Look­ing to solve the sol­id tu­mor puz­zle box, Caris­ma aims to take 'CAR-M' ground­break­er in­to ear­ly-stage tri­al

In an ef­fort to crack the code of hard-to-treat sol­id tu­mors, bio­phar­ma has tried nu­mer­ous path­ways to ef­fec­tive­ly tar­get those mass­es with­out dam­ag­ing healthy tis­sues. Philly’s Caris­ma Ther­a­peu­tics thinks it has a win­ner with its macrophage cell-based “CAR-M” can­di­dates, and now it’s tak­ing a new flush of in­vestor cash to try one in the clin­ic.

Steven Kel­ly

Caris­ma has scored a $47 mil­lion Se­ries B round to take its lead can­di­date, an­ti-HER2 CAR-M tu­mor fight­er CT-0508, in­to a Phase I tri­al as well as ad­vanc­ing the rest of its pre­clin­i­cal macrophage pipeline. Caris­ma has keyed in on the use of tar­get­ed macrophage cells and vec­tors to pen­e­trate the en­vi­ron­ment of sol­id can­cer tu­mors with­out hurt­ing health tis­sues — a puz­zle in the sol­id tu­mor field.

CT-0508’s ear­ly-stage study will turn out the first hu­man da­ta for a CAR-M ther­a­py based on those macrophage cells, Caris­ma said. CEO Steven Kel­ly told End­points News his com­pa­ny could of­fer an ef­fec­tive and safer way to tar­get tu­mors and “warm them up” for the im­mune sys­tem to at­tack.

“There are a num­ber of char­ac­ter­is­tics about macrophages that would lend them­selves to­wards ap­pli­ca­tions of sol­id tu­mors and oth­er in­di­ca­tions, but what we’re fo­cused on is sol­id tu­mors,” Kel­ly said. “Macrophages are pref­er­en­tial­ly re­cruit­ed in­to a tu­mor mi­croen­vi­ron­ment, and lym­pho­cytes like the CAR-T ap­proach­es are ac­tive­ly ex­clud­ed. So we think that we have an ad­van­tage by over­com­ing traf­fick­ing lim­i­ta­tions to sol­id tu­mors.”

This has been the stick­ing point for the in­dus­try: ther­a­peu­tics that can in­vade the walls which sur­round can­cer­ous tu­mors with­out dam­ag­ing oth­er­wise healthy cells.

Kel­ly is con­fi­dent that Caris­ma’s tech­nol­o­gy will ul­ti­mate­ly de­ci­pher how to do just that.

“Once it starts eat­ing (the can­cer­ous tu­mor cells), the macrophages will start pro­duc­ing cy­tokines that ef­fec­tive­ly warm up that en­vi­ron­ment and con­vert an im­muno­log­i­cal­ly cold tu­mor in­to a warm or hot tu­mor and re­cruit in oth­er cells, like T cells for ex­am­ple. So that last el­e­ment is re­al­ly unique to macrophages due to the anti­gen pre­sen­ta­tion ca­pa­bil­i­ty,” he said. “They en­gage in cells di­rect­ly, they warm up the tu­mor mi­croen­vi­ron­ment, and they gen­er­ate a true adap­tive im­mune re­sponse. That’s how we think of our­selves and how we’re dif­fer­en­ti­at­ed in the cell ther­a­py space.”

Kel­ly said it was a bit pre­ma­ture to know when Caris­ma would be­gin pub­lic read­outs of the da­ta sur­round­ing its macrophage ther­a­peu­tics, but he hoped they would be able to do so by the mid­dle of this year.

The to­tal cap­i­tal Caris­ma has raised since its Se­ries A fi­nanc­ing in 2018 now to­tals rough­ly $109 mil­lion, and is a key step in mov­ing the com­pa­ny from “ef­fec­tive­ly a dis­cov­ery-stage com­pa­ny to a clin­i­cal-stage com­pa­ny,” Kel­ly said.

“A lot of ef­fort has gone in­to build­ing this com­pa­ny. We had to tran­si­tion from a bench project at (the Uni­ver­si­ty of) Penn, we had to demon­strate all the things nec­es­sary to get an IND de­clared — (so) safe­ty and ef­fi­ca­cy — we had to de­vel­op a GMP man­u­fac­tur­ing process,” Kel­ly said. “All those were ef­fec­tive­ly de­vel­oped to FDA sat­is­fac­tion, and we’re mov­ing in­to the clin­ic now.”

In­vestors in the Se­ries B fi­nanc­ing are led by Sym­bio­sis II, with sub­se­quent in­vest­ment from So­las­ta Ven­tures and Liv­zon Phar­ma­ceu­ti­cal Group. Ad­di­tion­al­ly, Caris­ma said, ex­ist­ing in­vestors Ab­b­Vie Ven­tures, Health­Cap, Welling­ton Part­ners, IP Group, TPG Biotech, Agent Cap­i­tal, and MRL Ven­tures Fund con­tributed to the new round of fund­ing.

Op­ti­miz­ing Cell and Gene Ther­a­py De­vel­op­ment and Pro­duc­tion: How Tech­nol­o­gy Providers Like Corn­ing Life Sci­ences are Spurring In­no­va­tion

Remarkable advances in cell and gene therapy over the last decade offer unprecedented therapeutic promise and bring new hope for many patients facing diseases once thought incurable. However, for cell and gene therapies to reach their full potential, researchers, manufacturers, life science companies, and academics will need to work together to solve the significant challenges facing the industry.

David Baker working with a student on their protein design (Jason Mast)

Sci­en­tists are fi­nal­ly learn­ing how to de­sign pro­teins from scratch. Drug de­vel­op­ment may nev­er be the same

SEATTLE — It’s a cloudy Thursday afternoon in mid-July and David Baker is reclining into the futon in his corner office at the University of Washington, arms splayed out like a daytime talk show host as he coaches another one of his postdocs through the slings and arrows of scientific celebrity.

“Be jealous of your time,” he says, before plotting ways of sneaking her out of Zooms. “It’s this horrible cost to science that you’re tied up in some stupid meeting.”

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Pre­sent­ing a live End­points News event: Man­ag­ing a biotech in tur­bu­lent times

Biotech is one of the smartest, best educated industries on the planet. PhDs abound. We’ve had a long enough track record to see a new generation of savvy, experienced execs coming together to run startups.

And in these times, they are being tested as never before.

Biotech is going through quite a rough patch right now. For 2 years, practically anyone with a decent resume and some half-baked ideas on biotech could start a company and get it funded. The pandemic made it easy in many ways to pull off an IPO, with traditional road shows shut down in exchange for a series of quick Zoom meetings. Generalist investors flocked as the numbers raised soared into the stratosphere.

Clay Siegall (Photo by Dimitrios Kambouris/Getty Images for Gabrielle's Angel Foundation)

UP­DAT­ED: Clay Sie­gall re­signs from Seagen amid in­ves­ti­ga­tion in­to do­mes­tic vi­o­lence claims

A week after Seagen revealed that longtime CEO Clay Siegall was on leave due to an allegation of domestic violence, he has resigned.

Since that shocking revelation, more details about the claims have emerged into the public eye. As Endpoints News reported, Siegall was arrested on April 23. A police report about that night and a subsequent temporary restraining order described a pattern of abusive behavior against his wife and a physical altercation that left her with multiple bruises. Siegall denied the claims.

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Patty Murray, D-WA (Graeme Sloan/Sipa USA)(Sipa via AP Images)

Sen­ate user fee reau­tho­riza­tion bill omits ac­cel­er­at­ed ap­proval re­forms, shows wide gaps with House ver­sion

The Senate health committee on Tuesday released its first version of the bill to reauthorize all the different FDA user fees. But unlike the House version, there are only a few controversial items in the Senate’s version, which does not address either accelerated approval reforms or clinical trial diversity (as the House did).

While it’s still relatively early in the process of finalizing this legislation (the ultimate statutory deadline is the end of September), the House and Senate, at least initially, appear to be starting off in different corners on what should be included.

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Warren Buffett, Berkshire Hathaway CEO

Berk­shire Hath­away pulls out of Ab­b­Vie, Bris­tol My­ers Squibb in­vest­ments

It looks like Warren Buffett is sticking to ice cream and railroads for the moment.

The billionaire CEO of Berkshire Hathaway backed out of two major holdings in the pharma industry, Forexlive first reported, including a $410 million investment in AbbVie and a $324.4 million stake in Bristol Myers Squibb.

The move comes after Berkshire abandoned its Teva shares just last quarter, Bloomberg reported.

Long-ex­pect­ed UK lay­offs im­mi­nent for No­var­tis fol­low­ing sale

Nearly a year ago, more than 200 workers at Novartis’ Grimsby, UK, facility were able to hang on to their jobs after the pharma closed a Switzerland site as a part of its workforce restructuring plan. Now, it looks like those employees’ time is up, as the site has been sold, Grimsby Telegraph reported today.

The manufacturing site has been sold to Humber Industrials, a subsidiary of International Process Plants. None of the current staff members will be working with the new owners, however.

FDA lob­bies Con­gress over rare dis­ease court rul­ing with wide im­pli­ca­tions

Usually reserved for making decisions on drug applications or enforcing what Congress stipulates, the FDA is now dipping its toe into the wild world of congressional politics as it attempts to fix a major court decision that could have a chilling effect on rare disease R&D.

The case in question from last October saw a US appeals court overturn a prior FDA court win, saying that the agency never should’ve approved a rare disease drug because a previously approved but more expensive drug with the same active ingredient has orphan drug exclusivity barring such an approval.

Peter Marks (Greg Nash/Pool via AP)

Even FDA's Pe­ter Marks is wor­ried about the com­mer­cial vi­a­bil­i­ty of gene and cell ther­a­pies

When bluebird bio’s gene therapy to treat beta thalassemia won European approval in 2019, the nearly $2 million per patient price tag for the potential cure seemed like a surmountable hurdle.

Fast forward two years later, and bluebird has withdrawn Zynteglo, the beta thal drug, along with the rest of its gene therapy portfolio from Europe, which the company said is generally unwilling to pay a fair price for the treatment.