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, UroGen Pharma Ltd. (the "Company") reported that it has entered into a license agreement (the "License Agreement") with Agenus Inc. ("Agenus"), pursuant to which Agenus granted to the Company an exclusive, worldwide (not including Argentina, Brazil, Chile, Colombia, Peru, Venezuela and their respective territories and possessions), royalty-bearing, sublicenseable license under Agenus’s intellectual property rights to develop, make, use, sell, import, and otherwise commercialize products incorporating a proprietary antibody of Agenus known as AGEN1884 for the treatment of cancers of the urinary tract via intravesical delivery (Filing, 8-K, UroGen Pharma, NOV 8, 2019, View Source [SID1234551040]). AGEN1884 is an anti-CTLA-4 antagonist that is currently being evaluated by Agenus as a monotherapy in PD-1 refractory patients and in combination with Agenus’ anti-PD-1 antibody in solid tumors. Initially, the Company plans to develop AGEN1884 in combination with UGN-201 for the treatment of high-grade non-muscle invasive bladder cancer.

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Pursuant to the License Agreement, the Company paid Agenus an upfront fee of $10.0 million and has agreed to pay Agenus up to $115.0 million upon achieving certain clinical development and regulatory milestones, up to $85.0 million upon achieving certain commercial milestones, and royalties on net sales of licensed products in the 14%-20% range. The Company will be responsible for all development and commercialization activities. Under the terms of the License Agreement, Agenus has agreed to use commercially reasonable efforts to supply AGEN1884 to the Company for use in preclinical studies or clinical trials.

Unless earlier terminated in accordance with the terms of the License Agreement, the License Agreement will expire on a product-by-product and country-by-country basis at the later of (a) the expiration of the last to expire valid claim of a licensed patent right that covers the licensed product in such country or (b) 15 years after the first commercial sale of the licensed product in such country. The Company may terminate the License Agreement for convenience upon 180 days’ written notice to Agenus. Either party may terminate the License Agreement upon 60 days’ notice to the other party if, prior to the first commercial sale of a licensed product, the Company substantially ceases to conduct development activities of the licensed products for 12 consecutive months (and during such period, Agenus has complied with its obligations under the License Agreement) other than in response to a requirement of an applicable regulatory authority or an event outside of the Company’s control. In addition, either party may terminate the License Agreement in the event of an uncured material breach of the other party.

On November 8, 2019 SELLAS Life Sciences Group, Inc. (Nasdaq: SLS) ("SELLAS" or the "Company"), a clinical-stage biopharmaceutical company focused on the development of novel cancer immunotherapies for a broad range of cancer indications, reported that it will host a KOL Symposium for investors on Friday, November 15, 2019 from 8:15 a.m. to 10:00 a.m. ET in New York, NY (Press release, Sellas Life Sciences, NOV 8, 2019, View Source [SID1234550743]).

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The KOL Symposium will include an overview of the Company’s ongoing clinical development programs for galinpepimut-S (GPS), with a focus on its Phase 3 trial of GPS in acute myeloid leukemia (AML), which is expected to initiate in the fourth quarter of 2019.

The KOL Symposium will feature presentations and discussions from internationally renowned experts on immuno-oncology and myeloid malignancies including:

Hagop M. Kantarjian, M.D., Chair of the Department of Leukemia and Associate Vice President for Global Academic Programs at the University of Texas MD Anderson Cancer Center and principal investigator of SELLAS’ Phase 3 clinical trial of GPS in acute myeloid leukemia
Javier Pinilla-Ibarz, M.D., Ph.D., Senior Member of the Malignant Hematology & Immunology Program and Director for Immunotherapy for Malignant Hematology at the H. Lee Moffitt Cancer Center
David A. Scheinberg, M.D., Ph.D., Vincent Astor Chair and Chairman of the Molecular Pharmacology Program and Founder and Chair of the Center for Experimental Therapeutics at Memorial Sloan Kettering Cancer Center
Jeffrey S. Weber, M.D., Ph.D., Deputy Director of the Perlmutter Cancer Center and Co-Director of the Melanoma Research Program at the NYU Langone Cancer Center
A live audio webcast of the event will be available under "Events and Presentations" in the Investors section of SELLAS’ website at www.sellaslifesciences.com/investors. A replay of the webcast will be available for up to 30 days on SELLAS’ website following the event.

On November 8, 2019 Rubius Therapeutics, Inc. (Nasdaq: RUBY), a clinical-stage biopharmaceutical company that is genetically engineering red blood cells to create an entirely new class of cellular medicines, reported that the Company presented preclinical data supporting its lead artificial antigen presenting cell program, RTX-321, for the potential treatment of HPV 16-positive tumors at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 34th Annual Meeting (Press release, Rubius Therapeutics, NOV 8, 2019, View Source [SID1234550760]). Last month at the AACR (Free AACR Whitepaper)-NCI-EORTC International Conference on Molecular Targets and Cancer, Rubius Therapeutics presented data demonstrating that its Red Cell Therapeutics can be engineered to create a loadable system for personal neoantigens, unlocking a potential new use of our RED PLATFORM.

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"Current cell therapy approaches are limited by a number of challenges – they require harvesting and engineering a patient’s own T cells, undergo a lengthy manufacturing process, are limited in the number of targets that can be pursued, and, once administered to patients, can elicit unpredictable immune responses, including severe side effects. Today at SITC (Free SITC Whitepaper), we presented additional preclinical proof of concept data demonstrating that Rubius Therapeutics can engineer allogeneic artificial antigen presenting cells against a tumor-associated antigen that significantly expand antigen-specific T cells and nearly eliminates lung metastases in a melanoma mouse model with minimal, reversible toxicity," said Pablo J. Cagnoni, M.D., chief executive officer of Rubius Therapeutics. "Separately, current personalized neoantigen approaches are promising, but do not adequately stimulate and expand the right subset of T cells to the levels required to achieve robust efficacy. Last month at AACR (Free AACR Whitepaper)-NCI-EORTC, Rubius Therapeutics presented data showing that we can engineer our red cells to create a loadable system for personal neoantigens and dramatically expand primary T cells to induce an immune response, unlocking a potential new use of our RED PLATFORM."

Data Summaries

Red Cell Therapeutic Artificial Antigen Presenting Cells (aAPCs) at SITC (Free SITC Whitepaper)

(P233) RTX-321, an Allogeneic Artificial Antigen Presenting Red Cell Therapeutic, Expressing MHC I-Peptide, 4-1BBL and IL-12, Promotes Antigen-Specific T Cell Expansion and Anti-Tumor Activity in HPV16+ Tumors

Allogeneic Red Cell Therapeutic artificial antigen presenting cells (RTX-aAPCs) are engineered to induce a tumor-specific response by expanding antigen-specific T cells.
As preclinical proof of concept, mouse red cells were chemically engineered with hundreds of thousands of copies of the major histocompatibility complex (MHC) I loaded with the gp100 peptide, a melanoma antigen, 4-1BBL and IL-12 on the cell surface and were tested in a B16-F10 melanoma mouse model.
These cells (mRBC-gp100-4-1BBL-IL-12 ) nearly eliminated lung metastases at the highest dose levels.
mRBC-gp100-4-1BBL-IL-12 promoted gp100-specific T cell expansion in the circulation, secondary lymphoid organs and lungs.
RTX-aAPC was engineered with a cytomegalovirus (CMV) antigen, 4-1BBL and IL-12 and expanded CMV-specific T cells from healthy donor peripheral blood mononuclear cells (PBMCs).
RTX-321 (HPV+) was engineered to express an HPV peptide antigen bound to MHC I, 4-1BBL and IL-12 on the cell surface to mimic human T cell-APC interactions.
Expression of IL-12 as signal 3 on an aAPC resulted in more robust antigen-specific T cell expansion, memory formation and cytotoxicity against tumor cells when compared to IL-7 or IL-15, leading the Company to select IL-12 as signal 3 for RTX-321.
RTX-321 is selectively directed against an HPV dominant epitope and promoted T cell receptor (TCRs), 4-1BB and IL-12 receptor signaling in engineered cell lines.
RTX-321 expanded HPV-specific TCR-transduced primary human T cells.
RTX-321 is currently in IND-enabling studies.
Loadable Red Cell Therapeutic Artificial Antigen Presenting Cells for Neoantigens at AACR (Free AACR Whitepaper)-NCI-EORTC

(B062) Enabling the Rapid Generation of Allogeneic Artificial Antigen Presenting Cell (aAPC) Red Cell Therapeutics with a Loadable MHC System

Allogeneic Red Cell Therapeutic artificial antigen presenting cells (RTX-aAPCs) are engineered to induce an tumor-specific response by expanding antigen-specific T cells.
A loadable MHC system was engineered to enable the rapid generation of aAPCs targeting personal neoantigens.
Antigenic peptides can be loaded onto empty MHC constructs, which can be stably expressed at high levels.
RTX-aAPCs with peptide-loaded MHC constructs functionally engaged TCRs and achieved robust expansion of primary CMV-specific T cells in healthy donor PBMCs with prior exposure to CMV.
Rubius Therapeutics’ loadable aAPC system has the potential to generate aAPCs containing multiple neoantigens in a single therapeutic.
Further development of a loadable aAPC system may enable effective personalized neoantigen therapies.

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).