There are unmet medical needs in the limited biologic therapeutics for adults with rheumatoid arthritis [RA] associated with $39.2 billion annual US health care and societal costs. These are due to inadequate efficacy; prohibitive costs, poor adherence and safety issues (infections & malignancies). Oral small-molecule based therapies are warranted due to their inherent lower safety risks, lower costs and flexible drug delivery formulations. Persistent safety findings of oral kinase inhibitors in development for RA justify a target-selective approach that limits disease progression without the unwarranted toxicities associated with non-specific generalized over-immunosuppression. Selective inhibition of macrophage migration inhibitory factor [MIF] has been target validated demonstrating unprecedented superior safety and efficacy in preclinical RA and several animal models. The successful completion of the Phase I INV-88 lead development research led to the discovery of highly potent and efficacious first-in-class, best-in-class oral INV-88 MIF inhibitors reported to date, clearly differentiating INV-88 compounds from early MIF inhibitors. The INV team of drug discovery & development experts with an industry track record of successfully advancing > 35 RA and autoimmune disease [AD] therapeutics will lead the proposed Phase II Clinical Candidate Selection research of INV-88 to establish the optimal drug-like properties and the preclinical Proof of Concept [POC] of INV-88 in RA. The Phase II goal is to select the best single clinical lead compound that could advance to the Phase III IND-enabling phase and will be achieved by accomplishing the following 6 specific aims of: (1) INV-88 Compound Synthesis, (2) In vitro Biochemical Profile, (3) In vitro Pharmacology Screen, (4) In vitro ADMET Profile, (5) Establish the INV-88 in vivo Mouse Pharmacokinetic [PK] Profile, and (6) Establish the INV-88 in vivo Preclinical POC Efficacy in a Mouse Collagen-Induced Arthritis [CIA] Model. The successful selection of an INV-88 clinical candidate in Phase II will advance to a Phase III Preclinical/IND-enabling research stage with a goal to complete the ICH- M3(R2) requirements that will enable an FDA IND filing for RA and a Phase 1 First in Human clinical study start. Achieving these milestones would place INV in a position of strength as it seeks an outlicensing, M&A or codevelopment agreement with external stakeholders. INV will seek potential industry development partners and investors during Phase II, and thus securing a development partner early-on to support the INV-88 IND- enabling and clinical development, NDA approval and commercialization. An FDA approval for INV-88 as the first orally available target-selective cytokine inhibitor with a potential for better potency and efficacy, superior safety profile, wider therapeutic index, and cost-effective oral immunotherapy convenient for RA patients would fulfill all critical unmet medical needs by contributing to overall patient mortality and quality of life improvements, and reduced public health care and societal costs.