On March 10, 2021 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 that it will present data in three poster sessions at the upcoming Virtual 2021 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting being held from April 9-14, 2021 (Press release, Mersana Therapeutics, MAR 10, 2021, View Source [SID1234576402]).

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Details of the poster displays are as follows:

Poster Title: XMT-1660, a B7-H4-targeted Dolasynthen antibody-drug conjugate for the treatment of breast cancer
Abstract Number: 907
Abstract Summary: These data indicate that XMT-1660, a DAR 6 Dolasynthen ADC, exhibited a superior preclinical profile relative to DAR 2 and DAR 12 ADCs and thus support the clinical development of XMT-1660 for the treatment of B7-H4-expressing tumors such as breast cancer and other cancers. These results demonstrate the importance of DAR-ranging studies to identify the optimal ADC for a given target.
Date: April 10, 2021
Session Category: Experimental and Molecular Therapeutics
Session Title: Antibody Technologies

Poster Title: XMT-2056, a well-tolerated, Immunosynthen-based STING-agonist antibody-drug conjugate which induces anti-tumor immune activity
Abstract Number: 1738
Abstract Summary: These data demonstrate that XMT-2056 induced robust anti-tumor immune activity, with only minimal increases in systemic cytokine levels, and exhibited significant benefit over the benchmark IV administered free STING-agonist in mice. Additional studies demonstrate that Immunosynthen ADCs activate the STING pathway in both tumor-resident immune cells and tumor cells, offering a potential advantage over ADCs that modulate other innate immune activating pathways. XMT-2056 was well-tolerated in non-human primates at significantly higher exposure levels than those required for anti-tumor activity in mice and exhibited favorable pharmacokinetics after repeat doses. Together these data support the clinical development of XMT-2056.
Date: April 10, 2021
Session Category: Immunology
Session Title: Immunomodulatory Agents and Interventions

Poster Title: Tumor cell-intrinsic STING pathway activation leads to robust induction of Type III Interferons and contributes to the anti-tumor activity elicited by STING agonism
Abstract Number: 1773
Abstract Summary: The STING pathway induces anti-tumor immunity by upregulating an interferon response within the tumor microenvironment. Data presented in this study demonstrate that cancer cells activate a Type III interferon response downstream of STING pathway activation. Blocking Type III IFNs with neutralizing antibodies in cancer cell:immune cell co-cultures inhibits the production of key cytokines and cancer cell killing induced by STING-agonist ADC treatment. These results indicate that the Type III IFN response in cancer cells plays an important role in the anti-tumor activity induced by STING-agonist ADCs.
Date: April 10, 2021
Session Category: Immunology
Session Title: Innate Immunity to Tumors

On March 10, 2021 Surface Oncology (Nasdaq: SURF), a clinical-stage immuno-oncology company developing next-generation immunotherapies that target the tumor microenvironment, reported two scientific e-posters sharing updated preclinical data will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2021 Annual Meeting, to be held virtually April 10-15 and May 17-21, 2021 (Press release, Surface Oncology, MAR 10, 2021, View Source [SID1234576401]).

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The e-poster website will be launched at 8:30 a.m. ET on Saturday, April 10, and will remain available for viewing through Monday, June 21.

The posters include preclinical data from Surface Oncology’s two lead clinical-stage antibody therapies: SRF617 (targeting CD39) and SRF388 (targeting IL-27). Summaries are provided below; full posters will be placed on Surface Oncology’s website following the presentations.

Details of the AACR (Free AACR Whitepaper) presentations are as follows:
Presentation Type: e-poster (Abstract: 1802)
Title: CD39 inhibition shapes the transcriptional landscape of myeloid cells and induces proinflammatory states in the CT26 syngeneic tumor model
Lead Authors: Devapregasan Moodley, Ph.D. and Mayra Carneiro

Summary:

SRF617 is a potent inhibitor of CD39 enzymatic activity both in vitro and in vivo.
Increased activity of CD39 results in significant reductions in extracellular ATP and subsequent accumulation of adenosine, contributing to tumor immune escape, induction of angiogenesis and metastatic progression.
Immunological mechanisms associated with CD39 blockade reveal major changes to immunocyte transcriptional landscapes, including upregulation of several proinflammatory genes.
CD39 inhibition predominantly shaped the transcriptional landscape of myeloid cells and dendritic cells, and generally induced proinflammatory conditions.
These findings indicate that CD39 blockade induces proinflammatory responses, supporting future clinical studies of SRF617 in treating patients with cancer.
Presentation Type: e-poster (Abstract: 1607)
Title: IL-27 signaling serves as an immunological checkpoint for NK cells to promote hepatocellular carcinoma in multiple murine models
Lead Author: Turan Aghayev

Summary:

SRF388 is a fully human antibody designed to inhibit the immunosuppressive activity of IL-27.
IL-27 signaling suppresses natural killer (NK) cells within the tumor microenvironment, promoting hepatocellular carcinoma (HCC) development in vivo.
Elevated IL-27RA expression in cancer tissue and elevated EBI3 serum levels are associated with poor prognosis in patients with HCC.
Inhibiting IL-27 signaling leads to tumor growth inhibition and suppressed HCC development in a non-alcoholic steatohepatitis (NASH)-driven HCC model with concomitant enhancement of NK cell activity.
These findings indicate that IL-27 blockade regulates NK cell-mediated control of HCC and is a promising therapeutic target in liver cancer.

On March 10, 2021 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC) reported that it will present updated clinical data from its AWARE-1 window-of-opportunity study in patients with early-stage breast cancer, as well as results from preclinical studies evaluating pelareorep-based combination therapies, in poster presentations during Week 1 of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021, taking place virtually from April 10-15, 2021 (Press release, Oncolytics Biotech, MAR 10, 2021, View Source [SID1234576400]).

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Oncolytics Biotech Logo (PRNewsfoto/Oncolytics Biotech, Inc.)
Details on the posters and corresponding abstracts are shown below. All posters will be made available on the conference website on April 10, 2021.

Title: A window-of-opportunity study with atezolizumab and the oncolytic virus pelareorep in early breast cancer (AWARE-1)
Session Type: E-Poster Session
Session Category: Phase II Clinical Trials
Session Title: Phase II Clinical Trials
Abstract Number: CT191 (late-breaking abstract)

Oncolytics will provide details on the results described in this abstract following publication of the abstract and corresponding poster at the AACR (Free AACR Whitepaper) Annual Meeting in April, in accordance with conference embargo policies regarding late-breaking abstracts.

Title: Mechanisms of therapeutic synergy between pattern recognition response agonists and cdk4 inhibitors
Session Type: E-Poster Session
Session Category: Molecular and Cellular Biology / Genetics
Session Title: Cell Cycle
Abstract Number: 1960

New preclinical studies identify the mechanisms of therapeutic synergy between pelareorep and the CDK4/6 inhibitor palbociclib. Data show that combining pelareorep with palbociclib augmented pelareorep-induced endoplasmic reticulum (ER) stress signaling and increased innate immune activation and effector function. These results suggest that this combination can be exploited to enhance anti-cancer efficacy with pro-immunogenic consequences and suggest that pelareorep may have the potential to broaden the therapeutic applicability of CDK4/6 inhibitors.

The full text of the corresponding abstract is available on the AACR (Free AACR Whitepaper) Annual Meeting 2021 website (link).

Title: Talazoparib interacts with oncolytic reovirus to enhance death-inducing signaling complex (DISC)-mediated apoptosis and immune response
Session Type: E-Poster Session
Session Category: Molecular and Cellular Biology / Genetics
Session Title: Apoptosis
Abstract Number: 1932

New preclinical data show that combining pelareorep with talazoparib, a clinically approved poly(ADP)-ribose polymerase 1 (PARP-1) inhibitor, led to enhanced anti-tumor efficacy that correlated with an increased immune response in murine tumor models. These data provide a scientific rationale for combining pelareorep with PARP-1 inhibitors to exploit immunogenic responses in cancer treatment.

The full text of the corresponding abstract is available on the AACR (Free AACR Whitepaper) Annual Meeting 2021 website (link).

About AWARE-1
AWARE-1 is an open label window-of-opportunity study in early-stage breast cancer enrolling 38 patients into five cohorts:

Cohort 1 (n=10), HR+ / HER2- (pelareorep + letrozole)

Cohort 2 (n=10), HR+ / HER2- (pelareorep + letrozole + atezolizumab)

Cohort 3 (n=6), TNBC (pelareorep + atezolizumab)

Cohort 4 (n=6), HR+ / HER2+ (pelareorep + trastuzumab + atezolizumab)

Cohort 5 (n=6), HR- / HER2+ (pelareorep + trastuzumab + atezolizumab)
The study combines pelareorep, with or without atezolizumab, and the standard of care therapy according to breast cancer subtype. Patients are biopsied as part of their initial breast cancer evaluation, then again on day three following initial treatment, and a final tissue sample after three weeks, on the day of their mastectomy. Data generated from this study are intended to confirm that the virus is acting as a novel immunotherapy and to provide comprehensive biomarker data by breast cancer subtype. The primary endpoint of the study is overall CelTIL (a measurement of cellularity and tumor-infiltrating lymphocytes). Secondary endpoints for the study include CelTIL by breast cancer subtype, safety and tumor, and blood-based biomarkers.

For more information about the AWARE-1 study, refer to View Source

About Pelareorep
Pelareorep is a non-pathogenic, proprietary isolate of the unmodified reovirus: a first-in-class intravenously delivered immuno-oncolytic virus for the treatment of solid tumors and hematological malignancies. The compound induces selective tumor lysis and promotes an inflamed tumor phenotype through innate and adaptive immune responses to treat a variety of cancers and has been demonstrated to be able to escape neutralizing antibodies found in patients.

On March 10, 2021 Vincerx Pharma, Inc. (Nasdaq: VINC), a biopharmaceutical company aspiring to address the unmet medical needs of patients with cancer through paradigm-shifting therapeutics, reported a poster presentation at the upcoming American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021, being held virtually April 10-15, 2021 (Press release, Vincerx Pharma, MAR 10, 2021, View Source [SID1234576399]).

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Poster presentation details:
Poster Title: A novel small molecule drug conjugate -αvβ3 integrin antagonist linked to a cytotoxic camptothecin derivative- for the treatment of multiple cancer types
Presenter: Hans-Georg Lerchen
Session Type: E-Poster Session
Session Category: Experimental and Molecular Therapeutics
Session Title: Novel Drug Delivery Systems
Permanent Abstract Number: 1314
A copy of the presentation materials can be accessed on the Investors section of the Company’s website at www.vincerx.com once the presentation has concluded.

On March 10, 2021 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of resistance in cancer, reported four preclinical poster presentations at the 2021 American Association for Cancer Research (AACR) (Free AACR Whitepaper) virtual annual meeting on April 10-15, 2021 (Press release, ORIC Pharmaceuticals, MAR 10, 2021, View Source [SID1234576398]).

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"We are pleased to present these compelling preclinical data on our four product candidates, which continue to validate our scientific platform focused on overcoming resistance in cancer," said Lori Friedman, chief scientific officer. "In particular, we are encouraged to see our lead program ORIC-101 reversing GR-mediated resistance in a variety of tumor models and contexts. Furthermore, ORIC-533, ORIC-944 and ORIC-114 each continue to show mounting evidence of potential best-in-class differentiation. We look forward to the continued advancements of these programs and our discovery research pipeline as we work to improve the lives of patients with cancer."

ORIC-101: Glucocorticoid Receptor (GR) Antagonist

Title: GR antagonist ORIC-101 overcomes GR-mediated resistance to the combination of AR and AKT inhibition in preclinical prostate cancer cell lines
Date: Poster release on April 10, 2021
Session: Reversal of Drug Resistance
Abstract: 1420

ORIC-101 is a potent and selective GR antagonist, with two distinct mechanisms of action being evaluated in two Phase 1b trials in combination with: (1) Abraxane (nab-paclitaxel) in advanced or metastatic solid tumors and (2) Xtandi (enzalutamide) in metastatic prostate cancer. It has previously been demonstrated that ORIC-101 reverses GR-mediated resistance to enzalutamide and to AR degraders in preclinical prostate cancer cell lines. This preclinical study evaluated whether activated GR confers resistance to the combination of AKT inhibitors with enzalutamide and whether co-treatment with ORIC-101 reverses GR-mediated resistance to the combination. It was observed that GR upregulation and activation, an established resistance mechanism for antiandrogens, may drive resistance when antiandrogens are combined with AKT inhibitors, and our data demonstrated that ORIC-101 was able to overcome this resistance and restore antitumor activity.

ORIC-533: CD73 Inhibitor

Title: Blocking adenosine production with ORIC-533, a CD73 inhibitor with best-in-class properties, reverses immunosuppression in high-AMP environments
Date: Poster release on April 10, 2021
Session: Modifiers of the Tumor Microenvironment
Abstract: LB-163

ORIC-533 is a highly potent, orally bioavailable CD73 inhibitor and has demonstrated greater potency in preclinical studies compared to an antibody approach and other small molecule CD73 inhibitors. In these studies, nanomolar concentrations of ORIC-533 efficiently rescued cytotoxic T-cell function in the presence of high AMP concentrations, reflective of levels observed in tumors. Additionally, inhibitors of adenosine receptors A2A or A2A/B were only able to rescue CD8+ T-cell function in the context of low micromolar AMP, thus may be ineffective in tumors with moderate or high AMP and adenosine levels. These preclinical results indicate that ORIC-533 has potential best-in-class properties in reversing immunosuppression in tumors.

ORIC-944: PRC2 Inhibitor

Title: ORIC-944, a potent and selective allosteric PRC2 inhibitor, demonstrates robust in vivo activity in prostate cancer models
Date: Poster release on April 10, 2021
Session: Epigenetic Targets
Abstract: 1131

ORIC-944 is a potent and selective allosteric inhibitor of polycomb repressive complex 2 (PRC2) and targets its regulatory embryonic ectoderm development (EED) subunit. The unique EED targeting strategy may more completely inhibit PRC2, and may address certain resistance mutations in EZH2 and the possible compensatory escape mechanism of EZH1. ORIC-944 has potential best-in-class drug properties compared to first generation PRC2 inhibitors, and superior in vivo efficacy was observed when compared to tazemetostat in a DLBCL model. In prostate cancer, ORIC-944 demonstrated strong tumor growth inhibition as a single agent with once daily dosing in both enzalutamide-responsive and enzalutamide-resistant models.

ORIC-114: EGFR/HER2 Inhibitor

Title: ORIC-114, a brain penetrant, orally bioavailable, irreversible inhibitor selectively targets EGFR and HER2 exon20 insertion mutants and regresses intracranial NSCLC xenograft tumors
Date: Poster release on April 10, 2021
Session: Tyrosine Kinase and Phosphatase Inhibitors
Abstract: 1466

ORIC-114 is a brain penetrant, orally bioavailable, irreversible inhibitor designed to selectively target EGFR and HER2 with high potency against exon 20 insertion mutations. Assessment of kinase panels showed ORIC-114 is highly selective to the EGFR family of receptors, with superior kinome selectivity compared to other exon 20 inhibitors. ORIC-114 also demonstrated low nanomolar potency across exon 20 insertion variants in biochemical and cell-based assays. Regressions were observed in multiple EGFR exon 20 patient-derived xenograft models using once daily oral administration. Importantly, ORIC-114 displayed superior brain exposure relative to other compounds targeting exon 20 and significantly regressed established EGFR-driven intracranial NSCLC tumors, commensurate with the superior brain exposure of ORIC-114.