BioX­cel scores an­oth­er win with re­for­mu­lat­ed Pfiz­er seda­tive, this time in an Alzheimer's symp­tom

Less than six months af­ter re­port­ing pos­i­tive Phase III re­sults for its lead pro­gram in treat­ing ag­i­ta­tion re­lat­ed to schiz­o­phre­nia and bipo­lar dis­or­der, small AI biotech BioX­cel fol­lowed up Tues­day with top-line da­ta in an ear­ly stage tri­al for ag­i­ta­tion in de­men­tia and Alzheimer’s dis­ease.

The ex­per­i­men­tal drug, known as BX­CL501, met its pri­ma­ry and sec­ondary end­points in the high­er evalu­able dose of a 54-pa­tient Phase Ib/II tri­al, BioX­cel an­nounced, in­duc­ing a sta­tis­ti­cal­ly sig­nif­i­cant calm­ing ef­fect com­pared to place­bo with no se­vere or se­ri­ous side ef­fects. With the da­ta in hand, BioX­cel plans to meet with the FDA some­time in the first half of 2021 be­fore launch­ing a late-stage study some­time af­ter­wards.

BioX­cel $BTAI shares ticked up by as much as 10% in pre-mar­ket trad­ing Tues­day, but af­ter the open­ing bell were down about 7%.

BX­CL501 is a re­for­mu­la­tion of Pfiz­er’s 21-year-old se­da­tion drug Pre­cedex. BioX­cel cre­at­ed a dis­solv­ing film-based, sub­lin­gual ver­sion of the drug — think Lis­ter­ine strips, but placed un­der the tongue — that pa­tients ad­min­is­tered them­selves. It es­sen­tial­ly pro­duces a calm­ing ef­fect with­out knock­ing a pa­tient out and ac­ti­vates the al­pha-2 re­cep­tor, the path­way through which nor­ep­i­neph­rine, among oth­er neu­ro-chem­i­cals, trav­els.

Tues­day’s da­ta come from a dou­ble-blind­ed and ran­dom­ized study con­duct­ed en­tire­ly with­in as­sist­ed liv­ing fa­cil­i­ties. Pa­tients in the drug co­horts re­ceived ei­ther a 30 μg, 60 μg or 90 μg dose, though BioX­cel did not mea­sure ef­fi­ca­cy or safe­ty in the 90 μg arm due to high­er ex­po­sure lev­els. Six­teen pa­tients re­ceived the 30-μg dose, 20 took the 60-μg dose, four be­gan the 90-μg dose lev­el and 14 were ran­dom­ized to the place­bo group.

It’s the 60 μg lev­el where BX­CL501 dif­fer­en­ti­at­ed it­self from place­bo at a sig­nif­i­cant lev­el. The pro­gram hit on all three scales used to mea­sure change in ag­i­ta­tion from base­line, the PEC, PAS, and Mod-CMAI. For the PEC, the p-val­ue was p=0.0011, while the oth­er two p-val­ues reg­is­tered at p<0.0001.

The can­di­date al­so showed a rapid on­set, BioX­cel said, hit­ting sta­tis­ti­cal sig­nif­i­cance com­pared with place­bo in the PEC and PAS just one hour af­ter pa­tients took the film strips, with the com­pa­ny not­ing it didn’t mea­sure Mod-CMAI af­ter this time pe­ri­od. Calm­ing ef­fects at this dos­ing lev­el re­mained at sta­tis­ti­cal­ly sig­nif­i­cant lev­els through eight hours.

BX­CL501’s 30-μg dose did not hit sta­tis­ti­cal sig­nif­i­cance in any of the three scales, clock­ing in at p=0.0813 for PEC, p=0.0961 for PAS and p=0.0591 in the Mod-CMAI.

The most com­mon side ef­fect was som­no­lence, or drowsi­ness. Half of the 16 pa­tients in the 30-μg co­hort self-re­port­ed mild drowsi­ness, while 11 of 20 in­di­vid­u­als in the 60-μg co­hort did so. There was one case of mod­er­ate drowsi­ness in the 60-μg group as well.

In ad­di­tion, there were two cas­es of hy­poten­sion in the 60-μg co­hort, one mild and one mod­er­ate, as well as one case of mild dizzi­ness.

Jef­feries an­a­lyst Chris How­er­ton took a pos­i­tive view of the da­ta, writ­ing that the 60-μg dose ap­pears to “check all the box­es.” The safe­ty at this dose lev­el looked “clean,” though How­er­ton not­ed be­cause Pre­cedex is known to be more po­tent in el­der­ly pa­tients, he wouldn’t be sur­prised if BioX­cel al­so looked at a 45-μg dose in their piv­otal tri­al.

Vi­mal Mehta

The is­sue of a 45-μg dose al­so came up in a con­fer­ence call BioX­cel held Tues­day morn­ing with in­vestors. CEO Vi­mal Mehta said that al­though BioX­cel will like­ly pri­or­i­tize 60 μg for the Phase III giv­en Tues­day’s top-line re­sults, they aren’t rul­ing out al­so test­ing 45 μg.

Mehta al­so said on the call that he doesn’t an­tic­i­pate much dis­rup­tion in Phase III en­roll­ment re­lat­ed to the on­go­ing Covid-19 pan­dem­ic.

BioX­cel is one in a slate of biotechs that has raised mil­lions in re­cent years on the promise of us­ing ar­ti­fi­cial in­tel­li­gence to speed the drug de­vel­op­ment process. The com­pa­ny filed for a $69 mil­lion IPO in 2018 less than a year af­ter be­ing found­ed, and has aimed to use its tech to find com­pounds val­i­dat­ed to some de­gree by oth­er com­pa­nies and re­pur­pose them.

Back in Ju­ly, BioX­cel re­port­ed that in two near­ly 400-per­son Phase III tri­als for bipo­lar dis­or­der and schiz­o­phre­nia, the lead drug ef­fec­tive­ly calmed pa­tients’ ag­i­ta­tion.

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

Jacob Van Naarden (Eli Lilly)

Ex­clu­sives: Eli Lil­ly out to crash the megablock­buster PD-(L)1 par­ty with 'dis­rup­tive' pric­ing; re­veals can­cer biotech buy­out

It’s taken 7 years, but Eli Lilly is promising to finally start hammering the small and affluent PD-(L)1 club with a “disruptive” pricing strategy for their checkpoint therapy allied with China’s Innovent.

Lilly in-licensed global rights to sintilimab a year ago, building on the China alliance they have with Innovent. That cost the pharma giant $200 million in cash upfront, which they plan to capitalize on now with a long-awaited plan to bust up the high-price market in lung cancer and other cancers that have created a market worth tens of billions of dollars.

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So what hap­pened with No­var­tis' gene ther­a­py group? Here's your an­swer

Over the last couple of days it’s become clear that the gene therapy division at Novartis has quietly undergone a major reorganization. We learned on Monday that Dave Lennon, who had pursued a high-profile role as president of the unit with 1,500 people, had left the pharma giant to take over as CEO of a startup.

Like a lot of the majors, Novartis is an open highway for head hunters, or anyone looking to staff a startup. So that was news but not completely unexpected.

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Who are the women su­per­charg­ing bio­phar­ma R&D? Nom­i­nate them for this year's spe­cial re­port

The biotech industry has faced repeated calls to diversify its workforce — and in the last year, those calls got a lot louder. Though women account for just under half of all biotech employees around the world, they occupy very few places in C-suites, and even fewer make it to the helm.

Some companies are listening, according to a recent BIO survey which showed that this year’s companies were 2.5 times more likely to have a diversity and inclusion program compared to last year’s sample. But we still have a long way to go. Women represent just 31% of biotech executives, BIO reported. And those numbers are even more stark for women of color.

David Meek, new Mirati CEO (Marlene Awaad/Bloomberg via Getty Images)

Fresh off Fer­Gene's melt­down, David Meek takes over at Mi­rati with lead KRAS drug rac­ing to an ap­proval

In the insular world of biotech, a spectacular failure can sometimes stay on any executive’s record for a long time. But for David Meek, the man at the helm of FerGene’s recent implosion, two questionable exits made way for what could be an excellent rebound.

Meek, most recently FerGene’s CEO and a past head at Ipsen, has become CEO at Mirati Therapeutics, taking the reins from founding CEO Charles Baum, who will step over into the role of president and head of R&D, according to a release.

Volker Wagner (L) and Jeff Legos

As Bay­er, No­var­tis stack up their ra­dio­phar­ma­ceu­ti­cal da­ta at #ES­MO21, a key de­bate takes shape

Ten years ago, a small Norwegian biotech by the name of Algeta showed up at ESMO — then the European Multidisciplinary Cancer Conference 2011 — and declared that its Bayer-partnered targeted radionuclide therapy, radium-223 chloride, boosted the overall survival of castration-resistant prostate cancer patients with symptomatic bone metastases.

In a Phase III study dubbed ALSYMPCA, patients who were treated with radium-223 chloride lived a median of 14 months compared to 11.2 months. The FDA would stamp an approval on it based on those data two years later, after Bayer snapped up Algeta and christened the drug Xofigo.

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Mi­rati tri­umphs again in KRAS-mu­tat­ed lung can­cer with a close­ly watched FDA fil­ing now in the cards

After a busy weekend at #ESMO21, which included a big readout for its KRAS drug adagrasib in colon cancer, Mirati Therapeutics is ready to keep the pressure on competitor Amgen with lung cancer data that will undergird an upcoming filing.

In topline results from a Phase II cohort of its KRYSTAL-1 study, adagrasib posted a response rate of 43% in second-line-or-later patients with metastatic non-small cell lung cancer containing a KRAS-G12C mutation, Mirati said Monday.

When ef­fi­ca­cy is bor­der­line: FDA needs to get more con­sis­tent on close-call drug ap­provals, agency-fund­ed re­search finds

In the exceedingly rare instances in which clinical efficacy is the only barrier to a new drug’s approval, new FDA-funded research from FDA and Stanford found that the agency does not have a consistent standard for defining “substantial evidence” when flexible criteria are used for an approval.

The research comes as the FDA is at a crossroads with its expedited-review pathways. The accelerated approval pathway is under fire as the agency recently signed off on a controversial new Alzheimer’s drug, with little precedent to explain its decision. Meanwhile, top officials like Rick Pazdur have called for a major push to simplify and clarify all of the various expedited pathways, which have grown to be must-haves for sponsors of nearly every newly approved drug.

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Ted White, Verrica CEO

Ver­ri­ca hits an­oth­er bump in the road with CMO re­lat­ed let­ter from FDA

The FDA has rejected Verrica’s new drug application for VP-102 again, with the company pinning the CRL on problems at a CMO that it was partnered with, the company announced Monday.

The FDA didn’t raise issues that directly relate to the manufacturing of VP-102, the company said, but raised “general quality issues” at the CMO’s facility. There were also no clinical concerns, it said, or need to collect more data.