The hu­man el­e­ment: A biotech up­start hopes to carve a path around faulty an­i­mal mod­els

It’s been a rough few years for lab mice in the lit­er­a­ture. Re­port af­ter re­port scape­goat­ed sci­ence’s fur­ry sub­jects for the pil­ing num­ber of drugs that fail the clin­ic. A Sci­ence study pro­posed build­ing a new “wildling” lab mouse. A well-cov­ered Na­ture pa­per in­di­cat­ed the dif­fer­ences be­tween mice and hu­man brains were re­spon­si­ble for bil­lions of dead-end­ed Alzheimer re­search dol­lars. One Trans­la­tion­al Med­i­cine re­view cit­ed the suc­cess rate of trans­lat­ing can­cer drugs at 8% and an­oth­er con­clud­ed that “even if the next sev­er­al decades were spent im­prov­ing the in­ter­nal and ex­ter­nal va­lid­i­ty of an­i­mal mod­els, the clin­i­cal rel­e­vance of those mod­els would, in the end, on­ly im­prove to some ex­tent.” [ital­ics theirs]

Mark Kot­ter

The fail­ure of our mice ex­per­i­ments to con­sis­tent­ly mod­el drugs has fu­eled in­ter­est in more hu­man-cen­tric de­signs. That in­cludes an emerg­ing tech­nol­o­gy aimed at di­rect­ly pro­gram­ming hu­man cells. And one of the fields most close­ly watched star­tups — the new­ly re­named bit bio — has now an­nounced an ex­pand­ed team, bring­ing in for­mer ex­ec­u­tives from Tes­sa Ther­a­peu­tics and Hori­zon Dis­cov­ery Group for the C-suite and ex­perts in im­munother­a­py, stem cells, and cell pro­gram­ming for the sci­en­tif­ic ad­vi­so­ry board.

Ramy Ibrahim

Paul Mor­rill will be chief busi­ness of­fi­cer and Flo­ri­an Schus­ter COO and CFO, join­ing founder and CEO Mark Kot­ter.

The sci­en­tif­ic ad­vi­so­ry board points to the big po­ten­tial Kot­ter has al­ready billed for his com­pa­ny. Join­ing are Ramy Ibrahim, the CMO for the Park­er In­sti­tute of Can­cer Im­munother­a­py and a for­mer im­muno-on­col­o­gy de­vel­op­er at Bris­tol-My­ers Squibb, and Mar­ius Wernig, who all but in­tro­duced the con­cept of hu­man cell pro­gram­ming in a 2010 Na­ture pa­per. Roger Ped­er­son, a pi­o­neer in the pluripo­tent stem cells you know and love, will serve as chief sci­en­tif­ic ad­vi­sor.

The group will be build­ing a tech­nol­o­gy that promis­es to short­cut the some­times months-long process of gen­er­at­ing stem cells — which it­self was a No­bel prize-win­ning achieve­ment twelve years ago — and con­vert one cell type di­rect­ly in­to any an­oth­er. Orig­i­nal­ly known as Elpis Bio­med, af­ter an an­cient Greek word for the spir­it of hope, they changed their name to bit bio to un­der­score how their cell re­pro­gram­ming works sim­i­lar to giv­ing a com­put­er new code.

“It’s ba­si­cal­ly re­boot­ing a cell with a new pro­gram,” Kot­ter told End­points News.

Flo­ri­an Schus­ter

Since last year’s launch, Kot­ter has hint­ed at the broad ca­pac­i­ty he be­lieves his “Op­ti-OX” plat­form has. He’s spo­ken of ex­pe­dit­ing cell ther­a­py, build­ing off-the-shelf CAR-T, im­prov­ing re­gen­er­a­tive med­i­cine, and even — at the be­hest of a com­pa­ny in the Nether­lands — cul­tured meat.

At the top of their list now, though, are the cells in­volved in im­munother­a­py, in­clud­ing macrophages and den­drit­ic cells that can be lever­aged for at­tack­ing sol­id tu­mors.

Kot­ter, though, is a neu­ro­sur­geon by train­ing and he runs a Cam­bridge Uni­ver­si­ty lab that is tasked with trans­la­tion­al re­search for spinal in­juries and dis­eases. As he tells it, the tech­nol­o­gy is orig­i­nal­ly a re­sponse to prob­lems in trans­la­tion­al re­search; re­peat­ed­ly he was stymied by an­i­mal cells that didn’t prop­er­ly mod­el the hu­man ones.

“We re­al­ized that the an­i­mal cells we used for re­search were very dif­fer­ent from hu­man cells,” Kot­ter said. “I looked around and re­al­ized that this not my prob­lem alone. It’s the main rea­son that drugs fail.”

Cur­rent­ly, the com­pa­ny lists on­ly two cells in its prod­uct of­fer­ings: hu­man-in­duced skele­tal my­ocytes and hu­man-in­duced glu­ta­mater­gic cor­ti­cal neu­rons. But they’re build­ing more, test­ing thou­sands of tran­scrip­tion fac­tors — the code or “bit” — and com­par­ing the ar­ti­fi­cial­ly con­vert­ed cells with the re­al things. They then of­fer these cells out for us­es in­clud­ing ge­net­ic or drug screen­ing.

Could these en­gi­neered hu­man cells one day re­place mice? Kot­ter is hes­i­tant. A cell isn’t an or­gan­ism, he not­ed. You won’t be able to see the whole-body ef­fects of a drug. He does won­der, though, about a fu­ture where pro­grammed “or­gans-on-a-chip” built with this tech are con­nect­ed and used to sim­u­late a full or­gan­ism.

“What I do know is that a lot of ana­log ex­per­i­ments that we do at this point tell us lit­tle about what we do in hu­mans,” he said. “These an­i­mal mod­els are not pre­dic­tive. I think the on­ly so­lu­tion is to bring the hu­man el­e­ment back in­to the process.”

Kot­ter told End­points a fund­ing an­nounce­ment was com­ing soon. Last year, he said he hoped to ini­tial­ly raise £5 mil­lion, then worth rough­ly $6.5 mil­lion, and had the sup­port of a UK “Tier one VC.”

An­oth­er biotech aimed at di­rect cell re­pro­gram­ming, Mo­gri­fy, an­nounced $16 mil­lion in Se­ries A fund­ing last week. Mo­gri­fy was a fi­nal­ist for the 2018 Cam­bridge Start­up of the Year. bit bio won.

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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Usama Malik

Ex-Im­munomedics CFO charged with in­sid­er trad­ing, faces up to 20 years in prison af­ter al­leged­ly tip­ping off girl­friend and rel­a­tives of a PhI­II suc­cess

The former CFO of Immunomedics, who helped steer the company to its $21 billion buyout by Gilead last year, has been charged with insider trading, the Department of Justice announced Thursday.

Usama Malik tipped off his then-girlfriend and four others that a Phase III study for Trodelvy would be stopped early four days before Immunomedics publicly announced the result in April 2020, DoJ alleged in its complaint. The individuals then purchased Immunomedics shares, selling them after the news broke and Immunomedics’ stock price doubled.

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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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Ab­b­Vie tacks on a new warn­ing to Rin­voq la­bel as safe­ty frets crimp JAK class

The safety problems that continue to plague the JAK class as new data highlight some severe side effects are casting a large shadow over AbbVie’s Rinvoq.

As a result of a recent readout highlighting major adverse cardiac events (MACE), malignancy, mortality and thrombosis with Xeljanz a couple of months ago, AbbVie put out a notice late Friday afternoon that it is adding the new class risks to its label for their rival drug.

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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.

Pfiz­er, Am­gen and Janssen seek fur­ther clar­i­ty on FDA's new ben­e­fit-risk guid­ance

Three top biopharma companies are seeking more details from the FDA on how the agency conducts its benefit-risk assessments for new drugs and biologics.

While Pfizer, Amgen and Janssen praised the agency for further spelling out its thinking on the subject in a new draft guidance, including a discussion of patient experience data as part of the assessment, the companies said the FDA could’ve included more specifics in the 20-page draft document.

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Re­searchers move clos­er to de­ci­pher­ing blood clots from As­traZeneca, J&J's Covid-19 vac­cines

Researchers may be nearing an answer for the mysterious and life-threatening blood clots that appeared on very rare occasions in people who received the J&J or AstraZeneca Covid-19 vaccine.

The new work builds on an early hypothesis researchers in Norway put forward last spring, when the cases first cropped up. They proposed the events were similar to blood clots that can occur in a small subset of patients who receive heparin, one of the most commonly used blood thinners.

Janet Woodcock (AP Images)

Janet Wood­cock plots her fu­ture at FDA, with se­nior ad­vi­sor role to fall back on if Califf wins con­fir­ma­tion

Acting FDA commissioner Janet Woodcock has been the face of just about every drug approval decision at the agency since the turn of the century. Since the pandemic began, she’s moved between the top of the drugs center to the head of therapeutics at Operation Warp Speed, leading the drive for work on Covid-targeted mAbs and antivirals.

Looking forward — and pending a quick Senate confirmation to cement Rob Califf’s return to the top of FDA early next year — Woodcock’s role at the agency will again be in flux.

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