Core Viewpoint - The study reveals that macrophage PD-1 plays a critical role in the intersection of immune checkpoint blockade, energy expenditure, and metabolic dysfunction, providing a new theoretical basis for combating metabolic diseases induced by immune checkpoint inhibitors and high-fat diets [7]. Group 1: Research Findings - The research indicates that anti-PD-1 antibodies target macrophage PD-1, reducing energy expenditure without affecting food intake, thereby increasing susceptibility to obesity and systemic metabolic disorders induced by high-fat diets [4]. - The mechanism involves lipopolysaccharide (LPS) activating Unc-51-like autophagy activating kinase-1 (ULK1) in an mTOR-dependent manner, which phosphorylates PD-1 at the Thr250 site, preventing its ubiquitination and degradation by FBXO38 [4][8]. - Phosphorylated PD-1 interacts with IRE1α, inhibiting its phosphorylation and thereby suppressing inflammation driven by endoplasmic reticulum stress [4][8]. Group 2: Implications - The findings suggest that targeting IRE1α-XBP1 may offer a potential strategy to counteract metabolic dysfunction induced by immune checkpoint inhibitors [8]. - The study's insights into the dual role of macrophage PD-1 could lead to new therapeutic approaches for managing metabolic disorders associated with cancer treatments [7].

Financial Data and Key Metrics Changes - Revenue for Q3 2025 was $89.4 million, a decrease of 36.2% year-over-year, primarily due to a decrease in the number of active earning OPTAVIA coaches [16][21] - Gross profit decreased 41.2% year-over-year to $62.2 million, with a gross profit margin of 69.5%, down 590 basis points compared to the prior year [16][17] - Net loss for Q3 2025 was $2.3 million, or $0.21 loss per diluted share, compared to net income of $1.1 million, or $0.10 per share in the year earlier period [21] Business Line Data and Key Metrics Changes - Active earning OPTAVIA coaches decreased by 35% year-over-year, ending the quarter with approximately 19,500 coaches [16] - Average revenue per active earning OPTAVIA coach was $4,585, a year-over-year decrease of 1.9% [16] Market Data and Key Metrics Changes - The weight loss and wellness industry is experiencing a shift due to the rise of GLP-1 medications, which has changed consumer conversations around obesity and health [4][6] - Over 90% of US adults are metabolically unhealthy, presenting a significant opportunity for the company to redefine wellness [6] Company Strategy and Development Direction - The company is evolving from a weight loss focus to a broader emphasis on metabolic health, aiming to help clients not only lose weight but also improve their metabolic health [9][10] - Plans to launch significant product innovations using metabolic synchronization science and next-generation ingredients are underway, with expectations to bring new products to market next year [10][11] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the company's direction, highlighting a strong balance sheet with no debt and over $170 million in cash and investments [14][15] - The company anticipates a return to growth in 2025, with expectations for improved revenue per active earning coach in Q4 2025 [33][35] Other Important Information - The company is investing in digital platforms to enhance the coaching and client experience, providing better visibility into client progress and coach performance [12][13] - The Edge Leadership Development Program aims to improve coach productivity and stability, focusing on creating and duplicating high-performing Executive Directors [12][29] Q&A Session Summary Question: How will the company ensure consistent messaging among coaches regarding the new focus on metabolic dysfunction? - The company has conducted studies to show how its program can reverse metabolic dysfunction and is training coaches to communicate this effectively [23][24] Question: Can you elaborate on the Edge program and its incentive structure? - The Edge program focuses on creating and duplicating Executive Directors to improve productivity and revenue [29] Question: How does the company view the impact of economic softness on consumer spending for health programs? - Management noted that consumers continue to prioritize health spending, despite economic challenges, and the program remains relevant for those using GLP-1 drugs [36][37]