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.

2023 Spot­light on the Fu­ture of Drug De­vel­op­ment for Small and Mid-Sized Biotechs

In the context of today’s global economic environment, there is an increasing need to work smarter, faster and leaner across all facets of the life sciences industry.  This is particularly true for small and mid-sized biotech companies, many of which are facing declining valuations and competing for increasingly limited funding to propel their science forward.  It is important to recognize that within this framework, many of these smaller companies already find themselves resource-challenged to design and manage clinical studies themselves because they don’t have large teams or in-house experts in navigating the various aspects of the drug development journey. This can be particularly challenging for the most complex and difficult to treat diseases where no previous pathway exists and patients are urgently awaiting breakthroughs.

Spe­cial re­port 2022: Meet 20 women blaz­ing trails in bio­phar­ma R&D

When you run a special report for a fourth year, it can start feeling a little bit like a ritual. You go through the motions — in our case opening up nominations for top women in biopharma R&D and reviewing more than 500 entries — you make your choices of inclusion and exclusion. You host a ceremony.

But then things happen that remind you why you do it in the first place. Perhaps a Supreme Court rules to overturn the constitutional right to abortion and a group of women biotech leaders makes it clear they strongly dissent; perhaps new data on gender diversity in the industry come out that look all too similar to the old ones, suggesting women are still dramatically underrepresented at the top; perhaps protests and conflicts around the world put in stark terms the struggles that many women still face in earning the most basic recognition.

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Graphic: Shutterstock

Prometheus moves to raise cash hours af­ter PhII da­ta leads to stock surge

After releasing better-than-anticipated data on two mid-stage studies Wednesday morning, Prometheus Biosciences’ CEO said the company would “take some time to assess” its next financing options.

It only needed about seven hours. Wednesday afternoon after the market closed, the biotech announced it would seek $250 million through an equity offering as the company looks to edge out anti-TL1A competitor Pfizer and its new partner Roivant.

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Kristen Hege, Bristol Myers Squibb SVP, early clinical development, oncology/hematology and cell therapy (Illustration: Assistant Editor Kathy Wong for Endpoints News)

Q&A: Bris­tol My­er­s' Kris­ten Hege on cell ther­a­py, can­cer pa­tients and men­tor­ing the next gen­er­a­tion

Kristen Hege leads Bristol Myers Squibb’s early oncology discovery program carrying on from the same work at Celgene, which was acquired by BMS in 2019. She’s known for her early work in CAR-T, having pioneered the first CAR-T cell trial for solid tumors more than 25 years ago.

However, the eminent physician-scientist is more than just a drug developer mastermind. She’s also a practicing physician, mother to two young women, an avid backpacker and intersecting all those interests — a champion of young women and people of color in STEM and life sciences.

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Gossamer Bio CEO Faheem Hasnain at Endpoints' #BIO22 panel (J.T. MacMillan Photography for Endpoints News)

Gos­samer’s Fa­heem Has­nain de­fends a round of pos­i­tive PAH da­ta as a clear win. But can these PhII re­sults stand up to scruti­ny?

Gossamer Bio $GOSS posted a statistically significant improvement for its primary endpoint in the key Phase II TORREY trial for lead drug seralutinib on Tuesday morning. But CEO Faheem Hasnain has some explaining to do on the important secondary of the crucial six-minute walk distance test — which will be the primary endpoint in Phase III — as the data on both endpoints fell short of expectations, missing one analyst’s bar on even modest success.

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Alex Martinez, Intrinsic Medicine CEO

They with­drew their IPO. Then, they broke off their SPAC merg­er. Now what?

If at first an IPO doesn’t succeed, try, try a SPAC. But what happens when that fails too?

Intrinsic Medicine and its blank-check partner Phoenix Biotech Acquisition Corp. called off their reverse merger Tuesday night, citing “current market conditions” as the reason it went kaput. The pair decoupled just weeks after agreeing to combine in late October as investors’ appetite for new IPOs and SPACs has been limited, at best.

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Piper Trelstad, head of CMC, Bill & Melinda Gates Medical Research Institute

Q&A with Gates leader: Women tak­ing on more roles in phar­ma man­u­fac­tur­ing, but still work to do

More and more women are driving innovation and taking leadership roles in biotech – as evidenced today in the release of Endpoints News’ list of the top 20 women in the R&D world – but those gains are beginning to extend across pharma sectors.

In pharma manufacturing in the US today, around 46% of all roles are occupied by women, according to the US Bureau of Labor Statistics for 2021. And according to a Bloomberg report, women’s roles across manufacturing roles had a massive boost after the start of the pandemic.

Phar­ma rep­u­ta­tion re­tains 'halo' even as pan­dem­ic me­dia cov­er­age re­cedes — sur­vey

The Covid-19 halo effect on the pharma industry is continuing, according to a new global study from Ipsos. The annual survey for the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) finds considerable goodwill from consumers across measures of trust, cooperation with governments, and advancing research and drug development.

“Despite the pandemic in many countries no longer being the top of mind concern generally – although it does remain the top concern as a health issue – the industry’s reputation has remained positive,” said Ipsos research director Thomas Fife-Schaw.

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FDA commissioner Robert Califf (Jose Luis Magana/AP Images)

FDA pulls On­copep­tides' Pepax­to in­di­ca­tion, open­ing the door for dan­gling ac­cel­er­at­ed ap­proval en­force­ment

In a move all but ensured after an overwhelmingly negative adcomm vote this September, the FDA is yanking Oncopeptides’ dangling accelerated approval. And there may be more to come.

In recent months, US regulators have honed in on reforming the accelerated approval pathway and preventing drugmakers from continuing to sell their medicines in the event of a confirmatory study flop. The moves come after commissioner Rob Califf has called for companies to do more to produce post-marketing evidence quickly earlier this year.

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