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n e w h a v e n b i z . c o m | M a r c h 2 0 2 1 | n e w h a v e n B I Z 9 A s a researcher, Dr. Aaron Ring, an assistant professor of immunobiology at Yale, knows there are safer investments than life science. "I'm no economist, but there are definitely sectors of the economy with better historical returns than bioscience," he said. "But private and state investors understand we're doing something that can have real impact." In Ring's case, it's a new approach to targeting cancerous tumors that has not only drawn the eyes of the biomedical community, but also investors, to Simcha erapeutics, a New Haven-based startup By Matthew Broderick that Ring helps guide. Last June, the company — currently comprised of Ring and a handful of board members — received a $25 million investment, including $1.5 million from Connecticut Innovation's Bioscience Fund, to underwrite a phase one clinical trial that is set to begin in the first half of 2021. "Aaron is a bright young researcher whose scientific and entrepreneurial background is impressive," said Dan Wagner, senior managing director of investments for Connecticut Innovations (CI), the state's quasi venture capital arm, who currently serves on Simcha's board. Ring, who was recognized in Forbes 30 Under 30 Healthcare class in 2016 at age 29, is no stranger to biotech startups. As a grad student at Stanford University, Ring engineered an immuno-oncology agent, a compound that was licensed to another startup he helped found, ALX Oncology, which is now a publicly-traded company. e oncology agent Ring helped create is now in advanced clinical trials. Ring's latest work is a new protein, called DR-18, which builds upon the learning of earlier — but failed — trials using molecular immunotherapy to treat cancer. Immunotherapy is a type of cancer treatment designed to boost the body's natural ability to combat tumors. Ring's research found that a molecule called IL-18, which could be used to treat cancer by elevating T-cells and Killer T-cells to fight a tumor, was ineffective because decoy receptors around the tumors were neutralizing it. So Ring engineered a decoy-resistant protein that in essence, circumvented the negative effect of the decoy receptors and enabled the body's natural immune system to more effectively combat the tumor in a test environment. Testing in mice found that compared to a normal IL-18 molecule, Ring's decoy-resistant molecule inhibited tumor growth and, in some cases, created a complete regression of the tumor. Ring initially founded Simcha erapeutics in 2018 with $6 million in seed money. e subsequent lab results for his product have drawn another $19 million from four venture investors. "Dr. Ring's technology is novel and insightful," said Connecticut Innovations' Wagner. "In the oncology space, that has created large value in the marketplace." And the global cancer therapeutics market is huge and expected to grow from $98 billion in 2018 to an estimated $180 billion by 2026, reflecting a compound annual growth rate of 7.7%, according to Allied Market Research. Long haul One of the challenges with any bioscience company is that it takes potentially decades to bring a drug from lab to market. Ring said he understands that lengthy and costly process and the significant challenges to get through it. "Most biotech companies and research labs will not take their [discovery] to the finish line," he said, noting just opening up a phase one clinical trial costs more than $20 million. Ring said he enjoys playing an important role in early clinical development and accumulating the proof of concept data. "Smaller biotech companies need to partner their assets with a major pharmaceutical company or large biotech," he said. Last June, for instance, pharma giant Pfizer established a $500 million fund to invest in publicly-traded small and mid- sized companies working on discoveries within the company's core focus area. Likewise, the Connecticut Innovations Bioscience Fund, which launched in 2013, pledged to invest $200 million over the course of 10 years to provide grants, equity investments, loans and loan guarantees to bioscience companies and leverage private investment. CI has more than 170 biotech- related companies in its portfolio. While financial return on investment is an important part of the pharmaceutical ecosystem — to continue to fund new advances — Ring said he is motivated by the pure science of discovery. "We can't however ignore the translation potential of what we do in my lab," he said. He hopes that phase one of his DR-18 trials, which will involve 25 to 40 cancer patients, will show enough efficacy to warrant a second phase trial. Phase one trials, which test for dosage and safety, could run for 12 to 18 months. If proven successful, the implications of Ring's immunotherapy could have a significant impact on a cancer patient's ability to maximize their body's natural defenses against cancerous tumors. For now, for Ring and Simcha erapeutics' investors, it's wait and see. And hope for a strong return on investment. n S t a r t u p s , T e c h n o l o g y & I n n o v a t i o n New Haven's Simcha erapeutics to launch clinical trial for new cancer immunotherapy Simcha Therapeutics Top Executive: Aaron Ring, Scientific Director Industry: Bioscience Location: New Haven Website: www.simchatx.com Contact: info@simchatx.com PHOTO | CONTRIBUTED Simcha Therapeutics founder Aaron Ring.

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