• Mechanism & Potency : Quantify MC4R/MC3R cAMP EC50 (± bias), confirm NPY1R antagonism and OPRD1 modulation with orthogonal assays.
• Selectivity & Safety : Run broad off-target panel (e.g., CEREP/Eurofins), hERG, Ames, CYP/TDI, microsome/hepatocyte stability; human/rat microsomes and CYP/TDI.
• PK & Formulation : Establish oral exposure (F%, t1⁄2, dose linearity) in rodent (± dog); initiate salt/polymorph screen and early XR concept.
• In Vivo Signal : 2–4-week DIO mouse (food intake, body weight, indirect calorimetry, glucose/insulin, tolerability readouts).
• Chemistry & CMC : Lock a ≤8-step route, deliver >10 g non-GMP, stress/forced-degradation map, reference standards.
• IP & Regulatory : File CoM + degradants/analogs + combo claims; prepare ODD package for MC4R-axis obesity and schedule early agency interactions; organize a partner-ready data brief for option-to-license/co-dev.

The BIOS-GAL-2201 program represents a paradigm shift in CNS therapeutics, centered on a first-in-class, peripherally-restricted neuromodulator. Discovered from the microbiome, this orally available small molecule is designed to harness the gut-brain axis by acting on the enteric nervous system. The core innovation of this program is its potential to deliver the therapeutic benefits for high-unmet-need conditions like depression and anxiety while avoiding the central side effects that plague current treatments, offering a transformative safety and tolerability profile.

Next Steps:

The program is currently at the preclinical discovery stage, with all evidence based on computational modeling. The immediate next steps are focused on achieving in vitro proof-of-concept through a series of critical, de-risking experiments:

• Function : Experimentally confirm the predicted multi-activity profile through cell-based binding and functional assays
• Safety & Selectivity : Validate the selectivity and de-risk early safety liabilities via broad-panel off-target screening and preliminary in vitro cardiac safety (hERG) assessment.
• Pharmacokinetics (PK) : Prove the core therapeutic hypothesis by experimentally confirming the molecule is not blood-brain barrier permeant using an in vitro model (e.g., PAMPA-BBB).
• CMC & IP : Enable all testing by executing the first multi-gram synthesis and use the resulting experimental data to strengthen the program’s intellectual property position.

An advanced (undisclosed) dual inhibitor is being developed as an antibody-drug conjugate (ADC) for the treatment of acute leukemia. The ADC is designed with a next-generation dual action inhibitor payload that binds with 35 times greater potency than revumenib, aiming for superior efficacy in one key target. Through a partnership with a specialized antibody company, this highly potent payload will be delivered directly to the bone marrow, the “nursery” of leukemia cells. This targeted delivery strategy is hypothesized to minimize off-target liabilities and systemic toxicity, potentially enabling a broader treatment population beyond specific (KMT2A) and (NPM1) mutations, and ultimately leading to improved patient outcomes by precisely eliminating leukemia at its source.

Next Steps:

• Validate On-Target ADC Activity: Confirm successful antibody targeting, internalization, and intracellular payload release in relevant leukemia cell lines.
• Demonstrate In Vivo Proof-of-Concept: Establish superior anti-leukemia efficacy and survival benefit in patient-derived xenograft (PDX) animal models.
• Define Therapeutic Window: Conduct initial in vivo toxicology and pharmacokinetic (PK) studies to establish a preliminary safety margin and dosing strategy.
• Confirm Target Patient Population: Verify ADC effectiveness across a panel of diverse leukemia subtypes to define the intended clinical population beyond known mutations.
• Develop a Scalable Manufacturing Process: Secure a consistent and reproducible Chemistry, Manufacturing, and Controls (CMC) process for the antibody, payload, and final ADC.
• Align with Regulatory Agencies: Initiate a pre-IND (Investigational New Drug) meeting with the FDA to get crucial feedback on the preclinical data package and clinical trial design.