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

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

Graphic: Kathy Wong for Endpoints News

What kind of biotech start­up wins a $3B syn­di­cate, woos a gallery of mar­quee sci­en­tists and re­cruits GSK's Hal Bar­ron as CEO in a stun­ner? Let Rick Klaus­ner ex­plain

It started with a question about a lifetime’s dream on a walk with tech investor Yuri Milner.

At the beginning of the great pandemic, former NCI chief and inveterate biotech entrepreneur Rick Klausner and the Facebook billionaire would traipse Los Altos Hills in Silicon Valley Saturday mornings and talk about ideas.

Milner’s question on one of those mornings on foot: “What do you want to do?”

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Hal Barron, Endpoints UKBIO20 (Jeff Rumans)

'Al­tos was re­al­ly a once-in-a-life­time op­por­tu­ni­ty': Hal Bar­ron re­flects on his big move

By all accounts, Hal Barron had one of the best jobs in Big Pharma R&D. He made more than $11 million in 2020, once again reaping more than his boss, Emma Walmsley, who always championed him at every opportunity. And he oversaw a global R&D effort that struck a variety of big-dollar deals for oncology, neurodegeneration and more.

Sure, the critics never let up about what they saw as a rather uninspiring late-stage pipeline, where the rubber hits the road in the Big Pharma world’s hunt for the next big near-term blockbuster, but the in-house reviews were stellar. And Barron was firmly focused on bringing up the success rate in clinical trials, holding out for the big rewards of moving the dial from an average 10% success rate to 20%.

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Executive Director of the EMA Emer Cooke (AP Photo/Geert Vanden Wijngaert)

Eu­ro­pean Par­lia­ment signs off on strength­en­ing drug reg­u­la­tor's abil­i­ty to tack­le short­ages

The European Parliament on Thursday endorsed a plan to increase the powers of the European Medicines Agency, which will be better equipped to monitor and mitigate shortages of drugs and medical devices.

By a vote of 655 to 31, parliament signed off on a provisional agreement reached with the European Council from last October, in which the EMA will create two shortage steering groups (one for drugs, the other for devices), a new European Shortages Monitoring Platform to facilitate data collection and increase transparency, and on funding for the work of the steering groups, task force, working parties and expert panels that are to be established.

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FDA+ roundup: FDA's neu­ro­science deputy de­parts amid on­go­ing Aduhelm in­ves­ti­ga­tions; Califf on the ropes?

Amid increased scrutiny into the close ties between FDA and Biogen prior to the controversial accelerated approval of Aduhelm, the deputy director of the FDA’s office of neuroscience has called it quits after more than two decades at the agency.

Eric Bastings will now take over as VP of development strategy at Ionis Pharmaceuticals, the company said Wednesday, where he will provide senior clinical and regulatory leadership in support of Ionis’ pipeline.

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Sec­ondary patents prove to be key in biosim­i­lar block­ing strate­gies, re­searchers find

While the US biosimilars industry has generally been a disappointment since its inception, with FDA approving 33 biosimilars since 2015, just a fraction of those have immediately followed their approvals with launches. And more than a handful of biosimilars for two of the biggest blockbusters of all time — AbbVie’s Humira and Amgen’s Enbrel — remain approved by FDA but still have not launched because of legal settlements.

Hal Barron (GSK via YouTube)

GSK R&D chief Hal Bar­ron jumps ship to run a $3B biotech start­up, Tony Wood tapped to re­place him

In a stunning switch, GlaxoSmithKline put out word early Wednesday that R&D chief Hal Barron is exiting the company after 4 years — a relatively brief run for the man chosen by CEO Emma Walmsley in late 2017 to turn around the slow-footed pharma giant.

Barron is being replaced by Tony Wood, a close associate of Barron’s who’s taking one of the top jobs in Big Pharma R&D. He’ll be closer to home, though, for GSK. Barron has been running a UK and Philadelphia-based research organization from his perch in San Francisco.

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Troy Wilson, Kura CEO

FDA lifts par­tial hold on Ku­ra's Phase Ib AML pro­gram as biotech re­dou­bles mit­i­ga­tion ef­forts

Kura Oncology is clear to resume studies for its early-stage leukemia program after the FDA lifted a clinical hold Thursday afternoon.

Regulators had placed the hold on a Phase Ib study of KO-539, an experimental oral treatment for some genetic subsets of acute myeloid leukemia last November after a patient died while taking the drug. Kura expects to begin enrolling patients again imminently, CEO Troy Wilson told Endpoints News.

A Sen­ate bill wants to even an 'un­lev­el play­ing field' for do­mes­tic, for­eign in­spec­tion drop-ins amid back­log

Amid geopolitical tensions between the US and China, two Republican senators are calling for a bill that would aim to strike a balance on domestic and foreign inspection requirements from the FDA.

Sens. Mike Braun (R-IN) and Joni Ernst (R-IA) have penned a bill called the Creating Efficiency in Foreign Inspections Act. It contains a bit of rhetoric, highlighting “communist China” not once, but twice in the release, but states that the goal is to even the playing field between foreign and American manufacturers.

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