On November 8, 2019 Boston Biomedical, Inc. reported the presentation of new data from a phase 1 study evaluating DSP-7888, an investigational WT1 cancer peptide vaccine, in patients with advanced malignancies (Press release, Boston Biomedical, NOV 8, 2019, View Source [SID1234550776]). Findings from the phase 1 study investigating the safety, tolerability, and determination of the recommended phase 2 dose of DSP-7888 in patients with recurrent or progressive advanced malignancies will be presented in a poster presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 34th Annual Meeting, held in National Harbor, Maryland, on November 6-10, 2019. Patients enrolled in the study have progressed on standard therapy, were intolerant to standard therapy, or were patients for whom no standard therapy existed for their cancer.

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"The data presented at the SITC (Free SITC Whitepaper) Annual Meeting demonstrate our unwavering commitment to advancing a pipeline of novel cancer therapeutics to address unmet patient needs," said Patricia S. Andrews, Chief Executive Officer, Boston Biomedical, Inc. "We are excited to share more about the progress of our pipeline, including DSP-7888, with the scientific community."

Findings from the multicenter, open-label, dose-escalation study showed that DSP-7888 was well tolerated, with no dose-limiting toxicities identified in patients with advanced malignancies. In this study, 24 patients received escalating doses of intradermal (n=10) or subcutaneous (n=14) DSP-7888. Of the 24 patients, four had stable disease and 21 patients were evaluable for WT1-specific cytotoxic T-lymphocyte (CTL) detection. In the evaluable population, WT1-specific CTL induction was observed in six of nine intradermal patients (66.7%) and five of 12 subcutaneous patients (41.7%). An intradermal dose of 10.5 mg was determined as the recommended phase 2 dose, consistent with the findings of a separate phase 1/2 study of DSP-7888 in patients with myelodysplastic syndrome. The most frequently observed adverse event was Grade 1 or 2 injection site reaction.1

"We believe the WT1 antigen is a promising target for immunotherapy, as it is expressed across a range of cancer types and plays a key role in the proliferation, differentiation and apoptotic process of cells," said Alexander Spira, MD, PhD, FACP, lead author, and Director of Virginia Cancer Specialists Research Institute. "The findings from this study support the continuation of evaluating DSP-7888 in advanced cancers."

The company will also present background information on an ongoing phase 1/2 clinical study evaluating DSP-0509, an investigational toll-like receptor (TLR) 7 agonist, for the treatment of solid tumors.

Below are the details for the Boston Biomedical presentations:

Abstract Title

Details

Lead Author

Multicenter, open-label,
phase 1 study of DSP-7888
Dosing Emulsion (DSP-7888)
in patients with advanced
malignancies

Abstract #355

November 8, 2019

7:00 a.m. – 8:00 p.m. ET

Poster Presentation

Alexander Spira, MD, PhD,
FACP, Virginia Cancer
Specialists Research Institute
and The US Oncology
Network

A first-in-human phase 1/2,
multicenter trial of toll-like
receptor (TLR) 7 agonist
DSP-0509 as monotherapy
and in combination with
pembrolizumab in adult
patients with advanced solid
tumors

Abstract #426

November 9, 2019

7:00 a.m. – 8:00 p.m. ET

Poster Presentation

Shadia Jalal, MD, Indiana
University School of Medicine

About DSP-7888 (ombipepimut-S*)
DSP-7888 is an investigational cancer vaccine containing two peptides that induce WT1-specific cytotoxic T lymphocytes (WT1-CTL) and helper T cells to attack WT1-expressing cancerous cells found in various types of hematologic and solid tumors. Researchers have identified that by adding helper T cell inducing peptides, improved outcomes may be achieved compared to a killer peptide treatment regimen alone.

DSP-7888 is currently being investigated in combination with bevacizumab in a phase 2 trial in patients with recurrent or progressive glioblastoma (NCT03149003) and in a phase 1/2 trial in combination with nivolumab or pembrolizumab in patients with advanced solid tumors (NCT03311334). DSP-7888 is currently being investigated in two monotherapy studies: a phase 1/2 trial in myelodysplastic syndrome (MDS) (NCT02436252) and a phase 1/2 trial in pediatric patients with relapsed or refractory high grade gliomas (NCT02750891). In 2017, the U.S. Food and Drug Administration granted Orphan Drug Designations for DSP-7888 in MDS and brain cancer.

*Adegramotide/nelatimotide is also assigned as the international nonproprietary name (INN).

About DSP-0509
DSP-0509 is an investigational synthetic toll-like receptor (TLR) 7 agonist. In preclinical models, DSP-0509 was shown to promote the cytokine induction and cytotoxic T lymphocyte activation mediated by agonistic effect of TLR 7 expressed in plasmacytoid dendritic cells. DSP-0509 is hypothesized to sustain the immune-mediated anticancer activity by induction of immune system memory cells and is currently being evaluated in a phase 1/2 clinical trial in patients with advanced solid tumors (NCT03416335).

On November 8, 2019 Torque, a clinical-stage immuno-oncology company developing Deep Primed T cell immunotherapy to direct immune power deep within the tumor microenvironment, reported new preclinical data for its lead Deep IL-15 Primed T cell, Deep Il-12 Primed T cell, and Deep TLR Primed T cell therapeutics programs as well as for the company’s proprietary Slipstream process for manufacturing these first-in-class, multi-targeted cellular immunotherapies (Press release, Torque Therapeutics, NOV 8, 2019, View Source [SID1234550775]). The data are being presented today at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 34th Annual Meeting being held November 6–10, 2019 in National Harbor, Maryland.

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"These studies build on previous findings demonstrating the potential for the Deep-Primed technology platform to create a new class of multi-targeted T cell therapy that targets tumor antigens with specificity in the tumor microenvironment, with integrated and coordinated cytokine activation that drives a full response against tumors with heterogenous antigens," said Thomas Andresen, PhD, Chief Scientific Officer of Torque. "These preclinical studies provide the foundation for Torque’s first clinical trial for Deep IL-15 Primed multi-targeted T cells that is now under way, and for the Deep IL-12 and Deep TLR programs that we are preparing to move into clinical trials in the latter part of this year and in 2020, including a combination study of Deep IL-12 and Deep IL-15 Primed T cells."

Highlights of the four preclinical presentations follow, and copies of the posters are available on the Torque website: https://bit.ly/34yZnTU

Poster #P671: "Delivery of TLR7 agonists by Deep-Primed T cells induces immune activation and improves anti-tumor activity in mice while circumventing systemic toxicity"
Presenter: Austin Boesch, PhD, Torque
Key findings from the study:

In preclinical models, Deep TLR-Primed T cells display superior efficacy, pharmacodynamics, and safety compared to T cells alone or to T cells co-administered with systemic TLR agonists.
Torque’s Deep-Primed technology allows the delivery of small molecules to the tumor microenvironment, with controlled doses.
Compared to intratumoral delivery, agonist delivery via Deep-Primed tumor antigen-specific autologous T cells can target a wider variety of tumors, including distant metastases.
Deep TLR-Primed T cells have the potential to improve agonist pharmacokinetic profile through sustained delivery over time in the tumor microenvironment and draining lymph nodes, with limited systemic exposure.
Poster #P211: "Combining Deep IL-12 Primed and Deep IL-15 Primed T cells leverages complementary mechanisms to enhance anti-tumor activity"
Presenter: Katharine Sackton, PhD, Torque
Key findings from the study:

In preclinical models, modular tethering of Deep IL-12 and Deep IL-15 to T cells uniquely leverages their complementary functions as immunomodulators to maximize anti-tumor activity, without notable toxicity.
Poster #P473: "Adoptive Transfer of Deep IL-12 Primed T-cells Increases Sensitivity to PD-L1 Blockade for Superior Efficacy in Checkpoint Refractory Tumors"
Presenter: Gulzar Ahmad, PhD, Torque
Key findings from the study:

In a preclinical checkpoint-refractory cancer model, adoptive cell transfer with tumor-specific T cells carrying surface-tethered Deep IL-12, which focuses immune activity in the tumor microenvironment, repolarizes immunosuppressive cells in the tumor, enhances anti-tumor efficacy, and synergizes with checkpoint inhibition.
Poster #P157: "Optimized process for manufacturing Deep-Primed T cells creates product with improved functional characteristics and reactivity against multiple tumor-associated antigens"
Presenter: Shawn P. Carey, PhD, Torque
Key findings from the study:

Torque’s Slipstream cell manufacturing process is optimized to produce Deep-Primed multi-targeted T cells with substantive increases in characteristics associated with clinical efficacy: Antigen reactivity, memory phenotype, and polyfunctionality.
Modularity of the Slipstream process has been demonstrated by simultaneously training T cell clones reactive to cancer and virus-associated antigens.
Deep-Primed multi-targeted T cells with cell-associated Deep IL-15 or Deep IL-12 drives enhanced T cell function in vitro.
About Deep-Primed T Cell Therapeutics
Torque is developing a new class of Deep-Primed cellular immunotherapy designed to overcome the key challenges limiting broad use of cellular therapy in oncology, including the ability to target tumors that express multiple heterogeneous antigens, the ability to overcome the immunosuppressive tumor microenvironment that shuts down T cell function, and the need for cost-effective outpatient treatment with a high margin of safety. Deep-Priming is a unique technology platform that harnesses natural T cell biology and the power of cytokine activation to prime and boost a full immune response in the tumor microenvironment. Deep-Primed T cells are designed to:

Activate a Deep Immune Response Against Solid Tumors & Hematologic Cancers: Natural T cell receptors are primed to target multiple tumor antigens and retain their natural ability to integrate with the full immune system to direct a deep and comprehensive immune response against cancer.
Prime and Boost Broad Immune Cell Engagement to Overcome Immunosuppression in the Tumor Microenvironment: Deep-Primed T cells carry surface-anchored cytokines and immunomodulators to jump-start the engagement and coordination of the full network of immune cells to direct immune power in the tumor microenvironment, without significant systemic exposure.
Torque’s first clinical program, TRQ-1501 (Deep IL-15 Primed T cells), has received FDA Fast Track designation for the treatment of relapsed or refractory solid tumors and lymphomas and is currently in a Phase 1/2 clinical trial for this indication.

On November 8, 2019 BERG, a clinical stage biopharmaceutical company that uses artificial intelligence (AI) to discover the underlying biology of disease, reported results from a study of its investigational drug BPM31510 (ubidecarenone) characterizing its immunomodulatory properties ex vivo and in tumor bearing mice. The study, presented as a poster at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in National Harbor, Md., demonstrates a novel immuno-supportive activity of BPM31510 associated with enhanced T-cell function and diminished T-cell exhaustion which may contribute to its anti-tumor activity and synergize with Immuno-Oncology therapies (Press release, Berg, NOV 8, 2019, View Source [SID1234550774]).

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"Compromised T-cell function has a major impact on the effective anti-cancer response and outcomes observed in I/O therapies," said Dr. Niven R. Narain, BERG Co-founder, President and Chief Executive Officer. "The ability of BPM31510 to influence specific phenotypic attributes in T-cells to improve its effectiveness in the cancer microenvironment by targeting mitochondrial function represents a novel approach to impact immune system to improve cancer outcomes."

Combination of immunotherapies is under active investigation to improve anti-cancer outcomes. Immunometabolism is recognized as an important component of the immune function repertoire, an area with high untapped potential. BPM31510 impact on mitochondrial function and metabolism represents a novel and unique mechanism through its ability to synergize anti-cancer activities of I/O therapies in preclinical models and is under active investigation at BERG.

"These data set the stage to further explore BPM31510 impact on anti-tumor immunity and how to best deploy BPM31510 as part of an immunotherapy cocktail," said Vikas P. Sukhatme MD ScD, Professor of Medicine at Emory University School of Medicine and a Scientific Advisory Board member of BERG.

Details of the presentations include:
Date: Friday, November 8, 2019
BPM31510, a Metabolic Modulating Anti-Cancer Agent, Demonstrates Immune Potentiating Properties by Promoting Cytotoxic T Cells and Reversing Indices of Exhaustion and Immunosuppression
Abstract ID: P633 (Immune-stimulants and immune modulators)
Location: Poster Hall, Prince George AB of the Gaylord National Hotel & Convention Center, National Harbor MD, USA
Time: 7:00 AM – 8:00 PM

BERG collaborates with leading institutions like MD Anderson Cancer Institute (solid tumor and pancreatic trials), Harvard/BIDMC (Project Survival) and Stanford University (GBM trial), among others, in its commitment to serve patients afflicted with cancer.

On November 8, 2019 Orexo AB (publ), the fully integrated specialty pharmaceutical company addressing opioid addiction and pain, reported that the company will present at the Jefferies Healthcare Conference on Wednesday, November 20, 2019, at 10.40 am GMT at the Waldorf Hilton Hotel in London, UK (Press release, Orexo, NOV 8, 2019, View Source [SID1234550773]). President and CEO, Nikolaj Sørensen, will provide an update on Orexo’s market, sales development, pipeline progression and the growth strategy, focusing on broadening the product portfolio and building a presence in the increasingly important and complementary digital therapeutics market.

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The presentation will be made available at Orexo’s website, www.orexo.com, under the Investor section.

For further information, please contact
Orexo AB (publ.)
Lena Wange, IR and Communications Manager
Tel: +46 (0)18-780-88-00
E-mail: [email protected]

On November 8, 2019 BerGenBio ASA (OSE:BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for multiple cancer indications, reported comprehensive clinical and translational data from Cohort A of its Phase II clinical trial (BGBC008) evaluating bemcentinib, its first in class selective AXL inhibitor, in combination with MSD’s, (a tradename of Merck & Co., Inc., Kenilworth, NJ., USA) anti-PD-1 therapy KEYTRUDA (pembrolizumab), as a potential new treatment regimen for previously treated advanced non-small cell lung cancer (NSCLC) at an oral presentation at the prestigious High Impact Clinical Trial session at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (6-10 November 2019) conference in Washington DC (Press release, BerGenBio, NOV 8, 2019, View Source [SID1234550772]).

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In cohort A, 44 patients were evaluable for response; of IHC evaluable patients: 50% were composite AXL positive, 52% were PD-L1 negative (<1%TPS), and 38% patients were PD-L1 low positive (1-49% TPS). The primary endpoint of Overall Response Rate (ORR) was met, with 33% ORR in AXL positive patients; five times the response rate of AXL negative patients (7%).

A secondary endpoint of median Progression Free Survival (mPFS) reported significant 3-fold improvement in AXL positive vs negative patients – 8.4 months in composite AXL positive patients significantly surpassing what has been shown historically in second line treatment with PD-1 inhibitor monotherapy.

Dr. Matthew Krebs, MD, PhD, the lead investigator who will give the presentation at SITC (Free SITC Whitepaper) said: "The clinical benefit seen with the drug combination in AXL positive patients is impressive and provides a potential new treatment approach for patients with low or negative PD-L1 status. The mPFS observed for the AXL positive patients is far higher than that seen with pembrolizumab monotherapy results from earlier clinical trials for patients with PD-L1<50%. Furthermore, the combination is well tolerated by patients."

RNA sequence analysis of pretreatment patient biopsies revealed that clinical benefit from the combination therapy correlates with total tumor AXL expression. A proprietary predictive signature for response to bemcentinib and pembrolizumab combination derived from the transcriptional analysis is enriched for genes associated with epithelial-to-mesenchymal transition (EMT) and myeloid cell activation. "This is exactly where we know AXL is important." added Professor James Lorens PhD, Chief Scientific Officer of BerGenBio.

The gene expression measured in responding patients correlates with gene signatures known to be associated with poor prognosis and lack of response to immunotherapy. This indicates that previously treated patients are particularly benefiting despite exhibiting these adverse traits. Professor Hani Gabra MD PhD, Chief Medical Officer of BerGenBio said: "This indicates that bemcentinib is conditioning the tumor microenvironment in AXL positive patients and optimizing pembrolizumab response in these previously treated patients."

Multispectral immunofluorescence analysis detected tumor infiltrating AXL-expressing macrophages closely adjacent to T cells in the tumors of patients who responded to the combination therapy. "Seeing the AXL expressing macrophages interacting with T regulatory cells in the tumor of a patient who responded to the treatment really underscores the potential." added Dr. Krebs.

Prof. Lorens added: "Previously we only considered AXL expression in the tumor cells, ignoring the immune cell compartment of the tumor. Our deeper biomarker analysis clearly shows that our earlier tumor cell-only score did not fully capture the population of patients who benefit from the combination." A proprietary composite AXL tumor-immune score has now been developed, derived from gene expression and immunohistochemistry analysis that selects patients likely to benefit from bemcentinib.

Richard Godfrey, Chief Executive Officer of BerGenBio, said: "Our improved ability to select and predict patients with durable clinical benefit with a refined AXL composite biomarker is an important development for our AXL targeting clinical programs. Importantly for patients is the prolonged duration of benefit or mPFS and improved Overall Survival (mOS), which is still maturing, these are also critical regulatory end points. I look forward to reporting mOS and data from additional cohorts in the coming months."

Presentation details

A phase II study of bemcentinib (BGB324), a first-in-class selective AXL inhibitor, in combination with pembrolizumab in patients with advanced NSCLC: Updated analysis

Matthew G. Krebs, MD, PhD –The University of Manchester
Concurrent Session 206: High Impact Clinical Trials
Oral Session
08 November 2019: Prince George’s Exhibition Hall C
5:10 – 5:25 p.m. EST (Session runs from 4:50 – 6:15 p.m.)
Presentation will be available at www.bergenbio.com in the section: Investors/Presentations when the presentation starts.

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. Tumour AXL expression is associated with poor prognosis in NSCLC and most other cancer types. 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.