Binimetinib is a potent, selective MEK1/2 inhibitor with demonstrated efficacy against BRAF- and RAS-mutant tumors. Retinal adverse events associated with MEK inhibitors have been reported in some cases. The aim of this study was to assess single-agent binimetinib, with detailed ophthalmologic monitoring, in Japanese patients with advanced solid tumors.
This was an open-label phase I dose-escalation and dose-expansion study (NCT01469130). Adult patients with histologically confirmed, evaluable, advanced solid tumors were enrolled and treated with binimetinib 30 or 45 mg twice daily (BID). The primary objective was to determine the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of single-agent binimetinib in Japanese patients.
Twenty-one patients were enrolled; 3 and 8 patients had documented BRAF and KRAS mutations, respectively. Two of 6 patients (33 %) receiving binimetinib 45 mg BID in dose-escalation experienced recurrent grade 2 retinal adverse events (AEs) which were reversible, and this dose was declared the MTD and RP2D. All patients experienced ≥1 AE suspected to be treatment related; the most common (>50 %) were blood creatine phosphokinase increase (76 %), retinal detachment and aspartate aminotransferase increase (62 % each), and diarrhea (52 %). There were no complete or partial responses; 14 patients (67 %) had stable disease, which lasted >180 days in 5 patients. Expression of phospho-ERK decreased in the skin following binimetinib treatment at both dose levels, indicating target inhibition.
Binimetinib demonstrated efficacy and acceptable safety in Japanese patients with solid tumors, supporting the 45 mg BID dose of binimetinib as the RP2D.

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KAHR-102 is a fusion protein that links portions of two immune and cancer-related membrane proteins; CTLA-4 and FasL (Company Pipeline, KAHR Medical, APR 14, 2016, View Source [SID:1234510828]).

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The functions of KAHR-102 in immune settings are anticipated from its component parts; The CTLA-4 component of KAHR-102 binds to B7 costimulators on antigen-presenting-cells (APC), such as dendritic cells, and thereby prevents them from engaging and triggering their cognate stimulatory CD28 receptor on T cells. The FasL component of the KAHR-102 fusion protein, binds to its cognate Fas receptor, which is upregulated on activated T cells, and thereby triggers apoptosis in these cells. The net effect of combining these blocking and triggering functions is to convert a T cell activating signal into an inhibitory one, leading to immune suppression.

KAHR-102 has also shown significant activity in cancer – both in-vitro and in cancer animal models. The CTLA-4 side of the drug targets to B7 receptors on lymphatic cancer cells, while the FasL side of the drug induces specific apoptosis of these cancer cells.

KAHR-102 forms a homo-hexamer which allows an optimal hexameric FasL structure to be specifically targeted to B7-expressing cells, such as in lymphoma cells.

Oncbiomune has filed a 10-K – Annual report [Section 13 and 15(d), not S-K Item 405] with the U.S. Securities and Exchange Commission (Filing, 10-K, OncBioMune Pharmaceuticals, 2017, APR 13, 2016, View Source [SID1234522115]).

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On April 13, 2016 Pharmatines reported that Boehringer Ingelheim’s Giotrif has beaten AstraZeneca’s Iressa on a number of clinical measures investigated in a head-to-head study involving patients with EGFR mutation-positive advanced non-small cell lung cancer (Press release, PharmaTimes, APR 13, 2016, View Source [SID:1234510736]).

The company says data from the Phase IIb LUX-Lung 7 trial, published in The Lancet, show that Giotrif (afatinib) significantly cut the risk of lung cancer progression and treatment failure, and boosted the overall response rate versus Iressa (gefitinib), "without compromising overall health-related quality of life, safety and tolerability".
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Giotrif reduced the risk of disease progression by 27 percent compared to Iressa, and, after two years’ treatment, more than twice as many patients taking the drug were alive and progression free than those taking AZ’ drug (27 percent vs 15 percent after 18 months, and 18 percent vs 8 percent after 24 months).

In addition, Giotrif-treated patients had a significantly longer time on treatment and risk of treatment failure was reduced by 27 percent, while significantly more patients had an objective tumour response compared to Iressa (70 percent vs 56 percent), with a median duration of response of 10.1 months and 8.4 months, respectively.

Both drugs showed similar improvements in patient-reported outcome measures with no significant differences in health-related quality of life. Treatment with both was generally tolerable, leading to an equal rate of treatment-related discontinuation in both arms (6 percent). The overall frequency of serious adverse events was 44.4 percent for Giotrif and 37.1 percent for Iressa.

"The totality of the efficacy data from LUX-Lung 7 clearly differentiates the second-generation inhibitor afatinib from the first-generation inhibitor gefitinib with no significant differences observed in overall safety, tolerability and health-related quality of life between the two TKIs," noted Professor Klaus Dugi, medical director and managing director, Boehringer Ingelheim UK & Ireland. "This is really good news for patients, and it will provide clinicians with further evidence to guide treatment practice in EGFR mutated NSCLC."

Data for the co-primary endpoint of overall survival are not yet mature and will be presented in the future, BI said.

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On April 13, 2016 Intrexon Corporation (NYSE: XON), a leader in synthetic biology, reported it has entered into Exclusive Channel Collaborations (ECC) with two startups backed by the Harvest Intrexon Enterprise Fund, sponsored by Harvest Capital Strategies, LLC (Press release, Intrexon, APR 19, 2016, View Source [SID:1234511218]). Through the proprietary technologies of Intrexon, these companies will pursue new approaches for unmet needs in human health:

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Relieve Genetics, Inc. will focus on a breakthrough, non-opioid gene therapy approach for neuropathic pain; and
Exotech Bio, Inc. will utilize a novel exosome-based platform for delivering therapeutic RNA to treat select cancer indications.

"We are excited to enter into these new collaborations within Intrexon’s Health Sector to advance medicine on multiple fronts," said Samuel Broder, M.D., Senior Vice President, Head of Intrexon’s Health Sector. "Neuropathic pain is a tremendous unmet need in healthcare today. The collaboration with Relieve Genetics offers a significant opportunity to materially impact the lives of many patients who are in desperate need of relief from pain refractory to other therapies including opiates."

Neuropathic pain is a common, chronic complication caused by a number of different medical conditions. Current standard of care focuses mainly on easing discomfort as treatments are limited by incomplete efficacy and dose-limiting side-effects. Relieve Genetics, Inc. will instead center its therapeutic efforts on the underlying pathophysiology of neuropathic pain through gene therapy. With a designed viral vector delivery system, the collaboration will target delivery of an immunomodulatory protein alone or in combination with multiple therapeutic effectors under the control of the RheoSwitch Therapeutic System, providing localized, persistent, and regulatable drug delivery for pain management.

Dr. Broder continued, "Intrexon’s work in engineering complex miRNAs holds particular promise for an exosome-based platform to address certain cancers, for which conventional approaches have failed. In addition to the significant progress underway with our partner ZIOPHARM Oncology in the utilization of gene and adoptive cellular therapies against numerous cancer types, we look forward to introducing a new and important modality with Exotech Bio to treat cancer patients who have limited options under current treatment approaches."

Exosomes are micro-vesicles that naturally contain RNA, proteins and small molecule metabolites and are transmitted between the body’s cells to facilitate intercellular communication, immune modulation and developmental cell differentiation. A growing body of research supports the re-engineering of exosomes to transport drugs, including various RNA classes, as cell-specific cargoes that can mediate therapeutic responses to a variety of cancer cell types for which conventional treatments have been unsuccessful at effectively addressing.

Intrexon’s unique expertise in the design of subcellular localization motifs, unique protein-protein interaction motifs, multimeric miRNAs, and other RNA-based modalities can be applied in a coordinated fashion for the purpose of increasing anti-cancer therapy efficacy while reducing side effects. The collaboration with Exotech Bio, Inc. is focused on developing engineered cell lines for production of tumor-targeted allogeneic exosomes carrying bioactive RNAs to act directly on intracellular cancer pathways to suppress or eliminate specific tumor cells.

Under the terms of the ECC agreements for both collaborations, Intrexon will receive a technology access fee in the form of equity equating to 25% of each startup, reimbursement for all research and development costs, as well as potential milestones and backend economics in the form of royalties.