Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 600.00K | Year: 2011
DESCRIPTION (provided by applicant): The worldwide health problem created by malaria has been made more difficult by the spread of drug- resistant parasites. This project initiates preclinical development of one or more candidate(s) from an innovative newclass of potent antimalarials designed to overcome drug resistance. We have developed an orally available and inexpensive class of novel drugs that act against both chloroquine-resistant and chloroquine-sensitive malaria. A small set of carefully-selectedcandidates will be advanced through preclinical testing, leading to the selection of a single drug for a pre-Investigational New Drug meeting with the Food and Drug Administration. With guidance from the Food and Drug Administration, pharmacokinetics, pharmacodynamics, pharmacology, and toxicity evaluations will be performed in both rats and monkeys in phase II of this work. The overall goal will be completion of preclinical studies leading to approval of the Investigative New Drug (IND) application for a drug to be used in a Phase-1 human clinical trial. PUBLIC HEALTH RELEVANCE: Malaria is a disease that infects about half a billion people annually, and kills nearly one million, most of whom are children or pregnant women. The impact of malaria is increasing, partly because the parasite that causes malaria has evolved into strains that are resistant to the best current drugs for treating the disease. This project involves preclinical evaluation of novel drugs designed to circumvent this resistance, paving the way toward approval for human clinical trials. The drug candidates show promising results in early studies, and are designed to be inexpensive as well as safe for all target groups, including pregnant women and children.
Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 103.88K | Year: 2007
DESCRIPTION (provided by applicant): The intent of the work presented in this proposal is to counter the worldwide health problem brought on by the spread of chloroquine-resistant malaria. To address the need for an orally available and inexpensive replacement drug, we have developed a novel class of molecules called "reversed chloroquines" (RCQs) which act against both chloroquine-resistant and chloroquine-sensitive malaria. Herein we describe a new sub-class of RCQ molecules, which we term branched RCQ (bRCQ) molecules. These bRCQ molecules may be even better than the 'simple' RCQs. The goal of the described project is to understand how to optimize structural features in the bRCQ molecules to yield the best possible, orally available drug against malaria. This will be accomplished by producing a panel of varied bRCQ structures, and then testing them against chloroquine-sensitive and chloroquine-resistant malaria in red cell culture (an in vitro test), as well as for solubility, central nervous system receptor activity, and cytotoxicity. The most promising candidates will then be evaluated as orally available drugs against malaria in mice. Once these experiments demonstrate the feasibility of the bRCQ molecular design, as well as provide fundamental understanding of correlations between molecular features and efficacy of bRCQs against malaria, the bRCQ structures will be "tuned" in order to optimize practical aspects of their use in humans. Although we are directing this study specifically against P. falciparum, the most problematic human malaria variant, bRCQs should also be effective against the other human malarias. Although there may be a very thin profit margin to be had some 'endemic markets', there is an increasing ability to pay for drugs in countries such as India and China and the military and traveler markets have promise for reasonable commercialization.
Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase II | Award Amount: 1.33M | Year: 2009
DESCRIPTION (provided by applicant): DesignMedix has developed a novel class of compounds to address the pressing need for an orally available, inexpensive drug to counter the spread of chloroquine-resistant malaria. Preliminary data showed that this novel class of molecules, called reversed chloroquines (RCQs), acts against both chloroquine- resistant and chloroquine-sensitive malaria in vitro. In our Phase I study, we demonstrated the feasibility of this approach both in vitro and in an in vivo animal model, showing that compounds were orally available, had in vivo effectiveness similar to that of chloroquine, and were very effective against chloroquine-resistant human malaria parasites in vitro. The goal of this Phase II project is to choose and move specific RCQ drug candidates into preclinical studies to advance commercialization of a therapeutic product. In addition to focusing on the clearly-identified lead compounds from the Phase I, we will enlarge the initial panel of RCQ structures based on results from that initial feasibility study, and test them against chloroquine-sensitive and chloroquine-resistant malaria in human red blood cells in vitro, as well as for other in vitro tests for solubility, central nervous system receptor activity, mutagenic activity, and cytotoxicity. Oral availability will begin with mice, as will in vivo toxicity evaluations. The most promising of the original and modified RCQ candidates will be moved forward toward preclinical study through evaluation in animal models for their pharmacokinetics and metabolism. We expect that at the conclusion of the Phase II project, one or more lead RCQ drug candidates will be ready for study in a primate model system of chloroquine-resistant malaria, the final step before full preclinical GLP toxicity and ADME studies for filing an IND application for human clinical studies. DesignMedix is directing this study specifically against P. falciparum, the most problematic human malaria variant, but RCQs also should be effective against the other human malarias. The product addresses market opportunities that include large endemic markets with international non-profit and government buyers, smaller but substantial markets for military and travelers, as well as private markets in developing countries such as India and China. Further development of the product will be carried out with resources from multiple sources, including equity investment, company and global health non-profit partnerships, and additional grant funding. PUBLIC HEALTH RELEVANCE: Malaria is a disease that infects almost half a billion people annually and kills between one and three million people, most of whom are either children or pregnant women. Malaria is increasing, partly because the parasite that causes malaria has evolved into strains that are resistant to our best drugs for treating the disease. This work is to develop further promising lead candidates from a new class of drugs, reversed chloroquines' (RCQs), designed to overcome this resistance.
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: STTR | Phase: Phase I | Award Amount: 353.90K | Year: 2016
DESCRIPTION provided by applicant Trichomonas vaginalis is the causative agent of the most common non viral sexually transmitted infection with million new cases reported annually in the world and million cases in the U S In addition to infections of the urogenital tract trichomoniasis increases the risk of adverse pregnancy outcomes and HIV transmission and increases the incidence and severity of cervical and prostate cancers Only two drugs are FDA approved for the treatment of trichomoniasis the nitro heterocyclic compounds metronidazole Mz and tinidazole Oral dosing leads to clinical and microbiological cure in the majority of cases but treatment failures occur in a significant fraction of patients up to with reports of increasing resistance in the U S High oral Mz or tinidazole doses in combination with topical treatment of the same drug s have been used with success for Mz refractory vaginal trichomoniasis whereas topical Mz treatment alone is only modestly effective and so is not recommended While topical treatment is possible in principle as shown in murine models and would be attractive because low systemic absorption is likely to reduce systemic adverse effects compared to oral formulations current drugs are not sufficiently potent for this preferred administration route Given the prevalence of trichomoniasis its association with multiple disease outcomes and the increase in drug resistant strains as well as the potential for more resistance development of new antimicrobials against trichomoniasis is an urgent need Our preliminary studies of andgt newly synthesized nitro compounds provide compelling evidence that novel nitro drugs can be developed with marked improvements in potency and the ability to completely overcome existing drug resistance Such andquot next generationandquot nitro drugs have the distinct advantage that this antimicrobial class contrary to any other compound class is already established to be effective and safe against trichomoniasis The increased potency of our novel compounds should allow development of a topical treatment Therefore the project has the overall objective to develop a new lead nitro compound for the topical treatment of Mz sensitive and Mz resistant trichomoniasis Based on our prior data we have selected several of the most promising structural domains and will now perform focused structural explorations within these domains The new derivatives will be tested for activity and potency against Mz sensitive and Mz resistant T vaginalis in vitro for cytotoxicity and genotoxicity in mammalian cells in vitro and for efficacy in a murine model of vaginal trichomoniasis in vivo The comprehensive bioactivity and toxicity data to be generated in this project will be used to select two non toxic compounds with the best combination of high potency and ability to overcome resistance in vitro and good efficacy in vivo as lead and back up for subsequent preclinical development of a novel high potency compound for the topical treatment of trichomoniasis in phase II of the project PUBLIC HEALTH RELEVANCE Trichomonas vaginalis is the causative agent of the most common non viral sexually transmitted infection in the U S and worldwide Only two drugs metronidazole and tinidazole are currently FDA approved for the oral treatment of trichomoniasis but treatment failures and resistance occur in up to of cases and no topical treatment is effective without concurrent systemic therapy Supported by extensive preliminary work on potential new drugs the proposed project will develop the most potent candidates as novel high potency lead compounds for the topical treatment of trichomoniasis
News Article | July 18, 2014
DesignMedix, Inc., a Portland, Oregon-based biotech startup, has closed a $1.5m second round of angel funding. Investors include Portland Seed Fund, as well as members of Bellingham Angels, Oregon Angel Fund, Seraph Angel Network, Willamette Angel Conference, Keiretsu Angel Forum and Tacoma Angel Network. The company intends to use the funds for further development of a pipeline of drugs that combat drug resistance, including malaria drugs and new anti-bacterial drugs. Founded in 2008 and led by Dr. Sandra Shotwell, president and COO, DesignMedix develops drugs to overcome drug resistance. Its initial focus is on oral drugs to treat malaria, which kills over 600,000 people per year and affects up to 500 million people. The company has exclusive rights to four issued patents relating to drug candidates for malaria drugs. The company’s lab and office are housed in the PSU Business Accelerator. DesignMedix was recently awarded a $3m grant from the National Institutes of Health to support preclinical development of its malaria drug.