Core Viewpoint - Sanofi's Teizeild (teplizumab) has received approval from the European Commission to delay the onset of stage 3 type 1 diabetes (T1D) in patients aged eight years and older with stage 2 T1D, marking a significant advancement in the treatment of this autoimmune disease [1][2][8] Group 1: Approval and Study Results - Teizeild is the first disease-modifying therapy for T1D approved in the EU, based on the TN-10 phase 2 study, which showed a median delay of two years in the onset of stage 3 T1D compared to placebo [1][8] - In the TN-10 study, 57% of patients in the Teizeild group remained in stage 2 T1D at the end of the study, compared to 28% in the placebo group [2] - The median time to diagnosis of stage 3 T1D was 48.4 months for the Teizeild group versus 24.4 months for the placebo group, with a hazard ratio of 0.41 indicating a significant reduction in risk [6] Group 2: Safety and Efficacy - The safety profile of Teizeild was consistent with previous studies, with the most common adverse events being transient lymphopenia (75% of participants) and rash (36% of participants) [2][6] - The TN-10 study included 76 participants aged eight to 45, randomized to receive either Teizeild or placebo, focusing on the delay of stage 3 T1D [4][5] Group 3: Regulatory Status and Future Directions - Teizeild is already approved in multiple countries, including the US, UK, China, and Canada, for the same indication, with ongoing regulatory reviews in other regions [3][7] - Sanofi has decided not to pursue a second application for Teizeild in recently diagnosed stage 3 T1D at this time, with next steps under evaluation [3]

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]