On April 2, 2019 BerGenBio ASA (OSE: BGBIO) a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for multiple cancer indications, reported its preclinical data strengthening bemcentinib’s broad potential in reversing tumour-mediated immunosuppression and therapy resistance, presented by the Company’s academic collaborators at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019 (March 29 – April 3, Atlanta, Georgia) (Press release, BerGenBio, APR 2, 2019, View Source [SID1234534952]).

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Leading academic groups from the Gustave Roussy Cancer Centre in Paris, France, MD Anderson Cancer Center in Houston, TX, and UT Southwestern Medical Center in Dallas, TX, presented three posters describing pre-clinical findings generated in collaboration with BerGenBio on AXL’s role in aggressive cancer and bemcentinib’s therapeutic effect. The data presented lend further support to the Company’s ongoing clinical proof-of-concept programme and planned late stage strategy evaluating bemcentinib’s potential as a monotherapy and in combination across several indications.

A summary of results presented is given below.

(1) Salem Chouaib et al, Gustave Roussy Cancer Centre, Paris, France: AXL targeting enhances lymphocyte-mediated cytotoxicity of lung cancer cells. Abstract – 1200

Summary of results presented:

NSCLC cells expressing AXL were less prone to cell lysis mediated by cytotoxic T-lymphocytes (CTL) or NK-cells
Bemcentinib treatment led to increased CTL and NK-cell mediated killing of these AXL expressing NSCLC cells
(2) Kavya Ramkumar et al, The University of Texas, MD Anderson Cancer Center, Houston, TX: Targeting AXL sensitizes non-small cell lung cancer to ATR inhibitors by enhancing replication stress. Abstract – 276

Summary of results presented:

Bemcentinib treatment induces DNA damage and a subsequent DNA-damage response in NSCLC cells in a dose-dependent manner
Bemcentinib acts synergistically with DNA-damage-repair targeting agents (ATR inhibitors VX-970 or AZD6738) in reducing viability of NSCLC cells
(3) Wenting Du et al, The University of Texas Southwestern Medical Center, Dallas, TX: AXL is critical for pancreatic cancer progression and metastasis. Abstract –1037

Summary of results presented:

Downregulation of AXL via genetic engineering of pancreatic tumour models resulted in a more active immune microenvironment, prolonged survival and improved response to gemcitabine
Pharmacological intervention with bemcentinib similarly achieves immune activation and potentiates the effect of gemcitabine in pancreatic models where AXL is present on tumour and stroma cells
About AXL
AXL kinase is a cell membrane receptor and an essential mediator of the biological mechanisms underlying life-threatening diseases. In cancer, AXL suppresses the body’s immune response to tumours and drives cancer treatment failure across many indications. AXL inhibitors, therefore, have potential high value at the centre of cancer combination therapy, addressing significant unmet medical needs and multiple high-value market opportunities. Research has also shown that AXL mediates other aggressive diseases.

About Bemcentinib
Bemcentinib (formerly known as BGB324), is a potentially first-in-class selective AXL inhibitor in a broad phase II clinical development programme. Ongoing clinical trials are investigating bemcentinib in multiple solid and haematological tumours, in combination with current and emerging therapies (including immunotherapies, targeted therapies and chemotherapy), and as a single agent.Bemcentinib targets and binds to the intracellular catalytic kinase domain of AXL receptor tyrosine kinase and inhibits its activity. Increase in AXL function has been linked to key mechanisms of drug resistance and immune escape by tumour cells, leading to aggressive metastatic cancers.

On April 2, 2019 Pieris Pharmaceuticals, Inc. (NASDAQ: PIRS), a clinical-stage biotechnology company advancing novel biotherapeutics through its proprietary Anticalin technology platform for respiratory diseases, cancer and other indications, reported the presentation of preclinical data for PRS-342, a GPC3/4-1BB immuno-oncology bispecific drug candidate, at a poster session at the 2019 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Pieris Pharmaceuticals, APR 2, 2019, View Source [SID1234534885]).

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The poster, titled "Costimulatory T-cell engagement by PRS-342, a GPC3/4-1BB bispecific molecule, leads to activation of T cells and tumor growth inhibition in a HCC humanized mouse model," demonstrated that T-cell activation by PRS-342 led to NF-kB activation, increased production of IL-2 and dose-dependent cytolysis of GPC3-expressing tumor cells. PRS-342 also demonstrated a localized increase of tumor-infiltrating lymphocyte (TIL) levels in a humanized hepatocellular carcinoma (HCC) xenograft mouse model. The data presented suggest potent T-cell activation that is strictly dependent on the presence of GPC3-positive tumor cells. A copy of the poster presentation is available on the publications section of the Pieris website.

On April 2, 2019 Heat Biologics, Inc. (NASDAQ: HTBX), a biopharmaceutical company developing immunotherapies designed to activate a patient’s immune system against cancer, reported that it delivered a poster presentation yesterday, April 1, 2019, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Heat Biologics, APR 2, 2019, View Source [SID1234534901]). The Company’s presentation, entitled, ”Generation of a novel, allogeneic cell-based, Gp96-Ig/OX40L cancer vaccine, improves anti-tumor immunity and long-term memory T-cell generation,” is available online here.

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The poster presentation featured the Company’s next generation cellular vaccine platform, ComPACT (COMbination Pan-Antigen Cytotoxic Therapy), which incorporates a tumor antigen chaperone (gp96-Ig) with T-cell costimulation (OX40L-Ig), simulating a single tumor cell line source that secretes both products. The presentation modeled how the addition of human HS-130, which secretes OX40L-Ig, to HS-110 may ImPACT anti-tumor immune responses. This combination generated a three-fold increase in CD8+ T-cell expansion, increased numbers of long-lived tumor-specific T-cells, and potent short-lived killer T-cells required for tumor growth control.

Matt Seavey, Ph.D., Heat’s Senior Director of Research, commented, ”We are highly encouraged by these preliminary results in a mouse model, which demonstrate that the combination of HS-110 with OX40L co-stimulation has the potential to dramatically enhance anti-tumor immune responses. Moreover, this study further informed our selection of the ideal ratio of gp96 to OX40L, which will be helpful as we prepare to file an IND for our HS-130 ComPACT trial later this quarter.”

About AACR (Free AACR Whitepaper) Annual Meeting 2019

The AACR (Free AACR Whitepaper) Annual Meeting program covers the latest discoveries across the spectrum of cancer research – from population science and prevention; to cancer biology, translational, and clinical studies; to survivorship and advocacy – and highlights the work of the best minds in research and medicine from institutions all over the world.

On April 2, 2019 PureTech Health plc (LSE: PRTC) ("PureTech Health"), an advanced biopharmaceutical company developing novel medicines for dysfunctions of the Brain-Immune-Gut (BIG) axis, reported the presentation of two scientific posters at the 2019 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Atlanta, Georgia (Press release, PureTech Health, APR 2, 2019, View Source [SID1234534918]).

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Joseph Bolen, PhD, chief scientific officer at PureTech Health, said: "PureTech Health has built a leading position in BIG therapeutic development through its affiliate technologies and is now capitalizing on this critical mass of expertise through multiple internal development programs that are delivering clinical candidates. We’re proud to present data on these programs at AACR (Free AACR Whitepaper), one of the premiere scientific meetings focused on cancer research. Galectin-9 and γδ1 T cells represent powerful immunosuppressive mechanisms across both innate and adaptive immunity. We have moved quickly to advance development of compelling candidates that could act as both monotherapies and combination therapies against cancers that currently do not respond well to approved immunotherapies. In addition to our programs targeting the body’s immune cell trafficking highway – the lymphatic system – these immuno-oncology programs round out an exciting pipeline of therapeutics targeting important regulators of the immune system."

The posters detail the Company’s development of first-in-class, fully-human monoclonal antibodies (mAbs) targeting Galectin-9 (LYT-200) and immunosuppressive γδ1 (gamma delta) T cells (LYT-210). LYT-200 and LYT-210 are unique mAbs targeting foundational, novel mechanisms of tumoral immune escape and immunosuppression in cancer, and have been tested as single agents, as well as in combination with anti-PD1 in preclinical murine and human-derived ex vivo models. As such, they represent novel additions to the armamentarium of immuno-oncology agents, with potential across multiple solid tumors including malignancies that have historically proved difficult to treat. The AACR (Free AACR Whitepaper) posters describe their development, lead candidate characterization, and pre-clinical efficacy models.

Galectin-9 is a master immunosuppressor that affects multiple cell types (e.g., regulatory and effector T cells, myeloid-derived suppressor cells, and macrophages) to induce and maintain a tumor-permissive microenvironment. As it can be both expressed by cancer cells and present in cancer tissue, and it can also be secreted into the circulation of cancer patients, targeting Galectin-9 can enable multiple anti-tumor effects. PureTech’s anti-Galectin-9 antibody, dubbed LYT-200, is being developed for difficult-to-treat malignancies, including pancreatic, cholangiocarcinoma, and certain types of colorectal and liver cancers, which remain insufficiently responsive or resistant to currently approved checkpoint inhibitors. The research presented today details the development and comprehensive characterization of LYT-200 and its efficacy in preclinical human-derived ex vivo models and a murine model. The work demonstrates efficacy to reduce tumor growth, as well as the ability of LYT-200 to reactivate human effector T cells in patient-derived tumor culture models.

Gamma Delta 1 (γδ1) T cells are an immunosuppressive subset of the γδ T cell family of immune cells, which are upregulated in multiple solid tumors including breast cancer, glioblastoma, melanoma, and pancreatic cancer. Notably, an abundance of circulating γδ1 T cells has been associated with poor response to checkpoint therapy in melanoma patients. γδ1 T cells harbor a distinct phenotype characterized by expression of the δ1 chain in the T cell receptor. Immunosuppressive γδ1 T cells function to block effector T cells, restrict anti-tumoral γδ2 T cell subset, hinder antigen-presenting dendritic cells, and attract tumor-associated macrophages and myeloid-derived suppressor cells to enhance immunosuppression in cancer. Targeting γδ1 T cells therefore has the capacity to modulate both innate and adaptive immunity, and their distinct phenotypic and functional properties make them excellent therapeutic targets in cancer. The research presented today focuses on PureTech’s leading antibody candidate aimed at depleting γδ1 T cells, showing high specificity (e.g., binding to δ1 but not the δ2 chain present on cytotoxic γδ T cells), excellent binding affinity to both human and non-human primate δ1 chains, as well as functional properties to increase T cell effector activity in human derived ex vivo models. PureTech Health believes its anti-δ1 mAb program is the only one of its kind, and the Company is now finalizing the program’s lead clinical candidate selection.

The company anticipates filing an Investigational New Drug Application (IND) for LYT-200, which targets Galectin-9, in 2020 and anticipates continuing to advance the lead clinical candidate of the γδ1 program, LYT-210, into development

On April 2, 2019 MEI Pharma, Inc. (NASDAQ: MEIP), a late-stage pharmaceutical company focused on advancing new therapies for cancer, reported that Daniel P. Gold, Ph.D., president and chief executive officer, will present at the 18th Annual Needham Healthcare Conference on Tuesday, April 9, 2019 at 10:40 a.m. ET (Press release, MEI Pharma, APR 2, 2019, View Source [SID1234534953]). The conference will take place April 9-10, in New York, N.Y.

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A live audio webcast of the event can be accessed on the Events & Presentations page of the Investors section of MEI Pharma’s website at View Source

An archived replay of the webcast will be available on MEI Pharma’s website for at least 30 days after the live event concludes.