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.

At the In­flec­tion Point for the Next Gen­er­a­tion of Can­cer Im­munother­a­py

While oncology researchers have long pursued the potential of cellular immunotherapies for the treatment of cancer, it was unclear whether these therapies would ever reach patients due to the complexity of manufacturing and costs of development. Fortunately, the recent successful development and regulatory approval of chimeric antigen receptor-engineered T (CAR-T) cells have demonstrated the significant benefit of these therapies to patients.

Stéphane Bancel, Moderna CEO

'This is not go­ing to be good': Mod­er­na CEO Ban­cel warns of a 'ma­te­r­i­al drop' in vac­cine ef­fi­ca­cy as Omi­cron spreads

Even as public health officials remain guarded about their comments on the likelihood Omicron will escape the reach of the currently approved Covid-19 vaccines, there’s growing scientific consensus that we’re facing a variant that threatens to overwhelm the vaccine barricades that have been erected.

Stéphane Bancel, the CEO of Moderna, one of the leading mRNA players whose quick vault into the markets with a highly effective vaccine created an instant multibillion-dollar market, added his voice to the rising chorus early Tuesday. According to Bancel, there will be a significant drop in efficacy when the average immune system is confronted by Omicron. The only question now is: How much?

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FDA ad­comm nar­row­ly votes in fa­vor of Mer­ck­'s an­tivi­ral for out­pa­tient Covid-19

With little explanation for why Merck’s potential Covid-19 antiviral was less effective in reducing Covid hospitalizations and deaths in a full analysis of a Phase III trial versus an interim look, the FDA’s antimicrobial drugs advisory committee on Tuesday voted 13-10 in favor of the pill’s benefits outweighing the risks for adults within 5 days of developing Covid symptoms.

Molnupiravir will likely be authorized by FDA in the coming days for adults with mild or moderate Covid-19. While Pfizer’s antiviral may prove to be more effective, Merck’s pill will be another weapon in the armamentarium of Covid-19 treatments for countries around the world, adding to the mAb treatments already in use in the outpatient space from Regeneron, Eli Lilly and Vir/GlaxoSmithKline.

Philip Dormitzer, new GSK global head of vaccines R&D

Glax­o­SmithK­line poach­es Pfiz­er's vi­ral vac­cines lead in rush to cap­i­tal­ize on fu­ture of mR­NA

GlaxoSmithKline has appointed Philip Dormitzer, formerly chief scientific officer of Pfizer’s viral vaccines unit, as its newest global head of vaccines R&D, looking to leverage one of the leading minds behind Pfizer and BioNTech’s RNA collaboration that led to Covid-19 jab Comirnaty, the British drug giant said Tuesday.

Dormitzer had been with Pfizer for a little more than six years, joining up after a seven-year stint with Novartis, where he reached the role of US head of research and head of global virology for the company’s vaccines and diagnostics unit.

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In­tro­duc­ing End­points Stu­dio, a new way to ad­ver­tise with End­points-craft­ed brand­ing cam­paigns

Since our start in 2016, Endpoints has grown fast while executing our mission to cover biopharma’s most critical developments for industry pros worldwide. As readership has grown, our advertising business has too. Endpoints advertising partners support the mission and engage their desired audiences through announcements on our email and web platforms, brand recognition in our event coverage and sponsorships of Endpoints daily and weekly reports.

Ap­peals court puts the fi­nal nail in the cof­fin for Tec­fidera patent, adding to Bio­gen's bur­geon­ing set­backs

In another setback for Biogen, the big biotech lost its appeal to revive a patent for the once-blockbuster drug Tecfidera, marking a likely conclusion to the case.

The US Court of Appeals for the Federal Circuit issued the ruling Tuesday morning, saying Biogen failed to satisfy the “written description” requirement for patent law. As a result, Mylan-turned-Viatris will be able to sell its multiple sclerosis generic without fear of infringement and Biogen will have to find a new revenue driver elsewhere.

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Tillman Gerngross (Adagio)

Till­man Gern­gross on Omi­cron: 'It is a grim sit­u­a­tion...we’re go­ing to see a sig­nif­i­cant drop in vac­cine ef­fi­ca­cy'

Tillman Gerngross, the rarely shy Dartmouth professor, biotech entrepreneur and antibody expert, has been warning for over a year that the virus behind Covid-19 would likely continue to mutate, potentially in ways that avoid immunity from infection and the best defenses scientists developed. He spun out a company, Adagio, to build a universal antibody, one that could snuff out any potential mutation.

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In­cor­po­rat­ing Ex­ter­nal Da­ta in­to Clin­i­cal Tri­als: Com­par­ing Dig­i­tal Twins to Ex­ter­nal Con­trol Arms

Most drug development professionals are familiar with the nerve-racking wait for the read-out of a large trial. If it’s negative, is the investigational therapy ineffective? Or could the failure result from an unforeseen flaw in the design or execution of the protocol, rather than a lack of efficacy? The team could spend weeks analyzing data, but a definitive answer may be elusive due to insufficient power for such analyses in the already completed trial. These problems are only made worse if the trial had lower enrollment, or higher dropout than expected due to an unanticipated event like COVID-19. And if a trial is negative, the next one is likely to be larger and more costly — if it happens at all.

Mar­ket­ingRx roundup: Ab­b­Vie’s Hu­mi­ra TV turns fo­cus to HS skin con­di­tion; Sanofi amps par­ent­ing pol­i­cy

After years as the top spending pharma TV advertiser, AbbVie’s Humira brand finally downshifted earlier this year, ceding much of its marketing budget to up-and-coming sibling meds Skyrizi and Rinvoq. However, now Humira is back on TV with ads for another condition — Hidradenitis suppurativa (HS).

The chronic and painful skin condition results in lumps and abscesses caused by inflammation or infection of sweat glands, most often in the armpits or groin. Humira was first approved to treat HS in 2015 and remains the only FDA-approved drug for the condition. Two TV ads both note more than 30,000 people with HS have been prescribed Humira.