smart insulin (MK-2640) / Merck (MSD) - LARVOL DELTA

VOXEL-WISE FREE -WATER DIFFUSION AS A MARKER OF NEUROINFLAMAMTION AND CSF DISRUPTION IN ALZHEIMER'S DISEASE (ADPD 2025) - "Increased FVF Braak -like regions suggests that neuroinflammation in grey matter occurs secondary to tauopathy, not amyloidopathy. This non -invasive biomarker may help quantify AD neuroinflammation and what it responds to. Additionally, decreased FVF with i ncreased amyloid -β in the subarachnoid suggests CSF efflux failure, as CSF efflux into the superior sagittal sinus occurs via arachnoid granulations."

Alzheimer's Disease • CNS Disorders • Inflammation • Proteinopathy

KEYNOTE: The Risks and Rewards of Bootstrapping a Biotechnology Company (ACS-Sp 2024) - "This firsthand account delves into a CEO's journey employing these principles at SmartCells, Inc., a company built on MIT-licensed technology striving to pioneer the world's first glucose-responsive insulin for diabetes...Emphasis is placed on distinguishing frugality from miserliness, emphasizing that a company's fate hinges on judicious spending for maximum impact. The talk also underscores the significance of pivoting and highlights the resilience achieved during macro-environmental downturns, exemplified by SmartCells weathering the 2008-2009 financial crisis and Akston's adaptability in the post-Covid landscape."

CNS Disorders • Diabetes • Infectious Disease • Metabolic Disorders • Novel Coronavirus Disease • Oncology

In Silico Investigation of the Clinical Translatability of Competitive Clearance Glucose-Responsive Insulins. (PubMed, ACS Pharmacol Transl Sci) - "By scanning a large design space for CCM GRIs, we found that the mannose receptor physiology in humans remains limiting even for the most optimally designed candidate. Overall, we show that this computational approach is able to extract quantitative and mechanistic information of value from a posteriori analysis of preclinical and clinical data to assist future therapeutic discovery and development."

Journal

Acetalated dextran nanoparticles for rapid and glucose responsive insulin delivery (ACS-Fall 2017) - "Nanoparticles formulated with enzymes release 100% of encapsulated insulin within the first two hours in response to high concentrations of glucose (400 mg/dL). We further preconcentrate these nanoparticles by encapsulating them in alginate microgels to form an injectable subcutaneous depot for the modulation of glucose levels in vivo."

Preclinical • Biosimilar • Cardiovascular • Diabetes • Heart Failure • Metabolic Disorders • Renal Disease

"I'd settle for "Alexa, when will @Merck release results from their already completed clinical trial on smart insulin?" #diabetes"

Biosimilar • Diabetes • Metabolic Disorders

Ultrahigh performance liquid chromatography methods facilitate the development of glucose-responsive insulin therapeutics. (PubMed, Anal Bioanal Chem) - "The high specificity of the method allowed the separation of the degradation products from main peak, thus makes it suitable for stability monitoring. The major impurities in the DS were characterized by two-dimensional liquid chromatography-mass spectrometry (2D-LC-MS)."

Journal

A model-informed drug discovery and development (MID3) strategy for the novel glucose-responsive insulin MK-2640 enabled rapid decision making. (PubMed, Clin Pharmacol Ther) - "The development and application of in-silico modeling approaches by leveraging substantial published clinical insulin PKPD data and emerging (pre-)clinical data enabled rapid quantitative decision-making. Learnings can be applied to define PKPD properties of novel insulins that could become therapeutically meaningful for diabetic patients."

Journal

Clinical Evaluation of MK-2640: An Insulin Analog with Glucose-Responsive Properties. (PubMed, Clin Pharmacol Ther) - "In a randomized, 2-period crossover trial in 16 subjects with type 1 diabetes mellitus to evaluate glucose-responsiveness of i.v. administered MK-2640, we were unable to demonstrate a glucose-dependent change in MK-2640 clearance, though a significant glucose-dependent augmentation of glucose infusion rate was observed. These PK and PD data provide crucial insights into next steps for developing an insulin saccharide conjugate as a clinically effective glucose-responsive insulin analog."

Clinical • Journal