented opportunities for patient disease management across virtually all therapeutic areas. However, finding the right accredited clinical teams to take a therapy through to the clinic and manage the regulatory process can be a major challenge for biotechs with a CGT product.

Ursula von der Leyen, President of the European Commission

Omi­cron: Re­searchers scram­ble as new coro­n­avirus mu­ta­tion takes flight around the globe — Pfiz­er/BioN­Tech, Mod­er­na vow swift re­sponse

As Americans were waking up for their Black Friday rituals, they were greeted with the news that a new mutation of the Covid-19 virus has appeared and been sequenced — after it caught an international flight to Hong Kong. And two of the leading Covid-19 vaccine developers promised delivery of a new vaccine “within 100 days” if necessary while a third spelled out its 3-prong strategy hours later.

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Thanks­giv­ing edi­tion: Top 15 End­points sto­ries of 2021; Can you name that vac­cine?; Mer­ck­'s Covid an­tivi­ral dis­ap­points; FDA nom­i­nee's in­dus­try ties; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

Happy Thanksgiving to all those who are celebrating it — although, if we are being honest, this week’s abbreviated edition is really for those who are not. Wherever you’re tuning in from, we appreciate your support, hope you find this recap helpful and we wish you a wonderful weekend.

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Troy Wilson, Kura CEO

UP­DAT­ED: FDA hits the red light on an ear­ly-stage AML study af­ter a pa­tient dies

The FDA has slapped a clinical hold on the early-stage program for one of Kura Oncology’s cancer drugs following a patient’s death in a clinical trial.

The biotech $KURA reported early Wednesday that the Phase Ib study of KO-539 for acute myeloid leukemia would be halted, suspending enrollment, while researchers and the FDA probed the death. Patients already on the drug can continue taking it.

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What were End­points read­ers tun­ing in­to this year? Here’s a look at our 15 most pop­u­lar re­ports of the year (so far)

At the beginning of this year, I laid out a basic objective for Endpoints News as we headed to our 5th anniversary. We’ve long been doing a fine job covering the breaking news in R&D — if I do say so myself — but we needed to expand our horizons on industry coverage, increase the staff and go much, much deeper when the stories demanded it.

In a phrase: broader and deeper.

It’s safe to say, based on our daily web traffic, that you all seemed to like this idea. We’ve doubled the staff — thanks to a growing group of paid subscribers — ramped up the daily report and now publish a regular slate of in-depth articles. And traffic — those clicks you always read about — have gone up in volume too. Monthly sessions are up 43%, to close to 1.5 million. Unique readers are up 63%, to 874,480 in October, after setting a record of close to a million the month before. Page views are running at 3 million-plus a month. And the overall number of subscribers has surged to 124,000.

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Mar­ket­ingRx roundup: Am­gen, Lil­ly, Bio­haven mi­graine brand re­call low, study says; No­var­tis looks to re­make drug launch mod­el

Forget the migraine marketing brand wars. When it comes to patients, many can’t even name one despite substantial advertising efforts, according to a new study from Phreesia that concludes CGRP migraine drugmakers still need to work on brand recognition.

Almost half (47%) of the patients Phreesia surveyed couldn’t name one preventative migraine brand. The best performer was Topamax, a small molecule anticonvulsant that’s been around since 2004, which 26% of migraine patients could recall. Among the new CGRP brand names recognized, Amgen’s Aimovig ranked highest with 8% recall, while Eli Lilly’s Emgality and Biohaven’s Nurtec tied at 7% and Teva’s Ajovy was remembered by 3% of patients.

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Emma Walmsley, GlaxoSmithKline CEO (Fang Zhe/Xinhua/Alamy Live News)

Glax­o­SmithK­line places a risky bet on Ar­row­head­'s RNA drug in the fail­ure-strewn NASH field

As activist investors champ at the bit for change at drug giant GlaxoSmithKline, the pharma giant has turned over many rocks to find an R&D success to present to its detractors. In NASH, a field strewn with failures, GSK hopes a new license deal can churn out a much-needed winner.

GSK will pay $120 million in upfront cash and $910 million in downstream milestones to develop and sell ARO-HSD, Arrowhead Pharmaceuticals’ RNA interference drug targeting fatty liver disease nonalcoholic steatohepatitis (NASH), the companies said Monday.

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Name that vac­cine: From Comir­naty to Spike­vax to Nu­vax­ovid, Covid-19 shot­s' brand names re­main lit­tle-known

Most people know if they’re “Team Pfizer” or “Team Moderna,” but few know if they got the Comirnaty or Spikevax Covid-19 vaccine. Those are the brand names of Pfizer and Moderna vaccines, respectively, however they have yet to take hold with consumers, media or even medical professionals.

And there are others. Covid vaccine brand names also include AstraZeneca’s Vaxzevria, Novavax’s Nuvaxovid, and Sanofi and GlaxoSmithKline’s Vidprevtyn. J&J’s Janssen-developed Covid vaccine is the lone major holdout and is still yet to be named, if ever. In EMA filings approving its conditional use, the brand name is listed simply as “Covid-19 Vaccine Janssen.”

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Joan Perelló, Sanifit CEO

Joan Perel­ló set out 17 years ago to de­vel­op a drug. And to­day he's be­ing re­ward­ed with a $424M biotech buy­out

Joan Perelló beat all the odds with his little Spanish biotech startup Sanifit.

Working on the far perimeter of the big US/European drug development scene, he took a drug born out of his PhD work and got enough seed cash to get started. That’s one near miracle. In the second near miracle he gathered a previously unheard of venture raise in Spain — helping build an industry ecosystem from scratch — to pursue a successful search for solid human data for his drug, SNF472. And while gathering a virtual team of developers from Europe and the US, the CEO/co-founder steered it into the late-stage arena.

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