On June 22, 2020 ESSA Pharma Inc. (Nasdaq: EPIX); (TSXV: EPI), a clinical-stage pharmaceutical company focused on developing novel therapies for the treatment of prostate cancer, reported new preclinical data on ESSA’s clinical candidate, EPI-7386, at the 2020 American Association for Cancer Research (AACR) (Free AACR Whitepaper) ("AACR") Virtual Annual Meeting II (Press release, ESSA, JUN 22, 2020, View Source [SID1234561367]).

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In an oral poster presentation titled, "Preclinical development of the second-generation N-terminal domain androgen receptor inhibitor, EPI-7386, for the treatment of prostate cancer", a robust preclinical characterization of EPI-7386 including androgen receptor (AR) binding, gene expression analyses and the toxicologic profile was presented. The studies highlight new information about EPI-7386 including:

Full-length AR target engagement by EPI-7386 was confirmed in a cellular thermal shift assay.
In vitro cellular gene expression analyses demonstrate that EPI-7386:
Inhibits AR transcriptional activity similar to enzalutamide but with a few notable qualitative and quantitative differences in an enzalutamide-sensitive cellular model.
In the same cellular model, combination treatment of EPI-7386 with enzalutamide displays broader and deeper inhibition of AR-associated transcriptional activity than higher doses of each single agent alone.
Shows superior activity to enzalutamide in an AR-V7-driven cellular model by modulating both AR-FL and AR-V7-driven gene expression.
Toxicology studies evaluating the safety profile of EPI-7386 demonstrate that:
Very high plasma exposures of EPI-7386 were achieved across all studies.
Tolerability in 28-days tox studies in rats and dogs at AUC ≤ 2,000,000 ng*hr/mL, with activity seen on androgen-sensitive target organs in dogs.
The highest doses tested were characterized as the HNSTD (highest non-severely toxic dose) and only exhibited body weight loss and reduced food consumption. The drug plasma exposures achieved at this high dose were 7-10 fold higher than the efficacious exposures achieved in mouse xenograft models.
The starting clinical dose of EPI-7386 will be 200 mg given once-daily
"Our latest transcriptomic analyses add to the breadth of preclinical data supporting the development of EPI-7386 broadly in prostate cancer. With the favorable toxicologic profile of EPI-7386 observed in our IND-enabling studies at very high exposures, we will initiate dosing at 200 mg per day, which potentially could allow us to efficiently reach biologically relevant blood levels of EPI-7386 in patients," said Dr. David R. Parkinson, President & Chief Executive Officer. "We will soon begin dosing patients in our Phase 1 monotherapy study of EPI-7386 in castration-resistant prostate cancer patients whose tumors are progressing on current anti-androgens.".

On June 22, 2020 Forbius, a clinical-stage protein engineering company that develops biotherapeutics to treat cancer and fibrosis, reported that it will participate at SVB Leerink’s inaugural Biopharma Private Company Connect July 7th-9th, 2020 (Press release, Forbius, JUN 22, 2020, View Source [SID1234561276]).

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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 Halozyme Therapeutics, Inc. (NASDAQ: HALO) reported the company will receive a $10 million milestone payment from Janssen Biotech, Inc. (Janssen) triggered under the Collaboration and License Agreement between the two companies (Press release, Halozyme, JUN 22, 2020, View Source [SID1234561320]). The milestone payment is associated with the first commercial sale in the European Union of Janssen’s subcutaneous formulation of DARZALEX (daratumumab) utilizing ENHANZE, which was recently granted marketing authorization by the European Commission.

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On June 22, 2020 Exicure, Inc. (NASDAQ: XCUR), the pioneer in gene regulatory and immunotherapeutic drugs utilizing spherical nucleic acid (SNA) constructs, reported that updated pharmacodynamic and safety data at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II, occurring June 22 – 24, 2020 (Press release, Exicure, JUN 22, 2020, View Source [SID1234561336]).

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The AACR (Free AACR Whitepaper) poster, titled "Phase 1b/2 Study of an Intratumoral TLR9 Agonist Spherical Nucleic Acid (AST-008) and Pembrolizumab: Evidence of Immune Activation," is presenting new preliminary pharmacodynamic and safety data of cavrotolimod (AST-008), alone and in combination with pembrolizumab, from Exicure’s ongoing Phase 1b/2 clinical trial (ClinicalTrials.gov identifier: NCT03684785). Cavrotolimod (AST-008) is a novel SNA configuration of a toll-like receptor 9 (TLR9) agonist oligonucleotide, designed to trigger anti-tumor immune responses.

Gene expression analysis data from patient tumor biopsies demonstrated increases in leukocytes in injected tumors after intratumoral (IT) cavrotolimod (AST-008) alone and in combination with pembrolizumab versus baseline. Uninjected tumors also showed increased immune cell levels after patients received cavrotolimod (AST-008) and pembrolizumab, suggesting immune cell trafficking.

Dose-dependent activation of key immune cells, including cytotoxic T cells and natural killer cells, as well as increases in cytokine/chemokine levels were observed in patient blood after IT cavrotolimod (AST-008) treatment alone, and cavrotolimod (AST-008) plus pembrolizumab treatment. We expect that activation of these cell types and expression of immune system signaling proteins may help produce anti-tumor effects.

Cavrotolimod (AST-008) was well-tolerated, with a safety profile consisting primarily of injection site reactions and flu-like symptoms, which is believed to reflect local and systemic immune activation. No cavrotolimod (AST-008)-related serious adverse events or dose limiting toxicity have been reported.

Using these data, a recommended Phase 2 dose of 32 mg cavrotolimod (AST-008) has been identified for the Phase 2 portion of the clinical trial now underway, where cavrotolimod (AST-008) will be given in combination with pembrolizumab or cemiplimab for the treatment of locally advanced or metastatic Merkel cell carcinoma or cutaneous squamous cell carcinoma, respectively, in patients with progression despite approved anti-PD-(L)1 therapy.

This poster is being presented during the AACR (Free AACR Whitepaper) Virtual Meeting II in the session Late-Breaking Research: Clinical Research 1 / Endocrinology under abstract number LB-140. The poster will be available for viewing from June 22 – 24.