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BLOG: The Heterogeneity Challenges in Understanding Patient Treatment Response

Heterogeneity is defined as the state of diverseness. Although greatly appreciated as a unique part of human nature, it leads to immense unpredictability when treating human disease. Inter-patient heterogeneity is well studied where each patient responds differently to a particular therapy. However, intra-patient heterogeneity is under-recognized where individual disease sites within a patient respond differently to the same therapy at different times.

Intra-patient heterogeneity can be broken down into two components, spatial and temporal. Spatial heterogeneity is observed when the response to a particular treatment varies based on the location of the disease sites. Temporal heterogeneity is observed when the same disease site responds differently to the same treatment at various times during a treatment cycle. A full grasp of intra-patient heterogeneity requires a tool that provides a comprehensive insight into a patient’s spatial and temporal response dynamics. There are two distinct challenges in acquiring that insight. The first challenge is quantifying the spatial and temporal heterogeneity in every patient. The second challenge is deciphering the manner in which clinicians can use that information to improve patient outcome or analyze the efficacy of drug candidates in clinical trials.

AIQ Solutions has a software technology platform, driven by artificial intelligence, that can robustly quantify spatiotemporal heterogeneity of treatment response and pharmacodynamic effects. This technology easily addresses the first challenge as it utilizes scans of different imagining modalities and tracers to measure treatment response in every disease site within a patient, at specific times. This measurement is precise and can be viewed for every single disease lesion over time in bone as well as soft tissue. The technology not only monitors the number and volume of each disease lesion at different time intervals, but it also classifies each lesion as responsive, stable, or resistant at each time point.

Multiple studies have demonstrated that resistant lesions have a larger impact on disease burden than responsive lesions, where only a few resistant lesions can drive patient outcome. Therefore, the importance of early identification of resistant lesions is self-evident. To address the second challenge, AIQ technology identifies resistant lesions and pinpoints their exact loci. This has two benefits for a clinician. One, is the ability to consider alternative localized treatment, specific to those resistant lesions. Two, is the ability to perform directed biopsies to discover the biological drivers for the resistance through a genomic and/or proteomic analysis. Studies have also shown that early changes in disease burden can predict long term response to therapy. To that end, AIQ technology uses quantification of heterogeneity in treatment response and pharmacodynamic effects to track disease burden and provides clinicians early access to that important information. The technology takes this premise to the next level with its novel scoring system to further address the second challenge. The AIQ Score* allows for early categorization of a patient as an optimal or a suboptimal responder, hence delivering applicable and actionable intelligence to clinicians. This categorization is made possible through a complex algorithm that includes the heterogeneity in treatment response and pharmacodynamic effects for ALL disease lesions, which differentiates it from other current methodologies.

AIQ’s exclusive technology addresses the heterogeneity challenges in understanding patient treatment response. The technology empowers clinicians to quickly categorize and predict optimal and suboptimal responders. The technology can be used to refine patient inclusion and exclusion criteria as well as identify patients better suited for alternate therapies. The technology also enables the discovery of biological drivers for resistance. AIQ technology provides the necessary critical information that can help improve patient outcome and evaluate efficacy in clinical trials….no imaging analysis is complete without AIQ!

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Alessandra Cesano, MD, PhD
Chief Medical Officer, ESSA Pharma

Alessandra Cesano, MD, PhD is the Chief Medical Officer at ESSA Pharma since July 2019. Previously she has been the Chief Medical Officer of NanoString Inc from July 2015 until June 2019 where she focused in the development of translational and diagnostic multi-plexed assays for the characterization and measurement of mechanisms of immune response/resistance. Prior to joining NanoString, Dr. Cesano was Chief Medical Officer at Cleave Biosciences, Inc. and before then she served as Chief Medical Officer and Chief Operations Officer at Nodality, Inc., where she built and led the R and D group, while providing the overall clinical vision for the organization. Between 1998 and 2008, Dr. Cesano held various management positions at Amgen, Biogen Idec and SmithKline Beecham Pharmaceuticals, where she helped to advance various oncology drugs through late stage development and FDA approvals. Early in her professional career Dr. Cesano spent 12 years conducting research in tumor immunology, including nine years at the Wistar Institute, an NCI Basic Cancer Center connected with the University of Pennsylvania. She also holds membership in several professional and scientific societies including ASCO, ESMO, ASH, EHA, AACR and SITC. In the latter she serves as co-chair in the SITC Industry Committee, Associate Editor for the Biomarker section of JITC and is an active member of the SITC Biomarker Working Group. Over her careers she has been an author on over 140 publications. Dr. Cesano received an MD summa cum laude, a Board Certification in Oncology and a PhD in Tumor Immunology from the University of Turin.

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Giovanni Selvaggi, PhD
Chief Medical Officer, Xcovery

Dr. Selvaggi held global positions of increasing responsibility in clinical development at various global pharmaceutical companies prior to joining Xcovery in March 2019. Dr. Selvaggi joined the pharmaceutical industry in 2010 as Medical Director in the MAGE-A3 lung cancer vaccine program at GSK. He then played an instrumental role in the successful development and approval of ceritinib (Zykadia) in ALK-translocated NSCLC at Novartis in 2013. Most recently, Dr. Selvaggi was part of the immunotherapy team at Bristol-Myers Squibb, serving as a program lead in thoracic malignancies, with a focus on SCLC and mesothelioma, leading to the approval of nivolumab (Opdivo) in third line SCLC indication with NDA in 2018. Dr. Selvaggi received his medical degree at the University of Torino School of Medicine, in Torino, Italy, in 1992 and served as staff physician of thoracic oncology at the University Hospital in Torino, participating in several clinical trials in lung cancer and mesothelioma over a span of 16 years.

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Eric Horler
President and Chief Executive Officer, AIQ Solutions

Eric Horler joined AIQ Solutions as its first President and CEO in September 2018. He has led AIQ through two rounds of equity financing, team construction, product commercialization, and international expansion. Before joining the AIQ team, Eric was President and CEO of Swallow Solutions LLC, a medical device start-up with both therapeutic devices and functional beverages for dysphagia patients. Before that, Eric was General Manager, Premium Anesthesia and Respiratory Care at GE Healthcare. While at GEHC, Eric was responsible for a $220 million global business and a large team spread over three continents. He has also held a series of marketing and business development roles at Baxter Healthcare, including Director of Renal Products and Services for the Latin America region. Eric has a B.S. in Chemical Engineering from Rice University and both an MBA and Master of Engineering Management degrees from the Kellogg School of Business. He lives in Madison with his wife and two children.

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Information on this page is intended for research use only. Applications and/or claims listed are not currently cleared for use in treatment of patients.