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.

Lessons for biotech and phar­ma from a doc­tor who chased his own cure

After being struck by a rare disease as a healthy third year medical student, David Fajgenbaum began an arduous journey chasing his own cure. Amidst the hustle of this year’s JP Morgan conference, the digital trials platform Medable partnered with Endpoints Studio to share Dr. Fajgenbaum’s story with the drug development industry.

What follows is an edited transcript of the conversation between Medable CEO Dr. Michelle Longmire and Dr. Fajgenbaum, and it is full of lessons for biotech executives charged with bringing the next generation of medicines to patients.

Kathy High (file photo)

Gene ther­a­py pi­o­neer Kathy High has left Spark af­ter com­plet­ing $4.3B union with Roche

Kathy High dedicated the past seven years of her life shepherding experimental gene therapies she’s developed at Children’s Hospital of Philadelphia toward the market as president and head of R&D at Spark Therapeutics. Now that the biotech startup is fully absorbed into Roche — with an FDA approval, a $4.3 billion buyout and a promising hemophilia program to boast — she’s ready to move on.

Roche confirmed her departure with Endpoints News and noted “she will take some well-deserved time off and then will begin a new chapter in a sabbatical at a university.”

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Tim Mayleben (file photo)

Es­pe­ri­on's goldilocks cho­les­terol fight­er wins FDA ap­proval — will its 'tra­di­tion­al' pric­ing ap­proach spur adop­tion?

It’s more effective than decades-old statins but not as good as the injectable PCSK9 — the goldilocks treatment for cholesterol-lowering, bempedoic acid, has secured FDA approval.

Its maker, Esperion Therapeutics, is betting that their pricing strategy — a planned list price of between $10 to $11 a day — will help it skirt the pushback the PCSK9 cholesterol fighters, Repatha and Praluent, got from payers for their high sticker prices.

The sky-high expectations for the pair of PCSK9 drugs that were first approved in 2015 quickly simmered — and despite a 60% price cut, coupled with data showing the therapies also significantly cut cardiovascular risk, sales have not really perked up.

Esperion is convinced that by virtue of being a cheaper oral therapy, bempedoic acid will hit that sweet spot in terms of adoption.

“We’re kind of like the old comfortable shoe,” Esperion’s chief commercial officer Mark Glickman remarked in an interview with Endpoints News ahead of the decision date. “It’s an oral product, once-daily and nontitratable — these are things that just resonate so true with patients and physicians and I think we’ve kind of forgotten about that.”

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James Collins, Broad Institute via Youtube

UP­DAT­ED: A space odyssey for new an­tibi­otics: MIT's ma­chine learn­ing ap­proach

Drug development is complex, expensive and comes with lousy odds of success — but in most cases, if you make it across the finish line brandishing a product with an edge (and play your cards right) it can be a lucrative endeavor.

As it stands, the antibiotic market is cursed — it harbors the stink of multiple bankruptcies, a dearth of innovation, and is consequently barely whetting the voracious appetites of big pharma or venture capitalists. Enter artificial intelligence — the biopharma industry’s cure-all for the pesky process of making a therapeutic, including data mining, drug discovery, optimal drug delivery, and addressable patient population.

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Tal Zaks (Moderna via YouTube)

For two decades, a new vac­cine tech­nol­o­gy has been slow­ly ap­proach­ing prime time. Now, can it stop a pan­dem­ic?

Two months before the outbreak, Moderna CMO Tal Zaks traveled from Cambridge, MA to Washington DC to meet with Anthony Fauci and the leaders of the National Institutes of Health.

For two years, Moderna had worked closely with NIH researchers to build a new kind of vaccine for MERS, one of the deadliest new viruses to emerge in the 21st century. The program was one test for a new technology designed to be faster, cheaper and more precise than the ways vaccines had been made for over a century. They had gathered evidence the technology could work in principle, and Fauci, the longtime head of the National Institute of Allergy and Infectious Diseases and a longtime advocate for better epidemic preparedness, wanted to see if it, along with a couple of other approaches, could work in a worst-case scenario: A pandemic.

“[We were] trying to find a test case for how to demonstrate if our technology could rapidly prepare,” Zaks told Endpoints News.

Zaks and Fauci, of course, wouldn’t have to wait to develop a new test. By year’s end, an outbreak in China would short circuit the need for one and throw them into 24/7 work on a real-world emergency. They also weren’t the only ones with new technology who saw a chance to help in a crisis.

An ocean away, Lidia Oostvogels was still on vacation and relaxing at her mother’s house in Belgium when her Facebook started changing. It was days after Christmas and on most people’s feeds, the news that China had reported a novel virus to the World Health Organization blurred into the stream of holiday sweaters and fir trees. But on Oostvogels’s feed, full of vaccine researchers and virus experts, speculation boiled: There was a virus in China, something contained to the country, but “exotic,” “weird,” and maybe having to do with animals. Maybe a coronavirus.

Lidia Oostvogels

“I was immediately thinking like, ‘Hey, this is something that if needed, we can play a role,'” Oostvogels told Endpoints.

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Gilead los­es two more patent chal­lenges on HIV pill, set­ting up court­room fight in Delaware

Gilead sustained two more losses in their efforts to rid themselves of an activist-backed patent lawsuit from the US government over a best-selling HIV pill.

Urged on by activists seeking to divert a portion of Gilead’s revenue to clinics and prevention programs, the Department of Health and Human Services made a claim to some of the patents for the best-selling HIV prevention drug, Truvada, also known as PrEP. Gilead responded by arguing in court that HHS’s patents were invalid.

Today, the US Patent and Trademark Office ruled that Gilead was likely to lose the last two of those challenges as well. The USPTO ruled against Gilead on the first two patents earlier this month.

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Christos Kyratsous (via LinkedIn)

He built a MERS treat­ment in 6 months and then the best Ebo­la drug. Now Chris­tos Kyrat­sous turns his sights on Covid-19

TARRYTOWN, NY — In 2015, as the Ebola epidemic raged through swaths of West Africa, Kristen Pascal’s roommates sat her down on their couch and staged an intervention.

“Are you sure this is what you want to be doing with your life?” she recalls them asking her.

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Pascal, a research associate for Regeneron, had been coming home at 2 am and leaving at 6 am. At one point, she didn’t see her roommate for a week. For months, that was life in Christos Kyratsous’ lab as the pair led a company-wide race to develop the first drug that could effectively treat Ebola before the outbreak ended. For Pascal, that was worth it.

“I’m ok, I don’t have Ebola,” Pascal told them. “I see that death toll rising and I can’t not do something about it.”

Last August, Regeneron learned they had succeeded: In a large trial across West Africa, their drug, REGN-EB3, was vastly more effective than the standard treatments. It was surprise news for the company, coming just 10 months into a trial they thought would take several years and a major victory in the global fight against a deadly virus that killed over 2,000 in 2019 and can carry a mortality rate of up to 90%.

For Kyratsous and Pascal, though, it brought only fleeting reprieve. Just four months after the NIH informed them REGN-EB3 worked, Kyratsous was back in his office reading the New York Times for updates on a new outbreak on another continent, and wondering alongside Pascal and senior management whether it was time to pull the trigger again.

In late January, as the death toll swelled and the first confirmed cases outside China broke double digits, they made a decision. Soon they were back on the phone with the multiple government agencies and their coronavirus partners at the University of Maryland’s Level 3 bio lab. The question was simple: Can Kyratsous and his team use a process honed over two previous outbreaks, and create a treatment before the newest epidemic ends? Or worse, if, as world health experts fear, it doesn’t vanish but becomes a recurrent virus like the flu?

“Christos likes things immediately,” Matt Frieman, Regeneron’s coronavirus collaborator at the University of Maryland, told Endpoints. “That’s what makes us good collaborators: We push each other to develop things faster and faster.”

Kristen Pascal (Regeneron)

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The first time Regeneron tried to respond to a global outbreak, it was something of a systems test, Kyratsous explains from his office at Regeneron’s Tarrytown headquarters. Kyratsous, newly promoted, has crammed it with photos of his family, sketches of viral vectors and a shark he drew for his 3-year-old son. He speaks rapidly – an idiosyncrasy his press person says has only been aggravated this afternoon by the contents of his “Regeneron Infectious Diseases”-minted espresso glass – and he gesticulates with similar fluidity, tumbling through antibodies, MERS, the novel coronavirus, Ebola-infected monkeys.

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Bank­rupt an­tibi­otics mak­er Ar­a­digm turns to old part­ner/in­vestor for fi­nal $3M fire sale

Grifols once paid Aradigm $26 million for a stake in its inhaled antibiotics. But with Aradigm now in bankruptcy, the Spanish drugmaker is dishing out a final $3.2 million to buy it all.

The fire sale — which comes one year after Aradigm filed for Chapter 11 following a regulatory trifecta for disaster — will see Grifols obtain assets and IP to Apulmiq (formerly Pulmaquin and Linhaliq in Europe), Lipoquin and free ciprofloxacin. In addition to waiving its claims in the bankruptcy case, Grifols also agreed to milestone payments up to $3 million more upon any regulatory approvals.

DB­V's peanut pre­ven­tion patch ap­proach­es key stage of ap­proval process

Almost a year and a half after DBV Technologies pulled its peanut allergy immunotherapy patch from FDA review, the biotech will get their day in court. The FDA has scheduled an advisory committee hearing for May 15.

In the two-horse race to develop the first immunotherapy for peanut allergy, DBV had the early lead, filing an NDA for their patch in 2018. But on December 20 of that year, the company withdrew their application after, they said, meeting with regulators and determining they had not submitted “sufficient detail regarding data on manufacturing procedures and quality controls.” Aimmune filed their BLA 3 days later and won approval as the first immunotherapy for peanuts this month.