Delivering on the Promise of New Modalities: An Interview with George Wu, Co-Founder & CEO, Amberstone Biosciences

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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.

For our next interview as part of our featured series highlighting innovation in our ecosystem, we sat down with George Wu, Co-Founder & CEO of Amberstone Biosciences, an emerging biotech company with expertise in developing a new generation of ‘conditionally active’ cancer therapies. Earlier this year, Amberstone Biosciences secured $12 million in Series A Financing to advance the immuno-oncology pipeline of tumor microenvironment activated therapeutics. The company also recently announced the formation of a scientific advisory board comprised of industry leaders in the top fields of drug delivery, oncology, immunology, and pharmaceutical sciences.

Greetings George. Amberstone focuses on developing novel immuno-oncology therapeutics. In your opinion, what are the top challenges in current therapeutic intervention for cancer??

George: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, showing great clinical and commercial successes. But the majority of cancer patients don’t respond well to this class of treatments. There are still significant unmet medical needs for cancer patients. In search of novel cancer immune therapies, the field has encountered a major hurdle. Many potentially transformative new immunotherapeutics exhibit a very narrow therapeutic window, making them intractable for further development. Reducing the dose-limiting toxicities while maintaining efficacy of those promising agents is one of the biggest industrial-wide challenges. Inadequate tumor selectivity, poor adaptability to the heterogeneous patient immune systems, and suboptimal preclinical translational efficiency are some of key underlying gaps that the field endeavors to address in order to increase the chance of success.

Another major challenge is the alarmingly high cost that has been limiting the upside potential of some innovative treatments such as cell-based therapeutics. It also limits patient access to those novel and effective treatments.

What is your unique technological approach helping to address these challenges? How is it different from existing approaches?

George: Amberstone Biosciences has a singular focus on developing tumor microenvironment activated immunotherapeutics (T-MATEs). Our molecules are selectively activated in acidic tumor microenvironment but not in physiological normal tissues, thus offering a favorable expanded therapeutic window. Our rationale is based on the well-known tumor acidity, in part due to glycolytic metabolism, a near-universal cancer hallmark that has been established for about 100 years with the solid support of over 10,000 scientific research articles. Our two lead programs are T cell engagers that are uniquely designed to address large and diverse solid tumor patient populations. For the current stage, we only adopt clinically established modalities (e.g. antibodies and cytokines) that provide a clear path of development. We expect that our approach can be integrated with a variety of modalities to target many promising regulatory pathways around the tumor immunity cycle.

We are excited with the potential of our approach and are firmly committed to our mission of delivering a next generation of safe and effective treatments to benefit those with devastating cancer.

What are critical challenges in realizing the full potential of your new technologies? Could you share with us your solutions and your upcoming milestone?

George: While the overall path of development is fairly clear for our T-MATE programs, there is a shortage of highly-relevant preclinical models that can allow us to efficiently characterize our molecules’ efficacy, safety, and pharmacokinetics, thereby translating effectively to clinical benefits. We are working with several academic and industrial partners to address these challenges. For the time being, we are taking rigorous and somewhat redundant approaches to improve the chance of successful translation. Despite these challenges, we are optimistic with our next milestone goals in IND-enabling studies starting later this year.

With many new modalities advancing into the clinic and getting closer to patients, do you think the 2030 class of FDA new approvals may look similar or different from those today?

George: I think there will be increasingly more new modalities being approved — multispecific antibodies, off-the-shelf cell therapies, cancer vaccines, TLR agonists, and innovative personalized medicines, just to name a few. I also expect to see the approval of many nuanced combination strategies that can innovatively leverage existing treatments and therapeutics of various modalities. One example is to combine two or three immune-modulating molecules to achieve a balanced yet durable tumor-selective immunity to annihilate all cancer cells in a safe and effective manner; another example is to combine a “right” regimen of chemotherapy with a “right” kind of immunotherapy in a synergistic manner to improve the clinical outcome.

Do you think we as industry will be able to achieve 100+ new drug approvals at 50% of today’s cost by 2030? And in achieving so, do you foresee any major gaps to bridge? Or any upcoming breakthroughs that you are most excited about?

George: I expect there will be significant improvement of productivity for at least some modalities, particularly cell therapy. I am generally optimistic about technological innovations which are arising regularly. On the other hand, the production cost reduction may or may not adequately translate to favorable pricing on the healthcare systems or the improved affordability to patients. This is intricately related to individual countries’ respective situations.

Do you see novel data technologies, AI, or machine learning being used in the next couple of years?

George: Absolutely. I am a big fan of information/data technologies which have started and will only accelerate to create direct impact. Take a look at the quick evolution of the AlphaFold, as an example. There is no doubt that these enabling data technologies and tools will shape how we discover and develop new medicines in the future. This is not to say these new technologies will overtake or fully replace the established practices. We will have a clearer picture once we start to see more clinical stage assets that are significantly enabled or expedited by these technologies.


George Wu

Co-Founder & CEO, Amberstone Biosciences

George Wu is a life sciences technology innovator with great passion in developing innovative cross-field technologies to address unmet market needs. He has published over 40 manuscripts and abstracts in cancer biology, immunology, high-throughput drug discovery, single cell technologies, medicinal chemistry, and molecular diagnostics. With numerous patents relevant to anti-tumor molecules or single cell technologies, Wu is a recognized inventor committed to making a difference for the healthcare of patients. Before founding Amberstone, he was President/COO of GeneTex International, where he was closely involved in antibody and research product development, business scaling, and cross-border merger and acquisition. He received a BS in biology from the University of Science & Technology of China, and a PhD in molecular medicine from the University of Texas Health Science Center, San Antonio. As a Susan Komen Research Fellow at the University of California, Irvine, his primary focus was small molecule anti-tumor drug discovery and translational research.

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