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On September 5, 2016, Horizon Pharma Ireland Limited ("Horizon Ireland"), an indirect wholly-owned subsidiary of Horizon Pharma plc ("Horizon Pharma"), reported that it entered into a Fifth Amendment to Commercial Supply Agreement (the "Fifth Amendment") with Bio-Technology General (Israel) Ltd. ("BTG"), which amends that certain Commercial Supply Agreement, dated March 20, 2007, by and between Horizon Ireland and BTG, as amended (the "Agreement") (Press release, Horizon Pharma, SEP 8, 2016, View Source [SID:1234515008]).

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Pursuant to the Fifth Amendment, among other things, BTG rescinded its prior notice of termination that was sent to Crealta Pharmaceuticals LLC in December 2015 (and would have caused the Agreement to terminate on December 15, 2018), the term of the Agreement was extended until December 31, 2030 and renews automatically for successive three year periods unless earlier terminated by either party upon three years prior written notice, and Horizon Ireland agreed to purchase certain minimum annual order quantities. The Agreement, as amended, may be terminated prior to December 31, 2030 by either party in the event of a force majeure, liquidation, dissolution, bankruptcy or insolvency of the other party, uncured material breach by the other party or after January 1, 2024, upon three years prior written notice.

The foregoing description of the Fifth Amendment does not purport to be complete and is qualified in its entirety by reference to the complete text of the Fifth Amendment, which will be filed, with confidential terms redacted, with the Securities and Exchange Commission as an exhibit to Horizon Pharma’s Quarterly Report on Form 10-Q for the quarterly period ending September 30, 2016.

BioLineRx Presents Final Results from Phase 2a Trial for Relapsed/Refractory AML at SOHO Conference

On September 8, 2016 BioLineRx Ltd. (NASDAQ/TASE: BLRX) reported that the successful final results of BL-8040’s Phase 2a clinical trial in relapsed or refractory acute myeloid leukemia (r/r AML) were presented yesterday evening at the 4th Annual Meeting of the Society of Hematologic Oncology (SOHO), being held September 7-10, 2016, in Houston, Texas (Press release, BioLineRx, SEP 8, 2016, View Source;p=RssLanding&cat=news&id=2200457 [SID:1234514998]).

BL-8040, BioLineRx’s lead oncology platform, is a short cyclic peptide that functions as a high-affinity antagonist for CXCR4, a chemokine receptor that is directly involved in tumor progression, angiogenesis, metastasis and cell survival. The Phase 2a study assessed the efficacy of BL-8040, as a single agent and in combination with Cytarabine (Ara-C), for the treatment of r/r AML. The reported data set includes 45 patients. The majority of patients in the study were heavily pretreated, with 45% of patients being refractory to one or two remission induction treatments, 19% of patients having relapsed after a short first remission of less than 12 months, and 17% of patients having undergone two or more relapses. In addition, the treated patient population included patients that had relapsed post allogeneic stem-cell transplantation (17%), as well as secondary AML patients (24%), both conditions which represent difficult-to-treat populations with poor prognoses.

Results show that treatment with BL-8040 in combination with Ara-C was safe and well tolerated at all doses tested up to and including the highest dose level of 2.0 mg/kg. Response to treatment was associated with efficient CXCR4 inhibition, resulting in high mobilization of blasts and induction of their differentiation. The composite complete remission rate, including both complete remission (CR) and complete remission with incomplete blood count recovery (CRi), was 38% in subjects receiving up to two cycles of BL-8040 treatment at doses of 1 mg/kg and higher (n=39). In the 1.5 mg/kg dose selected for the expansion phase of the study (n=22), the composite complete remission rate was 41%. These response rates are superior to the historical response rate of approximately 20% reported for high-risk AML patients treated with Ara-C alone.

In addition, the ongoing follow-up of patients participating in the study’s expansion phase and responding to the combination treatment suggests long durability of the remissions achieved, with two-thirds of these patients still alive, based on a follow-up period to date of up to 12 months.

Philip Serlin, Chief Financial and Operating Officer of BioLineRx, commented, "The results from this study clearly confirm the anti-leukemic activity of BL-8040 and reinforce our interest in the AML space. The data demonstrate that sustained inhibition of the CXCR4-CXCL12 axis with BL-8040 is safe and well tolerated, and when given in combination with Ara-C, improves the response rate historically achieved with Ara-C alone. In addition, treatment with BL-8040 as a single agent rapidly and efficiently induces mobilization, differentiation and cell death of AML cells. This selective effect on chemotherapy-resistant cells may be translated into reduction of residual disease, thus pointing to incorporation of BL-8040 into earlier AML treatment lines."

"As previously reported, we are currently in the midst of a large, randomized, controlled, Phase 2b study in the AML consolidation treatment line. In light of the data seen in the Phase 2a study, we have been allocating additional resources to this Phase 2b study. In this regard, we have recently engaged an additional AML research group to participate in the study, and last month we met with regulatory authorities to discuss the development pathway towards registration for this treatment line. In addition, yesterday we announced a significant new cancer immunotherapy collaboration with Genentech, which includes, among other studies, a Phase 1b study in the AML maintenance treatment line. This new study emphasizes our commitment to further develop BL-8040 as a treatment for AML and validates the anti-leukemic effect of BL-8040 seen in the Phase 2a study," concluded Mr. Serlin.

About BL-8040

BL-8040 is a short peptide for the treatment of acute myeloid leukemia, solid tumors, and certain hematological indications. It functions as a high-affinity antagonist for CXCR4, a chemokine receptor that is directly involved in tumor progression, angiogenesis, metastasis and cell survival. CXCR4 is over-expressed in more than 70% of human cancers and its expression often correlates with disease severity. In a number of clinical and pre-clinical studies, BL-8040 has shown robust mobilization of cancer cells from the bone marrow, thereby sensitizing these cells to chemo- and bio-based anti-cancer therapy, as well as a direct anti-cancer effect by inducing apoptosis. In addition, BL-8040 has also demonstrated robust stem-cell mobilization, including the mobilization of colony-forming cells, and T, B and NK cells. BL-8040 was licensed by BioLineRx from Biokine Therapeutics and was previously developed under the name BKT-140.

Apollo Endosurgery and Lpath Sign Merger Agreement

On September 8, 2016 Lpath, Inc. (Nasdaq: LPTN) and Apollo Endosurgery, Inc. reported that they have entered into a definitive merger agreement under which the security holders of Apollo would become the majority owners of Lpath (Filing, 8-K, Lpath, SEP 8, 2016, View Source [SID:1234515015]). Under terms of the agreement, Lpath will issue new shares of its common stock or rights to acquire its common stock to Apollo security holders. The Apollo security holders are expected to own approximately 95.8 percent of the combined company and the Lpath security holders are expected to own approximately 4.2 percent of the combined company, subject to adjustments as described in the merger agreement.

Concurrent with the closing of the merger, Apollo’s major investors have committed to invest approximately $29 million of new equity in the combined company, which will form part of the Apollo 95.8 percent ownership. The major investors include affiliates of PTV Healthcare Capital, H.I.G. BioHealth Partners, Remeditex Ventures, Novo A/S, and CPMG Inc. As of June 30, 2016 Apollo’s cash was approximately $11.6 million and long term debt was approximately $50 million. Apollo’s consolidated revenue for the calendar year ended December 31, 2015 was approximately $68 million.

The boards of directors of both Lpath and Apollo have unanimously approved the transaction, which is subject to customary closing conditions, including approval by the stockholders of each of Lpath and Apollo. The merger agreement contains certain termination rights for both Lpath and Apollo.

The transaction is expected to close during the fourth quarter of 2016. Upon closing of the transaction Lpath will be renamed Apollo Endosurgery, Inc. and the combined company intends to apply for listing on The NASDAQ Global Market under a new trading symbol.

Todd Newton, chief executive officer of Apollo, said, "Executing this transaction with Lpath is an expedient way to introduce our company to the public market. With the additional equity support we will receive from Apollo’s major investors as part of this transaction, we will have the resources to meet our near-term business needs."

Gary Atkinson, Lpath’s chief executive officer added, "Following an extensive and thorough review of strategic alternatives, we have chosen to merge with Apollo because we believe the transaction provides Lpath stockholders with an attractive opportunity for value appreciation."

Piper Jaffray & Co. is the exclusive financial advisor for Apollo in this transaction and Cooley LLP is Apollo’s legal counsel. Lpath’s exclusive financial advisor in the transaction is Torreya Partners LLC and Lpath’s legal counsel is Gunderson Dettmer Stough Villeneuve Franklin & Hachigian, LLP.

Management and Organization

The directors and executive officers of Lpath will resign from their positions with Lpath upon the closing of the proposed merger, and the combined company will be under the leadership of Apollo’s Newton and its current executive management team. Following the closing of the proposed merger, the Board of Directors of the combined company is expected to consist of nine members all of whom will be designated by Apollo, including representatives of each of Apollo’s five major investors. Chairman of the Board of the combined company will be Richard J. Meelia, former Chairman and Chief Executive Officer of Covidien Ltd. The corporate headquarters will be located in Austin, TX.

Tokai Pharmaceuticals Announces Review of Strategic Alternatives

On September 8, 2016 Tokai Pharmaceuticals Inc. (NASDAQ: TKAI), a biopharmaceutical company focused on developing and commercializing innovative therapies for prostate cancer and other hormonally driven diseases, reported that its Board of Directors has initiated a review of strategic alternatives for the company focused on maximizing stockholder value (Press release, Tokai Pharmaceuticals, SEP 8, 2016, View Source [SID:1234515007]).

Potential strategic alternatives that may be explored or evaluated as part of this review include a sale of the company, a reverse merger, a business combination or a sale, license or other disposition of corporate assets of the company. There is no set timetable for this process and there can be no assurance that this process will result in any such transaction. In conjunction with this process, the company is continuing to assess the best path forward for its galeterone clinical trial program. The company now anticipates all patients enrolled in the ARMOR3-SV clinical trial will discontinue treatment by the end of the year.

As part of its review of strategic alternatives, Tokai has engaged Wedbush PacGrow as its financial advisor.

RedHill Biopharma Announces Phase Ib/II Study with YELIVA™ Initiated for Multiple Myeloma at a Leading U.S. Academic Medical Center

On September 8, 2016 RedHill Biopharma Ltd. (NASDAQ:RDHL) (TASE:RDHL) ("RedHill" or the "Company"), a biopharmaceutical company primarily focused on development and commercialization of late clinical-stage, proprietary, orally-administered, small molecule drugs for gastrointestinal and inflammatory diseases and cancer, reported that a Phase Ib/II clinical study evaluating YELIVA (ABC294640) in patients with refractory or relapsed multiple myeloma has been initiated (Press release, RedHill Biopharma, SEP 8, 2016, View Source [SID1234515006]).

The open-label, dose escalation Phase Ib/II study is being conducted at Duke University Medical Center and will enroll up to 77 patients with refractory or relapsed multiple myeloma who have previously been treated with proteasome inhibitors and immunomodulatory drugs.

Dr. Yubin Kang, MD, Associate Professor in the Division of Hematologic Malignancies and Cellular Therapy in the Department of Medicine at Duke University School of Medicine, is the lead investigator for the study.

The study is supported by a $2 million grant from the National Cancer Institute (NCI) Small Business Innovation Research Program (SBIR) awarded to Apogee Biotechnology Corp. (Apogee), in conjunction with Duke University, with additional support from RedHill.

YELIVA is a proprietary, first-in-class, orally-administered, sphingosine kinase-2 (SK2) selective inhibitor with anti-cancer and anti-inflammatory activities. By inhibiting the SK2 enzyme, YELIVA blocks the synthesis of sphingosine 1-phosphate (S1P), a lipid signaling molecule that promotes cancer growth and pathological inflammation.

RedHill is pursuing with YELIVA multiple clinical programs in oncology, inflammatory and gastrointestinal indications.

"We are very pleased that this study with YELIVA has been initiated at Duke University. Award of the NCI funding to support the study and the interest in the product by a major research university confirms the potential promise of YELIVA in this serious, chronic disease," said Terry Plasse, MD, RedHill’s Medical Director. "The clinical study follows a successful preclinical study demonstrating that sphingosine kinase-2 is overexpressed in multiple myeloma cell lines and in human specimens, and that its inhibition may fight the disease. This is the second Phase I/II study initiated with YELIVA. We expect to initiate additional clinical studies in the coming months, including studies in advanced hepatocellular carcinoma and prevention of mucositis in head and neck cancer patients undergoing therapeutic radiotherapy. Given YELIVA’s unique mechanism of action, we continue to evaluate its therapeutic potential for multiple oncology, inflammatory and gastrointestinal indications, as a single agent and in combination with other oncology drugs."

The primary objectives of the first portion of the study (Phase Ib) are to assess safety and determine the maximum tolerated dose (MTD) in refractory or relapsed multiple myeloma patients. Secondary objectives include assessment of antitumor activity and determination of the pharmacokinetic (PK) and pharmacodynamic (PD) properties of YELIVA in this group of patients. The Phase Ib will be conducted at Duke University Division of Hematologic Malignancies and Cellular Therapy.

The primary objectives of the second portion of the study (Phase II) are to assess the overall treatment response rate and overall survival. Secondary objectives include evaluating the treatment response to YELIVA in patients with refractory or relapsed multiple myeloma after three cycles of treatment and evaluation of pharmacodynamic markers. The Phase II portion will be conducted at multiple sites and will be managed by the Duke Cancer Network.

Results from the Phase I study with YELIVA in patients with advanced solid tumors confirmed that the study, conducted at the Medical University of South Carolina (MUSC), successfully met its primary and secondary endpoints, demonstrating that the drug is well-tolerated and can be safely administered to cancer patients at doses that provide circulating drug levels that are predicted to have therapeutic activity.

Among the 16 subjects that were assessable for response by RECIST 1.1 criteria (Response Evaluation Criteria in Solid Tumors), one subject had a partial response with a progression-free survival of 16.9 months, and six subjects had stable disease with a progression-free survival of between 3.5 and 17.6 months. Of the three patients with cholangiocarcinoma, one had a partial response and the other two had stable disease, one for over a year. YELIVA was well tolerated over a prolonged period at doses inducing the expected pharmacodynamic effects.

A Phase II study with YELIVA for the treatment of advanced hepatocellular carcinoma is planned to be initiated in the coming weeks. The study will be conducted at MUSC Hollings Cancer Center and additional clinical centers in the U.S. It is supported by a $1.8 million grant from the NCI awarded to MUSC, intended to fund a broad range of studies on the feasibility of targeting sphingolipid metabolism for the treatment of a variety of solid tumor cancers, including the Phase II study with YELIVA, and will be further supported by additional funding from RedHill.

A clinical study to evaluate YELIVA as a radioprotectant for prevention of mucositis in head and neck cancer patients undergoing therapeutic radiotherapy is also planned.

A Phase I/II clinical study evaluating YELIVA in patients with refractory/relapsed diffuse large B-cell lymphoma (DLBCL) was initiated at the Louisiana State University Health Sciences Center (LSUHSC) in New Orleans in June 2015 and is expected to resume later this year following administrative hold and pending a protocol amendment aimed at improving overall recruitment. The study is supported by a grant awarded to Apogee from the NCI, as well as additional support from RedHill.

The studies with YELIVA (ABC294640) are registered on www.ClinicalTrials.gov, a web-based service by the U.S. National Institute of Health, which provides public access to information on publicly and privately supported clinical studies.

About Multiple Myeloma:
Multiple myeloma is a malignant plasma cell disorder which is usually not curable1. Symptomatic multiple myeloma is characterized by a clonal proliferation of plasma cells preceding clinical findings that include bone lesions, fractures, anemia, renal failure and hypercalcemia2. Approximately 30,000 new cases of multiple myeloma are expected to be diagnosed in the U.S. in 2016, accounting for 1.8% of all cancers. The 5-year survival rate of myeloma is estimated at 48.5% and approximately 95,000 people are living with myeloma in the United States3. The risk of multiple myeloma increases as people age. Most patients diagnosed with this cancer are at least 65 years old4, making treatment with the most effective therapies problematic. The worldwide sales of multiple myeloma therapies are estimated to exceed $12 billion in 20165.

About YELIVA (ABC294640):
YELIVA (ABC294640) is a Phase II-stage, proprietary, first-in-class, orally-administered, sphingosine kinase-2 (SK2) selective inhibitor with anticancer and anti-inflammatory activities. RedHill is pursuing with YELIVA multiple clinical programs in oncology, inflammatory and gastrointestinal indications. By inhibiting the SK2 enzyme, YELIVA blocks the synthesis of sphingosine 1-phosphate (S1P), a lipid signaling molecule that promotes cancer growth and pathological inflammation. SK2 is an innovative molecular target for anticancer therapy because of its critical role in catalyzing the formation of S1P, which is known to regulate cell proliferation and activation of inflammatory pathways. YELIVA was originally developed by U.S.-based Apogee Biotechnology Corp. and completed multiple successful pre-clinical studies in oncology, inflammation, GI and radioprotection models, as well as the ABC-101 Phase I clinical study in cancer patients with advanced solid tumors. The development of YELIVA was funded to date primarily by grants and contracts from U.S. federal and state government agencies awarded to Apogee Biotechnology Corp., including the U.S. National Cancer Institute, the U.S. Department of Health and Human Services’ Biomedical Advanced Research and Development Authority (BARDA), the U.S. Department of Defense and the FDA Office of Orphan Products Development.