On June 22, 2020 Mersana Therapeutics, Inc. (NASDAQ:MRSN), a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody-drug conjugates (ADCs) targeting cancers in areas of high unmet medical need, reported preclinical data for XMT-1592, its clinical stage Dolasynthen ADC targeting NaPi2b, as well as progress on its Immunosynthen STING-agonist ADC platform at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2020 Virtual Annual Meeting (Press release, Synaffix, JUN 22, 2020, View Source [SID1234561304]).

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"The advancement of XMT-1592 is another example of our commitment to innovation in the ADC field and to extending our leadership in NaPi2b-targeted therapy. The ongoing Phase 1 study aims to clinically validate the advantages represented by the preclinical data shown in the AACR (Free AACR Whitepaper) poster," said Timothy B. Lowinger, Ph.D., Chief Science and Technology Officer of Mersana Therapeutics. "With Immunosynthen, we are leveraging our expertise to extend the benefits of ADCs into the realm of immuno-oncology with the aim of stimulating the innate immune system in a targeted, safe and effective manner. These data demonstrate that across multiple targets, antibodies and pre-clinical models, the Immunosynthen STING-agonist ADC platform delivers robust, target-dependent anti-tumor effects at well-tolerated doses and induces tumor-specific immune memory and other hallmarks of immune activation. We remain on track to select our first Immunosynthen STING-agonist ADC development candidate in the second half of 2020."

"We’ve made significant progress with our differentiated Dolasynthen and Immunosynthen ADC platforms to advance our pipeline," said Anna Protopapas, President and Chief Executive Officer of Mersana Therapeutics. "These novel platforms, together with our clinically validated Dolaflexin platform, represent significant breakthroughs in the ADC field. Our vision is to continue to leverage these platforms to deliver meaningful therapies to patients in need."

Details of the posters are as follows:

Poster Title: XMT-1592, a Site-Specific Dolasynthen-Based NaPi2b-Targeted Antibody-Drug Conjugate for the Treatment of Ovarian Cancer and Lung Adenocarcinoma

Poster Number: 2894

Date: June 22, 2020 at 9:00 a.m. ET and on demand

Session Type: Poster Session

XMT-1592 is an ADC created using Dolasynthen, Mersana’s proprietary, customizable and homogeneous platform designed to precisely optimize an ADC for a given target, drug-to-antibody ratio (DAR) and antibody. XMT-1592 is currently in an ongoing Phase 1 dose escalation study to determine the maximum tolerated dose (MTD) in patients with non-small cell lung cancer (NSCLC) adenocarcinoma and ovarian cancer. This poster evaluates the benefits of site-specific bioconjugation of Dolasynthen by reporting in vitro and in vivo comparisons of XMT-1592 to a stochastically conjugated version of the ADC. XMT-1592 shows improved in vivo activity, pharmacokinetics and clinical pathology relative to its stochastic counterpart. These data also show that XMT-1592 induced sustained tumor regressions in an NSCLC adenocarcinoma patient-derived xenograft.

Poster Title: Systemic Administration of STING-Agonist Antibody-Drug Conjugates Elicit Potent Anti-Tumor Immune Responses with Minimal Induction of Circulating Cytokines

Poster Number: 6706

Date: June 22, 2020 at 9:00 a.m. and on demand

Session Type: Poster Session

These data presented today show that Immunosynthen represents a novel STING-agonist ADC platform for the systemic administration of a therapeutic agent with targeted immune-stimulatory effects. These data show target-dependent anti-tumor immune responses in vitro and in vivo as a single well-tolerated dose for multiple targets in multiple preclinical models. The data also show that the STING-agonist ADC was more active (over 100-fold increased potency) with limited induction of systemic cytokines when compared to intravenously administered unconjugated (free) agonist, suggesting it may confer an improved therapeutic index. In addition, potent ADC-mediated tumor regression led to durable immunological memory in an immune competent model.

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.

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]).

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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.

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]).

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"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)

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.

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"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