AACR21 roundup: Ar­cus rolls out PhI da­ta on adeno­sine block­er for CRC; Co­di­ak's en­gi­neered ex­o­some for IL-12 shows ear­ly promise

Ar­cus Bio­sciences’ adeno­sine block­er etru­madenant showed some ben­e­fit in ex­tend­ing pa­tients’ lives as part of a Phase I/Ib tri­al in third-line-or-lat­er col­orec­tal can­cer pa­tients, ac­cord­ing to da­ta pre­sent­ed Sat­ur­day at the vir­tu­al AACR an­nu­al meet­ing.

Etru­madenant, a dual adeno­sine A2aR/A2b re­cep­tor an­tag­o­nist, is de­signed to in­hib­it adeno­sine’s role in pre­vent­ing lym­pocytes like CD8+ ef­fec­tor T cells and NK cells from in­fil­trat­ing the tu­mor mi­croen­vi­ron­ment, the com­pa­ny said. A com­bi­na­tion of etru­madenant and chemother­a­py reg­i­men FOL­FOX-6 post­ed a me­di­an PFS of 4.2 months, a me­di­an OS of 13.6 months and an ob­jec­tive re­sponse rate of 9.1%. The drug showed con­sis­tent ben­e­fits in BRAF/RAS mu­tat­ed can­cer cells, the com­pa­ny said.

The ARC-3 study wasn’t pow­ered to com­pare that com­bi­na­tion against place­bo so it’s hard to know ex­act­ly what sig­nif­i­cance these re­sults hold. But Ar­cus did high­light that pa­tients on two es­tab­lished stan­dards of care in that late-line set­ting re­port­ed a me­di­an PFS of 2 and 1 months, a me­di­an OS of 7.1 and 6.4 months and ORR of 1.6% and 1%, re­spec­tive­ly. The study al­so showed that pa­tients with high tu­moral mu­ta­tion bur­den and ex­pres­sion of CD73 with­in the tu­mor post­ed im­proved out­comes.

The re­sults are promis­ing enough that Ar­cus plans to ad­vance etru­madenant in­to a Phase II/IIb study dubbed ARC-9 that will eval­u­ate the drug in com­bi­na­tion with the biotech’s an­ti-PD-1 an­ti­body zim­bere­limab and FOL­FOX with or with­out be­va­cizum­ab in sec­ond- and third-line metasta­t­ic col­orec­tal can­cer.

Co­di­ak ekes out some ear­ly promise for its en­gi­neered ex­o­some for IL-12

Co­di­ak Bio­sciences is chas­ing a whole new class of drugs us­ing en­gi­neered ex­o­somes, and now it has su­per ear­ly hu­man da­ta it says may even­tu­al­ly pro­vide proof of con­cept there.

Co­di­ak’s ex­oIL-12, an ex­o­some en­gi­neered to present IL-12 on its sur­face and at­tack tu­mors with a lim­it­ed dose, post­ed new phar­ma­co­dy­nam­ic da­ta at AACR show­ing no sys­temic pro­duc­tion of in­ter­fer­on gam­ma, a byprod­uct of IL-12 ac­ti­va­tion as­so­ci­at­ed with se­ri­ous side ef­fects. Those da­ta are part of a ran­dom­ized, place­bo-con­trolled Phase I study Co­di­ak is run­ning in healthy vol­un­teers.

Ear­li­er re­sults showed no sys­temic ex­po­sure to IL-12 and no site or sys­temic treat­ment-re­lat­ed ad­verse events. A 6-nanogram dose of the drug was present in the skin 24 hours af­ter treat­ment, which Co­di­ak be­lieves could last­ing IL-12 path­way ac­ti­va­tion. The drug­mak­er will take that dose in­to an ex­pand­ed Phase II tri­al.

Hookipa touts ear­ly T cell boost for HPV can­cer im­munother­a­pies

Hookipa’s T cell im­munother­a­py can­di­dates post­ed ear­ly im­muno­genic­i­ty wins as part of a Phase I tri­al tar­get­ing HPV16+ tu­mor types, the com­pa­ny said.

Can­di­dates HB-201 and HB-202 drove an in­crease in HPV16-spe­cif­ic T cells, in­clud­ing an 8% jump in cir­cu­lat­ing CD8+ ef­fec­tor T cells af­ter a sin­gle dose. HB-201 us­es a sin­gle are­navirus vec­tor while HB-202 em­ploys two vec­tors, but both ex­press the same anti­gen, an E7E6 fu­sion pro­tein de­rived from HPV16.

The re­sults come as part of a Phase I/II dose-es­ca­la­tion study try­ing HB-201 as a monother­a­py, as part of an al­ter­nat­ing reg­i­men with HB-202 and in com­bi­na­tion with a PD-1 block­er.

How Pa­tients with Epilep­sy Ben­e­fit from Re­al-World Da­ta

Amanda Shields, Principal Data Scientist, Scientific Data Steward

Keith Wenzel, Senior Business Operations Director

Andy Wilson, Scientific Lead

Real-world data (RWD) has the potential to transform the drug development industry’s efforts to predict and treat seizures for patients with epilepsy. Anticipating or controlling an impending seizure can significantly increase quality of life for patients with epilepsy. However, because RWD is secondary data originally collected for other purposes, the challenge is selecting, harmonizing, and analyzing the data from multiple sources in a way that helps support patients.

Jason Kelly, Ginkgo Bioworks CEO (Kyle Grillot/Bloomberg via Getty Images)

UP­DAT­ED: Gink­go Bioworks re­sizes the de­f­i­n­i­tion of go­ing big in biotech, rais­ing $2.5B in a record SPAC deal that weighs in with a whop­ping $15B-plus val­u­a­tion

Ginkgo Bioworks execs always thought big. But today should redefine just how big an upstart biotech player can dream.

In the largest SPAC deal to clear the hurdles to Nasdaq, the biotech that envisioned everything from remaking synthetic meat to a whole new approach to developing drugs has joined forces with one of the biggest disruptors in biotech to slam the Richter scale on dealmaking.

Soon after becoming the darling of the VC crew and clearing the bar on a $4 billion valuation, Ginkgo — a synthetic biotech player out to reprogram cells with industrial efficiency — has now struck a deal to go public in the latest leviathan SPAC that sets its pre-money valuation at $15 billion. In one swift vault, Ginkgo will combine with Harry Sloan’s Soaring Eagle Acquisition Corp. and leap into the public markets.

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FDA un­veils six ICH guide­lines ahead of meet­ing with Health Cana­da

A sign that the FDA’s non-Covid-related processes are beginning to normalize: The release of six guidelines from the International Council of Harmonisation.

Years in development, the ICH documents offer an international perspective on drug development, with these latest guidelines covering everything from recommendations to support the classification of drug substances, featured in the M9 guidance, to standards for nonclinical safety studies for pediatric medicines in the S11 guideline.

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Sanofi, Glax­o­SmithK­line, Boehringer ac­cused of play­ing games, de­stroy­ing emails re­lat­ed to law­suit over con­t­a­m­i­nat­ed Zan­tac

A recent court filing raises new questions about how major pharma companies like Sanofi, GlaxoSmithKline, and Boehringer Ingelheim have dealt with a lawsuit related to recalls of certain over-the-counter heartburn drugs due to the presence of a potentially cancer-causing substance found in them.

More than 70,000 people who took Sanofi’s Zantac and other heartburn drugs containing ranitidine, which have been recalled over the past two years, have sued the manufacturers, including generic drugmakers, and other retailers and distributors as part of a consolidated suit before US District Court Judge Robin Rosenberg in Florida.

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Al Sandrock, Biogen R&D chief (Biogen via YouTube)

UP­DAT­ED: Bio­gen push­es in a fresh stack of chips and starts prep­ping a glob­al R&D game plan af­ter watch­ing the cards turn on ear­ly throm­bolyt­ic da­ta

After patiently steering through a decade-long journey for its early-stage clinical work, a small Tokyo biotech has clinched a deal to out-license its lead thrombolytic agent to US heavyweight Biogen — which sees a potentially game-changing impact on the clot-busting field after taking a careful look at some upbeat Phase IIa data.

Three years after Biogen anted up $4 million to gain an option on the drug from TMS, the big US biotech is making a small bet to beef up its stroke portfolio. The BD team inked a deal to go ahead and grab rights to the drug for $18 million, with another $335 million in milestone cash on the table for a successful outcome.

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Chris Garabedian (Xontogeny)

Per­cep­tive Ad­vi­sors, Xon­toge­ny bring the band back and then some with a $515M sec­ond fund sniff­ing out lead com­pounds

When Perceptive Advisors and startup accelerator Xontogeny initially teamed up on an early-stage VC round in 2019, the partners hoped to prove their investments could be a force multiplier for early-stage companies. Now, with that proof of concept behind them, the pair have closed a second VC round worth more than double the money.

Dubbed PXV Fund II and headed by Xontogeny CEO and former Sarepta head Chris Garabedian, the $515 million fund will target 10 to 12 early-stage preclinical companies with Series A rounds in the $20 million to $40 million range with opportunities for Series B follow-ups. The oversubscribed fund is bringing the band back with initial investors from PXVI as well as new investors that include “top-tier” asset managers, endowments, foundations, family offices, and individual investors.

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A clos­er look at the FDA’s more than 700 pan­dem­ic-re­lat­ed record re­quests to re­place on­site in­spec­tions

As the pandemic constrained the FDA’s ability to travel for onsite manufacturing inspections, the agency increasingly turned to requesting records to fill the gap, even for hundreds of US-based facilities.

FDA explains in its guidance on manufacturing inspections during the pandemic that the agency can request records (not to be confused with the FDA’s remote interactive evaluations) directly from facilities “in advance of or in lieu of” certain onsite inspections. Companies are legally required to fulfill those requests because a denial may be considered limiting an inspection, which could lead to the FDA deeming a drug made at that site to be adulterated.

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Stephen Squinto, Gennao Bio CEO (Gennao)

Alex­ion co-founder Stephen Squin­to is back in the game as CEO, this time for a small gene ther­a­py play­er

With his name already behind a rare disease success story in Alexion, Stephen Squinto was looking for a great story to drive him to jump back into the biotech game. He found that in a fledging non-viral gene therapy company, and now he’s got a few backers on board as well.

On Tuesday, Gennao Bio launched with a $40 million Series A co-led by OrbiMed and Logos Capital with participation by Surveyor Capital. The biotech, which is looking to use its cell-penetrating antibody platform to deliver nucleic acid “payloads” during into the nucleus, had to rush for its initial series — and had a name change along the way.

Alvotech takes Ab­b­Vie to court over al­leged patent 'mine­field' sur­round­ing megablock­buster Hu­mi­ra

AbbVie has so far been successful in shooing away competition to its megablockbuster Humira, deploying a number of patents and settlements to keep biosimilars off the US market until 2023. But one Icelandic drugmaker doesn’t want to wait — and on Tuesday, it filed a lawsuit challenging what it called a patent “minefield.”

Alvotech has accused AbbVie of trying to “overwhelm” and “intimidate” it with “an outrageous number of patents of dubious validity,” according to court documents. The company is currently seeking approval for its Humira copycat AVT02, which AbbVie says would infringe upon 62 patents.