# Preclinical pharmacology, toxicology, biodistribution and dosimetry, and radionuclide production CMC validation for Pb-212 receptor targeted alpha-particle therapy for neuroendocrine tumors.

> **NIH NIH R44** · VIEWPOINT MOLECULAR TARGETING, INC. · 2021 · $998,648

## Abstract

Neuroendocrine tumors (NET) are enigmatic malignancies, with an increasing incidence and poor outcomes (5-yr
survival <30%). Recently, peptide-receptor radionuclide therapy (PRRT) using [177Lu]DOTATATE beta(b)-particle
treatment (LutatheraÔ) improved survival vs standard of care and was FDA approved. However, objective tumor
responses were low (18%) in the Phase 3 trial. Nonetheless, Lutathera developer AAA, Inc. was subsequently
acquired by Novartis for $3.9 Bln demonstrating the commercial potential and significance of PRRT products.
Viewpoint’s next-generation PRRT employs alpha(a)-particle therapy, an emergent form of PRRT that is
producing objective (and even complete) responses. Viewpoint and the University of Iowa have secured an NIH
R01 (CA243014-01; Viewpoint CSO Michael Schultz is Co-PI) that supports a Phase 1 trial of Viewpoint’s
[203/212Pb]VMT-a-NET for NET in human subjects (a-therapy to begin Oct., 2021). VMT-a-NET (patent now
pending) is innovative because rationally-designed molecular modifications (patents now pending)
significantly improve radiolabeling, in vitro cell/internalization binding (20-fold) Kd (up to 6-fold) and in vivo PK
properties that significantly improve tumor accumulation/retention and reduce other organ retention (e.g.,
tumor:kidney ratio increased 8-fold) compared to competing agents. Thus, this research is significant because
new predicate biomarker and efficacy data demonstrate a therapeutic window that can significantly improve
outcomes for NET patients. This research is further significant because Viewpoint’s proprietary 212Pb
production device (VMT-a-GEN) establishes control of on-demand supply of 212Pb for commercialization. In this
revised Direct to Phase II SBIR project, Viewpoint will (i) procure GMP VMT-a-NET and conduct IND-enabling
toxicology prior to the therapy trial; and (ii) validate formulations and automate manufacturing of VMT-a-GEN.
PREDICATE MILESTONES: Secured $1.2Mln seed financing; signed terms for Series A investment; validated
SST2R target; secured R01 for [203/212Pb]VMT-a-NET Phase 1 therapy trial; GMP kits for production; exclusive
licenses; secured 203Pb supply (Lantheus); working prototype of therapeutic isotope (212Pb) production device
(VMT-a-GEN); VMT-a-GEN mfg. facilities established. Completing two Specific Aims readies Viewpoint for trials:
AIM 1. Manufacture and validate GMP VMT-a-NET peptide and conduct FDA-required toxicology in non-
human primates prior to a funded (R01) Phase 1 clinical therapy trial.
AIM 2. Automate, validate, and document manufacturing of 212Pb production device (VMT-a-GEN).
IMPACT: With success, we expect to have validated GMP VMT-a-NET and completed required toxicology
studies in non-human primates for CMC/IND submission/approval. We further expect to have automated
manufacturing of our 212Pb radioisotope generator (VMT-a-GEN). Thus, Viewpoint will be prepared to enter the
funded Phase 1 trial and have the competitive advantage of on-demand contro...

## Key facts

- **NIH application ID:** 10264081
- **Project number:** 5R44CA250872-02
- **Recipient organization:** VIEWPOINT MOLECULAR TARGETING, INC.
- **Principal Investigator:** Michael King Schultz
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $998,648
- **Award type:** 5
- **Project period:** 2020-09-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10264081

## Citation

> US National Institutes of Health, RePORTER application 10264081, Preclinical pharmacology, toxicology, biodistribution and dosimetry, and radionuclide production CMC validation for Pb-212 receptor targeted alpha-particle therapy for neuroendocrine tumors. (5R44CA250872-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10264081. Licensed CC0.

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