On September 5, 2017 MEI Pharma, Inc. (Nasdaq: MEIP), an oncology company focused on the clinical development of novel therapies for cancer, reported that it has entered into a license agreement with Presage Biosciences, Inc. for voruciclib, a clinical-stage, oral and selective cyclin-dependent kinase (CDK) inhibitor (Press release, MEI Pharma, SEP 5, 2017, View Source [SID1234520396]). Under the terms of the agreement, MEI Pharma receives exclusive worldwide rights to develop, manufacture and commercialize voruciclib. In exchange, Presage will receive near-term payments of $2.9 million and additional potential payments of up to $181 million upon the achievement of certain development, regulatory and commercial milestones. Presage will also receive mid-single-digit tiered royalties on the net sales of any product successfully developed.

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"We are very excited by this opportunity to add voruciclib to our growing pipeline of clinical-stage oncology drug candidates," said Daniel P. Gold, Ph.D., President and Chief Executive Officer of MEI Pharma. "Voruciclib is a selective CDK inhibitor, a class of drugs that has recently demonstrated significant clinical and commercial value, and is differentiated by its potent inhibition of CDK9. This is an attractive asset that comes with an established clinical safety profile, along with compelling pre-clinical data showing suppression of MCL1, a known mechanism of resistance to BCL2 inhibitors, and synergy with the FDA-approved BCL2 inhibitor venetoclax. We believe this provides a clear and efficient clinical development path forward in combination with venetoclax. We appreciate that Presage put their trust in us to execute this plan and we are eager to get started."

Voruciclib (formerly P1446A) has been tested in more than 70 patients in multiple Phase 1 studies and has been associated with manageable side effects consistent with other drugs in its class, including nausea, vomiting and diarrhea. In pre-clinical studies, voruciclib alone induces cell death in multiple patient-derived chronic lymphocytic leukemia (CLL) samples . In addition, voruciclib shows dose-dependent suppression of MCL1 at concentrations achievable with doses that appeared to be generally well tolerated in the Phase 1 studies. Studies have shown that MCL1 is an established resistance mechanism to the B-cell lymphoma 2 (BCL2) inhibitor venetoclax (marketed as Venclexta) .

"Voruciclib is a promising drug candidate with the potential to overcome mechanisms of drug resistance and significantly improve patient outcomes," said David Johnson, Chairman of Presage. "The management team at MEI Pharma has a proven track record in oncology therapeutic development and we believe they have the clinical, regulatory and CMC expertise to maximize the value of this asset. This transaction also enables us to focus our attention on identifying and advancing additional drug candidates and combinations using our powerful CIVO intratumoral microdosing platform.

There are currently two CDK inhibitors approved by the U.S. Food and Drug Administration, palbociclib (marketed as Ibrance) and ribociclib (marketed as Kisqali), both oral, selective CDK 4/6 inhibitors approved for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer in combination with hormonal therapy. A third, abemaciclib, was recently granted priority review by the FDA.

September 5, 2017 — MEI Pharma, Inc. (Nasdaq: MEIP), an oncology company focused on the clinical development of novel therapies for cancer, reported that it has entered into a license agreement with Presage Biosciences, Inc. for voruciclib, a clinical-stage, oral and selective cyclin-dependent kinase (CDK) inhibitor. Under the terms of the agreement, MEI Pharma receives exclusive worldwide rights to develop, manufacture and commercialize voruciclib. In exchange, Presage will receive near-term payments of $2.9 million and additional potential payments of up to $181 million upon the achievement of certain development, regulatory and commercial milestones. Presage will also receive mid-single-digit tiered royalties on the net sales of any product successfully developed.
"We are very excited by this opportunity to add voruciclib to our growing pipeline of clinical-stage oncology drug candidates," said Daniel P. Gold, Ph.D., President and Chief Executive Officer of MEI Pharma. "Voruciclib is a selective CDK inhibitor, a class of drugs that has recently demonstrated significant clinical and commercial value, and is differentiated by its potent inhibition of CDK9. This is an attractive asset that comes with an established clinical safety profile, along with compelling pre-clinical data showing suppression of MCL1, a known mechanism of resistance to BCL2 inhibitors, and synergy with the FDA-approved BCL2 inhibitor venetoclax. We believe this provides a clear and efficient clinical development path forward in combination with venetoclax. We appreciate that Presage put their trust in us to execute this plan and we are eager to get started."
Voruciclib (formerly P1446A) has been tested in more than 70 patients in multiple Phase 1 studies and has been associated with manageable side effects consistent with other drugs in its class, including nausea, vomiting and diarrhea. In pre-clinical studies, voruciclib alone induces cell death in multiple patient-derived chronic lymphocytic leukemia (CLL) samples . In addition, voruciclib shows dose-dependent suppression of MCL1 at concentrations achievable with doses that appeared to be generally well tolerated in the Phase 1 studies. Studies have shown that MCL1 is an established resistance mechanism to the B-cell lymphoma 2 (BCL2) inhibitor venetoclax (marketed as Venclexta) .
"Voruciclib is a promising drug candidate with the potential to overcome mechanisms of drug resistance and significantly improve patient outcomes," said David Johnson, Chairman of Presage. "The management team at MEI Pharma has a proven track record in oncology therapeutic development and we believe they have the clinical, regulatory and CMC expertise to maximize the value of this asset. This transaction also enables us to focus our attention on identifying and advancing additional drug candidates and combinations using our powerful CIVO intratumoral microdosing platform.
There are currently two CDK inhibitors approved by the U.S. Food and Drug Administration, palbociclib (marketed as Ibrance) and ribociclib (marketed as Kisqali), both oral, selective CDK 4/6 inhibitors approved for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer in combination with hormonal therapy. A third, abemaciclib, was recently granted priority review by the FDA.

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On September 4, 2017 Cellectis (Paris:ALCLS) (NASDAQ:CLLS) a clinical-stage biopharmaceutical company focused on developing immunotherapies based on gene-edited allogeneic CAR T-cells (UCART), reported having received notice from the U.S. Food and Drug Administration (FDA) that a clinical hold was placed on both UCART123 ongoing Phase 1 studies, respectively in acute myeloid leukemia (AML) and in blastic plasmacytoid dendritic cell neoplasm (BPDCN) (Press release, Cellectis, SEP 4, 2017, View Source [SID1234520368]).

Cellectis is working closely with the investigators and the FDA in order to resume the trials with an amended protocol including a lowered dosing of UCART123.

The clinical hold was initiated after Cellectis reported one fatality in the BPDCN clinical trial (ABC study). This was the first patient treated in the BPDCN study, a 78-year-old male treated with one prior therapy, who presented with relapsed/refractory BPDCN with 30% blasts in his bone marrow and cutaneous lesions (biopsy-proven BPDCN) at baseline prior to conditioning regimen. He received 30mg/m2/day fludarabine for 4 days and 1g/m2/day cyclophosphamide for 3 days, as a preconditioning regimen. On August 16, 2017 (Day 0), he received 6.25×105 UCART123 cells per kilogram, the first dose level explored in the protocol, without complication. At Day 5, the patient experienced a grade 2 Cytokine Release Syndrome (CRS)1, and a grade 3 lung infection, which quickly improved after a first dose of tocilizumab and institution of anti-infective therapy (broad spectrum intravenous antibiotics). He then experienced at Day 8 a grade 5 CRS, together with a grade 4 Capillary Leak Syndrome2. Despite a treatment in keeping with CRS management including administration of corticosteroids and tociluzumab x 2 as well as intensive care unit support, the patient died on Day 9.

The first patient treated in the AML study was a 58-year-old woman, with 84% blasts in her bone marrow at baseline prior to conditioning regimen. On June 27, 2017 (Day 0), the patient received the same preconditioning regimen and the same dose of UCART123 as the BPDCN patient, without complication. She experienced an initial grade 2 CRS at Day 8, worsening to a grade 3 at Day 9 and resolving at Day 11 with treatment management in intensive care unit. She also experienced a grade 4 Capillary Leak Syndrome at Day 9, resolved at Day 12.

No GvHD3 was reported for any of these patients.

The DSMB (Data Safety Monitoring Board) met on August 28 and recommended lowering the dose to 6.25×104 UCART123 cells per kilogram in both studies and capping cyclophosphamide to a total dose of 4g over 3 days.

On September 4, 2017 Takeda Pharmaceutical Company Limited (TSE: 4502) and Noile-Immune Biotech Inc. reported that they have entered into a collaboration to develop next generation chimeric antigen receptor T cell therapy (CAR-T) (Press release, Noile-Immune Biotech, SEP 4, 2017, View Source [SID1234533339]). The next generation CAR-T cell therapy was developed by Professor Koji Tamada at Yamaguchi University and Noile-Immune has exclusive license for this platform technology. The CAR-T therapy produces cytokines, chemokines, and other molecules, which is expected to potentially influence or alter the tumor microenvironment of solid tumor tissues to enhance the anti-tumor effect of the therapy. The companies intend to use this technology to discover and develop new CAR-T cell immunotherapies, with the aim of treating a broad range of cancers.

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The collaboration between Takeda and Noile-Immune Biotech will accelerate research and development of CAR-T cell therapy. In addition to providing resources required for implementation, Takeda will make a technology access payment to Noile-Immune Biotech and additionally Takeda will make an equity investment. Takeda will have exclusive options to obtain licensing rights for the development and commercialization of Noile-Immune’s pipeline and products resulting from this partnership on pre-agreed

terms. Additional terms of this agreement are not disclosed.

"This technology forms the basis for developing potentially transformational treatments for solid tumors," said Dr. Hidenobu Ishizaki, President of Noile-Immune. "The platform was developed by our founder, director, and CSMO, Professor Koji Tamada at the Department of Immunology at Yamaguchi University Graduate School of Medicine. We believe our collaboration with Takeda is a significant step towards rapidly delivering therapies that use this technology to cancer patients."

"We recognize the enormous potential of next-generation CAR-T cell therapy technology to deliver transformative medicines in oncology, one of our core therapeutic areas," said Chris Arendt, Head of the Oncology Drug Discovery Unit, Takeda. "This collaboration is another example of our commitment to invest in highly innovative technologies and to work with top external scientific and clinical teams as we seek to deliver therapies that address the needs of patients with cancer. We are especially excited that our

collaboration with the outstanding team at Noile-Immune will be located at our cutting-edge Shonan Research Center in Japan, allowing our Takeda scientists to work side-by-side with the Noile-Immune team to accelerate the advancement of innovative cellular immunotherapies to the clinic." Takeda signed an agreement with Noile-Immune through its wholly-owned subsidiary, Millennium Pharmaceuticals, Inc

IO101 is a peptide vaccine encompassing an HLA-A2-restricted, 9 amino acid IDO-derived CD8+ T-cell epitope. IO101 is currently in phase II clinical trial.

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A first-in-man clinical phase I vaccination trial using IO101 was conducted. The study comprised 15 HLA-A2+ patients with advanced NSCLC who were vaccinated with IO101 in Montanide adjuvant following pre-treatment with topical Imiquimod (Aldara Cream). The vaccine was well tolerated with manageable side effects and no CTCAE grade 3/4 toxicities.

One patient obtained an objective partial response after demonstrating continuous regression of liver metastases on vaccine treatment for 1 year.

Presently a small phase II study is ongoing in melanoma patients. In this study, IO101 together with an A2 Survivin peptide is used for vaccination in combination with temozolomide chemotherapy treatment.

More information can be found in this recent publication: Long-lasting disease stabilization in the absence of toxicity in metastatic lung cancer patients vaccinated with an epitope derived from indoleamine 2,3 dioxygenase