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.

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His­toric drug pric­ing re­forms pass; Pfiz­er ac­quires GBT; The long search for non-opi­oid pain drugs; 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.

The Endpoints Weekly has officially crossed the 60,000 mark on subscribers — thanks to all of your support. As the editorial team grows, we’ve been able to do a lot more, with many of those on display this week. Be sure to check out Lei Lei Wu’s deep dive on pain R&D. If you missed it, you may also rewatch her companion panel here.

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Gold for adults, sil­ver for in­fants: Pfiz­er's Pre­vnar 2.0 head­ed to FDA months af­ter Mer­ck­'s green light

Pfizer was first to the finish line for the next-gen pneumococcal vaccine in adults, but Merck beat its rival with a jab for children in June.

Now, two months after Merck’s 15-valent Vaxneuvance won the FDA stamp of approval for kids, Pfizer is out with some late-stage data on its 20-valent shot for infants.

Known as Prevnar 20 for adults, Pfizer’s 20vPnC will head to the FDA by the end of this year for an approval request in infants, the Big Pharma said Friday morning. Discussions with the FDA will occur first and more late-stage pediatric trials are expected to read out soon, informing the regulatory pathway in other countries and regions.

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No­var­tis re­ports two pa­tient deaths af­ter treat­ment with Zol­gens­ma

Two children with spinal muscular atrophy have died after receiving Novartis’ Zolgensma, a gene therapy designed as a one-time treatment for the rare fatal disease.

The deaths, which resulted from acute liver failure, occurred in Russia and Kazakhstan, Novartis confirmed in a statement to Endpoints News. Having notified health authorities across all the markets where Zolgensma is available, it will update the drug label “to specify that fatal acute liver failure has been reported,” a spokesperson wrote.

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House pass­es his­toric drug pric­ing re­forms, lin­ing up decades-in-the-mak­ing win for Biden and De­moc­rats

The US House of Representatives today voted along party lines (all Dems voted for it), 220-207 to pass new, wide-ranging legislation that will allow Medicare drug price negotiations for the first time ever, and cap seniors’ drug expenses to $2,000 per year and seniors’ insulin costs at $35 per month.

Setting up a major victory for President Joe Biden, representatives returned from their summer recess to pass the Inflation Reduction Act, even as many noted the bill would only modestly reduce inflation.

Senate Finance Committee Chair Ron Wyden (D-OR) (Francis Chung/E&E News/POLITICO via AP Images)

Sen­ate Fi­nance chair con­tin­ues his in­ves­ti­ga­tion in­to phar­ma tax­es with re­quests for Am­gen

Amgen is the latest pharma company to appear on the radar of Senate Finance Committee Chair Ron Wyden (D-OR), who is investigating the way pharma companies are using subsidiaries in low- or zero-tax countries to lower their tax bills.

Like its peers Merck, AbbVie and Bristol Myers Squibb, Wyden notes how Amgen uses its Puerto Rico operations to consistently pay tax rates that are substantially lower than the U.S. corporate tax rate of 21%, with an effective tax rate of 10.7% in 2020 and 12.1% in 2021.

FDA ap­proves sec­ond in­di­ca­tion for As­traZeneca and Dai­ichi's En­her­tu in less than a week

AstraZeneca and Daiichi Sankyo’s antibody-drug conjugate Enhertu scored its second approval in less than a week, this time for a subset of lung cancer patients.

Enhertu received accelerated approval on Thursday to treat adults with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, and who have already received a prior systemic therapy.

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J&J to re­move talc prod­ucts from shelves world­wide, re­plac­ing with corn­starch-based port­fo­lio

After controversially spinning out its talc liabilities and filing for bankruptcy in an attempt to settle 38,000 lawsuits, Johnson & Johnson is now changing up the formula for its baby powder products.

J&J is beginning the transition to an all cornstarch-based baby powder portfolio, the pharma giant announced on Thursday — just months after a federal judge ruled in favor of its “Texas two-step” bankruptcy to settle allegations that its talc products contained asbestos and caused cancer. An appeals court has since agreed to revisit that case.

CSL is gathering its four business units under a unified brand identity strategy (Credit: CSL company site)

CSL brings Se­qirus, Vi­for un­der par­ent um­brel­la brand in iden­ti­ty re­vamp

CSL is gathering its brands under the family name umbrella, renaming its vaccine and newly acquired nephrology specialty businesses with the parent initials.

CSL Seqirus and CSL Vifor join CSL Plasma and CSL Behring as the four now uniformly branded business units of the global biopharma. The Seqirus vaccine division was formed in 2015 with the combination of bioCSL and its purchase of Novartis’ flu vaccine business. CSL picked up Vifor Pharma late last year in an $11.7 billion deal for the nephrology, iron deficiency and cardio-renal drug developer.

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