Aaron Ring, Simcha Therapeutics founder

Go­ing af­ter an old GSK tar­get in a new way, a Yale spin­out hits the clin­ic and nabs a mod­est raise

About a year and a half ago, a Yale pro­fes­sor took a shot at en­gi­neer­ing a can­cer ther­a­py that had once flum­moxed re­searchers at Glax­o­SmithK­line. The com­pa­ny an­nounced its next steps Thurs­day, earn­ing a mod­est fundraise and en­ter­ing the clin­ic.

Sim­cha Ther­a­peu­tics closed a $40 mil­lion Se­ries B and has be­gun dos­ing pa­tients in a Phase I/II tri­al for its lead pro­gram, the biotech an­nounced. The raise should take Sim­cha in­to 2024 and help com­plete the just-launched Phase I por­tion, a Phase II monother­a­py study and a Phase Ib com­bi­na­tion tri­al with a check­point in­hibitor, founder Aaron Ring told End­points News.

Ring’s the­o­ry re­volves around stim­u­lat­ing the IL-18 path­way, try­ing to in­crease the body’s im­mune re­sponse to tu­mor mi­croen­vi­ron­ments us­ing what Sim­cha calls a “de­sign­er cy­tokine.” It’s es­sen­tial­ly the re-en­gi­neer­ing of an old GSK ef­fort that be­gan in 2004 and scut­tled ear­ly, as pa­tients’ tu­mors pro­gressed re­gard­less of how much IL-18 was ag­o­nized.

But by tar­get­ing a group of re­cep­tors that the mi­croen­vi­ron­ments had all but shut down, Ring found he could cre­ate a de­coy to evade the can­cer’s jam­ming sys­tem and get the prop­er cy­tokines where they need­ed to go. He out­lined the ini­tial re­sults in a Na­ture pa­per from June 2020, which proved foun­da­tion­al to Sim­cha’s ef­forts.

It’s part of a broad­er ef­fort by im­munother­a­py re­searchers to find the next big can­cer drug, fol­low­ing the suc­cess of oth­er med­i­cines like an­ti-PD-1 an­ti­bod­ies — though Ring not­ed Sim­cha is tak­ing the op­po­site ap­proach in an IL-18 ag­o­nist.

“Our con­vic­tion shared by many is that we can’t ac­cept a na­ture so­lu­tion. When it comes to cy­tokines, we need to en­gi­neer them for a de­lib­er­ate ther­a­peu­tic pur­pose,” Ring said. “What’s lim­it­ed many cy­tokines to date is just the fact that they’re too broad­ly ac­tive, too broad and a non­spe­cif­ic set of im­mune cells.”

Sim­cha’s mol­e­cule, known as ST-067, is the first IL-18 path­way ag­o­nist be­ing stud­ied in hu­mans since GSK’s last study was shut­tered near­ly 10 years ago, Ring added. Those ef­forts went through a Phase II melanoma study, and though it was well tol­er­at­ed for a cy­tokine, it in­duced on­ly one par­tial re­sponse out of 63 pa­tients.

When Ring first came across these re­sults, he found them “re­al­ly shock­ing,” be­cause it ap­peared to be the right sig­nal hit­ting the right cells. It led him to the mi­croen­vi­ron­ment bi­ol­o­gy Sim­cha is now try­ing to ag­o­nize, bring­ing a “laser fo­cus” on try­ing to repli­cate his ini­tial pre­clin­i­cal tests back in 2017.

The biotech is start­ing on a broad slate of sol­id tu­mors for its ini­tial test­ing, uti­liz­ing the Phase I por­tion as a dose-es­ca­la­tion study. Sim­cha’s plan is to re­cruit any pa­tient that’s pro­gressed on ex­ist­ing check­point im­munother­a­pies, not fo­cus­ing on spe­cif­ic can­cer types or ge­net­ic mu­ta­tion sub­sets.

It’s too ear­ly to say when Sim­cha might have the da­ta it needs to move on to Phase II, but Ring said he’s aim­ing for the typ­i­cal time­lines for what sim­i­lar agents in the class have achieved. The plan is to test the com­pound broad­ly, look­ing at monother­a­py reg­i­mens as well as in com­bi­na­tion with oth­er ap­proved ther­a­pies.

But Ring hopes his ap­proach will set Sim­cha apart from oth­er im­munother­a­py com­pa­nies.

“What dif­fer­en­ti­ates us from the oth­er path­ways is that there are now dozens of com­pa­nies pur­su­ing cy­tokine ther­a­pies in the IL-2, IL-15 space,” Ring said. “But this is a com­plete­ly dif­fer­ent path­way…Nev­er be­fore in pa­tients has any­one been able to de­cou­ple the ef­fects of IL-18 sig­nal­ing from the bind­ing pro­tein.”

Thurs­day’s round was led by SR One Cap­i­tal Man­age­ment and joined by oth­er new in­vestors, in­clud­ing BVF Part­ners, Sam­sara Bio­Cap­i­tal, Rock Springs Cap­i­tal, Ar­row­Mark Part­ners and Lo­gos Cap­i­tal.

Pi­o­neer­ing Click Chem­istry in Hu­mans

Reimagining cancer treatments

Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020, which is nearly one in six deaths. Recently, we have seen incredible advances in novel cancer therapies such as immune checkpoint inhibitors, cell therapies, and antibody-drug conjugates that have revamped cancer care and improved survival rates for patients.

Despite this significant progress in therapeutic targeting, why are we still seeing such a high mortality rate? The reason is that promising therapies are often limited by their therapeutic index, which is a measure of the effective dose of a drug, relative to its safety. If we could broaden the therapeutic indices of currently available medicines, it would revolutionize cancer treatments. We are still on the quest to find the ultimate cancer medicine – highly effective in several cancer types, safe, and precisely targeted to the tumor site.

Joshua Cohen (L) and Justin Klee, Amylyx co-CEOs

BREAK­ING: Af­ter long and wind­ing road, FDA ap­proves Amy­lyx's ALS drug in vic­to­ry for pa­tients and ad­vo­ca­cy groups

For just the third time in its 116-year history, the FDA has approved a new treatment for Lou Gehrig’s disease, or ALS.

US regulators gave the thumbs-up to the drug, known as Relyvrio, in a massive win for patients and their families. The approval, given to Boston-area biotech Amylyx Pharmaceuticals, comes after two years of long and contentious debates over the drug’s effectiveness between advocacy groups and FDA scientists, following the readout of a mid-stage clinical trial in September 2020.

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Ivan Cheung, Eisai US chairman and CEO

Bio­gen, Ei­sai re­fresh amy­loid hy­poth­e­sis with PhI­II show­ing Alzheimer's med slows cog­ni­tive de­cline

In the first look at Phase III data for lecanemab, Eisai and Biogen’s follow-up Alzheimer’s drug to the embattled Aduhelm launch, results show the drug passed with flying colors on a test looking at memory, problem solving and other dementia metrics.

One of the most-watched Alzheimer’s therapies in the clinic, lecanemab met the study’s primary goal on the CDR-SB — Clinical Dementia Rating-Sum of Boxes — giving the biotech the confidence to ask for full approval in the US, EU and Japan by next March 31. The experimental drug reduced clinical decline on the scale by 27% compared to placebo at 18 months, the companies said Tuesday night Eastern time and Wednesday morning in Japan.

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Nooman Haque, head of life sciences and healthcare at Silicon Valley Bank, and John Carroll

I’m head­ed to Lon­don soon for #EU­BIO22. Care to join me?

It was great getting back to a live ESMO conference/webinar in Paris followed by a live pop-up event for the Endpoints 11 in Boston. We’re staying on the road in October with our return for a live/streaming EUBIO22 in London.

Silicon Valley Bank’s Nooman Haque and I are once again jumping back into the thick of it with a slate of virtual and live events on October 12. I’ll get the ball rolling with a virtual fireside chat with Novo Nordisk R&D chief Marcus Schindler, covering their pipeline plans and BD work.

Some­one old, some­one new: Mod­er­na pro­motes CTO, raids No­var­tis for re­place­ment amid pipeline push

Moderna CEO Stéphane Bancel made clear on the last quarterly call that “now is not the time to slow down.” On Thursday, he made a bit more room in the cockpit.

The company unveiled a new executive role on Thursday, promoting former chief technical operations and quality officer Juan Andres to president of strategic partnerships and enterprise expansion, and poaching a former Novartis exec to take his place.

Gilead names 'k­ing­pin­s' in coun­ter­feit HIV med law­suit

Gilead is mounting its counterfeit drug lawsuit, naming two “kingpins” and a complex network of conspirators who allegedly sold imitation bottles of its HIV meds, some of which ended up in US pharmacies.

The pharma giant on Wednesday provided an update on what it called a “large-scale, sophisticated counterfeiting conspiracy,” accusing two new defendants of “leading and orchestrating” a scheme to sell hundreds of millions of dollars in illegitimate drugs posing as meds such as Biktarvy and Descovy.

Vlad Coric, Biohaven CEO (Photo Credit: Andrew Venditti)

As Amy­lyx de­ci­sion waits in the wings, Bio­haven’s ALS drug sinks (again) in plat­form tri­al

The FDA’s decision on Amylyx’s ALS drug is set to come out sometime Thursday. In a space with few drugs, any approval would be a major landmark.

But elsewhere in the ALS field, things are a bit more tepid.

Thursday morning, Biohaven announced that its drug verdiperstat failed its arm of an ALS platform trial led by Massachusetts General Hospital. According to a press release, the drug did not meet its primary endpoint — improvement on an ALS functional status test — or any key secondary endpoints at 24 weeks. The trial had enrolled 167 patients, giving them either verdiperstat or placebo twice a day.

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Tar­sus looks to raise aware­ness of eye­lid mite dis­ease in cam­paign aimed at eye­care spe­cial­ists

Eyelid mite disease may be “gross” but it’s also fairly common, affecting about 25 million people in the US.

Called demodex blepharitis, it’s a well-known condition among eyecare professionals, but they often don’t always realize how common it is. Tarsus Pharmaceuticals wants to change that with a new awareness campaign called “Look at the Lids.”

The campaign and website debut Thursday — just three weeks after Tarsus filed for FDA approval for a drug that treats the disease.

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Marcelo Bigal, Ventus Therapeutics CEO

No­vo Nordisk joins No­var­tis, Roche in NL­RP3 are­na, bet­ting $70M cash on NASH, car­diometa­bol­ic us­es

As a drug target, the NLRP3 inflammasome has drawn serious interest from Big Pharma, inspiring a series of M&A deals from Novartis and Roche on top of venture investments by others. Now Novo Nordisk is jumping on the bandwagon — and the Danish pharma giant is taking the target where it knows best.

Novo Nordisk is getting its NLRP3 inhibitors from Ventus Therapeutics, a Versant-backed startup that set out to make some of the best NLRP3 drugs out there by incorporating new insights into the structure of the target complex.

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