Shots
- PharmaShots welcomes Willis Lee, MS, CEO and Chairman of the Board at Emmaus Medical, for an in-depth perspective on the company’s exploration of pharmaceutical-grade L-glutamine in pancreatic ductal adenocarcinoma (PDAC). Lee discusses the encouraging Phase 1 findings from L-glutamine combined with gemcitabine and nab-paclitaxel, including a 44% objective response rate, tumor shrinkage in 94% of patients, and a median overall survival of 22 months, while highlighting the importance of confirming these early signals in larger, controlled studies.
- From chemotherapy sensitization to the gut microbiome, metabolism, and inflammation, Lee explores what may be driving the clinical signals observed with L-glutamine in PDAC. He also outlines how Emmaus is working with Cedars-Sinai to translate these findings into the next stage of development, with key milestones including Orphan Drug Designation, an adaptive Phase 2/3 study design, FDA engagement, IND submission, and clinical-site selection.
- As Emmaus looks beyond its established commercial business, Lee shares how the PDAC program could open a new chapter for L-glutamine and the company’s broader pipeline. He discusses the strategic value of the Cedars-Sinai collaboration, the clinical and regulatory evidence needed to advance the program, and how Emmaus plans to balance investment in pancreatic cancer development with its existing priorities and long-term growth vision.
Saurabh: The GlutaPanc Phase 1 study reported encouraging results with L-glutamine in combination with gemcitabine and nab-paclitaxel. What are the most important takeaways from the study for the pancreatic cancer community and for Emmaus?
Willis: These promising findings in patients with advanced PDAC suggest significantly improved survivability without introducing untoward adverse events. This combination can be further tested in a larger study and with other chemotherapy or targeted therapy combinations.
For Emmaus, Pharmaceutical Grade L-glutamine, with its broad activity in hematology and immunology, is our cornerstone for further development. With our patient-focused oncology vision, a new therapeutic-use patent (oral, intravenous, or both) will create a new development opportunity for our short- and long-term course.
Saurabh: The study reported a 44% objective response rate, 94% of patients experiencing tumor shrinkage, and a median overall survival of 22 months. How should these findings be interpreted in the context of the study’s small, single-arm Phase 1 design and the need for confirmation in a randomized setting?
Willis: This was a small Phase 1, dose-finding, safety and tolerability study in advanced PDAC conducted at a single center in a non-randomized, historical-control fashion. Given that the historical literature was contrary to L-glutamine therapy in cancer (i.e., one should starve cancer cells of glutamine), observing preliminary efficacy signals from providing supraphysiological amounts of L-glutamine was unexpected in both animals and human patients. As part of prudent drug development, the next step is to see if these would be replicated in a larger, well-designed, controlled study.
Saurabh: The study also generated exploratory findings around the gut microbiome, metabolism, inflammation, and gut barrier function. What insights do these findings provide into the potential role of L-glutamine in treating advanced pancreatic ductal adenocarcinoma?
Willis: The mechanism of action of L-glutamine in sustaining (or sensitizing) the activity of gemcitabine (and possibly Nab-paclitaxel) in advanced PDAC is not fully understood. However, a preclinical (animal) study has provided plausible findings. Nevertheless, the Phase 1 clinical outcome (nearly doubling the objective response rate and tripling the overall survival rate) is notable. Similarly, it remains unclear how L-glutamine’s effects on the gut, barrier function, metabolism, and inflammation contributed to these clinical findings. For many years, the literature has reported L-glutamine’s ubiquitous influences on microbial composition, bacterial regulation, crosstalk between microbial activity and host immunity, gut barrier function, cellular fuel, tight junction support, permeability reduction, pro-inflammatory suppression, immune modulation, metabolism and energy pools, and antioxidant synthesis.
Exploratory biomarker findings in this study (metabolism, microbiome, and inflammation) may serve as measures of L-glutamine activity beyond its findings of “chemo-sensitizing” clinical benefits, and these multiple functions may support overall health and promote anti-cachexia effects in PDAC patients.
Saurabh: Emmaus recently entered into an exclusive option agreement with Cedars-Sinai to continue evaluating L-glutamine in combination with chemotherapy for PDAC. What are the key objectives and development milestones for the program as it moves forward?
Willis: Emmaus’ next key objectives and milestones for management, clinical development, and regulatory include:
- Application for an Orphan Drug Designation
- Completing the Phase 2/3 adaptive study design
- Preparing a briefing package for the US FDA
- Submitting a request for a Pre-IND FDA meeting
- Submitting an IND
- Selecting the study CRO
- Site selections
Saurabh: What has the collaboration with Cedars-Sinai contributed to the development of the pancreatic cancer program, and how does the partnership complement Emmaus’ existing expertise in L-glutamine-based therapies?
Willis: The pre-clinical scientists, oncologists, and business development colleagues at Cedars-Sinai have performed their due diligence in developing, conducting, and publishing the Phase 1 study. With Cedars-Sinai’s expertise, combined with Emmaus’ drug development and regulatory experience, we are poised to design and manage a successful development program.
Saurabh: From a pipeline perspective, what role could the pancreatic cancer program play in Emmaus’ efforts to diversify its business and establish additional growth opportunities beyond sickle cell disease?
Willis: Emmaus will continue to pursue new development opportunities for L-glutamine in previously unexplored therapeutic areas, particularly in PDAC, to short-circuit cancer cell survivability and to drive short- and long-term growth in such diversified areas.
Saurabh: What clinical and regulatory evidence will be important in determining the future development path for L-glutamine in combination with chemotherapy for advanced PDAC?
Willis: For both clinical and regulatory, the Phase 1 results will need to be demonstrated in a Phase 2 proof-of-concept study. This study will need to begin as soon as possible before daraxonsarib is indicated for first-line treatment. Regulatory will work with clinical development to submit ODD and meeting requests, prepare briefing packages, prepare the IND for Phase 2/3 study, and conduct the study. The End of Phase 2 Meeting following the interim analysis will aid in determining next steps.
Saurabh: How does Emmaus envision balancing investment in the pancreatic cancer program with the company’s existing commercial business and other pipeline initiatives as the portfolio evolves?
Willis: The company would need to raise funds to support the pancreatic cancer program. The company’s existing commercial business is the highest priority. The pipeline initiatives including the pancreatic cancer program are secondary but are important for the company’s long-term vision and value.
About Willis Lee
Willis Lee, MS
Chief Executive Officer and Chairman of the Board
Willis Lee, MS, serves as Chief Executive Officer and Chairman of the Board, bringing more than two decades of leadership experience across operations, finance, business development, and strategic management. He was appointed Chief Executive Officer in July 2024 and Chairman of the Board in October 2023.
Mr. Lee has held several leadership roles within the organization, including Chief Operating Officer since 2011, director since 2015, Vice-Chairman of the Board, and Chief Financial Officer from 2016 to 2018. Previously, he served as Co-Chief Operating Officer and Chief Financial Officer and as a director of Emmaus Medical.
Earlier in his career, Mr. Lee led worldwide sales and business development for the Yield Dynamics product group at MKS Instruments, where he focused on commercial growth and strategic market development. He has also held managerial and senior leadership positions across the actuarial, semiconductor, and defense industries.
Mr. Lee holds a B.S. in Physics from the University of Hawaii and an M.S. in Physics from the University of South Carolina.
