Alice Zhang (Verge Genomics)

Eli Lil­ly makes mod­est bet on 'all-in-hu­man' dis­cov­ery out­fit for ALS drugs, deep­en­ing bid in pre­ci­sion neu­rol­o­gy

For years, Big Phar­ma has re­treat­ed from neu­rol­o­gy amid a se­ries of high-pro­file fail­ures in the big-tick­et in­di­ca­tions such as Alzheimer’s and ALS. But the tide has turned in re­cent years, and big drug­mak­ers like Eli Lil­ly have dou­bled down on their in­vest­ments in the space.

Now, look­ing to crack a new path to “pre­ci­sion neu­rol­o­gy,” Lil­ly is putting its name be­hind a ge­nomics play­er aim­ing for a nov­el path to neu­ro­log­i­cal dis­ease ther­a­pies.

Lil­ly will pay $25 mil­lion up­front and up to $694 mil­lion in biobucks for li­cens­ing rights to four po­ten­tial pro­grams from Verge Ge­nomics, a San Fran­cis­co-based dis­cov­ery out­fit boast­ing an “all-in-hu­man” dis­cov­ery and de­vel­op­ment plat­form us­ing AI to crunch through da­ta from the biotech’s pro­pri­etary brain tis­sue data­base, the part­ners said.

It’s a mod­est up­front in­vest­ment for Lil­ly and one with a game clock: The dis­cov­ery pact comes with a three-year term, adding some near-term stakes for Verge’s work.

The biotech is helmed by CEO Al­ice Zhang, who co-found­ed the ge­nomics play­er at the ten­der age of 26 back in 2015. She told End­points News the Lil­ly col­lab­o­ra­tion was a nat­ur­al off­shoot of Verge’s strat­e­gy to take as many of its in-house mol­e­cules through de­vel­op­ment as pos­si­ble. The ben­e­fit of hav­ing Lil­ly and its deep ex­pe­ri­ence in neu­rol­o­gy is an ob­vi­ous boost.

Where Verge seeks to dif­fer­en­ti­ate it­self is in its dis­cov­ery and pre­clin­i­cal ap­proach, which doesn’t re­ly on an­i­mal mod­els but rather us­es AI-de­vel­oped mol­e­cules test­ed in ex vi­vo hu­man neu­rons pri­or to clin­i­cal tri­als. Lean­ing on a grow­ing dataset of neu­ro ge­net­ic da­ta, Zhang en­vi­sions a fu­ture in which neu­rol­o­gy looks a lot like on­col­o­gy, with a se­ries of high­ly val­i­dat­ed path­ways of­fer­ing a re­al chance at de­vel­op­ing pre­ci­sion med­i­cines for pa­tients.

“One of the main val­ue propo­si­tions Lil­ly saw when they chose us as a part­ner is we had the abil­i­ty to ac­tu­al­ly iden­ti­fy ge­net­ic path­ways rather than in­di­vid­ual ge­net­ic mu­ta­tions that are shared across larg­er and more com­mer­cial­ly vi­able pa­tient pop­u­la­tions,” she said. “So we can find oth­er ‘nails’ for this kind of new ‘ham­mer’ of ge­net­ic ther­a­pies that we have.”

In terms of how Verge got on Lil­ly’s radar, CBO Jane Rhodes ex­plained the con­ver­sa­tion start­ed af­ter BIO 2020 with the drug­mak­er ex­press­ing in­ter­est in Verge’s dis­cov­ery plat­form and then its po­ten­tial in drug de­vel­op­ment. That se­ries of chit-chats, which in­clud­ed hash­ing out ex­act­ly how a deal would look, even­tu­al­ly turned in­to the pact you see to­day.

“We be­gan dis­cus­sions and quick­ly honed in a few key dis­eases, ul­ti­mate­ly fo­cus­ing on ALS,” Rhodes said. “We spent a lot of time get­ting to know each oth­er and re­al­ly fine tun­ing the agree­ment so it re­al­ly de­liv­ers on what Lil­ly needs and what is a strong strate­gic ad­van­tage for Verge as well in that it un­locks val­ue and tar­gets that we wouldn’t nec­es­sar­i­ly have tar­get­ed our­selves.”

Verge will not on­ly pur­sue the four can­di­dates along­side Lil­ly but al­so has a lead can­di­date in ALS the biotech hopes to hit the clin­ic by the end of the year, Zhang said. That drug in­hibits the PIK­fyve gene, which Verge said has shown a con­nec­tion in ALS. Verge will hold on­to rights for its lead pro­grams with Lil­ly hold­ing li­cens­ing rights for the four sep­a­rate can­di­dates.

Rhodes said Verge is look­ing to strike a bal­ance be­tween ad­vanc­ing its own in-house can­di­dates and bring­ing in out­side part­ners to bring oth­er mol­e­cules through the pipeline. In the mean­time, that could mean oth­er Big Phar­ma part­ners, but the sci­en­tif­ic fit is the ul­ti­mate de­cid­ing fac­tor.

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.