Thank you to all who attended WuXi Night in Boston! The WuXi Boston office along with WuXi’s International Discovery Service Unit (IDSU), Lab Testing Division (LTD), Chemistry Services Unit (CSU), our process development and manufacturing subsidiary STA, LabNetwork, and WuXi Healthcare Ventures II, were happy to host this event for colleagues and peers across specializations and industries to come together and celebrate innovation and collaboration at Boston’s beautiful seaport district. Despite the heat, the event drew close to 200 guests featuring leaders from the American Chemical Society, Pfizer, Novartis, Vertex Pharmaceuticals, Biogen, and many more local and out of town professionals in biotech, pharma, research institutions, and venture capital community. It was truly an exciting gathering of great minds and great fun!
See more pictures at WXPress.
WuXi presents a Q&A with Dr. Osvaldo (Lalo) Flores, CSO of Novira Therapeutics, a leading biotech based in Philadelphia, PA with novel approaches in anti-HBV drug discovery. Hepatitis B infection presents a significant unmet medical need. An estimated 350 million people worldwide are living with chronic HBV infection and many of these infected patients incur a higher risk of developing cirrhosis and liver cancer. Current drugs approved for the treatment of HBV can effectively suppress virus replication, but rarely lead to a cure. Novira Therapeutics is an antiviral drug discovery company that is focused on the discovery of first-in-class antiviral therapeutics for the treatment of chronic HBV and HIV infections. It recently began a Phase 1a clinical study of NVR-1221, a small molecule, direct-acting antiviral, for treatment of HBV infection.
Novira’s NVR-1221 is one of a new class of agent that targets the viral core. Can you explain why NVR-1221 is a promising approach for treatment of HBV? How would it work as a mono-therapy vs. in combination with existing therapies?
Flores: The problem with current HBV therapy is that it rarely leads to cures or durable response. NVR-1221 belongs to a new class of antiviral drugs that target the viral capsid or core protein. The HBV core protein forms the protein shell called capsid that protects the viral genome. Until recently it was believed that capsid assembly was the only role of HBV core in the virus life cycle. However, it turns out that HBV core is also involved in several processes that allow the virus to persist during antiviral therapy which include: 1) formation and maintenance of the viral mini-chromosome or cccDNA copy number in the nuclei of infected hepatocytes, 2) maintenance of the cccDNA in a transcriptionally active state and 3) suppression of the host antiviral innate immune response.
NVR-1221 was discovered and optimized based on the ability of the drug to bind to core and disrupt capsid assembly in vitro and HBV DNA synthesis in hepatoma cell lines. However, binding of NVR-1221 to HBV core has the potential to inhibit all the other HBV core functions mentioned above which is likely to translate in potent durable antiviral response in patients.
While we believe that NVR-1221 will be highly efficacious as monotherapy, the experience with other viral diseases such as HIV and HCV has taught us that cross-class combination regimes have usually proven to be more effective than monotherapy. For that reason we plan to study NVR-1221 both alone and in combination with Interferon and a first line nucleoside in the Phase 1b trial that we are about to start.
As a new class of therapeutic, what were some of the challenges in finding the lead candidate and how did you overcome those challenges?
Flores: An easy path would have been to identify and optimize proprietary leads using as starting point capsid inhibitor compounds already described in the literature. This is a common approach used by Pharma scientists but one that we decided upfront not to pursue for many reasons. Instead, our goal was to identify completely novel chemical classes of HBV core inhibitors and to do that we performed high throughput drug screens that allowed us to identify multiple novel, attractive chemical classes of HBV core inhibitors. The challenge was then to find the right CRO partner to help us prosecute an efficient and rigorous lead optimization program that could transform screening hits into viable drug candidates. We were fortunate to partner with WuXi AppTec who has been an outstanding partner. WuXi’s ability to provide integrated medicinal chemistry, pharmacology, DMPK, ADME and toxicology support was essential for the rapid progression of the lead program and to the selection of NVR-1221 as the clinical candidate.
Why did you pursue the CTA in New Zealand over other locations?
Flores: Pharma and Biotech companies are increasingly going to New Zealand for their first in man studies. New Zealand has established an efficient, independent regulatory body along with sophisticated, top tier clinical development capabilities.
Were there any unique regulatory challenges you faced in bringing this new class of agent into clinic?
Flores: We do not expect regulatory challenges. The regulatory path for HBV drugs has been established by HBV drugs approved over the last decade which includes 5 nucleos(t)ides (Nucs) and 2 interferons. Development of combination regimens with NVR-1221 and other HBV agents is expected to follow the path established in HIV and HCV which is also helpful.
Looking at the broader antiviral R&D landscape, do you see resurgence coming? What would be the most promising areas and innovations?
Flores: Yes, I think that the HCV field has created a lot of excitement that has had a positive impact on antiviral drug development in general and on HBV in particular. It is also apparent that many players in industry and academia are beginning to shift their focus from HCV into HBV.
I think HBV drug development will become a very exciting and active area of R&D and that core inhibitors such as NVR-1221 will become the cornerstone of future curative regimens for HBV.
WuXi’s EVP & COO Steve Yang was recently appointed as the new head of WuXi’s International Discovery Services Unit (IDSU). He brings with him years of industry experience and expertise. This summer, Steve has been visiting colleagues in the newly opened WuXi Boston office. We had the opportunity to sit down with him to learn more about him and the future of IDSU.
What inspired you to join WuXi?
Steve: I am inspired by the vision of Dr. Ge Li, co-founder, chairman, and CEO of WuXi. He wants to build an open access capability and technology platform to enable anyone and any company to discover and develop healthcare products to benefit patients. I believe that my prior experience in managing global R&D portfolio, operation, and networks in Asia and Emerging Markets could contribute to WuXi’s future growth.
What are your roles at WuXi?
Steve: I am Executive Vice President and Chief Operating Officer of WuXi. I have multiple responsibilities including operation support across sites in China, accountability for US Business Unit, and leadership of International Discovery Service Unit (IDSU).
What is the scope of services that International Discovery Services Unit (IDSU) provides to customers?
Steve: The mission of International Discovery Services Unit (IDSU) is to build capable teams and deliver comprehensive solutions in synthetic chemistry, medicinal chemistry design, and development candidate to clients around the globe. Our services include synthetic chemistry execution, synthetic chemistry design, medicinal chemistry design, and program delivery.
What is unique about IDSU’s service platform?
Steve: We are proud to be the global leader in discovery chemistry outsourcing service in terms of our size, scale, depth, and breadth of chemistry expertise.
Can you provide us any insight into IDSU’s future directions for technology development and service offerings?
Steve: IDSU has evolved to become the largest capability and technology platform for discovery chemistry service in pharmaceutical and biotech industry. We serve both major pharmaceutical companies as well as young and small biotech start-ups. We realize that one size does not fit all. Therefore, we are developing a range of tailored solutions to address different needs of our customers. We also continue to strengthen our technology capabilities to respond to the new challenges of discovery chemistry.
You recently visited the newly opened Boston office. How was your visit?
Steve: I really like our new office in Cambridge! It is conveniently located within walking distance of Kendall Square, close to many of our customers, partners, and stakeholders. We have a strong and diverse team based in Boston area, representing WuXi’s major business units to engage and service our customers. It is a great opportunity to be a member of Boston’s innovation community so more entrepreneurs, scientists can benefit from WuXi’s open access capability and technology platform.