Optimized 203Pb/212Pb image-guided alpha-particle radionuclide therapy for SST2R expressing tumors
Preclinical data of VMT-𝛼-NET demonstrated to significantly improve cell binding, tumor accumulation/retention and renal clearance of an SSTN analog
VMT-𝛼-NET currently in a Phase 1 imaging study to be followed by Phase 1/2a therapy study for the treatment of neuroendocrine tumors (NETs) being conducted at the University of Iowa
CORALVILLE, IA / ACCESSWIRE / December 21, 2021 / Viewpoint Molecular Targeting, Inc. ("Viewpoint" or the "Company"), a radiopharmaceutical company developing precision lead-212-based α-particle oncology therapeutics and complementary diagnostic imaging agents, today announced the presentation of preclinical data from its theranostic in development, VMT-𝛼-NET, at the 2021 International Chemical Congress of Pacific Basin Societies (Pacifichem 2021 Congress), taking place virtually, December 16-21, 2021.
The abstract titled, "Chemical structure modifications to chelator and linker compositions for improved pharmacokinetics of 203/212Pb peptide-based radiopharmaceuticals," was presented
In the Advancements in the Chemistry of Targeted Alpha Therapy (#180) symposium session by Michael K. Schultz, PhD, Chief Science Officer of Viewpoint.
"Emerging evidence suggests that alpha-particle therapy has the potential to significantly improve tumor response. The preclinical data from VMT-𝛼-NET demonstrated to-date provides strong evidence that our VMT-𝛼-NET image-guided approach can meet the need for an effective therapy with a promising toxicity profile. We are pleased with the progress of VMT-𝛼-NET and are committed to advancing the development of this important theranostic forward," commented Dr. Schultz.
The preclinical study was designed to explore chemical modifications to the chelator and chelator-peptide linker of SSTN analogs to optimize for 203Pb/212Pb image-guided alpha-particle radionuclide therapy for SST2R expressing tumors. PEG linkers of varying length were explored to improve tumor cell binding/internalization, in vivo tumor targeting, and renal clearance. In vitro and in vivo performance properties (e.g., radiolabeling, renal clearance) were compared to DOTATOC (203Pb/212Pb).
VMT-a-NET was identified with significantly improved performance. [203Pb]VMT-alpha-NET significantly improved: (1) SST2R IC50 binding affinity (>2-fold); (2) cellular uptake and internalization (a factor of 20); (3) tumor accumulation/retention; and (4) renal clearance compared to [203Pb]DOTATOC. With these improvements, the tumor:kidney ratio (%ID/ gram) improved more than 8-fold (24 h post injection) in AR42J tumor bearing mice compared to [203Pb]DOTATOC. [212Pb]VMT-alpha-NET therapy was effective and well-tolerated in mice (renal injury biomarkers NGAL' CREA), achieving a 70% complete response rate in tumor bearing mice.
Based on the preclinical data seen to-date, Viewpoint believes that VMT-𝛼-NET is well-positioned to apply the new transformative power of alpha-particle treatment to NET tumors and other cancers that express the SST2R biomarker.
The Company recently commenced an investigator-initiated Phase 1 imaging study of VMT-𝛼-NET for imaging somatostatin receptor subtype 2 (SSTR2)-positive neuroendocrine tumors, being conducted at the University of Iowa Hospitals and Clinics. The images obtained from the Phase 1 imaging study will inform future therapeutic trials of [212Pb]VMT-𝛼-NET alpha-particle therapy for this tumor type. In parallel to this investigator-initiated imaging trial, the Company plans to move forward with a Phase 1/2a therapy study of VMT-𝛼-NET for the treatment of neuroendocrine tumors.
About the Pacifichem 2021 Congress
The 2021 International Chemical Congress of Pacific Basin Societies will take place virtually, December 16-21, 2021. Pacifichem 2021 will be the eighth in the series of successful cosponsored scientific conferences of Pacific Basin Chemical Societies. Founded in 1984, these conferences have been held in Honolulu, Hawaii about every five years.
About Neuroendocrine Tumors
Neuroendocrine tumors are rare forms of cancers that occur most commonly in the pancreas or other areas of the gut such as the stomach, small intestine, rectum, colon, or appendix. A neuroendocrine tumor may grow slowly or aggressively and spread to other parts of the body. Diagnosis and treatment of neuroendocrine tumors depend on the type of tumor, its location, whether it produces excess hormones, how aggressive it is and whether it has spread to other parts of the body. Some approaches may include surgery, radiation, and chemotherapy.
Viewpoint Molecular Targeting is a radiopharmaceutical company developing precision oncology therapeutics and complementary diagnostic imaging agents. The Company's proprietary technology utilizes lead-212 to deliver powerful alpha radiation specifically to cancer cells via specialized targeting peptides. Viewpoint is also developing complementary imaging diagnostics that incorporate the same targeting peptides which provide the opportunity to personalize treatment and optimize patient outcomes. This "theranostic" approach allows the specific tumor to be recognized and precisely treated; this approach has the potential to improve efficacy and potentially minimize the toxicity associated with other types of cancer treatments.
The Company's Melanoma (VMT01) and Neuroendocrine Tumor (VMT-𝛼-NET) Programs are entering Phase 1 imaging studies, to be followed by Phase 1/2a therapy trials for the treatment of metastatic melanoma and neuroendocrine tumors at two leading academic institutions. The Company has also developed a proprietary lead-212 generator to secure isotope supply for clinical trial and commercial operations.
For more information, please visit the Company's website viewpointmt.com.
Chief Executive Officer
JTC Team, LLC
SOURCE: Viewpoint Molecular Targeting, Inc.