Hsiri Therapeutics is a development stage company focused on discovering and developing therapies for infections due to drug resistant bacteria. Hsiri’s research efforts are focused on two major areas – infections due to mycobacteria and infections due to usual bacterial pathogens. The research concepts for all of Hsiri Therapeutics products originated from the research efforts of Professor Marvin Miller at the University of Notre Dame.
For mycobacterial diseases, the Company is developing compounds that target both Tuberculosis and Non-tuberculous mycobacterial infections. The Company has enjoyed tremendous support from a number of collaborative partners including Eli Lilly and Company, the Infectious Disease Research Institute (IDRI), the Bill and Melinda Gates Foundation, the University of Notre Dame, Montana State University, Rutgers University, and the National Institutes of Health.
Hsiri Therapeutics is also developing compounds aimed at traditional bacterial infections caused by drug resistant bacteria, and we have two novel approaches to antibiotic research. One is to use the iron foraging mechanism of bacteria (siderophores) to serve as a targeting molecules for anti-bacterial compounds with known mechanisms of action. The other is to use modifications of a benzofuran scaffold as a novel mechanism to kill drug resistant bacteria. Hsiri has enjoyed support from both the Department of Defense and the National Institutes of Health in discovering these new therapies.
Bill has been in the pharmaceutical industry for over twenty-five years, initially at Searle and then at SmithKline Beecham. In the latter company, he held various positions and eventually was Senior-Vice President and Director of Worldwide Clinical Research. Bill was also the President, and CEO of Phoenix Data Systems before selling the company in 2008.
Marv is the George and Winifred Clark Professor Emeritus of Chemistry and Biochemistry at the University of Notre Dame. His research has been involved in the discovery of antibiotics for the last thirty years. He is a consultant to a number of pharmaceutical companies on drug design and antibiotic discovery.
Ivan was initially a commercial banker and then made his way into health care and pharmaceutical investing. He has also served in senior financial management roles in clinical data services companies including Phoenix Data Systems, BioClinica, and Numoda.
Denny has been In the pharmaceutical industry for over thirty years with previous large pharmaceutical company positions at Abbott and Rorer. Additionally, he has served in smaller companies such as Cytokine PharmaSciences where he was CEO, a King of Prussia, PA – based company that was sold at the end of 2011. He is currently the CEO of Women’s Choice Pharmaceuticals.
Hsiri has developed potent compounds targeted at both Tuberculous (TB) and Non-Tuberculous Mycobacterial (NTM) diseases. These compounds were discovered by a combination of rational design and serendipity. Patents on these compounds have now been issued in multiple countries and other patents have been filed in all major and relevant markets.
Hsiri Therapeutics has ongoing research initiatives in two areas. Using one approach, the Company utilizes the bacteria’s own iron capture molecules (known as siderophores) and couples them to conventional antibacterial compounds. This mechanism of using siderophore-conjugates targets the antibiotics to the bacteria and can avoid a number of bacterial resistance mechanisms. The WHO has identified carbapenem resistant A. baumannii as the most serious threat. Early studies of some of the Hsiri antibiotics have shown potent activity against this deadly bacteria.
Hsiri’s other approach to more the more common bacterial infections is the development of a patented small molecule antibiotic for both topical and systemic use. This compound has a broad spectrum of activity, including activity against most gram-positive bacteria we have evaluated including Staphylococcus, Streptococcus, and Enterococcus. This molecule also demonstrates some activity against selective gram-negative bacteria (Neisseria gonorrhoeae, and Acinetobacter baumannii). Most impressively, this compound is active against a variety of pathogenic anaerobic bacterial species. Because of this wide range of antimicrobial activity, Hsiri is evaluating this compound for several indications that include both systemic and topical applications.
Although Tuberculosis (TB) is an old disease, it continues to be a serious problem in much of the world. Approximately a third of the world has been infected with TB and there are more than 8 million new TB cases a year. TB in many areas is becoming a worsening problem because of the continually evolving drug resistance profile of the organism. The Hsiri drugs have been tested against the most resistant strains of TB and have been found to be active. Because of this profile, the lead Hsiri compounds are being testing in primate models of disease and pending the outcome of these tests, will be taken forward into formal studies leading to an IND at the FDA and clinical development.
Hsiri scientists realized several years ago that their anti-TB drugs might have potential against the NTM diseases. NTM diseases are complex in that they represent multiple species and strains of mycobacteria that do not all conform to the same antibiotic susceptibility. In fact, multiple species are resistant to most conventional therapies used and are extremely difficult to treat. NTM infections are seen in patients with immune compromised conditions, underlying structural lung disease, and now more frequently in otherwise healthy patients, particularly, post-menopausal women. The usual presentation of a patient with NTM disease is a lung infection although there can be several other presentations including skin infections. Hsiri Therapeutics has discovered highly potent and well tolerated compounds to treat NTM organisms. The Company is currently selecting a lead compound for further formal development for this indication.
Drug resistant bacterial disease is a frightening specter. As more bacteria become highly resistant to the standard therapies (such as penicillin or cephalosporin derivatives), physicians are forced into using other therapies that are often more toxic, more difficult to administer, and less effective. Many of these drug resistant bacteria are found in hospitals and often this is where these infections are acquired. Sadly, some bacteria are becoming virtually untreatable.