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Rakuten Medical Presents Data during AACR Characterizing how Illuminox (an Investigational Platform based on Photoimmunotherapy), Induces Cancer Cell Death and Enhances the Immune Response Preclinically

On June 22, 2020 Rakuten Medical, Inc. (Rakuten Medical) reported the results of two preclinical studies presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Meeting II (Press release, Rakuten Medical, JUN 22, 2020, View Source [SID1234561303]). These studies further demonstrate the mechanism of action of Rakuten Medical’s Illuminox technology platform with its antibody-IRDye 700DX conjugate and how this unique technology induces tumor cells and enhances the adaptive immune response.

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"We are excited to present data on the mechanism of action of the Illuminox technology to induce rapid cell membrane disruption of cells targeted with the antibody-IRDye 700DX conjugate and the induction of cell necrosis and immunogenic cell death," said Miguel Garcia-Guzman, Ph.D., Chief Scientific Officer, Rakuten Medical. "Consistent with this mechanism of action, the study also shows that Illuminox treatments induce robust anti-cancer effects in immunocompetent animals by activating tumor specific innate and adaptive anticancer immunity with long term immune memory."

The following preclinical poster presentations were showcased during the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Meeting II:

"Molecular mechanism of action of photoimmunotherapy with antibody-IR700 dye conjugates: Role of singlet oxygen in cell membrane disruption and necrotic cell death." (Abstract 480), presented by Roger Heim, Rakuten Medical.

This poster investigates the mechanism of action of Rakuten Medical’s proprietary Illuminox photoimmunotherapy through a series of preclinical experiments. These data describe the unique biophysical processes by which photoimmunotherapy with antibody-IR700 dye damages cell membranes and induces cell death.

"Anticancer activity by photoimmunotherapy is driven by adaptive immune responses and induces vaccinal effects in mice." (Abstract 949), presented by C. Daniel De Magalhaes Filho, Rakuten Medical.

This poster confirms previous data demonstrating that photoimmunotherapy induces cell death in tumor cells and ignites an immune response against the tumor [Hsu M, et al. AACR (Free AACR Whitepaper) 2019].

In this study, mice implanted with photoimmunotherapy-treated tumor cells rejected new tumor challenges, indicating that photoimmunotherapy induces immunogenic cell death and activates immune responses in the host mice protecting against future tumor challenges.

Nimbus Therapeutics Presents Data on Novel HPK1 Inhibitor, Demonstrating Robust Inhibition of Tumor Growth In Vivo

On June 22, 2020 Nimbus Therapeutics, a biotechnology company designing breakthrough medicines through structure-based drug discovery and development, reported a poster at the AACR (Free AACR Whitepaper) Virtual Annual Meeting II detailing promising preclinical findings from the company’s HPK1 pipeline program (Press release, Nimbus Therapeutics, JUN 22, 2020, View Source [SID1234561302]).

Nimbus developed multiple selective small-molecule inhibitors of HPK1 using the company’s proven structure-based drug discovery engine. The lead compound, NMBS-1, displays very high selectivity against T cell-specific kinases and kinases in the MAP4K family and promising activity in in vitro and in vivo models. NMBS-1 enhanced IL-2 production from stimulated human T cells, alleviated PGE2-mediated immunosuppression of T cell activation, and enhanced IL-6 production, proliferation, and IgG secretion from B cells. In a mouse syngeneic tumor model, oral administration of NMBS-1 resulted in significant tumor growth inhibition, both as a monotherapy and in combination with anti-CTLA4.

"These data are further evidence that HPK1 inhibition is a potentially powerful approach to achieve anti-tumor immunity — and we’re very pleased that our small-molecule inhibitor displays the selectivity that has long been a challenge for drug makers in this space," said Peter Tummino, Ph.D., Chief Scientific Officer of Nimbus. "We will continue rapidly advancing our preclinical studies, with the goal of initiating a first-in-human trial next year."

The poster is titled "A Highly Selective and Potent HPK1 Inhibitor Enhances Immune Cell Activation and Induces Robust Tumor Growth Inhibition in a Syngeneic Tumor Model."

The company will be hosting a webcast to further discuss these data on Thursday, June 25, from 11 a.m. to 12 p.m. ET. If you wish to attend the live webcast, please pre-register at https://bit.ly/NimbusHPK1Seminar. A replay of the webcast will be available at this link after the event.

ORIC Pharmaceuticals Presents Preclinical Data on Glucocorticoid Receptor Antagonist and CD73 Inhibitor Programs at the 2020 American Association for Cancer Research Virtual Annual Meeting II

On June 22, 2020 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported that preclinical data from the company’s glucocorticoid receptor (GR) antagonist and CD73 inhibitor programs in five poster presentations during the ongoing American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II (Press release, ORIC Pharmaceuticals, JUN 22, 2020, https://investors.oricpharma.com/news-releases/news-release-details/oric-pharmaceuticals-presents-preclinical-data-glucocorticoid-1 [SID1234561301]).

"We are pleased to be able to present these compelling preclinical data from our ORIC-101 and CD73 programs, which continue to validate our scientific platform focused on overcoming therapeutic resistance in cancer," said Lori Friedman, chief scientific officer. "In particular, we are encouraged to see ORIC-101 reversing GR-mediated resistance in a variety of tumor models, and preliminary evidence of differentiation of ORIC-533 versus competitor compounds in preclinical studies. We look forward to the continued advancements of these programs and our discovery research pipeline as we work to improve patients’ lives."

ORIC-101 (GR Antagonist):
ORIC-101 is a potent and selective small molecule antagonist of GR, which has been linked with resistance to multiple classes of cancer therapeutics across a variety of solid tumors. ORIC-101 is currently being investigated in two separate Phase 1b combination trials, with enzalutamide in prostate cancer and with nab-paclitaxel in solid tumors.

Key findings of the presentations:

A transcriptional signature of GR activity was identified in a panel of 32 cell lines across triple negative breast cancer, non-small cell lung cancer and pancreatic ductal adenocarcinoma, which translated from preclinical models to human tumors
ORIC-101 overcame GR-mediated resistance to chemotherapeutic agents including taxanes, antimetabolites and platinums, in both in vitro and in vivo efficacy studies spanning a variety of solid tumor types
Transcriptional and histological profiling showed that ORIC-101 reversed GR-activated pathways involved in drug resistance, and reversed in vivo markers of epithelial-to-mesenchymal transition, antiapoptosis, and hypoxia
The company is further assessing the GR activation signature and mechanistic findings in an ongoing Phase 1b trial of ORIC-101 in combination with nab-paclitaxel in adults with advanced or metastatic solid tumors
Poster Presentations:

ORIC-101 comprehensively inhibits glucocorticoid pathways to overcome therapeutic resistance in pan-cancer models (Poster #4120)
ORIC-101 overcomes resistance to diverse chemotherapeutics across cancer types (Poster #4121)
ORIC-101 overcomes glucocorticoid receptor-mediated chemoresistance in pancreatic cancer models (Poster #4123)
ORIC-533 (CD73 Inhibitor):
CD73 is a key node in the adenosine pathway believed to play a central role in resistance to chemotherapy and immunotherapy. ORIC discovered and characterized differentiated orally bioavailable small molecule inhibitors of CD73, including clinical candidate ORIC-533, that revert immunosuppression and promote anti-tumor responses in vivo.

Key findings of the presentations:

ORIC’s CD73 inhibitors demonstrated suppression of adenosine production in vitro across multiple cell types and rescued activation of CD8+ T cells exposed to AMP with greater potency than competitor compounds
ORIC-533 was shown to result in sustained inhibition of adenosine production after drug washout, consistent with its slow off-rate, and differentiating from other CD73 inhibitors
ORIC-533 potency in high AMP environments distinguishes it from other compounds, with activity in AMP concentrations as high as 1 millimolar, which may better reflect certain tumor microenvironments
Daily oral delivery of ORIC’s CD73 inhibitors significantly inhibited tumor growth, with corresponding in vivo reduction of adenosine levels in tumors, and immune modulation consistent with decreased immunosuppression
Poster Presentations:

CD73 inhibition with a novel orally bioavailable small molecule blocks adenosine production and rescues T-cell activation (Poster #1023)
An orally bioavailable inhibitor of CD73 reverts intratumoral immunosuppression and promotes anti-tumor response (Poster #LB-115)

HiFiBiO Therapeutics Presents Three Novel Immuno-Oncology Programs at 2020 AACR Virtual Annual Meeting II

On June 22, 2020 HiFiBiO Therapeutics is presenting its three lead pipeline programs at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II taking place today (Press release, HiFiBiO Therapeutics, JUN 22, 2020, View Source [SID1234561300]). The company is a pioneer of novel antibody drug discovery and development leveraging single-cell analytics to treat cancer, autoimmune and infectious diseases. HiFiBiO invites members of the scientific and medical communities to listen to these poster presentations online at the AACR (Free AACR Whitepaper) meeting website or, after the AACR (Free AACR Whitepaper) meeting has concluded, at the HiFiBiO Therapeutics website.

"These presentations demonstrate the rapid progress spearheaded by our scientists at HiFiBiO and the development of our pipeline, and we look forward to soon moving our lead programs to IND," said Liang Schweizer, PhD, President and CEO of HiFiBiO Therapeutics. "Given our depth of experience in immune modulation and cutting-edge single-cell science and technology, we believe that HiFiBiO is realizing the potential of single-cell analysis to develop novel, high-quality antibody targets into life-changing treatment options for patients."

POSTER PRESENTATION DETAILS:

Title: HFB301001, a novel OX40 agonistic antibody with a unique pharmacological profile and innovative biomarker strategy
Presenters: Andreas Raue, PhD, Project Leader, Senior Director, Head of Drug Intelligent Science (DIS) at HiFiBiO Therapeutics and Robert Petit, PhD, Senior Scientific Advisor
E-Poster: #2285
HFB301001 is being developed as a potential novel treatment option for cancer coupled with a patient stratification biomarker in solid tumor indications.

Title: Discovery and characterization of novel TNFR2 antibodies to modulate T cell activities in immunosuppressive environment
Presenters: Francisco Adrian, PhD, Senior Vice President, Head of Research and Shuo Wei, PhD, Project Leader, Principal Scientist, Disease Biology
E-Poster: #2282
HFB200301 is an anti-TNFR2 monoclonal antibody being developed as a potential first-in-class therapeutic for the treatment of biomarker-selected patients with advanced cancer.

Title: HFB9-2, a novel Galectin-9 neutralizing antibody to reverse immune suppression in the tumor microenvironment
Presenters: Roshan Kumar, PhD, Senior Director, Head of Discovery Biology and US External Innovation and Yun-Yueh Lu, PhD, Project Leader, Principal Scientist, Disease Biology
E-Poster: #6532
HFB2009 program focuses on developing anti-Gal-9 neutralizing antibodies as a potential first-in-class treatment for AML and solid tumors, both as a single agent and a combination therapy.

More information about these and other programs in the HiFiBiO Therapeutics pipeline is available at View Source

Phio Presents Additional Data Supporting Potential of TIGIT Targeting INTASYL Compound in the Tumor Microenvironment at AACR 2020

On June 22, 2020 Phio Pharmaceuticals Corp. (Nasdaq: PHIO), a biotechnology company developing the next generation of immuno-oncology therapeutics based on its proprietary self-delivering RNAi (INTASYL) therapeutic platform, reported a poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2020 Virtual Annual Meeting which further details data demonstrating the potential of a TIGIT targeting INTASYL compound as an immuno-oncology therapeutic through the suppression of TIGIT in the tumor microenvironment (TME) (Press release, Phio Pharmaceuticals, JUN 22, 2020, View Source [SID1234561299]). The Phio poster presentation will also be available under the "Investors – Events and Presentations" section of the Company’s website (click here).

"In our poster presentation at the AACR (Free AACR Whitepaper) 2020 Virtual Annual Meeting, we announced detailed data supporting the potential for PH-804, our TIGIT targeting INTASYL compound, as an immuno-oncology therapeutic and a viable alternative to anti-TIGIT antibodies. This data provides insight around the mechanisms of action of the tumor growth suppression with PH-804, as previously announced from a study in a validated animal model, namely through increases in immune cell count and immune cell activation in the tumor micro-environment," said Dr. Simon Fricker, Phio’s VP of Research. "These preclinical results build upon the recent data we announced at the ASCO (Free ASCO Whitepaper) 2020 Annual Meeting that show the ability and safety of INTASYL RNAi technology to reprogram immune cells, such as T cells or NK cells, to improve their efficacy."

In an in vivo study, tumor growth inhibition was determined for both PH-804 and an anti-TIGIT antibody in colorectal carcinoma tumor bearing mice. Results from the study demonstrated that our INTASYL compound was efficiently delivered intratumorally to immune cells, resulting in a dose dependent inhibition of tumor growth, reaching statistical significance levels for PH-804 and anti-TIGIT antibody treatment arms. More detailed data from the study provides evidence of an "on-target" effect of PH-804 as shown by silencing of TIGIT mRNA expression in tumor infiltrating lymphocytes isolated from the treated tumors. In addition, analysis of the TME of the PH-804 treated mice showed a dose dependent increase in cytotoxic effector T cells, and a dose dependent activation of such T cells as shown by the expression of activation makers such as CD25 and CD69.

These data demonstrate the potential of a TIGIT targeting INTASYL compound for the suppression of TIGIT in the TME and support the hypothesis that local TIGIT silencing with INTASYL is a promising therapeutic approach.