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BioLineRx Presents Preclinical Data from Triple Combination of BL-8040, Anti PD-1 and Chemotherapy Demonstrating Significant Reduction in Pancreatic Tumor Growth and Favorable Changes in Tumor Microenvironment

On November 5, 2019 BioLineRx Ltd. (NASDAQ/TASE: BLRX), a clinical-stage biopharmaceutical company focused on oncology, reported positive preclinical results further elucidating the mechanism of action of BL-8040 in combination with an anti PD-1 and chemotherapy (Press release, BioLineRx, NOV 5, 2019, View Source [SID1234550288]). The results, summarized in a poster entitled, "Combination of BL-8040, anti PD-1 and chemotherapy significantly reduced pancreatic tumor growth and changed the balance between CD4+/FOXP3+ cells and CD8+ cells in the tumor," will be presented on November 8, 2019 at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 34th Annual Meeting in National Harbor, Maryland.

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"The results seen in this preclinical pancreatic cancer study support our hypothesis that the triple combination of BL-8040, anti-PD-1 and chemotherapy helps combat this difficult to treat cancer," said Philip Serlin, Chief Executive Officer of BioLineRx. "These preclinical data from the triple combination study support the mechanism of action of BL-8040 demonstrated in earlier clinical data from the dual combination of BL-8040 and pembrolizumab, showing a reduction in immuno-suppressive cells, accompanied by an increase in activated effector CD8+ T cells. We believe the ability of BL-8040 to modulate the tumor microenvironment allows for better activation of immune effector cells when combined with chemotherapy and immunotherapy. We are very hopeful that this anti-tumor activity will be confirmed in humans as we eagerly await results from the triple combination arm of our COMBAT/KEYNOTE-202 Phase 2 study of BL-8040, KEYTRUDA and chemotherapy in metastatic pancreatic cancer, which we expect to report by year end."

About the Pre-Clinical Study
The pre-clinical study assessed the effects of BL-8040, anti-PD-1 and chemotherapy (Irinotecan, Fluorouracil and Leucovorin), both alone and in various combinations, on tumor growth and immune cell constitution in a mouse model for pancreatic cancer.

Key findings include:

•The triple combination of BL-8040+anti-PD-1+chemotherapy had a significantly better effect on tumor growth compared to chemotherapy alone or any dual combination with chemotherapy.

The triple combination of BL-8040+anti-PD-1+chemotherapy showed the best effect in modulation of the tumor microenvironment, resulting in reduction in immunosuppressive cells, and accompanied by increase of activated T effector cells.

About BL-8040
BL-8040 is a short synthetic peptide that functions as a high-affinity best-in-class antagonist for CXCR4, a chemokine receptor over-expressed in many human cancers. CXCR4 has been shown to be correlated with poor prognosis, and plays a key role in tumor growth, invasion, angiogenesis, metastasis and therapeutic resistance. CXCR4 is also directly involved in the homing and retention of hematopoietic stem cells (HSCs) and various hematological malignant cells in the bone marrow.

In a number of clinical and preclinical studies, BL-8040 has shown a critical role in immune cell trafficking, tumor infiltration by immune effector T cells and reduction in immunosuppressive cells within the tumor niche, turning "cold" tumors, such as pancreatic cancer, into "hot" tumors (i.e., sensitizing them to immune check point inhibitors). BL-8040-mediated inhibition of the CXCR4-CXCL12 (SDF-1) axis has also shown robust mobilization of HSCs for transplantation in hematological malignancies.

BL-8040 was licensed by BioLineRx from Biokine Therapeutics and was previously developed under the name BKT-140.

Heat Biologics Reports Positive Phase 2 Interim Data in NSCLC Patients Who Previously Failed Checkpoint Inhibitor Treatment

On November 5, 2019 Heat Biologics, Inc. (NASDAQ:HTBX), a biopharmaceutical company developing immunotherapies designed to activate a patient’s immune system against cancer, reported that an abstract has been posted on The Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) website in connection with the Company’s planned poster presentation at SITC (Free SITC Whitepaper)’s 34th Annual Meeting on November 8, 2019 (Press release, Heat Biologics, NOV 5, 2019, View Source [SID1234550287]).

The abstract summarizes the latest interim top line data from Cohort B of the Company’s Phase 2 trial of the Company’s "off-the-shelf" cell-based therapy, HS-110, in combination with Opdivo (Nivolumab) in advanced non-small cell lung cancer (NSCLC), which completed enrollment in July 2019. This cohort enrolled patients who had previously received a checkpoint inhibitor (CPI) and whose disease had subsequently progressed. The data suggests that re-challenging the immune system with nivolumab and HS-110 after checkpoint inhibitor treatment failure may restore responsiveness and clinical benefit. Additionally, the combination of HS-110 and nivolumab is well-tolerated, and no increase in the incidence of immune-related adverse events was observed to date, as compared to CPI monotherapy. The full abstract is available at: View Source

Jeff Wolf, Heat Biologics’ CEO, commented, "NSCLC patients who progressed after checkpoint inhibitor treatment have limited therapeutic options. The latest results are encouraging and suggest that HS-110 in combination with nivolumab may address this key unmet medical need. As of this data cut, the median overall survival (OS) is estimated to be 11.8 months, with 70% of the patients still alive. I am unaware of any published checkpoint combination studies that offered superior OS in patients that had experienced previous checkpoint inhibitor treatment failure in NSCLC. This data also compares favorably to reported studies using chemotherapy following checkpoint inhibitor progression 1, 2 ".

Signals of clinical efficacy were observed in the reported objective response rate (ORR), disease control rate (DCR) and progression free survival (PFS). Importantly, patients experiencing dermal injection site reactions (ISR) had statistically significant improvement in PFS and OS compared to those without ISR (Hazard Ratio = 0.40, p=0.0068 and Hazard Ratio = 0.16, p=0.0005, respectively). Additional data will be presented at SITC (Free SITC Whitepaper) on November 8 ,2019.

Details of Heat Biologics’ poster presentation:

Abstract Title: Treating advanced non-small lung cancer (NSCLC) patients after checkpoint inhibitor treatment failure with a novel combination of Viagenpumatucel-L (HS-110) plus nivolumab

Poster #: P411
Date: Friday, November 8, 2019, 7am – 8pm (Eastern Time)
Location: Gaylord National Hotel & Convention Center, Washington DC

References:

1 Costantini A, Corny J, Fallet V et al. Efficacy of next treatment received after nivolumab progression in patients with advanced nonsmall cell lung cancer. ERJ Open Res. 2018 Apr 20;4(2).

2 Schvartsman G, Peng SA, Bis G, et al. Response rates to single-agent chemotherapy after exposure to immune checkpoint inhibitors in advanced non-small cell lung cancer. Lung Cancer. 2017 Oct;112:90-95.

Evotec SE to announce results for the first nine months 2019 on 12 November 2019

On November 5, 2019 Evotec SE (Frankfurt Stock Exchange: EVT, MDAX/TecDAX, ISIN: DE0005664809) will reported its financial results for the first nine months of 2019 on Tuesday, 12 November 2019 (Press release, Evotec, NOV 5, 2019, View Source;announcements/press-releases/p/evotec-se-to-announce-results-for-the-first-nine-months-2019–on-12-november-2019-5860 [SID1234550286]).

The Company is going to hold a conference call to discuss the results as well as to provide an update on its performance. The conference call will be held in English.

Conference call details

Date: Tuesday, 12 November 2019
Time: 02.00 pm CET (08.00 am EST, 01.00 pm GMT)

From Germany: +49 69 20 17 44 220
From France: +33 170 709 502
From Italy: +39 023 600 6663
From UK: +44 20 3009 2470
From USA: +1 877 423 0830
Access Code: 25877742#

A simultaneous slide presentation for participants dialling in via phone is available at View Source

Engitix Receives a Golden Ticket to LabCentral from Takeda to Advance Fibrosis and Solid Tumour Research

On November 5, 2019 Engitix Ltd (‘Engitix’), a private company focused on drug discovery for fibrosis and solid tumours based on its pioneering human extracellular matrix (ECM) platform, reported that its subsidiary Engitix, Inc, has been awarded a Golden Ticket to LabCentral by Takeda Pharmaceutical Company Limited (Takeda) (Press release, Engitix, NOV 5, 2019, View Source [SID1234550282]).

The Golden Ticket provides Engitix one year of lab bench space at LabCentral, a world-class shared laboratory and office space in Cambridge, Massachusetts. It includes access to LabCentral’s shared infrastructure and services, such as first-class lab, facility, and administrative support, skilled laboratory personnel, and participation in LabCentral’s training programme and seminars. Engitix will use the Golden Ticket to advance its human extracellular matrix (ECM) research in fibrosis and solid tumours disease progression.

"We are honoured to have received this Golden Ticket from Takeda, bringing us immediate access to a world-class bioresearch facility. It is a first step in developing Engitix’s presence in the United States and I look forward to building our network in Cambridge and across the USA more widely. We are also delighted that Takeda, a leader in the area of gastrointestinal diseases, has recognised the potential in Engitix’s ECM technology," said Dr Giuseppe Mazza, Engitix co-founder and CEO.

Engitix has developed the world’s first proprietary drug discovery platform based on tissue-specific and disease-specific human ECM scaffolds. The company’s 3D human ECM scaffolds provide an enabling tool for a better understanding of the role of the ECM in disease development and progression, leading to the identification of more relevant targets for drug discovery and biomarker development. A key current limitation in developing more effective treatments in fibrosis and for various solid cancers has been the absence of human ECM in experimental models.

Engitix’s mission is to increase the quality of therapeutics targets selected for development and a reduction in the number of later-stage drug trial failures by establishing more advanced platforms for drug target identification and validation, in which healthy as well as diseased cells can be tested with potential therapeutic agents within their natural physiological and pathological microenvironment.

ADC Therapeutics Announces Publication of ADCT-402 Data in Clinical Cancer Research

On November 4, 2019 ADC Therapeutics SA, a clinical-stage oncology-focused biotechnology company pioneering the development of highly potent and targeted antibody drug conjugates (ADCs) for patients suffering from hematological malignancies and solid tumors, reported that ADCT-402 (loncastuximab tesirine) data have been published in Clinical Cancer Research, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper), in a paper titled, "A Phase 1 study of ADCT-402 (Loncastuximab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody Drug Conjugate, in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma (Press release, ADC Therapeutics, NOV 4, 2019, View Source [SID1234596053])."

The Phase 1 multi-center, open-label, single-arm, dose-escalation and dose-expansion clinical trial demonstrated the significant single-agent clinical activity and manageable tolerability profile of ADCT-402 in patients with CD19-positive relapsed or refractory B-cell non-Hodgkin lymphoma who had failed or were intolerant to established therapies. The published paper includes findings from the dose-escalation part of the trial. Notably, among the 61 patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who were evaluable for efficacy, a 55 percent response rate was observed at doses ≥120 µg/kg. Eighty-seven of the 88 patients enrolled in the trial experienced at least one treatment-emergent adverse event (TEAE). The most common TEAEs were low blood cell counts, fatigue, liver test abnormalities, nausea, rash, shortness of breath and tissue swelling.

Brad S. Kahl, MD, Professor of Medicine at Washington University School of Medicine and lead author of the paper, said, "The first-in-human study of ADCT-402 justified its continued evaluation and identified the initial 150 µg/kg dose for the Phase 2 clinical trial. The promising clinical activity and manageable toxicities observed thus far highlight the potential utility of ADCT-402 as an off-the-shelf therapy for heavily pre-treated patients with DLBCL, a population for which a significant unmet medical need remains."

Jay Feingold, MD, PhD, Senior Vice President, Chief Medical Officer and Head of Oncology Clinical Development at ADC Therapeutics, added, "The publication of early ADCT-402 data in a peer-reviewed journal further validates the potential of our lead product candidate to become an important part of the treatment paradigm for relapsed or refractory DLBCL. With enrollment in our pivotal 145-patient Phase 2 clinical trial of ADCT-402 complete, we plan to submit a Biologics License Application to the U.S. Food and Drug Administration for accelerated approval of ADCT-402 for the treatment of relapsed or refractory DLBCL in patients who have failed two or more treatment regimens in the second half of 2020."

ADCT-402 is also being evaluated in an ongoing Phase 1b clinical trial in combination with ibrutinib for the treatment of relapsed or refractory DLBCL or mantle cell lymphoma (MCL) and a Phase 1b clinical trial in combination with durvalumab for the treatment of relapsed or refractory DLBCL, MCL and follicular lymphoma.

About ADCT-402

ADCT-402 (loncastuximab tesirine) is an antibody drug conjugate (ADC) composed of a humanized monoclonal antibody directed against human CD19 and conjugated through a linker to a pyrrolobenzodiazepine (PBD) dimer cytotoxin. Once bound to a CD19-expressing cell, ADCT-402 is designed to be internalized by the cell, following which the warhead is released. The warhead is designed to bind irreversibly to DNA to create highly potent interstrand cross-links that block DNA strand separation, thus disrupting essential DNA metabolic processes such as replication and ultimately resulting in cell death. CD19 is a clinically validated target for the treatment of B-cell malignancies. ADCT-402 is being evaluated in a pivotal Phase 2 clinical trial in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) (NCT03589469), a Phase 1b trial in combination with ibrutinib in patients with R/R DLBCL or mantle cell lymphoma (MCL) (NCT03684694) and a Phase 1b trial in combination with durvalumab in patients with R/R DLBCL, MCL or follicular lymphoma (NCT03685344). The U.S. Food and Drug Administration granted orphan drug designation to ADCT-402 for the treatment of relapsed or refractory DLBCL and MCL.