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Boehringer Ingelheim launches ambitious ELUXA trial programme to broadly investigate promising lung cancer compound olmutinib

On June 2, 2016 Boehringer Ingelheim reported that it has initiated the ELUXA trial programme, designed to further investigate the therapeutic potential of olmutinib* (BI 1482694 / HM61713), a novel third-generation, epidermal growth factor receptor (EGFR) mutation-specific tyrosine kinase inhibitor (TKI) for the treatment of EGFR mutation-positive non-small cell lung cancer (NSCLC) (Press release, Boehringer Ingelheim, JUN 2, 2016, View Source [SID:1234512970]).

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The company will comprehensively investigate olmutinib as a monotherapy in different settings as well as in combination with investigational and established anti-cancer treatments, such as MSD’s anti-PD-1 therapy, pembrolizumab (Keytruda+). Third-generation EGFR TKIs, including olmutinib, aim to provide new, much-needed treatment options for patients who have developed resistance to first- and second-generation TKIs and their potential as new treatment options in first-line is currently being investigated.

The ELUXA trial programme builds on the encouraging clinical data seen in the Phase I/II HM-EMSI-101 trial investigating olmutinib in EGFR mutation-positive lung cancer patients who have become resistant to first-line TKI therapy. The trial was the basis for the first registration of olmutinib in South Korea. An updated analysis of this trial will be presented at ASCO (Free ASCO Whitepaper) 2016.

Dr Mehdi Shahidi, Medical Head, Solid Tumour Oncology, Boehringer Ingelheim commented, "With encouraging activity of olmutinib observed in patients with EGFR mutation-positive NSCLC, we are proudly announcing our extensive ELUXA trial programme. We are excited to apply our expertise in this field, gained during the continuing development of afatinib through the LUX-Lung programme, and launch another comprehensive clinical programme. The ELUXA trial programme is designed to shed further light on our understanding of EGFR mutation-positive lung cancer to ultimately improve the outcomes for patients with high unmet medical need."

Olmutinib will be investigated as a monotherapy through the following trials:

ELUXA 1 (HM-EMSI-202): This Phase II trial was initiated in 2015 and aims to help establish the safety and efficacy of olmutinib in patients with EGFR T790M mutation-positive lung cancer, following initial EGFR TKI treatment. The study has completed enrolment with more than 150 patients worldwide and will form the basis of regulatory submissions
ELUXA 2: This Phase III trial will be initiated in 2016 to investigate the efficacy and safety of olmutinib in comparison to standard, platinum-doublet chemotherapy for patients with EGFR T790M mutation-positive lung cancer, whose disease progressed on one prior EGFR TKI treatment
ELUXA 3: This Phase III head-to-head trial to be initiated in 2016 will investigate olmutinib as a first-line treatment compared to a second-generation EGFR TKI, afatinib** (Giotrif/Gilotrif), in patients with EGFR mutation-positive NSCLC
ELUXA 4: This Phase I/II trial in Japanese patients with EGFR T790M mutation-positive NSCLC will be initiated in 2016
ELUXA 6: This Phase II study will be the first trial to prospectively use blood-based biomarker testing to select patients with EGFR T790M mutation-positive NSCLC where a needle biopsy may not be appropriate
As the landscape of lung cancer care changes, and the development of novel therapies and biomarker testing continue to rapidly evolve, Boehringer Ingelheim is committed to investigating how treatment approaches might be combined to develop more effective therapies and sequences of treatments for patients. By targeting multiple oncogenic mechanisms, research suggests that combinations may overcome drug resistance and better control cancer, delivering improved outcomes for patients.

The ELUXA trial programme will investigate olmutinib in different settings of EGFR mutation-positive lung cancer in combination with both Boehringer Ingelheim compounds and treatments developed by external parties. These trials will include:

Olmutinib in combination with pembrolizumab (Keytruda+), a new collaboration through a subsidiary of MSD (MSD is also known as Merck in the U.S. and Canada)
Olmutinib plus afatinib** (Giotrif/Gilotrif)
Olmutinib plus IGF ligand-neutralizing antibody BI 836845****
Olmutinib plus oral nintedanib*** (Vargatef)
Olmutinib plus bevacizumab (Avastin)

* Olmutinib (BI 1482694 / HM61713) is approved in South Korea for the treatment of EGFR T790M mutation-positive lung cancer. Olmutinib is not approved in other indications and jurisdictions. Trials are ongoing and data will be submitted to other regulatory bodies in due course.

** Afatinib is approved in a number of markets, including the EU, Japan, Taiwan and Canada under the brand name Giotrif, in the US under the brand name Gilotrif and in India under the brand name Xovoltib for use in patients with distinct types of EGFR mutation-positive NSCLC. Afatinib is also approved in the EU, US and other markets for the treatment of patients with advanced SqCC of the lung whose disease has progressed (on or) after treatment with platinum-based chemotherapy. Afatinib is under regulatory review by health authorities in other countries worldwide. Registration conditions differ internationally, please refer to locally approved prescribing information.

*** Nintedanib is approved in the EU under the brand name Vargatef for use in combination with docetaxel in adult patients with locally advanced, metastatic or locally recurrent NSCLC of adenocarcinoma tumour histology after first-line chemotherapy. Nintedanib is not approved in other oncology indications. Nintedanib is under regulatory review by health authorities in other countries outside the EU.

**** BI 836845 is not approved and its efficacy and safety have not yet been fully established.

+ KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Onxeo announces development of Beleodaq® oral formulation opening new opportunities for its HDAC inhibitor

On June 2, 2016 Onxeo S.A. (Euronext Paris, Nasdaq Copenhagen: ONXEO), an innovative company specializing in the development of orphan oncology therapeutics, reported the first set of positive results from a preclinical pharmacokinetic (PK) study on the bioavailability of an oral formulation of belinostat (Beleodaq) and the next steps in its development plan for the new formulation (Press release, Onxeo, JUN 2, 2016, View Source [SID:1234512969]). Beleodaq is a histone deacetylase inhibitor (HDACi) currently approved in the US for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL).

The current formulation of belinostat is a lyophilized formulation for intravenous (IV) use. The aim of the company is to develop an oral formulation of belinostat offering strong benefits for patients and physicians in terms of compliance, as well as opening new opportunities for indications for which an oral formulation of belinostat is relevant.

As a key step in the development plan, the company has performed a canine PK bioavailability study to screen two enabling formulation technologies dedicated to improving solubility and assessed two prototypes selected based on dissolution properties, and physical and chemical stability.

Findings from this study showed a good level of bioavailability approaching the theoretical maximum achievable as indicated by the performance of the oral solution. Onxeo will then select the best of the two formulation technologies, to pursue formulation development and obtain a suitable clinical prototype and, in parallel, fine tune the optimal dosing regimen to then start clinical development in selected indications.

Judith Greciet, CEO of Onxeo, commented: "The positive results that we have obtained represent an important milestone towards developing a clinically-ready oral formulation of belinostat, which will provide multiple benefits to patients and physicians in terms of convenience, pain-free administration, and need for assistance from medical staff, especially as the other available PTCL treatments are injectable forms. Finally, it opens up a range of new opportunities in the orphan oncology field and beyond, giving Onxeo the opportunity to extend belinostat’s patent protection, thus reinforcing the interest to evaluate the compound in combination with other drugs for new indications."

Graham Dixon, PhD, Chief Scientific Officer of Onxeo, added: "The preclinical study conducted using the oral formulation of belinostat provides solid proof of achieving a good level of bioavailability and promising preliminary PK data. These data strongly support our next steps to conduct preclinical in vivo efficacy studies to confirm efficacy at achievable exposure levels and clinical trials with oral belinostat. "

Intensity Therapeutics Issued First US Patent for Immune-based Cancer Therapeutic Agents

On June 02, 2016 Intensity Therapeutics, Inc., a privately held biotechnology company developing proprietary cancer immunotherapy products, reported that the United States Patent and Trademark Office issued the Company US Patent 9,351,997 (Press release, Intensity Therapeutics, JUN 2, 2016, View Source;.pdf [SID:1234512967]).

"Intensity’s DfuseRxSM platform technology has identified our lead drug, INT230-6. This novel product has shown great promise in regressing tumors and extending life in murine models of severe metastatic cancer via a combination of tumor cell death and immune system activation. Animals with large tumors achieve a complete response and become immunized against re-inoculation of the same cancer," said Intensity’s President and CEO, Lewis H Bender. "This issued US patent allows us to protect the market exclusivity of our unique and potent drug product. As we continue to prosecute additional patent applications in the US and countries around the world, the issuance of patent 9,351,997 increases our confidence that the Company’s unique cancer treatment technology can be secured."

About INT230-6
INT230-6 is a novel, anti-cancer drug product able to disperse through tumors and diffuse into cancer cells. The product was identified from Intensity’s DfuseRxSM platform technology. Using preclinical in vivo models of severe cancer, INT230-6 treatment results in substantial improvement in overall survival compared to standard therapies. The product can completely clear large tumors in animal models. Complete responders have long-term, durable protection even after multiple re-inoculations of the cancer. INT230-6 administration has shown an increased recruitment of immune cells to the tumor micro-environment.

Mylan Launches Generic Vidaza® Injection

On June 2, 2016 Mylan N.V. (NASDAQ, TASE: MYL) reported the U.S. launch of Azacitidine for Injection, 100 mg/vial, which is a generic version of Celgene’s Vidaza Injection, 100 mg/vial. Mylan received final approval from the U.S. Food and Drug Administration (FDA) for its Abbreviated New Drug Application (ANDA) for this product (Press release, Mylan, JUN 2, 2016, View Source [SID:1234512966]). Azacitidine for Injection is a nucleoside metabolic inhibitor indicated for the treatment of the five French-American-British (FAB) subtypes of myelodysplastic syndrome, a blood cell disorder that can occur as a result of cancer treatments or can progress to leukemia.

Mylan
Azacitidine for Injection, 100 mg/vial, had U.S. sales of approximately $236.3 million for the 12 months ending March 31, 2016, according to IMS Health.
Mylan’s launch of this product adds to the company’s portfolio of more than 150 injectable products available to patients in the U.S. across a broad array of therapeutic categories. Azacitidine for Injection is also a part of a growing U.S. portfolio of more than 20 oncology medications that includes treatments for breast, lung, colorectal, ovarian and hematologic cancers.
Currently, Mylan has 254 ANDAs pending FDA approval representing $108.3 billion in annual brand sales, according to IMS Health. Forty-three of these pending ANDAs are potential first-to-file opportunities, representing $37.2 billion in annual brand sales, for the 12 months ending December 31, 2015, according to IMS Health.

MiNA Therapeutics Announces Initiation of Phase I Clinical Study of MTL-CEBPA in Patients with Liver Cancer

On June 2, 2016 MiNA Therapeutics, the pioneer in RNA activation therapeutics, reported the initiation and first patient treated in the OUTREACH Phase I clinical study of their lead program, MTL-CEBPA, in severe liver cancer (Press release, MiNA Therapeutics, JUN 2, 2016, View Source [SID:1234512962]).

The study is the first-in-human trial of a small activating RNA (saRNA) and is designed to assess the safety and tolerability of MTL-CEBPA, an saRNA restoring the expression of CCAAT/enhancer binding protein alpha (C/EBP-a). C/EBP-a plays an important role in normal liver function and the benefits of increasing its expression have been demonstrated in multiple pre-clinical models of disease.

"Initiation of the Phase I study is an important achievement in our mission to improve patients’ lives with our groundbreaking class of medicines known as small activating RNAs," said Robert Habib, CEO of MiNA Therapeutics. "There is increasing excitement about the possibility of using RNA to induce therapeutic protein production. We believe our unique approach, here applied to the upregulation of C/EBP-a protein, may provide to patients significant benefits over conventional medicines."

"MTL-CEBPA has shown great promise in pre-clinical studies in liver disease models," commented Dr. Debashis Sarker, Principal Investigator of the National Institute for Health Research Biomedical Research Centre at Guy’s and St. Thomas’ and King’s College London, and chief investigator of the study. "We are looking forward to evaluating this highly innovative therapy in the upcoming Phase I trial. We hope MTL-CEBPA could represent an important new treatment option for patients with advanced liver cancer."

About the OUTREACH Study

OUTREACH is a first-in-human Phase I clinical study in patients with severe liver cancer. The multi-centre Phase I study will assess the safety and tolerability of MTL-CEBPA in patients with advanced primary or metastatic liver cancer who are ineligible or resistant to standard therapies. The study consists of a dose-escalation followed by a dose expansion. MTL-CEBPA will initially be administered as an intravenous infusion once weekly for three weeks followed by one week of rest. To learn more about the OUTREACH clinical study, please visit our listing at clinicaltrials.gov.

About MTL-CEBPA

MTL-CEBPA consists of a double stranded RNA formulated into a SMARTICLES liposomal nanoparticle and is designed to activate the CEBPA gene. The CEBPA gene encodes for the CCAAT/enhancer binding protein alpha (C/EBP-a), a transcription factor that acts as a master regulator of cell lineage determination and differentiation in several tissues including liver, myeloid cells and adipose tissue. In the liver, C/EBP-a plays an important role in normal hepatocyte function and response to injury. By restoring C/EBP-a expression to normal levels, MTL-CEBPA has been demonstrated to attenuate or reverse liver disease in a range of pre-clinical studies including models of liver cancer, liver cirrhosis, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). In the future MiNA Therapeutics expects to initiate clinical trials of MTL-CEBPA in a number of diseases beyond liver cancer.