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.

BiTE® Plat­form and the Evo­lu­tion To­ward Off-The-Shelf Im­muno-On­col­o­gy Ap­proach­es

Despite rapid advances in the field of immuno-oncology that have transformed the cancer treatment landscape, many cancer patients are still left behind.1,2 Not every person has access to innovative therapies designed specifically to treat his or her disease. Many currently available immuno-oncology-based approaches and chemotherapies have brought long-term benefits to some patients — but many patients still need other therapeutic options.3

President Donald Trump (left) and Moncef Slaoui, head of Operation Warp Speed (Alex Brandon, AP Images)

UP­DAT­ED: White House names fi­nal­ists for Op­er­a­tion Warp Speed — with 5 ex­pect­ed names and one no­table omis­sion

A month after word first broke of the Trump Administration’s plan to rapidly accelerate the development and production of a Covid-19 vaccine, the White House has selected the five vaccine candidates they consider most likely to succeed, The New York Times reported.

Most of the names in the plan, known as Operation Warp Speed, will come as little surprise to those who have watched the last four months of vaccine developments: Moderna, which was the first vaccine to reach humans and is now the furthest along of any US effort; J&J, which has not gone into trials but received around $500 million in funding from BARDA earlier this year; the joint AstraZeneca-Oxford venture which was granted $1.2 billion from BARDA two weeks ago; Pfizer, which has been working with the mRNA biotech BioNTech; and Merck, which just entered the race and expects to put their two vaccine candidates into humans later this year.

Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

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Leen Kawas, Athira CEO (Athira)

Can a small biotech suc­cess­ful­ly tack­le an Ever­est climb like Alzheimer’s? Athi­ra has $85M and some in­flu­en­tial back­ers ready to give it a shot

There haven’t been a lot of big venture rounds for biotech companies looking to run a Phase II study in Alzheimer’s.

The field has been a disaster over the past decade. Amyloid didn’t pan out as a target — going down in a litany of Phase III failures — and is now making its last stand at Biogen. Tau is a comer, but when you look around and all you see is destruction, the idea of backing a startup trying to find complex cocktails to swing the course of this devilishly complicated memory-wasting disease would daunt the pluckiest investors.

GSK presents case to ex­pand use of its lu­pus drug in pa­tients with kid­ney dis­ease, but the field is evolv­ing. How long will the mo­nop­oly last?

In 2011, GlaxoSmithKline’s Benlysta became the first biologic to win approval for lupus patients. Nine years on, the British drugmaker has unveiled detailed positive results from a study testing the drug in lupus patients with associated kidney disease — a post-marketing requirement from the initial FDA approval.

Lupus is a drug developer’s nightmare. In the last six decades, there has been just one FDA approval (Benlysta), with the field resembling a graveyard in recent years with a string of failures including UCB and Biogen’s late-stage flop, as well as defeats in Xencor and Sanofi’s programs. One of the main reasons the success has eluded researchers is because lupus, akin to cancer, is not just one disease — it really is a disease of many diseases, noted Al Roy, executive director of Lupus Clinical Investigators Network, an initiative of New York-based Lupus Research Alliance that claims it is the world’s leading private funder of lupus research, in an interview.

Covid-19 roundup: Mod­er­na read­ies to en­ter PhI­II in Ju­ly, As­traZeneca not far be­hind; EU ready to ne­go­ti­ate vac­cine ac­cess with $2.7B fund

Moderna may soon add another first to the Covid-19 vaccine race.

In March, the mRNA biotech was the first company to put a Covid-19 vaccine into humans. Next month, they may become the first company to put their vaccine into the large, late-stage trials that are needed to prove whether the vaccine is effective.

In an interview with JAMA editor Howard Bauchner, NIAID chief Anthony Fauci said that a 30,000-person, Phase III trial for Moderna’s vaccine could start in July. The news comes a week after Moderna began a Phase II study that will enroll several hundred people.

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José Basel­ga finds promise in new class of RNA-mod­i­fy­ing can­cer tar­gets, lock­ing in 3 pre­clin­i­cal pro­grams with $55M

Having dived early into some of the RNA breakthroughs of the last decades — betting on Moderna’s mRNA tech and teaming up with Silence on the siRNA front — AstraZeneca is jumping into a new arena: going after proteins that modify RNA.

Their partner of choice is Accent Therapeutics, which is receiving $55 million in upfront payment to steer a selected preclinical program through to the end of Phase I. After AstraZeneca takes over, the Lexington, MA-based startup has the option to co-develop and co-commercialize in the US — and collect up to $1.1 billion in milestones in the long run. The deal also covers two other potential drug candidates.

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Pfiz­er’s Doug Gior­dano has $500M — and some ad­vice — to of­fer a cer­tain breed of 'break­through' biotech

So let’s say you’re running a cutting-edge, clinical-stage biotech, probably public, but not necessarily so, which could see some big advantages teaming up with some marquee researchers, picking up say $50 million to $75 million dollars in a non-threatening minority equity investment that could take you to the next level.

Doug Giordano might have some thoughts on how that could work out.

The SVP of business development at the pharma giant has helped forge a new fund called the Pfizer Breakthrough Growth Initiative. And he has $500 million of Pfizer’s money to put behind 7 to 10 — or so — biotech stocks that fit that general description.

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Joseph Kim, Inovio CEO (Andrew Harnik, AP Images)

Caught in a stand­off with its con­tract man­u­fac­tur­er over Covid-19 vac­cine, In­ovio files suit in an at­tempt to break free while ri­vals race ahead

Inovio was one of the first vaccine developers to snag attention for a jab that their execs said promised to end the Covid-19 pandemic. Using their own unique DNA tech, CEO Joseph Kim said it took just 3 hours to work it out.

But while rivals are racing to the finish line with ambitious plans to make vast quantities of their vaccines with billions of dollars of deals, Inovio is still stuck at the starting line on manufacturing.