Core Insights - Annovis Bio, Inc. is making significant progress in its pivotal Phase 3 Alzheimer's study, with all 84 clinical sites fully activated and participant recruitment ongoing [6][2] - The company has strengthened its intellectual property by transferring all patents to a new crystalline form of its drug, buntanetap, and published pharmacokinetic data supporting this transition [2][6] - Recent biomarker findings from a Phase 2/3 study indicate meaningful reductions in inflammation and neurodegeneration, suggesting the drug's potential as a disease-modifying therapy [2][6] Clinical Highlights - The pivotal Phase 3 study for early Alzheimer's disease is on track, with robust participation and a screen failure rate within expected projections [6] - The first patients have completed the 6-month treatment period, marking a key milestone for upcoming symptomatic readouts [6] - Biomarker results from the Phase 2/3 trial show significant reductions in neuroinflammation and neurodegeneration in patients treated with buntanetap compared to placebo [6] Business Highlights - The company appointed Mark Guerin as CFO, enhancing its leadership team during a critical phase [2][6] - Annovis presented four scientific posters at the AAIC 2025 conference, showcasing progress in its Alzheimer's trial and pharmacokinetics of buntanetap [6] Financial Results - As of September 30, 2025, Annovis reported cash and cash equivalents of $15.3 million, an increase from $10.6 million at the end of 2024 [6] - Research and development expenses for Q3 2025 were $6.3 million, up from $2.7 million in Q3 2024 [6] - The net loss per common share for Q3 2025 was $0.37, a decrease from $0.97 in Q3 2024 [7][15]

Encaleret & ADH1 Overview - Encaleret is an investigational oral calcilytic drug being developed as a potential treatment for Autosomal Dominant Hypocalcemia Type 1 (ADH1)[35, 38] - ADH1 is caused by activating variants in the CASR gene, leading to dysregulation of calcium homeostasis, decreased blood calcium, and increased urinary calcium[16, 17] - Diagnosis of ADH1 requires genetic testing, but is often delayed with a median age of 25 years[23, 24] - Conventional therapy for ADH1, including calcium and activated vitamin D, does not correct the underlying pathophysiology and may worsen long-term complications[17, 27] Clinical Development & Results - Phase 2 study of encaleret in 13 ADH1 patients showed rapid and sustained normalization of serum calcium, urine calcium, and PTH levels over 42 months[49, 56, 57] - In the Phase 2 study, 69% of participants responded to encaleret, achieving both blood and urine calcium in the target range at Week 24[59] - Encaleret was generally well-tolerated over 42 months of outpatient administration in the Phase 2 study, with most Treatment-Emergent Adverse Events (TEAEs) being mild[54] - The CALIBRATE Phase 3 study of encaleret in ADH1 is ongoing, with topline results expected in Fall 2025[62, 63] Market Opportunity - The estimated prevalent population of ADH1 in the US is approximately 12,000 individuals, with 73% being symptomatic[72] - ADH1 is emerging as the leading isolated cause of nonsurgical hypoparathyroidism, accounting for approximately 20% of all cases[76, 78] - The company projects peak year sales of encaleret to be over $1 billion, drawing a comparison to the XLH market[73]