A First-in-class Topical Immunoregulatory Therapeutic for Psoriasis

A First-in-class Topical Immunoregulatory Therapeutic for Psoriasis BioTherapeutics, Inc (BTI) is an emerging private biotech company that synergistically combines the power of advanced computational modeling with translational experimentation to accelerate the development of novel products for precision medicine and health. The BTI team has extensive expertise in developing novel first-in- class (FIC) therapeutics from discovery and IND filing and advancing them to Phase 1-3 clinical testing. Psoriasis (PsO) is a global health concern that affects 125 million people worldwide. PsO is an inflammatory skin disease characterized by a scaly and erythematous skin plaques, associated to severe itchiness, effects on appearance, and persistent rashes that negatively impact on quality of life. Despite advancements in treatments, particularly in biologic therapies, safety and tolerability concerns, loss of responsiveness, and elevated cost may result in treatment discontinuation. Thus, there is an urgent need for the development of safe and effective therapeutics. We have developed a novel topical therapeutic that significantly reduced disease severity and histology legions in mouse models of PsO, plus decreased topical and systemic exacerbated inflammation. This Phase 2 SBIR application will further characterize its therapeutic efficacy and PK properties. The Specific Aims for this SBIR Phase 2 application are to: AIM 1. Conduct PK and tissue distribution studies in a mouse model of PsO. We will conduct PK and target engagement studies in IMQ-induced model of psoriasis. We will evaluate study of bioavailability, local skin penetration and plasma profile. AIM 2. Determine the exposure-response relationships. We will use mouse models of PsO to robustly define the biomarker, mechanistic and efficacy responses to varying doses in combination with local and systemic PK. AIM 3. Evaluate cell specific contributions to therapeutic efficacy. We will use whole body and cell-specific, cre-lox knockout mice in an IMQ-induced model of PsO. Primary outcomes will be PASI, histological lesions, systemic and local inflammation. AIM 4. Examine combinatorial efficacy and interaction profile of our topical product candidate with current PsO drugs. We will evaluate the efficacy of combinatorial therapies the potential drug-to-drug interactions to define the inclusion/exclusion (I/E) criteria and allowable continued therapies during human clinical trials. Expected successful outcomes are: i) < 3% of bioavailability in IMQ-challenged mice, ii) generate a 5-8 parameter model that differentiates responders from non-responders, iii) >40% increased epidermal hyperplasia in tissue specific knock out mice, and iv) no abrogation efficacy measured as composite score on day 7. The long-term goal of this project is to develop a safe and effective topical immunomodulatory therapeutic for PsO and provide a path towards commercialization of an asset with a target population of over 8 million resulting in a market expected to reach over $68 billion in 2033.