Mahesh Karande (Omega)

'Ex­quis­ite con­trol': Flag­ship pulls off $85M ral­ly around Omega Ther­a­peu­tic­s' clin­i­cal push for epi­ge­net­ic pro­gram­ming tech

Omega Ther­a­peu­tics be­gan, as all biotech fledg­lings in­cu­bat­ed at Flag­ship Labs do, with an off-the-wall ques­tion: Can one con­trol gene ex­pres­sion but not cre­ate the mas­sive nu­cle­ic acid se­quence changes that are cre­at­ed by gene ther­a­py and gene edit­ing?

Not long af­ter the in­ter­nal team be­gan ru­mi­nat­ing on the idea, as chief Ma­hesh Karande ex­plained at the of­fi­cial launch last Sep­tem­ber, they found an an­swer in a sem­i­nal pa­per pub­lished by Rick Young’s group at the White­head In­sti­tute. Genes and their reg­u­la­to­ry el­e­ments, he found, gen­er­al­ly re­side in loops closed off by a pair of CTCF pro­teins — neigh­bor­hoods that were lat­er named “in­su­lat­ed ge­nom­ic do­mains,” or IGDs. By send­ing reg­u­la­tor or ef­fec­tor pro­teins to dys­reg­u­lat­ed IGDs (there are more than 15,000 of them in to­tal), Omega’s pitch was to cre­ate a con­trolled epi­ge­net­ic pro­gram­ming plat­form for what Karande calls the “con­trol room of hu­man bi­ol­o­gy.”

Thomas Mc­Cauley

“It wasn’t at all clear 20 years when the genome was se­quenced which reg­u­la­to­ry el­e­ments af­fect­ed which genes,” CSO Thomas Mc­Cauley tells End­points News. “And the recog­ni­tion that the 3-di­men­sion­al struc­ture was the key to that puz­zle was re­al­ly what the com­pa­ny was found­ed on.”

What the start­up was able to al­so tap in­to was a way to for­mu­late and de­liv­er their new in­ven­tion — a DNA bind­ing do­main lig­and­ed to an epi­ge­net­ic reg­u­la­tor pro­tein — with ex­ist­ing meth­ods. Through con­nec­tions to their Flag­ship kin who have bro­ken ground in mR­NA and lipid nanopar­ti­cle (LNP) tech­nolo­gies, Karande says even GMP man­u­fac­tur­ing wouldn’t be a prob­lem.

In Karande’s telling, it is the com­bi­na­tion of the new bi­ol­o­gy and the “ex­quis­ite con­trol” they can achieve with an “el­e­gant­ly sim­ple” ap­proach that en­ticed yet un­named in­vestors to join Flag­ship for the long haul in a $85 mil­lion fi­nanc­ing round.

“$85 mil­lion is bet­ter in our hands than in the hands of many oth­er modal­i­ties,” he says.

With five pro­grams lined up in can­cer, in­flam­ma­tion, au­toim­mune, meta­bol­ic and rare ge­net­ic dis­eases, the com­pa­ny ex­pects to start its first clin­i­cal tri­al in 2021. The Cam­bridge, MA-based team of 45 will like­ly grow to some­where be­tween 50 and 60 be­fore then.

Be­cause the drug sub­stance they are di­rect­ing to spe­cif­ic, in­su­lat­ed sites is es­sen­tial­ly nat­u­ral­ly oc­cur­ring and eas­i­ly-de­grad­ed pro­teins used by the hu­man body to tune genes up or down, Karande ex­pects few hur­dles on the safe­ty front. Lever­ag­ing mR­NA and LNP as de­liv­ery ve­hi­cles al­so lends it­self to mod­u­lar de­sign, a key draw for the soft­ware anal­o­gy-in­clined crowd.

“Even over the last year, year and a half, our cy­cle time in terms of con­cept to ini­tial test­ing to re­al­ly de­vel­op­ment-ready com­po­si­tion has short­ened dra­mat­i­cal­ly and re­al­ly will sup­port a very steady ca­dence of pro­grams to­ward the clin­ic,” Mc­Cauley says.

Once Omega proves its plat­form, he sug­gests, they might con­sid­er swap­ping out the time-test­ed LNP for oth­er de­liv­ery meth­ods.The same goes for tar­gets: You want to start out with onco­genes, growth fac­tors and oth­er known but pre­vi­ous­ly un­drug­gable ge­net­ic el­e­ments be­fore mov­ing in­to un­chart­ed ter­ri­to­ry.

Karande, who ran No­var­tis’ Africa di­vi­sion and head­ed up a can­cer fran­chise be­fore jump­ing to biotech, isn’t shy about reimag­in­ing med­i­cine with this new class of epi­ge­net­ic drugs. On top of all the po­ten­tial for spe­cif­ic tar­get­ing and fine-tun­ing, Omega can se­lect for the dura­bil­i­ty of the ef­fec­tor pro­teins that form their con­trollers, rang­ing from acute ap­pli­ca­tion to chron­ic use of up to two months.

“We are in un­prece­dent­ed times when it comes to con­trol of bi­ol­o­gy,” he says.

Late Fri­day ap­proval; Trio of biotechs wind down; Stem cell pi­o­neer finds new fron­tier; Biotech icon to re­tire; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

I hope your weekend is off to a nice start, wherever you are reading this email. As for me, I’m trying to catch the tail of the Lunar New Year festivities.

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Pfiz­er lays off em­ploy­ees at Cal­i­for­nia and Con­necti­cut sites

Pfizer has laid off employees at its La Jolla, CA, and Groton, CT sites, according to multiple LinkedIn posts from former employees.

The Big Pharma confirmed to Endpoints News it has let go of some employees, but a spokesperson declined to specify how many workers were impacted and the exact locations affected. Earlier this month, the drug developer had confirmed to Endpoints it was sharpening its focus and doing away with some early research on areas such as rare disease, oncology and gene therapies.

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Rodney Rietze, iVexSol CEO

Bris­tol My­ers, Charles Riv­er join Se­ries A fund­ing for iVex­Sol

Massachusetts-based iVexSol has secured funding to the tune of $23.8 million in its latest Series A round. The new investors include Bristol Myers Squibb, manufacturer Charles River Laboratories and Asahi Kasei Medical.

iVexSol is a manufacturer of lentiviral vectors (LVV), used in making gene therapies, and this latest round of fundraising brings its total Series A total over $39 million, which will be used to recruit more employees and bolster its technology.

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Jake Van Naarden, Loxo@Lilly CEO

Lil­ly en­ters ripe BTK field with quick FDA nod in man­tle cell lym­phoma

Eli Lilly has succeeded in its attempt to get the first non-covalent version of Bruton’s tyrosine kinase, or BTK, inhibitors to market, pushing it past rival Merck.

The FDA gave an accelerated nod to Lilly’s daily oral med, to be sold as Jaypirca, for patients with relapsed or refractory mantle cell lymphoma.

The agency’s green light, disclosed by the Indianapolis Big Pharma on Friday afternoon, catapults Lilly into a field dominated by covalent BTK inhibitors, which includes AbbVie and Johnson & Johnson’s Imbruvica, AstraZeneca’s Calquence and BeiGene’s Brukinsa.

Tony Johnson, Goldfinch Bio CEO (Goldfinch via YouTube)

Kid­ney dis­ease drug­mak­er Goldfinch Bio shuts down

Goldfinch Bio, attempting to make treatments for kidney diseases and diabetic nephropathy, is shutting down.

President and CEO Tony Johnson confirmed to Endpoints News Friday afternoon that the biotech shut down after “fundraising challenges in the current macro-environment.” Fierce Biotech first reported the news.

Johnson, who joined in 2017 after a stint as SVP of early clinical development at AstraZeneca, said in a text that the company “entered the ABC process recently,” referring to an assignment for the benefit of the creditors, which provides a different wind-down avenue than a bankruptcy.

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Filip Dubovsky, Novavax CMO

No­vavax gets ready to take an­oth­er shot at Covid vac­cine mar­ket with next sea­son plans

While mRNA took center stage at yesterday’s FDA vaccine advisory committee meeting, Novavax announced its plans to deliver an updated protein-based vaccine based on new guidance.

Vaccines and Related Biological Products Advisory Committee (VRBPAC) members voted unanimously in favor of “harmonizing” Covid vaccine compositions, meaning all future vaccine recipients would receive a bivalent vaccine, regardless of whether they’ve gotten their primary series.

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Steve Harr, Sana Biotechnology CEO

Four years in, Sana gets first FDA go-ahead to bring can­cer treat­ment in­to the clin­ic

Sana Biotechnology is finally headed to the clinic.

Thursday afternoon, the biotech announced the FDA had cleared its application to start a clinical trial for its allogeneic, or “off-the-shelf,” CAR-T cell therapy targeting the antigen CD19 for patients with B-cell lymphomas and leukemias. Sana said its therapy, dubbed SC291, was designed to evade the immune system, which could help cell therapy produce a more durable response in patients, a concern that has followed such off-the-shelf therapies that use donor cells as opposed to a patient’s own cells.

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Ying Huang, Legend CEO

J&J, Leg­end say Carvyk­ti beat stan­dard ther­a­py in ear­li­er-line blood can­cer

J&J and Legend Biotech’s next step in turning their CAR-T therapy Carvykti into a potential megablockbuster has succeeded, the companies said Friday.

Carvykti achieved the primary endpoint — progression-free survival — in an open-label Phase III study testing the treatment in second- to fourth-line multiple myeloma patients. The CARTITUDE-4 trial, for which there aren’t any hard data yet, represents the biggest development for Carvykti’s ability to compete with Bristol Myers Squibb’s Abecma since its approval last February.

Eliot Forster, F-star CEO (Rachel Kiki for Endpoints News)

F-star gets down to the wire with $161M sale to Chi­nese buy­er as na­tion­al se­cu­ri­ty con­cerns linger

With the clock ticking on F-star Therapeutics’ takeover by a Chinese buyer, the companies are still scrambling to remove a hold on the deal from the US government’s Committee on Foreign Investment in the United States.

F-star and invoX Pharma said they are “actively negotiating” with CFIUS “about the terms of a mitigation agreement to address CFIUS’s concerns regarding potential national security risks posed by the transaction.”

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