Dialogues on AI Digital Pathology

We’re very happy to bring you Part 4 that will wrap up the Special Episode podcast of Dialogues on AI Digital Pathology! In this Part 4 podcast, our guests – KOL Hepatologists and Pharma Thought Leaders in NASH – continue their discussions in response to questions by Pharma companies and clinical investigators. Find out their views on how AI Digital Pathology (AI-DP) can effectively impact NASH drug development, preclinical studies and clinical practice with granular histopathological data.  Please click here to view the Key Takeaways for Part 4 or go to https://tinyurl.com/b4ttvb4s. Our thanks and appreciation to our guest KOL hepatologists, thought leaders in NASH pharma and moderator! Guests Prof. Stephen Harrison (Pinnacle Clinical Research) Prof. Vlad Ratziu (Sorbonne University Pitié-Salpêtrière Hospital) Dr. Judith Ertle (Boehringer Ingelheim) Dr. Karin Conde-Knape (Novo Nordisk) Absent with Apologies - Ms. Kitty Yale (Akero Therapeutics) Moderator  Dr. Nikolai Naoumov (Novartis)

Dialogues on AI Digital Pathology is releasing Part 4 of its Special Episode real soon! Listen to this trailer for a snippet of Part 4 with our guests, KOL hepatologists and Pharma Thought Leaders in NASH, as they continue their discussions on AI Digital Pathology (AI-DP), and the application and future of AI-DP in clinical practice, liver research, and drug development.  Guests Prof. Stephen Harrison, Medical Director, Pinnacle Clinical Research Prof. Vlad Ratziu, Professor of Hepatology, Sorbonne University and Pitié-Salpêtrière Hospital Dr. Judith Ertle, Senior Clinical Program Lead NASH, Boehringer Ingelheim Dr. Karin Conde-Knape, ‎Senior Vice President Global Drug Discovery, Novo Nordisk Absent with Apologies Ms. Kitty Yale, EVP and Chief Development Officer, Akero Therapeutics Moderator Dr. Nikolai Naoumov, Senior Adviser, Clinical Research and Drug Development in Liver Diseases, Novartis Do remember to Subscribe to our Podcast to receive updates on new episodes!

Guests Prof. Stephen Harrison (Pinnacle Clinical Research) Prof. Vlad Ratziu (Sorbonne University Pitié-Salpêtrière Hospital) Dr. Judith Ertle (Boehringer Ingelheim) Dr. Karin Conde-Knape (Novo Nordisk) Ms. Kitty Yale (Akero Therapeutics) Moderator  Dr. Nikolai Naoumov (Novartis) Key Takeaways 1) The innovation and qualities that AI Digital Pathology (AI-DP) brings to drug development can be described as a disruptive technology as it expands the knowledge of NASH pathobiology, introduces standardization and reproducibility on a fully quantitative scale, allows to better define a dose-response to compounds with different Mechanism of Action (MoA) and regression or progression of NASH disease. In addition, AI-DP has the potential to stabilize placebo response rates and provide a better understanding of how the drugs are working in dose-dependent responses.  2) AI digital pathology brings two key novelties: firstly, it provides better understanding of liver injury, both for the clinical practice and for clinical trials with a robust and reproducible reading of NASH features and avoids the intra- and inter-observer variabilities; secondly, at a discovery level, AI-DP uncovers new parameters and greater details that cannot be detected by the human eye. 3) The use of AI-DP is not intended to replace routine pathology review of liver biopsies. It augments the information from conventional pathology by providing a standardised reading, helps reducing the rate of screen-failures as well as ensuring a more precise, granular quantitation of treatment response. AI-DP will be particularly valuable in clinical trials involving patients with cirrhotic NASH (as they have a wide range of collagen deposition) by providing quantitative understanding of collagen dynamics within F4 stage and accurate assessment of treatment efficacy. 4) In repeated screen failure situations due to inter-observer variabilities, AI-DP can also increase the sensitivity in detecting changes in the early fibrosis stages (between F1 to F3) and is critical for producing an integrative assessment combining liver histology results with other investigations to guide patients’ eligibility for clinical trials.  5) To-date, the application of AI-DP has revealed fibrosis reduction in response to several investigational drugs with different MoA which have not reached >1 stage fibrosis improvement by the current NASH-CRN scoring system. More AI data are needed to show how different treatments are impacting liver histology, comparison between doses, fibrosis dynamics in F4 cirrhosis NASH and effect of different treatment durations. To use AI-DP routinely along with conventional assessment of liver histology, it is also necessary to define the variability of AI readings, reproducibility between different laboratories’ staining and establish the differences in AI algorithms by different providers.  6) FDA is data-driven and the accumulated data from the use of AI-DP in various NASH clinical trials will be welcomed by the FDA and other regulators. In Phase 2 trials - the greater granularity and full quantification of novel parameters, as secondary or exploratory end-points, if congruent with routine histology will be useful in gaining confidence in the MoA, dose selection, show differences between active arms and placebo, thus providing greater confidence in the effects of the investigational drug. At present, for Phase 3 and for approval, the regulators require the traditional histological surrogate end-points or hard clinical outcomes and for the regulators to consider implementing AI-DP would depend on further demonstration of AI-DP endpoints’ close association with clinical outcomes.

Our Special Episode conversation on AI Digital Pathology in NASH Drug Development continues (in Parts 3 and 4) with our guests, KOL hepatologists and Pharma Thought Leaders in NASH, as they respond to questions by Pharma companies and clinical investigators on how AI Digital Pathology (AI-DP) can augment clinical trial data and work alongside pathologists to detect granular information that could be pivotal for determining patient recruitment, staging and treatment responses. The full Part 3 podcast will be launched early next week, so click here to listen to the Trailer of Part 3! A huge Thank You to our Guests and Moderator for their kind participation and professional views spoken in this entire Special Episode! Guests Prof. Stephen Harrison, Medical Director, Pinnacle Clinical Research Prof. Vlad Ratziu, Professor of Hepatology, Sorbonne University and Pitié-Salpêtrière Hospital Dr. Judith Ertle, Senior Clinical Program Lead NASH, Boehringer Ingelheim Dr. Karin Conde-Knape, ‎Senior Vice President Global Drug Discovery, Novo Nordisk Ms. Kitty Yale, EVP and Chief Development Officer, Akero Therapeutics Moderator Dr. Nikolai Naoumov, Senior Adviser, Clinical Research and Drug Development in Liver Diseases, Novartis Do remember to Subscribe to our Podcast to receive updates on new episodes!

Our guest KOL liver pathologists continue their conversation from Part 1 following the FDA Webcast, by responding to more questions by Pharma companies and clinical investigators on how AI Digital Pathology (AI-DP) can aid pathologists with precise assessment to better interpret the disease biology of NASH.  We’d like to thank our Guests and Moderator for their kind participation and professional views! Prof. Pierre Bedossa Professor of Pathology at the University of Paris; Consultant in Liver Pathology at LIVERPAT, Paris, France Prof. Zachary Goodman Director of Hepatic Pathology Consultation and Research, Inova Fairfax Hospital, Falls Church, Virginia, USA Prof. David Kleiner Senior Research Physician and Chief of Post-mortem Section, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA Moderator Dr. Nikolai Naoumov Adviser for Clinical Research and Drug Development in Liver Diseases, Novartis Pharma AG Key Takeaways from the KOLs in this Special Episode (Part 2) - According to the KOLs, regression of disease is not well delineated or understood. AI-DP offers new insights into the biology of NASH and additional information especially in the identification of ballooned hepatocytes, quantification of peri-sinusoidal fibrosis, septa quantification and others. - In the assessment of disease biology, it was highlighted that AI-DP can identify morphological/pathological features that cannot be detected by the human eye. This is an area where AI-DP plays a complementary role by providing precise details on liver architecture and reproducible quantitation with new parameters. - It was stated that it is not appropriate to attempt to quantitate ratio of different patterns like F1 to F4 in a single specimen, as the pathology objective is to provide an integrated assessment. - It was recommended that the role of AI-DP and the information it provides be regarded as an aid to extend the outputs of pathologists. Instead of being perceived as a replacement of pathologists, AI-DP could be seamlessly integrated into the pathologists’ daily workflow. We hope that you will enjoy Part 1 and 2 of our Special Episode. Do remember to Subscribe to our Podcast to receive updates on new episodes!

Here's the Official Trailer for Part 2 of our Special Episode of Dialogues on AI Digital Pathology, which is coming up in a week! Listen to these sound bites from our guest KOL liver pathologists, Professor Pierre Bedossa, Professor Zachary Goodman, and Professor David Kleiner as they speak to our Moderator, Dr Nikolai Naoumov about AI digital pathology as a complementary tool for pathologists in interpreting the disease biology of NASH. This is a continuation from Part 1, where the KOLs commented on the key takeaways from the recent FDA webcast on NASH Drug Development, and questions from the industry on designing clinical trial strategies with AI digital pathology. Do listen to their conversation in Part 1 if you haven't! Guests Prof. Pierre Bedossa Professor of Pathology at the University of Paris; Consultant in Liver Pathology at LIVERPAT, Paris, France. Prof. Zachary Goodman Director of Hepatic Pathology Consultation and Research, Inova Fairfax Hospital, Falls Church, Virginia, USA. Prof. David Kleiner Senior Research Physician and Chief of Post-mortem Section, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA. Moderator Dr. Nikolai Naoumov Adviser for Clinical Research and Drug Development in Liver Diseases, Novartis Pharma AG

We’re very excited to bring you a Two-Part Special Episode of Dialogues on AI Digital Pathology!  Listen to our guests, KOL liver pathologists as they discuss the recent FDA Webcast on NASH drug development and utilization of AI digital pathology as potential clinical trial endpoints. Here’s Part 1, where the KOL liver pathologists will discuss key takeaways from the recent FDA Webcast on NASH Drug Development, and respond to questions sent in by Pharma companies and clinical investigators on potential clinical trial strategies using AI digital pathology following the Webcast.  Guests Prof. Pierre Bedossa Professor of Pathology at the University of Paris; Consultant in Liver Pathology at LIVERPAT, Paris, France. Prof. Zachary Goodman Director of Hepatic Pathology Consultation and Research, Inova Fairfax Hospital, Falls Church, Virginia, USA. Prof. David Kleiner Senior Research Physician and Chief of Post-mortem Section, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA. Moderator Dr. Nikolai Naoumov Adviser for Clinical Research and Drug Development in Liver Diseases, Novartis Pharma AG Key Takeaways from the KOLs in this Special Episode (Part 1) - It was suggested that the liver biopsy should undergo a quality check for adequate amount of tissue with a core length of 2cm. Digital-read of stained glass slides would be possible only with a high level of quality control and rigour in tissue preparation and staining. - For liver histology adjudication in clinical trials, it was suggested that two pathologists will be adequate to reach an agreement without a need for a third pathologist. In the event of a disagreement, a consensus among the two pathologists could be achieved through a mutual discussion. - AI digital pathology (AI-DP) could serve its purpose on two fronts during NASH clinical trials – to train younger pathologists in scoring/staging biopsies and aid expert pathologists in assessing borderline cases. - AI-DP could be useful as secondary endpoints in NASH clinical trials to augment semi-quantitative read. Especially for quantitative parameters that cannot be seen or detected by the human eye, AI-DP provides additional data possibly into the biology of response or regression. - For AI-DP to be considered as primary endpoints, more data is needed to show the magnitude of effect change that correlates to clinical outcomes. The data should come from longitudinal studies evaluating the natural history of NASH vs placebo.

We're commencing a two-part Special Episode of Dialogues on AI Digital Pathology! This episode brings together our guests, Key Opinion Leaders in liver pathology, who will be speaking about the key takeaways from the recent FDA webcast on NASH Drug Development, and responding to questions from the industry on designing clinical trial strategies with AI digital pathology. Here's a Trailer of Part 1 with snippets from Professor Pierre Bedossa, Professor Zachary Goodman, and Professor David Kleiner as they speak to our Moderator, Dr Nikolai Naoumov. Guests Prof. Pierre Bedossa Professor of Pathology at the University of Paris; Consultant in Liver Pathology at LIVERPAT, Paris, France. Prof. Zachary Goodman Director of Hepatic Pathology Consultation and Research, Inova Fairfax Hospital, Falls Church, Virginia, USA. Prof. David Kleiner Senior Research Physician and Chief of Post-mortem Section, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA. Moderator Dr. Nikolai Naoumov Adviser for Clinical Research and Drug Development in Liver Diseases, Novartis Pharma AG

In this episode*, we speak to Dr. Nikolai Naoumov, MD, PhD, FRCP, FRCPAth, FAASLD (Adviser for Clinical Research and Drug Development in Liver Diseases at Novartis, and physician-scientist and specialist in liver diseases). With his current focus on AI digital pathology in assessing liver biopsies, NASH combination therapies, HBV cure and liver fibrosis, Nikolai speaks to us on the changing landscape of drug development for NASH fuelled by advances in AI digital pathology. *This episode concludes Season 1 of Dialogues on AI Digital Pathology, and we will be commencing our second podcast season in mid-2021. Meanwhile, the webinars series on AI Digital Pathology in both NASH preclinical studies and clinical trials will commence in the first half of 2021. We’ll keep you posted on our webinars. Do remember to hit the Subscribe or Follow buttons at the following platforms to be updated when the Podcast’s Season 2 begins!

In the upcoming episode 4 of Dialogues on AI Digital Pathology, we speak to Dr. Nikolai Naoumov, MD, PhD, FRCP, FRCPAth, FAASLD (Adviser for Clinical Research and Drug Development in Liver Diseases at Novartis). Nikolai is a physician-scientist with a professional career combining academic research, clinical care and drug development – all focused on liver diseases. With his current work focusing on digital pathology with AI assessment of liver biopsies, NASH combination therapies, HBV cure and liver fibrosis, Nikolai shares his views about the advantages and impact of AI digital pathology in drug development efforts for NASH.