Our “Meet the Researcher” series on The LLS Blog shares what our outstanding LLS-funded researchers are working on, the incredible impact they’re making in the fight against blood cancers, and what inspires their efforts to find better treatments and cures.
In honor of Asian American and Pacific Islander Heritage Month in May, LLS is highlighting the stories of volunteers, healthcare professionals, researchers, patients, survivors, and advocates from across our community. Recently, we caught up with Charlene Liao, Ph.D., Co-Founder, President, and Chief Executive Officer of Immune-Onc Therapeutics, a new LLS Therapy Acceleration Program® (LLS TAP) partner. Dr. Liao also previously received an LLS Career Development Program (CDP) grant, supporting her postdoctoral research in immunology at the University of California, San Francisco in Dr. Art Weiss's laboratory.
A trailblazer in biotech, Dr. Liao has 25 years of experience in drug development and business leadership. Before co-founding Immune-Onc Therapeutics in 2016, she held global drug development roles at Genentech, where she led development efforts across the product lifestyle for ten new molecular entities across immunology, infectious diseases, metabolic disorders, neuroscience, and oncology. Prior to this, she was a Director of Business Development at Rigel Pharmaceuticals and began her career as a scientist at Tularik. Dr. Liao received her Ph.D. from Brandeis University in the laboratory of Nobel Prize winner Dr. Michael Rosbash.
LLS continues to support her visionary work. In April, LLS TAP announced new investments, including funding to support Immune-Onc Therapeutics’ IO-202, a first-in-class antibody targeting myeloid checkpoint LILRB4 (also known as ILT3). The treatment is in a phase 1 clinical trial for advanced acute myeloid leukemia (AML) and chronic myelomonocytic leukemia (CMML), with potential in other blood cancers and solid tumors. LLS TAP is our strategic venture philanthropy funding initiative to accelerate high-risk, innovative blood cancer therapies and change the standard of care in leukemia, lymphoma, and multiple myeloma.
We invited Dr. Liao to share how her company’s work will help blood cancer patients and their families, what excites her about the future of cancer immunotherapy, and her inspiring career journey.
1. Why were you drawn to a career in biotech, and what drove you to co-found Immune-Onc Therapeutics?
I first came to the United States in the late 80s via a highly prestigious and competitive academic initiative similar to a Rhodes Scholarship program not long after China opened to the world. From academia, I moved on to industry, first at Tularik and then at Genentech, where I found a focus for my passion: to create new medicines that would make a real difference in the lives of patients. If forming a company as a CEO was the path to get there, that was a byproduct of this passion versus the end goal. When I founded Immune-Onc five years ago from the ground, I intentionally focused on pursuing truly novel science that would advance current treatment standards for hard-to-treat cancers. ‘Science at Our Core, Patients in Our Hearts,’ captures what Immune-Onc is founded on, and we work hard to achieve this through our work each day.
2. You received a Career Development Program (CDP) grant from LLS early in your career. Today, Immune-Onc Therapeutics is an LLS TAP partner. What’s been the impact of LLS research funding on your career and company?
I’m incredibly grateful for the support that LLS has provided me from my early days as a scientist in the laboratory of Dr. Art Weiss at UCSF and now, through their support of our clinical development programs at Immune-Onc Therapeutics. In my post-doctorate days, funding from LLS provided the means for me to pursue immunology research that forms the foundation of cancer immunotherapy. Today, the partnership with LLS TAP has been an invaluable resource to our team at Immune-Onc as we develop novel treatments for blood cancers.
3. At Immune-Onc Therapeutics, your team is driving forward the next frontier of immunotherapy, focusing on myeloid checkpoint inhibitors. Describe this exciting work for us and how blood cancer patients will benefit.
Cancer immunotherapy has been embraced as a new approach to treat cancer. While many patients have benefited from cancer immunotherapy, many more have not, particularly in hard-to-treat cancers like AML and CMML. As scientists, we recognize that cancer immunotherapy may not be working in these cancers due to the tumor microenvironment, and we sought to understand and address this.
AML has a unique tumor micro-environment where the immune system is heavily suppressed, and T cells (effector cells) aren’t as active in people with AML. But no one has understood why. For subsets of AML (monocytic and myelomonocytic AML), the data today strongly suggest that LILRB4 is the main regulator of immune suppression. By blocking LILRB4, we can overcome that immune-suppressive microenvironment and activate T cell killing. We think this is a very compelling target because of the LILRB4 expression and because these patients are largely resistant to standard therapies. Patients with monocytic and myelomonocytic AML represent about 30% of AML patients. They typically have worse survival and are more resistant to standards of care. They also tend to have leukemia that infiltrates other parts of the body, like the brain and the liver. CMML is another blood cancer that needs more effective therapies. Progression from CMML to AML occurs in 15 to 30% of cases, and median survival is dismal.
In collaboration with researchers at The University of Texas, our research team is among the first in the world to target these immune-suppressive pathways with novel myeloid checkpoint inhibitors, including our lead investigational treatment IO-202. This treatment has the potential to transform current treatment approaches for blood cancers. IO-202 is a first-in-class monoclonal antibody being evaluated in a Phase I trial in two forms of blood cancers, AML and CMML. The U.S. Food and Drug Administration granted IO-202 Orphan Drug Designation status for the treatment of AML in October 2020. In blood cancers, preclinical studies showed that IO-202 converts a “don’t kill me” to a “kill me” signal by activating T cell killing and converts a “don’t find me” to a “find me” signal by inhibiting infiltration of blood cancer cells.
4. Why do you believe collaboration is so critical to advancing new cancer treatments? And, tell us more specifically about Immune-Onc Therapeutics’ interaction with LLS TAP and the benefits that come with the collaboration.
Collaborations with leading institutions in cancer immunotherapy are an important component of our strategy as we translate leading-edge research from bench to bedside.
Through our partnership with LLS, we have access to their deep knowledge and expertise in blood cancers and their extensive physician and patient network. By working together, we can accelerate development of our lead product IO-202, a myeloid checkpoint inhibitor for AML and CMML, and help patients who need new treatment options.
5. You’ve been a passionate champion of our mission and are involved in fundraising for LLS. Who or what inspires you in the fight against blood cancers?
I’m motivated by the opportunity to make an impact and am inspired by blood cancer patients around me. Today, most blood cancer patients live beyond five years after diagnosis, and some are cured, thanks to new medicines available and a treatment paradigm shift over the last 20 years. On the other hand, AML and CMML are devastating diseases, and there still are very few options for these patients. For example, only one in four AML patients survives five years beyond diagnosis. And at the time of diagnosis, many are either too weak to tolerate intensive chemotherapy or are resistant to current treatments, including venetoclax. These patients report a lower quality of life compared to other cancer patients. It’s our goal to improve the prognosis and provide new treatment options for these patients. We are hopeful that we can help these patients with our investigational immunotherapy, IO-202.
6. When you’re not working to chart a new course in cancer immunotherapy, what do you enjoy doing in your spare time?
As CEO of a biotech start-up on a fast growth trajectory, I don’t have a lot of spare time. When I do, I enjoy spending time with my family and being in nature. For example, we recently visited Yosemite National Park. I’m also passionate about supporting organizations that serve people with disabilities and am active in fundraising and helping these communities thrive. In addition, I mentor up-and-coming scientists through various organizations I’m involved with. I so appreciate the mentors throughout my career and believe it’s important to nurture and support the dreams of the next generation of leaders, just as so many have done for me.
Learn more about LLS TAP here.