Dear readers,
I’m pleased to introduce the Angiex Founder’s Blog.
Angiex is pioneering an exciting new approach to cancer therapy: antibody-drug conjugates (ADCs) directed to TM4SF1.
TM4SF1 is an understudied protein and an underexplored oncology target. With only 166 papers in Pubmed as of November 25, 2024, TM4SF1 has received little interest from academic investigators. The lack of interest is surprising, considering that TM4SF1 was discovered in the 1980s as the tumor-associated antigen of the antibody L6, and L6 radioimmunoconjugates were studied in clinical trials from 1990 to 1997 and were the best performing radioimmunotherapies of the 1990s. Yet, when the industry gave up on radioactivity in 1997, TM4SF1 was abandoned as an oncology target, and never caught on as a subject for academic research
TM4SF1 is thus the exemplar of a drug target that has been overlooked by both academic researchers and the pharmaceutical industry. Angiex’s AGX101, which began its Phase 1 clinical trial in July 2024, is only the second TM4SF1-directed drug to reach the clinic, and the first ADC.
AGX101 is exciting because:
- It attacks two compartments of the tumor, giving meaningful clinical benefits through three mechanisms of action (MoAs): 1) activation of anti-tumor immunity, 2) tumor regressions through depriving the tumor of its blood supply, and 3) direct killing of invasive and metastatic tumor cells.
- These MoAs have the potential to bring transformative outcomes for cancer patients:
- Activation of anti-tumor immunity may greatly increase the number of patients responding to immune checkpoint inhibitors, enabling today’s best selling oncology drugs to benefit a much larger pool of patients.
- Tumor regressions through deprivation of the blood supply may be a robust avenue to achieving efficacy. This mechanism is thought to be universal in all growing tumors, and there is no known resistance mechanism.
- Killing of TM4SF1-positive tumor cells may eliminate invasive or metastatic tumor cells, potentially turning malignant tumors benign.
- Exceptional tumor homing fulfills Paul Ehrlich’s vision of a “magic bullet” that attacks tumors while avoiding normal tissue, enabling outstanding safety
An exciting drug deserves to have its story told. Here in the Angiex Founder’s Blog,
I look forward to telling the story of Angiex and the spunky scientists and drug developers who discovered TM4SF1’s importance and created a drug to fulfill TM4SF1’s potential
As AGX101 progresses through the clinic, this will be the first place we share news of its clinical performance. So please keep an eye out for upcoming posts!
Yours,
Paul Jaminet, Ph.D.
Founder & CEO, Angiex