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Ascentage Reports Bcl-2 Inhibitor Effective in Early Test

On June 10, 2021 Ascentage Pharma, a Suzhou company, reported promising data from an early test of its Bcl-2 inhibitor in hematologic malignancies. Lisaftoclax (APG-2575) showed an objective response rate of 80% in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma and other hematologic malignancies (Press release, Ascentage Pharma, JUN 10, 2021, View Source [SID1234583925]). Previously, patients had received a median of two treatments for their disease. The results were reported in an oral presentation at the 57th ASCO (Free ASCO Whitepaper) Annual Meeting, one of four Ascentage presentations at the meeting.

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Astellas’ Xtandi bags NICE approval in prostate cancer

On June 10, 2021 Astellas reported that oral treatment Xtandi has received approval from the National Institute for Health and Care Excellence (NICE) for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC) (Press release, Astellas, JUN 10, 2021, View Source [SID1234583924]).

The positive decision is supported by data from the Phase III ARCHES trial, which showed Xtandi (enzalutamide) plus standard androgen deprivation therapy (ADT) reduced the risk of metastatic progression or death by 61% compared to placebo plus ADT in mHSCPC patients.

Enzalutamide-01.svg
Prior to the NICE approval, the NHS provided interim special access to Xtandi during the pandemic as a ‘COVID-friendly’ oncology treatment.

Xtandi will now become widely available for mHSPC, an advanced form of prostate cancer where the cancer has progressed outside the prostate gland.

According to the National Prostate Cancer Audit 2020, up to 13% of men diagnosed with prostate cancer presented with metastases in the UK between April 2018 and March 2019 – men with metastatic prostate cancer typically have a 30% overall five-year survival rate.

"Every 45 minutes one man dies from prostate cancer in the UK, resulting in more than 11,500 deaths a year. The prevalence of advanced prostate cancer in the UK underlines the need for additional treatment options so that they can be tailored to suit individual patients" said Tim Patel, medical director, Astellas UK & Ireland.

"The NICE recommendation of enzalutamide promises another option to men with mHSPC, who face a poor prognosis, with hopes of providing them with another effective treatment choice," he added.

aTyr Pharma Presents Poster Demonstrating Functional Selectivity of Second Anti-NRP2 Antibody

On June 10, 2021 aTyr Pharma, Inc. (Nasdaq: LIFE), a biotherapeutics company engaged in the discovery and development of innovative medicines based on novel biological pathways, reported the presentation of a poster at the Antibody Engineering & Therapeutics Europe Virtual conference which was held June 8 – 10, 2021 (Press release, aTyr Pharma, JUN 10, 2021, View Source [SID1234583906]). The abstract and poster are available on the conference website.

The poster presents preclinical findings demonstrating in vitro and in vivo proof-of-concept that the anti-Neuropilin-2 (NRP2) antibody, aNRP2-14, is a high affinity, selective blocker of the Semaphorin 3F/NRP2 interaction. Class 3 Semaphorins are an important set of NRP2 ligands, with recent data implicating their role in sustaining chronic inflammation.

Details of the abstract and poster presentation are as follows:

Title: Engineering an anti-Neuropilin-2 (NRP2) antibody that selectively blocks NRP2 interactions with Semaphorin and Plexin
Authors: Kaitlyn Rauch, Luke Burman, Yanyan Geng, Liting Zhai, Yeeting E. Chong, Ann Menefee, Kristina Hamel, Zhiwen Xu, Nathaniel Bloom, Lauren Guy, Matt Seikkula, Christoph Burkart, Leslie A. Nangle. aTyr Pharma, San Diego, CA, Pangu Biopharma, Hong Kong.
Date: June 8 – 10, 2021

The poster is also available on the aTyr website.

"We are very excited to present these findings for aNRP2-14, which demonstrate the cutting-edge, in-house antibody engineering capabilities that the aTyr team has developed around creating highly specific, fully humanized, monoclonal antibodies targeting NRP2 and the different domains of the receptor," said Leslie Nangle, Ph.D., Vice President, Research at aTyr. "NRP2 interacts with several different protein ligands individually through these distinct domains to mediate signaling through diverse biological pathways associated with different disease states, and we have created a panel of antibodies targeting these distinct domains. While our lead anti-NRP2 antibody, ATYR2810, blocks the interaction with the VEGF ligand and is in preclinical development for cancer, aNRP2-14 targets the interaction between NRP2 and Sema3F/Plexin, a distinct signaling pathway modulated by this receptor. The data presented in this poster suggest that the blocking ability of aNRP2-14 could have potential utility as a therapeutic modality for targeting immune-mediated diseases where Sema3F/VEGF signaling is implicated and presents an additional pipeline opportunity for aTyr to explore."

About NRP2

Neuropilin-2 (NRP2) is a cell surface receptor that plays a key role in lymphatic development and in regulating inflammatory responses. In many forms of cancer, high NRP2 expression is associated with worse outcomes. NRP2 can interact with multiple ligands and co-receptors through distinct domains to influence their functional roles, making it a potential drug target with multiple distinct therapeutic applications. NRP2 interacts with type 3 semaphorins and plexins to impact inflammation and with forms of vascular endothelial growth factor (VEGF) and their receptors, to impact lymphangiogenesis. In addition, NRP2 modulates interactions between CCL21 and CCR7 potentially impacting homing of dendritic cells to lymphoid organs. aTyr is currently investigating NRP2 receptor biology, both internally and in collaboration with key academic thought leaders, as a novel target for new product candidates for a variety of diseases, including cancer and inflammation.

ImmunoPrecise to attend Biologics UK

On June 10, 2021 ImmunoPrecise reported thsat it will be attending Europe’s premier meeting for biologics and R&D, Biologics UK, September 6th-7th, 2021 (Press release, ImmunoPrecise Antibodies, JUN 10, 2021, View Source [SID1234583896]). The event is being hosted in London where we will be presenting a scientific poster and exhibiting a booth.

A NEW APPROACH TO CANCER THERAPY – Results of a placebo-controlled clinical trial published in Nature Communications

On June 10, 2021 HAMLET Pharma reported that The serendipitous discovery of HAMLET has provided novel insights into how to kill tumor cells without harming healthy tissues (Press release, HAMLET Pharma, JUN 10, 2021, View Source;utm_medium=rss&utm_campaign=a-new-approach-to-cancer-therapy-results-of-a-placebo-controlled-clinical-trial-published-in-nature-communications [SID1234583894]). The protein-lipid complex Alpha1-oleate, derived from HAMLET, is now identified as a molecule with significant therapeutic potential. The successful clinical translation and results of a placebo-controlled clinical bladder cancer trial has now been published in Nature Communications (link). View Source

The HAMLET complex, discovered in human milk, is formed by the protein alpha-lactalbumin and the fatty acid oleic acid. Early investigations in tumor cells and animal models detected potent therapeutic effects of HAMLET and clinical studies provided further evidence of efficacy.

The synthetic, peptide-based drug candidate Alpha1H is the N-terminal part of HAMLET and reproduces its tumor-killing properties. Detailed molecular characterization of the Alpha1-oleate complex in collaboration with Trinity College Dublin and NTU, Singapore has now allowed for full translation into the clinic in a placebo-controlled clinical trial. The clinical trial program is conducted by Professor M. Babjuk, Charles University and Motol Hospital, Praguge in collaboration with The HAMLET group at Lund University and Hamlet Pharma.

Potent effects of the complex were demonstrated in patients with non-muscle invasive bladder cancer (NMIBC). Highly significant differences between the Alpha1-oleate treated patients and the placebo group were detected for several crucial efficacy variables. The complex induced rapid shedding (within 2 hours) oftumor cells and tumor fragments into the urine, resulting in a significant reduction in tumor size.

Treatment was shown to be safe, as no drug-related side effects were observed. The Alpha1-oleate complex is attractive to cancer cells, which internalize it, but end up being killed. Healthy cells are less responsive and extensive toxicity studies have failed to detect adverse effects in the bladder. This low toxicity was confirmed here, as no drug-related side effects were observed in the treatment group. Alpha1-oleate triggered apoptotic cell death in the tumor and by gene expression analysis, massive inhibition of multiple cancer biofunctions was observed.

Bladder cancer is the 4th most common malignancy in the United States and the 5th in Europe. Bladder cancer is associated with the highest life time treatment costs per patient of all cancers, followed by colorectal-, breast- and prostate cancer. More than 80% of the patients recur after complete surgical removal of the first tumor and 15% progress to muscle invasive disease. Only three drugs have been approved for non–muscle-invasive disease in about 30 years and access to these drugs is limited by insufficient supply, including BCG immuno-therapy and common chemotherapeutics such as Mitomycin and Epirubicin.

The Food and Drug Administration has declared bladder cancer a great, unmet medical need. This study identifies alpha1-oleate treatment as a novel therapeutic concept and therapeutic option specifically in non-muscle invasive bladder cancer.
In view of the low toxicity observed so far, liberal intra-vesical administration in early stage NMIBC might be an interesting approach to postponing the introduction of more toxic and invasive therapeutic options.

"We hope that the readers will be as fascinated by this new therapeutic concept as we are. Publishing this translational study in such a high profile journal inspires our efforts to make Alpha1H available to cancer patients in the future," says Professor Catharina Svanborg, Lund University.

"This is an important milestone for HAMLET Pharma and we are grateful to all, who have made this possible. We need more evidence but hopefully this could be the gentle chemotherapy of the future," says Mats Persson, CEO of Hamlet Pharma Ltd.