NewHavenBIZ

22 n e w h a v e n B I Z | N o v e m b e r / D e c e m b e r 2 0 1 9 | n e w h a v e n b i z . c o m PERSONAL CURE Continued from Page 21 patients by first name who lived on the grounds of the hospital, and I became very interested in the brain chemistry that led to abnormalities." As a physician, Coric became increasingly frustrated with the lim- ited treatment options available. "ey wouldn't respond to our current therapies, so what do you have le for them?" he asks. "Either you say, 'I'm sorry, there's nothing le,' or 'I'll try really hard to find a new therapy.'" Today, Coric and Biohaven are doing just that. e company, headquartered at 215 Church St., develops drugs that target mental illness and neurological disease, from OCD and generalized anxiety to Alzheimer's, migraine, ALS and others. Coric's research at Yale led to the development of Biohaven's exper- imental drug troriluzole, a single compound that aims to treat four different diseases — OCD, general- ized anxiety disorder, Alzheimer's and spinocerebellar ataxia, a condi- tion marked by progressive loss of coordination — by regulating the brain chemical glutamate. While the body needs glutamate for normal functioning, too much of it leads to disease, Coric explains, and the type of affliction depends on where in the brain it is accumulating. "It's just a matter of where that pathophysiology is in the brain that tells you whether it's a behavior problem or whether it's a neurologic disease [such as ALS]," he explains. Biohaven's compound acts as a vacuum cleaner of sorts, removing the glutamate from neurons in parts of the brain that are flooded, so it can potentially impact multiple different diseases, Coric explains. e drug, one of several in Bio- haven's pipeline, is now in clinical trials for all four indications, with results expected early next year. If successful, it could be available to patients by 2021. (Biohaven's lead drug, a new mi- graine treatment called rimegepant that it licensed from Bristol-My- ers Squibb, has gone through the regulatory process and is expect- ed to win FDA approval in early 2020. Another drug targeting ALS, licensed from AstraZeneca, will be tested in a Massachusetts General Hospital-run trial next year.) "When we go into a therapeutic area, we act as though an immediate family member was suffering from that [disease]," Coric says. "at's how dedicated and passionate you have to be because these are tough indications to solve." "It's not just about the science. It's about getting involved [with patient groups] and advocating for every one of those patients [suffering from] the disease that we're study- ing," he adds. "Our team sacrifices their nights, their weekends, constantly working on these protocols in the hopes that one of these therapies will make a meaningful difference." A 'heat-seeking missile' for tumors Both Cybrexa erapeutics CEO Per Hellsund and the New Haven company's scientific co-founder, Ranjit Bindra, MD, have witnessed the pressing need for kinder, gentler cancer drugs. Hellsund's mother has been through multiple cancer therapy regimens since her breast cancer recurrence seven years ago, and she's been forced to abandon some that were working because the side effects were too toxic. e serial entrepreneur also lost his sister to lung cancer last year. Bindra, meanwhile, watched his own father suffer through brutal chemotherapy treatments in the early 2000s; he was diagnosed with advanced esophageal cancer and treated at Yale while Bindra was there attending medical school. He died just three weeks before Bindra's graduation. "My interest in finding new cancer treatments was, really, in large part motivated by that personal loss," Bindra says. "His parting words were: 'We need to get better treatment.'" From Cybrexa's laboratory in Science Park, Hellsund and Bindra are now advancing a new class of cancer therapies that can target tumors while sparing healthy tissue, potentially eliminating the bone marrow toxicity, gastrointes- tinal distress, hair loss and other troublesome side effects their own parents endured. Using technology developed at Yale and the University of Rhode Is- land, the three-year-old startup has created what Bindra describes as "a heat-seeking missile" for tumors. Featuring a molecule known as pHLIP (which stands for pH Low Insertion Peptide), the compound forms a corkscrew-like structure when it comes in contact with an acidic environment, which happens to be a universal feature of cancer cells. e structure then drills its way directly into the tumor cell, where it deposits a cancer-fighting agent and leaves the healthy cells around it unharmed. Cybrexa's experimental drug, CBX-11, combines that technology with an already approved DNA repair inhibitor known as a PARP inhibitor, a anti-cancer drug that works by preventing the cancer cells from repairing themselves. ere are already DNA-repair inhibitors that, when administered with chemotherapy, can kill almost any tumor, Bindra says. But the combination is oen too toxic to be given to patients safely. "By delivering these anti-cancer agents directly to the tumor, we're able to target the tumor and offset many or all of these horrible side effects," Hellsund says. Another advantage of CBX-11 is that it's "tumor-agnostic," says Bindra. Current DNA repair inhib- itors work only on tumors linked to specific genetic mutations, such as BRCA1 and BRCA2 "So many, many more patients now would be eligible for these re- ally active drugs," he says. "Patients like my own father would have been eligible." Although CBX-11 comes too late for Bindra's father, it could be just in time for Hellsund's mother, who told him she wants to take part in Cybrexa's upcoming clinical trial, which could begin in early 2020. "e therapies we are developing would certainly apply to her," says Bindra. "We keep saying that we're going to make sure she gets a spot." n The son of a psychiatrist and pharmacist, Biohaven CEO Vlad Coric spent much of his childhood on the grounds of Norwich State Hospital, which ignited a career-defining interest in the brain chemistry that led to abnormalities. PHOTO/ANDREW VENDETTI

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