NanoPharmaceuticals Logo

Research & Development

Therapeutic Focus


Preclinical studies have shown that tetrac-based molecules produced by the Company are extremely effective against all human cancer models tested in mice. These cancers include glioblastoma (GBM), acute myeloid leukemia (AML), neuroblastoma, breast, prostate, pancreas, kidney, lung, bladder, cervical, melanoma and thyroid cancers. It is important to note that treatment of various orthotopic or xenografted tumors resulted in >90% shrinkage, with residual apoptotic tumor tissue that continues to be eliminated without any relapse, unlike most other strategies. Additionally, the broad-spectrum anti-angiogenesis activities and the inhibitory platelet activities by the high affinity tetrac-modified molecules eliminate existing or prevent any additional tumor metastasis. This effectiveness has been demonstrated without any detectable adverse effects in animals at doses 100-fold greater than those proposed for use in human subjects.


The Company’s preclinical studies with fb-PMT established that subcutaneously administered fb-PMT is a highly effective intervention in the treatment of glioblastoma (GBM). First, and foremost, our compound is taken up by the transthyretin (prealbumin) transport mechanism and readily passes through the blood-brain barrier into the brain. fb-PMT immediately travels to the tumor and begins attacking the tumor’s vasculature. GBM is a highly vascular tumor associated with edema formation. The compound’s antiangiogenic effects destroy the tumor’s blood vessels, reducing the oxygen and nutrients needed by the tumor to survive and eliminating the leakage, thus reducing and/or eliminating the edema. Simultaneously, the pro-apoptotic effects begin triggering spontaneous cell death in the tumor. During the therapy, the agent reduced tumor weight and tumor cell viability by 90%, with no signs of intratumoral hemorrhage observed. fb-PMT works on a large group of cancer cell signaling pathways (e.g., Hedgehog, Notch, HIPPO/YAP, mTOR), interferes with multiple pathways mediating essential molecular functions such as the KRAS oncogenic pathway, and downregulates expression of several key cancer driver genes.

Following discontinuation of fb-PMT, tumors in treated animals did not re-grow over a 3-week period of observation.

A Phase I clinical trial with fb-PMT for glioblastoma is ongoing at Yale Cancer Center.

Pancreatic Cancer

fb-PMT proved to be extremely effective against pancreatic cancer and its metastases in numerous preclinical studies. It significantly reduced tumor weight and tumor viability by 90% or greater after 3 weeks of treatment with no relapse after treatment was discontinued. Furthermore, the compound was effective in preventing and eliminating metastases from the orthotopic primary xenograft to spleen, liver, kidney, lung, and other organs. By such elimination, the patient is open to a much wider array of treatment modalities, including surgery and radiotherapy, otherwise not available for a patient with distant metastases.

NanoPharmaceuticals anticipates conducting a Phase 2 clinical trial with fb-PMT for the treatment of pancreatic cancer after the Phase I trial for glioblastoma is completed.

Other Solid Tumors and Metastases

The target of the Company’s compounds on integrin αvβ3 is linked by a number of downstream mechanisms to regulation of transcription of specific genes and to functions of cell surface vascular growth factor receptors. At this target, tetrac-based formulations coherently trigger more than 50 effects in cancer cells. Preclinical studies have shown they disrupt cancer-linked angiogenesis, block cancer cell division and DNA repair, induce programmed cell death (apoptosis), and disorder expression of a panel of genes essential to cancer cell defenses. Tetrac-based formulations in preclinical studies have caused extensive devascularization, cell necrosis and apoptosis in twelve different human cancers grafted into animals. These cancers include glioblastoma (GBM), acute myeloid leukemia (AML; see below), neuroblastoma, cancers of the breast, prostate, pancreas, kidney, lung, bladder and ovary, as well as melanoma and several forms of thyroid cancers. A number of cancer driver genes implicated in development of metastases are downregulated by tetrac-containing products. The interaction of platelets and circulating tumor cells, tumor angiogenesis, cancer cell migration and invasion contribute to metastasis development and these interactions are blocked by tetrac-based products.

Hematologic malignancies

Acute Myeloid Leukemia (AML)

Our preclinical studies have shown that our lead clinical candidate fb-PMT effectively suppresses the progression of an AML cell line and primary AML cells harboring FLT3-ITD in a transgenic NSG mouse model. Daily treatment with fb-PMT for 3-4 weeks was associated with leukemogenesis regression, suppression of cancer invasion and extended survival. Peripheral blood counts and smears from fb-PMT treated animals at 10 mg/kg returned to normal. Bone marrow biopsies regained their normal maturation with abundant segmented neutrophil and megakaryocytes; this represented complete hematological remission along with complete suppression of leukemic cell metastasis and invasion into different organs. These effects were maintained in animals after treatment with fb-PMT was discontinued for 2 weeks.

Neuroendocrine tumors

BG-P-TAT, a dual norepinephrine transporter polymer conjugated to a thyrointegrin αvβ3 antagonist via a non-cleavable bond, was developed to target and treat neuroendocrine tumors such as neuroblastoma, pheochromocytoma, pancreatic neuroendocrine tumor, and carcinoid tumor.


Neuroblastoma is an extracranial childhood cancer that originates in embryonal remnants of the sympathetic nervous system (neural crest cells). In animal model studies, BG-P-TAT reduced tumor volumes by more than 95% after 3-4 weeks of treatment. Furthermore, tumor regression continued after 1 week of discontinued treatment to effectively complete eradication of the neuroblastoma tumors. The reduction in tumor size with BG-P-TAT administration is a function of anti-tumor activity and clearance of tumor debris. BG-P-TAT effectively modulated key molecular pathways involved in neuroendocrine tumor progression including VEGFA-VEGFR2, EGFR, TOLL-like receptor, IL1α, TNFβ and RNAKL/RNAK/NF-kB signaling pathways, all in a coherent manner.

Pathological Angiogenesis-Associated Disorders

Pathological angiogenesis-associated disorders are disorders caused by abnormally excessive angiogenesis. Examples of these disorders include diseases of the eye and nonmalignant skin disease.

Angiogenesis that creates excess blood vessels in the eye is a principal component of eye diseases such as diabetic retinopathy and wet age-related macular degeneration. The Company’s investigators and collaborators have determined that its tetrac-based molecules could significantly inhibit the action of vascular growth factors that stimulate this angiogenesis in the eye, based on pre-clinical studies.

Highly vascular nonmalignant skin diseases, usually with a pro-inflammatory component, are potential targets for management with topical preparations of the Company’s tetrac-based pharmaceuticals. These skin disorders include rosacea, poikiloderma and psoriasis. Tetrac-based pharmaceuticals inhibit the various pro-angiogenic growth factors that are the principal contributors to these skin diseases. They also have anti-inflammatory properties that provide added benefit for the treatment of these skin diseases by inhibiting the expression of multiple genes of pro-inflammatory cytokines—such as interleukin-1α (IL-1α), IL-1β and IL-6—and chemokines. The anti-inflammatory properties of tetrac-based molecules could provide added benefit for the treatment of these skin diseases.