Cell ther­a­py start­up rais­es $16 mil­lion to fund its quest for the Holy Grail in re­gen­er­a­tive med­i­cine

Shinya Ya­mana­ka No­bel Prize

In 2006, Shinya Ya­mana­ka shook stem cell re­search with his dis­cov­ery that ma­ture cells can be con­vert­ed in­to stem cells, re­liev­ing a long­stand­ing po­lit­i­cal-eth­i­cal block­age and throw­ing open med­ical re­search on every­thing from curb­ing eye de­gen­er­a­tion to or­gan print­ing.

But that process still has pit­falls, in­clud­ing in risk and scal­a­bil­i­ty, and some re­searchers are ex­plor­ing an­oth­er way first hint­ed at years ago: new tech­nol­o­gy to con­vert ma­ture cells di­rect­ly in­to oth­er ma­ture cells with­out the com­plex and time-con­sum­ing process of first mak­ing them in­to stem cells.

One of those com­pa­nies, Mo­gri­fy, just raised $16 mil­lion in Se­ries A fi­nanc­ing to bring its over­all fund­ing to over $20 mil­lion since its Feb­ru­ary launch. Led by CEO Dar­rin Dis­ley, the fund­ing will help ex­pand their new base in Cam­bridge to a 60-strong staff and push for­ward their di­rect-con­ver­sion ap­proach to cell ther­a­py through re­search and li­cens­ing. In­vestors in­clude Park­walk Ad­vi­sors and Ahren In­no­va­tion Cap­i­tal.

They list po­ten­tial ap­pli­ca­tions as treat­ments for mus­cu­loskele­tal and au­to-im­mune dis­or­ders, can­cer im­munother­a­py, and ther­a­pies for oc­u­lar and res­pi­ra­to­ry dis­eases. For ex­am­ple, you could use it re­gen­er­ate car­ti­lage in arthri­tis pa­tients.

“If you could take a cell from one part of the body and turn it in­to any oth­er cell at any oth­er stage of de­vel­op­ment for an­oth­er part of the body, you ef­fec­tive­ly have the Holy Grail of re­gen­er­a­tive med­i­cine,” Dis­ley told Labiotech.eu in April.

Mo­gri­fy’s ad­van­tage over the Ya­mana­ka method called in­duced pluripo­tent stem cells (iPS), is that in the­o­ry it can be more scal­able and avoid the prob­lems as­so­ci­at­ed with iPS. These in­clude in­sta­bil­i­ties aris­ing from the in­duced im­ma­ture state and an in­creased risk of can­cer if any pluripo­tent cells re­main in the body.

The con­cept be­hind Mo­gri­fy ac­tu­al­ly pre­dates, by near­ly 19 years, Ya­mana­ka’s dis­cov­ery, which fast won him the 2012 No­bel Prize in Med­i­cine. A 2017 Na­ture study on “trans­d­if­fer­en­ti­a­tion,” as the process is called, of fi­brob­lasts in­to car­diac tis­sue traced the idea to a 1987 find­ing that a mas­ter gene reg­u­la­tor could con­vert mice fi­brob­lasts in­to skele­tal mus­cle.

The prob­lem though, ac­cord­ing to Mo­gri­fy, is that most cur­rent ef­forts re­ly on an ex­haust­ing guess-and-check process. With hun­dreds of cell types and an even greater num­ber of tran­scrip­tion fac­tors — the pro­gram that re­codes the cell — find­ing the right fac­tor for the right cell can be like a cus­to­di­an with a jan­gling, un­marked key ring try­ing to get in­to a build­ing with thou­sands of locks.

Mo­gri­fy’s key tech is a com­put­er mod­el they say can pre­dict the right com­bi­na­tion. The sci­en­tists be­hind the plat­form pub­lished a 2016 study in Na­ture ap­ply­ing the mod­el to 173 hu­man cell types and 134 tis­sues.

Be­fore Mo­gri­fy, Dis­ley led the Cam­bridge-based gene-edit­ing com­pa­ny Hori­zon Dis­cov­ery.

How Pa­tients with Epilep­sy Ben­e­fit from Re­al-World Da­ta

Amanda Shields, Principal Data Scientist, Scientific Data Steward

Keith Wenzel, Senior Business Operations Director

Andy Wilson, Scientific Lead

Real-world data (RWD) has the potential to transform the drug development industry’s efforts to predict and treat seizures for patients with epilepsy. Anticipating or controlling an impending seizure can significantly increase quality of life for patients with epilepsy. However, because RWD is secondary data originally collected for other purposes, the challenge is selecting, harmonizing, and analyzing the data from multiple sources in a way that helps support patients.

Re­gen­eron's Evkeeza shows promise in curb­ing high triglyc­erides, but will ge­net­ic dis­par­i­ties lim­it use?

When Regeneron scored an early approval for lipid lowering antibody Evkeeza back in February, the drugmaker cracked open a new pathway to lower abnormally high cholesterol levels. Now, Regeneron is chasing high triglycerides as well with some promising mid-stage data — but will genetic restrictions limit the drug’s use?

Regeneron’s Evkeeza (evinacumab) cut median triglyceride levels by more than 800 mg/dL (57%) in patients with a rare disorder causing abnormally high triglyceride levels compared with an overall increase of 50 mg/dL (1.8%) in participants on placebo, according to Phase II data presented Sunday at the virtual American College of Cardiology meeting.

$DNA is once again on NYSE; FDA clears Soliris chal­lenger for the mar­ket; Flag­ship’s think­ing big again with eR­NA; and more

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I still remember the uncertainty in the air last year when nobody was sure whether ASCO would cancel their in-person meeting. But it’s now back again for the second virtual conference, and Endpoints News is here for it. Check out our 2-day event reviewing the landscape of cancer R&D and send news our way.

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As­traZeneca's Farx­i­ga missed big on Covid-19 study, but it's tak­ing SGLT2 safe­ty da­ta as a sil­ver lin­ing

AstraZeneca hasn’t seen many setbacks in recent months for SGLT2 inhibitor Farxiga, which broke ground in heart failure and kidney disease regardless of diabetes diagnosis. But the British drugmaker had to admit defeat in taking Farxiga into Covid-19, but follow-up results add a bit of a silver lining to that trial’s safety data.

Of hospitalized Covid-19 patients dosed with AstraZeneca’s Farxiga, 11.2% experienced an organ failure or died after 30 days of therapy compared with 13.8% of those given placebo, according to follow-up data from the DARE-19 study revealed Sunday at the virtual American College of Cardiology meeting.

Pfiz­er, Bris­tol My­er­s' Eliquis flops in post-heart surgery pa­tients, spurring an 'un­ex­plained sig­nal' in cer­tain deaths

Pfizer and Bristol Myers Squibb’s non-warfarin blood thinner Eliquis has raced out to become the most prescribed drug of its class on the market — even overtaking warfarin’s long-time lead. But in tricky-to-treat patients after a valve replacement, an investigator-sponsored study couldn’t turn up benefit and raised a troubling safety signal.

Eliquis failed to show benefit over standard of care in preventing serious clinical outcomes after a transaortic valve replacement (TAVR) and was linked to an “unexplained signal” in a subset of populations with a higher rate of non-CV deaths who did not need blood thinners apart from the surgery, according to data presented Saturday at the virtual American College of Cardiology meeting.

Gene ther­a­py from Bio­gen's $800M buy­out flops in mid-stage study, deal­ing blow to new am­bi­tions

The #2 candidate from Biogen’s $800 million ocular gene therapy buyout has failed in a mid-stage trial, dealing an early blow to the big biotech’s plans to revitalize its pipeline with new technologies.

Biogen announced that the candidate, an experimental treatment for a rare and progressive form of blindness called X-linked retinitis pigmentosa (XLRP), failed to sufficiently improve vision in patients’ treated eye — patients only received an injection in one eye — after a year, on a standard scale, compared to their untreated eye. The company said they saw “positive trends” on several secondary endpoints, including visual acuity, but declined to say whether the trial actually hit any of those endpoints.

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Michael Dell (Richard Drew, AP Images)

'Dude, you're get­ting a Del­l' — as a new deep-pock­et biotech in­vestor

What happens when you marry longtime insiders in the global biotech VC game with the family fund of tech billionaire Michael Dell, a synthetic biology legend out of MIT and Harvard and the former director of the NCI?

Today, the answer is a newly financed, $200 million biotech SPAC now cruising the industry for a top player interested in finding a short cut to Nasdaq.

Orion Biotech Opportunities priced their blank check company today, raising $200 million with Dell’s multibillion-dollar MSD group’s commitment on investing another $20 million in a forward-purchase agreement.

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Bris­tol My­ers backs up its case for heart drug mava­camten as FDA weighs app in car­diomy­opa­thy

When Bristol Myers Squibb signed off on its $13 billion acquisition of MyoKardia back in October, it was making a big bet that lead drug mavacamten could prove a game changer in cardiac myopathy. Now, with the drug up for FDA review, Bristol Myers is backing up its case with new quality of life data.

Patients dosed with myosin inhibitor mavacamten posted a clinically significant increase in scores on the Kansas City Cardiomyopathy Questionnaire, a catch-all summary of symptoms and quality of life markers, over placebo at 30 weeks, according to data from the Phase III EXPLORER-HCM study presented Saturday at the virtual American College of Cardiology meeting.

Vas Narasimhan (Photographer: Simon Dawson/Bloomberg via Getty Images)

No­var­tis whiffs on En­tresto study af­ter heart at­tacks — but that does­n't mean it's go­ing down qui­et­ly

If Novartis learned one thing from its interaction with the FDA over its latest heart failure approval for Entresto, it was that missing a primary endpoint may not be the nail in the coffin. Now, Entresto has missed again on a late-stage study in high-risk heart patients, and it’s already sowing the seeds for a path forward regardless.

Novartis’ Entresto couldn’t best standard-of-care ramipril in staving off a composite of deaths and heart failure events in patients with left ventricular systolic dysfunction and/or pulmonary congestion who have had a prior heart attack, according to topline data from the Phase III PARADISE-MI study revealed Saturday at the virtual American College of Cardiology meeting.