In 1-2 punch, Mol­e­c­u­lar Tem­plates cuts first-gen can­di­date and los­es a Big Phar­ma part­ner; Charles Riv­er teams up with Va­lence to pro­vide AI dis­cov­ery plat­form

It’s been sev­er­al months since a treat­ment-re­lat­ed death led the FDA to put a par­tial hold on Mol­e­c­u­lar Tem­plates’ on­ly first-gen­er­a­tion en­gi­neered tox­in body (ETB) can­di­date. Now the com­pa­ny is nix­ing the pro­gram, and Take­da is re­turn­ing the rights to one of its next-gen can­di­dates.

MT-3724, Mol­e­c­u­lar’s EBT in de­vel­op­ment for non-Hodgkin lym­phoma, will be no more, the com­pa­ny said on Mon­day morn­ing. The FDA first placed a par­tial hold on the can­di­date in No­vem­ber, fol­low­ing the death of a Phase II pa­tient who ex­pe­ri­enced Grade 5 cap­il­lary leak syn­drome.

“Marked­ly high phar­ma­co­ki­net­ic as­say read­ings were ob­served in this and oth­er sub­jects treat­ed with a spe­cif­ic lot of MT-3724 ma­te­r­i­al,” ac­cord­ing to Mol­e­c­u­lar.

The agency fol­lowed up with a full hold in late March, and re­quest­ed ad­di­tion­al in­for­ma­tion and the de­vel­op­ment of a new quan­ti­ta­tive as­say spe­cif­ic to MT-3724, which Mol­e­c­u­lar says “would take sig­nif­i­cant time and in­vest­ment away” from its pri­or­i­ties.

$MTEM shares dropped more than 25% on the news Mon­day.

In the same an­nounce­ment, Mol­e­c­u­lar said Take­da is back­ing out of a col­lab­o­ra­tion deal for TAK-169, a sec­ond-gen­er­a­tion ETB tar­get­ing CD38 for the treat­ment of mul­ti­ple myelo­ma. Take­da forked over $30 mil­lion up­front for the part­ner­ship back in 2018, and promised mile­stones up to $632.5 mil­lion.

Take­da is turn­ing the full rights over to Mol­e­c­u­lar, which will owe Take­da “low-sin­gle dig­it roy­al­ties” on fu­ture net sales. The drug, which was de­signed to over­come tu­mor re­sis­tance ob­served with Janssen and Gen­mab’s dara­tu­mum­ab (the first ap­proved mon­o­clon­al an­ti­body tar­get­ing CD38), is in a Phase I study.

Ac­cord­ing to Mol­e­c­u­lar, Take­da says its de­ci­sion to back out of the part­ner­ship was the re­sult of “on­go­ing port­fo­lio pri­or­i­ti­za­tion.”

So far, Take­da has en­rolled and treat­ed four sub­jects in the TAK-169 Phase I study, and Mol­e­c­u­lar says there have been no life-threat­en­ing tox­i­c­i­ties or signs of CLS.

Mol­e­c­u­lar’s EBTs use ge­net­i­cal­ly en­gi­neered ver­sions of the Shi­ga-like Tox­in A sub­unit. They go af­ter can­cer cells and al­so add anti­gens in­to the can­cer cells them­selves, help­ing prime the im­mune sys­tem to tar­get them for de­struc­tion. CEO and CSO Er­ic Po­ma says the com­pa­ny plans to “take im­me­di­ate steps to ac­cel­er­ate new site ac­ti­va­tion and pa­tient en­roll­ment in the TAK-169 study to gen­er­ate da­ta this year.” — Nicole De­Feud­is

Charles Riv­er part­ners with Va­lence to pro­vide AI dis­cov­ery plat­form

Big-name CD­MO Charles Riv­er Lab­o­ra­to­ries has swung an­oth­er deal, this time giv­ing its clients ac­cess to a new AI plat­form.

The Wilm­ing­ton, MA-based firm has teamed up with Va­lence Dis­cov­ery, the com­pa­nies an­nounced Tues­day, in an ef­fort to ex­pand Va­lence’s AI plat­form for mol­e­c­u­lar prop­er­ty pre­dic­tion, gen­er­a­tive chem­istry and mul­ti­pa­ra­me­ter op­ti­miza­tion. Fi­nan­cial terms of the deal were not dis­closed.

Va­lence says its plat­form en­ables the de­sign of small mol­e­cule drugs in new re­gions of chem­i­cal space, al­low­ing for rapid op­ti­miza­tion against po­ten­cy, se­lec­tiv­i­ty, safe­ty and phar­ma­col­o­gy cri­te­ria on a project-by-project ba­sis. Com­pa­nies tak­ing ad­van­tage of Charles Riv­er’s CD­MO of­fer­ings can opt in­to the Va­lence pro­gram.

Charles Riv­er has been busy to start off 2021, se­cur­ing a $104 mil­lion buy­out of Dis­tri­b­u­tion Bio in Jan­u­ary and Cog­nate in an $875 mil­lion ac­qui­si­tion in Feb­ru­ary. — Max Gel­man

With topline PhII da­ta in hand, Schol­ar Rock races to­ward piv­otal tri­al launch

Schol­ar Rock says it got the topline Phase II da­ta it was look­ing for with its spinal mus­cu­lar at­ro­phy (SMA) drug apite­gromab, and is rac­ing to launch a piv­otal tri­al by the end of this year.

The Phase II tri­al en­rolled pa­tients across three co­horts: pa­tients be­tween 5 and 21 years old with am­bu­la­to­ry type 3 SMA; pa­tients be­tween 5 and 21 years old with type 2 and non-am­bu­la­to­ry type 3 SMA who start­ed the treat­ment nusin­ersen when they were old­er than 5 years old; and pa­tients old­er than 2 years old with type 2 SMA who ini­ti­at­ed nusin­ersen younger than 5.

In the first co­hort, pa­tients re­ceived ei­ther apite­gromab ei­ther as a monother­a­py or in com­bo with nusin­ersen. A to­tal of 57% of pa­tients ob­served a main­te­nance or im­prove­ment on the Re­vised Ham­mer­smith Scale (RHS), and 22% of pa­tients achieved at least a 3-point in­crease in RHS score from base­line, ac­cord­ing to Schol­ar Rock.

In Co­hort 2, which ex­clud­ed one pa­tient who was al­so re­ceiv­ing an acetyl­cholinesterase in­hibitor and one who missed con­sec­u­tive dos­es due to Covid-19, the mean change from base­line on  Ham­mer­smith Func­tion­al Mo­tor Scale Ex­pand­ed was a 1.2-point im­prove­ment.

And in Co­hort 3, where pa­tients ei­ther re­ceived a low or high dose of apite­gromab in com­bi­na­tion with nusin­ersen, the mean change from base­line in HFMSE score was a 7.1-point and a 5.3-point im­prove­ment for the 20 mg/kg and 2 mg/kg dose arms, re­spec­tive­ly. The ma­jor­i­ty (59%) of pa­tients in Co­hort 3 achieved at least a 5-point in­crease in HFMSE and 35% of pa­tients achieved greater than a 10-point in­crease in HFMSE over base­line, ac­cord­ing to Schol­ar Rock. That analy­sis al­so ex­clud­ed three pa­tients who had missed dos­es due to Covid-19 chal­lenges.

Apite­gromab aims to boost mus­cle mass and strength in SMA pa­tients by in­hibit­ing the growth fac­tor myo­statin, which breaks down mus­cle mass in the body.

“These top-line 12-month da­ta pro­vide fur­ther sup­port to­wards es­tab­lish­ing apite­gromab as a po­ten­tial first mus­cle-di­rect­ed ther­a­py for pa­tients with SMA,” CMO Yung Chyung said in a state­ment. “The find­ings al­so of­fer im­por­tant in­sights in­to myo­statin bi­ol­o­gy and our sci­en­tif­ic ap­proach of tar­get­ing the la­tent forms of growth fac­tors. — Nicole De­Feud­is

Sor­ren­to Ther­a­peu­tics snaps up a late-stage TKI in ACEA Ther­a­peu­tics buy­out

Sor­ren­to Ther­a­peu­tics is buy­ing out ACEA Ther­a­peu­tics — and with it, a late-stage ty­ro­sine ki­nase in­hibitor, an ex­ten­sive li­brary of small mol­e­cules, and a 23-acre cGMP fa­cil­i­ty in Quzhou, Chi­na.

The com­pa­nies be­gan talk­ing about the merg­er back in Oc­to­ber, and of­fi­cial­ly signed the agree­ment on Mon­day.

With the deal, $SRNE is snap­ping up abiver­tinib, a small mol­e­cule TKI that was orig­i­nal­ly dis­cov­ered us­ing ACEA’s com­pound li­brary. The can­di­date has com­plet­ed a Phase III tri­al in NSCLC, and is cur­rent­ly in Phase II for Covid 19-in­duced res­pi­ra­to­ry com­pro­mise in the US and Brazil. It’s al­so get­ting AC0058, a next gen­er­a­tion BTK in­hibitor cur­rent­ly in a Phase Ib tri­al for lu­pus. — Nicole De­Feud­is

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

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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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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.

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.

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.

Philip Mor­ris gets share­hold­er back­ing in Vec­tura saga; Tarve­da strikes ex­clu­sive li­cens­ing agree­ment with Sci­Clone

Tobacco giant Philip Morris now has crossed the 50% threshold it needs for shareholder backing for its controversial, $1.5 billion takeover of asthma inhaler maker Vectura.

Investors have accepted a $2.28-per-share offer from the company behind Marlboro cigarettes, according to Sky News — and those investors represent nearly 75% of the company’s shares.

Acquiring the British inhaler maker is only a part of Philip Morris’ long term plan to develop “smoke-free” products, with a desire to ultimately become a “broader healthcare and wellness” company.

Skin tu­mors in mice force Pro­tag­o­nist to halt lead pro­gram, crush­ing stock

Protagonist Therapeutics just can’t catch a break.

Six months after the Newark, CA-based biotech unveiled grand plans to launch its lead candidate for blood disorders into a Phase III trial, the FDA has slapped the program with a clinical hold. The halt — which applies to all trials involving the candidate, rusfertide — comes after skin tumors were discovered in mice treated with the drug, according to Protagonist.

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