Part pro­ce­dure, part drug: Robert Ang joins Sid­dhartha Mukher­jee in pi­o­neer­ing a new type of cell en­gi­neer­ing

In a re­cent chron­i­cle on the promise and price of cell ther­a­pies, Sid­dhartha Mukher­jee — au­thor, on­col­o­gist and Co­lum­bia pro­fes­sor among his oth­er ti­tles — mused about how en­gi­neered T cells had blurred the tra­di­tion­al bound­aries sep­a­rat­ing a pro­ce­dure and a drug. “Pro­ce­dures come alive in the tin­ker­ing, fuss­ing hands of their op­er­a­tors,” he ob­served, while a “drug, in con­trast, is a de­per­son­al­ized en­ti­ty.” For the new gen­er­a­tion of metic­u­lous­ly man­u­fac­tured CAR-T to reach the mass­es, in­no­va­tors must mar­ry the it­er­a­tive na­ture of a pro­ce­dure with the pro­duc­tion ef­fi­cien­cy of a drug — and add a ruth­less pur­suit of the lean­est, cheap­est process pos­si­ble.

Robert Ang

He’s putting that con­cept to work in a new ven­ture. Vor Bio­phar­ma, a biotech fledg­ling bred at PureTech and now set­tling in­to a new nest at Kendall Square, is en­gi­neer­ing hematopoi­et­ic stem cells to rid them of the anti­gen CD33 so that acute myeloid leukemia pa­tients may reap the ben­e­fits of CD33- tar­get­ed ther­a­pies with­out the tox­i­c­i­ties.

What Mukher­jee came up with is an “ex­treme­ly el­e­gant” ap­proach, says Robert Ang, who’s start­ing his first week as CEO of Vor. The prod­uct, VOR33, would in ef­fect shield healthy blood cells and the bone mar­row from a T cell at­tack.

Sid­dhartha Mukher­jee

An ex vi­vo pro­ce­dure in­volv­ing a sin­gle ge­net­ic ed­it of healthy donor cells rep­re­sent “ide­al en­try points for CRISPR-based ther­a­peu­tics, and that’s pre­cise­ly what VOR33 is,” he says. “And so we ex­pect the pro­duc­tion process to be rel­a­tive­ly straight­for­ward with on­ly sev­er­al-day process but of course you can nev­er take that for grant­ed.”

“I’ve just been itch­ing to get go­ing,” adds the biotech vet­er­an, who had keen­ly learned lessons about com­pa­ny build­ing as em­ploy­ee #5 and chief busi­ness of­fi­cer of neoanti­gen play­er Neon Ther­a­peu­tics.

Kush Par­mar

Soon af­ter he start­ed pon­der­ing about lead­ing a com­pa­ny of his own he got in touch with Kush Par­ma, man­ag­ing part­ner at 5AM Ven­tures and Vor chair­man who’s al­so work­ing with Mukher­jee on an­oth­er CAR-T project. 5AM was joined by RA Cap­i­tal Man­age­ment, Os­age Uni­ver­si­ty Part­ners and PureTech, as well as J&J’s ven­ture arm and No­var­tis In­sti­tutes for Bio­Med­ical Re­search, for a $42 mil­lion Se­ries A an­nounced ear­li­er this year.

It’s still ear­ly days — so ear­ly that he’s not ready to share how many are on the team — but Ang al­so has a clear time­line for en­ter­ing the clin­ic in 18 months. A more near-term goal would be to sit down with the FDA about an IND by the end of the year.

“We want to make sure that the prod­uct is safe, and that the prod­uct en­grafts just like oth­er typ­i­cal trans­plants,” he says of the first hu­man tri­al they are work­ing to­ward. “But at the same time we’re al­so very in­ter­est­ed to see what hap­pens when the pa­tients — if they do progress, how the trans­plants be­have when tar­get­ed ther­a­py is ap­plied.”

The com­par­i­son to stan­dard-of-care would be cru­cial as Vor proves that it’s just as good, if not bet­ter than the bone mar­row trans­plants that AML pa­tients would oth­er­wise have re­ceived.

As for the sub­se­quent tar­get­ed ther­a­py that VOR33 would dove­tail in­to, the sea­soned BD ex­ec main­tains there’s a good amount of op­tion­al­i­ty as to which modal­i­ty they go with. So far Pfiz­er claims the on­ly mar­ket­ed drug hit­ting CD33 in My­lotarg, and a slate of oth­ers are in de­vel­op­ment. Nonethe­less, he notes that J&J and No­var­tis both have strong pipelines in tar­get­ed ther­a­py and CAR-T.

It’s not just CD33, ei­ther. Vor plans to ap­ply the same gene-edit­ing ap­proach to a num­ber of tar­gets, cre­at­ing com­pan­ion pro­ce­dures for mul­ti­ple tar­get­ed ther­a­pies.

Ang, who trained as a doc­tor in Aus­tralia and had stints at both Boston Con­sult­ing Group and Fra­zier Health­care Ven­tures be­fore tak­ing on front­line biotech roles, sees build­ing up the cul­ture at Vor as one of his key tasks.

“Neon’s cul­ture is ab­solute­ly in­cred­i­ble, I’d love to em­u­late that, and al­so build on the great cul­ture that Vor it­self has cre­at­ed over the past few months,” he says. “Vor peo­ple are high­ly col­lab­o­ra­tive, love sci­ence, but are al­so dri­ven by a high­er pur­pose. So build­ing on that and for­mal­iz­ing that will be re­al­ly im­por­tant in the months ahead.”

UP­DAT­ED: In a stun­ning turn­around, Bio­gen says that ad­u­canum­ab does work for Alzheimer's — but da­ta min­ing in­cites con­tro­ver­sy and ques­tions

Biogen has confounded the biotech world one more time.

In a stunning about-face, the company and its partners at Eisai say that a new analysis of a larger dataset on aducanumab has restored its faith in the drug as a game-changer for Alzheimer’s and, after talking it over with the FDA, they’ll now be filing for an approval of a drug that had been given up for dead.

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Vas Narasimhan. Getty Images

UP­DAT­ED: Failed PhI­II fe­vip­iprant tri­als pour more cold wa­ter on No­var­tis' block­buster R&D en­gine — and briefly spread the chill to a high-pro­file biotech

Back in July, during an investor call where Novartis execs ran through an upbeat assessment of their Q2 performance, CEO Vas Narasimhan and development chief John Tsai were pressed to predict which of the two looming Phase III readouts — involving cardio drug Entresto and asthma therapy fevipiprant, respectively — had a higher likelihood of success. Tsai gave the PARAGON-HF study with Entresto minimally better odds, but Narasimhan emphasized that their strategy of giving fevipiprant to more severe patients gave them confidence.

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UP­DAT­ED: The FDA sets a reg­u­la­to­ry speed record, pro­vid­ing a snap OK for Ver­tex's break­through triplet for cys­tic fi­bro­sis

The FDA has approved Vertex’s new triplet for cystic fibrosis at a record-setting speed.

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David Liu, Liu Group

David Liu un­veils newest ad­vance­ment in CRISPR tech: Prime edit­ing

The researcher behind base-editing is out with what some scientists are hailing as the biggest advancement in CRISPR technology since that 2016 breakthrough: “prime editing.” The new molecular gadget is capable of erasing any base pair and stenciling in another and cutting or adding long segments of DNA without breaking both strands of the helix.

David Liu, base editing pioneer and founder of Beam Therapeutics, published the findings in Nature alongside Andrew Anzalone. They estimated that the breakthrough “in principle” puts 89% of human diseases in purview — although experts cautioned that human therapies were a long way off.

Bhaskar Chaudhuri. Frazier Healthcare Partners

Fra­zier Health­care Part­ner­s' der­ma­tol­ogy up­start at­tracts a mar­quee syn­di­cate, $94M+ for 'in-be­tween' top­i­cal drug

For the past three years Frazier Healthcare Partners’ Bhaskar Chaudhuri has been carefully and quietly grooming Arcutis Therapeutics, a new dermatology play he co-founded to deliver topical formulations of well-known drugs. Now that the biotech is poised to enter Phase III, he’s being joined by a marquee syndicate for its $94.5 million Series C.

HBM Healthcare Investments, Vivo Capital, BlackRock, Omega Funds, Pivotal BioVentures, and Goldman Sachs jumped on board, joining Bain Capital Life Sciences, OrbiMed and RA Capital Management in backing Arcutis’ lead topical cream for plaque psoriasis.

A new com­pa­ny en­ters the Tec­fidera fight, of­fer­ing to kill two birds

The remedy for the most common side effect for one of the most common multiple sclerosis drugs is simple: aspirin.

Taking aspirin with Biogen’s Tecfidera will reduce the flush, a sometimes painful form of red skin irritation, many patients experiences. The problem is that the aspirin has to be taken at least 30 minutes before Tecfidera, turning a simple twice-a-day, one-dose oral drug into a staggered two-drug regimen.

UP­DAT­ED: Bris­tol-My­ers makes Op­di­vo pitch for front­line lung can­cer with open la­bel PhI­II study

Despite a head start, when Bristol-Myers Squibb and its pioneering checkpoint inhibitor Opdivo suffered a key lung cancer setback in 2016, they found themselves relegated to the backseat as Merck’s Keytruda seized the wheel on the road to immunotherapy stardom. Bristol-Myers has since suffered blow after blow in its quest to take a big slice of the lucrative market, peppered with some small successes. On Tuesday, the New Jersey drugmaker touted positive data from a Phase III open-label study in a bid to carve itself a piece of the frontline lung cancer market.

Take­da tees up $420M deal for celi­ac an­ti­dote, con­tin­u­ing R&D re­fo­cus

Sometime in the 1st century AD, a patient presented to Arataeus looking like a varicose ghost. He was “emaciated and atrophied, pale, feeble and incapable of performing any of his accustomed works,” the Greek physician wrote, with hollow temples and huge veins running all over his body.

A dysfunctional digestive system, Arataeus concluded – an imbalance he attributed to a “heat” deficiency in a system he and other Greeks regarded as functioning similarly to an oven – and coined a term: coeliac disease, after the Greek word for abdomen.

IM­brave150: Roche’s reg­u­la­to­ry crew plans a glob­al roll­out of Tecen­triq com­bo for liv­er can­cer as PhI­II scores a hit

Just weeks after Bristol-Myers Squibb defended its failed pivotal study pitting Opdivo against Nexavar in liver cancer, Roche says it’s beat the frontline challenge with a combination of their PD-L1 Tecentriq with Avastin. And now they’re rolling their regulatory teams in the US, Europe and China in search of a new approval — badly needed to boost a trailing franchise effort.
Given their breakthrough and Big Pharma status as well as the use of two approved drugs, FDA approval may well prove to be something of a formality. And the Chinese have been clear that they want new drugs for liver cancer, where lethal disease rates are particularly high.
Researchers at their big biotech sub, Genentech, say that the combo beat Bayer’s Nexavar on both progression-free survival as well as overall survival — the first advance in this field in more than a decade. We won’t get the breakdown in months of life gained, but it’s a big win for Roche, which has lagged far, far behind Keytruda and Opdivo, the dominant PD-1s that have captured the bulk of the checkpoint market so far.
Researchers recruited hepatocellular carcinoma — the most common form of liver cancer — patients for the IMbrave150 study who weren’t eligible for surgery ahead of any systemic treatment of the disease.
Roche has a fairly low bar to beat, with modest survival benefit for Nexavar, approved for this indication 12 years ago. But they also plan to offer a combo therapy that could have significantly less toxicity, offering patients a much easier treatment regimen.
Cowen’s Steven Scala recently sized up the importance of IMbrave150, noting:

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