Month: September 2016

Boehringer Ingelheim returns development and commercial rights of olmutinib to Hanmi Pharmaceutical

On September 30, 2016 Boehringer Ingelheim reported that development and global commercialization rights of olmutinib, a third-generation EGFR targeted therapy, will be returned to Hanmi Pharmaceutical Co. Ltd (Press release, Boehringer Ingelheim, SEP 30, 2016, http://us.boehringer-ingelheim.com/news_events/press_releases/press_release_archive/2016/9-30-2016-boehringer-ingelheim-returns-development-commercial-rights-olmutinib-hanmi-pharmaceutical.html [SID:SID1234515686]).

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The decision is based on a re-evaluation of all available clinical data on olmutinib and recent treatment advances made in the treatment of EGFR mutation-positive lung cancer. Boehringer Ingelheim will not initiate new clinical trials for this compound and will work closely with Hanmi Pharmaceutical to ensure a seamless transition of the responsibilities of the current olmutinib clinical development program back to Hanmi Pharmaceutical.

Dr. Jörg Barth, Corporate Senior Vice President, Therapeutic Area Head Oncology, Boehringer Ingelheim said, "We would like to thank Hanmi Pharmaceutical for their collaboration and commitment during our joint development of olmutinib. Partnering is a key pillar of our oncology strategy at all stages of research and development, in order to offer cancer treatments that fit the needs of patients, caregivers and healthcare professionals. Boehringer Ingelheim’s oncology pipeline is robust and transformative, with several compounds currently in clinical development and we strive for best-in-class, breakthrough cancer medications."

Boehringer Ingelheim has successfully launched two products for the treatment of non-small cell lung cancer (NSCLC), which have been widely adopted and established as important additions to current clinical practice. The company continues to increase its investment in research and development and a third of Boehringer Ingelheim’s human pharmaceutical pipeline, that is planned to enter phase I clinical trials in the next 12 months, is in oncology.

Boehringer Ingelheim’s oncology pipeline is built on in-house scientific innovation as well as strong academic and industry collaborations. Two recent examples include a partnership with ViraTherapeutics to develop novel cancer treatments based on oncolytic viruses, with an option to acquire the company at a later time point. The other strategic collaboration is with Sarah Cannon Research Institute (SCRI) that brings together Boehringer Ingelheim’s extensive experience in cancer drug development and SCRI’s expertise in designing and executing clinical trials of investigational oncology drugs.

Acorda Therapeutics, Inc. Gains Title To All Shares In Biotie Therapies Corp. And The Shares Will Delist From Nasdaq Helsinki

On September 30, 2016 Acorda Therapeutics, Inc. (Nasdaq: ACOR) ("Acorda") reported that it had lodged security approved by the Arbitral Tribunal and thus gained title to all the shares in Biotie Therapies Corp. (Nasdaq Helsinki: BTH1V) ("Biotie") in accordance with Chapter 18, Section 6 of the Finnish Companies Act (Press release, Acorda Therapeutics, SEP 30, 2016, View Source [SID:SID1234515532]). After the security has been lodged, the minority shareholders of Biotie being parties to the redemption proceedings are only entitled to receive the redemption price and the interest payable thereon. Upon application by Biotie, Nasdaq Helsinki Ltd ("Nasdaq Helsinki") has on 25 August 2016 decided that the Biotie shares will be delisted from the Official List of Nasdaq Helsinki upon title to all shares in Biotie having been transferred to Acorda. The quoting of the Biotie shares on Nasdaq Helsinki will thus cease in accordance with a separate release to be published by Nasdaq Helsinki.

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LabCorp Subsidiary Sequenom, Inc. Announces Early Tender Results for Tender Offers and Successful Completion of Consent Solicitations for 5% Convertible Senior Notes Due 2017 and 5% Convertible Senior Exchange Notes Due 2018

On September 30, 2016 Sequenom, Inc. ("Sequenom"), a wholly-owned subsidiary of Laboratory Corporation of America Holdings (LabCorp) (NYSE: LH), reported the results, as of 5:00 p.m., New York City time, on September 29, 2016 (the "Early Tender and Consent Payment Deadline"), of (A) the cash tender offers (the "Tender Offers") for any and all of the outstanding 5% Convertible Senior Notes Due 2017 (CUSIP No. 817337 AB4, the "2017 Notes") and 5% Convertible Senior Exchange Notes Due 2018 (CUSIP No. 817337 AC2, the "2018 Notes" and, together with the 2017 Notes, the "Notes") issued by Sequenom, and (B) the solicitations (the "Consent Solicitations") of consents of the holders of Notes (the "Consents") to enact certain proposed amendments (the "Proposed Amendments") to the indentures governing the Notes to eliminate various reporting obligations and restrictive provisions related to the incurrence of indebtedness, as well as make certain other changes in the indentures (Press release, LabCorp, SEP 30, 2016, View Source;p=RssLanding&cat=news&id=2207126 [SID:SID1234515520]). The Tender Offers will expire at 5:00 p.m., Eastern Time, on Monday, October 17, 2016, unless extended or terminated (the "Expiration Date").

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As of the Early Tender and Consent Payment Deadline, (i) a total of $44,841,000 aggregate principal amount of the outstanding 2017 Notes, representing approximately 99.647% of the outstanding 2017 Notes, were validly tendered (and not validly withdrawn) and (ii) a total of $85,000,000 aggregate principal amount of the outstanding 2018 Notes, representing 100.00% of the outstanding 2018 Notes, were validly tendered (and not validly withdrawn) in the Tender Offers. All tendered Notes were accompanied by Consents to the Proposed Amendments.

As a result, as of the Early Tender and Consent Payment Deadline, Sequenom received the requisite Consents from holders of at least a majority of the outstanding principal amount of both series of Notes to meet the Consent Condition and to adopt the Proposed Amendments. On September 29, 2016, Sequenom and the trustee for the Notes entered into a supplemental indenture to each of the indentures governing the 2017 Notes and the 2018 Notes (the "Supplemental Indentures"), giving effect to the Proposed Amendments. The Supplemental Indentures are binding as of their execution and will become operative on the settlement date of the Tender Offers (the "Settlement Date"), which is expected to occur on October 20, 2016.

Sequenom will accept for purchase such amount of 2017 Notes and 2018 Notes properly tendered and not validly withdrawn in the Tender Offers as of the Early Tender and Consent Payment Deadline. Holders whose 2017 Notes were validly tendered and accompanied by a Consent on or before the Early Tender and Consent Payment Deadline, and not withdrawn, will receive, in respect of each $1,000 principal amount of 2017 Notes, the "2017 Total Consideration" of $1,037.50 plus Accrued Interest (such price being rounded to the nearest $0.01 per $1,000 principal outstanding amount of Notes) on the Settlement Date. Holders whose 2018 Notes were validly tendered and accompanied by a Consent on or before the Early Tender and Consent Payment Deadline, and not withdrawn, will receive, in respect of each $1,000 principal amount of 2018 Notes, the "2018 Total Consideration" of $1,046.25 plus Accrued Interest (such price being rounded to the nearest $0.01 per $1,000 principal outstanding amount of Notes) on the Settlement Date.

Holders who validly tender their 2017 Notes after the Early Tender and Consent Payment Deadline but on or prior to the Expiration Date and do not withdraw their tender will not receive the respective Total Consideration but will be eligible to receive, in respect of each $1,000 principal amount of 2017 Notes tendered, the "Purchase Price" of $1,000.00, plus accrued interest to but excluding the Settlement Date. No tenders of Notes will be valid if submitted after the Expiration Date.

The Tender Offers and Consent Solicitations are being made pursuant to an Offer to Purchase and Consent Solicitation Statement, dated September 16, 2016 (as supplemented on September 22, 2016, and as amended or further supplemented from time to time, the "Offer to Purchase") and the accompanying Consent and Letter of Transmittal.

Barclays is the Dealer Manager and Solicitation Agent for the Tender Offers and Consent Solicitations and may be contacted at 1-888-610-5877 (toll free) or 212-526-7255. Requests for documents may be directed to Morrow Sodali Global, LLC, the Information Agent, at 1-203-658-9400 for banks and brokers or 1-800-662-5200 (toll free) for Holders and all others.

This announcement is not an offer to purchase or the solicitation of an offer to sell the Notes or a solicitation of Consents. The Tender Offers for the Notes and the related Consent Solicitations are only being made pursuant to the Offer to Purchase and the related Consent and Letter of Transmittal. Holders of the Notes should read the Offer to Purchase and the Consent and Letter of Transmittal carefully prior to making any decision with respect to the Tender Offers and Consent Solicitations because they contain important information.

This announcement has been issued by and is the sole responsibility of Sequenom, Inc. In accordance with normal practice, Barclays expresses no opinion on the merits of the Tender Offers or the Consent Solicitations, nor does it accept any responsibility for the accuracy or completeness of this announcement or any other document prepared in connection with the Tender Offers or the Consent Solicitations.

Cancer Research UK, MSD and Verastem Collaborate to Trial New Combination of Immunotherapy Drugs

On September 30, 2016 CANCER RESEARCH UK reported its first cross-company deal as part of its Experimental Cancer Medicine Centre (ECMC) Combinations Alliance (Press release, Verastem, SEP 30, 2016, View Source [SID:SID1234515522]).

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MSD, Verastem, Inc. and Cancer Research UK will trial a new combination of immunotherapy drugs in mesothelioma, non small cell lung and pancreatic cancers. The trial will run through the ECMC network at centres in Edinburgh-Dundee, Southampton, Glasgow, Leicester and Belfast.

The phase Ib/IIa trial will investigate whether a focal adhesion kinase (FAK) inhibitor drug from Verastem called VS-6063 (defactinib)* can boost the effectiveness of a PD-1 immunotherapy drug from MSD called Keytruda (pembrolizumab).

It is based on discoveries by scientists at the Edinburgh Cancer Research UK Centre at the University of Edinburgh who showed that inhibiting FAK can release the cancer immune response. Defactinib may be able to take down a barrier of immune cells which are tricked into protecting the cancer cells while pembrolizumab can activate cancer-killing immune cells to attack those exposed cancer cells.

Around 50-60 cancer patients will take the drug combination, starting with a small dose and building this up to find what is safe. The scientists will also study how the treatments target the cancers and what effects the drug combination has on the tumours.
The trial will open between late 2016 and early 2017. It will be managed by the Cancer Research UK clinical trials unit in Glasgow and co-sponsored by the University of Glasgow and NHS Greater Glasgow and Clyde.

Dr Mercia Page, medical director of oncology at MSD, said: "We look forward to working with Cancer Research UK and Verastem on this promising combination. Strategic collaborations such as this reinforce the commitment we have to bringing a range of new treatments to the forefront, helping people with cancer who need a number of options available to them."
Dr Greg Berk, Verastem chief medical officer, said: "Combining defactinib and MSD’s pembrolizumab through the Combinations Alliance expands our potential to deliver transformative therapies to patients with many types of cancer.

"We are delighted to be working with the Combinations Alliance, MSD, and world class scientists and medical centres throughout the UK on this trial. This study will build on the single agent activity of defactinib observed in early clinical trials in patients with non-small cell lung cancer and other tumour types, and follows from substantial preclinical research which has demonstrated that FAK inhibition optimizes the tumour immune balance and potentiates efficacy of PD-1 checkpoint inhibition."
Dr Ian Walker, director of clinical research at Cancer Research UK, said: "It’s vital that we find new treatments for these three cancers which take tens of thousands of lives each year in the UK and we’re delighted to be working with MSD and Verastem on this.

"Our Combinations Alliance was set up to help develop partnerships between drug development companies and researchers to try new combinations of drugs in the hope of improving treatments and saving more lives from cancer. This is our first success in bringing together two organisations and we hope that this combination of immunotherapy drugs will benefit patients."
Mesothelioma, pancreatic and non small cell lung cancers have very low survival – with more than half (60 per cent) of mesothelioma patients, more than three quarters (79 per cent) of pancreatic cancer patients and two thirds (68 per cent) of lung cancer patients dying within a year of diagnosis in England and Wales.*

Trial co-lead Dr Stefan Symeonides, from the University of Edinburgh, said: "Immunotherapy is a very exciting area of cancer research and we’ve seen remarkable benefits from pembrolizumab for some patients with hard-to-treat cancers, like melanoma and lung cancer. We’re hoping that the addition of defactinib will extend those benefits to more patients.
"This work could one day give a new treatment option that saves lives for this group of patients who have few options."

EISAI TO INITIATE PHASE III CLINICAL STUDY OF ANTICANCER AGENT LENVATINIB AS POTENTIAL FIRST-LINE THERAPY FOR ADVANCED RENAL CELL CARCINOMA

On September 30, 2016 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") reported the initiation of a global Phase III Clinical Study (Study 307, CLEAR Study) of its in-house developed multiple receptor tyrosine kinase inhibitor lenvatinib mesylate (lenvatinib) in respective combination regimens with the anticancer agent everolimus and the anti-PD-1 antibody pembrolizumab as a potential first-line treatment for advanced renal cell carcinoma (Press release, Eisai, SEP 30, 2016, View Source [SID:SID1234515517]).

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The CLEAR (Comparison of the efficacy and safety of Lenvatinib in combination with Everolimus or pembrolizumab versus sunitinib alone in first-line treatment of subjects with Advanced Renal cell carcinoma) study is a multicenter, randomized, open-label Phase III clinical study to compare the efficacy and safety of lenvatinib/everolimus and lenvatinib/pembrolizumab versus sunitinib alone in first-line treatment in patients with advanced renal cell carcinoma. The primary outcome measure will be progression-free survival.

Non-clinical research into the combination of lenvatinib and everolimus suggested synergistic enhancement of antiangiogenic activity and a stronger antitumor effect than either monotherapy in renal cell carcinoma models through the respective inhibition of signaling pathways which facilitate tumor angiogenesis, upstream (vascular endothelial growth factor receptor [VEGFR] and fibroblast growth factor receptor [FGFR]) with lenvatinib and downstream (mammalian target of rapamycin [mTOR]) with everolimus. 1,2 Furthermore, non-clinical research into the combination of lenvatinib and anti-PD-1 antibody suggested that the combination has a mechanism of action in which lenvatinib enhances the antitumor activity of the anti-PD-1 antibody by reducing immunosuppressive cells. 3

The number of patients with renal cancer is estimated to be approximately 338,000 worldwide, including approximately 115,000 in Europe, 58,000 in the United States and 17,000 in Japan.4 Renal cell carcinoma comprises more than 90% of all malignancies of the kidney, 5 and occurs when malignant cells are found in the lining of the tubules of the kidney. The incidence of renal cell carcinoma in people over 55 years of age is rising, and it is more likely to affect men than women. For advanced or metastatic renal cell carcinoma that is difficult to treat with surgery, the standard treatment is molecular targeted drug therapy, however with low 5-year survival rates, this remains a disease with significant unmet medical need.

Currently lenvatinib has been approved in over 45 countries including the United States, Japan and in Europe as a treatment for refractory thyroid cancer. In May 2016, lenvatinib was approved in combination with everolimus for the treatment of patients with advanced renal cell carcinoma following one prior anti-angiogenic therapy by the U.S. Food and Drug Administration in the United States. Furthermore, lenvatinib was approved in combination with everolimus for the treatment of adult patients with advanced renal cell carcinoma following one prior vascular endothelial growth factor targeted therapy in Europe in August 2016.


Eisai regards oncology as a key therapeutic area and is aiming to discover revolutionary new medicines with the potential to cure cancer. Eisai remains committed to providing further clinical evidence for lenvatinib aimed at maximizing value of the drug as it seeks to contribute further to addressing the diverse needs of, and increasing the benefits provided to, patients with cancer, their families, and healthcare providers.

1. About lenvatinib mesylate ("lenvatinib", generic name, product names: Lenvima , Kisplyx ) Discovered and developed in-house, lenvatinib is an orally administered multiple receptor tyrosine kinase (RTK) inhibitor with a novel binding mode that selectively inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors (VEGFR1, VEGFR2 and VEGFR3) and fibroblast growth factor (FGF) receptors (FGFR1, FGFR2, FGFR3 and FGFR4) in addition to other proangiogenic and oncogenic pathway-related RTKs (including the platelet-derived growth factor (PDGF) receptor PDGFRα; KIT; and RET) involved in tumor proliferation.
Currently, Eisai has obtained approval for lenvatinib as a treatment for refractory thyroid cancer in over 45 countries including in the United States, Japan, in Europe, Korea, Canada, and Mexico, and is undergoing regulatory review in countries throughout the world including South Africa and Malaysia. Specifically, Eisai has obtained approval for the agent indicated in the United States for the treatment of locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer, in Japan for the treatment of unresectable thyroid cancer, and in Europe for the treatment of adult patients with progressive, locally advanced or metastatic differentiated (papillary, follicular, Hürthle cell) thyroid carcinoma (DTC), refractory to radioactive iodine, respectively.
Lenvatinib was also approved in the United States in May 2016 for an additional indication in combination with everolimus for the treatment of patients with advanced renal cell carcinoma following one prior anti-angiogenic therapy. Furthermore, lenvatinib was approved in combination with everolimus for the treatment of adult patients with advanced renal cell carcinoma (RCC) following one prior vascular endothelial growth factor (VEGF) targeted therapy in Europe in August 2016. Lenvatinib will be launched in Europe under the brand name Kisplyx for this indication.
Meanwhile, Eisai is conducting clinical studies of lenvatinib in several other tumor types such as hepatocellular carcinoma (Phase III), endometrial carcinoma (Phase II), biliary tract cancer (Phase II), and in combination with pembrolizumab for various types of cancer (Phase Ib/II).
2. About the Phase III Clinical Study (Study 307, CLEAR Study)
CLEAR Study is a global, multicenter, randomized, open-label, Phase III clinical study to compare the efficacy and safety of lenvatinib in combination with everolimus or pembrolizumab versus sunitinib as first-line treatment of patients with advanced renal cell carcinoma. The study will be initially conducted in the United States and Europe, and Eisai is currently considering adding Japan to the study in the future. Approximately 735 patients aged 18 years or older with histological or cytological confirmation of advanced renal cell carcinoma with a clear-cell component and Karnofsky Performance Status6 of 70 or greater are randomized 1:1:1 to one of three treatment arms to receive either lenvatinib 18 mg (orally, once daily) plus everolimus 5 mg (orally, once daily) [arm A], lenvatinib 20 mg (orally, once daily) plus pembrolizumab 200 mg (intravenously every three weeks) [arm B], or sunitinib 50 mg (orally, once daily) on a schedule of four weeks on treatment followed by two weeks off [arm C]. The primary outcome is to compare progression-free survival between the arm A versus arm C, and the arm B versus arm C. Secondary outcomes are objective response rate, overall survival, and safety.
3. About Non-clinical Research into lenvatinib in Combination with everolimus1,2
It is known that lenvatinib inhibits VEGFR and FGFR which are upstream RTK signaling pathways, and that everolimus suppresses the protein mTOR (mammalian target of rapamycin) found downstream of these signaling pathways. In vitro and animal models have suggested that the combination of lenvatinib and everolimus suppresses RTK signaling pathways, which facilitate tumor angiogenesis, at two points both upstream and down, enabling synergistic signaling inhibition for enhanced antiangiogenesis in vitro. The combination demonstrated stronger antitumor activity than either monotherapy in the in vivo animal model using A498 and Caki-1 human renal cell carcinoma xenograft models.
4. About Non-clinical Research into lenvatinib in Combination with Anti-PD-1 Antibody3
Animal models have shown that lenvatinib activates tumor immunity via the modulation of tumor associated macrophages. Tumor associated macrophages have been reported as a negative regulator of cytotoxic T-cells and a promoter of tumor cell metastasis. Animal models suggest that when lenvatinib is combined with an anti-PD-1 antibody, lenvatinib enhances antitumor activity of the anti-PD-1 antibody by suppressing tumor associated macrophages.