MSQ brought to you valuable insights into strategic partnerships and modality development in the biopharma world. The webinar was moderated by, Echo Hindle-Yang, President & CEO of MSQ Ventures, with the participation of the following distinguished speakers: 

• Nikhil Mutyal, Executive Director, BD&L, Merck 

• Randy Teel, SVP of Corporate and BD, Arvinas 

• Lily Zou, CEO, Degron Therapeutics 

• Sahm Nasseri, CBO, Biotheryx, Inc. 

Advancing Therapies through Transformative Partnerships:  A Deep Dive into Protein Degradation Collaborations in Biopharma 

Randy Teel highlighted Arvinas’ significant growth attributed to strategic partnerships, notably with its strategic alliance with Pfizer in 2021. This collaboration allowed Arvinas to target late-stage breast cancer patients and conduct multiple trials concurrently, boosting its position as a major player in the industry. The company continues to seek further partnerships, including utilizing AI to develop innovative treatments for both validated and challenging targets, as an effort to fuel its continuous growth. 

Nikhil Mutyal shared insights into Proxygen’s groundbreaking collaborations with Arvinas and Proxygen in the field of protein degradation. Their unique platform enables simultaneous screening for multiple targets, increasing potential success through target validation in various modalities. Comprehensive landscape exercises are conducted to ensure successful collaborations aligned with strategic objectives. Proxygen's strategic molecular clues and multi-target screening capability make it an exceptional partner of choice. 

Sahm Nasseri discussed the collaboration between Biotheryx and Incyte, which focuses on developing molecular glue degraders for challenging oncology targets. This partnership allows both companies to take on more risk and explore innovative treatments. Molecular glues have garnered significant interest in the pharma industry, and Biotheryx sees this collaboration as a crucial step in promoting their platform and contributing to advancements in targeted protein degradation. Sahm also highlighted the importance of staying at the forefront of scientific advancements for success in a competitive biotech industry environment. 

Lily Zou also discussed the factors influencing Big Pharma's selection of specific data companies for collaboration. These factors include the uniqueness of the company's data archetype, a validated platform with advanced programs, and strategic synergies. Degron Therapeutics positions itself as a global player with labs in both China and the US, highlighting its commitment to technological advancement and global competition. They believe that collaboration can be facilitated despite challenges in China as long as they maintain technology leadership globally. 

Advancing Protein Degradation: Global Perspectives and Innovative Strategies 

Nikhil Mutyal discusses the global impact of scientific advancements in TPD highlighting contributions from regions like China, Asia, and Korea. These regions are actively pursuing cutting-edge approaches like autophagy-based degradation and induced proximity. Chinese companies, such as Degron, are rapidly emerging with innovative strategies involving molecular degraders, and this trend suggests increased collaboration with Chinese firms, similar to that seen with ADC companies. 

Randy Teel focuses on two aspects of drug development: clinical development and creating protein degraders or molecular glues. Global scale and rapid enrollment are crucial in clinical development, while a strong chemical foundation is emphasized for protein degraders. Investing in screening capabilities for difficult-to-drug proteins is considered valuable. Arvinas is collaborating with Pfizer for Phase 3 trials of (ARV-471), building upon Pfizer's global network and infrastructure to fully operationalize the trials. 

Sahm Nasseri discusses various aspects of protein degradation, including autophagy-mediated degradation and novel E3 ligases. E3 ligases are considered the most validated approach, and there are growing interests in tissue-specific applications. Protein degradation has mainly focused on oncology, but there's an increasing interest in exploring immunology and CNS applications. Smaller biotech companies like Sahm's leverage partnerships and validate their platform using existing degraders with specific characteristics. Combining protein degraders as payloads for ADCs is being explored for tissue-specific targeting. 

Lily Zou agrees with Sahm's summary and describes their small company's specialization in specific drug indications, focusing more on oncology targets. Their technology has potential applications in PROTACs and molecular glues, with a preference for the latter due to its drug-like properties. The company's foundation was based on discovering a novel degrader from a small compound library. While oncology remains their primary focus, they are open to expanding into other therapeutic areas, with a commitment to solidifying their core in oncology first.  

Optimizing Collaborations: Strategies and Timing for Successful Deals in New Modalities 

Nikhil Mutyal addresses the varying approaches companies take with new modalities, some favoring risk-taking and larger deals, while others opt for caution and clinical validation. He stresses the importance of understanding larger companies' perspectives and the advantages of partnering with global players like Merck or Pfizer. Nikhil also suggests considering alternative options, such as evaluation agreements, to leverage risks and foster fruitful collaboration outcomes. Ultimately, he advises companies to align their decisions with their specific interests and goals. 

Randy Teel emphasizes the significance of making timely decisions in data analysis and collaboration opportunities, discouraging prolonged waiting for more information. Each deal requires a tailored approach with a shared vision between parties for successful collaboration. He highlights the involvement of scientists throughout the process to maintain their enthusiasm and ensure effective execution. Ongoing communication is vital for achieving fruitful collaborations.  

Echo Hindle-Yang discusses the common CEO behaviors of getting overly excited about data readouts, leading to delays in deals making for better valuations. However, waiting for more data often results in varied outcomes. She cites C4 Therapeutics' well-timed success with a Chinese company before filing their IND as an example. Thorough due diligence and confident decision-making are essential for achieving mutually beneficial and competitive deals. Echo stresses the significance of timing and being well-informed to achieve positive outcomes in such transactions. 

Navigating Investor Interest and Contrasting Environments in Protein Degradation Therapies   

Sahm Nasseri notes a recent decline in investor appetite for target protein degradation due to underwhelming clinical readouts and industry trends. Investors are now carefully evaluating the differentiation of bifunctional degraders compared to inhibitor counterparts, leading to prolonged decision-making processes and impacting valuations. 

Lily Zou highlights the contrasting investor environments in China and the US, particularly in Business Development (BD). Chinese investors previously found success with companies targeting the local market but now seek more innovative and sustainable technologies. To attract funding, companies must have a validated and unique platform. Presently, investors focus on the value of lead programs developed on the platform, especially their ability to target undruggable molecules. Having broad applications, efficacy, and safety in lead programs are essential for attracting investors. Staying innovative is crucial for securing investments from both US and Chinese investors.  

Advancing Protein Degradation: Perspectives on Investor Excitement and Future Breakthroughs  

Randy Teel discusses reinvigorating investor excitement in the protein degradation field by showcasing success in non-PROTAC approaches and breakthroughs in different therapeutic areas. He emphasizes the need for innovation and diversification to capture investor attention. 

Nikhil Mutyal agrees with Sahm Nasseri's observation of a slowdown in new company formations in the field. He highlights the cautious approach of investors and the need for conclusive clinical data to demonstrate the superiority of protein degradation over inhibitors for specific targets.  

Sahm Nasseri shares two key aspects he eagerly anticipates - a favorable clinical readout for a new molecular glue targeting a novel substrate and a clinical readout from a bifunctional degrader showcasing differentiation from inhibitors. 

Lily Zou agrees with the importance of waiting for success in other Arvinas compounds to demonstrate the potential of bifunctional degraders. She highlights the significance of IKZF1/3 degraders and the excitement around the next target, GSPT1. Lily emphasizes that any degrader demonstrating clinical efficacy and safety will strengthen the protein degradation field. 

Overall, the webinar showcased the significance of partnerships, global collaboration, and investor interest in driving transformative breakthroughs in targeted protein degradation therapies.  

To watch the full recording of the webinar, please go to MSQ Webinar page or click here.