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.”

Brian Kaspar. AveXis via Twitter

AveX­is sci­en­tif­ic founder fires back at No­var­tis CEO Vas Narasimhan, 'cat­e­gor­i­cal­ly de­nies any wrong­do­ing'

Brian Kaspar’s head was among the first to roll at Novartis after company execs became aware of the fact that manipulated data had been included in its application for Zolgensma, now the world’s most expensive therapy.

But in his first public response, the scientific founder at AveXis — acquired by Novartis for $8.7 billion — is firing back. And he says that not only was he not involved in any wrongdoing, he’s ready to defend his name as needed.

I reached out to Brian Kaspar after Novartis put out word that he and his brother Allen had been axed in mid-May, two months after the company became aware of the allegations related to manipulated data. His response came back through his attorneys.

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FDA to Sarep­ta: Your wide­ly an­tic­i­pat­ed fol­lowup to Ex­ondys 51 is not get­ting an ac­cel­er­at­ed OK for Duchenne MD

In one of the least anticipated moves of the year, the FDA has rejected Sarepta’s application for an accelerated approval of its Duchenne MD drug golodirsen after fretting over safety issues.

In a statement that arrived after the bell on Monday, Sarepta explained the CRL, saying:

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Novartis CEO Vas Narasimhan [via Bloomberg/Getty]

I’m not per­fect: No­var­tis chief Vas Narasimhan al­most apol­o­gizes in the wake of a new cri­sis

Vas Narasimhan has warily stepped up with what might pass as something close to a borderline apology for the latest scandal to engulf Novartis.

But he couldn’t quite get there.

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Levi Garraway. Broad Institute via Youtube

Roche raids Eli Lil­ly for its next chief med­ical of­fi­cer as San­dra Horn­ing plans to step down

We found out Monday morning where Levi Garraway was headed after he left Eli Lilly as head of oncology R&D a few days ago. Roche named Garraway as their new chief medical officer, replacing Sandra Horning, who they say is retiring from the company.

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Af­ter a posse of Wall Street an­a­lysts pre­dict a like­ly new win for Sarep­ta, we're down to the wire on a crit­i­cal FDA de­ci­sion

As Bloomberg notes, most of the Wall Street analysts that cover Sarepta $SRPT are an upbeat bunch, ready to cheer on the team when it comes to their Duchenne MD drugs, or offer explanations when an odd setback occurs — as happened recently with a safety signal that was ‘erroneously’ reported last week.

Ritu Baral Cowen
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UP­DAT­ED: No­var­tis spin­off Nabri­va fi­nal­ly scores its first an­tibi­ot­ic ap­proval

In May, Nabriva Therapeutics suffered a setback after the FDA rejected its antibiotic for complicated urinary tract infections — the Novartis spinoff has now had some better luck with the US agency, which on Monday approved its other drug for community-acquired bacterial pneumonia.

The drug, lefamulin, has been developed as an intravenous and oral formulation and been tested in two late-stage clinical trials. The semi-synthetic compound, whose dosing can be switched between the two formulations, is engineered to inhibit the synthesis of bacterial protein by binding to a part of the bacterial ribosome.

Saqib Islam. CheckRare via YouTube

Spring­Works seeks $115M to push Pfiz­er drugs across fin­ish line while Sat­suma sells mi­graine play in $86M IPO

SpringWorks and Satsuma — both biotech spinouts that have closed B rounds in April — are loading up with IPO cash to boost their respective late-stage plans.

Bain-backed SpringWorks is the better-known company of the two, and it’s gunning for a larger windfall of $115 million to add to $228 million from previous financings. In the process, the Stamford, CT-based team is also drawing the curtains on the partnerships it has in mind for the pair of assets it had initially licensed from Pfizer.

Mi­nor­i­ty racial groups con­tin­ue to be dis­mal­ly rep­re­sent­ed in can­cer tri­als — study

Data reveal that different racial and ethnic groups — by nature and/or nurture — can respond differently in terms of pharmacokinetics, efficacy, or safety to therapeutics, but this disparity is not necessarily accounted for in clinical trials. A fresh analysis of the last decade of US cancer drug approvals suggests the trend continues, cementing previous research that suggests oncology trials are woefully under-representative of the racial makeup of the real world.

Van­da shares slide af­ter FDA spurns their big end­point and re­jects a pitch on jet lag re­lief

Back in the spring of last year, Vanda Pharmaceuticals $VNDA served up a hot stew of mixed data for a slate of endpoints related to what they called clear evidence that their melatonin sleep drug Hetlioz (tasimelteon) could help millions of travelers suffering from jet lag.

Never mind that they couldn’t get a planned 90 people in the study, settling for 25 instead; Vanda CEO Mihael H. Polymeropoulos said they were building on a body of data to prove it would help jet-lagged patients looking for added sleep benefits. And that, they added, would be worth a major upgrade from the agency as they sought to tackle a big market.