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.

Com­mu­ni­cat­ing the val­ue of pre­ci­sion med­i­cine

By Natasha Cowan, Content Marketing Manager at Blue Latitude Health.
Many stakeholders are confused by novel precision medicines, including patients and healthcare professionals. So, how can industry help them to navigate this complexity?

Precision medicine represents a new paradigm in healthcare. It embodies the shift from treating many patients with the same therapy, to having the tools to identify the best treatment for every patient.

Spe­cial re­port: Twen­ty ex­tra­or­di­nary women in bio­phar­ma R&D who worked their way to the top

What differentiates a woman leader in biopharma R&D from a man?

Not much, except there are fewer of them in senior posts. Data suggest women are not more risk-averse, family-oriented or less confident than their male counterparts — indeed the differences between the two sexes are negligible. But a glance at the top R&D positions in Big Pharma leaves little doubt that upward migration in the executive ranks of biopharma R&D is tough.

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The lat­est Cin­derel­la sto­ry in on­col­o­gy ends with a sud­den rout as up­dat­ed da­ta dis­play spooks in­vestors

NextCure’s turn as the Cinderella of cancer-focused biotechs was short-lived.
Just a few days after its shares $NXTC zoomed up more than 250% on some very early stage results in a SITC abstract, a more complete analysis over the weekend spiked the hype and left investors in high dudgeon as the stock price collapsed back towards earth Monday.
The focus at NextCure is centered on NC318, an antibody that is intended to shut down the immunosuppressive Siglec-15 — or S-15 — target. After adding a small group of patients to the readout, investigators circled 2 clinical responses, a complete and partial response, along with 4 stable disease cases in non-small cell lung cancer.

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Te­va spin­out rais­es $85M in IPO; No­var­tis beefs up gener­ics unit with $440M deal

→ After Teva spinout 89bio recently announced that its IPO was being held up, the company is back in the game offering 5,304,687 shares at a price of $16 per share. The company has raised $84.9 million IPO in gross proceeds and will be listed under the ticker symbol $ETNB. BofA Securities, SVB Leerink and RBC Capital Markets are the joint book-running managers for the offering. Oppenheimer & Co is the co-manager for the offering.
→ Looking to amp up its presence in Japan’s hospitals, Novartis has struck a deal to buy out Aspen’s portfolio of generics in the world’s third largest healthcare market. The pharma giant is paying $440 million for Aspen’s Japanese subsidiary.
→ Novartis said tropifexor, a non-bile acid FXR agonist, has scored on several key biomarkers of NASH in a Phase IIb trial, including reductions in hepatic fat, alanine aminotransferase and body weight compared to a placebo at 12 weeks.

Break­through sta­tus and promise of a speedy re­view ar­rives for Op­di­vo/Yer­voy com­bi­na­tion as Bris­tol-My­ers bites at Bay­er

Its frontline and single-agent aspirations have been set back, but Bristol-Myers Squibb just took a big step forward in its efforts to apply its checkpoint inhibitor Opdivo to liver cancer. The FDA has granted breakthrough status and priority review to a combination, second-line treatment.

The designation is for Opdivo (nivolumab) in combination with Yervoy (ipilimumab),  for treating advanced hepatocellular carcinoma (HCC), the most common form of liver cancer. The PD-L1 drug was already approved as a single-agent, second-line treatment for HCC. A PDUFA date was set for March 10, 2020 — just 4 months from now.

Third time un­lucky: Lipocine's lat­est quest to mar­ket their oral testos­terone drug snubbed again by FDA

Lipocine’s latest attempt at securing approval for its oral testosterone drug has fizzled yet again.

The Utah-based drug developer on Monday said the FDA has spurned its marketing application, indicating that some efficacy data on the drug, Tlando, was not up to scratch to treat male hypogonadism, a condition characterized by low production of the hormone testosterone, which is responsible for maintaining muscle bulk, bone growth, and sexual function.

UP­DAT­ED: De­cry­ing 'ar­bi­trary and capri­cious' ac­tion, Re­genxBio sues FDA over clin­i­cal holds on gene ther­a­py

When RegenxBio disclosed that the FDA had placed a partial clinical hold on one of its lead gene therapies, execs outlined several customary next steps: continuing assessment and monitoring, delaying a related IND filing, and working with the FDA to address the matter.

As it turned out, they were planning something much less mundane. Two days after announcing the hold in its Q3 update, RegenxBio filed a lawsuit seeking to set it aside, the FDA Law Blog noted.

Roche's SMA chal­lenge to Bio­gen's Spin­raza fran­chise looms larg­er with piv­otal win

Roche has just landed a crucial advance in scoring a come-from-behind win on the spinal muscular atrophy field, giving Novartis and Biogen a run for their money.

The update was brief, but Roche said risdiplam hit the primary endpoint in the placebo-controlled pivotal SUNFISH trial, meeting the threshold for change from baseline in the Motor Function Measure 32 (MFM-32) scale after one year of treatment. The results, which is the second, confirmatory portion of a two-part study, involved 180 patients with type 2 or 3 spinal muscular atrophy between 2 and 25 years old.

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Roche steers Gazy­va in­to a new PhI­II pro­gram af­ter com­bo shows promise in lu­pus nephri­tis study

Roche is working on putting together a late-stage study for its monoclonal antibody Gazyva in patients with severe kidney disease associated with lupus after a combination approach helped patients in a mid-stage study.

The 125-patient NOBILITY trial evaluated Gazyva, combined with standard-of-care treatment mycophenolate mofetil or mycophenolic acid and corticosteroids, versus standard treatment alone. The combo met the main goal of inducing a statistically superior complete renal response (CRR) of 40% at week 76, versus 18% in patients given standard treatment, Roche said.