Day Two

• Harnessing the “Bio-Blueprint” via MYO Technology™ by utilizing proprietary DNAencoded plasmid delivery to transform skeletal muscle or subcutaneous adipocytes into a sustainable bio-factory, enabling the continuous, endogenous production of therapeutic proteins that bypass the pharmacokinetic “spikes” and “troughs” of traditional biologics
• Engineering long-acting metabolic resilience by deploying the LNP-based Prometheus system to deliver genetic instructions for multi-pathway modulators (such as EX4 or modified GLP-1/GIP) that remain localized and active for over six months, providing a “one-and-done” metabolic reset that significantly improves liver and pancreatic function without systemic toxicity
• Pioneering a “Zero-Adherence” Treatment Framework by eliminating the psychological and physical hurdles of “jab fatigue” by replacing weekly or daily injections with ultra-long-acting DNA therapeutics, ensuring real-world efficacy that matches clinical trial performance by removing patient adherence from the therapeutic equation

• Harnessing in-silico molecular design to engineer high-potency thermogenic candidates with superior target specificity, ensuring the activation of fat-burning pathways while avoiding the off-target cardiovascular effects common in historical thermogenic attempts
• Validating novel lipid-degradation variants through metagenomic adipocyte analysis and in-vitro lipolysis assays, providing a data-driven proof-of-concept for direct adipose tissue reduction independent of caloric intake
• Optimizing specificity for adipose tissue metabolism to inhibit lipid accumulation at the cellular level, delivering a durable metabolic solution that targets the root cause of obesity-related comorbidities

• Utilizing a transient polydopamine polymer coating to precisely block nutrient absorption in the duodenum for 24 hours, providing a non-systemic “take-anytime” oral convenience that triggers the body’s natural satiety cascade (GLP-1 and PYY) without the gastrointestinal side effects of exogenous peptide hormones
• Matching the 1% weekly weight-loss efficacy observed in preclinical models while achieving 100% preservation of lean muscle mass, offering a potent oral alternative that solves the “muscle-wasting” crisis of current injectables and could capture significant market share among patients seeking “healthy” functional weight loss
• Optimizing the metabolic environment of the small intestine to ensure steady-state glycemic control and appetite suppression, bypassing the “peaks and troughs” of injectable delivery and establishing a sustainable, low-cost maintenance therapy that prevents the biological “rebound” of weight regain

• All currently approved obesity drugs act by reducing food intake, causing a drop in metabolic rate (thermogenesis) • To achieve durable weight control and cardiometabolic benefits, agents that increase metabolic rate are needed to complement existing therapies
• Energesis Pharmaceuticals is developing oral small molecules and proteins that boost energy expenditure – the missing therapeutic dimension in obesity treatment
• Energesis uses a proprietary platform of human brown/beige/brite adipocyte adult stem cells to discover novel targets and develop therapies that increase the amount of brown fat and induce long-term weight loss
• Our drug candidates drive robust fat-specific weight loss – without muscle loss – and show strong synergy with GLP-1 agents

• Utilizing an Activin IIA/B bispecific antibody to lift the “biological brake” on muscle growth, addressing the critical limitation of current GLP-1s where up to 40% of weight loss is derived from lean muscle mass
• Matching the fat-loss potency of high-dose injectables while simultaneously driving muscle hypertrophy, offering a “best-in-class” body composition profile that accelerates adipose-specific weight loss and boosts basal energy expenditure
• Optimizing the pharmacokinetic profile of lead candidate SPX-001 and its GLP-1 conjugates to ensure stable, monthly dosing that preserves metabolic fitness, prevents weight regain “rebound,” and provides a durable foundation for long-term cardiometabolic health

Participate in an interactive, discussion-led session with industry experts to exchange diverse perspectives and solve complex industry challenges within the obesity drug development space without formal presentations.

• Standardizing “High-Quality Weight Loss” (HQWL) indices as a core regulatory endpoint to move beyond “undifferentiated-mass-reduction” as the gold standard for adult and geriatric success, leading to a more nuanced and accurate reflection of metabolic health across the aging spectrum
• Evaluating the ethics and logistics of “metabolic-reset” benchmarks to track the off-treatment persistence of weight stability, building the robust safety database required for universal payer approval and long-term chronic management
• Integrating objective functional outcome assessments (FOAs) regarding “physical-resilience” and “metabolic-reserve” to capture the human impact of treatment, ensuring that drug development remains focused on functional longevity rather than just cosmetic weight loss

• Harnessing the power of RJx-01 to target mitochondrial health, autophagy, and neuromuscular junction stability, providing a multimodal defense against the muscle strength loss often triggered by rapid weight loss
• Utilizing clinical proof-of-mechanism data that demonstrates significant improvements in muscle strength recovery and fatigue resistance in human subjects, ensuring muscle protection
• Implementing synergistic clinical development with GLP-1 agonists to decouple muscle strength loss from fat loss, ultimately delivering a superior “high-quality” weight loss profile that improves long-term patient mobility and clinical outcomes

• Engineering next-generation small-molecule GLP-1 platforms to bypass the gastric proteolytic barrier, utilizing high-potency synthetic chemistry to deliver therapeutic concentrations that achieve weight-loss efficacy comparable to high-dose injectables (~9.7% reduction in 16 weeks) without the need for complex peptide absorption enhancers
• Implementing an “Oral-First” clinical strategy where patients bypass injectable induction entirely or transition to a long-term oral maintenance continuum, allowing companies to protect market share by offering highly tolerable, needle-free options for life-long weight stability and enhanced patient adherence
• Optimizing large-scale synthetic small-molecule manufacturing processes to bypass the global constraints of “cold-chain” distribution and specialized injection hardware, ensuring consistent drug availability to meet the projected 40%+ annual growth in global patient demand across U.S. and Asian markets

• Engineering next-generation MPC-inhibitor platforms to bypass the gastric proteolytic barrier, utilizing selective mitochondrial reprogramming to deliver metabolic benefits that achieve muscle-preserving efficacy comparable to lean-body controls while augmenting the weight-loss power of high-dose injectables
• Implementing a “Synergy-First” clinical strategy where patients utilize oral MPC inhibitors alongside injectable induction or as a long-term maintenance continuum, allowing companies to protect market share by offering metabolic-correcting, needle-free options for life-long weight stability and the prevention of post-treatment regain
• Optimizing large-scale synthetic small-molecule manufacturing processes to bypass the global constraints of “cold-chain” distribution and specialized injection hardware, ensuring consistent drug availability to meet the projected 40%+ annual growth in global patient demand for high-quality, body-composition-focused obesity care

• Synthesizing “injectable-strength” efficacy in oral formats to challenge the historical potency gap, evaluating how synthetic small-molecule platforms are bypassing gastric proteolytic barriers to achieve double-digit weight loss without the strict fasting requirements or the bioavailability limitations of traditional oral peptides
• Assessing the “persistence-pivot” from induction to maintenance, examining realworld adherence data to determine if the convenience of a needle-free daily pill can overcome the 90-day discontinuation risk prevalent in long-term injectable therapy, effectively securing a stable market share in the chronic management phase
• Strategizing for global scalability and payer alignment by leveraging the cost and distribution advantages of synthetic manufacturing to bypass the “cold-chain” bottleneck, ensuring that the next wave of metabolic innovation can meet the 85 million-patient demand while providing the robust evidence required for universal insurance coverage

• Prioritizing the resolution of co-morbidities such as MASH, CKD, and heart failure to move beyond BMI reduction as the sole metric of clinical success, establishing obesity drugs as essential “foundation therapies” for lifelong cardiometabolic protection
• Implementing evidence-based “step-down” protocols, transitioning patients from high-dose injectable peptides to low-dose oral small molecules or RNA-based silencers to suppress the biological “rebound effect” after reaching goal weight for durable weight stability and higher long-term therapy persistence
• Integrating longitudinal data on physical function, hospitalization rates, and employment status to quantify the total economic value of long-term obesity treatment, providing a robust scientific justification for expanded reimbursement and universal patient access across diverse socioeconomic populations