On August 21, 2018 Imago BioSciences, a clinical-stage pharmaceutical company developing novel anti-cancer therapies, reported that the Phase 1/2a clinical trial of IMG-7289 for the treatment of high-risk acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) has fully enrolled at 45 patients (Press release, Imago BioSciences, AUG 21, 2018, View Source [SID1234529013]). This study assessed the safety, pharmacokinetics, pharmacodynamics and anti-neoplastic activity of IMG-7289, an inhibitor of the epigenetic enzyme lysine-specific demethylase 1.

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"We are extremely grateful to have worked with terrific investigators and staff that enrolled and cared for a population of patients in great need of therapeutic options," said Hugh Young Rienhoff, Jr. M.D., Imago’s Chief Executive Officer. "This study generated a wealth of knowledge about the pharmacokinetics, pharmacodynamics, and safety profile of our LSD1 inhibitor IMG-7289 as a single agent and in combination with ATRA. This study provides very clear guidance on how to use IMG-7289 at a variety of doses and in a variety of indications."

Upon the successful completion of the Phase 1 multiple ascending dose portion of the trial assessing IMG-7289 as a single agent, the study progressed into the Phase 2a expansion arm which evaluated the combination treatment regimen of IMG-7289 plus ATRA for extended dosing durations. Treatment of the final 2a expansion cohort remains ongoing.

About IMG-7289

IMG-7289 is a small molecule developed by Imago BioSciences that inhibits lysine-specific demethylase 1 (LSD1 or KDM1A), an enzyme regulating cytokine expression and shown to be vital in sustaining self-renewal in cancer stem/progenitor cells, particularly neoplastic bone marrow cells. In non-clinical studies, IMG-7289 demonstrated robust in vivo anti-tumor efficacy across a range of myeloid malignancies and models of myeloproliferative neoplasms as a single agent and in combination with other therapeutic agents. IMG-7289 also shows activity against solid tumors in combination with other agents in non-clinical models. IMG-7289 is an investigational agent currently being evaluated in a second Phase 1/2a clinical trial in high-risk myelofibrosis patients aged 18 or older is currently enrolling patients in both United States and Australia. (www.clinicaltrials.gov Identifier NCT03136185).

On August 21, 2018 Inovio Pharmaceuticals, Inc. (NASDAQ: INO) reported that the Company will participate in the following upcoming investment conferences (Press release, Inovio, AUG 21, 2018, View Source [SID1234529012]):

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Rodman and Renshaw 20th Annual Global Investment Conference, sponsored by H.C. Wainwright & Co., LLC
Presentation
Dr. J. Joseph Kim, President & CEO
September 5, 2018, 10:25 AM ET
New York, NY

Citi’s 13th Annual Biotech Conference
1×1 meetings only
September 6, 2018
Boston, MA

Cantor Fitzgerald 2018 Global Healthcare Conference
Presentation
Dr. J. Joseph Kim, President & CEO
October 2, 2018, 10:55 AM ET
New York, NY

Live and archived versions of the presentations will be available through the Inovio Investor Relations Events page at View Source

On August 21, 2018 Aclaris Therapeutics, Inc. (NASDAQ:ACRS), a dermatologist-led biopharmaceutical company focused on identifying, developing, and commercializing innovative therapies to address significant unmet needs in aesthetic and medical dermatology and immunology, reported a publication in the journal Cancer Research (Press release, Aclaris Therapeutics, AUG 21, 2018, View Source [SID1234529011]).

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The title of the article is: "Inhibition of the stromal p38MAPK/MK2 pathway limits breast cancer metastases and chemotherapy-induced bone loss."

ATI-450, an investigational drug, is a selective inhibitor of p38 mitogen-activated protein kinase-activated protein kinase 2 (p38MAPK/MK2) interface and an attractive candidate for stromal-targeted therapy. Levels of p38MAPKα expressed by a tumor and the surrounding stromal cells correlate with poor prognosis. In addition, p38MAPK signaling plays a key role in regulating osteoclast differentiation. In this paper, mouse models were utilized to explore the stromal inhibition of p38MAPK/MK2 pathway with oral ATI-450 in limiting breast cancer metastasis and protecting against bone loss, a major comorbidity of breast cancer.

Key Preclinical findings:

Pharmacologically targeting the stromal p38MAPK/MK2 pathway limits breast cancer metastasis, preserves bone quality, and extends survival.
The role of the stromal compartment in tumor progression is strongly illustrated in breast cancer bone metastases, where the stromal compartment supports tumor growth, albeit through poorly defined mechanisms.
p38MAPKα is frequently expressed in tumor cells and surrounding stromal cells, and its expression levels correlate with poor prognosis. This observation led the authors to investigate whether inhibiting the p38MAPKα pathway could reduce breast cancer metastases in a clinically relevant model.
Orally administered ATI-450 limited outgrowth of metastatic breast cancer cells in the bone and visceral organs.
This effect was primarily mediated by p38MAPKα-MK2 pathway inhibition within the stromal compartment. Beyond limiting metastatic tumor growth, ATI-450 reduced tumor-associated and chemotherapy-induced bone loss, a serious comorbidity that greatly diminishes quality of life for cancer patients.
These data: a) support a central role for stromal-derived factors in tumor progression; and (b) identify the p38MAPK-MK2 pathway as a promising therapeutic target for treating metastatic disease and preventing chemotherapy- and tumor-induced bone loss.
Several studies have shown that the stroma plays a significant role in tumor progression, thereby establishing a rationale for developing stroma-targeted anti-tumor therapies. The findings of Dr. Stewart and her colleagues suggest that stromal-targeted therapies have the potential to provide durable responses, help circumvent drug resistance, and synergize with tumor-targeted therapies.

This study was carried out by the laboratory of Sheila Stewart, Ph.D., at the Washington University School of Medicine in St. Louis in collaboration with Aclaris Therapeutics, Inc.

The article is available at View Source and will appear in print form in the future.

On August 21, 2018 AstraZeneca reported that the Japanese Ministry of Health, Labour and Welfare (MHLW) has approved Tagrisso (osimertinib) for the 1st-line treatment of patients with inoperable or recurrent epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC), following priority review (Press release, AstraZeneca, AUG 21, 2018, View Source [SID1234529010]). The approval is based on results from the global Phase III FLAURA trial which included Japanese patients and which were published in the New England Journal of Medicine.

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Dave Fredrickson, Executive Vice President, Head of the Oncology Business Unit, said: "Tagrisso is already approved in Japan for the treatment of patients with EGFR T790M mutation-positive inoperable or recurrent NSCLC that is resistant to existing 1st-line EGFR-inhibitor medicines. Today’s approval moves the use of Tagrisso to the 1st-line setting, replacing older medicines which, given the high prevalence of the EGFR mutation in Japan, offers an important new treatment option for these patients."

The FLAURA trial compared Tagrisso to current 1st-line EGFR tyrosine kinase inhibitors (TKIs), erlotinib or gefitinib in previously-untreated patients with locally-advanced or metastatic EGFR-mutated (EGFRm) NSCLC. In the trial, Tagrisso demonstrated superior progression-free survival (PFS) of 18.9 months compared with 10.2 months for the comparator arm (see table below), and this benefit was consistent across all subgroups including in patients with or without central nervous system (CNS) metastases, an important benefit for lung cancer patients.

FLAURA trial efficacy results according to investigator assessment

Safety data for Tagrisso in the FLAURA trial were in line with those observed in prior clinical trials. Tagrisso was generally well tolerated, with Grade 3 or higher adverse events (AEs) occurring in 34% of patients taking Tagrisso and 45% in the comparator arm. The most common adverse reactions in patients treated with Tagrisso were rash/acne (54.5%), diarrhoea (49.5%), dry skin/eczema (33.3%) and nail disorder including paronychia (32.6%) (at the time of supplementary approval).

Tagrisso has now received approval in 40 countries for the 1st-line treatment of patients with metastatic EGFRm NSCLC, including the US, Japan and in Europe. Other global health authority reviews and submissions are ongoing.

About EGFRm NSCLC

Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths, more than breast, prostate and colorectal cancers combined. Lung cancer is broadly split into NSCLC and small cell lung cancer (SCLC), with 80-85% classified as NSCLC. Approximately 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC. These patients are particularly sensitive to treatment with EGFR-TKIs which block the cell-signalling pathways that drive the growth of tumour cells. Approximately 25% of patients with EGFRm NSCLC have brain metastases at diagnosis, increasing to approximately 40% within two years of diagnosis. The presence of brain metastases often reduces median survival to less than 8 months.

About Tagrisso

Tagrisso (osimertinib) is a third-generation, irreversible EGFR-TKI designed to inhibit both EGFR-sensitising and EGFR T790M-resistance mutations, with clinical activity against CNS metastases. Tagrisso 40mg and 80mg once-daily oral tablets have now received approval in 40 countries, including the US, Japan and in Europe, for 1st-line EGFRm advanced NSCLC, and more than 75 countries, including the US, Japan, China and in Europe, for 2nd-line use in patients with EGFR T790M mutation-positive advanced NSCLC. Tagrisso is also being developed in the adjuvant setting (ADAURA), in the locally-advanced unresectable setting (LAURA), and in combination with other treatments.

About the FLAURA trial

The FLAURA trial assessed the efficacy and safety of Tagrisso 80mg orally once daily vs. standard-of-care EGFR-TKIs (either erlotinib [150mg orally, once daily] or gefitinib [250mg orally, once daily]) in previously-untreated patients with locally-advanced or metastatic EGFRm NSCLC. The trial was double-blinded and randomised, with 556 patients across 29 countries.

On August 21, 2018 Kyowa Hakko Kirin Co., Ltd. (Tokyo: 4151 President and COO: Masashi Miyamoto; "Kyowa Hakko Kirin") reported that it has obtained the partial change approval for POTELIGEO* (code name: KW-0761; generic name: mogamulizumab) from the Ministry of Health, Labor and Welfare in Japan (Press release, Kyowa Hakko Kirin, AUG 21, 2018, View Source [SID1234529005]). The approved partial change includes removing the requirement for pre-treatment diagnostic testing, and changing the dosage and administration in patients with relapsed or refractory cutaneous T-cell lymphoma (CTCL)*

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The approval is based on data from the MAVORIC (Mogamulizumab anti-CCR4 Antibody Versus ComparatOR In CTCL) study, the largest global randomized clinical trial of systemic therapy in CTCL. In the MAVORIC study, identification of CCR4 positive cells in patients before enrollment into the study was not required and the enrolled patients were treated with mogamulizumab 1.0 mg/kg intravenously on a weekly basis for the first 28-day cycle, then on days 1 and 15 of subsequent cycles. With the partial change approval, the requirement for diagnostic testing for CCR4 expression will be unnecessary and the dosage schedule will be changed for CTCL in Japan.

"With this approval, I believe POTELIGEO is more helpful for patients with relapsed or refractory cutaneous T-cell lymphoma and healthcare professionals in Japan," said Mitsuo Satoh Ph.D., Executive Officer, Vice President Head of R&D Division of Kyowa Hakko Kirin, "Kyowa Hakko Kirin is dedicated to using advanced science and research methodologies to contribute to patients with unmet medical needs."

On August 8, POTELIGEO was approved for the treatment of adult patients with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) after at least one prior systemic therapy by the U.S. Food and Drug Administration (FDA). The marketing authorization application for mogamulizumab is currently under review by the European Medicines Agency (EMA) in Europe. The Kyowa Hakko Kirin Group companies strive to contribute to the health and well-being of people around the world by creating new value through the pursuit of advances in life sciences and technologies.

About CTCL (Cutaneous T-cell Lymphoma)
CTCL is a rare type of non-Hodgkin’s T-cell lymphoma. The two most common types of CTCL are mycosis fungoides (MF) and Sézary syndrome (SS), and depending on the stage, the disease may involve skin, blood, lymph nodes, and viscera. In advanced stage CTCL is associated with significant morbidity and mortality.

About POTELIGEO (KW-0761)
News Release
POTELIGEO is a humanized monoclonal antibody (mAb) directed against CC chemokine receptor 4 (CCR4), which is frequently expressed on leukemic cells of certain hematologic malignancies including CTCL (cutaneous T-cell lymphoma). POTELIGEO was produced using Kyowa Hakko Kirin’s proprietary POTELLIGENT platform, which is associated with enhanced antibody-dependent cellular cytotoxicity (ADCC). It was approved first in japan for treatment of relapsed or refractory CCR4 positive adult T cell lymphoma (ATL) in March 2012 (brand name: POTELIGEO). In addition, mogamulizumab received approvals in Japan for an additional indication for relapsed or refractory CCR4-positive peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL) in March 2014 and for chemotherapy-naïve CCR4-positive adult T-cell leukemia-lymphoma (ATL) in December 2014.

About MAVORIC
MAVORIC is a Phase 3 open-label, multi-centre, randomized study of mogamulizumab versus Vorinostat, active comparator in patients with CTCL who have failed at least one prior systemic treatment. The study was the largest comparative trial in patients with CTCL conducted in the US, Europe, Japan and Australia, and randomized 372 patients.