PracticeUpdate Conference Series: IID 2018

Gene expression profiles of BLZ 100-positive and -negative tumors were substantially similar. Significantly, differ- entially expressed genes were cytosolic, extracellular, and cell death genes. These modest differences were correlated to a binary staining profile that suggested that BLZ 100 can discriminate between subtle molecular subtypes of basal cell carcinoma, and possibly, melanoma. Dr. Yamada concluded that the results support the safety of BLZ 100 at doses up to 18 mg. Ongoing studies are evaluating BLZ 100 safety and tissue tissue uptake in patients with other solid tumors. Over an extended treatment period from year 1 (week 52) to the end of year 5 (week 260), Psoriasis Area and Severity Index 75/90/100 response rates remained consistent. At year 1, 89% and 69%, respectively, of 168 patients with psoriasis achieved Psoriasis Area and Severity Index 75 and 90. This high rate was maintained at year 5 with 126 patients observed (89% and 66%, respectively). In addition, 44% of patients with psoriasis achieved completely clear skin (Psoriasis Area and Severity Index 100) at year 1. This rate was maintained to year 5 (41%). The safety profile continued to exhibit a favorable and consistent safety profile. In the present study, Dr. Yang and col- leagues used a novel flow cytometry protocol based on protein expression to analyze individual cell population activ- ity in skin disease. They characterized changes in immune cell populations in psoriatic lesions treated with secuki- numab, an interleukin 17A inhibitor. as an aid to surgery has tremendous potential… " " Successful surgery is a foundation of treatment and extent of resection is the single best predictor of survival in pediatric patients with brain tumors. I believe BLZ-100

An open-label phase I dose escalation and expansion study is evaluating BLZ- 100 in pediatric subjects with primary central nervous system tumors. The dose escalation part of the study has enrolled 15 pediatric patients at five prespecified dose levels to evaluate the safety and tolerability of BLZ-100 and provide clin- ical proof of principle data for BLZ-100 to detect tumors in pediatric subjects. The dose expansion part of the study is ongoing. Lead investigator Sarah Leary, MD, of Seattle Children’s Hospital, said, in a press

release, “We are continually inspired by our pediatric patients and their families, and aim to provide the best outcomes possible for these children.” She continued, “Successful surgery is a foundation of treatment and extent of resection is the single best predictor of survival in pediatric patients with brain tumors. I believe BLZ-100 as an aid to surgery has tremendous potential and look forward to further clinical testing in the pediatric population.”

www.practiceupdate.com/c/68650

" From weeks 0–12, the percentage of interleukin 17-expressing CD4-positive T effector cells in lesional skin decreased from 11.6% to 5.8%, vs a baseline percentage of 7.5% in healthy controls. "

Lesional skin biopsies of 11 patients with psoriasis were obtained at weeks 0, 2, 4, and 12 of secukinumab treatment. They were analyzed via flow cytometry and compared to healthy control skin. At week 12, mean Psoriasis Area and Severity Index improvement form week 0 of treatment was 87.1%, with 100% of patients achieving at least 75% improve- ment in mean Psoriasis Area and Severity Index. From weeks 0–12, the percentage of interleukin 17-expressing CD4-positive T effector cells in lesional skin decreased from 11.6% to 5.8%, vs a baseline percent- age of 7.5% in healthy controls. The percentage of interleukin 17-express- ing CD8-positive T cells decreased from 13.5% to 7.6%, vs 2.0% in controls.

The percentage of CD4-positive Treg cell-expressing interleukin 17 decreased from 3.6% to 0.9%, vs to 1.6% among controls. Dr. Yang concluded that secukinumab treatment reduced the percentage of interleukin 17-expressing immune cells greatly in lesioned skin. The proportion of interleukin 17-expressing CD4-positive T effector and Treg cells decreased to levels similar to or below that of healthy controls. Not only CD4-positive Th17 cells, but also CD8- and CD4-positive Treg cells produce interleukin 17 in psoriasis. Secukinumab reduces these significantly.

www.practiceupdate.com/c/68649

15 IID 2018 • PRACTICEUPDATE CONFERENCE SERIES

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