Near­ly a year ago, as the pan­dem­ic en­croached and the stock mar­ket cratered, Flag­ship and ARCH Ven­ture an­nounced three mega-funds worth a com­bined $2.6 bil­lion. They want­ed, ARCH’s Bob Nelsen said, to re­store con­fi­dence “that there was mon­ey out there and a lot of it” to in­vest in biotech.

Since then, the stock mar­ket has re­turned — al­most fright­en­ing­ly so — and Nelsen has kept rais­ing and spend­ing cash. On Thurs­day, he an­nounced a new fund, worth $1.85 bil­lion. It’s the largest pot yet for a VC fa­mous for its deep pock­ets.

This time, he said, there’s no mes­sage oth­er than what they’ve been say­ing for years.

“It’s just a con­tin­ued con­fi­dence in ba­sic sci­ence, and in­no­va­tion that’s hap­pen­ing in health­care; it’s re­al­ly a rev­o­lu­tion­ary time,” he told End­points News. It’s “keep­ing your head down and con­tin­u­ing to do what you do.”

His­tor­i­cal­ly, ARCH has been known for back­ing huge plays with record in­vest­ments, most re­cent­ly launch­ing Re­silience with $800 mil­lion and a plan to re­think how all bi­o­log­ic drugs are made. An­oth­er ma­jor bet, the in­fec­tious dis­ease start­up Vir, may yet play a ma­jor role in the pan­dem­ic, lead­ing one of the ma­jor ef­forts to de­vel­op a neu­tral­iz­ing an­ti­body for Covid-19.

In an­nounc­ing the new fund, Nelsen ticked off a range of ar­eas the firm will look to pur­sue, most of which ARCH has pre­vi­ous­ly pushed for­ward, in­clud­ing gene edit­ing and cell ther­a­py.

“Men­tal health is at the top of my mind,” he said.

ARCH has played a key role in pre­vi­ous men­tal health biotechs, most no­tably back­ing Sage Ther­a­peu­tics and Karuna. Nelsen said they may al­so in­vest in ap­proach­es to the is­sue out­side drug de­vel­op­ment, back­ing ef­forts in con­sumer health and health tech.

Al­though known for its huge plays, ARCH al­so hands out about 20 so-called “poor” deals that can range as low as $50,000 and ei­ther pro­vide seed cash for a par­tic­u­lar idea or help feed in­to a larg­er com­pa­ny. Both Vir and Re­silience, for ex­am­ple, com­bined mul­ti­ple small­er com­pa­nies in­to a large one, which then gar­nered sig­nif­i­cant in­vest­ment.

Not all those in­vest­ments, though, have worked out. Last year, Nelsen stepped away from the board of Uni­ty Biotech­nol­o­gy, an an­ti-ag­ing start­up that at­tract­ed sig­nif­i­cant in­vest­ment but failed a ma­jor tri­al last year. It’s at least the sec­ond ma­jor set­back he’s seen in an an­ti-ag­ing play, af­ter a late 90s, ear­ly 2000s bet on Cyn­thia Keny­on’s Elixir Phar­ma­ceu­ti­cals went un­der.

Still, ARCH in­clud­ed it on a list of po­ten­tial ar­eas for the new fund, and Nelsen said he hasn’t lost faith. They’re con­tin­u­ing to mon­i­tor the field, he said.

Since losing a controversial court case over orphan drug exclusivity last year, the FDA’s Office of Orphan Products Development has remained entirely silent on orphan exclusivity for any product approved since last November, leaving many sponsors in limbo on what to expect.

That silence means that for more than 70 orphan-designated indications for more than 60 products, OOPD has issued no public determination on the seven-year orphan exclusivity in the Orange Book, and no new listings of orphan exclusivity appear in OOPD’s searchable database, as highlighted recently by George O’Brien, a partner in Mayer Brown’s Washington, DC office.

The first generation of personalized CAR-T therapies made big waves in the treatment of lymphoma for their stunning efficacy. Nkarta is hoping its off-the-shelf natural killer cell approach will stand out on safety — while keeping some of those impressive numbers on responses.

In a new update from its Phase I dose escalation study, the South San Francisco-based biotech reported that seven out of 10 patients treated with the highest doses of its NK cell therapy, NKX019, achieved a complete response, translating to a complete response rate of 70%.

A biotech centered on treating fibrosis — born out of Mass General and Brigham and Women’s Hospital — has received a financial boost.

According to an SEC filing, the company has raised $31,761,186 in its latest funding round, which includes 17 investors. The filing lists six names attached to the company, including Meredith Fisher, a partner at Mass General Brigham Ventures and Mediar’s acting CEO.

We now know why Verve’s lead candidate was placed on hold last month by US regulators.

In an SEC filing, Verve laid out the FDA’s conditions for lifting the hold on its lead therapy, VERVE-101. That includes submitting preclinical data about potency differences in human versus non-human cells, risks of gene editing germline cells, and off-target analyses in non-hepatocyte cell types.

The FDA also wants clinical data from the ongoing Heart-1 trial, and to modify the trial protocol in the US to add additional contraceptive measures and increase the length of a staggering interval between the dosing of participants.