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.

On March 10, 2021 Theratechnologies Inc. (Theratechnologies) (TSX: TH) (NASDAQ: THTX), a biopharmaceutical company focused on the development and commercialization of innovative therapies, reported that new positive pre-clinical data on TH1902, its lead peptide-drug conjugate (PDC) for the treatment of sortilin positive (SORT1+) solid tumors, will be presented in two e-posters during AACR (Free AACR Whitepaper) Annual Meeting 2021 (Press release, Theratechnologies, MAR 10, 2021, View Source [SID1234576397]).

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Presentation Title: TH1902, a docetaxel peptide-drug conjugate, shows pre-clinical efficacy in several sortilin positive (SORT1+) cancers
Abstract Number: 1313
E-Poster website launch date and time: Saturday, April 10, 2021, 8:30 AM

Presentation Title: Increasing potency of anticancer drugs through SORT1+ Technology: A new targeted approach for the treatment of ovarian and endometrial cancers
Abstract number: 1439
E-Poster website launch date and time: Saturday, April 10, 2021, 8:30 AM

On March 10, 2021 MEI Pharma, Inc. (NASDAQ: MEIP), a late-stage pharmaceutical company focused on advancing new therapies for cancer, reported that the abstract, Voruciclib, a CDK9 inhibitor, downregulates MYC and inhibits proliferation of KRAS mutant cancers in preclinical models, was selected for an E-Poster Session presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021 and will be available on April 10, 2021 (Press release, MEI Pharma, MAR 10, 2021, View Source [SID1234576396]). Voruciclib is an orally available inhibitor of cyclin-dependent kinase 9 (CDK9), part of a family of regulatory enzymes important to cell cycle regulation associated with cell proliferation and increased survival.

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KRAS mutated cancers are frequently associated with overexpression of MYC, a transcription factor regulating cell proliferation and growth. Inhibition of CDK9 leads to reduced transcription of MYC. As reported in the abstract to be presented at AACR (Free AACR Whitepaper) 2021, voruciclib decreased cell viability among multiple KRAS mutant cancer cell lines in vitro and was associated with significant tumor growth inhibition in vivo. Voruciclib treatment was associated with rapid inhibition of MYC phosphorylation at Ser62 resulting in a decrease in MYC protein. The research presented suggests that voruciclib could be an attractive therapeutic target for cancers driven by KRAS mutated cancers.

MEI pharma is also engaged in additional pre-clinical studies to explore the potential synergistic activity in various cancers of voruciclib in combination with drug-candidates that directly inhibit KRAS.

Details of MEI’s e-poster presentation at AACR (Free AACR Whitepaper) Annual Meeting 2021:

Abstract Title: Voruciclib, a CDK9 inhibitor, downregulates MYC and inhibits proliferation of KRAS mutant cancers in preclinical models
Poster Number: 1962
Poster Session Title: Cell Cycle
Date: Saturday, April 10, 2021

Abstracts and full session details can be found at View Source

About Voruciclib
Voruciclib is an orally administered cyclin-dependent kinase (CDK) inhibitor differentiated by its potent in vitro inhibition of CDK9 in addition to CDK6, 4 and 1. The CDK family of proteins are important cell cycle regulators.

CDK9 is a transcriptional regulator of the myeloid leukemia cell differentiation protein ("MCL1"), a member of the family of anti-apoptotic proteins which, when elevated, may prevent the cell from undergoing cell death. Inhibition of CDK9 blocks the production of MCL1, which is an established resistance mechanism to the B-cell lymphoma ("BCL2") inhibitor venetoclax (marketed as Venclexta).

CDK9 is also a transcriptional regulator of MYC proto-oncogene protein ("MYC"), a transcription factor regulating cell proliferation and growth which contributes to many human cancers and is frequently associated with poor prognosis and unfavorable patient survival. Targeting MYC directly has historically been difficult, but CDK9 is a transcriptional regulator of MYC and is a promising approach to target this oncogene.

Voruciclib is being currently evaluated in a Phase 1b trial evaluating dose and schedule in patients with acute myeloid leukemia ("AML") and B-cell malignancies.