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.

Daphne Koller, Getty

Bris­tol My­er­s' Richard Har­g­reaves pays $70M to launch a neu­rode­gen­er­a­tion al­liance with a star play­er in the ma­chine learn­ing world

Bristol Myers Squibb is turning to one of the star upstarts in the machine learning world to go back to the drawing board and come up with the disease models needed to find drugs that can work against two of the toughest targets in the neuro world.

Daphne Koller’s well-funded insitro is getting $70 million in cash and near-term milestones to use their machine learning platform to create induced pluripotent stem cell-derived disease models for ALS and frontotemporal dementia.

Eli Lilly CEO David Ricks at the Rose Garden, May 26, 2020 (Evan Vucci/AP Images)

Eli Lil­ly lines up a block­buster deal for Covid-19 an­ti­body, right af­ter it failed a NI­AID tri­al

Two days after Eli Lilly conceded that its antibody bamlanivimab was a flop in hospitalized Covid-19 patients, the US government is preparing to make it a blockbuster.

The pharma giant reported early Wednesday that it struck a deal to supply the feds with 300,000 vials of the drug at a cost of $375 million — once it gets an EUA stamp from the FDA. And once that 2-month supply deal is done, the government has an option on another 650,000 doses on the same terms — which could potentially add another $812 million.

Eli Lilly CEO David Ricks (Evan Vucci/AP Images)

A P val­ue of 0.38? NE­JM re­sults raise new ques­tions for Eli Lil­ly's vaunt­ed Covid an­ti­body

Generally, a P value of 0.38 means your drug failed and by a fair margin. Depending on the company, the compound and the trial, it might mean the end of the program. It could trigger layoffs.

For Eli Lilly, though, it was part of the key endpoint on a trial that landed them a $1.2 billion deal with the US government to supply up to nearly 1 million Covid-19 antibodies.

So what does one make of that? Was the endpoint not so important, as Lilly maintains? Or did the US government promise a princely sum for a pedestrian drug?

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Noubar Afeyan, Flagship founder and CEO (Victor Boyko/Getty Images)

UP­DAT­ED: Flag­ship launch­es Sen­da Bio­sciences with $88M in back­ing, look­ing to pi­o­neer the field of 'In­ter­sys­tems Bi­ol­o­gy'

Flagship Pioneering has a fresh company out this week, one that aims to lay the groundwork for a whole new discipline.

Senda Biosciences launched Wednesday with $88 million in Flagship cash. The goal? Gain insights into the molecular connections between people and coevolved nonhuman species like plants and bacteria, paving the way for “Intersystems Biology.”

Guillaume Pfefer has been tapped to run the show, a 25-year biotech veteran who comes from GSK after leading the development of the company’s shingles vaccine.

Ar­cus and As­traZeneca part­ner on a high stakes an­ti-TIG­IT/PD-L1 PhI­II can­cer study, look­ing to im­prove on a stan­dard of care

For AstraZeneca, the PACIFIC trial in Stage III non-small cell lung cancer remains one of the big triumphs for AstraZeneca’s oncology R&D group. It not only made their PD-L1 Imfinzi a franchise player with a solid advance in a large niche of the lung cancer market, the study — which continues to offer data on the long-range efficacy of their drug — also helped salve the vicious sting of the failure of the CTLA-4 combo in the MYSTIC study.

No­var­tis buys a new gene ther­a­py for vi­sion loss, and this is one pre­clin­i­cal ven­ture that did­n't come cheap

Cyrus Mozayeni got excited when he began to explore the academic work of Ehud Isacoff and John G. Flannery at UC Berkeley.

Together, they were engaged in finding a gene therapy approach to pan-genotypic vision restoration in patients with photoreceptor-based blindness, potentially restoring the vision of a broad group of patients. And they did it by using a vector to deliver the genetic sequence for light sensing proteins.

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CMO Merdad Parsey (Gilead)

Gilead hits the brakes on a tri­fec­ta of mid- and late-stage stud­ies for their trou­bled fil­go­tinib pro­gram. It's up to the FDA now

Gilead $GILD execs haven’t decided exactly what to do with filgotinib in the wake of the slapdown at the FDA on their rheumatoid arthritis application, but they’re taking a time out for a slate of studies until they can gain some clarity from the agency. And without encouraging guidance, this drug could clearly be axed from the pipeline.

In their Q3 report out Wednesday afternoon, the company says researchers have “paused” a Phase III study for psoriatic arthritis along with a pair of Phase II trials for ankylosing spondylitis and uveitis. Late-stage studies for ulcerative colitis and Crohn’s are continuing, but you can see for yourself how big a hole this leaves in the inflammatory disease pipeline, with obvious implications if the company abandons filgo altogether.

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Patrick Soon-Shiong at the JP Morgan Healthcare Conference, Jan. 13, 2020 (David Paul Morris/Bloomberg via Getty Images)

Af­ter falling be­hind the lead­ers, dissed by some ex­perts, biotech show­man Patrick Soon-Sh­iong fi­nal­ly gets his Covid-19 vac­cine ready for a tri­al. But can it live up to the hype?

In January, when dozens of scientists rushed to start making a vaccine for the then-novel coronavirus, they were joined by an unlikely compatriot: Patrick Soon-Shiong, the billionaire doctor most famous for making big, controversial promises on cancer research.

Soon-Shiong had spent the last 4 years on his “Cancer Moonshot,” but part of his project meant buying a small Seattle biotech that specialized in making common-cold vectors, called adenoviruses, to train the immune system. The billionaire had been using those vectors for oncology, but the company had also developed vaccine candidates for H1N1, Lassa fever and other viruses. When the outbreak began, he pivoted.

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Jude Samulski, Marianne De Backer

Bay­er buys a biotech ‘race horse’ with a $4B deal — $2B in cash — aimed at go­ing big in­to gene ther­a­py

In the latest sign that Big Pharma wants a leading place in the push to develop a new generation of cell and gene therapies, Bayer is stepping up today with a $2 billion cash deal to buy out one of the fast-moving pioneers in the field, while adding up to $2 billion more in milestones if the new pharma subsidiary can deliver the goods.

As part of a continuing series of deals engineered by Bayer BD chief Marianne De Backer, the pharma player has snapped up Asklepios, more commonly referred to in more casual fashion as AskBio. And they are paying top dollar for a Research Triangle Park-based company that raised $225 million a little more than a year ago to back the brainchild of Jude Samulski, the gene therapy pioneer out of the University of North Carolina Gene Therapy Center.

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