Haul­ing in a $100M mega-round, gene ther­a­py start­up Gen­er­a­tion Bio builds al­ter­na­tive to po­ten­tial­ly risky vi­ral vec­tors

A gene ther­a­py com­pa­ny head­ed up by big­wigs and backed ear­ly on by At­las has pulled in a mega-round of $100 mil­lion. The 2-year-old start­up cap­tured in­vestors’ at­ten­tion by sug­gest­ing it knows a bet­ter way to do gene trans­fer than the po­ten­tial­ly tox­ic vi­ral vec­tor strate­gies of late.

Gen­er­a­tion Bio is the Boston/Cam­bridge up­start, and it’s a com­pa­ny that’s strayed from the pack when it comes to the how of gene ther­a­py. While its ri­vals in the field are buck­ling down on vi­ral ve­hi­cles like ade­no as­so­ci­at­ed virus­es (AAV), Gen­er­a­tion Bio is tak­ing a dif­fer­ent route.

Robert Kotin

Found­ed in part by ex-NIH, ex-Voy­ager ex­ec­u­tive Robert Kotin, whom you may know as one of the world’s top ex­perts on vi­ral trans­port, the new com­pa­ny cen­ters on a tech they’re call­ing close-end­ed DNA (ceD­NA). This can move from the cy­to­plasm of the cell to the nu­cle­us with­out an AAV car­ry­ing it along. Once in­side the nu­cle­us, it can cre­ate high lev­els of gene ex­pres­sion ca­pa­ble of ad­dress­ing a broad range of ge­net­ic dis­eases.

Gen­er­a­tion Bio says the hope is that this tech can ad­dress the emerg­ing con­cern re­volv­ing around vi­ral vec­tors. Well-known gene ther­a­py com­pa­nies like Spark and Sol­id Bio­sciences are us­ing AAVs as vec­tors, a method that, when used in high dos­es, has re­cent­ly been called in­to ques­tion by a pi­o­neer in the field, Penn pro­fes­sor James Wil­son.

Wil­son sur­prised the gene ther­a­py com­mu­ni­ty in Jan­u­ary when he quit the ad­vi­sor board of Sol­id and raised alarms about the po­ten­tial tox­i­c­i­ty of high-dose AAV stud­ies.

Gen­er­a­tion Bio is cap­i­tal­iz­ing on the un­cer­tain­ty cloud­ing the lead­ing tech in the field by por­tray­ing their ther­a­pies as po­ten­tial­ly safer.

Last month, the com­pa­ny’s CEO Ge­off Mc­Do­nough told End­points the com­pa­ny would start by us­ing a lipid nanopar­ti­cle to de­liv­er ceD­NA to the liv­er, where it will make sys­temic pro­teins to fight dis­eases.

“These ther­a­pies are de­signed to over­come the im­muno­genic­i­ty as­so­ci­at­ed with vi­ral-vec­tor gene ther­a­pies, which has his­tor­i­cal­ly lim­it­ed the num­ber of pa­tients that can be treat­ed and pre­vent­ed re-dos­ing,” Gen­er­a­tion Bio stat­ed in a press re­lease. “Since its found­ing in 2016, Gen­er­a­tion Bio has demon­strat­ed durable, dose-de­pen­dent ex­pres­sion and the abil­i­ty to in­crease ex­pres­sion in the liv­er with re-dos­ing in vi­vo with the Ge­neWave plat­form.”

In­vestors ap­pear to be in­trigued. The $100 mil­lion fi­nanc­ing was a Se­ries B led by Fi­deli­ty Man­age­ment & Re­search Com­pa­ny, with par­tic­i­pa­tion from In­vus, Deer­field Man­age­ment Com­pa­ny, Cas­din Cap­i­tal, Fore­site Cap­i­tal, and Leerink Part­ners’ Af­fil­i­ates.

This round comes less than two months af­ter Gen­er­a­tion Bio an­nounced its $25 mil­lion Se­ries A backed by At­las.

The new mon­ey will be used to take two ther­a­peu­tic can­di­dates through IND-en­abling stud­ies.

“This will be a crit­i­cal­ly im­por­tant year for us as we de­vel­op the Ge­neWave plat­form and work to­wards our first de­vel­op­ment can­di­dates to ad­dress rare dis­eases of the liv­er,” Mc­Do­nough said in a state­ment. “The round will al­so sup­port the de­vel­op­ment of ap­proach­es to de­liv­er ceD­NA to oth­er tis­sues such as the eye, the cen­tral ner­vous sys­tem and the lungs.”

Im­age: Gen­er­a­tion Bio’s pres­i­dent and CEO Ge­off Mc­Do­nough. Gen­er­a­tion Bio

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.