On November 5, 2019 EpicentRx, Inc., a clinical cancer immunotherapy company targeting both sides of the immune system to deliver cancer treatments with minimal toxicity, reported that it has dosed the first patient in the Phase 3 REPLATINUM trial evaluating RRx-001 for the treatment of third-line and beyond small cell lung cancer (SCLC) (Press release, EpicentRx, NOV 5, 2019, View Source [SID1234550370]). REPLATINUM is EpicentRx’s first Phase 3 study of RRx-001, a small molecule immunotherapy targeting CD47 – SIRPα.

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Lung cancer is one of the most common cancers in the world, and the most common cause of cancer-related death. SCLC accounts for about 15% of all lung cancers, with a prevalence of over 300,000 patients globally. Almost 70% of SCLC patients present with extensive-stage disease at time of diagnosis and do not respond well to first- and second-line therapies due to the development of treatment resistance.

"The need for progress in third-line or beyond SCLC is clear, as the outcomes for these patients are uniformly fatal," said Corey A. Carter, M.D., President & CEO of EpicentRx and former head of thoracic oncology at Walter Reed Military Medical Center. "SCLC, especially SCLC in third-line or beyond, is dramatically underserved with ineffective options for patients."

REPLATINUM, an open-label, multicenter, crossover trial designed in collaboration with FDA, will evaluate the efficacy and safety of RRx-001 plus platinum doublet chemotherapy versus platinum doublet chemotherapy alone in 126 patients. REPLATINUM’s primary endpoint is progression-free survival, with overall survival and overall response rate as secondary endpoints.

The REPLATINUM trial follows positive results from EpicentRx’s ongoing Phase 2 QUADRUPLE THREAT trial, which is testing RRx-001 plus platinum chemotherapy in multiple cancer types, including SCLC. In patients with previously treated SCLC, RRx-001 plus platinum chemotherapy dramatically increased response rates, overall survival and progression-free survival compared to historical controls while suggesting a decrease in toxicities from chemotherapy. The QUADRUPLE THREAT data were recently published in the British Journal of Cancer.

"The strength of the Phase 2 trial allows us to keep REPLATINUM at a manageable size and should reduce the time and costs associated with a Phase 3 clinical trial. We are excited to have enrolled the first patient and look forward to working closely with our excellent clinical sites," said Dr. Carter.

RRx-001 has Orphan Drug designation from FDA for SCLC, neuroendocrine cancer and glioblastoma, and from EMA for SCLC.

About RRx-001

RRx-001 is a next generation small molecule immunotherapy being developed by EpicentRx. The therapy targets the CD47 – SIRPα axis and repolarizes tumor associated macrophages (TAMs) and other immunosuppressive cells in the tumor microenvironment to an immunostimulatory phenotype. RRx-001 stimulates the immune system and can be used as monotherapy or in combination with chemotherapy, immunotherapy, radiation and targeted agents, giving the therapy the potential to convert "treatment-resistant" tumors into "treatment-sensitive" tumors. RRx-001 is currently in the Phase 3 REPLATINUM trial for the treatment of third-line and beyond small cell lung cancer (SCLC). RRx-001 is also in the Phase 2 QUADRUPLE THREAT trial for the treatment of SCLC, non-small cell lung cancer, neuroendocrine tumors, ovarian and prostate cancer, and the Phase 2 PREVLAR trial for the prevention of oral mucositis. Clinical studies for the drug have also been conducted for the treatment of colorectal cancer, brain metastases and glioblastoma.

On November 5, 2019 Bicycle Therapeutics plc (NASDAQ: BCYC) a clinical-stage biotechnology company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycles) technology, reported that new preclinical data from BT7480, a potent tumor-targeted immune cell agonist (TICA) targeting Nectin-4 and agonizing CD137 (4-1BB), will be presented during speaker and poster sessions at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 2019 Annual Meeting on November 6-10, 2019 in National Harbor, MD (Press release, Bicycle Therapeutics, NOV 5, 2019, View Source [SID1234550369]).

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"Our novel and proprietary Bicycle tumor-targeted immune cell agonists, or TICAs, are fully synthetic approaches engineered to overcome the limitations of other immunomodulatory mechanisms," said Kevin Lee, Ph.D., Chief Executive Officer of Bicycle Therapeutics. "The constrained nature of Bicycles confers high affinity and selectivity and enables us to easily link tumor targeting Bicycles to Bicycles that agonize CD137, providing tumor-specific effects. In preclinical experiments with BT7480, we have shown these characteristics promote rapid tumor penetration and powerful anti-tumor activity. We believe that these features, along with the modular nature of the Bicycle platform, could position Bicycles at the cutting edge of next generation immuno-oncology treatments and we look forward to progressing BT7480 into IND-enabling studies."

BT7480 has shown very potent and tumor antigen dependent CD137 agonism in ex vivo experiments using patient-derived lung tumor samples that have intact immune microenvironments. In a Nectin-4 overexpressing syngeneic tumor model, 92% (n=24) of animals dosed with BT7480 experienced complete tumor regressions. Five of the complete responder animals were subsequently re-challenged with the same tumor cell implantation and no tumor growth was observed, implying development of immunogenic memory. In addition to these data on BT7480, the Company will also present preclinical data at SITC (Free SITC Whitepaper) on other emergent Bicycle TICA strategies.

Details on Bicycle’s SITC (Free SITC Whitepaper) presentations are as follows:

Session Title: Session 2: Novel Platforms and Innovation
Location: Cherry Blossom Ballroom
Oral Presentation Title: A novel fully synthetic dual targeted Nectin-4/4-1BB Bicycle peptide induces tumor localized 4-1BB agonism
Presenter: Nicholas Keen, Ph.D., Chief Scientific Officer of Bicycle Therapeutics
Date & Time: Wednesday, November 6, 2019 4:35 p.m. – 4:45 p.m. ET

Session Title: Novel Single-Agent Immunotherapies
Location: Prince George’s Exhibition Halls AB
Poster Presentation Title: A novel fully synthetic dual targeted Nectin-4/4-1BB Bicycle peptide induces tumor localized 4-1BB agonism
Abstract #: P782
Date & Time: Saturday, November 9, 2019, 7:00 a.m. – 8:30 p.m. ET

Session Title: Novel Single-Agent Immunotherapies
Location: Prince George’s Exhibition Halls AB
Poster Presentation Title: A novel fully synthetic dual targeted EphA2/4-1BB Bicycle peptide induces tumor localized 4-1BB agonism
Abstract #: P794
Date & Time: Saturday, November 9, 2019, 7:00 a.m. – 8:30 p.m. ET

The posters will be available on the Publications section of bicycletherapeutics.com following presentation.

On November 5, 2019 Silverback Therapeutics, Inc., a biopharmaceutical company developing a pipeline of systemically delivered, locally active therapies, reported that will present preclinical data on its lead candidate, SBT6050, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 34th Annual Meeting taking place November 6-10, 2019 at the Gaylord National Hotel & Convention Center in National Harbor, Maryland (Press release, Silverback Therapeutics, NOV 5, 2019, View Source [SID1234550368]).

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The presentation, titled "SBT6050, a HER2-Directed TLR8 Agonist Antibody Conjugate, Designed to Overcome Primary Resistance to and Synergize with Checkpoint Inhibition in HER2-Expressing Tumors," shows the potential for ImmunoTAC SBT6050, a novel therapeutic comprised of a potent TLR8 agonist conjugated to a HER2-directed monoclonal antibody, to drive robust anti-tumor efficacy as a single agent and in combination with checkpoint inhibition. SBT6050 potently activates myeloid cells in a HER2-dependent manner, resulting in the stimulation of multiple anti-tumor immune mechanisms and enabling tumor-localized activity via systemic delivery. In preclinical tumor models refractory to checkpoint inhibition, including T cell deficient xenograft models, an SBT6050 surrogate led to curative single-agent efficacy. Moreover, the single agent efficacy of the SBT6050 surrogate in an immune-competent, checkpoint refractory tumor model was enhanced when combined with an anti-PD1 agent. These preclinical data demonstrate the ability of activated myeloid cells to drive robust anti-tumor efficacy and support clinical evaluation of SBT6050 as a single agent and in combination with checkpoint inhibition in HER2-expressing tumors.

"These data continue to demonstrate the ability of Silverback’s technology to localize delivery of potent therapies to specific sites in the body," said Valerie Odegard, Ph.D., Silverback’s chief scientific officer. "Our preclinical data highlight SBT6050’s ability to activate T cell dependent and independent anti-tumor mechanisms, and its potential to be efficacious as a single agent and in combination, even in settings where immunotherapy has traditionally been ineffective. We look forward to initiating clinical investigation of SBT6050 in 2020."

Presentation details are as follows:

Poster P784: SBT6050, a HER2-directed TLR8 agonist antibody conjugate, designed to overcome primary resistance to and synergize with checkpoint inhibition in HER2-expressing tumors

Category: Novel Single-Agent Immunotherapies
Session Date and Time: Saturday, Nov. 9, poster displayed 7:00 a.m. – 8:30 p.m. EST, poster presented 12:35 – 2:05 p.m. and 7:00 – 8:30 p.m. EST.
Location: Prince George’s Exhibition Hall AB
About Silverback’s Platform Technology

Silverback’s proprietary technology and integrated R&D approach enables the design and development of ImmunoTAC antibody conjugate product candidates that can be administered systemically, but act only at the sites of disease. This approach is designed to spare healthy tissues from unwanted side effects, while modifying disease processes in a targeted and potent manner. Silverback’s platform is useful for developing systemic therapies that can modulate fundamental pathways underlying serious or life-threatening diseases in a targeted manner, in contrast to traditional antibody and small molecule-based approaches that have not been successful due to inadequate activity and/or unacceptable toxicities. Silverback has over 20 patent families directed to the platform and related product candidates.

On November 5, 2019 OncoNano Medicine, Inc., a biotechnology company developing ultra pH-sensitive micelles for the detection, staging and treatment of cancer, reported two poster presentations – including a late-breaking abstract – for the Society for the Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting to be held in National Harbor, Maryland, November 6-10 (Press release, OncoNano Medicine, NOV 5, 2019, View Source [SID1234550367]). OncoNano’s core technology is a library of tunable, ultra pH-sensitive micelles that exist intact under baseline physiological pH conditions but dissociate to release their payload under different, predesignated pH levels.

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"We are very pleased to share data for two of our lead products at the SITC (Free SITC Whitepaper) Annual Meeting this year," commented Ravi Srinivasan, CEO of OncoNano Medicine. "Our proprietary micelle technology is designed to enable us to deliver high-value and challenging payloads to target tissues with high specificity in ways that have not been possible before."

The first poster, which is a late-breaking abstract, will feature ONM-500 [Mi-Vax] – an injectable micelle composed of STING (Stimulator of Interferon Genes)-activating polymers and packaged with a human papilloma virus tumor specific antigen. These micelles are subcutaneously injected where they accumulate in the lymph nodes and are endocytosed by dendritic cells. The lower pH of intracellular endosomes causes micelle dissociation, releasing both the antigen and STING-activating polymer to coordinate a targeted attack on cancer cells. OncoNano was awarded a grant from the Cancer Prevention and Research Institute of Texas (CPRIT) to continue the advancement of ONM-500 through pre-clinical and clinical development.

The second poster features ONM-400 [ON-BOARD], OncoNano’s injectable pH-sensitive therapeutic delivery platform that exploits a universal feature of cancer, the relatively acidic tumor microenvironment. ONM-400 can be loaded or conjugated with a variety of cancer therapeutics including cytokines, small molecules and engineered antibody fragments to focus therapeutic delivery specifically at the site of the tumor, minimizing off-target delivery to potentially improve the efficacy and safety profile. OncoNano plans to continue advancing the ONM-400 program through preclinical development and toward the clinical stage where there is substantial unmet need for more effective strategies to target cancer.

Late-breaking Poster Presentation
Abstract title: ONM-500 – A Novel STING-Activating Therapeutic Nanovaccine Platform for Cancer Immunotherapy
Presenting Author: Jason B. Miller, Ph.D., OncoNano Medicine, Inc.
Poster Number: P857
Date: November 8, 2019, 12:30-2:00 PM and 6:30-8:00 PM

Poster Presentation
Abstract title: Delivery of Interleukin-2 to the Acidic Tumor Microenvironment by Ultra-pH Sensitive Nanoparticles for Immunotherapy
Presenting Author: Xinliang Ding, Ph.D., OncoNano Medicine, Inc.
Poster Number: P617
Date: November 8, 2019, 12:30-2:00 PM and 6:30-8:00 PM

On November 5, 2019 KIYATEC, Inc. reported that it will present data characterizing in vitro response to checkpoint inhibitors in solid tumors, a capability that addresses an important need in preclinical development of immuno-oncology (I/O) therapies (Press release, KIYATEC, NOV 5, 2019, View Source [SID1234550366]). The data will be presented at the 2019 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting, to be held November 6-10 in National Harbor, MD.

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Biologically relevant replication of complex interactions of human immune cells with tumor cells is an ongoing challenge using traditional preclinical models. Evidence presented by KIYATEC will highlight the utility of its in vitro 3D cell culture technology platform to characterize the tumor biology and immune activation and infiltration that precipitates response to checkpoint inhibitors across multiple solid tumor types. Data includes:

Complex 3D cultures derived from tumor cell lines or primary tumor tissue, incorporating allogeneic or autologous immune cells
High-throughput spheroid models used to detect dose-dependent response to checkpoint blockade and correlate with immune cell activation
Complex microtumor models that mirror immune cell infiltration, therapy-mediated reduction of microtumor growth and secretion of cytokines
"KIYATEC is pioneering advances in 3D cell culture technologies to address the unmet needs of biopharmaceutical companies engaged in pre-clinical testing of their I/O compounds," said Matthew Gevaert, CEO of KIYATEC. "Our emerging I/O models are currently being productively deployed across a number of pre-clinical initiatives and we anticipate that activity to increase as more drug developers become aware of our unique capabilities."

Presentation Details
Following are key details of the SITC (Free SITC Whitepaper) poster presentation:

Poster: P3
Title: Predicting patient response to checkpoint blockade therapy using in vitro 3D cultures
Date and Time: Friday, November 8, 12:30 – 2:00 pm, 6:30 – 8:00 pm, EST