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.

Jan Hatzius (Photographer: Christopher Goodney/Bloomberg via Getty Images)

When will it end? Gold­man econ­o­mist gives late-stage vac­cines a good shot at tar­get­ing 'large shares' of the US by mid-2021 — but the down­side is daunt­ing

It took decades for hepatitis B research to deliver a slate of late-stage candidates capable of reining the disease in.

With Covid-19, the same timeline has devoured all of 5 months. And the outcome will influence the lives of billions of people and a multitrillion-dollar world economy.

Count the economists at Goldman Sachs as optimistic that at least one of these leading vaccines will stay on this furiously accelerated pace and get over the regulatory goal line before the end of this year, with a shot at several more near-term OKs. That in turn should lead to the production of billions of doses of vaccines that can create herd immunity in the US by the middle of next year, with Europe following a few months later.

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Sean Nolan and RA Session II

Less than 3 months af­ter launch, the AveX­is crew’s Taysha rais­es $95M Se­ries B. Is an IPO next?

The old AveXis team is moving quickly in Dallas.

Three months ago, they launched Taysha with $30 million in Series A funding and a pipeline of gene therapies out of UT Southwestern. Now, they’ve announced an oversubscribed $95 million Series B. And the biotech is declining all interview requests on the news, the kind of broad silence that can indicate an IPO is in the pipeline.

Biotechs, including those relatively fresh off launch, have been going public at a frenzy since the pandemic began. Investors have showed a willingness to put upwards of $200 million to companies that have yet to bring a drug into the clinic. Still, if Taysha were to go public in the near future, it would be perhaps the shortest path from launch to IPO in recent biotech memory.

UP­DAT­ED: No­vavax her­alds the lat­est pos­i­tive snap­shot of ear­ly-stage Covid-19 vac­cine — so why did its stock briefly crater?

High-flying Novavax $NVAX became the latest of the Covid-19 vaccine players to stake out a positive set of biomarker data from its early-stage look at its vaccine in humans.

Their adjuvanted Covid-19 vaccine was “well-tolerated and elicited robust antibody responses numerically superior to that seen in human convalescent sera,” the company noted. According to the biotech:

All subjects developed anti-spike IgG antibodies after a single dose of vaccine, many of them also developing wild-type virus neutralizing antibody responses, and after Dose 2, 100% of participants developed wild-type virus neutralizing antibody responses. Both anti-spike IgG and viral neutralization responses compared favorably to responses from patients with clinically significant COVID‑19 disease. Importantly, the IgG antibody response was highly correlated with neutralization titers, demonstrating that a significant proportion of antibodies were functional.

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Lund­beck sounds taps on an­oth­er CNS drug, re­treat­ing from a mine field still oc­cu­pied by a Mer­ck team

Lundbeck has snipped another clinical-stage branch of its CNS research, dumping a schizophrenia program after determining that their therapy would have no positive influence on the disease.

Designed originally as a 240-patient study, researchers set out in early 2019 to see if a homegrown drug dubbed Lu AF11167 could make it through a proof-of-concept study. The drug is a PDE10Ai inhibitor, targeting an enzyme which it said at the time offered a new pathway to retuning the body’s neurotransmitter dopamine. The big idea was that by hitting their target, the drug would modulate “dopamine D1 and D2 receptor-mediated intraneuronal signaling without binding to these receptors,” influencing negative symptoms of schizophrenia.

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RA, No­var­tis back Gen­tiBio's seed round, plans to launch de­vel­op­ment of En­gTreg ther­a­pies

Boston, MA-based startup GentiBio landed a $20 million seed fund from three investors to dive into engineered regulatory T cell (EngTreg) development.

Marquee investors OrbiMed, Novartis Venture Fund and RA Capital Management have backed GentiBio’s mission to develop EngTregs for the treatment of autoimmune, alloimmune, autoinflammatory, and allergic diseases. Unlike other companies studying treatments using a patient’s own Tregs, GentiBio plans to make use of CD4+ immune cells, found in the blood.

Stéphane Bancel, Moderna CEO (Steven Ferdman/Getty Images)

Mod­er­na CEO Stéphane Ban­cel out­lines a prospec­tive moth­er­lode of Covid-19 vac­cine rev­enue — will a back­lash fol­low?

Moderna shows no sign of slowing down, or turning charitable when it comes to pricing supplies of its Covid-19 vaccine.

One of the leaders in the Phase III race to get a Covid-19 vaccine across the finish line in record time, Moderna says it’s on track to complete enrollment in one of the most avidly watched studies in the world next month. And the biotech has already banked some $400 million in deposits for vaccine supply as it works through negotiations with countries around the world — as CEO Stéphane Bancel sets out to hire a commercial team.

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Ver­sant de­buts Ridge­line's start­up #4, armed with $30M and al­ter­na­tive TCR cell ther­a­pies for sol­id tu­mors

For all the iterations and advances in TCR therapies for cancer, any experimental treatments involving T cell receptors share one trait: By definition, they only recognize antigens presented as peptides on the major histocompatibility complex (MHC) on cells.

Versant reckons it’s time to expand the arsenal. With $30 million in initial funding, its Ridgeline Discovery Engine in Switzerland has been working on a non-peptidic approach that it says has tumor-agnostic potential, especially in solid tumors. They’ve named it Matterhorn, after a Swiss mountain as they did with the three other companies that have emerged from the Basel-based incubator.

CF Foun­da­tion, Long­wood team on new in­cu­ba­tor for com­pa­nies with cut­ting-edge CF treat­ments

Nine months after launching a $500 million hunt for a cure for cystic fibrosis, the Cystic Fibrosis Foundation said it will use a portion of those funds to do something it has never done before: help launch new companies.

The CF Foundation, whose venture philanthropy efforts helped fund Vertex’s line of powerful CF drugs, is teaming with Longwood Fund to create a CF incubator. The incubator will identify new companies with platforms or technologies that can be applied in the rare genetic condition. The partners can then finance early development in exchange for a commitment from the companies to focus on applications in cystic fibrosis.

Covid-19 roundup: J&J and BAR­DA agree to $1 bil­lion for 100 mil­lion dos­es; Plas­ma re­duces mor­tal­i­ty by 50% — re­ports

J&J has become the latest vaccine developer to agree to supply BARDA with doses of their Covid-19 vaccine, signing an agreement that will give the government 100 million doses in exchange for $1 billion in funding.

The agreement, similar to those signed by Novavax, Sanofi and AstraZeneca-Oxford, provides funding not only for individual doses but to help J&J ramp up manufacturing. Pfizer, by contrast, received $1.95 billion for the doses alone. Still, if one looked at each agreement as purchase amounts, J&J’s deal would be $10 per dose, slotting in between Novavax’s $16 per dose and AstraZeneca’s $4 per dose.

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