Fac­tor Bio­science spins out a new cell ther­a­py play­er with eyes on the clin­ic with­in 2 years

The quest for CAR-T 2.0 is gain­ing an mR­NA play­er, as Cam­bridge, Mass­a­chu­setts-based Fac­tor Bio­science sends a spin­off rac­ing to­ward the clin­ic.

Gre­go­ry Fiore

Fac­tor drew the cur­tains on Exacis Bio­ther­a­peu­tics on Wednes­day morn­ing, with Sol­lis Ther­a­peu­tics co-founder Gre­go­ry Fiore at the helm of a small im­muno-on­col­o­gy fo­cused team built around Fac­tor’s tech­nol­o­gy. The spin­off has the rights to 51 patents and just a bit of seed mon­ey from friends and fam­i­ly to get it go­ing — but Fiore says an IND sub­mis­sion is on the hori­zon.

“We are 18 to 24 months from an IND sub­mis­sion, and we’ve iden­ti­fied our first tar­get, which will be CD19,” Fiore told End­points News. 

The com­pa­ny will be un­veil­ing a CD19-tar­get­ed CAR-T and CAR-NK, Fiore said, with ROR1 as its next tar­get.

The CEO says Exacis’ ap­proach is what dif­fer­en­ti­ates it from oth­ers in the crowd­ed cell ther­a­py field, be­gin­ning with mR­NA tech­nol­o­gy in-li­censed from Fac­tor. The process starts with in­duced pluripo­tent stem cells (iP­SC), which are blood or skin cells that have been en­gi­neered back in­to an em­bry­on­ic-like stem cell state. They’re cre­at­ed with mR­NA re­pro­gram­ming, and then edit­ed to avoid host im­mune sur­veil­lance, add a CAR and en­hance the cells for po­ten­cy against tu­mors.

“That iP­SC is quite a ro­bust cell. It can han­dle a lot of edit­ing and the cells are able to re­cov­er from a lot of edit­ing and ma­nip­u­la­tion,” Fiore said. And the fact that no virus­es or DNA are used “sig­nif­i­cant­ly de­creas­es the re­source re­quire­ment for man­u­fac­tur­ing,” he added lat­er.

The idea of an off-the-shelf CAR-T or CAR-NK ther­a­py — as op­posed to har­vest­ing a pa­tient’s cells, en­gi­neer­ing them in­to a can­cer at­tack ve­hi­cle and rein­ject­ing them — isn’t a new one. Al­lo­gene re­leased a pos­i­tive snap­shot of their off-the-shelf CAR-T pro­gram at AS­CO 2020, and CRISPR Ther­a­peu­tics of­fered a glimpse at their own CAR-T suc­cess in Oc­to­ber al­though it was cloud­ed by the death of a pa­tient giv­en a high dose of the treat­ment.

Dim­itrios Goundis

Exacis’ team of four — in­clud­ing co-founder James Pan and for­mer Max­i­VAX CEO Dim­itrios Goundis as CBO — is shoot­ing for a Se­ries A in the com­ing months to bol­ster its team and pipeline. The com­pa­ny al­so says it’s in talks with sev­er­al po­ten­tial de­vel­op­ment part­ners.

“We are work­ing to­wards a Se­ries A fund­ing to be com­plet­ed in Q1 of 2021, and we’ll use those funds to build out our in­ter­nal team and lab, as well as fur­ther the de­vel­op­ment along the lines of dif­fer­en­ti­a­tion in­to T and NK, ob­tain­ing CARs, re­al­ly putting to­geth­er these tar­get cell types,” Fiore said.

While Fiore stayed mum about the the spe­cif­ic terms of Exacis’ li­cens­ing deal with Fac­tor, he said that Fac­tor has a ma­jor­i­ty own­er­ship in ex­change for the ex­e­cu­tion of the li­cense.

The CEO, who was in­spired to get in­to the field by his fa­ther’s bat­tle with can­cer, said Fac­tor and Exacis’ in­cen­tives were aligned. “There’s plen­ty of op­por­tu­ni­ty to im­prove the pa­tient ex­pe­ri­ence as well as out­comes,” he said.

BY­OD Best Prac­tices: How Mo­bile De­vice Strat­e­gy Leads to More Pa­tient-Cen­tric Clin­i­cal Tri­als

Some of the most time- and cost-consuming components of clinical research center on gathering, analyzing, and reporting data. To improve efficiency, many clinical trial sponsors have shifted to electronic clinical outcome assessments (eCOA), including electronic patient-reported outcome (ePRO) tools.

In most cases, patients enter data using apps installed on provisioned devices. At a time when 81% of Americans own a smartphone, why not use the device they rely on every day?

Image: Shutterstock

Eli Lil­ly asks FDA to re­voke EUA for Covid-19 treat­ment

Eli Lilly on Friday requested that the FDA revoke the emergency authorization for its Covid-19 drug bamlanivimab, which is no longer as effective as a combo therapy because of a rise in coronavirus variants across the US.

“With the growing prevalence of variants in the U.S. that bamlanivimab alone may not fully neutralize, and with sufficient supply of etesevimab, we believe now is the right time to complete our planned transition and focus on the administration of these two neutralizing antibodies together,” Daniel Skovronsky, Lilly’s CSO, said in a statement.

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Alise Reicin (L) and Tim Springer

Har­vard bil­lion­aire Tim Springer has lined up his lat­est biotech launch. And he's re­cruit­ed a star R&D ex­ec to man­age their break­through game plan

Tectonic Therapeutic isn’t your average biotech startup story. For all sorts of reasons.

There’s your billionaire Harvard scientist and philanthropist who’s personally bankrolling much of the operation. The CEO is one of the most prominent women involved in the global drug hunting business. And they have enough collective cachet between them to command virtually as much cash as they might dream of, at a time that biotech dreams are running beyond the fantastic.

But this story isn’t about them right now, so much as it is about a scientist who’s never quite been center stage in the floodlights of biostardom. There’s a whole group of prominent players, though, who believe that’s about to change. Players perfectly happy to gamble some significant coin to give that hope every chance possible of becoming a reality.

Andrew Kruse may not be an immediately recognizable name to you. But to his Harvard colleague Tim Springer, he’s a rock star. They co-founded the Institute for Protein Innovation together, a non-profit that the internationally renowned Springer has been funding with a fortune earned from a remarkable run of successful startups, from his first $100 million out of Millennium to the gusher of wealth that followed his decision to back Stéphane Bancel and the crew at mRNA pioneer Moderna.

Kruse has specialized in work revolving around GPCRs, or G protein-coupled receptors, that make up about a third of all — while still only scratching the surface of potential targets. He was a student of Brian Kobilka at Stanford, who won the Nobel Prize in 2012 for his contribution on the work on GPCRs. And Kruse has published extensively on his lab’s structural analysis of GPCRs, which Springer believes will open the door to a whole new field of drug R&D that can crack open a slew of currently “undruggable” targets to biologics — covering a gamut of both agonists and antagonists.

“We just have unparalleled experience in the biochemistry and biophysics of GPCRs,” says Springer about this new venture of his. “Andrew Kruse is a real star. He went from being a PhD student at Stanford to an assistant professor at Harvard Medical School — he had many papers out of his PhD — and he’s gone on to full professor at Harvard Medical School in 7 years. That is a record at least in modern times. The guy is just amazing. And he’s a nice guy.”

Springer is so convinced by the potential of Kruse’s research that he put up the first $5 million to seed the company 18 months ago. Terry McGuire — the co-founder at Polaris who goes back a long way with Springer — chipped in a million.

Which brings us to the nut of today’s news story.

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J&J faces CDC ad­vi­so­ry com­mit­tee again next week to weigh Covid-19 vac­cine risks

The CDC’s Advisory Committee on Immunization Practices punted earlier this week on deciding whether or not to recommend lifting a pause on the administration of J&J’s Covid-19 vaccine, but the committee will meet again in an emergency session next Friday to discuss the safety issues further.

The timing of the meeting likely means that the J&J vaccine will not return to the US market before the end of next week as the FDA looks to work hand-in-hand with the CDC to ensure the benefits of the vaccine still outweigh the risks for all age groups.

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Osman Kibar (Samumed, now Biosplice)

Os­man Kibar lays down his hand at Sa­mumed, step­ping away from CEO role as his once-her­ald­ed an­ti-ag­ing biotech re­brands

Samumed made quite the entrance back in 2016, when it launched with some anti-aging programs and a whopping $12 billion valuation. That level of fanfare was nowhere to be found on Thursday, when the company added another $120 million to its coffers and quietly changed its name to Biosplice Therapeutics.

Why the sudden rebrand?

“We did that for obvious reasons,” CFO and CBO Erich Horsley told Endpoints News. “The name Biosplice echoes our science much more than Samumed does.”

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Ex­clu­sive in­ter­view: Pe­ter Marks on why full Covid-19 vac­cine ap­provals could be just months away

Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, took time out of his busy schedule last Friday to discuss with Endpoints News all things related to his work regulating vaccines and the pandemic.

Marks, who quietly coined the name “Operation Warp Speed” before deciding to stick with his work regulating vaccines at the FDA rather than join the Trump-era program, has been the face of vaccine regulation for the FDA throughout the pandemic, and is usually spotted in Zoom meetings seated in front of his wife’s paintings.

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Near­ly a year af­ter Au­den­tes' gene ther­a­py deaths, the tri­al con­tin­ues. What hap­pened re­mains a mys­tery

Natalie Holles was five months into her tenure as Audentes CEO and working to smooth out a $3 billion merger when the world crashed in.

Holles and her team received word on the morning of May 5 that, hours before, a patient died in a trial for their lead gene therapy. They went into triage mode, alerting the FDA, calling trial investigators to begin to understand what happened, and, the next day, writing a letter to alert the patient community so they would be the first to know. “We wanted to be as forthright and transparent as possible,” Holles told me late last month.

The brief letter noted two other patients also suffered severe reactions after receiving a high dose of the therapy and were undergoing treatment. One died a month and a half later, at which point news of the deaths became public, jolting an emergent gene therapy field and raising questions about the safety of the high doses Audentes and others were now using. The third patient died in August.

“It was deeply saddening,” Holles said. “But I was — we were — resolute and determined to understand what happened and learn from it and get back on track.”

Eleven months have now passed since the first death and the therapy, a potential cure for a rare and fatal muscle-wasting disease called X-linked myotubular myopathy, is back on track, the FDA having cleared the company to resume dosing at a lower level. Audentes itself is no more; last month, Japanese pharma giant Astellas announced it had completed working out the kinks of the $3 billion merger and had restructured and rebranded the subsidiary as Astellas Gene Therapies. Holles, having successfully steered both efforts, departed.

Still, questions about precisely what led to the deaths of the 3 boys still linger. Trial investigators released key details about the case last August and December, pointing to a biological landmine that Audentes could not have seen coming — a moment of profound medical misfortune. In an emerging field that’s promised cures for devastating diseases but also seen its share of safety setbacks, the cases provided a cautionary tale.

Audentes “contributed in a positive way by giving a painful but important example for others to look at and learn from,” Terry Flotte, dean of the UMass School of Medicine and editor of the journal Human Gene Therapy, told me. “I can’t see anything they did wrong.”

Yet some researchers say they’re still waiting on Astellas to release more data. The company has yet to publish a full paper detailing what happened, nor have they indicated that they will. In the meantime, it remains unclear what triggered the events and how to prevent them in the future.

“Since Audentes was the first one and we don’t have additional information, we’re kind of in a holding pattern, flying around, waiting to figure out how to land our vehicles,” said Jude Samulski, professor of pharmacology at UNC’s Gene Therapy Center and CSO of the gene therapy biotech AskBio, now a subsidiary of Bayer.

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Pascal Soriot (AstraZeneca via YouTube)

Af­ter be­ing goad­ed to sell the com­pa­ny, Alex­ion's CEO set some am­bi­tious new goals for in­vestors. Then Pas­cal So­ri­ot came call­ing

Back in the spring of 2020, Alexion $ALXN CEO Ludwig Hantson was under considerable pressure to perform and had been for months. Elliott Advisers had been applying some high public heat on the biotech’s numbers. And in reaching out to some major stockholders, one thread of advice came through loud and clear: Sell the company or do something dramatic to change the narrative.

In the words of the rather dry SEC filing that offers a detailed backgrounder on the buyout deal, Alexion stated: ‘During the summer and fall of 2020, Alexion also continued to engage with its stockholders, and in these interactions, several stockholders encouraged the company to explore strategic alternatives.’

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Vik Bajaj (Foresite)

Ex­clu­sive: Vik Ba­jaj set out al­most 2 years ago to hatch new com­pa­nies that would shake up health­care with da­ta sci­ence. Here are 5 di­rec­tions he's tak­ing at Fore­site Labs

If it was clear in late 2019 that the US healthcare system is poised for transformation, Vik Bajaj believes the Covid-19 pandemic rammed the gas pedal by laying bare the “fundamental inefficiencies and inequalities.”

Take, for instance, the idea that the most cost-effective way to treat disease is to catch it early. That was the mission at Grail, the high-flying cancer detection startup that he had been CSO of. But at Foresite, where he’s now managing director, they expected widespread emphasis on preventative care would take about a decade to achieve — as with many of the changes in business models that they were hoping for.