Anthony Sun, Zentalis CEO (Zentalis)

AACR21: Zen­tal­is keeps the heat on As­traZeneca with ear­ly WEE1 da­ta show­ing a group of 'ex­cep­tion­al' re­spon­ders

Long a tar­get for drug­mak­ers, the DNA dam­age re­pair path­way has picked up some new steam in re­cent years with Big Phar­ma plac­ing its bets. One of the lead­ing can­di­dates there is a WEE1 en­zyme in­hibitor from As­traZeneca, and now a small biotech play­er is look­ing to play catch up.

Zen­tal­is’ WEE1 in­hibitor, ZN-c3, post­ed par­tial re­spons­es across a slate of tu­mor types with a tol­er­a­ble safe­ty pro­file as monother­a­py for sol­id tu­mor pa­tients who are ei­ther treat­ment-re­sis­tant or have no es­tab­lished stan­dard of care, ac­cord­ing to in­ter­im Phase I da­ta pre­sent­ed as a late break­er Sat­ur­day at the vir­tu­al AACR an­nu­al meet­ing.

In what the Zen­tal­is team hopes will be a mean­ing­ful com­peti­tor to As­traZeneca’s own WEE1 in­hibitor, ZN-c3 post­ed three “ex­cep­tion­al re­spons­es” among 55 pa­tients by the Feb. 12 da­ta cut­off, in­clud­ing in pa­tients with a long his­to­ry of pri­or ther­a­py and across tu­mor types. Ex­cep­tion­al re­spon­ders are pa­tients who post a com­plete or par­tial re­sponse where less than 10% of the pa­tient pop­u­la­tion is ex­pect­ed to show re­sults.

In one case, a Stage IV ovar­i­an can­cer pa­tient with 18 pri­or lines of ther­a­py — 11 of those in the metasta­t­ic set­ting — post­ed a 56% re­duc­tion in tar­get le­sions with a key bio­mark­er show­ing rapid on­set at the four-week mark of ther­a­py. Re­searchers al­so saw par­tial re­spons­es in pa­tients with col­orec­tal can­cer and non-small cell lung can­cer and two non-ex­cep­tion­al par­tial re­spons­es in uter­ine serous car­ci­no­ma.

It’s ear­ly days, but Zen­tal­is has enough to go on to move along in­to the Phase II por­tion of the monother­a­py study with an op­ti­mal dose — 300 mg — that the biotech says can min­i­mize side ef­fects while show­ing PD bio­mark­er ac­tiv­i­ty.

The monother­a­py study — which CEO An­tho­ny Sun said showed “re­mark­able safe­ty and tol­er­a­bil­i­ty” — is part of a broad clin­i­cal pro­gram for ZN-c3, one of a class of WEE1 in­hibitors that tar­gets tu­mor cells’ DNA dam­age re­pair path­way. Giv­en its aim to pre­vent cell re­pair caused by oth­er agents, WEE1s are a nat­ur­al tar­get for com­bi­na­tion ther­a­py, and Zen­tal­is is cur­rent­ly work­ing on a ZN-c3/chemo com­bo tri­al as well as planned stud­ies in com­bi­na­tion with PARP in­hibitors, which al­so tar­get the DDR path­way.

But Zen­tal­is is al­so keep­ing its eye on As­traZeneca’s WEE1, AZD1775, which has shown OS ben­e­fit in pan­cre­at­ic can­cer pa­tients and is be­ing en­vi­sioned as a suc­ces­sor drug to PARP in­hibitor Lyn­parza. Back in Au­gust 2019, the drug spurred an OS of 22 months with pro­gres­sion-free sur­vival of 9 months in a small-scale study of 32 pan­cre­at­ic can­cer pa­tients.

Zen­tal­is thinks ZN-c3 could even­tu­al­ly best AZD1775 with a bet­ter safe­ty pro­file, which Sun said was the re­sult of the mol­e­cule be­ing more se­lec­tive with bet­ter phar­ma­co­ki­net­ic qual­i­ties. The biotech is al­so in the process of de­vel­op­ing what it calls nov­el bio­mark­ers to help iden­ti­fy sol­id tu­mor pa­tients who could best ben­e­fit from ZN-c3’s use.

Ed­i­tor’s Note: This sto­ry has been up­dat­ed to cor­rect an er­ror. Zen­tal­is record­ed three ex­cep­tion­al tu­mor re­spons­es in the Phase I da­ta. 

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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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.

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.