Siddhartha Mukherjee (Evan Agostini/Invision/AP)

With lessons learned from Vor, Sid­dhartha Mukher­jee takes a dif­fer­ent route to tar­get sol­id tu­mors with start­up Myeloid

Sid­dhartha Mukher­jee is a busy man these days.

The Pulitzer Prize-win­ning au­thor, Co­lum­bia pro­fes­sor, on­col­o­gist, hema­tol­o­gist and lead­ing can­cer re­searcher in 2016 launched Vor, a Cam­bridge, MA-based start­up fo­cused on a new can­cer treat­ment in which cell sur­face anti­gens such as CD33 are re­moved from hematopoi­et­ic stem cells. They can then un­leash a CAR-T ther­a­py — made from T cells in a pa­tient’s blood and ge­net­i­cal­ly en­gi­neered to hunt for the anti­gens — to treat can­cer us­ing the body’s own im­mune sys­tem with­out at­tack­ing healthy cells that would’ve shared those anti­gens.

Now, Mukher­jee is adding a new start­up to his plate, still fo­cused on treat­ing can­cer us­ing the im­mune sys­tem. But this time, his fo­cus is on types of can­cers that have demon­strat­ed they can’t be cured by the CAR-T cell tech­nol­o­gy he pri­or­i­tizes at Vor.

This start­up, al­so based in Cam­bridge, is called Myeloid Ther­a­peu­tics, named for the spe­cif­ic cells which play a crit­i­cal role in a new ther­a­py found­ed by Mukher­jee and renowned bio­chemist Ronald Vale. The two are backed by over $50 mil­lion in Se­ries A fund­ing from around the bio­phar­ma in­dus­try, led by New­path Part­ners out of Boston.

Mukher­jee told End­points News in an in­ter­view that us­ing myeloid cells to tar­get can­cers — most­ly those in sol­id tu­mors — has the po­ten­tial to meet an “enor­mous” un­met med­ical need.

“Most sol­id can­cers such as ovar­i­an can­cer or col­orec­tal can­cer or esophageal can­cer for what­ev­er rea­son are not amenable to CAR-T cell ther­a­py or to so-called check­point in­hibitor ther­a­pies, which ac­ti­vat­ed T cells against these can­cers,” he said. “We now know a lot about why, and that’s be­cause when you look at these can­cers, even af­ter you treat them with these (ther­a­pies), you find that they form a kind of shell and re­sis­tance shell around the can­cer … which ex­clude T cells from en­ter­ing the tu­mor.”

It’s al­most like the shell on the out­side of a Star Wars bat­tle­ship, Mukher­jee said.

Ronald Vale

This is where myeloid cells come in­to play. Un­like T cells, myeloid cells are ac­tu­al­ly “in­trin­si­cal­ly de­signed” to pen­e­trate sol­id can­cer tu­mors, he said, as if they have a free pass to in­vade the mass and sur­vey what’s hap­pen­ing in­side of it.

Mukher­jee and Vale dis­cov­ered that they could ge­net­i­cal­ly en­gi­neer re­cep­tors in the myeloid cells to not on­ly pen­e­trate a tu­mor, but to rec­og­nize the tu­mor and be ac­ti­vat­ed by the tu­mor it­self. In oth­er words, the tech­nol­o­gy bridges the gap be­tween the hu­man body’s in­nate im­mune sys­tem, which can gen­er­al­ly scan the body for virus­es and the like, and the im­mune sys­tem’s ca­pac­i­ty to rec­og­nize and lat­er at­tack can­cer cells.

Thus be­came Myeloid There­apeu­tics.

“Those were the two cru­cial in­sights that drove this com­pa­ny and the ther­a­pies that this com­pa­ny is pro­duc­ing,” Mukher­jee said. “The fact that you can take the in­nate im­mune sys­tem, which is not de­signed to rec­og­nize one par­tic­u­lar virus or mi­crobe or can­cer, but en­gi­neer the im­mune sys­tem to rec­og­nize can­cer and be­come ac­ti­vat­ed by the can­cer … We’re en­abling the most an­cient part of the im­mune sys­tem to be­come can­cer-spe­cif­ic and can­cer-ac­ti­vat­ed.”

Daniel Getts

Myeloid will ded­i­cate much of the ini­tial $50 mil­lion fund­ing to­ward ini­ti­at­ing clin­i­cal tri­als for its two main pro­grams, which tar­get T cell lym­phoma, glioblas­toma and oth­er sol­id tu­mors. The team will al­so con­tin­ue to de­sign and ad­vance a broad pipeline of tar­get­ed myeloid cell ther­a­pies, in­clud­ing primed myeloid cells, myeloid mul­ti-spe­cif­ic en­gagers and oth­er de­vel­op­ment can­di­dates cre­at­ed with Myeloid’s nov­el mR­NA de­liv­ery tech­nolo­gies.

The com­pa­ny ex­pects to en­ter the clin­ic with its two lead pro­grams in glioblas­toma and T cell lym­phoma in 2021.

Myeloid CEO Daniel Getts told End­points that through­out his ca­reer in the biotech in­dus­try, he’s been in­volved with oth­er ven­tures that looked at the use of T cells in fight­ing can­cer­ous tu­mors. But be­fore now, it’s seemed like the tech­nolo­gies and can­cer reme­dies avail­able were dis­joint­ed, he said. Where Myeloid hopes to be dif­fer­ent is that it com­bines the con­cepts of those past ther­a­pies in­to a sin­gle ther­a­peu­tic through the myeloid-cell mech­a­nism.

“I think the pow­er of what we have is un­sur­passed right now. And, you know, we’re ben­e­fi­cia­ries,” Getts said. “We’re stand­ing on the shoul­ders of a lot of these oth­er gene en­gi­neer­ing com­pa­nies be­cause they’re show­ing the world what’s pos­si­ble.”

Image courtesy of The Janssen Pharmaceutical Companies of Johnson & Johnson.

Pro­tect­ing the glob­al phar­ma­ceu­ti­cal in­no­va­tion ecosys­tem – what’s at stake?

We are living in a new era of healthcare that is rapidly advancing progress impacting patient outcomes and experiences. We’ve seen a remarkable pace of transformational innovation, applied research, and advanced clinical development over the last decade.

Despite this tremendous progress, there is much more work to be done, and patients are counting on us – now more than ever – to continue that momentum. At the heart of our industry is a focus on developing and delivering medicines for some of the world’s most challenging diseases, including those that have few or no effective treatments today.

End­points 20(+2) un­der 40, 2023; Bio­phar­ma's high­est-paid CEOs; N-of-1 CRISPR sto­ry goes on af­ter tragedy; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

We will be off Monday in observance of Memorial Day — and when we get back, it will be a straight march to ASCO, BIO and more. Enjoy the (long) weekend!

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Rich Horgan (R) with his late brother, Terry

Rich Hor­gan spear­head­ed a gene ther­a­py for his broth­er. The tri­al end­ed in tragedy, but the work con­tin­ues for more pa­tients

Rich Horgan’s quest to create a custom gene therapy for his brother, Terry, ended in tragedy. But Horgan doesn’t believe it’s the end of the story.

Terry, a 27-year-old patient with Duchenne muscular dystrophy, died last October just eight days after receiving the therapy in a clinical trial in which he was the only participant. The case raised questions about the safety of certain gene therapies and what would happen to other drug programs under a nonprofit that Horgan created, called Cure Rare Disease.

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Bio­phar­ma's 20 high­est-paid CEOs of 2022, each bring­ing in $20M+ pay­days

Even in a down year for much of the biopharma market, 20 CEOs brought in pay packages valued at more than $20 million, an Endpoints News analysis found.

Endpoints collected data on more than 350 CEO compensation packages, covering a wide range of pharma, biotech, and life sciences companies. All told, the 20 largest earners made over $725 million in 2022 — an average package of $36.4 million. Three brought in paydays over $50 million, and one CEO broke the $100 million mark.

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Mi­rati’s drug sitra­va­tinib flops PhI­II in com­bo with Op­di­vo for cer­tain lung can­cer

Mirati Therapeutics’ path to a second drug approval will likely have to wait. The San Diego biotech company said Wednesday that its investigational lung cancer drug failed a Phase III trial testing it in combination with Bristol Myers Squibb’s Opdivo.

The drug, sitravatinib, and Opdivo weren’t better than the chemo drug docetaxel at keeping patients alive, Mirati said in a press release. The spectrum-selective kinase inhibitor missed the primary goal of overall survival in patients with second- or third-line advanced non-squamous, non-small cell lung cancer.

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Athena Countouriotis, Avenzo Therapeutics CEO (website via Nasdaq)

Ex-Turn­ing Point ex­ecs plan to have their next bet, Aven­zo, on the Nas­daq next sum­mer

The crew at Turning Point Therapeutics is back together for a new biotech that wants to acquire early-stage oncology small molecules, including antibody drug conjugates, and potentially form partnerships with China-based drug developers for ex-China rights as it eyes a speedy leap onto the Nasdaq around this time next year, CEO Athena Countouriotis told Endpoints News.

After selling Turning Point to Bristol Myers Squibb, announced at the onset of last year’s ASCO confab, she and colleague Mohammad Hirmand founded Avenzo Therapeutics. The CEO and CMO already have approximately $200 million in seed and Series A financing from five big-name investors to evaluate which drugs to bring into its pipeline. That includes SR One, OrbiMed, Foresite Capital, Citadel’s Surveyor Capital and Lilly Asia Ventures. Bidding wars for assets have led Avenzo to miss out on some deals in recent months, but the biotech has three active term sheets and hopes to bring in its first asset in the third quarter, Countouriotis said in a Friday morning interview.

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The 20(+2) un­der 40: Your guide to the next gen­er­a­tion of biotech lead­ers

This year’s list of 20 biotech leaders under the age of 40 includes a huge range of ambitions. Some of our honorees are planning to create the next big drug giant. Others are pushing the bounds of AI. One is working to revolutionize TB testing. All are compelling talents who are still young in age, but already far along in achievement.

And, as in years past, we went over. The 20 are actually 22 because of two double profiles that reflect how important teamwork is in the industry. As one of our honorees, Joe Illingworth of DJS Antibodies, told me in our interview, “It takes a village to raise a biotech.”

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Car­mot rais­es an­oth­er $150M for obe­si­ty drugs, though race by com­peti­tors is well un­der­way

Carmot Therapeutics announced a $150 million Series E round that it plans to use to fund several trials of its obesity drugs.

Its lead candidate is a GLP-1/GIP dual receptor modulator heading into testing for obesity and diabetes. The latest round brings the startup’s total raised to around $370 million, according to the company.

Similar to Eli Lilly’s Mounjaro, Carmot’s lead drugs target hormones that together can impact insulin production and appetite. Its lead compound is CT-388, a once-weekly injection it is taking into Phase II. It also has a daily injection with the same mechanism and an oral GLP-1; a Phase I trial is in the works.

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FDA ap­proves Lex­i­con’s heart-fail­ure drug af­ter de­feat in di­a­betes

The FDA on Friday approved Lexicon’s heart failure drug sotagliflozin following a string of setbacks for the pharma company, including an FDA rejection in diabetes and the loss of a development deal with Sanofi.

The dual SGLT1 and SGLT2 inhibitor will be marketed as Inpefa and is a once-daily tablet. It’s been approved to reduce the risk of cardiovascular death and heart failure-related hospitalization or urgent visits in adults with heart failure or type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors. The label spans the range of left ventricular ejection fraction, including preserved ejection fraction and reduced ejection fraction, as well as patients with or without diabetes, Lexicon said Friday.

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