Revolixys (anivamersen/pegnivacogin) / AbbVie - LARVOL DELTA

ROS-scavenging ‘stealth’ polymer, poly(thioglycidyl glycerol)(PTGG), outperforms PEG in protein conjugates and nanocarriers, and enhances protein stability to environmental and biological stressors (ACS-Sp 2023) - "Poly(ethylene glycol)(PEG) is commonly used for extending plasma half-lives of biologics but has significant drawbacks; for example, immunogenicity has led to market withdrawal of peginesatide (Omontys), pegloticase (Krystexxa) and the cessation of pegnivacogin (Revolixys) trials, while dozens of other PEG formulations present antiPEG antibodies, accelerated blood clearance (ABC), infusion reactions and reduced efficacy overtime. B. Unlike with PEG, no anti-polymer antibodies were formed in PTGG/OVA treated mice."

LYZ

Accuracy of registrations between cone-beam computed tomography and conventional computed tomography images and dose mapping methods in RaySearch software for the bladder during brachytherapy of cervical cancer patients. (PubMed, J Contemp Brachytherapy) - "Cone-beam computed tomography (CBCT) images (BRT) were aligned with CT images (EBRT) using four registration Reg_1 (rigid), Reg_2a, Reg_2b (hybrid), and Reg_3 (biomechanical)...Satisfactory registration results of anatomical structures do not guarantee a correct mapping of primary BRT doses on the bladder delineated on CT images during EBRT. The results of dose transformation based on biomechanical registration had an error of less than 5% for only 50% of the observations."

Clinical • Journal • Cervical Cancer • Oncology • Solid Tumor

Accelerated FASTK mRNA degradation induced by oxidative stress is responsible for the destroyed myocardial mitochondrial gene expression and respiratory function in alcoholic cardiomyopathy. (PubMed, Redox Biol) - "Collectively, ROS-accelerated FASTK mRNA degradation via Reg1 underlies chronic ethanol ingestion-associated mitochondrial dysfunction and cardiomyopathy. Restoration of FASTK expression through genetic approaches might be a promising therapeutic strategy for ACM."

Journal • Cardiomyopathy • Cardiovascular • Fibrosis • Immunology • Metabolic Disorders • FAS

[VIRTUAL] Creating CT- and MRI-guided urethra planning-risk-volumes for urethra-sparing prostate stereotactic body radiotherapy (ASTRO 2020) - "MRI was first registered to the CT (reg1) using automated rigid registration of fiducial markers; u_MRI in this position was labelled uMRI_1... Three-quarters of potential urethra variability on CT and MRI are included in an A-P 3 mm PRV around a catheter. Additional uniform, or A-P, uPRV expansions for urethral protection must be weighed against clinically relevant declines in PTV-uPRV."

Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • MRI

Widely used mutants of eiger, encoding the Drosophila Tumor Necrosis factor, carry additional mutations in the NimrodC1 phagocytosis receptor. (PubMed, G3 (Bethesda)) - "Genome sequencing uncovered mutations in the NimC1 coding region that are predicted to truncate the NimC1 protein before its transmembrane domain, and provide an explanation for the lack of NimC staining. The work that we report here demonstrates the presence of these NimC1 mutations in the widely used egr mutant, its sister allele, egr , and its parental strain, Regg1 As the egr and egr alleles have been used in numerous studies of immunity and cell death, it may be advisable to re-evaluate their associated phenotypes."

Journal • Oncology • TNFA

Proton Pump Inhibitor Use, Hypergastrinemia, and Gastric Carcinoids-What Is the Relationship? (PubMed, Int J Mol Sci) - "Overall, the risk of developing a g-NET appears greatest in patients who are more than 10 years on drug and on higher doses: those affected by chronic H. pylori gastritis and/or consequent gastric atrophy may also be at increased risk. While the overall risk of g-NETs induced by PPI therapy is undoubtedly low, it is real: this necessitates caution in using PPI therapy for long periods of time, particularly when initiated in young subjects."

Journal • Review • Gastric Cancer • Gastrointestinal Disorder • Immunology • Neuroendocrine Tumor • Oncology • Solid Tumor

Nucleic acid therapeutics: A focus on the development of aptamers. (PubMed, Expert Opin Drug Discov) - "The analysis of adverse effects observed with the pegnivacogin/anivamersen pair has highlighted the need to screen for pre-existing PEG antibodies in any clinical trial involving pegylated molecules. Surprisingly, and promisingly, the ability of nucleic acid therapeutics to breach the blood brain barrier seems achievable. The recognition of specific motifs, e.g. G-quadruplex in thrombin-binding aptamers, or a 'nucleation' zone while designing aptamer-antidote pairs, is likely to accelerate the discovery of therapeutically efficacious molecules."

Journal • F2

Non-immunological biomarkers for assessment of villous abnormalities in patients with celiac disease. (PubMed, J Gastroenterol Hepatol) - "Plasma citrulline  ≤ 30 μM/L is the most consistent, highly reproducible non-invasive biomarker that can predict the presence of villous abnormality and has the potential for avoiding duodenal biopsies in 78% patients suspected to have CeD."

Biomarker • Clinical • Journal • Celiac Disease • Immunology

Fine-Tuning of Energy Levels Regulates SUC2 via a SNF1-Dependent Feedback Loop. (PubMed, Front Physiol) - "Our systems biology approach proposes a negative feedback mechanism that works through the SNF1 complex and is controlled by energy levels. We further show that Reg1 likely is involved in the negative feedback mechanism."

Journal

Reg-1α Promotes Differentiation of Cortical Progenitors via Its N-Terminal Active Domain. (PubMed, Front Cell Dev Biol) - "Notably, the N-terminal soluble domain, but not the C-type lectin domain, is largely responsible for Reg-1α effects on cortical neuronal differentiation. We thus conclude that Reg-1α via its proteolytically generated N-terminal domain is required for basic development processes."

Journal • CNS Disorders • Targeted Protein Degradation

Spontaneous mutations that confer resistance to 2-deoxyglucose act through Hxk2 and Snf1 pathways to regulate gene expression and HXT endocytosis. (PubMed, PLoS Genet) - "Missense alleles of the HXK2, REG1, GLC7 and SNF1 genes were shown to confer significant resistance to 2-deoxyglucose and all had the potential to alter the activity and or target selection of the Snf1 kinase signaling pathway...These findings suggest the common adaptive response to 2DG is to limit the magnitude of the response. Genetic studies of 2DG resistance using the dominant SNF1-G53R allele in cells that are genetically compromised in both the endocytosis and DOG pathways suggest that at least one more mechanism for conferring resistance to this glucose analog remains to be discovered."

Journal • Oncology

Amino acid starvation inhibits autophagy in lipid droplet-deficient cells through mitochondrial dysfunction. (PubMed, Biochem J) - "It can be pharmacologically induced by rapamycin even in the absence of lipid droplets. We correlate the autophagy failure with mitochondria aggregation and we show that amino acid starvation-induced autophagy is restored in lipid droplet-deficient yeast by increasing mitochondrial biomass physiologically (respiration) or genetically (REG1 deletion). Our results establish a new functional link between lipid droplets, ER and mitochondria during nitrogen starvation-induced autophagy."

Journal • Metabolic Disorders

REG01 Satellite Registration (ACOG 2020) - No abstract available

"The revision of Reg.1/2005 provides the @EU_Commission with the opportunity to shift to meat/carcass/genetic material intra- and extra-EU trade. For #environmental, #AnimalWelfare and #publichealth reasons, it‘s time for the EU to #StopLiveTransport @SKyriakidesEU @EU_Health" (@FrancescaEG4A)

Regado Biosciences, Inc. enrolls first patient in phase 3 trial of REG1 (PRNewswire) - P3, N=13,200; Sponsor: Regado; REGULATE-PCI; "Regado Biosciences, Inc....announced the enrollment of the first patient in its REGULATE-PCI clinical trial....If successful, REGULATE-PCI will become the cornerstone of Regado's international new drug applications, expected to be filed in early 2016. The first of three key interim analyses in the trial will occur after enrollment of the first 1,000 patients and is expected to occur during the second quarter of 2014."

Anticipated NDA • Enrollment open • Acute Coronary Syndrome

Safety of very early sheath removal in patients treated with REG1 for acute coronary syndromes: Insights from the RADAR trial (J Invasive Cardiol) - P2, N=461; RADAR (NCT00932100); Sponsor: Regado; "There was no increase in median time from sheath removal to hemostasis (10 minutes [10, 20] and 10 minutes [10, 20]; P=.60); vascular accesssite bleeding complications were numerically fewer with REG1 than UFH (6% vs 11%; odds ratio [OR], 0.57; 95% CI, 0.27-1.18; P=.14)."

P2 data • Acute Coronary Syndrome

Regado Biosciences Inc (RGDO): An under $10 stock to transform, dominate ACS market (istockanalyst) - "...expect that REG1 will enter the market in 2017 and increase its market share to roughly 50% by 2022, in both NSTEMI-ACS and elective PCI patients and remain at that level through 2025...estimate initial launch of REG1 in the US in 2017 with $63M in estimated sales and $12.6M in REG1 royalties, assuming 20% royalty rate on future partnership....estimate US sales increasing to $611M in 2022..."

Stock price • Acute Coronary Syndrome

Impact of Motivational Interviewing on Self-Management in Patients With Type 2 Diabetes: Protocol for a Pilot Randomized Controlled Trial. (PubMed, JMIR Res Protoc) - "MI skills constitute the main strategies primary care nurses use on their patients. Having economical, simple, effective, and applicable techniques is essential for primary care professionals to help their patients change their lifestyle and improve their health. This study will provide scientific evidence on the effectiveness of MI. It will be performed with strict control over the data collection, ensuring the maintenance of therapeutic integrity."

Clinical • Interview • Journal

Anti-PEG Antibodies Inhibit the Anticoagulant Activity of PEGylated Aptamers. (PubMed, Cell Chem Biol) - "Moreover, in parallel studies we detected the presence of anti-PEG antibodies in nonhuman primates after a single administration of a PEGylated aptamer. Our results suggest that anti-PEG antibodies can limit the activity of PEGylated drugs and potentially compromise the activity of otherwise effective therapeutic agents."

Journal

To PEGylate or Not To PEGylate Therapeutics? (PubMed, Cell Chem Biol) - "In this issue of Cell Chemical Biology, Moreno et al. (2019) show anti-PEG antibodies may directly inhibit the activity of a PEGylated aptamer, RB006, both in vitro and in vivo, and the issues surrounding anti-PEG antibodies are discussed."

Journal

HIV prevention in men who have sex with men as inferred from their adherence to daily versus event-driven pre-exposure prophylaxis: Cross-over clinical trial (IAS-HIV 2019) - "...The trial was approved by the Joint CUHK-NTEC Clinical Research Ethics Committee (Ref:2016.719) and registered in Centre for Clinical Research and Biostatistics Clinical Trials Registry (Ref:CUHK_CCRB00606)... Daily and event-driven PrEP are similarly effective in achieving HIV protection in MSM. More effective protection could be achieved by advising MSM to adopt a regimen best suited to their behavioral lifestyles and sex-networking practices."

Clinical

Temporal dynamics of sexual behaviour among MSM on sequential daily and event-driven PrEP: Results from a crossover study (IAS-HIV 2019) - "...The study was approved by the Joint CUHK-NTEC Clinical Research Ethics Committee (Ref:2016.719) and registered in Centre for Clinical Research and Biostatistics Clinical Trials Registry (Ref:CUHK_CCRB00606)... PrEP per se did not modify MSM''s sexual behaviors. Reduction of sex networking occurred as a result of one''s knowledge of the baseline STI diagnosis; its monitoring appears to be important in affecting the dynamics of sexual behaviors. The implications of chemsex and PrEP status disclosure require further investigation."