Lit­tle Tetra is prep­ping a PhII Alzheimer’s study. In fact, they just got $40M to fund it

Af­ter all the no­to­ri­ous late-stage fail­ures in Alzheimer’s over the past year, you could say it’s con­sid­er­ably hard­er to win peo­ple over to a new mech­a­nism of ac­tion for the mem­o­ry-wast­ing plague.

But Mark Gur­ney isn’t let­ting a lit­tle neg­a­tiv­i­ty stop him now.

The CEO of Tetra Dis­cov­ery Part­ners in Grand Rapids, MI, be­lieves he and his 11-mem­ber team can ac­com­plish what the ma­jor league play­ers with far big­ger op­er­a­tions and a whole lot more mon­ey have failed at. And to­day he has an ex­tra $40 mil­lion in hard cash to help pay for the mid-stage tri­al that’s need­ed to help prove whether it works in pa­tients.

Sh­iono­gi is hand­ing over a very mod­est $5 mil­lion up­front and a more sub­stan­tial $35 mil­lion for an eq­ui­ty stake in Tetra in ex­change for a re­gion­al set of Asian rights to BPN14770, a PDE4D al­losteric in­hibitor for Alzheimer’s and Frag­ile X dis­ease. Aside from their shot at an his­toric break­through against some of the tough­est odds in R&D, Sh­iono­gi — which has a long­stand­ing in­ter­est in neu­ronal R&D — is al­so on the hook for $120 mil­lion in mile­stones plus roy­al­ties.


“This is a non-amy­loid mech­a­nism, not pre­vi­ous­ly ex­plored in hu­mans,” Gur­ney tells me ear­ly on in our con­ver­sa­tion, putting some quick dis­tance be­tween his work and the land­mark fail­ures that have cast doubt on the amy­loid the­o­ry.

The work is based on ob­ser­va­tions of cog­ni­tive re­silience in pa­tients who have clas­sic bio­mark­ers for the dis­ease — amy­loid and tau — with­out demon­strat­ing any symp­toms. 

By se­lec­tive­ly in­hibit­ing PDE4D — which falls un­der a well-known mech­a­nism of ac­tion — Tetra will set out to prove in a loom­ing Phase II that their ap­proach can bol­ster neu­ronal con­nec­tions, pro­tect­ing them from dam­age and im­prov­ing the prospects of ear­ly-stage pa­tients.

Gur­ney be­lieves their drug can im­prove symp­toms of the dis­ease over a 3-month span, but even a sig­nif­i­cant im­prove­ment in the de­cline of pa­tients — or as much as a flatlin­ing on de­te­ri­o­ra­tion — would be greet­ed with con­sid­er­able en­thu­si­asm.

He got here with an aw­ful lot of help from grants and con­tracts with the NIH, which pro­vid­ed the li­on’s share of the $30 mil­lion they’ve need­ed so far. There was al­so $7.3 mil­lion in A-round cash by late 2016 from Apjohn Group, Grand An­gels, Dol­by Fam­i­ly Ven­tures and the Alzheimer’s Drug Dis­cov­ery Foun­da­tion.

Gur­ney was en­gaged ear­ly in the dis­cov­ery of be­ta-sec­re­tase, a field in amy­loid re­search that in­spired huge in­vest­ments and colos­sal fail­ures. He al­so was a se­nior in­ves­ti­ga­tor at de­CODE. Scott Reines, the CMO, has held se­nior posts in neu­ro­sciences R&D at J&J and Mer­ck.

There are PDE4s on the mar­ket as an­ti-in­flam­ma­to­ries, of course, car­ry­ing no­table names like apre­mal­ist. But the broad­band in­hi­bi­tion of PDE4 has al­so been linked with tox­i­c­i­ty. Tetra’s goal was to find a more se­lec­tive ap­proach in neu­ro­sciences — where in­flam­ma­tion it­self is a grow­ing tar­get — while al­so re­serv­ing a sep­a­rate pro­gram (PDE4B)that is specif­i­cal­ly a next-gen ap­proach to mega-block­buster in­flam­ma­to­ry dis­eases like pso­ri­a­sis.

That’s al­so no easy task.

We’ve been here with oth­er new drugs of course, many times; wait­ing it out through a mid-stage or piv­otal study to demon­strate whether a 5HT6 can guard cog­ni­tion — on­ly to watch one pro­gram af­ter an­oth­er go down in flames un­til the tar­get it­self is wiped off the R&D map. Ax­o­vant’s crown­ing fail­ure af­ter re­peat­ed ex­pres­sions of op­ti­mism like­ly put the ki­bosh on that one.

Gur­ney is used to be­ing greet­ed with skep­ti­cism. That goes with the ter­ri­to­ry for any­one work­ing in Alzheimer’s R&D to­day.

Now that he has the deal he need­ed to do the Alzheimer’s study, which will fol­low a crit­i­cal Phase II in Frag­ile X, he can en­dure the head­winds bet­ter. Af­ter­wards, if he’s proved right, there should be no prob­lem find­ing a part­ner for a piv­otal tri­al in Azheimer’s. Frag­ile X is the kind of rare in­di­ca­tion they can go it alone on. 

But the lit­tle team has some very big hur­dles to clear first.

Con­quer­ing a silent killer: HDV and Eiger Bio­Phar­ma­ceu­ti­cals

Hepatitis delta, also known as hepatitis D, is a liver infection caused by the hepatitis delta virus (HDV) that results in the most severe form of human viral hepatitis for which there is no approved therapy.

HDV is a single-stranded, circular RNA virus that requires the envelope protein (HBsAg) of the hepatitis B virus (HBV) for its own assembly. As a result, hepatitis delta virus (HDV) infection occurs only as a co-infection in individuals infected with HBV. However, HDV/HBV co-infections lead to more serious liver disease than HBV infection alone. HDV is associated with faster progression to liver fibrosis (progressing to cirrhosis in about 80% of individuals in 5-10 years), increased risk of liver cancer, and early decompensated cirrhosis and liver failure.
HDV is the most severe form of viral hepatitis with no approved treatment.
Approved nucleos(t)ide treatments for HBV only suppress HBV DNA, do not appreciably impact HBsAg and have no impact on HDV. Investigational agents in development for HBV target multiple new mechanisms. Aspirations are high, but a functional cure for HBV has not been achieved nor is one anticipated in the forseeable future. Without clearance of HBsAg, anti-HBV investigational treatments are not expected to impact the deadly course of HDV infection anytime soon.

Am­gen chops 172 more staffers in R&D, op­er­a­tions and sales amid neu­ro­science ex­it, rev­enue down­turn

Neuroscience wasn’t the only unit that’s being hit by a reorganization underway at Amgen. As well as axing 149 employees in its Cambridge office, the company has disclosed that 172 others nationwide, including some from its Thousand Oaks, CA headquarters, are being let go.

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Ahead of strate­gic up­date, new Sanofi CEO mulls op­tions for con­sumer health­care arm — re­ports

Big pharma has made moves to sharpen its focus on developing new medicines, while slow-growing consumer health divisions fall by the wayside. Looks like another large drugmaker is considering a similar move. On Thursday, reports citing sources indicated that Sanofi is reportedly mulling a joint venture, sale, or a public listing of its consumer health arm.

The French group is in discussions for options that could value the division at $30 billion, Bloomberg and Reuters reported, citing sources familiar with the matter.

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The triple crown in biotech: An all-or-noth­ing bet on an FDA ap­proval of 3 drugs over 16 months starts to­day

Bristol-Myers Squibb’s $74 billion Celgene deal closed as expected Wednesday evening. And now a new clock has begun to tick down for Celgene shareholders who came away from the deal with CVRs — contingent value rights — worth $9 or nothing. Those CVRs start trading today as $BMYRT.

The new deadline they have is the end of March 2021, a little more than 16 months from now, when Bristol-Myers will need to gain approvals on 3 late-stage drugs it’s picking up in the buyout: Ozanimod and liso-cel (JCAR017) are due up at the end of 2020, with bb2121 deadlined at the end of Q1 in 2021.

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Genap­sys fi­nal­ly un­veils vaunt­ed se­quencer, but can it dent Il­lu­mi­na?

Hesaam Esfandyarpour holds what looks like a mini-cooler up to the computer screen in his California office.

Esfandyarpour is in his late-30s, with crows feet creeping up against a youthful face. He wears a gray polo and the device in his hand — with its hard plastic-looking shell, blue-and-white pattern, and a white plastic paddle resembling a handle jutting out the front — might contain diced strawberries and peanut-butter sandwiches to meet mom and the kids at a SoCal park. Instead, Esfandyarpour tells me it’s going to change medicine and biopharma research.

Brii Bio backs in­fec­tious dis­ease start­up while ink­ing deal for its lead TB drug, dou­bling down on an­tibi­otics

Almost two years after leaving GSK to launch Brii Bio with a whopping $260 million in funding, Zhi Hong is seeing the trans-Pacific infectious disease specialist he set out to build take shape.

“Our pipeline is coming together,” he told Endpoints News, with 12 partnered assets plus some internal programs.

As its latest partner, AN2 Therapeutics, comes into the limelight for the first time with a $12 million seed round, so is Brii’s plans in the antibiotics space. Brii has obtained China rights to AN2’s antibacterial targeting mycobacterium tuberculosis for multi-drug resistant TB, which it says is in the clinical stage.

UP­DAT­ED: Make that 2 ap­proved RNAi drugs at Al­ny­lam af­ter the FDA of­fers a speedy OK on ul­tra-rare dis­ease drug

Seventeen years into the game, Alnylam’s pivot into commercial operations is picking up speed.
The bellwether biotech $ALNY has nabbed their second FDA OK for an RNAi drug, this time for givosiran, the only therapy now approved for acute hepatic porphyria. This second approval came months ahead of the February deadline — even after winning priority review following their ‘breakthrough’ title earlier.
AHP is an extremely rare disease, with some 3,000 patients in Europe and the US, not all diagnosed, and analysts have projected peak revenue of $600 million to $700 million a year. The drug will be sold as Givlaari.

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David Ricks. Eli Lilly

Eli Lil­ly touts $400M man­u­fac­tur­ing ex­pan­sion, 100 new jobs to much fan­fare in In­di­anapo­lis — even though it's been chop­ping staff

Eli Lilly is pouring in $400 million to beef up manufacturing facilities at its home base of Indianapolis. The investment, which was lauded by the city’s mayor, is expected to create 100 new jobs.

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No­var­tis, Bay­er, Long­wood back ge­nomics start­up to speed search for im­munother­a­py tar­gets

Nearly a century passed between the first proto-immunotherapy attempts in cancer — crude and obscure but nonetheless with some scientific basis — and Jim Allison’s first T cell paper. Thirty-plus years flipped between the discovery of CTLA-4 as an off-switch and the approval of Yervoy. Twenty-two rolled between PD-1’s isolation and Opdiva and Keytruda. 

Longwood co-founder Lea Hachigian is betting she can hasten that. It’s a bet on newly established single-cell genomic analysis tech and the ability to crunch endless troves of data at a rate few others can, and investors including Leaps by Bayer and Novartis Venture Fund just put $39 million behind it. They call it Immunitas.