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.”

Dan Skovronsky, Eli Lilly CSO

UP­DAT­ED: An­a­lysts are quick to pan Eli Lil­ly's puz­zling first cut of pos­i­tive clin­i­cal da­ta for its Covid-19 an­ti­body

Eli Lilly spotlighted a success for one of 3 doses of their closely-watched Covid-19 antibody drug Wednesday morning. But analysts quickly highlighted some obvious anomalies that could come back to haunt the pharma giant as it looks for an emergency use authorization to launch marketing efforts.

The pharma giant reported that LY-CoV555, developed in collaboration with AbCellera, significantly reduced the rate of hospitalization among patients who were treated with the antibody. The drug arm of the study had a 1.7% hospitalization rate, compared to 6% in the control group, marking a 72% drop in risk.

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Christian Itin, Autolus CEO (Autolus)

#ES­MO20: Au­to­lus pro­vides glimpse of next-gen­er­a­tion CAR-T pro­gram, show­ing ear­ly pos­i­tive safe­ty da­ta

CAR-T therapies were hailed as a breakthrough when Novartis received the first FDA approval for Kymriah back in 2017. Though highly effective at treating certain types of blood cancers, CAR-Ts are also associated with severe and potentially deadly side effects, including lethal instances of cytokine release syndrome.

With this in mind, Autolus Therapeutics is looking to take a crack at a safer CAR-T and presented Phase II cohort data for its AUTO3 program at virtual ESMO 2020. The data showed that, among the 35 patients in the cohort being treated for r/r diffuse large B cell lymphoma, there were no instances of Grade 3 or higher CRS. Eight individuals saw Grade 1 inflammation while another four patients reached Grade 2.

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Sean Bo­hen's break from bio­phar­ma is over. The ex-As­traZeneca CMO has re­tired his Big Phar­ma jer­sey and is now — hap­pi­ly — run­ning a lit­tle biotech

The last I had heard about Sean Bohen, he had stepped out of his high-profile job as chief medical officer at AstraZeneca at the beginning of 2019 as CEO Pascal Soriot triggered a broad-ranging R&D shakeup. And then, earlier this week, I got a chance to catch up.

It turns out that Bohen decided at the time that he would not just jump into a new job in the booming biopharma business. As an oncologist, he had worked on the big programs at AstraZeneca, and before that he was at Genentech. That was good for a ticket to just about anyplace in the big biopharma world. But he felt it was time to stop and think things through.

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Rep. Andy Harris (R-MD) (Tasos Katopodis/Pool via AP Images)

UP­DAT­ED: A mi­cro-cap with a po­ten­tial­ly promis­ing coro­n­avirus drug en­lists mask-skep­tic con­gress­man for DSMB

A small biotech that has talked up a potentially promising but unproven treatment for Covid-19 enlisted an unusual member for its study’s Data and Safety Monitoring Board: a sitting Republican congressman with close ties to the CEO and a history of mask skepticism.

NeuroRx, an Israeli biotech testing a lung inflammation drug in Covid-19 patients, tapped Maryland Rep. Andy Harris for the DSMB, Politico reported. Harris is an anesthesiologist but not a biostatistician, and he has questioned the CDC about a “cult of masks” in the US. Harris has known NeuroRx CEO Jonathan Javitt since the two worked at Johns Hopkins together over 20 years ago.

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#ES­MO20: Alk­er­mes of­fers their first snap­shot of a ben­e­fit for their next-gen IL-2 drug. But why did 1 pa­tient starve to death?

Everyone in the cancer R&D arena is looking to build new franchises around better drugs and combos. And one busy pocket of that space is centered entirely on creating an IL-2 drug that can be as effective as the original without the toxicity that damned it to the sidelines.

Alkermes $ALKS formally tossed its hat into the ring of contenders at virtual ESMO today, highlighting the first glimpse of efficacy for their candidate, ALKS 4230, as both a monotherapy as well as in combination with Merck’s Keytruda.

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Albert Bourla (Photo by Steven Ferdman/Getty Images)

Pfiz­er match­es Mod­er­na with their full Covid-19 tri­al blue­print — As­traZeneca says it will un­veil its pro­to­col 'short­ly'

Yesterday, after sustained public pressure as Moderna released its Phase III Covid-19 trial blueprint, Pfizer released its own full trial design for their vaccine trials. The move was designed to boost transparency and shore up public trust in the vaccines, but it also revealed differences in how the two companies are approaching the much-watched studies while failing to satisfy the demands of the fiercest advocates for transparency.

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Stronger to­geth­er? Boehringer and Mi­rati team to put first KRAS-KRAS com­bo in the clin­ic

Researchers are still waiting to see how much any of the vaunted KRAS drugs now in the clinic can, after decades of preclinical research and some early human studies, help patients. But while they do, two of the leading developers will look to see whether a KRAS-KRAS combo might pose a better shot than any KRAS alone.

Boehringer Ingelheim and Mirati have signed a collaboration to combine Mirati’s closely-watched lead KRAS inhibitor, MRTX849, in a clinical trial with the pan-KRAS blocker that Boehringer has quietly developed with high expectations behind their flashier contenders.

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#ES­MO20: Re­gen­eron, Sanofi eye an­oth­er first for their PD-1 con­tender Lib­tayo with promis­ing da­ta for on­col­o­gy niche

Regeneron and Sanofi took another step forward in the long march towards a greatly expanded market for their late-bloomer PD-1 checkpoint Libtayo.

The two occasional allies posted an objective response rate of 31% for Libtayo among 84 patients suffering from advanced cases of basal cell carcinoma at virtual ESMO. That spotlights progress for 26 patients, 5 of whom had a complete response. The data also reflect a boost in the number of responses seen from the last cut of the numbers.

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A long­time Cy­tomX ex­ec re-emerges at Syn­thekine, an $82M Stan­ford spin­out

Debanjan Ray apparently had big plans when he quietly left his long-held CFO spot at CytomX back in March 2019. He had gotten his own biotech.

Still in its early stages at the time, that biotech, known as Synthekine, is now ready to start talking. They are breaking out of stealth mode today with $82 million in Series A funding led by Canaan Partners, Samsara BioCapital and The Column Group, and plans to rapidly bring a handful of engineered cytokines, including a rejigged IL-2, into the clinic.