Brendan Frey, Deep Genomics

SpaceX in­vestor backs Toron­to AI up­start's jour­ney in­to the 'dark re­gion' of ge­net­ic dis­eases

Bren­dan Frey set out, when he be­gan the project to pick out a lead pro­gram for Deep Ge­nomics, to prove that the ar­ti­fi­cial in­tel­li­gence sys­tems his lab has de­signed can iden­ti­fy new drug tar­gets and find a win­ning can­di­date much faster than tra­di­tion­al meth­ods. Now that they have ze­roed in on an an­ti­sense oligonu­cleotide ex­on-skip­ping ther­a­py for a sub­type of Wil­son dis­ease — se­lect­ed out of 2,400 ail­ments and 120,000 un­der­ly­ing ge­net­ic mu­ta­tions — as their face case, the Toron­to-based biotech is ready to delve in­to new fron­tiers with their AI tech.

Deep Ge­nomics plans to spend rough­ly half of its new $40 mil­lion on clin­i­cal de­vel­op­ment of DG12P1, whose first-in-hu­man tri­al is slat­ed for 2021; and the oth­er half on strength­en­ing var­i­ous com­po­nents of its ma­chine learn­ing sys­tems, from ro­bot­ics to as­says. Fu­ture Ven­tures, an in­vestor in Tes­la and SpaceX, led the Se­ries B round while Am­pli­tude Ven­tures, Mag­net­ic Ven­tures, Khosla Ven­tures and True Ven­tures joined.

While they took a splice mod­u­lat­ing ap­proach for their first AI-dis­cov­ered com­pound akin to what Bio­gen has with Spin­raza, Deep Ge­nomics is next fo­cused on hap­loin­suf­fi­cien­cies — dis­or­ders where in­creased ex­pres­sion lev­els of one func­tion­al gene would be valu­able. In oth­er words, where­as the pre­vi­ous chal­lenge lied in find­ing the right mu­ta­tion to tin­ker, the new puz­zle is how best to boost a known tar­get.

It’s a rel­a­tive­ly new ap­pli­ca­tion of oligonu­cleotides with no ap­proved drugs, which is al­so be­ing ex­plored at Stoke Ther­a­peu­tics.

“There are many dif­fer­ent mech­a­nisms that could be rel­e­vant, and so when you look at all these dif­fer­ent mech­a­nisms and all these dif­fer­ent re­gions of the gene that you could de­sign the oli­go for, there are tens of thou­sands, or even hun­dreds of thou­sands of pos­si­ble com­pounds,” says Frey, a star re­searcher that in­sil­i­co’s Alex Zha­voronkov con­sid­ers “with­out doubt in top 10 sci­en­tists in this field in the world.”

Frey elab­o­rates:

That could be in the 5’ UTR, it could be in the in­tron, it could be in an ex­on, in­tron­ic se­quences are very large, could be in a 3’ UTR, dif­fer­ent kinds of mech­a­nisms may be in­volved. It could be a mat­ter of al­ter­ing the up­stream open read­ing frame, or it could be a mat­ter of an in­tron or ten­sion bot­tle neck, it could be a mat­ter of chang­ing the polyadeny­la­tion site, it could be a com­pound that al­ters sec­ondary struc­tures.

New tools will be re­quired to test all these paths they can po­ten­tial­ly trav­el down, and Deep Ge­nomics’ team of 40-plus is al­ready per­fect­ing one mod­el de­signed to pre­dict polyadeny­la­tion pat­terns.

“Mul­ti­lin­gual­ism is an im­por­tant core val­ue for us,” he pre­vi­ous­ly said. “Every­one at the com­pa­ny has had AI train­ing, and every­one at the com­pa­ny has done wet lab work. In fact I ac­tu­al­ly se­quenced the ge­nom­ic DNA for the Wil­son tar­get to val­i­date it once we edit­ed the cell line to put the pa­tient mu­ta­tion in­to the cells.”

In ad­di­tion to deep­en­ing the clin­i­cal bench, Frey is al­so re­cruit­ing for the busi­ness de­vel­op­ment unit.

“Our pipeline is over­flow­ing, and so we’re fo­cused on sign­ing some busi­ness deals,” he tells End­points News in the lead­up to the an­nu­al JP Mor­gan con­fab in San Fran­cis­co.

That in­cludes two ad­di­tion­al pro­grams for Wil­son’s dis­ease that, to­geth­er with the lead pro­gram, would ad­dress up to a quar­ter of the 230,000 pa­tients world­wide. There’s one oth­er undis­closed meta­bol­ic can­di­date for which Frey plans to sub­mit an IND this year, some com­pounds for retinopa­thy, and a dozen hap­loin­suf­fi­cient projects in de­vel­op­ment, he says.

The Fac­tors Dri­ving a Rapid Evo­lu­tion of Gene & Cell Ther­a­py and CAR-T Clin­i­cal Re­search in APAC

APAC is the fastest growing region globally for cell & gene therapy trials representing more than a third of all cell & gene studies globally, with China leading in the region. 

APAC is the leading location globally for CAR-T trials with China attracting ~60% of all CAR-T trials globally between 2015-2022. The number of CAR-T trials initiated by Western companies has rapidly increased in recent years (current CAGR of about 60%), with multiple targets being explored including CD19, CD20, CD22, BCMA, CD30, CD123, CD33, CD38, and CD138.

The End­points 11; blue­bird's $3M gene ther­a­py; Bio­gen tout new neu­ro da­ta; Harsh re­views for can­cer drugs; 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.

Reading about John Carroll’s pick of biotech’s most promising startups has become a treasured tradition. If you ever get curious about previous classes of the Endpoints 11, you can find all of them (plus a number of our other regular specials) here.

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EMA warns of short­ages of two Boehringer heart drugs due to a spike in de­mand

The EMA is putting EU member states on alert over the shortage of two drugs that counter heart attacks due to an uptick in demand.

On Friday, the EMA sent out a warning that two Boehringer Ingelheim drugs are experiencing a shortage: Actilyse and Metalyse. The drugs are used as emergency treatments for adults experiencing acute myocardial infarction, or a heart attack, by dissolving blood clots that have formed in the blood vessels.

The End­points 11: The top pri­vate biotechs in pur­suit of new drugs. Push­ing the en­ve­lope with pow­er­ful new tech­nolo­gies

Right around the beginning of the year, we got a close-up look at what happens after a boom ripples through biotech. The crash of life sciences stocks in Q1 was heard around the world.

In the months since, we’ve seen the natural Darwinian down cycle take effect. Reverse mergers made a comeback, with more burned out shells to go public at a time IPOs and road shows are out of favor. And no doubt some of the more recent arrivals on the investing side of the business are finding greener pastures.

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As­traZeneca, Mer­ck cull one Lyn­parza in­di­ca­tion in heav­i­ly pre­treat­ed ovar­i­an can­cer pa­tients

Just one day after blockbuster Lynparza got access to another indication in China, its Big Pharma owners have decided to withdraw it in certain patients after reviewing Phase III data.

The two companies that work together on Lynparza decided to recall one of the indications several weeks ago in a specific type of ovarian cancer, Lynparza’s first indication when it was first FDA-approved in 2014. Initial data showed that rates of overall survival in patients with at least three rounds of chemo before getting on the PARP inhibitor were lower than in patients with less previous chemo treatment.

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Fu­ji­film con­tin­ues CD­MO ex­pan­sion, break­ing ground on $435M UK site

Fujifilm’s CDMO arm, Fujifilm Diosynth, has been on a roll this month as the company has recently broken ground on a major project in Europe and it appears to be keeping up the momentum.

Fujifilm Diosynth announced that it has kicked off an expansion project for its microbial manufacturing facility at its campus in the town of Billingham, UK, in the northeast of England.

The 20,000 square-foot, £400 million ($435 million) expansion will add clean rooms, purification suites and a packing area along with more space for the manufacturing itself.

An­oth­er Cipla site lands a Form 483 over clean­ing is­sues and QC con­trols

A Cipla drug manufacturing site in India has once again landed in the crosshairs of FDA inspectors.

The facility in question is Cipla’s drug manufacturing facility in the village of Verna, in the state of Goa in India’s southwest. In a sign that foreign inspections might ramp up again, the FDA’s visit from Aug. 16 to Aug. 22 uncovered six observations.

The 11-page report noted that environmental monitoring at the site did not properly ensure that microbial contaminants were not making any impact in the aseptic filling areas. It also found that procedures meant to stop microbial contamination were not adequately conducted in aseptic areas of the facility.

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FDA ad­comm takes down Se­cu­ra Bio's leukemia drug af­ter fi­nal tri­al re­sults show po­ten­tial OS detri­ment

The FDA’s Oncologic Drugs Advisory Committee on Friday voted 8-4 against the benefit-risk profile of Secura Bio’s PI3K inhibitor Copiktra (duvelisib), which won approval in September 2018 as a third-line treatment for relapsed or refractory CLL or SLL, but updated pivotal trial results raised safety questions.

In addition to the serious and fatal toxicities of duvelisib, FDA speakers at the ODAC meeting pointed to an evolved treatment landscape for CLL and SLL, with targeted BTK or BCL2 inhibitors (front-line or second-line), and data pointing to a “potential detriment” in overall survival for duvelisib. But some ODAC members noted that the detriment was likely small and that there is some efficacy even as the data are difficult to interpret.

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Solicitor General Elizabeth Prelogar

Should SCO­TUS hear Am­gen's Repatha case? So­lic­i­tor gen­er­al says no

Back in April, Amgen said it was encouraged by the solicitor general’s anticipated review of its Supreme Court petition to rehear a Repatha patent case. They’re likely much less optimistic about the outcome now.

Solicitor General Elizabeth Prelogar wrote in a recent 27-page brief that Amgen’s arguments “lack merit and further review is not warranted.”

The case traces back to a suit filed in 2014 against Sanofi and Regeneron’s Praluent, which ended up beating Amgen’s PCSK9 blockbuster Repatha to market by a month just a year later.