On October 29, 2017 Esanex, Inc., a clinical stage company developing Heat Shock Protein inhibitors for the treatment of cancer, reported that it is presenting preclinical data from its Heat Shock Protein 90 (Hsp90) inhibitor SNX-5422 program, showing promising anti-tumor effects both alone and in combination with checkpoint inhibitors, at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) (Press release, Esanex, OCT 29, 2017, View Source [SID1234521339]).

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"Results from these two studies reaffirm our belief in the potential of SNX-5422 both as a monotherapy and in combination with immuno-oncology drugs," said Everardus (Eric) Orlemans, Ph.D, Chief Scientific Officer and Senior Vice President, Development, Esanex. "We are conducting further research to explore the potential of SNX-5422 in other indications as well as through our ongoing Phase 1b trial in chronic lymphocytic leukemia. The results from the combination research support further development of SNX-5422 in combination with checkpoint inhibitors for the potential treatment of a number of cancer types."

The two posters will be presented October 29th at 12:30 – 4:00 pm EST, in Hall E, Pennsylvania Convention Center.

Poster B139: "Promising antitumor effects of SNX-5422 in combination with checkpoint inhibitors in an MC38 murine model", presented at the session PO.B20 – Therapeutic Agents: Other Topics.
SNX-5422 is an orally active prodrug of SNX-2112, a potent, highly selective inhibitor of Hsp90. The results described in the poster show that SNX-5422 at either 25 mg/kg or 40 mg/kg, in combination with the immune checkpoint inhibitors anti-PD1, PD-L1 or CTLA4, demonstrated significant antitumor activity in the MC38 murine colon cancer model.

Poster B026: "SNX-2112 interferes with mitochondrial metabolism in TP53 mutant tumors", presented at the session PO.B05 – Metabolism.
In vitro work with SNX-2112, the active derivative of SNX-5422, demonstrated significant antitumor activity in TP53 null tumors and in rearranged MYC hematologic and selected solid tumors (e.g., hepatocellular carcinoma, mesothelioma). This activity appears to be, in part, the result of interference with cancer related metabolic pathways.

About SNX-5422
SNX-5422 is a chemically unique, orally active Hsp90 inhibitor that has provided durable clinical responses in open label trials in non-small cell lung cancer (NSCLC) and neuroendocrine tumors (NET). The potential of SNX-5422 in hematologic cancers is currently being explored in a chronic lymphocytic leukemia (CLL) open label clinical trial (clinicaltrials.gov ID#NCT02973399). With approximately 200 patients treated to date, SNX-5422 has a well-established safety profile that supports studying it in combination with existing approved drugs in a variety of clinical settings.

On October 28, 2017 Kura Oncology, Inc. (Nasdaq:KURA), a clinical stage biopharmaceutical company focused on the development of precision medicines for oncology, reported new results for KO-539, the company’s potent and selective inhibitor of the menin-MLL protein-protein interaction, which is currently in preclinical development as a potential treatment for patients with genetically-defined subsets of acute leukemias (Press release, Kura Oncology, OCT 28, 2017, View Source [SID1234521274]). The results were featured in a late-breaking presentation today at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) in Philadelphia.

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Although KO-539 was originally designed as a potential therapy for the MLL-rearranged leukemias, the new results demonstrate significant activity in preclinical models of additional genetically-defined subsets of AML, including those with oncogenic driver mutations in NPM1, IDH1, IDH2 and DNMT3A. Preliminary pharmacodynamic data suggests that KO-539 exerts anti-leukemic activity by induction of myeloid differentiation in AML blasts, a mechanism that is distinct from and potentially complementary to existing cytotoxic and antiproliferative therapies. The menin-MLL complex appears to be a central node in epigenetic dysregulation driven by several distinct oncogenic driver mutations known to be important in diverse leukemias and myeloproliferative disorders.

“Although AML is a relatively common hematologic malignancy with a generally poor prognosis, the development of novel therapeutic approaches has been hampered by the many different genetic and clinical subgroups found in the disease and the relatively short durations of response,” said Yi Liu, Ph.D., Chief Scientific Officer, Kura Oncology. “We’re encouraged by the results presented today because they demonstrate that menin-MLL inhibitors have the potential to be active in subtypes representing approximately half of the patients with AML and drive robust and persistent responses in preclinical models.”

A copy of the poster, entitled “A novel small molecule menin-MLL inhibitor for potential treatment of MLL-rearranged leukemias and NPM1/DNMT3A-mutant AML,” is now available on the company’s website at www.kuraoncology.com.

On October 27, 2017 Kyowa Hakko Kirin Co., Ltd. (Tokyo: 4151 President and CEO: Nobuo Hanai, “Kyowa Hakko Kirin”) reported that its marketing authorisation application (MAA) for mogamulizumab, for the treatment of cutaneous T-cell lymphoma (CTCL) in adults who have received at least one prior systemic therapy, has been validated by the European Medicines Agency (EMA) and is now under review (Press release, Kyowa Hakko Kirin, OCT 27, 2017, View Source [SID1234521240]).

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This MAA is based on the data from the MAVORIC (Mogamulizumab anti-CCR4 Antibody Versus ComparatOR In CTCL) study, the largest global randomised clinical trial of systemic therapy in CTCL.

“This is a significant milestone for our subsidiary, Kyowa Kirin Pharmaceutical Development,” said Mitsuo Satoh, Ph.D., Executive Officer, Vice President Head of R&D Division of Kyowa Hakko Kirin. “I believe mogamulizumab has the potential to be an advance in therapy for patients with CTCL and we will keep working to make it available to patients as soon as possible.”

Mogamulizumab was first approved in Japan 2012 for other haematological malignancies and in 2014 for use in CTCL. Kyowa Hakko Kirin has also initiated discussions with regulatory authorities concerning plans for marketing authorisation applications for mogamulizumab in CTCL in other countries.

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 humanised 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).

About MAVORIC
MAVORIC is a Phase 3 open-label, multi-centre, randomised study of mogamulizumab versus active comparator in patients with mycosis fungoides (MF) and Sézary syndrome (SS) who have failed at least one prior systemic treatment. The study was conducted in the US, Europe, Japan and Australia, and randomised 372 patients.

About CTCL (Cutaneous T-cell Lymphoma)
CTCL is a rare type of non-Hodgkin’s T-cell lymphoma. The two most common types of CTCL are MF and SS, and depending on the stage, the disease may involve skin, blood, lymph nodes, and viscera. In advanced stage CTCL is associated with significant morbidity and mortality.

On October 27, 2017 Kura Oncology, Inc. (Nasdaq:KURA), a clinical stage biopharmaceutical company focused on the development of precision medicines for oncology, reported presented updated preliminary results from its Phase 2 open-label trial of tipifarnib, a farnesyltransferase inhibitor, in patients with head and neck squamous cell carcinomas (HNSCC) with HRAS mutations (Press release, Kura Oncology, OCT 27, 2017, View Source [SID1234521243]).

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The results were featured in a late-breaking, oral presentation by Dr. Alan Ho of Memorial Sloan Kettering Cancer Center at the Spotlight on Proffered Papers Session 1 at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper), taking place today in Philadelphia.

Four out of six evaluable HRAS mutant HNSCC patients enrolled in the study achieved a confirmed partial response, as defined by standard RECIST criteria. In addition, as of the data cutoff date of October 4, 2017, four HRAS mutant HNSCC patients remained on study in cycles 21, 7, 5 and 3. The patients in cycles 21, 7 and 5 had all experienced partial responses while the patient in cycle 3 experienced stable disease as of the first response assessment in cycle 2. One HRAS mutant HNSCC patient with a confirmed partial response remained on study through cycle 20 and withdrew in cycle 21 with progressive disease. Another HRAS mutant HNSCC patient experienced a best response assessment of stable disease and withdrew from the study in cycle 8.

Tipifarnib has demonstrated clinical activity in previously treated patients, including those who have progressed on chemotherapy with or without cetuximab or immune therapy. The majority of adverse events reported by the investigators have been mild to moderate and are consistent with the adverse event profile previously reported for tipifarnib.

“The responses, durability and safety data with tipifarnib clearly suggest this is an important drug candidate for patients with HRAS mutant head and neck cancers,” said Alan Ho, M.D., Ph.D., of Memorial Sloan Kettering Cancer Center and presenter of the tipifarnib oral presentation. “We are excited to continue to follow these patients and treat additional HRAS mutant patients in the ongoing Phase 2 trial.”

“The consistent clinical activity of tipifarnib in HNSCC patients with HRAS mutations is very encouraging,” said Antonio Gualberto, M.D., Ph.D., chief medical officer of Kura Oncology. “Based on these positive results, we continue to explore available options to rapidly advance the development of tipifarnib and subject to input from regulatory authorities, we plan to initiate a registration-enabling study in HRAS mutant HNSCC in 2018.”

About HRAS Mutant HNSCC

Head and neck cancer is one of the leading causes of cancer-related deaths worldwide, with squamous cell carcinomas accounting for most head and neck cancers. Response rates for the three agents approved for treatment of HNSCC in the second line, including cetuximab and immune therapy agents, are in the range of 13-16%, and median overall survival is up to 7.5 months. HRAS is a proto-oncogene that has been implicated in the development and progression of HNSCC and has been established to be uniquely farnesylated.

Eli Lilly has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission (Filing, 10-Q, Eli Lilly, 2017, OCT 27, 2017, View Source [SID1234521270]).

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