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8 n e w h a v e n B I Z | J u n e 2 0 2 1 | n e w h a v e n b i z . c o m O n T h e R e c o r d | Q & A Growing biotech Arvinas makes big bet on New Haven By Michelle Tuccitto Sullo N ew Haven-based biopharmaceutical company Arvinas is making strides toward developing treatments for deadly ailments such as cancer and Alzheimer's disease. According to the company, its protein degraders harness the body's natural protein disposal system to eliminate disease-causing proteins. Yale University scientist Craig Crews founded the company in 2013, and Arvinas is building upon Crews' research. Arvinas' two leading oral drug candidates, ARV-110 and ARV-471, are showing early signs of working in patients. ARV-110 targets the androgen receptor, a factor in prostate cancer, while ARV-471 targets the estrogen receptor, a driver of breast cancer. Both are in phase two clinical studies. e company is also growing in staff and footprint. Arvinas, which has been working out of Science Park, plans to lease three floors, or 160,000 square feet of lab and office space, in developer Carter Winstanley's soon-to-be-built 101 College St. bioscience tower, slated to open in 2024. e move will more than double Arvinas' space. PHOTO | CONTRIBUTED New Haven BIZ recently chatted with Arvinas' president and CEO John Houston about the company's future. What made you want to be part of the new bioscience tower in New Haven? Arvinas has been around since 2013 as a spinout from Yale University and professor Crews. ey set up business in 5 Science Park in 2013. ey only had initially six people. We now have over 211 people. We have taken over a huge space in Building 5 and Building 4, and we have run out of places to grow. Even during the pandemic, we hired 75 people. It's clear we need a bigger space. We were very excited to sign the 101 College St. lease. at will allow us to really map out our growth projections between now and 2024. Will the Arvinas name be at the top of the tower? (Laughs) We don't know yet. Out of 10 floors, we will have three floors initially. We have some optionality for more floors if we need to grow. We are hoping to be the biggest tenant in the building. It should be a good grouping of academic and biotech companies there. We'll see if we end up with our name at the top like Alexion (at 100 College.) New Haven is garnering a reputation as a bioscience hub — what has been the attraction? When big pharma companies make decisions — like leaving the state or down- sizing — those scientists and leaders don't necessarily decide to leave the state. I was at Bristol Myers Squibb for many years, and the company decided to move out of Wallingford. ey were moving peo- ple to New Jersey and Cambridge. A lot of people didn't want to move. When you have great experienced scientists and leaders who stay in the state, you can really start to build a biotech cluster. On top of that, there are great ideas com- ing out of Yale and other universities. Have you been able to recruit enough biotech talent? We have been able to hire really well. People want to join Arvinas, they are excited about its story. ey are excited by the novelty of the platform and the data we have generated. People want to be part of the journey that we are on. We initially were hiring people who were Connecticut-based, whose companies had either downsized or le. But now we are hiring people outside the state. How can Arvinas' protein degrader impact the future of fighting stubborn diseases? e company was founded with this concept from Craig Crews of harnessing the cell's natural process for getting rid of dysfunctional proteins. In every cell of your body, there is the ubiquitous proteosome system. is is basically a garbage disposal unit in a cell. All the proteins in your body that are past their useful life get dragged to this garbage disposal unit. Craig was hoping to see whether or not the system could degrade the protein he wanted to degrade as opposed to the cell monitoring and making those decisions. at is exactly what he did. He invented these molecules called PROTACs, (short for proteolysis-targeting chimeras). ese hijack the cell's natural machinery and bind to the protein you want to specifically degrade, so that protein is dragged off to this garbage disposal unit. With our drugs, we get rid of the protein. It is unique and different. What's the status of ARV-110? If eventually approved for use, what will it mean for prostate cancer patients? It is a drug completely focused on targeting the androgen receptor in patients who have metastatic prostate cancer. We are designing molecules that degrade the androgen receptor, so it can no longer send signals to the tumor to allow it to grow, so the tumor ideally dies off. We are in phase two with the study. Hopefully the data will continue to show that we are having good results in a very late-stage patient population. ese are pa- tients who have resistance to current thera- pies. We are seeing good signs of efficacy. If that continues, we are hoping to move the compound forward into phase three and eventually into the marketplace. We are hoping the safety profile will be good enough so we can get it to patients earlier in the disease. Over the next two or three years, we should be on a path, hope- fully, to get an approved drug. And what about ARV-471 — what could it mean for breast cancer patients? In this one, we are targeting the estrogen receptor, which is very involved in driving tumors in breast cancer patients. e con- cept is to get rid of the estrogen receptor as opposed to inhibiting it. e clinical trial we are now in is phase two, with very late-stage patients. Our drug is showing signs of efficacy. It is very excit- ing for those patients who are responding. What can you tell me about the company's goals related to fighting neurological diseases, such as Alzheimer's, Parkinson's and Huntington's? When we first had the proven concept of protein degradation working in an oncolo- gy setting, the team had already started to do experiments in other disease areas. One of the areas they picked was Alzheimer's. Can you degrade one of the proteins that is thought to cause aspects of Alzheimer's, a protein called tau? e team showed they could make a molecule that would degrade tau. ey did an animal study where they injected it and showed, in John Houston Arvinas President and CEO Education: Ph.D. in microbial biochemistry from Heriot-Watt University, Edinburgh, Scotland Age: 61 Rendering of 101 College Street project by Elkus Manfredi Architects of Boston. Arvinas has leased space and plans to occupy three floors of the building once it is ready for occupancy. John Houston IMAGES | CONTRIBUTED

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