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RGENIX Presents Results from Preclinical Safety and Efficacy Studies of RGX-019 at the 2020 AACR Annual Meeting

On June 22, 2020 RGENIX, Inc., a clinical stage biopharmaceutical company developing first-in-class small molecule and antibody cancer therapeutics, reported it is presenting an abstract on RGX-019, RGENIX’s pre-clinical antibody program in development (Press release, Rgenix, JUN 22, 2020, View Source [SID1234561348]). RGENIX’s abstract, "In Vivo Safety and Efficacy of RGX-019, a MerTK Targeting Monoclonal Antibody" was accepted for the 2020 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, which this year was scheduled as two virtual meetings. The abstract results will be presented as a virtual poster presentation (LB-090) during the Late-Breaking Research: Immunology 1 session on June 22, by RGENIX’s Vice President of Research Dr. Isabel Kurth, who is senior author on the abstract.

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MerTK is a member of the TAM family of receptor tyrosine kinases and is predominantly expressed on macrophages as well as on cancer cells from a number of solid and hematologic malignancies. The binding of ligands to MerTK on cancer cells activates signaling that increases proliferation, angiogenesis, and drug resistance. On immune-suppressive M2 macrophages, MerTK signaling promotes immune tolerance. Therefore, there is rationale to target MerTK both to suppress tumor growth and activate anti-tumor immunity.

RGX-019 is a novel humanized MerTK targeting monoclonal antibody with a unique mechanism of action. As outlined in the presentation, RGX-019 was found to bind with high affinity to human and monkey MerTK, without detectable binding to related TAM receptors AXL or Tyro. RGX-019’s unique mechanism drives MerTK degradation through receptor internalization and lysosomal trafficking, resulting in the elimination of MerTK from the surface of treated cells. In vitro, RGX-019 inhibited human cancer cell viability and induced immune-stimulatory cytokine expression in M2 macrophages, consistent with robust inhibition of MerTK signaling. RGX-019 treatment in vivo led to near complete elimination of MerTK from the surface of tumor cells, which was associated with anti-tumor efficacy in mouse xenograft models.

Importantly, RGX-019 demonstrated a favorable safety profile in a 28-day dose-range finding toxicology study in monkeys. Of note, retinal toxicity – a finding associated with other MerTK targeting approaches – was not observed at any dose of RGX-019. The results overall demonstrate that RGX-019 can potently target MerTK signaling on both cancer cells and immune-suppressive M2 macrophages with a novel mechanism, resulting in anti-tumor activity with a wide therapeutic window.

Masoud Tavazoie, M.D., Ph.D., and Chief Executive Officer of RGENIX, said, "The results presented today demonstrate the potential for RGX-019 to be a best-in-class MerTK inhibitor. Its unique characteristics have yielded a favorable safety and efficacy profile in animals that provides a solid foundation for further development of RGX-019. We are excited to move RGX-019 through further IND-enabling studies and ultimately into clinical development."

Cancer Diagnostics Innovator KIYATEC Advancing Functional Ex Vivo 3D Cell Culture Models that Reveal Response Dynamics to Immuno-Oncology Drugs

On June 22, 2020 KIYATEC, Inc. reported that it will present data at the 2020 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, June 22-24, revealing how its 3D cell culture models characterize ex vivo tumor response and immunoreactivity to immune checkpoint inhibitors (i.e. PD-1, PD-L1 inhibitors) in solid tumors (Press release, KIYATEC, JUN 22, 2020, View Source [SID1234561347]). These emerging capabilities address a significant unmet need in both preclinical drug development and clinical decision-making in oncology.

PD-1/L1 inhibitors have experienced meteoric growth over the last decade, offering hope to hundreds of thousands of cancer patients every year in the US alone. However, typically no more than 25-30% of eligible cancer patients who receive PD-1/L1 inhibitors actually respond to them. Given that the direct costs associated with PD-1/L1 therapy can run into the hundreds of thousands of dollars per patient, KIYATEC believes that pre-treatment, patient-specific PD-1/L1 response prediction could one day offer clinicians, patients and payers a more objective basis for determining PD-1/L1 inhibitor patient eligibility vs. today’s commonly used population-based biomarkers.

Evidence presented by KIYATEC at AACR (Free AACR Whitepaper) 2020 will highlight findings of the company’s ability to detect dose-dependent response to checkpoint blockade and corresponding correlation with immune cell activation in high-throughput ex vivo 3D tumor spheroid models. KIYATEC believes these recent advances may represent key building blocks toward the eventual development and validation of clinical assays capable of accurate pre-treatment, patient-specific prediction of response to immuno-oncology drugs.

"We’re constantly innovating and expanding the capabilities of our 3D cell culture technologies to reduce the cost and risk of preclinical drug development for our immuno-oncology customers," said Matthew Gevaert, CEO of KIYATEC. "As we continue to make these advances in immuno-oncology drug response on higher-throughput platforms, we can begin to envision a time when such capability would inform clinical decision-making for cancer patients as well."

KIYATEC’s poster presentations at AACR (Free AACR Whitepaper) 2020 are as follows:

Title: Multifaceted functional assessment of checkpoint inhibitor efficacy using 3D tumor spheroids

Abstract: 7397 / Poster: 315 / Session: 3D & Tissue Recombinant Models / June 22-24
Title: PARP inhibition in combination with pembrolizumab enhances cytotoxicity in ovarian cancer patient-derived 3D spheroids

Abstract: 7132 / Poster: 2244 / Session: Immune Checkpoints 2 / June 22-24
Title: The perfused 3DKUBE rare tumor assay models in vivo drug response

Abstract: 7132 / Poster: 2244 / Session: Immune Checkpoints 2 / June 22-24

PureTech Presents New Data Reinforcing Galectin-9 as a Compelling Therapeutic Target and Biomarker for a Range of Cancers at the American Association for Cancer Research Annual Meeting

On June 22, 2020 PureTech Health plc (LSE: PRTC) ("PureTech" or the "Company"), a clinical-stage biotherapeutics company dedicated to discovering, developing and commercializing highly differentiated medicines for devastating diseases, reported that new data establishing galectin-9 as a novel target for cancer immunotherapy and providing compelling evidence that therapies targeting galectin-9 may enable the immune system to attack an array of solid tumors (Press release, PureTech Health, JUN 22, 2020, View Source [SID1234561346]). The data were shared in a scientific poster presented at the June session of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2020 Virtual Annual Meeting.

PureTech is developing a first-in-class, fully human monoclonal antibody targeting galectin-9. The product candidate, LYT-200, is expected to enter a first-in-human, Phase 1a/1b study in 2020 in hard-to-treat cancers, including pancreatic, cholangiocarcinoma and certain types of colorectal and liver cancers, which remain insufficiently responsive or resistant to currently approved checkpoint inhibitors. PureTech has previously presented data demonstrating LYT-200’s efficacy in reducing tumor growth and reactivating human effector T cells in preclinical, patient-derived tumor culture models.

"These new data clearly establish the importance of galectin-9 as a therapeutic target, given that its high expression across tumor types correlates with poor patient outcomes. Our analysis of more than 1,000 samples from human breast cancer tumors found that high levels of galectin-9 are associated with shorter time to disease relapse as well as with a tumor microenvironment that lacks cytotoxic CD8+ T cells that would otherwise be able to attack the tumor," said Joseph Bolen, PhD, chief scientific officer at PureTech. "Our first-in-class monoclonal antibody, LYT-200, is designed to target and inhibit galectin-9 and thereby reverse this suppression of the immune system to boost its ability to destroy tumors. We’re proud to be presenting this research at AACR (Free AACR Whitepaper) and look forward to advancing LYT-200 into the clinic later this year, as well as to progressing our work on galectin-9 as a biomarker."

The AACR (Free AACR Whitepaper) poster details a study undertaken by PureTech and its academic collaborators to evaluate the importance of galectin-9 expression in the tissues of cancer patients. The study is believed to include the largest cohort of breast cancer patient samples ever evaluated in this context, as well as robust cohorts of pancreatic and cholangiocarcinoma cases, and it found high expression of galectin-9 across all of these tumor types. Importantly, the highest levels of galectin-9 correlated with shorter time to disease relapse and poor survival. Strong galectin-9 expression was observed on the membranes of tumors with poor prognosis, which indicates this target is attractive for an antibody therapeutic such as LYT-200. In breast cancer, galectin-9 expression was associated with tumors showing worse pathological features, such as high tumor grade and estrogen receptor negativity, as well as features characteristic of an immunosuppressed tumor microenvironment, including the absence of CD8+ T cells. Collectively, these data suggest that galectin-9 could be significant both as a therapeutic target for a range of cancers and as a cancer biomarker, which PureTech intends to explore further for patient stratification.

Calidi Biotherapeutics Announces Two Abstracts Accepted for Presentation at AACR 2020 Virtual Annual Meeting II

On June 22, 2020 Calidi Biotherapeutics, Inc., a clinical-stage biotechnology company at the forefront of oncolytic virus-based immunotherapies for cancer, reported that data from clinical studies on their oncolytic agent, CAL1 vaccinia virus, and stem cell delivery system will be presented at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting II, which will be held in virtual format June 22 through June 24, 2020, due to COVID-19 concerns (Press release, Calidi Biotherapeutics, JUN 22, 2020, View Source [SID1234561345]).

Calidi’s respective e-poster presentations will highlight findings from translational research on the potential use of the CAL1 vaccinia virus, a version of the ACAM2000 smallpox vaccine delivered via an allogeneic adipose-derived mesenchymal stem cell (MSC) system, as well as insights from clinical trials analyzing the potential use of Calidi’s autologous SVF delivery platform to modulate innate and adaptive immunity in patients with solid tumors and hematological malignancies.

CAL1 was evaluated for abilities to safely replicate and selectively kill cancer cells, to be genetically modified (generating next generation armed-oncolytic viruses) without affecting its natural tumor selectivity, and to determine if its anti-tumor effects can be enhanced and protected from inactivation by immune system response when delivered via Calidi’s off-the-shelf MSC platform. The modified vaccinia virus strain demonstrated efficacy as an oncolytic agent, exhibiting heightened therapeutic capacity when loaded into adipose-derived mesenchymal stem cells to create Calidi’s SuperNova (SNV) product.

Calidi’s study on the immunomodulatory potential of vaccinia virus delivered by autologous SVF-derived cells expanded on their recent first-in-human Phase I clinical trial, which confirmed the safety and feasibility of their approach for improving virus delivery and tumor targeting. This study establishes a timeline of treatment-related immunological changes, identifies potential immunological correlations with continued amplified oncolytic therapy, and provides insights into the role of interpatient immunological variability and future oncolytic virotherapy evaluation.

Both abstracts indicate significant advantages and fundamental rationale for the development of vehicles like Calidi’s cell-based delivery platform (View Source), designed to protect and potentiate oncolytic viruses by circumventing innate and adaptive immune barriers, resulting in enhanced oncolytic virotherapy.

AACR presentation details are as follows:

Abstract 6542: CAL1 vaccinia virus as oncolytic agent and potential use of cell-based platform to enhance its therapeutic effects
Date: June 22, 2020, from 9:00 AM to 6:00 PM

Abstract 4473: Evaluation of the potential of oncolytic vaccinia virus delivered by autologous SVF to modulate innate and adaptive immunity in patients with diverse solid and hematological malignancies
Date: June 22, 2020, from 9:00 AM to 6:00 PM

Silverback Therapeutics to Present Preclinical Data on SBT6050 Demonstrating Potent Activation of Human Myeloid Cells and the Potential for Single Agent Clinical Activity

On June 22, 2020 Silverback Therapeutics ("Silverback"), a biopharmaceutical company advancing a pipeline of therapies that are systemically delivered but locally active, reported that preclinical data for its lead ImmunoTAC candidate, SBT6050, will be presented at AACR (Free AACR Whitepaper) Virtual Annual Meeting 2020 Session II at 9:00 a.m. ET on June 22, 2020 (Press release, Silverback Therapeutics, JUN 22, 2020, View Source [SID1234561344]).

The presentation, titled "SBT6050, a HER2-Directed TLR8 ImmunoTAC Therapeutic, is a Potent Human Myeloid Cell Agonist that Provides Opportunity for Single Agent Clinical Activity," shows that TLR8 agonism potently and uniquely activates human myeloid cells, driving a broad spectrum of anti-tumor immune mechanisms, including those not dependent on T cells.

In preclinical studies, SBT6050 activates human myeloid cells in the presence of HER2 expressing tumor cells, resulting in proinflammatory cytokine and chemokine production, inflammasome activation, and the indirect activation of cytolytic activity associated with T and NK cells. SBT6050’s functional profile was not replicated with conjugates comprised of TLR7-specific or resiquimod-derived agonists.

Robust, durable single agent activity is observed with the SBT6050 mouse surrogate in multiple tumor models, including those with low tumor infiltrating lymphocytes. In a human xenograft model lacking T, B, and NK cells, the SBT6050 mouse surrogate is curative as a single agent, demonstrating the ability of myeloid cells to mediate strong anti-tumor activity.

"TLR8’s robust expression and functional profile in human myeloid cells uniquely positions SBT6050 to potentiate anti-tumor responses through the activation of these innate immune cells present in tumors," said Valerie Odegard, Ph.D., Silverback’s chief scientific officer. "Our preclinical data highlight SBT6050’s potential to maximize anti-tumor immune responses, even in tumors lacking T cells. We are excited to be developing a much-needed immunotherapy for patients with HER2-expressing disease and will enter the clinic later this year."