Why did you decide to join Monte Rosa Therapeutics?
I am an MD by training, having attended medical school in Germany where I developed a fascination with the molecular mechanisms of diseases, particularly through my thesis work on the pathogenesis of chronic myeloid leukemia. This interest coincided with the emergence of targeted small molecule therapies, exemplified by imatinib, a groundbreaking drug from Novartis. My career then took me to Novartis' Genomics Institute in San Diego, followed by a role in Cambridge where I contributed to the development of several small molecule drugs. Later, I took leadership positions in smaller biotech companies, including H3 Biomedicine, which was a venture with a Japanese pharma company, Eisai. After delivering on our promises ahead of schedule, I joined Third Rock Ventures in Boston and was later recruited by Versant Ventures to join Monte Rosa Therapeutics, eventually becoming its CEO.
Upon joining Monte Rosa, I moved the headquarters to Boston, though we maintain a significant presence in Basel, Switzerland. Monte Rosa was named after a mountain in the Alps, reflecting our Swiss origins and the company's incubation by Versant Ventures. This transition from academia to industry leadership has allowed me to leverage my medical and scientific background towards innovative drug discovery and development.
Could you explain the concept of Molecular Glue Degraders (MGDs) and how they differ from traditional small molecule therapies?
MGDs are a subcategory of small molecules that promote protein-protein interactions, leading to the degradation of specific proteins. This approach is distinct from traditional small molecule drugs as it targets and eliminates proteins altogether, mimicking the effects of gene knockouts or mRNA knockdowns. Unlike traditional inhibitors that require a druggable pocket on the target protein, molecular glue degraders work by inducing complementarity on the protein surface, expanding the range of potential targets. This methodology not only allows for longer-lasting pharmacodynamic effects but also broadens the scope of undruggable proteins that can now be targeted for therapeutic interventions.
What are the current and potential applications of MGDs?
Our work at Monte Rosa has been pioneering in the rational design of MGDs, with a focus on selective targeting to expand into various disease areas. Historically, drugs like lenalidomide emerged serendipitously as molecular glue degraders. Our approach is to apply rational design to achieve selectivity, making these drugs applicable not just in oncology, where safety requirements are different, but also in diseases like inflammation, autoimmune disorders, and even neurological conditions. We have initiated a collaboration with Roche to explore targets in neuroscience and beyond, underscoring our commitment to leveraging molecular glue degradation technology across a broad range of therapeutic areas.
Can you discuss your collaboration with Roche and the implications for drug discovery and development?
Our partnership with Roche, based on mutual interests and proximity in Basel, is a discovery collaboration that allows us to combine our strengths without encumbering Monte Rosa’s existing portfolio. This venture focuses on targets of interest to Roche, utilizing our expertise in MGDs to initiate projects from scratch. The collaboration, which includes projects in oncology and neurological diseases, not only validates our approach but also demonstrates confidence in our platform's ability to develop selective and safe molecules for applications beyond oncology. This partnership is particularly exciting as it opens new avenues for treating rare diseases and metabolic conditions with the potential for broad application of our technology.
How does the QuEEN platform incorporate AI and machine learning in the development of MGDs?
QuEEN uniquely combines machine learning and AI with experimental validation to create a self-learning platform for drug discovery. This approach allows us to explore the human proteome for ligases that can be reprogrammed for our purposes, overcoming the limitations of traditional drug discovery methods. AI plays a crucial role in identifying compatible ligases and in fitting molecular glue degraders within complex protein interactions, streamlining the process from concept to clinic-ready drug candidates. This innovative use of technology not only accelerates our drug discovery process but also enhances our ability to tackle previously undruggable targets, marking a significant advancement in the field of therapeutic development.
How has the depressed economic climate for biotech affected Monte Rosa?
The life sciences industry has faced significant challenges in the past two to three years, with the biotech sector experiencing a period of hype at the pandemic's onset, followed by difficulties due to inflation and higher interest rates. This environment has proven particularly challenging for early biotech, small, and mid-cap companies due to their higher risk profiles and the negative impact of high interest rates. Despite these obstacles, recent months have shown signs of improvement, with an increase in initial public offerings (IPOs) and financing activities, though not yet at the levels seen three years ago.
For Monte Rosa, the focus remains on advancing quality science and drug candidates. The company has maintained a positive performance, attributed to its leadership in molecular glue degraders and a unique portfolio that includes promising partnerships, underscoring confidence in its platform and the potential of its lead candidates.
Could you outline Monte Rosa's approach to addressing cancer, including the types of cancer you target and the delivery method of your drugs?
Monte Rosa's therapeutic candidates, designed as orally bioavailable drugs, offer a novel approach to cancer treatment by targeting specific genomic aberrations or oncogene over-expressions. This method stands out for its convenience and potential for higher market penetration compared to injectable therapies. The company's lead program, MRT-2359, focuses on a subset of MYC-driven cancers, particularly targeting the GSPT1 protein pivotal in these cancers. Initial clinical trials are concentrating on lung cancer, with exploratory studies extending to breast cancer, prostate cancer, and neuroendocrine tumors, among others. This approach underscores Monte Rosa’s commitment to developing treatments for a broad range of cancers, leveraging the extensive expression of MYC transcription factors across various cancer types.
What are your goals for next five years?
Over the next five years, we will aim to solidify our position as a leader in the field of molecular glue degraders, demonstrating the unique and broad applicability of our platform across multiple disease areas. Despite the challenging economic environment, the company is focused on advancing its highly differentiated platform and establishing molecular glue degraders as a valuable modality in small molecule therapeutics. Monte Rosa aspires to be recognized for taking this concept to the next level, much like the advances seen in RNA interference (RNAi) and gene editing technologies over the past decades, showcasing the potential to revolutionize treatment paradigms across a range of conditions.
