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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.

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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.

8-K – Current report

On September 8, 2016 The Food and Drug Administration ("FDA") has notified Clovis Oncology, Inc. (the "Company") that FDA is not currently planning to hold an advisory committee meeting to discuss the Company’s New Drug Application for rucaparib (Filing, 8-K, Clovis Oncology, SEP 8, 2016, View Source [SID:1234515002]). As previously announced by the Company, FDA has accepted the Company’s NDA for accelerated approval of rucaparib and granted priority review status to the application with a Prescription Drug User Fee Act (PDUFA) date of February 23, 2017.

GTx Achieves Stage 1 Milestone in Phase 2 Clinical Trial of Enobosarm in ER+/AR+ Breast Cancer

On September 8, 2016 GTx, Inc. (Nasdaq: GTXI) reported the achievement of the Stage 1 milestone for the 9 mg cohort of its Phase 2 clinical trial of enobosarm (GTx-024) to treat women with advanced, estrogen receptor positive (ER+), androgen receptor positive (AR+) breast cancer (Press release, GTx, SEP 8, 2016, View Source [SID:1234514999]). A pre-defined number of patients demonstrated clinical benefit per protocol to allow the clinical trial to advance to the second and final stage of the trial (Stage 2). GTx also expects to provide an update on Stage 1 of the second dosing cohort (18 mg) in the clinical trial once there are sufficient evaluable patients to assess clinical benefit in this cohort. The Company anticipates reporting Stage 1 data from the clinical trial in the fourth quarter of 2016.

"The demonstration of clinical benefit among a pre-defined number of evaluable patients in Stage 1 of the 9 mg cohort of our ER+/AR+ breast cancer study represents an important milestone for GTx since we have met the protocol specified success criteria to continue with enrollment in Stage 2 of this cohort," said Robert J. Wills, Ph.D., Executive Chairman of GTx. "We believe enobosarm may provide a new hormonal approach for the treatment of estrogen receptor positive breast cancer and may delay the need for chemotherapy in these women."

About the Phase 2 Clinical Trial in ER+/AR+ Breast Cancer

The open-label, multi-center, multinational Phase 2 clinical trial (NCT02463032) will assess the efficacy and safety of orally administered enobosarm in up to 88 evaluable patients with metastatic or locally advanced, ER+/AR+ breast cancer. Patients will receive orally-administered enobosarm (9 mg or 18 mg) daily for up to 24 months. The two cohorts in the trial will be treated independently for the purpose of assessing efficacy. The first stage of evaluation will be assessed among the first 18 evaluable patients for each cohort. If at least 3 of 18 patients achieve clinical benefit at week 24, then the trial will proceed to the second stage of enrollment for that cohort to assess clinical benefit in a total of 44 evaluable patients per arm. Clinical benefit is defined as a complete response, partial response, or stable disease, as measured by Response Evaluation Criteria in Solid Tumors (RECIST) at 24 weeks. The lead investigator for the trial is Dr. Beth Overmoyer from the Dana Farber Cancer Institute and the Harvard Medical School.

About enobosarm

Enobosarm, a selective androgen receptor modulator (SARM), has been evaluated in 24 completed or ongoing clinical trials enrolling over 1,500 subjects, of which approximately 1000 subjects were treated with enobosarm at doses ranging from 0.1 mg to 100 mg. At all evaluated dose levels, enobosarm was observed to be generally safe and well tolerated.

Previously, enobosarm 9 mg has been tested in a Phase 2, proof of concept clinical trial of 22 postmenopausal women with ER+ metastatic breast cancer who have previously responded to endocrine therapy. 17 of the 22 patients were confirmed to be AR+, and 6 of those 17 patients demonstrated clinical benefit at six months. In total, 7 patients (one patient with indeterminate AR status) achieved clinical benefit at six months. The results also demonstrated that, after a median duration on study of 81 days, 41 percent of all patients (9/22) achieved clinical benefit as best response and also had increased PSA which appears to be an indicator of AR activity. Enobosarm was well tolerated. The most common adverse events reported were pain, fatigue, nausea, hot flash/night sweats, and arthralgia.

About ER+/AR+ Breast Cancer

Breast cancer is the most commonly diagnosed cancer in women, and one in eight women will develop invasive breast cancer in their lifetime. In 2012, 1.7 million women world-wide were diagnosed with breast cancer, and there were 6.3 million women alive who had been diagnosed with breast cancer in the previous five years. Clinical assessment of breast cancer provides for routine characterization of receptor status, including the presence or absence of estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2 (HER2) in the tumor tissue. Receptor status is used to assess metastatic potential as well as to guide treatment decisions. The majority of breast cancers are considered hormone receptor positive (expressing ER or progesterone receptor). Approximately 70 percent of women in the U.S. with breast cancer have ER+ tumors, and 75 to 90 percent of these cancers are also AR+.

Estrogen promotes the growth of breast cancers that are hormone receptor positive. Therefore, treatment is directed at blocking the effects of estrogen on the breast cancer either through blocking the estrogen receptor or minimizing the production of estrogen. This endocrine therapy is the cornerstone of treatment for the majority of women with hormone receptor positive advanced breast cancer and is the preferred initial treatment over alternative approaches such as chemotherapy, due to its efficacy and favorable safety profile. Patients who respond to one endocrine therapy are likely to respond to subsequent hormonal therapies. Therefore, the standard of care for women with hormone receptor positive breast cancer typically involves the sequencing of endocrine agents until intolerance or development of resistance occurs, or metastatic progression necessitates a transition to chemotherapy.

Enobosarm may offer an alternate hormonal approach for the treatment of endocrine sensitive advanced breast cancer prior to the introduction of chemotherapy.