Ep­i­darex, Sofinno­va dou­ble down on a par­al­lel take on 3rd-gen CAR-T — aim­ing straight at ovar­i­an can­cer

When John Ma­her treat­ed the first head and neck can­cer pa­tient at Guy’s Hos­pi­tal in Lon­don with his pan-ErbB CAR-T back in 2015, he was among a small club of re­searchers con­vinced they had an an­swer to the chal­lenges that had kept those en­gi­neered T cells — wild­ly suc­cess­ful in hema­to­log­i­cal can­cers — ei­ther too dan­ger­ous or out of reach for pa­tients with sol­id tu­mors.

John Ma­her

The field has blos­somed since then, with a pro­lif­er­a­tion of tech­nolo­gies that promise to ad­dress any num­ber of chal­lenges iden­ti­fied as unique to sol­id tu­mors. And Ma­her him­self has rethought his ap­proach and come up with a new CAR-T plat­form to gen­er­ate the next slate of can­di­dates.

Now that the first can­di­date is near­ing the end of Phase I, his biotech spin­out, Leu­cid Bio, will have al­most $16 mil­lion (£11.5 mil­lion) to take those new pro­grams in­to the clin­ic.

T4, as the CAR-T Ma­her has ad­min­is­tered to 18 pa­tients with squa­mous cell can­cer of the head and neck is known, be­longs to the sec­ond gen­er­a­tion, ex­plained Leu­cid Bio CEO Artin Mous­savi. Those CARs con­sist of a bind­ing re­cep­tor on the sur­face mem­brane, a se­ries of sig­nal­ing do­mains, plus one of two cos­tim­u­la­to­ry do­mains: CD28 or 4-1BB.

It was a struc­ture Ma­her knew well af­ter work­ing as part of Michel Sade­lain’s Memo­r­i­al Sloan Ket­ter­ing team be­hind a cru­cial part of what be­came Bris­tol My­ers Squibb’s CD19 CAR-T, Breyanzi.

Artin Mous­savi

As sci­en­tists moved in­to the third gen­er­a­tion of CARs, they com­bined the two cos­tim­u­la­to­ry do­mains in hopes of get­ting more pow­er­ful T cell ac­ti­va­tion. But in his own re­search, Ma­her con­clud­ed that the way most of his peers did it — putting the CD28 and 4-1BB on top of each oth­er — didn’t quite en­hance the po­ten­cy as much as ex­pect­ed.

So he tried a dif­fer­ent con­fig­u­ra­tion, ar­rang­ing the two cos­tim­u­la­to­ry do­mains in a par­al­lel fash­ion, close to the cell sur­face, and get­ting rid of the ze­ta chain sig­nal­ing.

“What he dis­cov­ered there was he was get­ting far bet­ter po­ten­cy, far bet­ter sig­nal­ing but wasn’t in­duc­ing a senes­cence or an over­stim­u­la­tion and was able to stim­u­late those cells to kill tu­mor cell lines — many more cy­cles than the sec­ond gen­er­a­tion or third gen­er­a­tion CAR,” Mous­savi said.

Over the past few years, Ma­her — who jug­gles sev­er­al jobs teach­ing and see­ing pa­tients at King’s Col­lege Lon­don and East­bourne Hos­pi­tal while al­so serv­ing as Leu­cid’s CSO — has moved that tech­nol­o­gy from in vit­ro stud­ies to in vi­vo pre­clin­i­cal mod­els. They call it pCAR, short for par­al­lel CAR.

“It’s a plat­form,” Mous­savi said. “It gives us the abil­i­ty to add in aux­il­iary tech­nolo­gies that will en­hance its ef­fi­ca­cy against par­tic­u­lar chal­lenges in sol­id tu­mor space. So with ovar­i­an can­cer, we’re in­tro­duc­ing hom­ing en­hance­ments. We’re al­so in­tro­duc­ing our ex­pe­ri­ence in terms of route of ad­min­is­tra­tion.”

Al­though it tech­ni­cal­ly falls be­hind T4 (or LEU-001), LEU-011 — the au­tol­o­gous CAR-T be­ing po­si­tioned for plat­inum-re­sis­tant ovar­i­an can­cer — is now Leu­cid’s lead pro­gram. The biotech has de­vel­oped a pCAR ver­sion of T4 as well as ad­di­tion­al tech­nolo­gies to sup­port al­lo­gene­ic CAR-T in the fu­ture.

“I don’t be­lieve there is one tech­nol­o­gy on its own that will over­come all the bar­ri­ers for a par­tic­u­lar in­di­ca­tion,” he said. “So I see this as an evo­lu­tion in the CAR-T field.”

The Se­ries A fi­nanc­ing should fund a Phase I for ‘011 AND get the al­lo­gene­ic pro­grams ready for fur­ther test­ing, the CEO said.

Ep­i­darex and Sofinno­va, which had pro­vid­ed the seed fund­ing to sus­tain the com­pa­ny up to this point, were back for this round, joined by new in­vestors Vulpes In­vest­ment Man­age­ment, 2In­vest and Fu­ture Fund of the British Busi­ness Bank.

Thanks to a close re­la­tion­ship with Guy’s Hos­pi­tal (where the team of few­er than 20 is based), Leu­cid gets its clin­i­cal drug sup­ply from a GMP man­u­fac­tur­ing suite there. And don’t look for the splash mon­ey on pro­duc­tion any time soon.

“We’re not try­ing to rein­vent the wheel in terms of elab­o­rate man­u­fac­tur­ing,” Mous­savi said. “What we’re try­ing to do is to make sure that we have a very cost-ef­fec­tive man­u­fac­tur­ing sys­tem that’s scal­able.”

IDC: Life Sci­ences Firms Must Em­brace Dig­i­tal Trans­for­ma­tion Now

Pre-pandemic, the life sciences industry had settled into a pattern. The average drug took 12 years and $2.9 billion to bring to market, and it was an acceptable mode of operations, according to Nimita Limaye, Research Vice President for Life Sciences R&D Strategy and Technology at IDC.

COVID-19 changed that, and served as a proof-of-concept for how technology can truly help life sciences companies succeed and grow, Limaye said. She recently spoke about industry trends at Egnyte’s Life Sciences Summit 2022. You should watch the entire session, free and on-demand, but here’s a brief recap of why she’s urging life sciences companies to embrace digital transformation.

Tom Barnes, Orna Therapeutics CEO

UP­DAT­ED: 'We have failed to fail': Mer­ck gam­bles $250M cash on a next-gen ap­proach to mR­NA — af­ter punt­ing its big al­liance with Mod­er­na

Merck went in deep on its collaboration with Moderna on new mRNA programs, and dropped them all over time, including their RSV partnership. But after writing off what turned out as one of the most successful infectious disease players in the business, Merck is coming in this morning with a new preclinical alliance — this time embracing a biotech that hopes to eventually outdo the famously successful mRNA in a new run at vaccines and therapeutics.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 148,200+ biopharma pros reading Endpoints daily — and it's free.

Bayer's first DTC ad campaign for chronic kidney disease drug Kerendia spells out its benefits

Bay­er aims to sim­pli­fy the com­plex­i­ties of CKD with an ABC-themed ad cam­paign

Do you know the ABCs of CKD in T2D? Bayer’s first ad campaign for Kerendia tackles the complexity of chronic kidney disease with a play on the acronym (CKD) and its connection to type 2 diabetes (T2D).

Kerendia was approved last year as the first and only non-steroidal mineralocorticoid receptor antagonist to treat CKD in people with type 2 diabetes.

In the TV commercial launched this week, A is for awareness, B is for belief and C is for cardiovascular, explained in the ad as awareness of the connection between type 2 and kidney disease, belief that something can be done about it, and cardiovascular events that may be reduced with treatment.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 148,200+ biopharma pros reading Endpoints daily — and it's free.

James Mock, incoming CFO at Moderna

Mod­er­na taps new CFO from PerkinElmer af­ter for­mer one-day CFO oust­ed

When Moderna hired a new CFO last year,  it didn’t expect to see him gone after only one day. Today the biotech named his — likely much more vetted — replacement.

The mRNA company put out word early Wednesday that after the untimely departure of then brand-new CFO Jorge Gomez, it has now found a replacement in James Mock, the soon-to-be former CFO at diagnostics and analytics company PerkinElmer.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 148,200+ biopharma pros reading Endpoints daily — and it's free.

Etleva Kadilli, director of UNICEF’s supply division

GSK lands first-ever UNICEF con­tract for malar­ia vac­cine worth $170M

GSK has landed a new first from UNICEF the first-ever contract for malaria vaccines, worth up to $170 million for 18 million vaccine doses distributed over the next three years.

The vaccine, known as Mosquirix or RTS,S, won WHO’s backing last October after a controversial start, but UNICEF said these doses will potentially save thousands of lives every year.

“We hope this is just the beginning,” Etleva Kadilli, director of UNICEF’s supply division, said. “Continued innovation is needed to develop new and next-generation vaccines to increase available supply, and enable a healthier vaccine market. This is a giant step forward in our collective efforts to save children’s lives and reduce the burden of malaria as part of wider malaria prevention and control programmes.”

FDA ap­proves one of the prici­est new treat­ments of all time — blue­bird's gene ther­a­py for be­ta tha­lassemia

The FDA on Wednesday approved the first gene therapy for a chronic condition — bluebird bio’s new Zynteglo (beti-cel) as a potentially curative treatment for those with transfusion-dependent thalassemia.

The thumbs up from the FDA follows a unanimous adcomm vote in June, with outside experts pointing to extraordinary efficacy, with 89% of subjects with TDT who received beti-cel having achieved transfusion independence.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 148,200+ biopharma pros reading Endpoints daily — and it's free.

Joel Dudley, new partner at Innovation Endeavors (Tempus Labs)

For­mer Google CEO’s VC is mak­ing a big­ger push in­to the biotech world, hir­ing promi­nent Ther­a­nos skep­tic

Venture capital firm Innovation Endeavors has mainly had its focus on investments across the tech space, but it has been slowly turning its attention to the biotech world. Now, a new partner is coming into the fold showing that its interest in biotech is likely to grow further.

The Silicon Valley-based company, which is headed up by former Google CEO Eric Schmidt, has brought on Joel Dudley as a partner. According to Dudley’s LinkedIn page, he is joining Innovation Endeavors after serving as the chief science officer of biotech startup Tempus Labs from 2020.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 148,200+ biopharma pros reading Endpoints daily — and it's free.

Joe Jonas (Photo by Anthony Behar/Sipa USA)(Sipa via AP Images)

So­lo Jonas broth­er car­ries Merz's new tune in Botox ri­val cam­paign

As the lyrics of his band’s 2019 pop-rock single suggest, Joe Jonas is only human — and that means even he gets frown lines. The 33-year-old singer-songwriter is Merz’s newest celebrity brand partner for its Botox rival Xeomin, as medical aesthetics brands target a younger audience.

Merz kicked off its “Beauty on Your Terms” campaign on Tuesday, featuring the Jonas brother in a video ad for its double-filtered anti-wrinkle injection Xeomin.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 148,200+ biopharma pros reading Endpoints daily — and it's free.

Paul Perreault, CSL Behring CEO

CSL CEO Paul Per­reault de­ter­mined to grow plas­ma col­lec­tion af­ter full-year sales dip

As the ink dries on CSL’s $11.7 billion Vifor buyout, the company posted a dip in profits, due in part to a drop in plasma donations amid the pandemic.

However, CEO Paul Perreault assured investors and analysts on the full-year call that the team has left “no stone unturned” when assessing options to grow plasma volumes. The chief executive also spelled out positive results for the company’s monoclonal antibody garadacimab in hereditary angioedema (HAE), though he isn’t revealing the exact numbers just yet.