Dr. George Hartman is the Vice-President of Chemistry and Preclinical Development and cofounder of Novira Therapeutics, a clinical stage, privately-held company that discovers and develops small molecule antiviral drugs for the treatment of chronic hepatitis B (CHB) infection.  Novira’s lead core inhibitor candidate, NVR 3-778, disrupts the HBV lifecycle by inducing the assembly of defective capsids and is a potent inhibitor of HBV replication both in cell culture models and a humanized liver mouse model of CHB. An excellent preclinical safety profile has been established for NVR 3-778 and a Phase 1 clinical trial is underway in New Zealand.  This novel mechanism of action promises to change the paradigm for CHB treatment.  Recently, Novira Therapeutics and Johnson & Johnson have signed a definitive agreement under which Johnson & Johnson will acquire 100% of the capital stock of Novira.

Prior to his work at Novira, Dr. Hartman was Executive Director of Medicinal Chemistry at Merck where he was the lead inventor of the antiplatelet agent Aggrastat® (tirofiban hydrochloride) used in the treatment of ischemic coronary syndrome and was associated with several additional drug candidates that progressed into advanced clinical studies.   Dr. Hartman is author of over 200 publications in leading journals and over 140 US patents covering a range of therapeutic areas.  Innovation That Matters (ITM) had the honor of talking with Dr. Hartman on Novira, NVR 3-778, and Novira’s collaboration with WuXi.

Novira Therapeutics offers an interesting approach to Hepatitis B therapies. Can you provide us with your perspectives on this indication?

Hartman: Hepatitis B infection presents a significant unmet medical need with an estimated 350 million people worldwide living with chronic HBV infection. A significant number of patients with chronic infection incur a higher risk of developing cirrhosis and cancer. It is estimated that 60% of hepatocellular carcinoma (liver cancer) is a direct consequence of HBV infection. Current drugs approved for the management of CHB include PEG-Interferon and nucleot(s)ides which can effectively suppress virus replication, but rarely lead to a cure.  Novira’s novel antiviral drug candidates have the potential to address the limitations of current CHB therapies when used either as mono-therapy or in combination with existing standards of care.

NVR 3-778 has made it to Phase 1A Clinical Trials – what distinguishes this therapy from others in the market?

Hartman: NVR 3-778 is a small molecule, direct acting antiviral drug candidate that inhibits the HBV core or capsid protein and being investigated for oral administration in patients with Chronic Hepatitis B (CHB). HBV core protein is a novel and promising drug target with multiple activities that enable viral replication and persistence. NVR 3-778 inhibition of the HBV core protein function offers the potential for a more efficient suppression of virus production and replication which could lead to improved durable viral suppression and functional cure rates.

Novira is a relatively young company and has already completed its first clinical trials. Can you elaborate on your discovery strategy?  

Hartman: Novira is employing innovative chemistry and biology technologies to discover small molecule inhibitors of the HBV core or capsid protein as well as other drug candidates with novel modes of action.  Our employees are experienced preclinical and clinical researchers with broad understanding of the individual disciplines necessary to advance projects with high quality and efficiency.  Key to our advances has been the identification of and collaboration with CROs that provide high quality discovery services.  WuXi has been a very important partner as Novira progressed from the early discovery phase to a clinical-level development company by providing excellent chemistry, biology, ADME and CMC collaboration opportunities.  The competitive advantage provided by WuXi’s integrated access to services across disciplines was an important feature of achieving speed and results. 

How would you characterize the Novira-WuXi collaboration?

Hartman: Efficient drug discovery requires medicinal chemistry to be matched with excellent synthetic chemistry and it was therefore important that our interactions with WuXi chemistry turned out to be highly flexible and productive.  WuXi chemists have been very interactive and skillful as synthetic schemes are developed and targets are pursued.  Our discovery paradigm has also benefited from the opportunistic use of library synthesis matched with chiral separation and SFC purification methods in place at WuXi. 

You have such diverse experiences from working at Merck for over 35 years on various disease areas to co-founding Novira, a smaller company focused on a specific disease area. What have you learned in the transition and what insights can you share from these experiences?

Hartman:  The transition from big pharma to the biotech realm has provided very stimulating opportunities and changes.  However, the feature that remains the same is that it is always the quality of the individual scientist and the level of dedication that determines the level of success in the discovery process.  At Novira, we have been able to attract truly world-class colleagues in biology, chemistry and clinical research and that has meant the difference.  Also, we decided early on that innovation and efficient and focused use of resources would empower the company to exceed expectations.  The goal has always been to make quality drugs and to engage and work with whomever could assist in that goal.  We are at an inflection point both in our corporate and scientific endeavors and we are looking forward to that next stage.

Thank you, Dr. Hartman, for taking the time to talk with us about the important work you and Novira have been doing over the years.  We wish you much success in this next stage for you and Novira.

 

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