Nello Mainolfi PhD is the founder and CTO of Kymera Therapeutics LLC, the Cambridge(MA)-based biotech company pioneering targeted-protein degradation as a transformative new approach to creating breakthrough medicines.
Nello, born in Napoli (Italy), has received his PhD in Chemistry from Imperial College, University of London and has continued postdoctoral training at The Scripps Research Institute in California. He then started his professional career at the Novartis Institute for Biomedical Research in Cambridge, MA where he advanced several programs from research into preclinical and clinical development. While at Novartis he also championed new technologies such as using fragment-based drug discovery as a core strategy to deliver multiple development candidates. Nello is also Entrepreneur-in-Resident at Atlas Venture, a Cambridge based VC firm focused on investing in early stage biotech. Nello is married with Paola Castaldi (also a scientist-manager at AstraZeneca) and father of 2. He enjoys running and sailing in his spare time.
GoINPHARMA™: Nello, thank you for sitting down with us to talk about your company and the idea behind. How did it begin and what has been the journey so far?
Nello Mainolfi: The journey began towards the end of 2015. The opportunity that the technology offered was too great to pass on. The notion that using a technology that would allow to potentially target the unchartered percentage of the human proteome (80-90%) was an exciting and potentially transformational prospect. In it also important that the field of targeted protein degradation (that for many years had been relegated to a purely academic chemical biology tool) was beginning to show early signs of potentially therapeutics application.
I was able to find in Bruce Booth (partner at Atlas Venture) a believer in the investment thesis.
After putting together a business and scientific plan Kymera Therapeutics was incorporated early in 2016. With a small team we were able to show not only really powerful data but also we were able to generate insights into this (so far) really empirically driven modality that propelled the science that Kymera was building to the next level. We had several venture firms and venture arms of Pharma companies interested in investing in us and after about 16 months we closed our Series A financing. In the meanwhile we have built a team of 18 scientists and managers in Cambridge and a network of about 50 collaborators around the world.
GoINPHARMA™: One of the most innovative aspect of your company is the way you go about drug discovery, would you help us to understand how you implement it and what are the benefits of your approach vs the more conventional ones?
Nello Mainolfi: Traditionally small molecules are used to inhibit a particular function of a protein/receptor/enzyme. The inhibition of that particular function leads to a phenotype that can ameliorate or cure diseases.
The problem is that only about 15% of proteins in our cells have a function that one can inhibit with a small molecule. For this reason the remaining 85% of the proteome, most of whose dis-regulation drives many diseases from cancer to neurodegenerative disease to autoimmune disease, has been elusive.
Kymera’s technology, using heterobifunctional small molecules, allows to target most of the elusive 85% because driven by binding and not by inhibition. This binding event of our heterobifunctional molecules brings together the protein target of interest with an E3 ligase.
The E3 ligase tags the protein with a polyubiquitin chain. The tagged protein is then recognized by the proteasome and destroyed. This is why there is so much excitement in the whole biotech/pharma world around this technology, the potential upsides could be un-imaginable. We are in fact going into intact malfunctioning cells and completely removing proteins that are disease causing.
GoINPHARMA™: Then the very core of your technology is the regulation of cellular processes via redirecting the ubiquitin proteasome system (UPS), how is the future development, do you have any clinical trial planned for the near future?
Nello Mainolfi: We plan to take our first molecule in human clinical trials starting from 2020 and to show that the technology we have developed brings benefits to patients.
GoINPHARMA™: In October last year Kymera Therapeutics has been able to raise $30m in a Series A financing round with important investors such as Atlas Venture, Lilly Ventures and Amgen Ventures. What do you think was the convincing argument for the investors?
Nello Mainolfi: As mentioned before the technology has real transformational potential, in addition the team at Kymera had generated really enticing data from both therapeutics prospective but also from the standpoint of understanding the technology platform in a way that was/is unprecedented.
GoINPHARMA™: and now I would like we talk about the future, what comes next for Kymera Therapeutics?
Nello Mainolfi: 2018 is a transformational year for us. We continue to build the internal team and are looking for scientists and managers excited to help us transform this huge potential into groundbreaking medicines for patients in need. In fact we plan to be 25 at our headquarters in Cambridge, MA by the end of 2018. We are also engaged with the scientific and investment community to raise non dilutive as well as dilutive funding to continue to build Kymera towards being a clinical company by 2020. Stay tuned as exciting developments on this front will be disclosed in the next few weeks and months.
About Kymera Therapeutics
Kymera Therapeutics is a transformational biotechnology company focused on advancing the new therapeutic modality of targeted protein degradation.