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Kura Oncology Doses First Patient in Phase 1 Trial of ERK Inhibitor KO-947

On April 7, 2017 Kura Oncology, Inc. (NASDAQ:KURA), a clinical stage biopharmaceutical company focused on the development of precision medicines for oncology, reported that the first patient has been dosed in its Phase 1 clinical trial of KO-947, a potent and selective small molecule inhibitor of extracellular-signal-regulated kinases 1 and 2 (ERK1/2) (Press release, Kura Oncology, APR 7, 2017, View Source [SID1234518509]).

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"We are committed to the discovery and development of product candidates that target oncogenes and oncogenic pathways for the treatment of cancer," said Troy Wilson, Ph.D., J.D., President and CEO of Kura. "We believe KO-947 holds much promise as a potential therapeutic, and its advancement into the clinic underscores Kura’s productivity and commitment to building a diverse pipeline of precision medicines."

"The RAS/RAF/MEK/ERK pathway is dysregulated in more than 30% of human cancers, including tumors arising from mutations in KRAS, NRAS and BRAF, encompassing a number of cancer indications with significant unmet medical need," said Antonio Gualberto, M.D., Ph.D., Chief Medical Officer of Kura. "We believe the unique and differentiated drug properties of KO-947, as well as a significant body of preclinical data including data just presented at the AACR (Free AACR Whitepaper) meeting this week, make it a compelling therapeutic candidate, and we look forward to evaluating its tolerability and activity in the clinic."

The Phase 1 trial of KO-947 is designed to determine the maximum tolerated dose of KO-947 in patients with locally advanced unresectable or metastatic, relapsed and/or refractory, non-hematological malignancies. The trial design includes a dose escalation, maximum–tolerated dose expansion and one or more tumor-specific extension cohorts. Currently, two tumor-specific cohorts, non-small cell lung cancer with mutations in RAS or BRAF and squamous cell carcinomas, have been identified as potential extension cohorts. Additional information about this clinical trial is available at clinicaltrials.gov using the identifier: NCT03051035

About KO-947

KO-947 is a potent and selective small molecule inhibitor of ERK1/2 kinases. KO-947 exhibits potent anti-proliferative activity across a broad panel of tumor cell lines with mutations in BRAF, NRAS or KRAS and demonstrates prolonged pathway inhibition, both in vitro and in vivo. Durable tumor regression has been observed with KO-947 in preclinical cell line and patient derived xenograft models, including KRAS- and BRAF-mutant adenocarcinomas and squamous cell carcinomas lacking BRAF/RAS mutations.

[PDF]Kyowa Hakko Kirin Announces Positive Results of the Phase 3 Clinical Study of Mogamulizumab (KW-0761) in Patients with Cutaneous T-cell Lymphoma

On April 7, 2017 Kyowa Hakko Kirin Co., Ltd. (Tokyo: 4151, President and CEO: Nobuo Hanai, "Kyowa Hakko Kirin") reported the Global Phase 3 study (MAVORIC: Mogamulizumab anti-CCR4 Antibody Versus ComparatOR In CTCL) investigating the use of mogamulizumab (KW-0761) in patients with cutaneous T-cell lymphoma (CTCL) met its primary endpoint of progression free survival (Press release, Kyowa Hakko Kirin, APR 7, 2017, View Source [SID1234518503]).

MAVORIC is a Phase 3 Open-Label, Multi-Center, Randomized Study of mogamulizumab versus vorinostat in patients with CTCL who have failed at least one prior systemic treatment. The study is conducted in the US, Europe, Japan and Australia, and randomized 372 patients to receive either mogamulizumab or vorinostat. The top-line results demonstrated a statistically significant improvement in progression free survival in the mogamulizumab arm compared to the control (vorinostat) arm, and tolerable safety profile of mogamulizumab.

Kyowa Hakko Kirin will complete a full evaluation of the data from the MAVORIC study and work with investigators on the future presentation and publication of results. Kyowa Hakko Kirin plans to initiate discussions with global regulatory authorities in 2017 about plans for pursuing marketing authorizations for mogamulizumab in CTCL.

"We are delighted with the positive results from the MAVORIC study which is the largest, global randomized phase 3 clinical study ever conducted in patients with CTCL." said Mitsuo Satoh, Executive Officer, Vice President, Head of Research and Development Division of Kyowa Hakko Kirin.
"We look forward to reviewing the data with regulatory agencies in the near future." said Stephen Letrent, Pharm.D, Ph.D, Senior Vice President, Kyowa Kirin Pharmaceutical Development.

The Kyowa Hakko Kirin Group companies strive to contribute to the health and well-being of people around the world by creating new value through the pursuit of advances in life sciences and technologies.

About Mogamulizumab
Mogamulizumab is a humanized monoclonal antibody (mAb) directed against CC chemokine receptor 4 (CCR4), which is frequently expressed on leukemic cells of certain hematologic malignancies including CTCL. Mogamulizumab was produced using Kyowa Hakko Kirin’s proprietary POTELLIGENT platform, which is associated with enhanced antibody-dependent cellular cytotoxicity (ADCC). Mogamulizumab was first granted marketing authorization in Japan in March 2012 for the treatment of patients with relapsed or refractory CCR4-positive Adult T-cell Leukemia-Lymphoma (ATL) under the trade name POTELIGEO. The drug was subsequently granted marketing authorization in Japan for the treatment of patients with relapsed or refractory CCR4-positive, peripheral T-cell lymphoma (PTCL) and CTCL in March 2014, and with chemotherapy-naive CCR4-positive ATL in December 2014.

About Cutaneous T-cell Lymphoma (CTCL)
CTCL is a rare type of non-Hodgkin’s lymphoma which is characterized by localization of malignant T lymphocytes to the skin. The two most common types of CTCL are mycosis fungoides (MF) and Sézary syndrome (SS), and depending on the stage, the disease may involve skin, blood, lymph nodes, viscera and other organs.

Innocrin Pharmaceuticals Appoints Fred Eshelman, PharmD as CEO and is Granted Fast Track Designation by FDA for Seviteronel Treatment of Women with Triple-negative Breast Cancer and Women or Men with Estrogen Receptor-positive Breast Cancer

On April 6, 2017 Innocrin Pharmaceuticals, Inc., a clinical-stage company focused on the development of the oral, selective CYP17-lyase/androgen receptor (AR) inhibitor, seviteronel, reported the appointment of Fred Eshelman, PharmD, of Eshelman Ventures as Chief Executive Officer, effective March 15, 2017 (Press release, Innocrin Pharmaceutical, APR 6, 2017, View Source [SID1234518507]).

Douglas Reed, MD, Innocrin Chairman of the Board stated, "I am pleased to have Fred lead the Innocrin team as the company enters mid-stage clinical development for breast and prostate cancer. His transactional and drug development expertise will serve Innocrin well as the company and its clinical programs continue to mature."

Fred Eshelman is the founder of Eshelman Ventures LLC, an investment company primarily interested in private healthcare companies. Previously he founded and served as CEO and Executive Chairman of Pharmaceutical Product Development (NASDAQ: PPD). After PPD he served as Founding Chairman and largest shareholder of Furiex Pharmaceuticals (NASDAQ: FURX), which was sold to Forest Labs/Actavis in July, 2014. His career has also included positions as senior vice president of development and board member of the former Glaxo, Inc., as well as various management positions with Beecham Laboratories and Boehringer Mannheim Pharmaceuticals.

"As the lead investor of Innocrin’s last round of financing, I am fully committed to the success of the seviteronel clinical development programs, since the drug provides novel treatment options for breast and prostate cancer sub-types where patients have failed other therapies. I am not only investing in seviteronel, but also betting on members of the development team as I join the company’s day-to-day leadership," said Dr. Eshelman.

Innocrin also announced that the FDA granted a second Fast Track Designation for seviteronel (VT-464). The new designation is for the treatment of women with advanced AR+ triple-negative breast cancer (TNBC) and women or men with advanced estrogen receptor-positive (ER+) breast cancer.

Established under the FDA Modernization Act of 1997, the Fast Track program is designed to facilitate the development and review of drugs intended to treat serious conditions and fill an unmet medical need. A drug development program with Fast Track designation is afforded greater access to FDA for the purpose of expediting the drug’s development, review and potential approval.

"We believe that the award of a second Fast Track designation for seviteronel, in addition to men with castration resistant prostate cancer (CRPC), is continued FDA recognition of the compound’s potential to address significant unmet medical need in hormone-dependent cancers," stated Dr. Eshelman.

Edwina Baskin-Bey, M.D. Innocrin Chief Medical Officer stated, "Granting of the FDA Fast Track Designation for seviteronel treatment of women and men with advanced breast cancer helps to accelerate our already aggressive clinical development programs. Increased FDA collaborations and rolling reviews for both CRPC and breast cancer will allow for us to continue our momentum of bringing seviteronel to patients in need of new treatment options."

Innocrin also announced that it recently completed enrollment of women with ER+ breast cancer in the Phase 2 CLARITY (CYP17 Lyase and Androgen Receptor Inhibitor Treatment with Seviteronel) study (INO-VT-464-006; NCT02580448) and enrollment of women with TNBC and men with ER+ breast cancer is ongoing. Phase 2 enrollment in its prostate cancer studies are also ongoing in men who have progressed following abiraterone, enzalutamide or both.

Innocrin also announced presentations at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) annual meeting (1-5 April 2017) and the upcoming American Urological Association (AUA) annual meeting (12-16 May 2017) describing new combination and single-agent seviteronel results in breast and prostate models resistant to approved therapies. Updated Phase 2 breast cancer clinical results will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (2-6 June 2017).

About Seviteronel (VT-464)

Seviteronel is a once-daily oral therapeutic given without prednisone. Seviteronel selectively inhibits CYP17 lyase, an enzyme needed for the synthesis of androgens and estrogens, and also directly blocks the AR.

It is thought that the AR may stimulate disease progression of breast cancer tumors that no longer are ER+ (e.g., are triple-negative) or are ER+ but have become resistant to ER-directed therapies such as aromatase inhibitors or tamoxifen. Preclinical study results presented at the 2015 San Antonio Breast Cancer Symposium, confirmed that seviteronel, due to its multiple mechanisms of action, blocks the growth of resistant ER+ and AR+ breast cancer cells more potently than enzalutamide. Phase 2 enrollment of women and men with breast cancer is ongoing in the CLARITY-01 (CYP17 Lyase and Androgen Receptor Inhibitor Treatment with Seviteronel) study (NCT02580448).

A growing body of preclinical and clinical evidence shows that seviteronel blocks the growth of deadly CRPC that is resistant to abiraterone (a CYP17 hydroxylase inhibitor) or enzalutamide (an AR antagonist). CRPC disease progression following treatment with abiraterone, enzalutamide or both represents a major unmet medical need due to the widespread and growing use of both agents, as well as the high cross-resistance between these agents (e.g., cancers that are resistant to abiraterone are typically resistant to enzalutamide and vice versa). Fast Track Designation was granted for seviteronel treatment of men with CRPC 10 December 2015. Enrollment is ongoing in two Phase 2 studies (NCT02012920, NCT02445976).

About Breast Cancer

Each year over 230,000 women and 2,300 men are diagnosed with breast cancer in the United States, with almost 40,000 and 440 deaths attributable to the disease. While estrogen deprivation is currently the standard of care for ER+ BCa, the majority of patients eventually develop resistance. ER+ patients comprise ~75% of all metastatic breast cancer cases, and TNBC accounts for ~15-20%. TNBC has a more aggressive course than ER+ BCa does but both have poor survival rates post-failure of endocrine and/or chemotherapy.

About Prostate Cancer

Prostate cancer is the second most common form of cancer affecting men in the United States: an estimated one in six will be diagnosed with prostate cancer in his lifetime. Prostate cancer afflicts nearly 240,000 men each year in the US and approximately 36,000 men die due to metastatic CRPC.

Myriad Genetics and BeiGene Sign Agreement to Develop Companion Diagnostics for Use with BeiGene’s Novel PARP Inhibitor, BGB-290

On April 6, 2017 Myriad Genetics, Inc. (NASDAQ:MYGN), a leader in molecular diagnostics and personalized medicine, reported that it has entered into a companion diagnostic development collaboration with BeiGene, a clinical-stage biopharmaceutical company developing molecularly-targeted and immuno-oncology drugs for the treatment of cancer, to accelerate precision medicine in oncology (Press release, Myriad Genetics, APR 6, 2017, View Source [SID1234518501]).

Under the agreement, BeiGene will use Myriad’s myChoice HRD and BRACAnalysis CDx companion diagnostic tests to support the clinical development of its novel PARP inhibitor, BGB-290. Specific terms of the deal were not disclosed.

"We are excited to collaborate with BeiGene to help identify patients who stand to benefit the most from treatment with BGB-290," said Mark C. Capone, president and CEO, Myriad Genetics. "As the pioneer in companion diagnostics for PARP inhibitors, we recognize that precision medicine only can be achieved by molecularly matching patients to the right therapy. Together with BeiGene, we are in a unique position to integrate advanced genetic information into clinical practice and achieve better patient outcomes."

About BRACAnalysis CDx
BRACAnalysis CDx is an in vitro diagnostic device intended for the qualitative detection and classification of variants in the protein coding regions and intron/exon boundaries of the BRCA1 and BRCA2 genes using genomic DNA obtained from whole blood specimens.

About myChoice HRD
Myriad’s myChoice HRD is the first homologous recombination deficiency test that can detect when a tumor has lost the ability to repair double-stranded DNA breaks, resulting in increased susceptibility to DNA-damaging drugs such as platinum drugs or PARP inhibitors. It is estimated that 1.8 million people in the United States and Europe who are diagnosed with cancers annually may be candidates for treatment with DNA-damaging agents.

Kite Wins ‘Clinical Trial Result of the Year’ for its Pivotal CAR-T Trial of Axicabtagene Ciloleucel in Patients with Aggressive Non-Hodgkin Lymphoma at the 2017 Clinical and Research Excellence Awards

On April 6, 2017 Kite Pharma, Inc., (Nasdaq:KITE) reported that it won the Clinical Trial Result of the Year award for ZUMA-1, its pivotal CAR-T trial of axicabtagene ciloleucel, in patients with refractory aggressive B-cell non-Hodgkin lymphoma (NHL) at the Clinical and Research Excellence (CARE) Awards (Press release, Kite Pharma, APR 6, 2017, View Source [SID1234518500]). The award recognizes clinical achievements in the pharmaceutical industry and contribution to the advancement of therapies for unmet medical needs.

"This award is an important acknowledgement of the ZUMA-1 trial, the first multicenter CAR-T therapy trial in aggressive NHL, and the potential of CAR-T therapy to significantly transform the treatment of cancer," said Arie Belldegrun, M.D., FACS, Chairman, President and Chief Executive Officer of Kite. "We thank the Kite research and development team for their dedication and congratulate them on this well-deserved recognition for their central role in advancing the development of this potentially paradigm changing treatment."

The study met the primary endpoint of objective response rate (ORR) recorded after a single infusion of axicabtagene ciloleucel with 82 percent (p < 0.0001). At a median follow-up of 8.7 months, 44 percent of patients were in ongoing response, which included 39 percent of patients in complete response (CR). These results from 101 patients demonstrate the treatment effect of axicabtagene ciloleucel in diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL) and transformed follicular lymphoma (TFL), which are types of aggressive NHL.

The most common grade 3 or higher adverse events included anemia (43 percent), neutropenia (39 percent), decreased neutrophil count (32 percent), febrile neutropenia (31 percent), decreased white blood cell count (29 percent), thrombocytopenia (24 percent), encephalopathy (21 percent) and decreased lymphocyte count (20 percent). As compared to the interim analysis, grade 3 or higher cytokine release syndrome (CRS) decreased from 18 percent to 13 percent and neurologic events decreased from 34 percent to 28 percent. There were three deaths throughout the course of the trial not due to disease progression, of which two events, were deemed related to axicabtagene ciloleucel. There were no cases of cerebral edema.

Full data from the primary analysis of ZUMA-1 were most recently presented at the 2017 American Association of Cancer Research Annual Meeting in Washington, D.C. in April. In December 2015, axicabtagene ciloleucel received Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration (FDA) for DLBCL, TFL, and PMBCL. Kite completed its submission of a Biologics License Application (BLA) for axicabtagene ciloleucel with the FDA in March 2017 and, if approved, plans to commercially launch axicabtagene ciloleucel in 2017.

The awards, presented by Informa’s Pharma Intelligence, were announced at a ceremony in Boston on April 5, 2017.

ZUMA-1 is supported in part by funding from The Leukemia & Lymphoma Society (LLS) Therapy Acceleration Program.

About axicabtagene ciloleucel

Kite’s lead product candidate, axicabtagene ciloleucel, is an investigational therapy in which a patient’s T cells are engineered to express a chimeric antigen receptor (CAR) to target the antigen CD19, a protein expressed on the cell surface of B-cell lymphomas and leukemias, and redirect the T cells to kill cancer cells. Axicabtagene ciloleucel has been granted Breakthrough Therapy Designation status for diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (TFL), and primary mediastinal B-cell lymphoma (PMBCL) by the U.S. Food and Drug Administration (FDA) and Priority Medicines (PRIME) regulatory support for DLBCL in the EU.