On May 24, 2022 Alpine Immune Sciences, Inc. (NASDAQ: ALPN), a leading clinical-stage immunotherapy company focused on developing innovative treatments for cancer and autoimmune and inflammatory diseases, reported that the U.S. Food and Drug Administration (FDA) has removed the partial clinical hold placed on its NEON-2 trial evaluating davoceticept (ALPN-202), a first-in-class conditional CD28 costimulator and dual checkpoint inhibitor, in combination with pembrolizumab in adults with advanced malignancies (Press release, Alpine Immune Sciences, MAY 24, 2022, View Source [SID1234614973]).

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 FDA removed the hold after review of the Company’s Complete Response, which included a comprehensive review of the davoceticept safety database, as well as a revised investigator brochure and study protocol. As previously disclosed, under the terms of the hold, previously enrolled participants continued to receive study drug, but no new participants could be enrolled until the partial clinical hold was removed. The ongoing NEON-1 study was not subject to the hold.

About Davoceticept (ALPN-202)

Davoceticept (ALPN-202) is a first-in-class, conditional CD28 costimulator and dual checkpoint inhibitor intended for the treatment of cancer. Preclinical studies of davoceticept have successfully demonstrated superior efficacy in tumor models compared to checkpoint inhibition alone. NEON-1 (NCT04186637), a Phase 1 monotherapy dose escalation and expansion trial in patients with advanced malignancies, has completed dose escalation and is currently enrolling its expansion cohorts. NEON-2 (NCT04920383), a combination study of davoceticept (ALPN-202) and pembrolizumab, was initiated in June 2021.

On May 24, 2022 LUMICKS, a leading life science tools company that develops instruments for dynamic single-molecule and cell avidity analysis, reported the publication in Cancer Cell of preclinical research identifying "Avidity Enhancement" as a new strategy to improve therapeutic outcome of Chimeric Antigen Receptor (CAR) T cell immunotherapy in Acute Myeloid Leukemia (AML) (Press release, LUMICKS, MAY 24, 2022, View Source;utm_medium=rss&utm_campaign=avidity-enhancement-new-strategy-for-improving-car-t-therapy [SID1234614972]).

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!

AML poses significant clinical challenges due to its resistance to therapies and its bleak prognosis. Approximately 20,000 people in the US and 300,000 worldwide die from AML every year, making it the most common form of acute leukemia in adults and a major public health issue.

The Cancer Cell paper (May 9, 2022), entitled "Non-cleavable hinge enhances avidity and expansion of CAR-T cells for acute myeloid leukemia," was authored by a team of CAR T cell researchers led by Dr. Marcela V. Maus, Associate Professor of Medicine at Harvard Medical School and Director of the Cellular Immunotherapy program at Massachusetts General Hospital.

The study details a novel strategy for better cancer treatment with CAR T cells for AML. "Avidity Enhancement", increasing cell-cell binding from both the tumor and CAR T cell side, led to a more effective eradication of tumors in mouse models of AML. In this paper, data generated using the LUMICKS z-Movi Cell Avidity Analyzer provided superior correlation with CAR T cell activity in vivo compared to the standard in vitro assays in assessing the potency of CAR variants.

Building upon previous research from the Maus Lab indicating ‘avidity escape’ as an evasion mechanism when CAR T cell therapies are deployed against solid tumors, "avidity enhancement" is a promising strategy for improving clinical success of CAR T therapies.

"We continue to be excited about the pivotal research emerging from The Maus Lab and other leading laboratories that demonstrates how researchers can leverage the technological and scientific power of measuring cell avidity with the z-Movi Cell Avidity Analyzer," said Andrea Candelli, PhD, Chief Scientific Officer of LUMICKS. "This work further solidifies the idea that cell avidity can be a unique biomarker to improve the selection of CAR T therapies for superior therapeutic outcomes in hematological malignancies as well as in solid tumors. We are delighted to collaborate with researchers worldwide in uncovering meaningful new insights, such as the new treatment approaches suggested for AML contained in this new paper in Cancer Cell."

The z-Movi Cell Avidity Analyzer measures cell avidity, or level of binding, between immune cells and their targets, enabling researchers to identify the most potent immunotherapeutic effector cells. This unique technology provides predictive, reproducible, and fast results at single-cell resolution. LUMICKS’ cell avidity solutions use acoustics to measure forces and interactions between cells, with the goal of shortening the drug development cycle of immunotherapies and reducing failure rates in clinical trials. First introduced in 2020, the z-Movi is being rapidly adopted by academic and biopharma laboratories around the world.

About the Study Findings

Unlike other forms of leukemia, AML has been notoriously difficult to successfully target using CAR T cells. Researchers believe this is due to both low expression of the antigenic targeted protein on the cancer cells and unstable expression of activating receptors on the T cells.

In this publication, the researchers have shown that increasing avidity of the CAR T cells to their target cells leads to enhanced tumor killing in vitro as in mouse models. Target protein expression on the cancer cells was chemically enhanced using available therapeutics and/or changing the design of the CAR to stabilize its expression on the T cells. Through this method, the researchers show that enhancing cell avidity for therapeutic efficacy can be achieved by modulating the tumor cell or modulating the surface of the T cell. Either strategy increased the sensitivity of the tumor to CAR T mediated clearance, confirming cell avidity as a crucial biomarker in immune oncology.

On May 24, 2022 Indica Labs, the leading provider of computational pathology software and services, reported a CE-IVD Mark for HALO Prostate AI, a deep learning-based screening tool designed to assist pathologists in identifying and grading prostate cancer in core needle biopsies (Press release, Indica Labs, MAY 24, 2022, View Source [SID1234614970]).

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!

Prostate cancer is the most common cancer diagnosed in men. With over 1.4 million cases reported worldwide in 2020, the incidence rates continue to rise with wider availability of screening tests, such as PSA. Each prostate case consists of multiple biopsy core whole slide images, which must be assessed by a pathologist for the presence of tumor and, if present, a Gleason score is reported. This represents a large workload for pathologists who screen multiple cases daily. HALO Prostate AI is designed to work alongside the pathologist to improve efficiency and to add a layer of quality control to ensure diagnostic accuracy.

Developed in close collaboration with Dr. Yuri Tolkach and colleagues from the University of Cologne, HALO Prostate AI was trained using over 870,000 training patches obtained from the annotation of digital scans representing the full spectrum of prostate cancer subtypes and Gleason grades, as well as benign tissue. The algorithm achieved high sensitivity (95- 100%), specificity (88-98%) and negative predictive value (98- 100%) in validation studies performed on 4,973 core needle biopsies from three independent cohorts sourced from hospitals in Austria and Germany. Highlighting the unique benefit of HALO Prostate AI screening on diagnostic accuracy and patient care, the algorithm correctly detected tumor in 26 cores within the validation study that were originally reported as tumor negative.

In a separate study, Gleason scores obtained from HALO Prostate AI were compared against scores assigned by pathologists located in ten globally distributed hospitals. Nine pathologists who participated in the study were board-certified in genitourinary pathology. High concordance was achieved for two separate cohorts with representative average quadratic Kappa scores of 0.8 and 0.7.

"I am very excited about the digital future of pathology," commented Dr. Tolkach. "With tools such as HALO Prostate AI, our work can be substantially optimized while controlling for high-quality, reliable, and objective diagnostics. HALO Prostate AI showed very high accuracy in the large multi-institutional study for tumor detection and Gleason Grading in prostate biopsies. It’s really enjoyable to work back-to-back with such a powerful AI assistant".

Dr. Peter Caie, Principal Scientist of AI Collaboration at Indica Labs, added, "This has been a hugely positive collaboration with Dr. Tolkach and contributing pathologists from around the world. We set out to build a clinical-grade algorithm that could improve turn-around time and diagnostic accuracy for prostate cancer patients, and I believe that is exactly what we have achieved. We are thrilled to see the first of many AI algorithms from Indica Labs attain CE-IVD marking and to begin to be used in clinical settings to help alleviate the pressure of ever-increasing workloads."

HALO Prostate AI is deployed through Indica Labs’ CE-IVD marked HALO AP platform to provide a fully validated and automated end-to-end workflow. HALO AP can operate as a fully functional, standalone case management system or can integrate with existing LIS solutions to allow outputs from HALO Prostate AI or other AI diagnostics to be accessible directly from the LIS. Designed to be scanner agnostic, HALO Prostate AI was trained using digital scans obtained from multiple scanning platforms and was clinically validated against the Hamamatsu NanoZoomer S360 and Leica GT450 platforms.

On May 24, 2022 Pierre Fabre and the European Organisation for Research and Treatment of Cancer (EORTC) reported the screening of the first patient with a resected stage II BRAF-mutant melanoma for the phase III study COLUMBUS-AD (NCT05270044; EORTC-2139-MG) (Press release, EORTC, MAY 24, 2022, View Source [SID1234614969]).

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!

COLUMBUS-AD is a pioneering study to evaluate whether the combination of BRAF and MEK inhibitors encorafenib (Braftovi) and binimetinib (Mektovi) can prolong recurrence-free survival (RFS) and improve distant metastasis-free survival (DMFS) and overall survival (OS) as compared to placebo in participants with surgically resected stage IIB-C BRAF V600E/K-mutant cutaneous melanoma.

"Pierre Fabre’s partnership with EORTC is now accelerating with the opening of COLUMBUS-AD", said Dr Deborah Szafir, Executive Vice President, Head of Medical and Patient Consumer Division at Pierre Fabre. "Building on the clinical benefits that our medicines have demonstrated in advanced disease, we are eager for patients with a BRAF-mutated tumour to explore the adjuvant setting in an earlier stage of the disease as the unmet medical need remains high."

Despite the remarkable progress made in the treatment of advanced melanoma activating the BRAF mutation, unfortunately there remains a high unmet need in earlier stages of the disease. It is estimated that 18% of stage IIB and 25% of stage IIC patients die from melanoma within 10 years from diagnosis.

"The screening of patients for COLUMBUS-AD focuses on patients with surgically resected high-risk IIB-C BRAF V600E/K-mutant cutaneous melanoma", said study coordinator assoc. prof. Dr. Alexander C.J. Van Akkooi, MD PhD, from the Melanoma Institute Australia (MIA) and past chairman of the EORTC Melanoma Group. "It is essential to test the tumour as early as possible for BRAF mutation, so that eligible patients can get a chance to participate into COLUMBUS-AD".

Approximately 815 patients will be enrolled in COLUMBUS-AD. More than 160 sites in up to 25 countries worldwide will participate in the study.

Patients included in the study must have undergone resection of a stage IIB-C melanoma with a BRAF V600E/K mutation, confirmed on resected tumour sample by a central laboratory, and a negative result on sentinel node biopsy. Patients must also have fully recovered from the surgery, have a good performance status (ECOG 0/1), and adequate hematologic, hepatic, cardiac, coagulation and renal functions.

Patients will receive encorafenib and binimetinib or placebo for up to 12 months. They will be followed-up monthly during the treatment period, then every 3 months up to year 3, and then at regular intervals. The participants will be followed-up for 10 years in total.

Pierre Fabre has a long-standing commitment to the melanoma community and takes a unique holistic approach to skin health with expertise in oncology, dermatology and dermo-cosmetics. EORTC, a unique academic clinical research organisation uniting clinical cancer research experts across the globe, shares Pierre Fabre’s commitment to improving the standard of cancer treatment for patients.

About Melanoma

Melanoma develops when unrepaired DNA damage to skin cells triggers mutations that may lead them to multiply and form malignant tumours.1 There are about 324,000 new cases of melanoma diagnosed worldwide each year, approximately half of which have BRAF mutations, a key target in the treatment of metastatic melanoma.2,3,4 By 2025, the number of cases is expected to increase to over 340,000.5

On May 24, 2022 BerGenBio ASA (OSE: BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for severe unmet medical needs, reported its results for the first quarter 2022 (Press release, BerGenBio, MAY 24, 2022, View Source [SID1234614968]).

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!

A briefing by BerGenBio’s senior management team will take place at 10:00am CEST today via a webcast presentation, followed by a Q&A session. Please see below for details.

Operational Highlights – first quarter 2022 (including post-period end)

Post-period end, business strategy update announced, focusing on two key indications; 1st line STK11m non-small cell lung cancer (NSCLC) and COVID-19. ​
Primary endpoint met in hospitalized COVID-19 patients in complete data analysis of ACCORD2 (BGBIL019), a randomized Phase II study of bemcentinib in combination with standard of care therapy.
Presented clinical trial data from Phase IIa bemcentinib COVID-19 clinical trial (BCBC020) at 32nd European Congress of Clinical Microbiology and Infectious Diseases (ECCMID).​
Cristina Oliva, MD appointed as Chief Medical Officer, bringing over 20 years of senior clinical development experience across large pharmaceutical, biotechnology and Clinical Research Organizations.
Publication of a peer-reviewed article entitled "AXL targeting restores PD-1 blockade sensitivity of STK11/LKB1 mutant NSCLC through expansion of TCF1+ CD8+ T cells" in the journal Cell Reports Medicine.
Announced inclusion of bemcentinib, in the EUSolidAct platform study of hospitalized COVID-19 patients designed to enroll up to 500 patients across European centers participating in the EUSolidAct platform.
Financial Highlights – first quarter 2022

(Figures in brackets = same period 2021 unless otherwise stated)

Revenue amounted to NOK 0.0 million (NOK 0.0 million) for the first quarter 2022
Total operating expenses for the first quarter were NOK 78.6 million (NOK 83.4 million)
The operating loss for the first quarter came to NOK 78.6 million (NOK 83.4 million)
Cash and cash equivalents amounted to NOK 367.8 million at the end of the first quarter 2022 (NOK 436.6 million by end of December 2021)
Martin Olin, Chief Executive Officer of BerGenBio, commented: "Earlier this month, we provided an update on the Company’s strategy. BerGenBio’s mission remains unchanged, and we believe that the announced focus provides an optimal path to unlock the potential of AXL inhibition as a transformative treatment modality for severe diseases.​

By focusing the development of our lead asset bemcentinib to two key areas, STK11 mutated (STK11m) 1st line non-small cell lung cancer (NSCLC) and COVID-19, we believe we have defined the path to efficiently advance BerGenBio’s clinical and commercial potential. Both indications represent significant unmet medical needs and our defined plans for each of these indications provides a strong foundation for bringing new drug to market with the aim of achieving better outcomes for patients and the generation of significant value for our shareholders.​

With a focused strategy and rightsized organization, I believe we are well positioned to unlock significant potential value related to the two indications selected and define the path to market."

Presentation and Webcast Details

The live webcast link is available at www.bergenbio.com in the Investors/Financial Reports section. A recording will be available shortly after the webcast has finished.

Webcast link: https://channel.royalcast.com/hegnarmedia/#!/hegnarmedia/20220524_3

The first quarter report and presentation are available on the Company’s website in the Investors/Financial Reports section and a recording of the webcast will be made available shortly after the webcast has finished.