Delivering on the Promise of New Modalities: An Interview With Yann Chong Tan, Founder & CEO, Nuevocor – Marketscreener.com

As part of WuXi AppTec's ongoing efforts to collaboratively foster new thinking and actionable approaches in advancing breakthroughs for patients, we have launched a new interview series in 2022 - "Delivering on the Promise of New Modalities" - so leading voices of R&D can share how their approaches are addressing the barriers standing in the way of breakthroughs.

We continue our interview series with Yann Chong Tan, Founder & CEO of Nuevocor, a preclinical-stage biotech company specializing in gene therapy for cardiomyopathies. Recently, Nuevocor closed on $24 million Series A Financing to advance their novel gene therapies. The company believes they are well-positioned to treatLMNA (lamin A/C gene) and other genetic cardiomyopathies, amongst other cardiac diseases.

Nuevocor focuses on developing gene therapy-based treatments that have the potential to restore cardiac function in diseased hearts. In your opinion, what are the top challenges in current therapeutic intervention for this disease?

Yann Chong: At Nuevocor, we focus on using gene therapy to treat genetic cardiomyopathies. Cardiomyopathy is estimated to affect more than 1 in 250 people and is a disease where the heart gradually loses its ability to pump blood efficiently. Treatment options are limited and the only cure is a heart transplant. With the advent of precision medicine over the past decades, we now know that a large fraction of cardiomyopathies has genetic causes. As each of these genetic cardiomyopathies has a different mechanistic driver, a challenge is understanding the underlying root causes to design targeted treatments.

How is your gene therapy approach helping to address these challenges? How is it different from existing approaches?

Yann Chong: The majority of genetic cardiomyopathies are inherited in an autosomal dominant manner where one copy of the mutated gene drives the disease even though the patient has a second, normal copy of the gene. This makes a gene replacement approach unworkable. There are also no mutation hotspots for gene editing to be attractive. Our approach is to identify genetic modifiers of cardiomyopathies and deliver them to patients via AAV-mediated gene therapy. To identify such genetic modifiers as therapeutic targets for genetic cardiomyopathies, we utilize our PrOSIA mechanobiology platform to understand the molecular and biomechanical basis of genetic cardiac disease.

To illustrate the power of our approach, our lead programme targets LMNA dilated cardiomyopathy. This is the second most common genetic dilated cardiomyopathy and has the worst prognosis, with 70% of patients having cardiac death, a heart transplant or a major cardiac event by the age of 45. Our treatment reduces biomechanical stress on the nucleus of LMNA mutant heart cells, thereby reducing nuclear damage in LMNA dilated cardiomyopathy. In animal models, we have extended lifespan by more than 4-fold with our approach, which is unprecedented for this rare disease.

What are critical challenges in realizing the full potential of your gene threapy? What are Nuevocor's solutions?

Yann Chong: The benefits of AAV-mediated gene therapy have been demonstrated with drug approvals and have made a significant difference in patients' lives. Recent clinical trials, however, have highlighted that there are still quite some ways to go in ensuring that the therapy is safe for patients especially at high doses. The field is coming together to solve these issues and there has been incredible progress in understanding the cause of the safety challenges and in designing solutions.

We are actively working on addressing these safety challenges by examining how we can lower the AAV dose and ensuring that our therapeutic protein is not immunogenic. We have made significant progress in the past year and we are confident that we will be able to have a solution in the coming year.

To make a prediction, what could be the next big scientific breakthrough in the life science industry?

Yann Chong: It is difficult to predict the next big invention, but what is clear is that techniques regularly used in research to perturb systems and answer biological questions, such as anti-sense oligos, or mRNA and DNA vectors for expressing and regulating genes, have formed the basis for new drugs in recent years. There is no turning back from these new nucleic acid therapeutic modalities, which promise to address the root cause of diseases so as to provide cures for patients. Enabling wider use of these technologies is in the interest of patients and their families.A challenge for these modalities is delivering the therapeutic molecule to the intended cell types, ideally with good specificity and importantly, also in a way that is safe. We expect current delivery methods to mature, and at the same time, a proliferation of different delivery methods, both viral and non-viral. It is likely that each delivery method will have its own advantage in being able to deliver well to different organs and cell types. We anticipate the next breakthrough to be the ability of the field to deliver to different cell types achieved through the coexistence of multiple viral and non-viral delivery technologies.

Thank you for your insights! Any closing remarks to our readers?

Yann Chong: We believe in moving our therapies as quickly as possible into the clinic, and collaborations between different groups with complementary capabilities can accelerate the process. Capabilities do not respect borders and ideally collaborations should be cross-border too. Nuevocor is headquartered in Singapore, a cosmopolitan global city with English as the main communication and is in many ways a bridge between Asia and the West. It should come as no surprise that we already have global collaborations with our strong ties to North America, Europe and Asia. We are always actively seeking more collaborations to move the science forward.

Yann Chong Tan, PhD, brings a decade of experience in biotech and commercialisation leadership roles to Nuevocor. He is an inventor on multiple patents and an entrepreneur who has founded multiple biotech companies. Dr. Tan was previously the Chief Innovation Officer at the Genome Institute of Singapore, where he initiated and led strategic programmes resulting in multiple healthcare and biotech spin-offs, one of which is Nuevocor. Previously, as Chief Technologist at Atreca, Inc., a company he co-founded in 2012 from his academic work, Dr. Tan led and built up Atreca's core foundational antibody discovery technology and discovered the antibody now in clinical trials. Atreca is listed on NASDAQ.

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Delivering on the Promise of New Modalities: An Interview With Yann Chong Tan, Founder & CEO, Nuevocor - Marketscreener.com