Can B cells break the bound­aries of cell ther­a­py? Long­wood start­up has $52M to prove a new en­gi­neer­ing tech

Back in De­cem­ber 2017, as the cell ther­a­py world was still bask­ing in the vir­tu­al­ly back-to-back ap­provals of two pi­o­neer­ing CAR-Ts, re­searchers at Seat­tle Chil­dren’s Re­search In­sti­tute re­port­ed a sci­en­tif­ic first in a dif­fer­ent cor­ner of the field: en­gi­neer B cells to treat dis­ease.

Aleks Radovic-Moreno

The team, led by David Rawl­ings and Richard James, even­tu­al­ly worked with Long­wood Fund to start a biotech around those find­ings. And now At­las Ven­ture and RA Cap­i­tal Man­age­ment are com­ing on board to lead a $52 mil­lion launch round, joined by Al­ta Part­ners, for Be Bio­phar­ma.

“B cells have been such an at­trac­tive cell type,” Aleks Radovic-Moreno, an en­tre­pre­neur-in-res­i­dence who co-found­ed the biotech, told End­points News. “It just wasn’t their time yet. But now we feel con­fi­dent that it’s their time to step in­to the lime­light.”

The two clas­sic stum­bling blocks, he added, are fig­ur­ing out how to en­gi­neer them ef­fi­cient­ly and cul­ture them in suf­fi­cient quan­ti­ties.

David Rawl­ings

But once Rawl­ings and James cracked the code through ho­mol­o­gy-di­rect­ed re­pair, it opened up po­ten­tial ap­pli­ca­tions be­yond what cur­rent cell ther­a­pies can do. While T cells are de­signed to kill cells marked by cer­tain anti­gens, B cells’ unique func­tion is that they make “un­be­liev­able quan­ti­ties of pro­teins” — from an­ti­bod­ies to im­mune mod­u­lat­ing fac­tors.

You can al­so pro­gram a B cell to go to a spe­cif­ic tis­sue, with­out the need for con­di­tion­ing or lym­phode­ple­tion, while re­tain­ing an op­tion to titrate and re­dose if you don’t get it right the first time.

“If you think about what dis­ease you want where you want a pro­tein to be se­cret­ed in a tar­get­ed fash­ion, that’s ac­tu­al­ly a re­al­ly big list,” Radovic-Moreno said, list­ing can­cer, au­toim­mune dis­eases, mono­genic dis­or­ders and in­fec­tious dis­eases as ar­eas be­ing ex­plored.

Richard James

In a pre­vi­ous in­ter­view, James al­so gave he­mo­phil­ia B as an ex­am­ple of a pro­tein de­fi­cien­cy dis­ease where a B cell ther­a­py can po­ten­tial­ly cure pa­tients.

Be Bio ben­e­fits from the trail that hun­dreds of T cell ther­a­py play­ers have now trav­eled, step­ping in­to a world where lo­gis­tics, ge­net­ic mod­i­fi­ca­tion and cell pu­rifi­ca­tion tools are read­i­ly avail­able. But its core area of ex­per­tise — map­ping out the bi­ol­o­gy of B cells and ma­nip­u­lat­ing them — re­mains one that’s on­ly hous­ing aca­d­e­m­ic groups so far.

David Stein­berg

Cur­rent­ly man­aged by an in­ter­im team con­sist­ing of Radovic-Moreno as pres­i­dent and David Stein­berg as CEO, the team is grow­ing every week at the Alexan­dria Launch­Labs in Kendall Square. In ad­di­tion to the sci­en­tif­ic founders, it’s al­so guid­ed by an il­lus­tri­ous sci­en­tif­ic ad­vi­so­ry board, con­sist­ing of Frances Eun-Hyung Lee, an asth­ma ex­pert at Emory, as well as Har­vard’s Shiv Pil­lai and UCSF’s Ja­son Cys­ter, who bring years of ex­pe­ri­ence study­ing B cells.

He may not be ready to dis­cuss con­crete drug tar­gets or time­lines yet, but for Radovic-Moreno, who played a lead­ing role in get­ting Sid­dhartha Mukher­jee’s en­gi­neered hematopoi­et­ic stem cells off the ground at Vor Bio, it’s all rem­i­nis­cent of the ear­ly days of T cell work.

“I wouldn’t be sur­prised if we see a sim­i­lar tra­jec­to­ry 5 years from to­day,” he said. “I don’t think there will be hun­dreds of B cell com­pa­nies, but I’m gonna bet it’s more than one.”

At the In­flec­tion Point for the Next Gen­er­a­tion of Can­cer Im­munother­a­py

While oncology researchers have long pursued the potential of cellular immunotherapies for the treatment of cancer, it was unclear whether these therapies would ever reach patients due to the complexity of manufacturing and costs of development. Fortunately, the recent successful development and regulatory approval of chimeric antigen receptor-engineered T (CAR-T) cells have demonstrated the significant benefit of these therapies to patients.

All about Omi­cron; We need more Covid an­tivi­rals; GSK snags Pfiz­er’s vac­cine ex­ec; Janet Wood­cock’s fu­ture at FDA; and more

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Lisa Deschamps, AviadoBio CEO

Ex-No­var­tis busi­ness head hops over to a gene ther­a­py start­up — and she's reeled in $80M for a dash to the clin­ic

Neurologist and King’s College London professor Christopher Shaw has been researching neurodegenerative diseases like ALS and collaborating with drugmakers for the last 25 years in the hopes of pushing new therapies forward. But unfortunately, none of those efforts have come anywhere close to fruition.

“So, you know, after 20 years in the game, I said, ‘Let’s try and do it ourselves,’” he told Endpoints News. 

Merck's new antiviral molnupiravir (Quality Stock Arts / Shutterstock)

As Omi­cron spread looms, oral an­tivi­rals ap­pear to be one of the best de­fens­es — now we just need more

After South African scientists reported a new Covid-19 variant — dubbed Omicron by the WHO — scientists became concerned about how effective vaccines and monoclonal antibodies might be against it, which has more than 30 mutations in the spike protein.

“I think it is super worrisome,” Dartmouth professor and Adagio co-founder and CEO Tillman Gerngross told Endpoints News this weekend. Moderna CEO Stéphane Bancel echoed similar concerns, telling the Financial Times that experts warned him, “This is not going to be good.”

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Biospec­i­men M&A: Dis­cov­ery ac­quires Al­bert Li's he­pa­to­cyte project; PhI­II tri­al on Bay­er's Nube­qa reached pri­ma­ry end­point

Discovery Life Sciences has acquired what claims to be the Maryland-based host of the world’s largest hepatocyte inventory, known as IVAL, to help researchers select more effective and safer drug candidates in the future.

The combined companies will now serve a wider range of drug research and development scientists, according to Albert Li, who founded IVAL in 2004 and is set to join the Discovery leadership team as the CSO of pharmacology and toxicology.

Radek Spisek, Sotio CEO (Cellestia)

A qui­et Czech biotech bags $315M to dri­ve its blos­som­ing can­cer pipeline through the clin­ic

In the rather insular world of biotech, most innovation inevitably comes from a cluster of R&D hubs — Cambridge, San Francisco, etc. But sometimes success stories sprout from rocky soil, which is most certainly the case with Prague-based Sotio Biotech and its suddenly jam-packed pipeline of cancer drugs.

After years in quiet development, Sotio now has $315 million in new funds to play with from parent company PPF Group, an investment group founded in the Czech Republic, as the biotech looks to advance its growing pipeline through early- and mid-stage trials.

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In­cor­po­rat­ing Ex­ter­nal Da­ta in­to Clin­i­cal Tri­als: Com­par­ing Dig­i­tal Twins to Ex­ter­nal Con­trol Arms

Most drug development professionals are familiar with the nerve-racking wait for the read-out of a large trial. If it’s negative, is the investigational therapy ineffective? Or could the failure result from an unforeseen flaw in the design or execution of the protocol, rather than a lack of efficacy? The team could spend weeks analyzing data, but a definitive answer may be elusive due to insufficient power for such analyses in the already completed trial. These problems are only made worse if the trial had lower enrollment, or higher dropout than expected due to an unanticipated event like COVID-19. And if a trial is negative, the next one is likely to be larger and more costly — if it happens at all.

With on­ly burns to show in gene ther­a­py, Astel­las inks deal with AAV spe­cial­ist Dyno in push for a bet­ter cap­sid

On the hunt for a better AAV capsid for gene therapy, Eric Kelsic’s Dyno Therapeutics has set itself apart with its focus on machine learning to help speed discovery. Now, Japanese drugmaker Astellas — fresh off a slate of gene therapy burns — is taking a bet on Dyno as it looks to the future.

Astellas and Dyno will work together as part of an R&D pact to develop next-gen AAV vectors for gene therapy using Dyno’s CapsidMap platform directed at skeletal and cardiac muscle, the companies said Wednesday. Under the terms of the deal, Dyno will design AAV capsids for gene therapy, while Astellas will be responsible for conducting preclinical, clinical and commercialization activities for gene therapy product candidates using the capsids.

Paul Hudson, Sanofi CEO (Cyril Marcilhacy/Bloomberg via Getty Images)

Sanofi snaps up new vac­cine can­di­date and de­vis­es mR­NA game plan around it — but not for what you think

Paul Hudson has spotlighted vaccines, immunology and dermatology as some of the top R&D focuses at Sanofi. His latest deal brings all of them together.

The French pharma giant isn’t sharing any financial details about the buyout of Origimm, a low-profile, private Austrian biotech whose technology promises to identify antigens causing skin disease and build vaccines against them. Their lead candidate targets acne vulgaris.

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