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.

In his­toric Covid-19 ad­comm, vac­cine ex­perts de­bate a sea of ques­tions — but of­fer no clear an­swers

The most widely anticipated and perhaps most widely watched meeting in the FDA’s 113-year history ended late Thursday night with a score of questions and very few answers.

For nearly 9 hours, 18 different outside experts listened to public health agencies and foundations present how the United States’ Covid-19 vaccine program developed through October, and they debated where it should go from there: Were companies testing the right metrics in their massive trials? How long should they track patients before declaring a vaccine safe or effective? Should a vaccine, once authorized, be given to the volunteers in the placebo arm of a trial?

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Ul­tragenyx in­jects $40M to grab Solid's mi­crody­s­trophin trans­gene — while side­step­ping the AAV9 vec­tor that stirred up safe­ty fears

Since before Ilan Ganot started Solid Bio to develop a gene therapy for kids like his son, who has Duchenne muscular dystrophy, Ultragenyx CEO Emil Kakkis has been watching and advising the former investment banker as he navigated the deep waters of drug development.

Just as Solid is getting back up on its feet after a yearlong clinical hold, Kakkis has decided to jump in for a formal alliance.

With a $40 million upfront, Ultragenyx is grabbing 14.45% of Solid’s shares $SLDB and the rights to its microdystrophin construct for use in combination with AAV8 vectors. Solid’s lead program, which utilizes AAV9, remains unaffected. The company also retains rights to other applications of its transgene.

Bo Cumbo, AavantiBio CEO (file photo)

Bo Cum­bo jumps from the top com­mer­cial post at Sarep­ta to the helm of a gene ther­a­py start­up with some in­flu­en­tial back­ers, big plans and $107M

After a 7-year stretch building the commercial team at Sarepta, longtime drug salesman Bo Cumbo is jumping to the entrepreneurial side of the business, taking the helm of a startup that’s got several deep-pocket investors. And he’s not just bringing his experience in selling drugs.

He tells me that when he told Sarepta CEO Doug Ingram about it, his boss got excited about the venture and opted to jump in with a $15 million investment from Sarepta to add to the launch money, alongside 3 of the busiest investors in biotech.

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Pascal Soriot, AstraZeneca CEO (Zach Gibson/Bloomberg via Getty Images)

UP­DAT­ED: FDA gives As­traZeneca the thumbs-up to restart PhI­II Covid-19 vac­cine tri­als, and J&J is prepar­ing to re­sume its study

Several countries had restarted their portions of AstraZeneca’s global Phase III Covid-19 vaccine trial after the study was paused worldwide in early September, but the US notably stayed on the sidelines — until now. Friday afternoon the pharma giant announced the all clear from US regulators. And on top of that, J&J announced Friday evening that it’s preparing to resume its own Phase III vaccine trial.

Pfiz­er scoops up an an­tibi­ot­ic in rare M&A deal, bag­ging a vir­tu­al start­up op­er­at­ing on a shoe­string bud­get

Pfizer is stepping up with a rare antibiotics buyout deal today, grabbing Palo Alto, CA-based Arixa Pharmaceuticals in a bid to add a new oral version of avibactam, a beta lactamase inhibitor — or BLI — approved back in 2015 as part of the IV treatment Avycaz.

The Arixa acquisition follows some encouraging Phase I responses demonstrating that 60% to 80% of the oral drug is absorbed into the bloodstream. Only 7% of the IV version is absorbed orally, far below the 30% threshold Arixa has pointed to as a therapeutic threshold. The buyout gives Pfizer’s hospital group a line on a new oral combo with antibiotics like ceftibuten to go after drug-resistant cases of urinary tract infections and other ailments.

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A top drug pro­gram at Bay­er clears a high bar for CKD — open­ing the door to an FDA pitch

Over the past 4 years, Bayer has been steering a major trial through a pivotal program to see if their drug finerenone could slow down the pace of chronic kidney disease in patients suffering from both CKD as well as Type 2 diabetes.

Today, their team jumped on a virtual meeting hosted by the American Society of Nephrology to offer a solid set of pivotal data to demonstrate that the drug can delay dialysis or a kidney replacement as well as cardio disease, while also adding some worrying signs of hyperkalemia among the patients taking the drug. And they’re hustling it straight to regulators in search of an approval for kidney disease and cardio patients — one of the toughest challenges in the book, as demonstrated by repeated past failures.

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Adam Koppel and Jeffrey Schwartz, Bain

Bain ex­ecs Adam Kop­pel and Jef­frey Schwartz line up $125M for their first blank check deal as Wall Street con­tin­ues to em­brace biotech

Adam Koppel and Jeffrey Schwartz have jumped into the blank check game, raising $125 million for a stock listing in search of a company.

Their SPAC, BCLS Acquisition Corp, raised $125 million this week, with a line on $25 million more as it scouts for a biotech in search of money and a place on Wall Street.

The two principals at Bain Life Sciences have been on a romp since they set up the Bain operation 4 years ago. Their S-1 spells out a track record of 22 deals totaling $650 million for the life sciences group, which led to 9 IPOs.

Covid-19 roundup: An mR­NA play­er gets a boost out of the lat­est round of an­i­mal da­ta; Phase­Bio pulls the plug on treat­ment tri­al

The big tell for CureVac $CVAC is coming up with a looming early-stage readout on their mRNA Covid-19 vaccine in the clinic. But for now they’ll make do with an upbeat assessment on the preclinical animal data they used to get into the clinic.

Researchers for the German biotech say they got the high antibody titers and T cell activation they were looking for, lining up a hamster challenge to demonstrate — in a simple model — that the vaccine could protect the furry creatures. Like the other mRNA vaccines, the drug sends instructions to spur cells to decorate themselves with the distinctive spike on the virus to elicit an immune response.

Chi­nese in­vestors wa­ger $105M on an IPO-bound biotech look­ing to push RNAi as main­stream can­cer ther­a­py

Shortly after Sirnaomics brought in a $47 million Series C for its small interfering RNA pipeline last year, Patrick Lu — the founder, president and CEO — was asked to outline the scientific advances that will be necessary to make better drugs out of RNA tech.

“The next step in the evolution of RNAi as a leading therapeutic will be the ability to safely target organs outside the liver such as lung, brain, etc,” he had offered. “This will revolutionize disease treatments if the industry can demonstrate similar data sets for non-liver targets as we have seen in liver-based diseases.”