Fluorescence Visualization in Lung Cancer: John Santini from Vergent Bioscience in Conversation with PharmaShots

Shots:

With the growing significance of minimally invasive surgery comes the need for enhanced visualization to optimize surgical outcomes for both surgeons and patients.

Vergent BioScience’s VGT-309 shows promising potential for tumor visualization during lung cancer surgeries. VGT-309 is an investigational intraoperative molecular imaging (IMI) agent that utilizes near-infrared (NIR) fluorescence imaging to improve precision.

Today at PharmaShots, we are joined by John Santini, President and CEO of Vergent BioScience, to discuss the results from the Phase II study on VGT-309.

Saurabh: Could you share how VGT-309 enhances tumor visualization vs. traditional surgical techniques? What types of tumor tissues were visualized in the study, and why is this diversity important?     

John: While traditional open surgery is the first line of treatment for many solid tumors, it can be traumatic and costly. Minimally invasive and robotic-assisted surgery methods are increasingly utilized in lung cancer resection because these procedures are associated with shorter hospital stays, smaller incisions, less blood loss, and decreased post-operative complications including chronic pleural pain. While minimally invasive surgery (MIS) methods offer important advantages, a surgeon’s sight and ability to feel the tissue are often compromised during these procedures, making it difficult for them to distinguish tumors from normal tissue and ensure all tumor tissue is removed. 

VGT-309 works primarily by binding to cathepsins, a family of proteases that are highly overexpressed in a broad range of solid tumors. The potential benefits of this approach include: 

Due to the fact that cathepsins are over-expressed in tumor vs. normal cells, VGT-309 targets the tumor microenvironment while minimizing signal in healthy tissue.

Because VGT-309 binds tightly to cathepsins, it is retained at the tumor site during surgical procedures, generating a sustained molecular signal that is visible when using a near-infrared (NIR) camera.

VGT-309 fluorescence is only visible with an NIR camera once the agent is bound and “activated” by the increased cathepsin protease activity in tumor tissue.

In Phase 2 clinical studies, VGT-309 has demonstrated the ability to light up tumors that would otherwise not be visible during MIS and robotic-assisted surgeries and has provided real-time intraoperative visual feedback to surgeons to help ensure all tumor tissue is removed during surgery.    

Vergent Bioscience is initially evaluating VGT-309 in lung cancer given the breadth of patients who could benefit from improved MIS approaches. Additionally, in our clinical experience to date, VGT-309 has visualized a range of primary and metastatic tumor types, including non-small cell lung cancer (NSCLC; adenocarcinoma and squamous cell carcinoma subtypes), large cell neuroendocrine carcinoma, colorectal, breast, prostate, carcinoid, sarcoma, and lymphoma.   

Saurabh: What were the main takeaways from the P-II study on VGT-309's effectiveness in lung cancer surgeries? How do these results pave the way for its continued development?     

John: A single-center Phase 2 efficacy study demonstrated that VGT-309 visualizes primary and metastatic tumor tissue in the lung during surgery and appeared safe and well tolerated with no infusion reactions and no drug-related adverse events. The primary efficacy endpoint for this study was the proportion of patients with at least one clinically significant event (CSE), defined as localization of lesions not found by standard surgical techniques, discovery of previously unknown synchronous and occult cancers, and identification of inadequate surgical margin. Of the 40 participants administered VGT-309 who underwent the standard-of-care surgical resection for suspected lung cancer, 17 (42.5%) had at least one clinically significant event.1 

Based on these results, Vergent is further evaluating the efficacy of VGT-309 in the Phase 2 multicenter VISUALIZE study. Investigators at six sites in the United States and Australia plan to enroll up to 100 patients. We expect to complete this trial by the end of 2024.     

Saurabh: What are the next steps in VGT-309's clinical development, and what are you hoping to see from the ongoing P-II multicenter VISUALIZE study?    

John: We expect to complete the international, multi-center Phase 2 VISUALIZE study this year, followed by a Phase 3 study. Assuming the results of the Phase 3 study are positive, we would then file an NDA for FDA approval for the use of VGT-309 during surgery for cancer in the lung.    

The VISUALIZE study is evaluating the efficacy and safety of VGT-309 in patients with cancer in the lung. Specifically, it is assessing the potential of VGT-309 to improve the visibility of difficult-to-find and previously undetected tumors during minimally invasive and robotic-assisted surgical procedures.    

Saurabh: How do you envision VGT-309 impacting the future landscape of cancer surgeries and tumor visualization technologies?      

John: VGT-309 was designed to fill the existing deficits in lung tumor and other solid tumor surgical visualization. We believe that VGT-309, if approved, could provide a meaningful benefit to surgeons and cancer patients. Data to date from our clinical studies have shown the potential to build surgeons’ confidence in MIS, allowing them to see the tissue, but also the nature or biology of the tissue, helping to minimize normal tissue loss while ensuring that all tumor tissue is removed.    

Further, these innovations also have the potential to be used alongside AI to provide surgeons with additional guidance to further optimize surgery.    

Saurabh: If the P-II and subsequent trials are successful, what do you think will be the broader implications for the global adoption of VGT-309 in clinical practice?    

John: VGT-309 has potential applications in surgery for patients diagnosed with other solid tumors, including colon, rectal, esophageal, breast, prostate, ovarian, and other cancers, which are planned to be investigated in future clinical trials. We believe VGT-309 could help surgeons achieve a complete oncologic resection and potentially build their confidence in MIS and robotic-assisted procedures.   

References: 

1. Bou-Samra, M.D., P. (2024, January 27-29). A Phase 2 Clinical Trial of VGT-309, a Quenched Activity-Based Probe for Intraoperative Molecular Imaging of Pulmonary Malignancies [Conference presentation abstract]. Sixtieth annual meeting of The Society of Thoracic Surgeons, San Antonio, TX, United States. https://www.sts.org/calendar-of-events/60th-sts-annual-meeting  

Image Source: Canva

About the Author:

John Santini

Dr. Santini is a life science executive, serial entrepreneur, inventor, and scientist who has focused on the creation and growth of businesses developing next-generation pharmaceuticals, drug delivery systems, biosensors, and surgical oncology products for more than 20 years. He currently serves as the President and CEO of Vergent Bioscience.

During his career, Dr. Santini has negotiated and executed collaborations and license agreements with major pharmaceutical and medical device companies and has raised over $100M in venture capital and corporate funding for his companies. Dr. Santini was the first industry scientist to be honored as one of Popular Science Magazine’s “Brilliant Ten,” and he was named one of the Top 100 “Young Innovators” in the world by Technology Review Magazine. He has published work in top scientific journals such as Nature, Nature Biotechnology, and Science Translational Medicine, has over 80 issued US and international patents, and his work has garnered a Technology Pioneer award from the World Economic Forum (Davos, Switzerland) and a Gold Medal from the Edison Awards in the Science and Medical, Game Changers category. Dr. Santini earned a PhD in chemical engineering from MIT in the laboratories of Professors Robert Langer and Michael Cima as a National Science Foundation Fellow, and a bachelor’s degree in chemical engineering from the University of Michigan.