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

Qual­i­ty Con­trol in Cell and Gene Ther­a­py – What’s Re­al­ly at Stake?

In early 2021, Bluebird Bio was forced to suspend clinical trials of its gene therapy for sickle cell disease after two patients in the trial developed cancer. As company scientists rushed to assess whether there was any causal link between the therapy and the cancer cases, Bluebird’s stock value plummeted – as did those of multiple other biopharma companies developing similar therapies.

While investigations concluded that the gene therapy was unlikely to have caused cancer, investors and the public may be more skittish regarding the safety of gene and cell therapies after this episode. This recent example highlights how delicate the fields of cell and gene therapy remain today, even as they show great promise.

Law pro­fes­sors call for FDA to dis­close all safe­ty and ef­fi­ca­cy da­ta for drugs

Back in early 2018 when Scott Gottlieb led the FDA, there was a moment when the agency seemed poised to release redacted complete response letters and other previously undisclosed data. But that initiative never gained steam.

Now, a growing chorus of researchers are finding that a dearth of public data on clinical trials and pharmaceuticals means industry and the FDA cannot be held accountable, two law professors from Yale and New York University write in an article published Wednesday in the California Law Review.

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Novavax CEO Stanley Erck at the White House in 2020 (Andrew Harnik, AP Images)

As fears mount over J&J and As­traZeneca, No­vavax en­ters a shaky spot­light

As concerns rise around the J&J and AstraZeneca vaccines, global attention is increasingly turning to the little, 33-year-old, productless, bankruptcy-flirting biotech that could: Novavax.

In the now 16-month race to develop and deploy Covid-19 vaccines, Novavax has at times seemed like the pandemic’s most unsuspecting frontrunner and at times like an overhyped also-ran. Although they started the pandemic with only enough cash to last 6 months, they leveraged old connections and believers into $2 billion and emerged last summer with data experts said surpassed Pfizer and Moderna. They unveiled plans to quickly scale to 2 billion doses. Then they couldn’t even make enough material to run their US trial and watched four other companies beat them to the finish line.

FDA of­fers scathing re­view of Emer­gent plan­t's san­i­tary con­di­tions, em­ploy­ee train­ing af­ter halt­ing pro­duc­tion

The FDA wrapped up its inspection of Emergent’s troubled vaccine manufacturing plant in Baltimore on Tuesday, after halting production there on Monday. By Wednesday morning, the agency already released a series of scathing observations on the cross contamination, sanitary issues and lack of staff training that caused the contract manufacturer to dispose of millions of AstraZeneca and J&J vaccine doses.

Brad Bolzon (Versant)

Ver­sant pulls the wraps off of near­ly $1B in 3 new funds out to build the next fleet of biotech star­tups. And this new gen­er­a­tion is built for speed

Brad Bolzon has an apology to offer by way of introducing a set of 3 new funds that together pack a $950 million wallop in new biotech creation and growth.

“I want to apologize,” says the Versant chairman and managing partner, laughing a little in the intro, “that we don’t have anything fancy or flashy to tell you about our new fund. Same team, around the same amount of capital, same investment strategy. If it ain’t broke, don’t fix it.”

But then there’s the flip side, where everything has changed. Or at least speeded into a relative blur. Here’s Bolzon:

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Sen. Patty Murray (D-WA) (Graeme Sloan/Sipa USA/Sipa via AP Images)

Sen­a­tors to NIH: Do more to pro­tect US bio­med­ical re­search from for­eign in­flu­ence

Although Thursday’s Senate health committee hearing was focused on how foreign countries and adversaries might be trying to steal or negatively influence biomedical research in the US, the only country mentioned by the senators and expert witnesses was China.

Committee chair Patty Murray (D-WA) made clear in her opening remarks that the US cannot “let the few instances of bad actors” overshadow the hard work of the many immigrant researchers in the US, many of which have won Nobel prizes for their work. But she also said, “There is more the NIH can be doing here.”

LLS backs 5 new can­cer drug projects with up to $50M; Trodelvy con­tin­ues to im­press with more TNBC da­ta

The Leukemia and Lymphoma Society has tapped 5 new early-stage projects to back with up to $10 million each in fresh investments. The 5 biotechs are:

— Caribou, headed by Rachel Haurwitz and co-founded by Jennifer Doudna, is working on next-gen, off-the-shelf CAR-Ts to replace the patient-derived cells now in use.

— The LLS supported NexImmune’s IPO, helping fund its work on nanoparticles that can gin up an immune response directed at cancer cells. The biotech has 2 projects now in Phase I trials.

Jenny Rooke (Genoa Ventures)

Ear­ly Zymer­gen in­vestor Jen­ny Rooke re­flects on 'chimeras' in biotech, what it takes to spot a $500M gem

When Jenny Rooke first heard of Zymergen back in 2014, she knew she was looking at something different and exciting. The Emeryville, CA biotech held the promise of blending biology and technology to solve a huge unmet need for cost-effective chemicals — of all things — and a stellar founding team to boot.

But back then, West Coast venture capitalists didn’t see in Zymergen the one thing they were looking for in a winning biotech: therapeutic potential. Rooke, however, saw an opportunity and made her bets. Seven years later, that bet is paying off in a big way.

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Saurabh Saha at Endpoints News' #BIO19

On the heels of $250M launch, Centes­sa barges ahead with an IPO to fu­el its 10-in-1 Medicxi pipeline

Francesco De Rubertis made no secret of IPO plans for Centessa, his 10-in-1 legacy play. Barely two months later, the S-1 is in.

The hot-off-the-press filing depicts the same grand vision that the longtime VC touted when he did the rounds in February: Take the asset-centric mindset that he’s been preaching at Medicxi over the years, and roll up a bunch of biotech upstarts, with unrelated risk profiles, into 1 pharma company that can carry on the development at scale.