Delivering on the Promise of New Therapies for Rare Diseases: An Interview with Lili Mao, Director of Clinical Development Unit and Head of Project Management Office at GEXVal

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Rare diseases represent a significant unmet medical need, impacting the lives of millions of patients and their caregivers worldwide. At WuXi AppTec, we believe that our ongoing collaborative efforts to raise disease awareness and foster innovative thinking will accelerate development of breakthrough treatments to address the healthcare challenges of rare diseases. As we continue on this exciting journey to bring transformational medicines to patients, we are thrilled to share with you a new interview series from worldwide leading experts, “Delivering on the Promise of New Therapies for Rare Diseases”.

Thanks for taking the time to join us today, Lili! Before we start, could you please introduce yourself to our audience?

Lili: My name is Lili Mao, Director of Clinical Development Unit and Head of Project Management Office at GEXVal. I’m a biochemist by training. After finishing research in academia as a postdoc fellow, I started my career in the pharma industry in drug discovery at Takeda, where this was the first time I realized the beauty of drug repurposing. GEXVal was founded in 2018 as a spin-out company from Takeda, focusing on rare diseases. We hope to deliver cost-effective and innovative treatment options to help improve the health and quality of life for patients and their families who are affected by rare diseases.

What inspired you to work on Fragile X, and what issues are you trying to address?

Lili: Access to medicine is extremely important in the area of rare diseases. We believe that all patients who are living with Fragile X syndrome should have accessibility to all the innovative drugs, but the current R&D approaches in the industry sometimes may not be a very good fit for drug discovery for Fragile X. As you hear from major media that research and development costs per approval has grown significantly in the past two decades. The current emerging therapies as treatment options, such as gene therapy or cell therapy, may further increase the R&D cost.

In the current fast-moving pharma industry, there are so many shelved assets. Probably they are discontinued or put on hold for development, just due to changes in corporate strategy. So these shelved assets or shelved drug candidates are usually of high quality, and are brushed up, ready for clinical development. What we are trying to do here is to address this issue by repurposing the shelved assets, and reinvent alternative use of these assets to seek every opportunity, deliver an innovative and affordable drug for Fragile X syndrome patient.

What unique approaches are you taking in the context of drug repurposing for Fragile X?

Lili: When we think about to develop a drug for Fragile X syndrome, we believe that it is very important to deliver user-friendly medicine when we consider the daily life of patients and the caregivers. Our approach, or our drug candidate, is an orally-available small molecule. The mechanism of action has been proven to be clinically very safe. And actually the compound we are working on is a new chemical entity which was previously developed for non-rare neuropsychiatric disease, and IND-approved in the US for safety tolerability study. Now through our internal repurposing activity, we redirect the compound to Fragile X syndrome.

What is the greatest and differentiated value of your modality or technical approach to the treatment of Fragile X patients?

Lili: So when we study the publications or the current treatment regimen for Fragile X patients, we noticed that existing treatment options or drug candidates are very target limited. So we discovered that our candidate, GXV-001, preclinically has triple actions on the axis of hormone, neurotransmitter and the neurotrophic factors. And in fact, we also found this compound quite efficacious in addressing anxiety, autistic behavior symptoms, and social stress in non-rodent and rodent animal models. So with this data, we want to aim to develop a drug that has impact on a broad spectrum of symptoms in Fragile X syndrome, thereby to provide the patients with better treatment options, and hope to avoid polypharmacy.

Could you share with us your progress with this candidate so far? What is the next milestone?

Lili: Yeah, so we are very happy to announce that in June 2022 we received the approval for a phase I trial in Australia and we have started the enrollment of healthy volunteers for the study. We hope to have the first dose in human in July, or the third quarter this year. The next milestone will be, of course, safety, the first priority. So we want to first demonstrate the safety, tolerability in human, and also to prove that this compound has a favorable PK profile in human. We also want to obtain biomarker data, which will help us define the starting dose in phase II study, at which pharmacological effect can be affected in the patient population.

In your view, how can we better address the complexity of Fragile X disease biology using biomarkers?

Lili: So from my personal opinion and during my experience in drug discovery for Fragile X syndrome, I feel biomarkers studies are of high value. Ideally, I hope that there will be a biomarker that has a very good translatability from animal studies to clinical trials. So this biomarker, it can be a soluble biomarker, or a passive biomarker, and can be measured by wearable or portable devices. And with the biomarker studies, we hope to further expedite clinical trials in the future with such validated biomarker that may help to monitor advancing Fragile X syndrome disease biology.

What do you hope the field will do differently in order to advance better medicines faster for Fragile X patients? What do you hope to see in Fragile X R&D in maybe the next 10 years?

Lili: Yeah, so clinical feasibilities sometimes can be a challenge, such as access to the right patient population, and how to measure the endpoints or the outcomes, especially we have some interaction with our local clinicians in Japan. So to address such a challenge in terms of feasibility, we hope that our effort as a biotech or venture startup, together with the Fragile X community, can get this issue resolved by, for example, engaging in global study or employment of wearable electronic device, or having more validated or regulatory-approved evaluation tools to optimize the clinical trials. So eventually, I think we have the same goal; we want to deliver a better drug faster in the next 10 years, so I hope to see the first drug approval for Fragile X syndrome. And with this approval, I believe it’ll further raise awareness of the Fragile X syndrome. And then I think more Fragile X syndrome patients will get diagnosed and get treated at the earliest time point.

Are there any innovative collaborations or partnerships models that the Fragile X community can follow in order to advance the field faster?

Lili: That’s a very good question. So collaboration and partnerships are always appreciated, particularly that we are venture startups. As always, we require additional fundraising to move the project forward. So for this purpose, it’s very important for us to prove that we do have the right partnership with the patient advocacy groups and the clinical community to ensure we have the clear and correct path to deliver a drug. We also require a clear target product profile based on appropriate understanding of the unmet needs from the patients’ caregivers or clinicians. So it is always the best for us to have a long-term relationship with the patient advocacy group, and we hope to get support on say, clinical strategy, execution of the trials, and of course, fundraising.

Patient centricity is important in ensuring high quality healthcare for patients. So what does patient-centric drug development mean for the Fragile X field?

Lili: Yeah, so for Fragile X, patient-centric drug development means that we have to carefully understand the patients’ needs and then deliver the clinical strategy to address the needs. That is the basic principle. It also show me the shortest path to deliver an innovative and affordable drug accessible to anyone who are affected by Fragile X syndrome and are waiting for better treatment options.

Finally, let’s think beyond Fragile X, in 2021 the FDA approved 50 new drugs. If we now imagine in 2030, do you think we will collectively be able to achieve 100 or more new drug approvals at half of today’s cost? And in doing so, will there be any major gaps to bridge? Are there any upcoming breakthroughs which you are most excited about?

Lili: I am very confident that we can achieve such goal. I think the gap would be the R&D cost; however, I think this is something that can be solved. We’re very excited about the combination of strategically providing shelved assets, together with AI-assisted drug discovery. So we want to uncover the hidden value of such assets in a very unbiased manner. By doing this, we will definitely increase the R&D efficiency to finally successfully deliver a good, innovative drug to the patients. In fact, we have already been taking such approach at GEXVal for rare disease drug discovery. Now we are very excited in entering the next stage to prove that such a strategy will be one of the solutions to address the access issue to medicines in rare diseases.

Thank you for your insights, Lili!

Lili: You are welcome!



Lili Mao


Dr. Lili Mao has extensive knowledge and experience in drug discovery for rare diseases. After receiving her PhD from University of Medicine and Dentistry of New Jersey, she continued basic research in Rutgers University and University of Minnesota as a postdoctoral fellow. Dr. Mao completed her doctoral degree in biochemistry and postdoctoral training in anti-viral drug development, where she achieved publications of research articles and book chapters including a chapter in Encyclopedia of Biophysics (2013), as well as two patents issued in the U.S.

In 2015, she joined Takeda and started her career in extra value generation research unit for early drug discovery. In 2018, she started a new career as an entrepreneur and spun out from Takeda to focus on the rare disease drug discovery. At GEXVal, Dr. Mao is intensively engaged in business planning, fundraising, and served as CSO for two terms during startup phase leading the research unit to successfully complete the IND-submission. She is now Director of Clinical Development and Head of Project Management of GEXVal based in Fujisawa, Kanagawa, Japan.

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