Neu­rotrope this week joined the long line of bio­phar­ma com­pa­nies that have been mauled by clin­i­cal fail­ure for Alzheimer’s drugs. But their crushed shares ($NTRP down from more than $8 in June to pen­ny stock range to­day) rep­re­sent­ed just a tiny drop in the buck­et of red ink that has drained from play­ers which have pur­sued the great­est of all Holy Grails in drug R&D. Decades of de­feat, head­lined by the likes of solanezum­ab at Eli Lil­ly stretch­ing to the most re­cent sna­fu with Bio­gen’s ad­u­canum­ab, have forced a slew of play­ers to change course on their R&D strat­e­gy — or just leave it in lim­bo.

How bad is it?

Bio­gen’s shares tanked when ad­u­canum­ab bombed, forc­ing an ear­ly halt to the late-stage ef­fort. The mar­ket cap shriv­eled by bil­lions, and it’s still down about 29% from pre-cri­sis lev­els. That plunge came af­ter Roche’s crenezum­ab flopped, though Roche was much bet­ter po­si­tioned to han­dle the fail­ure. But its part­ner, AC Im­mune $ACIU saw its share price halved in the fall­out.

The field went over the cliff in 2019.

What makes this im­por­tant for the long run?

In­vestors and an­a­lysts don’t gen­er­al­ly care to en­ter a mine­field where the chance of be­ing blown sky-high has been run­ning 100% — a mes­sage that has been heard loud and clear in re­cent months. Bio­gen — still al­lied to Ei­sai — has es­sen­tial­ly been ad­vised to write off Alzheimer’s al­to­geth­er as a com­plete loss. The amy­loid hy­poth­e­sis lies in tat­ters, while a se­ries of BACE fail­ures al­so un­der­scored some trou­bling safe­ty is­sues that made it all the way in­to a se­ries of late-stage stud­ies.

No one here re­al­ly knows what they’re do­ing. And any new rounds of mid-stage da­ta claim­ing suc­cess against bio­mark­ers are wide­ly ig­nored. Be­cause the bio­mark­ers have nev­er been proven to be in­dica­tive of suc­cess.

And with­out in­vestor sup­port, you can for­get any ma­jor new for­ays in late-stage test­ing.

The fo­cus now has shift­ed to tau and com­bo ther­a­pies, as new com­pa­nies start to tout ques­tion­able ev­i­dence of “suc­cess” in or­der to try to lure in­vestors back. But af­ter you’ve been burned this many times, that ar­gu­ment will be hard to make.

Weeks away from the results of ongoing US and China trials testing its experimental antiviral remdesivir, Gilead is going to trial the failed Ebola drug in a small group of coronavirus patients in England and Scotland. The United Kingdom is also home to a range of other therapeutic efforts, as the pandemic rages on across the globe.

On Tuesday, Southampton, UK-based startup Synairgen kicked off a mid-stage placebo-controlled study testing its experimental drug, SNG001 — an inhaled formulation of interferon-beta-1a — that has previously shown to be safe and effective in improving lung function in asthma patients with a respiratory viral infection in a pair of Phase II trials.

Just before Christmastime, Howard Federoff got a tip from Washington: There was a new virus in China. And this one could be bad.

News report of the virus had not yet appeared. Federoff, a neuroscientist, was briefed because years before, he was vetted as part of a group — he didn’t give a name for the group — to consult for the US government on emerging scientific issues. His day job, though, was CEO of Aspen Neurosciences, a Parkinson’s cell therapy startup that days before had come out of stealth mode and gave word to investors they were hoping to raise $70 million. That, Federoff realized, would be difficult if a pandemic shut down the global economy.

Despite worries about regulatory delays due to new work arrangements under Covid-19, the FDA appears intent to go full speed ahead with its everyday work, not only granting priority review to a stem cell therapy for acute graft versus host disease but also plotting an advisory committee meeting for it.

With a PDUFA date of September 30, the journey of the drug — remestemcel-L, or Ryoncil — could shed light on the agency’s capacity to facilitate drug development unrelated to Covid-19.