At TG Therapeutics in New York City the company didn’t start out looking for new therapies for Multiple Sclerosis (MS). TG began as an oncology focused company but as the data came in from their research the company and President and CEO Michael Weiss believed their assets could be applied in additional disease spaces and are developing a new therapy for MS.

More than 2.5 million people suffer from MS worldwide. It is a long-lasting disease that can affect your brain, spinal cord, and the optic nerves in your eyes. It can cause problems with vision balance, muscle control, and other basic body functions.

MS is a rare autoimmune disease. Normally, antibodies produced by the immune system help protect the body against viruses, bacteria, and other foreign substances. In people who have MS, the immune system attacks the body. There is no known cure for MS, but Mr. Weiss believes that real progress has been made in developing new treatment options for MS sufferers, and that TG may be offering its own new therapy for MS. WuXi AppTec Communications as part of its special series on MS spoke to Mr. Weiss about the advanced therapeutic approaches TG is developing to treat this debilitating disease.

Mr. Weiss founded and has served as the Company’s Executive Chairman, President and CEO since December 2011. Prior to TG, Mr. Weiss founded and was the CEO of ACCESS Oncology (1999) which merged with Keryx Biopharmaceuticals (2004) for which he served as Chairman and CEO until mid-2009. Previously, Mr. Weiss spent several years as a lawyer and then investor in biotech venture capital. Mr. Weiss continues to have a passion for helping early stage biotech companies and serves as Vice Chairman of Fortress Biotech and Chairman of Checkpoint Therapeutics and Mustang Bio. 

WuXi AppTec: Many biotech companies are involved in cancer research; how did you chose to target MS as well?

Michael Weiss: At TG our number one goal and priority is to create the best possible treatment solutions for patients with B-cell diseases. While we began with a focus on oncology, we’ve known that many autoimmune diseases also result from aberrant B-cell activity, so from very early on we had a vision to also bring our drug candidates into autoimmune disease. When we saw the early data evaluating CD20s in MS we knew this was a great place to start helping patients.

WuXi AppTec: What makes MS so difficult to develop effective therapies for?

Michael Weiss: One of the biggest challenges in treating MS is that the cause remains unknown. It’s still unclear exactly why this autoimmune CNS disease develops in some people and not in others Most available data points to some combination of genetic and environmental factors sharing the responsibility. In addition, signs and symptoms of MS patients vary widely. That said, while this lack of critical information has so far made targeting the root cause of MS extremely difficult, we believe CD20 treatment is extremely beneficial to patients and is a significant step forward for the treatment landscape.

WuXi AppTec: Have you encountered any patient recruitment challenges in your MS program that were different from your experience with other trials you’ve conducted in the past?

Michael Weiss: The ULTIMATE trials enrolled incredibly well with a total of approximately 1100 patients across both trials and target enrollment achieved approximately 9 months ahead of schedule.

WuXi AppTec: How much progress has been made in MS drug research and development over the last 20 years?

Michael Weiss: Progress has been significant to say the least. Think about it: 30 years ago, there were no approved MS drugs in the United States at all. Ten years ago, there were still no oral treatments available. The use of anti-CD20 monoclonal antibodies in treating MS was only first approved in 2017. We’re witnessing several MS treatments in development, and while a true cure remains elusive, I have hope this research will serve to further advance novel therapies and provide new treatment options for the millions of MS patients worldwide.

WuXi AppTec: We have been talking about MS research in general. I would like to switch to your specific drug program. What phase is it in? What is its MOA? And what results have you seen so far? And will it treat all stages of the disease?

Michael Weiss: Our ULTIMATE I and ULTIMATE II Phase 3 trials in relapsing forms of multiple sclerosis (RMS) are two independent, global, randomized, multi-center, double-blinded, double-dummy, active controlled trials comparing ublituximab to oral teriflunomide. The primary endpoint for each study is annualized relapse rate following 96 weeks of treatment and the trials are designed to support submission for full approval of ublituximab in relapsing forms of MS.

As I had touched on earlier, ublituximab is a novel glycoengineered monoclonal antibody that targets a specific and unique epitope on the CD20 antigen found on mature B-lymphocytes. Its mechanism of action is similar to the approved anti-CD20 monoclonal antibodies, but the innovation of ublituximab is that it has been bioengineered to remove certain naturally occurring sugar molecules from the anti-CD20 antibody in a process called glycoengineering. By removing the sugar molecules we enhance the potency of ublituximab, with data showing 50-100x greater activity than non-bioengineered anti-CD20 antibodies.

The ULTIMATE I & II trials are fully enrolled and being conducted under Special Protocol Assessment with the FDA. We are targeting top line data from these trials in the second half of this year.

WuXi AppTec: Why do you think your approach can be more successful than other companies’ drug programs in this disease? How will it fit in the MS market space?

Michael Weiss: Right now, we expect that ublituximab will be the third CD20 to market, following ocrelizumab, which is currently selling, and ofatumumab, which is expected to enter the market in the next six months or so. To my knowledge, there are no other CD20s in development or late-stage development for MS.

We believe ublituximab may offer several advantages over the other CD20’s for MS, including the convenience of being a one-hour infusion every six months, versus the current 3-4 hour standard of care with ocrelizumab, at what we expect to be a competitive price designed to optimize patient access.

WuXi AppTec: Sounds very promising! Finally, when do you think your drug may be available to patients?

Michael Weiss: Assuming all goes well, we plan to possibly prepare a regulatory filing next year. If that is the case, we may be looking at FDA approval in late 2021/2022.