silatecan (AR-67) / Vivacitas - LARVOL DELTA

Phase 2 safety and efficacy of AR-67 (7-t-butyldimethylsiltyl-10-hydroxycamptothecin) in patients with recurrent Glioblastoma Multiforme (GBM) or Gliosarcoma (SNO 2019) - "Cohort 1 patients (N=31/46 enrolled) had not received (or had not recently failed) bevacizumab. AR-67 was well tolerated and exhibited a safety profile consistent with or better than currently approved camptothecins. 6/30 treated patients in Cohort 1 and 2/13 patients in Cohort 2 achieved the primary endpoints of 6- and 2-month PFS, respectively. PR was the best overall response in 3/45 treated patients and SD was the best overall response in 7/45 patients."

Clinical • P2 data

Vivacitas Oncology to Present a Poster on AR-67 at the 3rd Annual Glioblastoma Drug Development Summit (GlobeNewswire) - "Vivacitas Oncology, Inc...will be attending and presenting a poster on its lead asset, AR-67 at the 3rd Annual Glioblastoma Drug Development Summit, a virtual event held from January 18th to 20th, 2022. The Glioblastoma Drug Development Summit is the only industry-led forum for large pharma, biotech, and academic key opinion leaders to unite under the common goal of accelerating the practical translation and clinical development of meaningful therapies for the treatment of glioblastoma. Vivacitas will be presenting a poster on its lead compound, AR-67, a highly potent and novel lipophilic small molecule compound, in a retrospective response evaluation of AR-67 from a Phase II recurrent Glioblastoma ('reGBM') trial by IAG's Artificial Intelligence ('AI')-assisted tumor volumetric estimation."

P2 data • Glioblastoma • Oncology

Vivacitas Oncology, Inc. to Present on AR-67 at the Annual 5th Meridian Clinical Trials Conference (GlobeNewswire) - “Vivacitas Oncology, Inc….will present its lead development candidate, AR-67, at this year's 5th Meridian Clinical Trials (MCT) conference, Nov. 22-23, 2021, via their online platform."

Clinical data • Brain Cancer • CNS Tumor • Glioblastoma • Oncology

Response evaluation of AR-67 from a Phase-2 recurrent Glioblastoma trial by Artificial Intelligence assisted tumor volumetric estimation: comparison with the sum of the perpendicular diameters product (SNO 2021) - "This is particularly true for measuring large lesions, and may also allow for more accurately differentiating between pseudo- and true disease progression. The data included eight patients’ MRI images from a Phase-2 reGBM study, showing that five patients achieved the primary end-point of six months Progression-Free Survival, suggesting AR-67’s therapeutic potential."

P2 data • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • MRI

Vivacitas Oncology and IAG Partner to Integrate Novel Imaging Markers in the Development of AR-67 in Recurrent Glioblastoma Patients (Issuer Direct) - “Vivacitas Oncology…and Image Analysis Group…are collaborating to apply Artificial Intelligence (AI) technology and advanced imaging strategies to further the development of AR-67, a third generation Camptothecin, in patients with recurrent glioblastoma multiforme (reGBM).”

Licensing / partnership • Brain Cancer • CNS Tumor • Glioma • Gliosarcoma • Oncology

Second Report of Chronic Granulomatous Disease in Jordan: Clinical and Genetic Description of 31 Patients From 21 Different Families, Including Families From Lybia and Iraq. (PubMed, Front Immunol) - "AR67 CGD and AR22 CGD appeared to be the most frequently found sub-types but also the most severe clinical forms compared to AR47 CGD. As a geographical clustering of 11 patients from eight Jordanian families exhibited the c.1171_1175delAAGCT mutation in NCF2, segregation analysis with nine polymorphic markers overlapping NCF2 indicates that a common ancestor has arisen ~1,075 years ago."

Clinical • Journal • Immunology • Primary Immunodeficiency

Platelet Endothelial Cell Adhesion Molecule-1 Gene Polymorphisms are Associated with Coronary Artery Lesions in the Chronic Stage of Kawasaki Disease. (PubMed) - Acta Cardiol Sin - "The haplotype of platelet endothelial cell adhesion molecule-1 Leu-Ser-Arg might be associated with the increased platelet counts and the following risk of chronic coronary artery lesions in a dominant manner in Kawasaki disease."

Journal • Biosimilar • Cardiovascular • Heart Failure

A Pilot Study Assessing the Impact of 3-D Printed Models of Aortic Aneurysms on Management Decisions in EVAR Planning. (PubMed) - Vasc Endovascular Surg - "The 3-D printed models may be potentially useful in planning cases with EVAR. It is a paradigm that warrants further investigation."

Journal • Biosimilar

Purinergic Signaling as a Regulator of Th17 Cell Plasticity. (PubMed) - "Remarkably, we show that CD39 activity regulates the conversion of Th17 cells to IL-10-producing cells in vitro, which is abrogated in the presence of ATP and the CD39-specific inhibitor ARL67156. All these data suggest that CD39 expression by Th17 cells allows the depletion of ATP and is crucial for IL-10 production and survival during the resolution of intestinal inflammation."

Journal • Biosimilar • Immunology

Micrornas Mir-30b-5p, Mir-34a-5p, and Mir-431-3p Are Highly Expressed in the Plasma of Patients with Ankylosing Spondylitis (ACR-ARHP 2016) - " This study demonstrates that specific miRNAs are differentially expressed between AS patients and healthy subjects and thus can be developed as potential biomarkers. This work was supported in part by USPHS/NIH grants (RO1 AT007373, RO1 AT005520, RO1 AR067056, R21 AR064890) and funds from North East Ohio Medical University to TMH."

Biomarker • Clinical • Ankylosing Spondylitis • Biosimilar • Gene Therapies • Immunology • Lupus • Psoriasis • Rheumatoid Arthritis

Recovery of the poisoned topoisomerase II for DNA religation: coordinated motion of the cleavage core revealed with the microsecond atomistic simulation. (PubMed) - "We observed a nearly vectorial transition in the recovery of the enzyme and identified the previously uncharacterized roles of Asn508 and Arg677 in DNA rejoining. Our findings delineate the dynamic mechanism of the DNA religation conducted by type II topoisomerases."

Journal • Biosimilar • Oncology

Population pharmacokinetic analysis of AR-67, a lactone stable camptothecin analogue, in cancer patients with solid tumors. (PubMed, Invest New Drugs) - "Exposure PK metrics C and AUC were shown to predict hematological toxicity. Further efforts to identify clinically relevant determinants of AR-67 disposition and effects in a larger patient population are warranted."

Clinical • Journal • PK/PD data • Hematological Disorders • Leukopenia • Oncology • Thrombocytopenia

Efficient removal of dyes using carboxymethyl cellulose/alginate/polyvinyl alcohol/rice husk composite: Adsorption/desorption, kinetics and recycling studies. (PubMed, Int J Biol Macromol) - "In present study, the adsorption-desorption behavior of Direct Orange-26 (DO-26), Direct Red-31 (DR-31), Direct Blue-67 (DB-67) and Ever direct Orange-3GL (EDO-3) dyes on to native modified rice husk (MRH), polyvinyl alcohol (PVA), carboxymethyl cellulose (CMC) and alginate (ALG) immobilized biomasses were investigated under different experimental conditions...The involvement of -OH (hydroxyl), -COOH (carboxylic) and -NH (amino) groups in the adsorption of dyes onto biomasses was shown by FTIR analysis. Studies exhibited that of all the biomasses employed, the MRH is the excellent potential candidate for the dyes degradation from textile effluents."

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Pharmacokinetic Modeling of the Blood-Stable Camptothecin Analogue AR-67 in Two Different Formulations. (PubMed, Biopharm Drug Dispos) - "AR-67 in the SBE-β-CD formulation exhibited dose linearity following both oral and intravenous administration. Our studies indicate the SBE-β-CD is a viable alternative to Cremophor EL as a pharmaceutical excipient for formulating AR-67."

Journal • PK/PD data

Formulation, Evaluation and release rate characteristics of medicated jelly of vitamin C. (PubMed, Pak J Pharm Sci) - "All the medicated jellies were found to remain stable stored for 60 days at different temperatures. The present study revealed that medicated jellies of vitamin C could be employed orally in an effective form as an alternative solid oral dosage form for special population such as pediatrics, geriatrics and patients with dysphagia."

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