CEO Stephen Yoder (Pieris)

Pieris fi­nal­ly vaults FDA hold on next-gen sol­id tu­mor hunter, clear­ing the path for mid-stage tri­al

Fi­nal­ly freed from the re­straints of a par­tial FDA clin­i­cal hold on its lead HER2-pos­i­tive sol­id tu­mor can­di­date, Pieris Phar­ma­ceu­ti­cals is now rac­ing to­ward Phase II.

The FDA slapped a par­tial hold on Pieris’ PRS-343 back in Ju­ly, re­strict­ing the biotech from en­rolling new pa­tients in a Phase I tri­al. While Pieris was al­lowed to con­tin­ue dos­ing pa­tients who were al­ready en­rolled, the agency re­quest­ed they con­duct an ad­di­tion­al “in-use and com­pat­i­bil­i­ty study” be­fore re­cruit­ing any more.

PRS-343 con­sists of a 4-1BB-tar­get­ing An­ti­calin pro­tein and a HER2-tar­get­ing an­ti­body. It’s a frozen for­mu­la­tion that’s re­moved from a freez­er and pre­pared for IV in­fu­sion at the tri­al site, CEO Stephen Yo­der said.

“There was a re­quest from FDA to test the mol­e­cule, the drug prod­uct, un­der var­i­ous con­di­tions in­clud­ing stress con­di­tions to show that it has a very ro­bust sta­bil­i­ty pro­file, giv­en the vari­abil­i­ty that can hap­pen in the dif­fer­ent clin­i­cal sites,” Yo­der told End­points. 

At the time, the biotech had en­rolled pa­tients in the two high­est-dose co­horts — 8 mg/kg and 18 mg/kg — and in com­bi­na­tion stud­ies with Tecen­triq un­der a drug sup­ply agree­ment with Roche.

At vir­tu­al ES­MO 2020, Pieris said the drug showed a “durable clin­i­cal ben­e­fit in the ac­tive dose co­horts, in­clud­ing a con­firmed com­plete re­sponse, in heav­i­ly pre-treat­ed pa­tients across mul­ti­ple HER2-pos­i­tive tu­mor types” in Phase I monother­a­py and Tecen­triq com­bi­na­tion stud­ies.

As of a Ju­ly 27 cut­off date, re­searchers not­ed a con­firmed com­plete re­sponse at the 18mg/kg dose lev­el and three par­tial re­spons­es in the 8 mg/kg lev­el (out of 33 evalu­able pa­tients), ac­cord­ing to the ES­MO da­ta. And in the ate­zolizum­ab com­bi­na­tion tri­al, four out of 29 evalu­able pa­tients achieved a con­firmed par­tial re­sponse at ac­tive dose lev­els.

“We’re sat­is­fied that we have da­ta for our rec­om­mend­ed Phase II dose and we’re now re­al­ly fo­cused on mo­bi­liz­ing for Phase II ini­ti­a­tion,” Yo­der said on Wednes­day, adding that the study is ex­pect­ed to launch this year.

Pieris $PIRS has worked for years on en­gi­neer­ing pro­teins that are lighter and more ver­sa­tile than an­ti­bod­ies, so that they can work where an­ti­bod­ies find their en­try barred. On Wednes­day, their stock was up 1.5%, pric­ing in at $2.71 per share.

“What sets our ap­proach apart from even oth­er im­muno-on­col­o­gy agents such as the check­point in­hibitors is that we are ag­o­niz­ing po­tent­ly in the tu­mor mi­croen­vi­ron­ment tu­mor-spe­cif­ic T cells by tar­get­ing 4-1BB,” Yo­der said. “What that does is it im­proves the meta­bol­ic fit­ness of T cells, and it caus­es al­so their pro­lif­er­a­tion.”

“You don’t just re­ac­ti­vate T cells, but you ex­pand them, and you can po­ten­tial­ly give them a lot more longevi­ty and more dura­bil­i­ty,” he added.

De­spite the par­tial clin­i­cal hold, Eli Lil­ly struck a col­lab­o­ra­tion deal with Pieris in Au­gust to fur­ther ad­vance PRS-343 stud­ies in com­bi­na­tion with its Cyra­mza and chemother­a­py pa­cli­tax­el for the sec­ond-line treat­ment of pa­tients with HER2-pos­i­tive gas­tric can­cer. Lil­ly agreed to sup­ply the ad­di­tion­al com­pounds and col­lab­o­rate on da­ta while Pieris pre­pared to ini­ti­ate Phase II.

That isn’t Pieris’ first Big Phar­ma pact. Back in 2017, As­traZeneca com­mit­ted up to $57.5 mil­lion to seed an R&D pact with Pieris, which was charged with tak­ing PRS-060 — an An­ti­calin against in­ter­leukin-4 re­cep­tor al­pha — in­to a Phase I asth­ma tri­al. And be­fore that, it inked a deal to work with Servi­er for PRS-332 and four more im­muno-on­col­o­gy pro­grams.

UP­DAT­ED: Agenus calls out FDA for play­ing fa­vorites with Mer­ck, pulls cer­vi­cal can­cer BLA at agen­cy's re­quest

While criticizing the FDA for what may be some favoritism towards Merck, Agenus on Friday officially pulled its accelerated BLA for its anti-PD-1 inhibitor balstilimab as a potential second-line treatment for cervical cancer because of the recent full approval for Merck’s Keytruda in the same indication.

The company said the BLA, which was due for an FDA decision by Dec. 16, was withdrawn “when the window for accelerated approval of balstilimab closed,” thanks to the conversion of Keytruda’s accelerated approval to a full approval four months prior to its PDUFA date.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 120,400+ biopharma pros reading Endpoints daily — and it's free.

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

NYU surgeon transplants an engineered pig kidney into the outside of a brain-dead patient (Joe Carrotta/NYU Langone Health)

No, sci­en­tists are not any clos­er to pig-to-hu­man trans­plants than they were last week

Steve Holtzman was awoken by a 1 a.m. call from a doctor at Duke University asking if he could put some pigs on a plane and fly them from Ohio to North Carolina that day. A motorcyclist had gotten into a horrific crash, the doctor explained. He believed the pigs’ livers, sutured onto the patient’s skin like an external filter, might be able to tide the young man over until a donor liver became available.

How to col­lect and sub­mit RWD to win ap­proval for a new drug in­di­ca­tion: FDA spells it out in a long-await­ed guid­ance

Real-world data are messy. There can be differences in the standards used to collect different types of data, differences in terminologies and curation strategies, and even in the way data are exchanged.

While acknowledging this somewhat controlled chaos, the FDA is now explaining how biopharma companies can submit study data derived from real-world data (RWD) sources in applicable regulatory submissions, including new drug indications.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Marty Duvall, Oncopeptides CEO

On­copep­tides stock craters as it pulls can­cer drug Pepax­to from the mar­ket

Shares of Oncopeptides crashed more than 70% in early Friday trading after the company said it’s pulling its multiple myeloma drug Pepaxto (melphalan flufenamide) from the US market after failing a confirmatory trial. The move will force the company to close its US and EU business units and enact significant layoffs.

The FDA had scheduled an adcomm meeting next Thursday to discuss Pepaxto, which first won accelerated approval in February and costs about $19,000 per course of treatment. The committee was to weigh in on whether the confirmatory trial demonstrated a worse overall survival in the treatment arm compared to the control arm.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 120,400+ biopharma pros reading Endpoints daily — and it's free.

Pfiz­er pitch­es its Covid-19 vac­cine for younger chil­dren ahead of ad­comm next week

Pfizer will present its case to the FDA’s vaccine adcomm next week, seeking authorization for a lower-dose version of its Covid-19 vaccine for kids ages 5 through 12, which the Biden administration said will likely begin rolling out early next month.

Two primary doses of the 10 µg vaccine (the dose for those ages 12 and up is 30 μg) given 3 weeks apart in this group of children “have shown a favorable safety and tolerability profile, robust immune responses against all variants of concern including Delta, and vaccine efficacy of 90.7% against laboratory-confirmed symptomatic COVID-19,” the company said in briefing documents ahead of next Tuesday’s meeting of the FDA’s Vaccines and Related Biological Products Advisory Committee.

Sen. Richard Durbin (D-IL, foreground) and Sen. Richard Blumenthal (D-CT) (Patrick Semansky/AP Images)

Sen­a­tors back FDA's plan to re­quire manda­to­ry pre­scriber ed­u­ca­tion for opi­oids

Three Senate Democrats are backing an FDA plan to require mandatory prescriber education for opioids as overdose deaths have risen sharply over the past decade, with almost 97,000 American opioid-related overdose deaths in the past year alone.

While acknowledging a decline in overall opioid analgesic dispensing in recent years, the FDA said it’s reconsidering the need for mandatory prescriber training through a REMS given the current situation with overdoses, and is seeking input on the aspects of the opioid crisis that mandatory training could potentially mitigate.

David Lockhart, ReCode Therapeutics CEO

Pfiz­er throws its weight be­hind LNP play­er eye­ing mR­NA treat­ments for CF, PCD

David Lockhart did not see the meteoric rise of messenger RNA and lipid nanoparticles coming.

Thanks to the worldwide fight against Covid-19, mRNA — the genetic code that can be engineered to turn the body into a mini protein factory — and LNPs, those tiny bubbles of fat carrying those instructions, have found their way into hundreds of millions of people. Within the biotech world, pioneers like Alnylam and Intellia have demonstrated just how versatile LNPs can be as a delivery vehicle for anything from siRNA to CRISPR/Cas9.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 120,400+ biopharma pros reading Endpoints daily — and it's free.

David Livingston (Credit: Michael Sazel for CeMM)

Renowned Dana-Far­ber sci­en­tist, men­tor and bio­phar­ma ad­vi­sor David Liv­ingston has died

David Livingston, the Dana-Farber/Harvard Med scientist who helped shine a light on some of the key molecular drivers of breast and ovarian cancer, died unexpectedly last Sunday.

One of the senior leaders at Dana-Farber during his nearly half century of work there, Livingston was credited with shedding light on the genes that regulate cell growth, with insights into inherited BRCA1 and BRCA2 mutations that helped lay the scientific foundation for targeted therapies and earlier detection that have transformed the field.