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.

Fenlai Tan still gets chills thinking about the darkest day of his life.

Three out of eight lung cancer patients who received a tyrosine kinase inhibitor developed by his company, Betta Pharma, died in the span of a month. Tan, the chief medical officer, was summoned to Peking Union Medical College Hospital, where the head of the clinical trial department told him that the trial investigators would be conducting an autopsy to see if the patients had died of the disease — they were all very sick by the time they enrolled — or of interstitial lung disease, a deadly side effect tied to the TKI class that’s been reported in Japan.

After flopping a test in Covid-19 earlier this year, Angion’s lead organ damage drug has now hit the skids again in kidney transplant patients.

Angion and partner Vifor Pharma’s ANG-3777 failed to beat out placebo in terms of improving eGFR, a measure of kidney function, in patients who had received a deceased donor kidney transplant and were at high risk of developing what is known as delayed graft function, according to Phase III results released Tuesday.

The FDA’s Vaccines and Related Biological Products Advisory Committee on Tuesday voted 17-0, with one panelist abstaining, that the benefits of the Pfizer-BioNTech Covid-19 vaccine outweigh the risks for children between the ages of five and 12.

The vote will likely trigger a process that could allow the shots to begin rolling out as early as next week.

The vaccine, which is one-third of the adult Pfizer dose, proved to be about 90% effective in a placebo-controlled trial in which about 1,500 kids in this age range received the vaccine, and only about 12% of those receiving the vaccine had any adverse event. All serious adverse events in the trial were unrelated to the vaccine.

In a sign of its growing commitment to the continent, Moderna will supply up to 110 million doses of its Covid-19 vaccine to the African Union, the company announced Tuesday. And CEO Stéphane Bancel said it’s just the first step.

“We believe our vaccine can play an important role in addressing the needs of low-income countries given its combination of high Phase 3 efficacy against COVID-19, strong durability in the real-world evidence, and superior storage and handling conditions. We recognize that access to COVID-19 vaccines continues to be a challenge in many parts of the world and we remain committed to helping to protect as many people as possible around the globe,” Bancel said in a statement.

BioNTech’s first mRNA-based vaccine site in Africa will call Rwanda home, and construction is set to start in mid-2022, the company announced Tuesday at a public health forum.

The German company signed a memorandum of understanding, after a meeting between Rwanda’s Minister of Health, Daniel Ngamije, Senegal’s Minister of Foreign Affairs Aïssata Tall Sall, and senior BioNTech officials. Construction plans have been finalized, and assets have been ordered. The agreement will help bring end-to-end manufacturing to Africa, and as many as several hundred million doses of vaccines per year, though initial production will be more modest.