Member Spotlight: Q&A with Wave Life Sciences

Feb 01, 2023

Every month, MassBio spotlights a member company and the great work they’re doing to advance the life sciences industry and support the patients we serve. In February, we spoke with Paul Bolno, President and CEO of Wave Life Sciences since 2013. During his tenure, Wave has grown from a team of five into a fully integrated clinical-stage genetic medicines company, with a broad pipeline of preclinical and clinical programs supported by scalable, in-house manufacturing capabilities. Prior to joining Wave, he was Vice President, Worldwide Business Development with positions as Head of Asia BD and Investments and Head of Global Neuroscience BD, as well as Head of Oncology BD at GSK. Prior to his time at GSK he was Director of Research at Two River Group. Dr. Bolno earned a medical degree from MCP-Hahnemann School of Medicine and an MBA from Drexel University and was a general surgery resident and cardiothoracic surgery postdoctoral research fellow at Drexel University College of Medicine.

Tell us about your organization, its mission, and current initiatives 

At Wave Life Sciences, we’re driven by a resolute sense of urgency and are on a mission to bring life-changing medicines to people affected by devastating genetic diseases. We’ve built a unique oligonucleotide platform (PRISMTM) that combines novel chemistry with the means to optimally address disease biology through multiple RNA-targeting modalities – editing, splicing, and silencing (including siRNA and antisense). In 2022, we delivered on the initial promise of our platform with the first data showing target engagement across all three of our clinical programs: WVE-N531 for Duchenne muscular dystrophy, WVE-003 for Huntington’s disease and WVE-004 for amyotrophic lateral sclerosis and frontotemporal dementia. Simultaneously, we continued to advance our leading RNA editing capability and named our first clinical candidate: WVE-006 for alpha-1 antitrypsin deficiency. Finally, we recently announced a strategic collaboration with GSK to advance transformative oligonucleotide therapeutics, which will bring multiple new programs aimed at novel, genetically-validated targets into our pipeline over the next four years.

How will your organization’s activities help patients now and into the future? 

Since the beginning of Wave we have been patient focused, having strong engagement with the patients and families we serve. Our pipeline addresses devastating diseases where scientific progress has been extremely limited. We have also pioneered innovative clinical trial designs to incorporate the feedback of patients and their families and reduce the burden on those who are already bravely enduring the challenges associated with these diseases. For example, our WVE-003 and WVE-004 studies have adaptive designs to rapidly optimize dose level and frequency based on early indicators of target engagement, and Wave was also among the first companies selected for FDA’s Complex Innovative Trial Designs pilot program in 2019.

While our current clinical pipeline includes candidates for monogenic disorders, we are particularly excited about our growing capability to leverage RNA editing for upregulation and modification of protein-protein interactions. This approach has the potential to reach significantly larger populations, such as those with cardiometabolic, liver and renal diseases.

What do you see as the biggest challenge facing the life sciences industry today? 

As an industry we have made incredible strides with understanding the relationship between certain genes and diseases, yet those insights have not meaningfully increased the universe of targets that are considered “druggable.” For this reason, there is significant overlap among RNA and DNA therapeutics companies on the genetic targets they are working on. Our belief is that combining novel nucleic acid chemistry with novel targets is crucial for realizing the full potential of genetic medicines.

This is the precise reason behind our recently announced collaboration with GSK. To continue to build a pipeline of transformational oligonucleotide therapeutics and gain access to new areas of disease biology, we recognized the need to partner with a company that has significantly invested in genetics and genomics to validate novel targets. Likewise, GSK recognized a need for a complementary discovery capability to translate these insights into medicines. This collaboration has potential to deliver a substantial number of first-of-their-kind therapeutics to patients and families.

What’s next for your organization / what are you focused on in the coming year? 

In 2023, we’re focusing on advancing WVE-003, WVE-004 and WVE-N531 to additional clinical data milestones. These data will include relevant biomarkers and safety/tolerability to inform next steps for each program. We also expect to bring the first-ever RNA editing therapeutic into the clinic with WVE-006. WVE-006 represents a novel treatment approach for AATD and is designed to correct the single point mutation on the SERPINA1 Z RNA transcript, thereby addressing both lung and liver manifestations of the disease. The WVE-006 first-in-patient study would both validate WVE-006 as potential best-in-class approach for AATD, as well as the viability of RNA editing as a new therapeutic modality. We will continue our preclinical research on RNA editing for upregulation and modulating protein-protein interactions, and expect 2023 to be a year where we share more on potential therapeutic applications. Finally, we’re excited to progress our GSK collaboration leveraging novel targets and our PRISM platform.

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