Neu­ro­science biotech led by for­mer Pfiz­er crew wins $17M to tar­get tox­ic tau

With big phar­ma play­ers march­ing out of the dis­as­ter-prone field of neu­ro­sciences one-by-one, small biotechs are pick­ing up the tab.

Cam­bridge, Mass­a­chu­setts-based Pin­teon Ther­a­peu­tics is the lat­est ini­tia­tive. The com­pa­ny, found­ed in 2014, is de­vel­op­ing a tau an­ti­body to ad­dress an ar­ray of neu­rode­gen­er­a­tive dis­or­ders. On Thurs­day, it un­veiled $17 mil­lion in se­ries A fund­ing from Morn­ing­side Ven­tures.

Its ex­per­i­men­tal drug PNT001 tar­gets a tox­ic con­for­ma­tion of tau, called cis-pT231 tau, which en­cour­ages the ab­nor­mal ag­gre­ga­tion of tau pro­teins in neu­rons. The ac­cu­mu­lat­ed tau cre­ates neu­rofib­ril­lary tan­gles, which cause neu­ronal death, thwart com­mu­ni­ca­tion and im­pair mem­o­ry and learn­ing. 

The biotech is hop­ing the drug could po­ten­tial­ly tack­le tau-dri­ven dis­eases, such as chron­ic trau­mat­ic en­cephalopa­thy, trau­mat­ic brain in­jury, pro­gres­sive supranu­clear pal­sy and maybe even Alzheimer’s.

The quest for treat­ments to pre­vent and treat Alzheimer’s, the most com­mon form of de­men­tia, is lit­tered with fail­ure. For long, re­searchers were par­tial to the amy­loid hy­poth­e­sis, which sug­gests that tar­get­ing be­ta-amy­loid plaques that col­lect be­tween neu­rons and dis­rupt cell func­tion could make a ma­te­r­i­al im­pact on the pro­gres­sion of the dis­ease.

How­ev­er, set­back af­ter set­back seem­ing­ly put the nail in the amy­loid cof­fin ear­li­er this year af­ter Bio­gen, one of the last flag bear­ers of the the­o­ry ac­knowl­edged their fail­ure. But in a dra­mat­ic twist last week, Bio­gen in­di­cat­ed it had res­ur­rect­ed its faith in the amy­loid the­o­ry, at least in a sub­set of pa­tients, fol­low­ing a pro­tract­ed pe­ri­od of da­ta min­ing.

Mean­while, re­searchers are al­so look­ing at tau. Ini­tial­ly, an­ti-tau ther­a­pies were fo­cused on in­hibit­ing ki­nas­es or tau ag­gre­ga­tion, or on sta­bi­liz­ing mi­cro­tubules (which help guide nu­tri­ents and mol­e­cules from the cell body to the ax­on and den­drites) — but most of these ap­proach­es have been aban­doned due to tox­i­c­i­ty or a lack of ef­fi­ca­cy, or both. Sci­en­tists are now look­ing at de­vel­op­ing tau-tar­get­ing im­munother­a­pies.

Lar­ry Alt­stiel

“If we talk about the de­vel­op­ment of Alzheimer’s dis­ease, ob­vi­ous­ly this is a chal­lenge. To call it a chal­lenge is an un­der­state­ment, to be sure,” said Pin­teon’s chief med­ical of­fi­cer Lar­ry Alt­stiel, who has for­mer­ly worked in the neu­ro­sciences di­vi­sions at Pfiz­er and Eli Lil­ly.

“One of the rea­sons that we’re in­ter­est­ed in tau is that we know that the cog­ni­tive de­cline in Alzheimer’s dis­ease is di­rect­ly re­lat­ed to the ex­tent of tau de­po­si­tion.”

Pin­teon has on­ly just kicked off its phase I study in healthy vol­un­teers, which is de­signed to test the safe­ty, tol­er­a­bil­i­ty, and phar­ma­co­ki­net­ics of PNT001. There will be an­oth­er set of ear­ly-stage as­cend­ing dose stud­ies in one or more pa­tient pop­u­la­tions to de­ter­mine a dose where the cere­bral spinal flu­id con­cen­tra­tion (CSF) of the drug could be con­sid­ered po­ten­tial­ly ef­fec­tive.

“When we get the ap­pro­pri­ate CSF con­cen­tra­tion from our phase one stud­ies we’ll move in­to a (tau-dri­ven) dis­ease pop­u­la­tion and the choice of that pop­u­la­tion is re­al­ly go­ing to be da­ta-dri­ven,” Alt­stiel said.

Mar­tin Jef­son

The pro­ceeds from the se­ries A have large­ly been uti­lized in pre­clin­i­cal de­vel­op­ment of the com­pound, Pin­teon chief Mar­tin Jef­son, who led CNS re­search at Pfiz­er, not­ed in an in­ter­view with End­points News.

“We’re go­ing to need ad­di­tion­al funds and we’re be­gin­ning to now ap­proach both Morn­ing­side as well as ad­di­tion­al in­vestors to put to­geth­er a fol­low on round to sup­port the com­ple­tion of phase I stud­ies and prepa­ra­tion for phase II.”

Three months af­ter Am­gen fold­ed up a late-stage Alzheimer’s study of their failed No­var­tis-part­nered BACE in­hibitor, the large drug­mak­er on Wednes­day an­nounced its ex­it from neu­ro­sciences. Pfiz­er de­sert­ed the field ear­ly last year, spin­ning out a start­up, Cerev­el, which Bain elect­ed to fund.

Com­mu­ni­cat­ing the val­ue of pre­ci­sion med­i­cine

By Natasha Cowan, Content Marketing Manager at Blue Latitude Health.
Many stakeholders are confused by novel precision medicines, including patients and healthcare professionals. So, how can industry help them to navigate this complexity?

Precision medicine represents a new paradigm in healthcare. It embodies the shift from treating many patients with the same therapy, to having the tools to identify the best treatment for every patient.

Spe­cial re­port: Twen­ty ex­tra­or­di­nary women in bio­phar­ma R&D who worked their way to the top

What differentiates a woman leader in biopharma R&D from a man?

Not much, except there are fewer of them in senior posts. Data suggest women are not more risk-averse, family-oriented or less confident than their male counterparts — indeed the differences between the two sexes are negligible. But a glance at the top R&D positions in Big Pharma leaves little doubt that upward migration in the executive ranks of biopharma R&D is tough.

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The lat­est Cin­derel­la sto­ry in on­col­o­gy ends with a sud­den rout as up­dat­ed da­ta dis­play spooks in­vestors

NextCure’s turn as the Cinderella of cancer-focused biotechs was short-lived.
Just a few days after its shares $NXTC zoomed up more than 250% on some very early stage results in a SITC abstract, a more complete analysis over the weekend spiked the hype and left investors in high dudgeon as the stock price collapsed back towards earth Monday.
The focus at NextCure is centered on NC318, an antibody that is intended to shut down the immunosuppressive Siglec-15 — or S-15 — target. After adding a small group of patients to the readout, investigators circled 2 clinical responses, a complete and partial response, along with 4 stable disease cases in non-small cell lung cancer.

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Te­va spin­out rais­es $85M in IPO; No­var­tis beefs up gener­ics unit with $440M deal

→ After Teva spinout 89bio recently announced that its IPO was being held up, the company is back in the game offering 5,304,687 shares at a price of $16 per share. The company has raised $84.9 million IPO in gross proceeds and will be listed under the ticker symbol $ETNB. BofA Securities, SVB Leerink and RBC Capital Markets are the joint book-running managers for the offering. Oppenheimer & Co is the co-manager for the offering.
→ Looking to amp up its presence in Japan’s hospitals, Novartis has struck a deal to buy out Aspen’s portfolio of generics in the world’s third largest healthcare market. The pharma giant is paying $440 million for Aspen’s Japanese subsidiary.
→ Novartis said tropifexor, a non-bile acid FXR agonist, has scored on several key biomarkers of NASH in a Phase IIb trial, including reductions in hepatic fat, alanine aminotransferase and body weight compared to a placebo at 12 weeks.

Break­through sta­tus and promise of a speedy re­view ar­rives for Op­di­vo/Yer­voy com­bi­na­tion as Bris­tol-My­ers bites at Bay­er

Its frontline and single-agent aspirations have been set back, but Bristol-Myers Squibb just took a big step forward in its efforts to apply its checkpoint inhibitor Opdivo to liver cancer. The FDA has granted breakthrough status and priority review to a combination, second-line treatment.

The designation is for Opdivo (nivolumab) in combination with Yervoy (ipilimumab),  for treating advanced hepatocellular carcinoma (HCC), the most common form of liver cancer. The PD-L1 drug was already approved as a single-agent, second-line treatment for HCC. A PDUFA date was set for March 10, 2020 — just 4 months from now.

Third time un­lucky: Lipocine's lat­est quest to mar­ket their oral testos­terone drug snubbed again by FDA

Lipocine’s latest attempt at securing approval for its oral testosterone drug has fizzled yet again.

The Utah-based drug developer on Monday said the FDA has spurned its marketing application, indicating that some efficacy data on the drug, Tlando, was not up to scratch to treat male hypogonadism, a condition characterized by low production of the hormone testosterone, which is responsible for maintaining muscle bulk, bone growth, and sexual function.

UP­DAT­ED: De­cry­ing 'ar­bi­trary and capri­cious' ac­tion, Re­genxBio sues FDA over clin­i­cal holds on gene ther­a­py

When RegenxBio disclosed that the FDA had placed a partial clinical hold on one of its lead gene therapies, execs outlined several customary next steps: continuing assessment and monitoring, delaying a related IND filing, and working with the FDA to address the matter.

As it turned out, they were planning something much less mundane. Two days after announcing the hold in its Q3 update, RegenxBio filed a lawsuit seeking to set it aside, the FDA Law Blog noted.

Roche's SMA chal­lenge to Bio­gen's Spin­raza fran­chise looms larg­er with piv­otal win

Roche has just landed a crucial advance in scoring a come-from-behind win on the spinal muscular atrophy field, giving Novartis and Biogen a run for their money.

The update was brief, but Roche said risdiplam hit the primary endpoint in the placebo-controlled pivotal SUNFISH trial, meeting the threshold for change from baseline in the Motor Function Measure 32 (MFM-32) scale after one year of treatment. The results, which is the second, confirmatory portion of a two-part study, involved 180 patients with type 2 or 3 spinal muscular atrophy between 2 and 25 years old.

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Roche steers Gazy­va in­to a new PhI­II pro­gram af­ter com­bo shows promise in lu­pus nephri­tis study

Roche is working on putting together a late-stage study for its monoclonal antibody Gazyva in patients with severe kidney disease associated with lupus after a combination approach helped patients in a mid-stage study.

The 125-patient NOBILITY trial evaluated Gazyva, combined with standard-of-care treatment mycophenolate mofetil or mycophenolic acid and corticosteroids, versus standard treatment alone. The combo met the main goal of inducing a statistically superior complete renal response (CRR) of 40% at week 76, versus 18% in patients given standard treatment, Roche said.