SBIR-STTR Award

According to the Oral Cancer (OC) Foundation, oral and pharyngeal cancer will cause 8,000 deaths this year, killing roughly one person per hour. Currently, cisplatin (CIS) is at the forefront of platinum- based chemotherapeutics for treating OC. However, its efficacy is often hindered by its significant systemic toxicity as a result of traditional bolus systemic intravenous (IV) doses. In this proposal, Privo's specific aims focus ondeveloping and optimizing an effective and safe nano engineered drug delivery platform, i.e., chemo-wafer (CW) that reformulates a known anticancer chemotherapy agent ( e.g. cisplatin) for the local and topical treatment of OC, thus replacing injection, increasing the drug's efficacyand significantly reducing its systemic toxicity. The CW platform contains FDA approved chemotherapy drugs and generally recognized as safe (GRAS) materials. It utilizes nano-encapsulation techniques to incorporate drugs into NPs with a controlled-release design that releases chemo drugs at fully tunable and pre-determined rates. The design has the potential to deliver a highly concentrated amount of chemotherapy agents directly to the cancer tissue while minimizing toxic side effects to the surrounding healthy tissues. Part of the project is the development of a novel bilayered vehicle, CW, consisting of a NP front end and a plasticized, non-porous, non-permeable back end. It consists of a mucoadhesive material with unidirection delivery of the drug, which prevents the chemo agent from reaching the taste buds. This addresses the unpleasant taste issues, and increases patient compliance. This project can change the chemotherapy treatment of OC patients by replacing IV delivery with topical delivery of CW, significantly reducing the overall cost of OC treatment. The American Cancer Society has emphasized that oral chemotherapy is truly the wave of the future for oral cancer treatments because it offers patients distinct advantages over traditional IV. The 5- year survival of patient with OC has not significantly improved over the past several decades. Moreover, the survival rate for early detection is significantly higher than later stages (80-90% vs. 25- 35%). Therefore,for patients with pre-malignant to non-metastasized malignant OC, this reformulated nano-encapsulated CW delivery platform has the opportunity to considerably reduce the morbidity and mortality rate of this devastating cancer. The CW has the potential to be administered by the patient and in the privacy of their own homes, avoiding the inconvenience of travel to and from chemotherapy clinics and reducing healthcare cost. The ultimate objectives of Privo Technologies are to develop and commercialize an effective, safe and convenient chemotherapy treatment accessible to many OC patients.

Thesaurus Terms:
Address;Adverse Effects;American Cancer Society;Animals;Applications Grants;Architecture;Area;Back;Base;Biological Availability;Biotechnology;Bolus Infusion;Cancer Patient;Cancer Site;Cancer Surgery;Cancer Therapy;Canis Familiaris;Cessation Of Life;Charge;Chemistry;Chemotherapy;Chitosan;Chronic Disease;Cisplatin;Clinic;Collaborations;Compliance Behavior;Controlled Release;Cost;Data;Design;Development;Diffusion;Distant;Dose;Drug Controls;Drug Delivery Systems;Drug Efficacy;Drug Formulations;Early Diagnosis;Efficacy Evaluation;Encapsulated;Entrepreneurship;Experience;Fda Approved;Figs - Dietary;Foundations;Funding;Future;Goals;Hamsters;Hand;Health Care Costs;Home Environment;Hour;Improved;In Vitro;In Vivo;Injection Of Therapeutic Agent;Innovation;Institutes;Intravenous;Investigation;Kidney;Killings;Kinetics;Lesion;Malignant - Descriptor;Malignant Mouth Neoplasm;Malignant Neoplasm Of Pharynx;Malignant Neoplasms;Masks;Membrane;Modeling;Monitor;Morbidity - Disease Rate;Mortality Vital Statistics;Mus;Nano;Nanodrug;Nanoencapsulated;Nanoengineering;Nanoparticle;Nanotechnology;Neoplasm Metastasis;Novel;Oncology;Oral;Organ;Paper;Particle Size;Patients;Persons;Pharmaceutical Preparations;Phase;Plasticizers;Platinum;Polymers;Preclinical Study;Premalignant;Prevent;Privacy;Property;Provider;Public Health Relevance;Research;Safety;Severities;Skills;Staging;Success;Surface;Survival Rate;System;Taste Buds;Taste Perception;Techniques;Technology;Therapeutic;Tissue Model;Tissues;Toxic Effect;Travel;Treatment Efficacy;Tumor;

In this proposal, Privo describes its research and development plans in order to obtain Food and Drug Administration (FDA) Investigational New Drug (IND) status for its localized nanoparticle based chemotherapy wafer for safely treating oral cancer. According to the Oral Cancer Foundation, over 43,250 Americans will be diagnosed with oral and pharyngeal cancer this year, causing over 8,000 deaths, roughly one person every hour. In 2011, over 640,000 new oral cancer cases were diagnosed worldwide, and only half will live more than 5 years after initial diagnosis. By 2020, the annual worldwide incidence is predicted to increase to over 840,000, a 30% rise, and the annual mortality to increase to nearly 480,000, approximately a 37% increase. Currently, cisplatin is at the forefront of platinum based chemotherapeutics for treating oral cancer. However, its successful administration is frequently hindered by its significant systemic toxicity as a result of traditional bolus systemic intravenous (IV) administration. Privo Technologies is a company with roots in MIT's Langer Lab which has developed a nanoengineered ChemoThin Wafer (CTW(c)) for topical and local delivery of chemotherapy agent cisplatin (CIS) to oral cancer tumors. This technology has been awarded more than $3 million in non- dilutive funding, including a recent approval of $2.3 million funding from the National Cancer Institute (NCI) for its IND enabling preclinical studies. Privo's treatmen has been shown to be safer and more effective than the gold standard intravenous (IV) cisplatin. CTW(c) is easy to administer, and takes only 1 hour to complete the application. It has caused complete tumor regression in animals after 6 treatments. In this proposal, Privo requests funding from NIDCR which, when combined with the NCI funding, will provide Privo the adequate resources to obtain its FDA Investigational New Drug (IND) status. This proposal includes performing the Chemistry Manufacturing and Control (CMC) process required prior to clinical trials, developing required assays including the identity assay, potency assay of the active pharmaceutical ingredient (cisplatin), and purity assay, the establishment of GMP manufacturing, and sourcing pharmaceutical grade raw materials. Privo believes that its CTW(c) aligns closely with the aims of NIDCR in providing a safer, more effective, and less costly treatment for oral cancer.

Public Health Relevance Statement:


Public Health Relevance:
Privo's nano-engineered topical ChemoThin Wafer (CTW(c)) treatment will deliver highly concentrated cisplatin topically and locally in a targeted manner directly to oral cancer tumors. In three sets of in-vivo studies, CTW(c) has proven to be more effective and significantly safer than the current gold standard intravenous chemotherapy. It is cost effective, simple to administer and the procedure takes only one hour. Complete tumor regression has been achieved with six doses of CTW(c) with no recurrence within 9 months post treatment. Privo aims to obtain the FDA's Investigational New Drug (IND) status at the completion of this proposal.

Project Terms:
Aftercare; American; Animals; Award; base; Biological Assay; Bolus Infusion; Businesses; cancer therapy; Cessation of life; Chemicals; Chemistry; chemotherapy; Cisplatin; Clinical; Clinical Trials; commercialization; Contracts; cost effective; design; Development; Development Plans; Diagnosis; Disease; Documentation; Dose; Drug Delivery Systems; Drug Exposure; Elements; Ensure; Evaluation; Exposure to; Foundations; Funding; Goals; Gold; Grant; Guidelines; Hamsters; High Pressure Liquid Chromatography; Hour; Hygiene; improved; In Vitro; in vivo; Incidence; Intravenous; intravenous administration; Investigation; Investigational Drugs; Life; local drug delivery; malignant mouth neoplasm; Malignant neoplasm of pharynx; manufacturing process; manufacturing scale-up; meetings; Methodology; Methods; Mortality Vital Statistics; Mus; nanoengineering; nanoparticle; Nanotechnology; National Cancer Institute; National Institute of Dental and Craniofacial Research; novel therapeutics; Persons; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Plant Roots; Platinum; preclinical study; Procedures; Process; Production; programs; Property; public health relevance; Quality Control; Recurrence; Research; research and development; Research Contracts; Research Design; research study; Resources; Rest; Risk; Safety; safety study; scale up; Scientist; Seasons; Small Business Innovation Research Grant; Solubility; Specific qualifier value; sterility testing; Sterilization; Survival Rate; systemic toxicity; Technology; Testing; Topical application; Toxic effect; tumor; United States Food and Drug Administration; Work