Japan­ese bil­lion­aire Hi­roshi Mik­i­tani bankrolls As­pyr­i­an with a $150M mega-round, back­ing a glob­al roll­out plan for PhI­II can­cer ther­a­py

Among the world’s bil­lion­aires, Hi­roshi Mik­i­tani is one of the most promi­nent en­thu­si­asts. Start­ing with 6 staffers and a small sum of cash, he turned Rakuten in­to an on­line pow­er­house in Japan that is ranked among the world’s top e-tail­ers. An icon­o­clast in an econ­o­my dom­i­nat­ed by tra­di­tion­al­ists, he’s man­dat­ed that every­one in his com­pa­ny learn and speak Eng­lish as their first lan­guage. His re­cent ven­tures in­clude a part­ner­ship with Wal­mart for an on­line su­per­mar­ket in Japan. 

And he’s worth an es­ti­mat­ed $7 bil­lion.

Now, Mik­i­tani is putting in the li­on’s share of a $150 mil­lion mega-round in­to a small, pre­vi­ous­ly low-pro­file San Diego biotech he di­rects as chair­man of the board, adding to the eq­ui­ty he had al­ready bought up. And he’s putting some of that trade­mark gung-ho en­thu­si­asm be­hind a new ven­ture that is jump­ing from a small, sin­gle-arm Phase I/II tri­al in ad­vanced, treat­ment-re­sis­tant cas­es straight in­to a Phase III pro­gram.

A chunk of that new mon­ey is be­ing re­served for build­ing the foun­da­tion of their com­mer­cial pro­gram for ASP-1929, ahead of any mid-stage demon­stra­tion of proof-of-con­cept suc­cess. And Rakuten As­pyr­i­an is go­ing all out to build a ful­ly in­te­grat­ed out­fit, with plans to de­vel­op a pipeline of ther­a­peu­tic pro­grams that it plans to mar­ket on its own, with of­fices in the US, Japan and Eu­rope.

Miguel Gar­cia-Guz­man

CEO Miguel Gar­cia-Guz­man tells me that the mid-stage por­tion of ef­fi­ca­cy and safe­ty da­ta from their 42-pa­tient study of their pho­toim­munother­a­py is weeks away from a pub­lic un­veil­ing. But it’s all for­ward mo­tion now that the com­pa­ny has raised a to­tal of $238 mil­lion.

“We have enough con­fi­dence to move in­to a Phase III straight on,” says Gar­cia-Guz­man, point­ing to their lead ef­fort on an EGFR-tar­get­ing ther­a­py for head and neck squa­mous cell car­ci­no­mas. New mid-stage stud­ies are al­so be­ing set up for oth­er can­cers with an EGFR tar­get, which is quite com­mon.

Why the ear­ly con­fi­dence?

The Japan­ese bil­lion­aire is back­ing a new tech­nol­o­gy that was de­vel­oped at the Na­tion­al Can­cer In­sti­tute in the lab of Hisa­ta­ka Kobayashi, an imag­ing ex­pert who made a some­what serendip­i­tous dis­cov­ery that con­ju­gat­ing an an­ti­body with a dye called IRDye700DX (IR700), in­fus­ing it in­to pa­tients and then hit­ting it with a near in­frared light would cre­mate can­cer cells with­out off-tar­get tox­i­c­i­ty. Kobayashi out-li­censed it to As­pyr­i­an Ther­a­peu­tics, which now goes by the name of Rakuten As­pyr­i­an.

Mik­i­tani be­came fa­mil­iar with the work at the NCI as he was hunt­ing down a bet­ter ther­a­py for his fa­ther, who was dy­ing of pan­cre­at­ic can­cer. And while it was too late to save his fa­ther, he seized on it as the next big thing in can­cer, back­ing As­pyr­i­an from the be­gin­ning.

There’s been a lot more work on the tech­nol­o­gy since those ear­ly days at the NCI, says the CEO. The com­pa­ny has been work­ing on laser tech and dif­fer­ent fiberop­tics “to il­lu­mi­nate large in­ter­nal tu­mors, which can be eas­i­ly im­plant­ed in the tu­mor.” Once the fiberop­tics are in­side the tu­mor, you “switch on the light for 5 min­utes (a day af­ter the in­fu­sion), and treat­ment is com­plete.”

If the an­ti­body con­ju­gate is bound to can­cer cells, says Gar­cia-Guz­man, cell mem­brane in­tegri­ty is de­stroyed and necro­sis is trig­gered.

“This is not a phar­ma­co­log­i­cal ef­fect,” he adds, “it’s more bio­phys­i­cal, this al­lows a very tar­get­ed ap­proach.”

Mik­i­tani is the on­ly named in­vestor in this round, but the CEO tells me that he’s the lead play­er, with a ma­jor­i­ty in­ter­est in the com­pa­ny. Oth­er pri­vate in­vestors have stepped in, but Gar­cia-Guz­man says the biotech has steered clear of the VC set, de­ter­mined to con­trol their own fu­ture and main­tain their in­de­pen­dence.

With Mik­i­tani’s sup­port, the com­pa­ny has swelled from a start­up crew of 10 a cou­ple of years ago to 85 now. By the end of this year, you can ex­pect 100 to 110 on the pay­roll. And they plan to keep on grow­ing ag­gres­sive­ly, look­ing to build out all the func­tions of a biotech up­start with glob­al as­pi­ra­tions.

That’s a tall or­der. But Mik­i­tani seems to spe­cial­ize in tall or­ders. And the staff at As­pyr­i­an is all in.

Im­age: Hi­roshi Mik­i­tani at a con­fer­ence in 2018. AP IM­AGES

Con­quer­ing a silent killer: HDV and Eiger Bio­Phar­ma­ceu­ti­cals

Hepatitis delta, also known as hepatitis D, is a liver infection caused by the hepatitis delta virus (HDV) that results in the most severe form of human viral hepatitis for which there is no approved therapy.

HDV is a single-stranded, circular RNA virus that requires the envelope protein (HBsAg) of the hepatitis B virus (HBV) for its own assembly. As a result, hepatitis delta virus (HDV) infection occurs only as a co-infection in individuals infected with HBV. However, HDV/HBV co-infections lead to more serious liver disease than HBV infection alone. HDV is associated with faster progression to liver fibrosis (progressing to cirrhosis in about 80% of individuals in 5-10 years), increased risk of liver cancer, and early decompensated cirrhosis and liver failure.
HDV is the most severe form of viral hepatitis with no approved treatment.
Approved nucleos(t)ide treatments for HBV only suppress HBV DNA, do not appreciably impact HBsAg and have no impact on HDV. Investigational agents in development for HBV target multiple new mechanisms. Aspirations are high, but a functional cure for HBV has not been achieved nor is one anticipated in the forseeable future. Without clearance of HBsAg, anti-HBV investigational treatments are not expected to impact the deadly course of HDV infection anytime soon.

UP­DAT­ED: In a land­mark first glimpse of hu­man da­ta from Ver­tex, CRISPR/Cas9 gene ther­a­py sig­nals ear­ly ben­e­fit

Preliminary data on two patients with blood disorders that have been administered with Vertex and partner CRISPR Therapeutics’ gene-editing therapy suggest the technology is safe and effective, marking the first instance of the benefit of the use of CRISPR/Cas9 technology in humans suffering from disease.

Patients in these phase I/II studies give up peripheral blood from which hematopoietic stem and progenitor cells are isolated. The cells are tinkered with using CRISPR/Cas9 technology, and the edited cells — CTX001 — are infused back into the patient via a stem cell transplant. The objective of CTX001 is to fix the errant hemoglobin gene in patents with two blood disorders: beta-thalassemia and sickle cell disease, by unleashing the production of fetal hemoglobin.

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UP­DAT­ED: Make that 2 ap­proved RNAi drugs at Al­ny­lam af­ter the FDA of­fers a speedy OK on ul­tra-rare dis­ease drug

Seventeen years into the game, Alnylam’s pivot into commercial operations is picking up speed.
The bellwether biotech $ALNY has nabbed their second FDA OK for an RNAi drug, this time for givosiran, the only therapy now approved for acute hepatic porphyria. This second approval came months ahead of the February deadline — even after winning priority review following their ‘breakthrough’ title earlier.
AHP is an extremely rare disease, with some 3,000 patients in Europe and the US, not all diagnosed, and analysts have projected peak revenue of $600 million to $700 million a year. The drug will be sold as Givlaari.

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David Ricks. Eli Lilly

Eli Lil­ly touts $400M man­u­fac­tur­ing ex­pan­sion, 100 new jobs to much fan­fare in In­di­anapo­lis — even though it's been chop­ping staff

Eli Lilly is pouring in $400 million to beef up manufacturing facilities at its home base of Indianapolis. The investment, which was lauded by the city’s mayor, is expected to create 100 new jobs.

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Am­gen chops 172 more staffers in R&D, op­er­a­tions and sales amid neu­ro­science ex­it, rev­enue down­turn

Neuroscience wasn’t the only unit that’s being hit by a reorganization underway at Amgen. As well as axing 149 employees in its Cambridge office, the company has disclosed that 172 others nationwide, including some from its Thousand Oaks, CA headquarters, are being let go.

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Stephen Hahn (via Senate HELP Committee)

Stephen Hahn gets through Sen­ate’s soft­ball job in­ter­view — but most­ly plays dodge­ball on the is­sues fac­ing the FDA

Anyone looking for fresh insights on what kind of FDA commissioner Stephen Hahn will be got precious few clues during Wednesday’s Senate hearing on the nomination.

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Op­di­vo/Yer­voy com­bo for melanoma fails in key pa­tient pop­u­la­tion

Bristol-Myers Squibb’s efforts to expand their checkpoint inhibitor combination have run into another recalcitrant cancer.

The NJ-based pharma announced that a combination of Yervoy and Opdivo didn’t beat out Opdivo alone in patients with resected high-risk melanoma who had very low levels of PD-L1. The drug combo couldn’t improve recurrence-free survival in these post-surgery patients.

Ver­tex's stel­lar quar­ter car­ries on with French re­im­burse­ment deal

Vertex’s golden quarter just got brighter. About a month after the US drugmaker finally clinched a deal with UK authorities to cover its slate of cystic fibrosis (CF) drugs following years of protracted negotiations, the company on Wednesday secured a deal with France for its CF therapy, Orkambi.

After the UK, France has one of the largest CF populations outside the United States. Achieving French reimbursement unlocks an ~7000-patient CF population, around ~2500-3000 of which will likely be eligible to receive (and be reimbursed for) Orkambi, Stifel’s Paul Matteis wrote in a note.

Nello Mainolfi, Kymera via Youtube

Kymera hands the helm to No­var­tis vet — and found­ing CSO — Nel­lo Main­olfi

Kymera Therapeutics is turning to a co-founder to run the company.
The protein degradation specialist with a deep-pocket syndicate behind them has opted to give the helm officially to Nello Mainolfi. The new CEO is a veteran of the Novartis Institutes for Biomedical Research. He joined Atlas Venture in their entrepreneur-in-residence program and helped launch Kymera as the CSO three years ago with Atlas’ Bruce Booth.
The boast at Kymera is that they’re angling to create a new class of protein degraders, a popular field where there’s been a variety of startups. One of its chief advocates is NIBR head Jay Bradner, who launched C4 just ahead of joining Novartis, where he’s also been doing new work in the field.