We are focusing our drug discovery and development efforts on infectious disease areas with great unmet medical need. Using a proprietary AI-based algorithm, our chemistry team has been designing a number of novel small molecules for the treatment of fungal, bacterial and viral infections. Our scientific team has also gained substantial experience in the areas of autoimmune and inflammatory diseases.
Unmet medical needs in various infectious disease areas
Systemic Fungal Infections
In addition to superficial skin infections, fungal pathogens can cause deep systemic infections, which constitute a major health threat, especially for immunocompromised patients. Opportunistic fungi are a leading cause for nosocomial infections with significant rise in health care costs. The most notable invasive infections are candidiasis, aspergillosis, mucormycosis, cryptococcosis and pneumocystosis. Two of the most prominent fungal pathogens are Candida and Aspergillus species causing infections which lead to severe invasive disease potentially involving any organ. An emerging problem has been the rise of multidrug resistant (MDR) candida species such as Candida auris. There are mostly four main classes of therapeutics which are approved to treat fungal infections. First and foremost, these compounds belong to the chemical class of azoles, followed by the echinocandins and polyenes, as well as nucleoside analogues. Common mechanisms of resistance include the induction of efflux transporters and the occurrence of genetic mutations in the drug targets leading to a decrease in drug affinity and hence to a drop in efficacy. This makes effective treatment with existing drugs from the azole and echinocandin families challenging and warrants the development of new molecules which can overcome drug resistance. Surprisingly, development efforts for these new antifungal drugs have been low in recent years stressing the urgency for compounds with new mechanism of action. Rhea’s research has focused on the discovery and development of broadly active small molecule therapeutics thereby overcoming emerging drug resistance in fungi.
Emergence of multidrug-resistant bacteria
It is of great concern that at some point in the future a large number of bacterial infections will no longer be treatable with the current set of approved antibiotics due to emerging multi-drug resistance. This puts a large population of patients at significant risk. The US Centers for Disease Control and Prevention (CDC) have published regular reports classifying the spread of antibiotic resistance ( www.cdc.gov/DrugResistance/Biggest-Threats.html). There are four major categories mentioned in the recent CDC report with various degrees of urgency and threat potential. The Urgent Threat category comprises microorganisms such as Carbapenem-resistant Acinetobacter and Enterobacteriaceae (CRE), as well as drug resistant Clostridioides difficile, Candida auris and Neisseria gonorrhoeae. Others such as Methicillin-resistant Staphylococcus aureus (MRSA) and drug-resistant Streptococcus pneumoniae (S. pneumoniae) are pathogens constituting a serious threat level. Rhea’s compounds were found to be efficacious against a broad spectrum of these drug resistant microbial pathogens and will hence be valuable novel therapeutic tools to significantly counteract the continuous rise of antibiotic resistance.
Many of the worst pandemics in human history were caused by respiratory viruses with great potential for human-to-human transmission. Examples range from the flu pandemic (1889-1890), the so-called Spanish Flu (1918-1920) to the more recent examples of the H1N1 swine flu (2009-2010), SARS-CoV-1 (2003) and the current SARS-CoV-2 pandemic. Experience has shown that societies have been ill-prepared to successfully battle the emergence and spread of new viruses, with virtually no approved treatment available for Coronavirus infections. Apart from vaccines being rolled-out, new therapies are emerging based on biologics such as monoclonal antibodies targeting the SARS-CoV-2 spike protein. In addition, multiple efforts aim to develop either novel or repurpose known small molecule drugs targeting crucial viral proteins of SARS-CoV-2. However, Coronaviruses are known to mutate frequently (as shown by the latest SARS-CoV-2 variants) and hence, some of the currently deployed strategies, especially the antibody drugs may no longer be as efficacious against new SARS-CoV-2 strains. At Rhea, we are determined to develop antivirals with a novel mechanism of action, which will be effective not only against SARS-CoV-2, but also against all emerging variants and other coronaviruses known to cause severe lung disease (such as MERS-CoV) or the common cold (such as OC43, 229E and NL63). Hence, one of our latest compounds is envisioned to be developed as a pan-Coronavirus inhibitor, which will also be very useful as a therapeutic weapon against any future outbreak of any novel Coronavirus.