Eliot Forster, F-star CEO

As­traZeneca takes a chance on the STING path­way with F-star

Af­ter a slew of Big Phar­ma com­pa­nies and biotechs walked away from the STING path­way in the last few years, As­traZeneca is ap­proach­ing the field with a new bet on the drug class’ next gen­er­a­tion.

The British drug­mak­er is team­ing up with F-star Ther­a­peu­tics on a slate of pre­clin­i­cal STING in­hibitor com­pounds, the com­pa­nies an­nounced Thurs­day morn­ing. It’s a mod­est sum as these things go, with $12 mil­lion up­front and over $300 mil­lion in mile­stones, plus sin­gle-dig­it roy­al­ties.

STING plays a cen­tral role in reg­u­lat­ing how the im­mune sys­tem rec­og­nizes for­eign in­vaders, F-star CEO Eliot Forster tells End­points News, and com­pa­nies have for years been look­ing at ways to ei­ther stim­u­late or in­hib­it the path­way to treat dis­eases. Re­searchers can ag­o­nize the path­way to try to treat can­cer — get­ting the im­mune sys­tem to at­tack tu­mors — or in­hib­it it in con­di­tions like rheuma­toid arthri­tis to tamp down on im­mune re­spons­es gone hay­wire.

F-star had been work­ing on both sides of the STING coin, and al­ready has a slate of STING ag­o­nists in the clin­ic. These weren’t for sale, Forster says, and As­traZeneca is get­ting on­ly the pre­clin­i­cal STING in­hibitors for yet-to-be dis­closed tar­gets. It’s a slate of can­di­dates that F-star had been look­ing to part­ner out from the start, and As­traZeneca will take over full de­vel­op­ment with an ex­clu­sive glob­al li­cense.

The path­way has run up against sev­er­al is­sues in the past, par­tic­u­lar­ly on the ag­o­nist side of things. Aduro’s high-pro­file stum­bles dealt in part with a STING ag­o­nist pro­gram for can­cer, which No­var­tis walked away from in 2019. And af­ter Chi­nook ac­quired Aduro, it too dumped the last of the STING ag­o­nist can­di­dates ear­li­er this year.

There was al­so a cGAS-STING in­hibitor where Aduro part­nered with Eli Lil­ly, which end­ed up auc­tioned off once Aduro be­gan cut­ting bait. The deals proved cost­ly for the Big Phar­mas, as No­var­tis had teed up $250 mil­lion up­front with $500 mil­lion in mile­stones, while Lil­ly front­ed $12 mil­lion in cash and promised up to $620 mil­lion in mile­stones.

Nim­bus Ther­a­peu­tics al­so piv­ot­ed away from its STING pro­grams in June 2020 as it built out part­ner­ships with Gilead and Cel­gene pri­or to the Bris­tol My­ers Squibb ac­qui­si­tion.

But Forster said the STING ag­o­nist pro­grams F-star is re­tain­ing are rep­re­sen­ta­tive of the next gen­er­a­tion of the class, and that the in­hibitors li­censed out Thurs­day were in­formed by sim­i­lar emerg­ing re­search. Where­as the old STING ag­o­nists for can­cer could on­ly be in­ject­ed di­rect­ly in­to the tu­mor, lead­ing to a host of prob­lems, the clin­i­cal can­di­dates F-star kept are re-en­gi­neered to be giv­en through an IV.

“The cen­tral­i­ty of the STING path­way to the im­mune re­sponse in both di­rec­tions is key,” Forster said. “That’s why the whole in­dus­try has been in­ter­est­ed in it for the past decade … The first gen­er­a­tion was a good go, but the sec­ond gen­er­a­tion drugs are re­al­ly get­ting to that drug­ga­bil­i­ty point where we can be­gin to ma­nip­u­late the path­way.”

What Will it Take to Re­al­ize the Promise and Po­ten­tial of Im­mune Cell Ther­a­pies?

What does it take to get to the finish line with a new cancer therapy – fast? With approvals in place and hundreds of immune cell therapy candidates in the pipeline, the global industry is poised to create a fundamental shift in cancer treatments towards precision medicine. At the same time, unique challenges associated with cell and process complexity present manufacturing bottlenecks that delay speed to market and heighten cost of goods sold (COGS) — these hurdles must be overcome to make precision treatments an option for every cancer patient. This series of articles highlights some of the key manufacturing challenges associated with the production of cell-based cancer therapies as well as the solutions needed to transcend them. Automation, process knowledge, scalability, and assured supply of high-quality starting material and reagents are all critical to realizing the full potential of CAR-based therapies and sustaining the momentum achieved in recent years. The articles will highlight leading-edge technologies that incorporate these features to integrate across workflows, accelerate timelines and reduce COGS – along with how these approaches are enabling the biopharmaceutical industry to cross the finish line faster with new treatment options for patients in need.

The biggest ques­tions fac­ing gene ther­a­py, the XLMTM com­mu­ni­ty, and Astel­las af­ter fourth pa­tient death

After three patients died last year in an Astellas gene therapy trial, the company halted the study and began figuring out how to safely get the program back on track. They would, executives eventually explained, cut the dose by more than half and institute a battery of other measures to try to prevent the same thing from happening again.

Then tragically, Astellas announced this week that the first patient to receive the new regimen had died, just weeks after administration.

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Lat­est news: It’s a no on uni­ver­sal boost­ers; Pa­tient death stuns gene ther­a­py field; In­side Tril­li­um’s $2.3B turn­around; 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.

Next week is shaping up to be a busy one, as our editor-in-chief John Carroll and managing editor Kyle Blankenship lead back-to-back discussions with a great group of experts to discuss the weekend news and trends. John will be spending 30 minutes with Jake Van Naarden, the CEO of Lilly Oncology, and Kyle has a brilliant panel lined up: Harvard’s Cigall Kadoch, Susan Galbraith, the new head of cancer R&D at AstraZeneca, Roy Baynes at Merck, and James Christensen at Mirati. Don’t miss out on the action — sign up here.

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Mi­rati's KRAS drug looks like the fa­vorite in colon can­cer with new da­ta, putting the pres­sure square on Am­gen

With Amgen already providing proof-of-concept for KRAS inhibitors with its sotorasib, Mirati Therapeutics is piecing together a follow-up effort in lung cancer with data it thinks are superior. But in colon cancer, where solo sotorasib has turned in a dud, Mirati may now have a strong case for superiority.

Mirati’s adagrasib, dosed solo or in combination with chemotherapy cetuximab, showed response rates grater than sotorasib solo  and as part of combination study in a similar patient population also revealed this week at #ESMO21. Mirati’s data were presented as part of a cohort update from the Phase II KRYSTAL-1 study testing adagrasib in a range of solid tumors harboring the KRAS-G12C mutation.

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President Biden and Pfizer CEO Albert Bourla (Patrick Semansky/AP Images)

Chaot­ic ad­comm sees Pfiz­er/BioN­Tech boost­ers re­ject­ed for gen­er­al pop­u­la­tion, but rec­om­mend­ed for old­er and high-risk pop­u­la­tions

With just days before President Joe Biden’s Covid-19 booster rollout is set to go into effect, an FDA advisory committee appeared on the verge of not recommending boosters for anyone in the US before a last-minute change of wording laid the groundwork for older adults to have access to a third dose.

The FDA’s adcomm on Vaccines and Related Biological Products (VRBPAC) roundly rejected Pfizer/BioNTech booster shots for all individuals older than 16 by a 16-2 vote Friday afternoon. Soon after, however, the agency posed committee members a new question limiting booster use to the 65-and-older population and individuals at high risk of disease due to occupational exposure or comorbidities.

The best of the rest: High­lights from the be­low-the-fold pre­sen­ta­tions at #ES­MO21

This year’s ESMO Congress has had a major focus on Big Pharma drugs — most notably candidates from Merck and AstraZeneca — but there have also been updates from smaller biotechs with data looking to challenge the big-name drugmakers.

Today, we’re highlighting some of the data releases that flew under the radar at #ESMO21 — whether from early-stage drugs looking to make a mark or older stalwarts with interesting follow-up data.

As­traZeneca, Dai­ichi Sanky­o's ADC En­her­tu blows away Roche's Kad­cy­la in sec­ond-line ad­vanced breast can­cer

AstraZeneca and Japanese drugmaker Daiichi Sankyo think they’ve struck gold with their next-gen ADC drug Enhertu, which has shown some striking data in late-stage breast cancer trials and early solid tumor tests. Getting into earlier patients is now the goal, starting with Enhertu’s complete walkover of a Roche drug in second-line breast cancer revealed Saturday.

Enhertu cut the risk of disease progression or death by a whopping 72% (p=<0.0001) compared with Roche’s ADC Kadcyla in second-line unresectable and/or metastatic HER2-positive breast cancer patients who had previously undergone treatment with a Herceptin-chemo combo, according to interim data from the Phase III DESTINY-Breast03 head-to-head study presented at this weekend’s #ESMO21.

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Merck Research Laboratories CMO Roy Baynes

Mer­ck­'s Keytru­da un­corks full da­ta on lat­est ad­ju­vant win — this time in melanoma — adding bricks to ear­ly can­cer wall

In recent months, the battle for PD-(L)1 dominance has spilled over into early cancer with Merck’s Keytruda and Bristol Myers Squibb’s Opdivo all alone on the front lines. Keytruda now has another shell in its bandolier, and it could spell a quick approval.

Keytruda cut the risk of relapse or death by 35% over placebo (p=0.00658) in high-risk, stage 2 melanoma patients who had previously undergone surgery to remove their tumors, according to full data from the Phase III KEYNOTE-716 presented Saturday at #ESMO21.

Mer­ck flesh­es out Keytru­da win in first-line cer­vi­cal can­cer, adding more fire­pow­er to its ear­ly can­cer push

Merck has worked hard to bring its I/O blockbuster Keytruda into earlier and earlier lines of therapy, and now the wonder drug appears poised to make a quick entry into early advanced cervical cancer.

A combination of Keytruda and chemotherapy with or without Roche’s Avastin cut the risk of death by 33% over chemo with or without Avastin (p=<0.001) in first-line patients with persistent, recurrent or metastatic cervical cancer, according to full data from the Phase III KEYNOTE-826 study presented Saturday at #ESMO21.