Scientists blend AI, 3D tissue imaging to identify aggressive prostate cancer

On June 21, 2022 Researchers at Case Western Reserve University and the University of Washington reported that expect to gain valuable new insights into highly aggressive prostate cancer by combining Artificial Intelligence (AI)-powered diagnostic imaging with three-dimensional (3D) tissue imaging (Press release, Case Western Reserve University, JUN 21, 2022, View Source [SID1234616172]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

This new AI-3D collaboration will provide a never-before-seen, expanded view and understanding of prostate cancer cells, made possible by a new approach called "light sheet microscopy," the researchers said. (Seen in photo above by Mark Stone/University of Washington).

Prostate cancer is the most common non-skin cancer in the United States. Doctors will diagnose one in eight men nationally with prostate cancer, and one in 40 will die from the disease, according to the Prostate Cancer Foundation.

Anant Madabhushi, director of the Center for Computational Imaging and Personalized Diagnostics at Case Western Reserve, and Jonathan Liu, a professor of mechanical engineering and bioengineering at the University of Washington (UW), are co-leaders in the new work and will split the funding. The National Cancer Institute (NCI), part of the National Institutes of Health, is supporting the research with a five-year, $3.13 million grant.

"This is an unprecedented meshing of the two most powerful technologies in this area," said Madabhushi, also the Donnell Institute Professor of Biomedical Engineering at the Case School of Engineering. "We’ll take the AI we’ve developed and, for the first time, be able to apply it to 3D tissue-imaging that the University of Washington excels in—and gain fine, granular detail."

Liu said collaboration with Madabhushi’s lab at Case Western Reserve was "an obvious and ideal choice since developing explainable AI methods will facilitate clinical adoption of a new imaging technology such as ours."

Identifying aggressive cancer
That fine detail will hopefully reveal even more information about how to identify which prostate cancer cases will be more aggressive in patients, Madabhushi said.

Knowing that could help clinicians determine who would benefit from surgery or radiation therapy—and which patients might be actively monitored instead, he said.

Researchers could also be laying the groundwork to develop what are called "pathomic-based classifiers" of disease outcome for a host of other cancers, Madabhushi said.

Pathomics refers to the application of computer vision and AI to extract a large number of features from tissue images using data-characterization algorithms. The features can then help uncover tumors and other characteristics usually invisible to the naked eye.

Madabhushi’s lab, established in 2012, has become a global leader in the field, specializing in the detection, diagnosis and characterization of various cancers and other diseases by meshing medical imaging, machine learning and AI.

Until now, researchers were using machine learning to focus entirely on two-dimensional images.

"We believe that we’ll be able to train our AI to interrogate 3D tissue images with the same success we have had with two-dimensional images," Madabhushi said. "But there are so many new possibilities for finding new information in 3D."

How 3D fits in
Liu and his team have developed a new, non-destructive method that images entire 3D biopsies instead of just a slice. This technique provides full-view images of the tissue and improved predictions of whether the patient had an aggressive cancer.

Jonathan Liu
"With the success of our open-top light-sheet microscopy technologies, an obvious next challenge to overcome was processing and analyzing the massive feature-rich 3D datasets that we were generating from clinical specimens," Liu said. He said collaborating with Madabhushi’s lab at Case Western Reserve was an "obvious and ideal choice, since developing explainable AI methods will facilitate clinical adoption of a new imaging technology such as ours."

"This (grant) will help us to scale up our existing collaboration to demonstrate that computational 3D pathology can improve critical treatment decisions for diverse populations of men with prostate cancer," Liu said.

The 3D images, of course, provide more information than a 2D image. In this case, that means details about the intricate tree-like structure of the glands throughout the tissue.

The advances in 3D technology made by Liu were detailed in a paper published in December 2021 in the journal Cancer Research. Madabushi and three others at Case Western Reserve contributed to the academic paper.

The UW researchers reported in that paper that the 3D features made it easier for a computer to identify which patients were more likely to have cancer return within five years.

Liu had said in a UW news blog that this "non-destructive 3D pathology" would become increasingly valuable in clinical decision-making, such as which patients would require more aggressive treatment or respond to certain drugs.

This new NCI grant complements work supported in an ongoing U.S. Department of Defense grant led by Madabhushi, with Liu as a collaborator. That project combines AI and light sheet-based 3D tissue-imaging technology for studying health disparities in prostate cancer.

Abcuro Appoints H. Jeffrey Wilkins, M.D., as Chief Medical Officer

On June 21, 2022 Abcuro, Inc., a clinical-stage biotechnology company developing therapies for the treatment of autoimmune diseases and cancer through precise modulation of cytotoxic T and NK cells, reported the appointment of H. Jeffrey Wilkins, M.D., as Chief Medical Officer (Press release, Abcuro, JUN 21, 2022, View Source [SID1234616124]). Dr. Wilkins brings deep experience in advancing clinical programs with a focus in immunology, rare diseases, and immuno-oncology.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Jeff’s impressive track record and extensive experience in immunology, immuno-oncology, and rare disease clinical development make him an ideal fit for Abcuro at this pivotal time in our evolution," said John Edwards, Executive Chairman of Abcuro. "We are excited to welcome Jeff to our leadership team and look forward to working closely with him as we advance ABC008 into a late-stage clinical trial in inclusion body myositis (IBM) and initiate a clinical trial in T cell large granular lymphocytic leukemia (T-LGLL) this year."

"I am eager to bring my clinical development expertise to a talented Abcuro team at such an important time. I am impressed with ABC008’s ability to selectively deplete highly cytotoxic T cells, an immune cell population driving tissue damage in several autoimmune disorders, most prominently in IBM," said Dr. Wilkins. "I look forward to the opportunity to guide the clinical advancement of ABC008 across multiple indications and to progress ABC015 towards the clinic – both of which represent novel approaches to address important medical needs."

Dr. Wilkins brings more than twenty years of clinical research experience to Abcuro, most recently serving as Chief Medical Officer of Avalo Therapeutics, where he was responsible for clinical development for programs in immuno-oncology, immunology and orphan disease. Previously, he held the position of Chief Medical Officer at Lycera, and Ceptaris Therapeutics, where he led clinical programs from IND Phase I trials to regulatory approval (including Valchlor). Prior to this, Dr. Wilkins was Vice President, Worldwide Clinical Research, Inflammation/Oncology at Cephalon, Inc., where he was responsible for clinical development, medical affairs, and business development efforts in both therapeutic areas. He joined Cephalon via its acquisition of Ception Therapeutics, and as Senior Vice President of Clinical Development, headed a successful program in eosinophilic asthma. Dr. Wilkins entered the pharmaceutical industry with GlaxoSmithKline, where he rose to become Vice President of Discovery Medicine for GSK’s Center of Excellence in External Drug Discovery. Dr. Wilkins received his M.D. from Temple University School of Medicine and his B.S. from Bucknell University.

About ABC008
ABC008 is a first-in-class anti-KLRG1 antibody capable of selectively depleting highly cytotoxic T cells, while sparing regulatory and central memory T cells. ABC008 has been designed to treat diseases mediated by highly cytotoxic T cells, including the autoimmune muscle disease inclusion body myositis (IBM), T cell large granular lymphocytic leukemia (T-LGLL), and other mature T cell malignancies. The US Food and Drug Administration (FDA) has granted Orphan Drug Designation to ABC008 for the treatment of IBM.

Nordic Nanovector to Seek Regulatory Feedback Following its Preliminary Review and Independent Data Evaluation of PARADIGME, its Phase 2b Trial with Betalutin® in R/R Follicular Lymphoma

On June 21, 2022 Nordic Nanovector ASA (OSE: NANOV) reported an update following its comprehensive review and independent data evaluation of PARADIGME, its ongoing Phase 2b trial of Betalutin (177Lu lilotomab satetraxetan) in 3rd-line relapsed rituximab/anti-CD20 refractory follicular lymphoma (3L R/R FL) (Press release, Nordic Nanovector, JUN 21, 2022, View Source [SID1234616140]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The independent expert panel reviewed the efficacy data collected to date. Betalutin, at the selected dose of 15 MBq/kg after a pre-dose of 40 mg lilotomab (40/15), has continued to display an attractive safety profile. While Betalutin showed signs of efficacy in this frail, elderly and difficult-to-treat patient population, the independent expert panel reported that the efficacy data are less promising than the data reported from the Phase 2a LYMRIT 37-01 trial. The Company intends to seek further guidance from the competent regulatory authorities, including the US Food and Drug Administration (FDA), regarding the way forward for PARADIGME. Pending regulatory feedback, the study will remain open for recruitment.

Following interaction with the regulatory authorities, the Company will provide an additional update, which is expected in August. The Company will not be commenting further until then. The Company’s Q2 results will be rescheduled to August and a new date will be confirmed in due course.

Given the continuing slow patient recruitment, Nordic Nanovector does now not expect to deliver preliminary top line data from PARADIGME in H2 2022.

U.S. Department of Defense Awards $5.1 Million to Humanetics Corporation for Continued Development of Radiation Countermeasure

On June 21, 2022 Minneapolis-based Humanetics Corporation (Humanetics) reported that it has entered into a new $5.1 million cooperative research agreement with the U.S. Department of Defense (DOD) to continue advanced development of BIO 300, a medical countermeasure to protect military personnel and first responders from the harm caused by radiation exposure (Press release, Humanetics, JUN 21, 2022, View Source [SID1234616156]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The new funding will be used to create, manufacture, and test a new formulation of BIO 300 that can be self-administered using an auto injector. Auto injectors are commonly used by the military to deliver fast-acting drugs such as atropine and naloxone. This new formulation of BIO 300 will complement the existing suite of oral formulations in the Humanetics portfolio that have been tested extensively and are in phase 2 trials. It is envisioned that the DOD would have access to both oral and auto injectable forms of BIO 300, which each have a unique use case.

"With the increasing potential for use of radiological or nuclear weaponry in the current global environment, especially with events in Ukraine, it’s a strategic imperative to protect our armed forces and first responders from radiation exposure and enable them to operate in areas of concern," said Ronald Zenk, President and CEO at Humanetics.

BIO 300’s radioprotective attributes were originally discovered by researchers within the DOD at the Armed Forces Radiobiology Research Institute. The drug was licensed to Humanetics Corporation, which is leading its advanced development toward FDA approval. In parallel to the drug’s development for use as a medical countermeasure, Humanetics is evaluating the drug in clinical trials to determine its potential to reduce the toxic side effects of radiation in cancer patients and to reduce lung damage in COVID-19 long-haulers.

"We are enthused and encouraged by the DOD’s continued investment in the development of BIO 300 as a medical countermeasure," said Zenk. "We see this drug not only providing protection for our warfighters, but also for our embassy personnel around the world and civilian populations who are at risk of radiation exposure from nuclear incidents and, furthermore, to improve the lives of cancer and COVID-19 patients."

Theralase® Phase Ib NMIBC Clinical Study Published

On June 21, 2022 Theralase Technologies Inc. ("Theralase" or the "Company") (TSXV: TLT) (OTCQB: TLTFF), a clinical stage pharmaceutical company dedicated to the research and development of light activated Photo Dynamic Compounds ("PDC") and their associated drug formulations intended to safely and effectively destroy various cancers reported that Theralase’s Phase Ib Non-Muscle Invasive Bladder Cancer ("NMIBC") clinical study ("Study") has been peer reviewed and published in the European Urology Open Science ("EUOS") Journal, Volume 41, July 2022 (Press release, Theralase, JUN 21, 2022, View Source [SID1234616125]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

According to EUOS’s website, EUOS is dedicated to the publication of high quality, innovative research that will benefit patients with urological conditions. EUOS covers research in the urological field, including clinical, basic and translational research.

The publication can be accessed online at no charge at:

https://www.sciencedirect.com/science/article/pii/S2666168322005900

The publication states, "Despite efforts to bring new treatment strategies forward for Bacillus Calmette Guérin ("BCG")-Unresponsive NMIBC, a clear consensus for a standard treatment other than radical cystectomy has yet to be established. An effective therapy that provides a high initial and durable responses remains an unmet need."

The publication is entitled, "A Phase 1b Clinical Study of Intravesical Photodynamic Therapy in Patients with Bacillus Calmette-Guérin–unresponsive Non–muscle-invasive Bladder Cancer" and states, "Although limited by the small sample size typically inherent in phase 1 trials, we feel that the photosensitizer TLD-1433 and the delivery device TLC-3200 hold promise for the treatment of NMIBC. In this study, Photo Dynamic Therapy ("PDT") was well tolerated and demonstrated safety and potential efficacy, thus warranting further study."

As a result, the Medical and Scientific Advisory Board ("MSAB") unanimously agreed that Theralase should further investigate PDT in a multi-site, pivotal Phase II NMIBC Clinical Study ("Study II"). Study II is currently underway at 5 Clinical Study Sites ("CSS") in Canada and 7 CSSs in the United States, with 41 patients treated to date.

Girish Kulkarni, M.D., Ph.D., lead principal investigator of the Study at the Divisions of Urology and Surgical Oncology, Department of Surgery, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada ("UHN") stated, "I am delighted that the high-quality research conducted at UHN, in conjunction with Theralase, was successful, in this challenging patient population, both for safety and potential efficacy. Patients with BCG-Unresponsive NMIBC are a difficult patient population to treat since they have unfortunately failed the standard of care, BCG. Many also failed other investigational therapies prior to being treated with Theralase’s PDT. The clinical data that we collected was robust and clinically relevant. I am fully supportive of the multi-site Phase II NMIBC clinical study, currently in progress, to further investigate the role of PDT in BCG-Unresponsive NMIBC."

Dr. Arkady Mandel M.D., Ph.D., D.Sc., Interim Chief Executive Officer and Chief Scientific Officer of Theralase stated "The Company is very pleased to share the Study clinical data that has been peer-reviewed and published in EUOS. Indeed, the publication of clinical results in a peer reviewed journal like EUOS validates the quality of the Theralase research and the professionalism of the clinical study team, who conducted it. As a direct result of the success of this initial Study, Theralase elected to undertake Study II, which I am happy to report is proceeding well. I am encouraged by the clinical data generated to date with intravesical TLD-1433, activated by laser light therapy, as I believe Theralase’s PDT is a viable alternative for the BCG-Unresponsive NMIBC patient population, although significant data is still pending. The ongoing analysis of the patients supports that up to 50% of evaluable patients (patients who have been clinically assessed by the principal investigators at study visits and whose response to a treatment can be measured because enough information has been collected) have achieved the primary study objective. We are grateful for the ongoing support to all clinical and technical personnel involved in the successful completion of the Study and in the strong clinical data collected to date for Study II. Based on the strength of the clinical data collected and the consistently high safety and efficacy profile of Theralase’s PDT, I am confident that TLD-1433-based therapy has the potential to become the next gold-standard in the treatment of BCG-Unresponsive patients."

About Study I

The Study’s primary objective was safety and tolerability of PDT, with a secondary objective of pharmacokinetics ((drug evacuation from the body)) and a tertiary objective of efficacy (CR primarily at 90 and secondarily at 180 days for patients treated at the maximum recommended starting dose (0.35 mg/cm2 ) and the therapeutic dose (0.70 mg/cm2)). Patients who were treated at the therapeutic dose, consented to be followed clinically for 18 months, post initial treatment.

About Study II

Study II utilizes the therapeutic dose of TLD-1433 (0.70 mg/cm 2 ) activated by the proprietary TLC-3200 medical laser system. Study II is focused on enrolling and treating approximately 100 to 125 BCG-Unresponsive NMIBC Carcinoma In-Situ ("CIS") patients in up to 15 CSSs located in Canada and the United States.

Study II Objectives:

Primary – Efficacy (defined by CR) at any point in time.
Secondary – Duration of CR (defined by duration of CR lasting a minimum 360 days post-initial CR).
Tertiary – Safety measured by incidence and severity of AEs Grade 4 or higher that do not resolve within 450 days post primary study treatment. (Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Serious, Grade 4 = Life Threatening and Grade 5 = Death)
About TLD-1433

TLD-1433 is a patented PDC with over 10 years of published peer-reviewed preclinical and clinical research and is currently under investigation in Study II.