SBIR-STTR Award

The long-term goal of this proposal is to discover and develop small molecule drugs against Head and Neck Cancers (HNC). The focus is on drug candidates that target processes critical for repopulation after radiation treatment. The current proposal is to perform preliminary pharmacokinetics and toxicity studies and test the efficacy of a proprietary drug candidate on preclinical models of human HNC. Head and Neck Cancers remain hard to control even with surgery and high doses of radiation, both of which have devastating side effects. New drugs that enhance standard therapies by reducing resistance and preventing re-population after these treatments have the potential to improve clinical practices. Successful completion of this project will yield a drug candidate that can be carried into PD/ADME/toxicology analysis towards IND filing.

Project Terms:
Adverse effects; Aftercare; Biological Assay; cancer cell; cell growth; clinical practice; Dose; drug candidate; Drug Kinetics; efficacy testing; Goals; Head and Neck Cancer; Human; improved; in vivo; Normal tissue morphology; Operative Surgical Procedures; Pharmaceutical Preparations; Population; Pre-Clinical Model; prevent; Process; Radiation; radiation effect; Research Design; Resistance; small molecule; Toxic effect; Toxicity Tests; Toxicology; Treatment Protocols; Xenograft Model

SuviCa, Inc. (SuviCa) is discovering and developing best-in-class small molecule drugs for the treatment of Cancer. Their drug candidates take advantage of a differential requirement for protein synthesis between tumor and normal tissue, and thus have the potential to achieve therapeutic gain. Importantly, preliminary and published data indicate that SuviCa’s drug candidates have the potential to fulfill four areas of unmet need in the treatment of Head and Neck Cancer (HNC). (1) Their drug candidates synergize with Radiation in human Cancer cell growth assays, and enhance the effect of Radiation in clonogenic assays and in human tumor xenografts in mice. Drugs that increase the efficacy of Radiotherapy could improve clinical practice in the treatment of HNC, for example by allowing use of fewer and/or lower doses of Radiation, thereby reducing side effects. (2) Their lead molecules were found in a propriety screen for inhibitors of tissue regeneration after Radiation treatment in a model organism [2, 3]. Since growth and regeneration of tumors after Radiation treatment contributes to recurrence, our drug candidates have the potential to prevent recurrence. (3) Their drug candidates inhibit a specific step in translation elongation, which is not targeted by any FDA-approved drugs. In fact, for the whole process of translation elongation, there are only 2 FDA-approved oncology drugs (Homoharringtonine or omacetaxine mepesuccinate and denileukin diftitox). They can apply their compounds at non-toxic doses and yet render tumor xenografts that normally do not respond to Radiation to become responsive. (4) They have data, much of which were obtained through the Phase I SBIR Contract, that the drug candidates synergize with Radiation in HPV-negative HNC cell lines, offering hope for improved therapy of radio-resistant HPV-negative tumors.

NIH Spending Category:
Cancer; Dental/Oral and Craniofacial Disease; Orphan Drug; Rare Diseases; Regenerative Medicine

Project Terms:
Adverse effects; Animal Model; Area; Binding; Biological Assay; Biological Markers; Cancer cell; Cancer Cell Growth; Cancer cell line; Cancer therapy; Canis familiaris; Cisplatin; Clinical; clinical practice; Clinical Research; Contracts; Data; Denileukin Diftitox; Development; Dose; drug candidate; Drug Formulations; FDA approved; Future; Growth; Head and Neck Cancer; homoharringtonine; Human; Human Papillomavirus; improved; In Vitro; in vivo; inhibitor/antagonist; Lead; Low Dose Radiation; Modeling; Mus; Natural regeneration; Normal Cell; Normal tissue morphology; oncology; Outcome Study; patch clamp; patient population; Patients; Pharmaceutical Preparations; Pharmacodynamics; Phase; Pilot Projects; Plasma; prevent; Protein Biosynthesis; Publishing; Radiation; Radiation effect; Radiation therapy; Rattus; Recurrence; Resistance; Route; scale up; Schedule; Small Business Innovation Research Grant; small molecule; Solid; Solutions; Testing; Therapeutic; tissue regeneration; Toxic effect; Translation Process; Translations; tumor; Tumor Tissue; tumor xenograft; Xenograft Model; Xenograft procedur