KEY MTTI ASSETS IN DEVELOPMENT – SNMMI June 2019
NAME: EBTATE (177Lu-DOTA-EB-TATE)
INDICATION: Neuroendocrine Neoplasms (NEN)
USE: First-in-human studies demonstrated remarkably higher uptake and retention in neuroendocrine neoplasms than Lutathera®. A single low-dose EBTATE treatment appears to be safe and effective in the treatment of NEN. EBTATE may be effective with fewer, significantly lower doses than Lutathera®. The best EBTATE patient population includes metastatic, SSTR-positive NET patients.
TECHNOLOGY: EBTATE is a peptide receptor radionuclide therapy (PRRT) for the treatment of somatostatin receptor positive gastroenteropancreatic neuroendocrine tumors. The drug binds to and destroys somatostatin receptor expressing NET cells. 80% of NETs overexpress somatostatin receptors (particularly SSTR2) .
EBTATE was designed to overcome rapid clearing of Lutathera ® by chemically incorporating an Evans Blue moiety in its backbone. By increasing residence in albumin, EBTATE substantially lengthens the in vivo half-life, increasing the probability of binding between drug and target. That enables fewer, lower doses of the radiotherapeutic.
UNMET NEED: SSAs (Somatostatin Analogs) like Sandostatin, Somatuline and Lutathera that bind to somatostatin receptors have been used to treat NETs. All have limitations.
PROOF OF CONCEPT: Extensive preclinical and two Phase I studies (targeting 50 patients) at Peking Union Medical College Hospital(China).
STAGE OF DEVELOPMENT:
· GLP preclinical, analytical, stability and process development through 2019.
· Phase I trial in US beginning Spring 2020.
· Phase II Trial planned Sep 2021
PRINCIPAL COLLABORATORS: NIH & Memorial Sloan Kettering Medical Center
IP: “Chemical Conjugates of Evans Blue Derivatives and their use as Radiotherapy and Imaging Agents (PCT/US2017/054863) filed October 3, 2017, pending
FUNDING: Applied for Fast Track Phase 1 &2 SBIR.
OWNERSHIP: MTTI awarded world-wide-exclusive rights by NIH 10/8/2018.
CLASS: Imaging Agent
INDICATIONS: cancer, drug toxicity,...
USES: demonstrated in multiple preclinical studies visualizing:
- Tumor response to chemotherapy
- Systemic inflammatory response syndrome (SIRS)
- Injury due to drug toxicity
- Organ transplant rejection
- Atherosclerotic plaque
- Acute myocardial infarction
TECHNOLOGY: Cell death is the surrogate endpoint for most disease states and anticancer therapies (tumor death). There is no direct cell death imaging agent yet accepted in routine clinical practice.
TDURA, a small, peptide-based radiopharmaceutical imaging agent labeled with 99mTc, sees cell death, in vivo, directly. It enables early, actionable efficacy tracking of tumor cell death within days of the first treatment. It has a unique mechanism of action, binds well to markers on dying cells, and clears readily, a model imaging agent.
Lack of response to therapy is a major hurdle for cancer treatment. Early tracking of tumor response to therapy is critical. Current methods to measure tumor response observe tumor shrinkage or metabolic changes, which may not be detectable for weeks. Ending ineffective therapy early minimizes costs and patient stress.
Systemic inflammatory response syndrome (SIRS) is associated with the presence of pro- and anti-inflammatory cytokines in serum, including tumor necrosis factor (TNF). TNF has multiple effects and leads to cytokine production, leukocyte infiltration, blood pressure reduction and coagulation, contributing to tissue damage and organ failure. TDURA imaging can be used for whole body assessment of tissue damage due to inflammation and injury.
PROOF OF CONCEPT: 35 publications prove concept and demonstrate utility in multiple indications (see above). Concentrated on visualizing tumor death in colorectal cancer.
STAGE OF DEVELOPMENT: Phase 0/1 development at Univ of Antwerp in Q4 2019.
PRINCIPAL COLLABORATOR: University of Antwerp MICA (Molecular Imaging Center Antwerp)
IP: US 7,877,783 B2, US 8,778,303B2, Chinese patent CN102014970B, European approved 2017. These patents are secure through 2029 in US, EU and China. MTTI obtained an exclusive license from the Medical College of Wisconsin.
FUNDING: ~$3 million non-dilutive grants from NIH & EU.
NAME: 131I SapC-DOPS
CLASS: Therapeutic Agent
INDICATION: glioblastoma multiforme (brain cancer)
USE: Targeted radio- and biotherapy of glioblastoma multiforme.
TECHNOLOGY: SapC-DOPS, a nanovesicle composed of saposin C (SapC) polypeptide and dioleoylphosphatidylserine (DOPS), has proven tumor targeting properties (crossing the blood-brain and blood-tumor barriers, then binding a lipid tumor marker, extracellular phosphatidylserine(PS)). It shows antitumor activities in preclinical glioblastoma (GBM) models.
Incorporating a radiotherapeutic iodine in the SapC-DOPS nanovesicle provides a novel agent with potentially superior efficacy for targeted radionuclide therapy (TRT) of glioblastomas (GBMs). NIH NCI funded Proof of Concept studies demonstrate a 43% increase in mouse survival over a non-radioactive nanovesicles.
UNMET NEED: GBM is among the most aggressive and intractable cancers. Current average survival is <2 years. Treatment options are limited. Standard therapies with surgery, radiation and/or chemotherapy provide modest survival improvement. Frequent, severe side effects from surgery and subsequent therapy seriously impact Quality of Life. Micrometastatic spread of tumor cells and residual disease are common, demanding further treatment.
PROOF OF CONCEPT: Backed by extensive, published and unpublished, preliminary data, an FDA Orphan Drug designation and an ongoing Phase I clinical trial of non-radioactive SapC-DOPS by Bexion Pharmaceuticals, Inc. An MTTI collaborator at the Univ. of Cincinnati has shown:
- 127I SapC-DOPS -CVM targets GBM
- 125I SapC-DOPS -CVM selectively accumulates in GBM
- 131I SapC-DOPS increases survival 43% over 127I SapC-DOPS
STAGE OF DEVELOPMENT: Preclinical. GBM drugs benefit from accelerated clinical development (GBM Agile) , Orphan designation and speedy FDA approval after Phase II trials.
PRINCIPAL COLLABORATOR: University of Cincinnati
FUNDING $349,989 funding from NCI. Fast track Phase I/II SBIR application submitted.