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.

Up­dat­ed: FDA re­mains silent on or­phan drug ex­clu­siv­i­ty af­ter last year's court loss

Since losing a controversial court case over orphan drug exclusivity last year, the FDA’s Office of Orphan Products Development has remained entirely silent on orphan exclusivity for any product approved since last November, leaving many sponsors in limbo on what to expect.

That silence means that for more than 70 orphan-designated indications for more than 60 products, OOPD has issued no public determination on the seven-year orphan exclusivity in the Orange Book, and no new listings of orphan exclusivity appear in OOPD’s searchable database, as highlighted recently by George O’Brien, a partner in Mayer Brown’s Washington, DC office.

Big week for Alzheimer’s da­ta; As­traZeneca buys cell ther­a­py start­up; Dig­i­tal ther­a­peu­tics hits a pay­er wall; and more

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Illustration: Assistant Editor Kathy Wong for Endpoints News

As mon­ey pours in­to dig­i­tal ther­a­peu­tics, in­sur­ance cov­er­age crawls

Talk therapy didn’t help Lily with attention deficit hyperactivity disorder, or ADHD. But a video game did.

As the 10-year-old zooms through icy waters and targets flying creatures on the snow-capped planet Frigidus, she builds attention skills, thanks to Akili Interactive Labs’ video game EndeavorRx. She’s now less anxious and scattered, allowing her to stay on a low dose of ADHD medication, according to her mom Violet Vu.

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Am­gen, years be­hind ri­vals, says PhI obe­si­ty drug shows dura­bil­i­ty signs

While NBC ran “The Biggest Loser” for 17 seasons, deemed toxic by critics for the reality show’s punishing exercise and diet upheavals, researchers in pharmaceutical labs have been attempting to create prescription drugs that induce weight loss — and one pharma betting it can require less frequent dosing is out with a new crop of data.

Amgen was relatively late to the game compared to its approved competitor Novo Nordisk and green light-approaching rival Eli Lilly. But early data suggested Amgen’s AMG 133 led to a 14.5% weight reduction in the first few months of dosing, buoying shares earlier this fall, and now the California pharma is out with its first batch of durability data showing that figure fell slightly to 11.2% about 150 days after the last dose. Amgen presented at the 20th World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease on Saturday afternoon.

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Eli Lil­ly’s Alzheimer’s drug clears more amy­loid ear­ly than Aduhelm in first-ever head-to-head. Will it mat­ter?

Ahead of the FDA’s decision on Eli Lilly’s Alzheimer’s drug donanemab in February, the Big Pharma is dropping a first cut of data from one of the more interesting trials — but less important in a regulatory sense — at an Alzheimer’s conference in San Francisco.

In the unblinded 148-person study, Eli Lilly pitted its drug against Aduhelm, Biogen’s drug that won FDA approval but lost Medicare coverage outside of clinical trials. Notably, the study didn’t look at clinical outcomes, but rather the clearance of amyloid, a protein whose buildup is associated with Alzheimer’s disease, in the brain.

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Chris Kim, Liminatus Pharma CEO

A fledg­ling biotech goes SPAC route to bankroll can­cer vac­cine, CAR-T and CD47

A relatively unknown clinical-stage biotech — backed by a Korean lighting company and focused on a cancer vaccine out of a Thomas Jefferson University lab — is headed to Nasdaq via the blank check route.

Liminatus Pharma will get about $316 million in proceeds from the SPAC combination to fund its ongoing Phase IIa study of a cancer vaccine, bring a CAR-T therapy into the clinic and prep a CD47 immune checkpoint inhibitor for human trials, the company said this week.

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Uğur Şahin, BioNTech CEO (ddp images/Sipa USA/Sipa via AP Images)

BioN­Tech bets on dif­fi­cult STING field via small mol­e­cule pact with a Pol­ish biotech

BioNTech is beefing up its relatively thin small molecule pipeline by adding weight to a clinically difficult corner of oncology R&D: STING agonists. To do so, BioNTech is teaming up with a 15-year-old Polish biotech and doling out €40 million, about $41.5 million, to start.

The deal is broken into two parts: First, BioNTech obtains an exclusive global license to develop and market Ryvu Therapeutics’ STING agonist portfolio as small molecules, whether alone or in combination with other agents.

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Bay­er starts work on $43M+ ex­pan­sion of OTC man­u­fac­tur­ing site in Penn­syl­va­nia

German pharma giant Bayer will be looking to make a significant investment into one of its US plants that produces over-the-counter drugs.

Bayer announced that it will spend $43.6 million to expand its facility in Myerstown, PA, a small town east of Harrisburg. Bayer plans to increase the site by 70,000 square feet and will have room for the installation of eight packaging lines and an area to install rooftop solar panels. The project is expected to be completed by 2025 and will add around 50 to 75 jobs.

US month­ly costs for biosim­i­lars 'sub­stan­tial­ly high­er' than Ger­many or Switzer­land, JA­MA re­search finds

As the global biologics market is expected to hit nearly the half-trillion-dollar mark this year, new JAMA research points to the importance of timely biosimilar entry, particularly as fewer biosimilars are entering the US than in Europe, and as monthly treatment costs for biosimilars were “substantially higher” in the US compared with Germany and Switzerland.

Among the three countries, biosimilar market share at launch was highest in Germany, but increased at the fastest rate in the US, the authors from the University of Zurich’s Institute of Law wrote in JAMA Network Open today.