On December 21, 2017 FLX Bio, Inc., a biopharmaceutical company focused on the discovery and development of oral small-molecule drugs to activate the immune system against cancer, reported the completion of a $60 million Series C private financing (Press release, FLX Bio, DEC 21, 2017, View Source [SID1234522770]). The financing included new investments from GV (formerly Google Ventures) and other undisclosed investors as well as existing investors including The Column Group, Kleiner Perkins, Topspin Partners and Celgene Corporation.

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"With a discerning syndicate of investors committed to our science, our strategy and our team, we look forward to using the proceeds of this Series C financing to advance our robust pipeline of small molecule immuno-oncology compounds focused on regulatory T cell and tumor myeloid cell modulation," said Brian Wong, M.D., Ph.D., President and CEO. "In addition to initiating Phase 1 testing for our lead molecule FLX475, a highly potent and selective oral CCR4 antagonist for the treatment of cancer, we intend to select a clinical candidate targeting USP7 and continue advancement of our GCN2 program, with all three programs representing differentiated and important mechanisms to stimulate an immune response within the tumor microenvironment."

Initiation of Phase 1 Clinical Study of FLX475, CCR4 Antagonist
In addition to announcing its financing, FLX Bio recently dosed its first subject in a Phase 1 clinical trial for FLX475, a best-in-class, oral small molecule antagonist of CCR4. The company’s strategy is to accelerate early clinical development in cancer patients by first rapidly obtaining pharmacokinetic, pharmacodynamic, and preliminary safety data in healthy volunteers. Findings from the healthy volunteer study will enable a more focused and efficient Phase 1 study in cancer patients, potentially resulting in faster achievement of clinical proof of concept.

"We are pleased to move our lead program forward into the clinic," commented Bill Ho, M.D., Ph.D., Chief Medical Officer of FLX Bio. "Regulatory T cells are highly potent suppressors of the adaptive immune response and their presence in most tumors are correlated with a poor prognosis. With very few agents in development selectively inhibiting these cells, we believe targeting CCR4 represents a differentiated and exceptionally promising approach to treating cancer."

About FLX475
FLX475 is a best-in-class oral, small molecule antagonist of CCR4. In preclinical studies, FLX475 inhibited tumor growth and increased tumor regression as a single agent. In addition, FLX475 enhanced the antitumor effects of various checkpoint inhibitors including anti-PD-L1 and anti-CTLA4 antibodies as well as immune agonists such as anti-4-1BB. FLX475 also has the potential to enhance cell-based immunotherapies such as CAR-T and cancer vaccines. Unlike antibodies to CCR4, FLX475 selectively blocks the recruitment of regulatory T cells to the tumor site, and does not deplete cells beneficial to an anti-tumor response or regulatory T cells in healthy tissue such as blood, spleen and skin cells. In addition to the study ongoing in healthy volunteers, FLX Bio intends to initiate a clinical trial of FLX475 alone and in combination with a checkpoint inhibitor in oncology patients in 2018.

About USP7
Ubiquitin specific protease 7 (USP7) plays a key role in two important cancer pathways: it promotes the formation and function of regulatory T cells by deubiquitinating and stabilizing FOXP3; and it maintains low levels of p53, a prevalent tumor suppressor protein, thereby allowing the tumor to grow unchecked. USP7 is an enzyme that removes a tag called ubiquitin from proteins and stabilizes the expression of those proteins in the cell. USP7 stabilizes a regulatory protein called FOXP3 found within regulatory T cells, and promotes the number and activity of regulatory T cells. In addition, USP7 stabilizes MDM2, causing p53 levels go down, thus allowing cancer cells to proliferate. A USP7 inhibitor elicits two beneficial effects – increased immune system response to the tumor and enhanced tumor suppression by p53. FLX Bio expects to select a clinical candidate in late 2018.

About GCN2
GCN2 is a myeloid-derived suppressor cell (MDSC) target that works downstream of IDO and arginase. GCN2 inhibition has the potential for superior efficacy as it can reverse immune-suppression caused by depletion of both tryptophan and arginine. We are developing orally-bioavailable, highly-selective GCN2 inhibitors that stimulate an immune response by limiting myeloid derived suppressor cell functions as well as encouraging effector T cell proliferation in the amino acid-deprived tumor microenvironment.

On December 21, 2017 ZIOPHARM Oncology, Inc. (Nasdaq: ZIOP), reported that Laurence Cooper, M.D., Ph.D., Chief Executive Officer, will present at the 36th Annual J.P. Morgan Healthcare Conference in San Francisco on Thursday, January 11, 2018 at 10 a.m. PST (Press release, Ziopharm, DEC 21, 2017, View Source [SID1234522761]). The presentation will include a detailed update on the Company’s clinical development programs and corporate development efforts.

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To access a live audio webcast of the presentation, please visit the Investor Relations section at www.ziopharm.com. The webcast will be archived for 90 days.

On December 21, 2017 Janssen Biotech, Inc. ("Janssen"), a Janssen Pharmaceutical Company of Johnson & Johnson, reported that it has entered into a worldwide collaboration and license agreement with Legend Biotech USA Inc. and Legend Biotech Ireland Limited ("Legend"), subsidiaries of Genscript Biotech Corporation, to develop, manufacture and commercialize a chimeric antigen receptor (CAR) T-cell drug candidate, LCAR-B38M, which specifically targets the B-cell maturation antigen (BCMA) (Press release, Johnson & Johnson, DEC 21, 2017, View Source [SID1234522753]). LCAR-B38M is currently accepted for review by the China Food and Drug Administration (CFDA) and in the planning phase of clinical studies in the United States for multiple myeloma.

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"Despite significant advances, multiple myeloma remains an incurable disease for most patients, creating the need for additional, highly active options. LCAR-B38M provides an innovative approach with the potential to transform the treatment of myeloma," said Peter F. Lebowitz, M.D., Ph.D., Global Therapeutic Area Head, Oncology, Janssen Research & Development, LLC. "We look forward to collaborating with the pioneering scientific team at Legend and applying our expertise to the development of this cell therapy, with the goal of building regimens aiming for a cure."

LCAR-B38M is the first CAR-T therapy accepted for review by the CFDA. Under terms of the agreement, Legend will grant Janssen a worldwide license to jointly develop and commercialize LCAR-B38M in

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multiple myeloma with the Legend team of experts. Janssen will record worldwide net trade sales, except for sales made in Greater China. The companies have entered into a 50/50 percent cost-sharing/profit-split arrangement, except in Greater China, where Janssen and Legend have a 30/70 percent cost-sharing/profit-split arrangement. Janssen will make an upfront payment of $350 million that will be recorded in the fourth quarter and additional payments based upon the achievement of certain development, regulatory and sales milestones.

Johnson & Johnson reaffirms its previously announced adjusted earnings guidance for full-year 2017 of $7.25-$7.30 per share.

"We are pleased to enter into a partnership with Legend to gain access to their CAR-T platform, an important future therapeutic modality for Janssen," says Mathai Mammen, M.D., Ph.D., Global Head, Science & Development, Janssen Research & Development, LLC. "Legend is an innovative biotech company that has developed a differentiated CAR-T therapy, which has shown promising results in early-stage multiple myeloma trials conducted in China. We are excited to bring Janssen’s global expertise in drug development to advance this innovation into potential new treatment options for patients around the world."

About CAR-T and BCMA
CAR T-cells are an innovative approach to eradicate cancer cells by harnessing the power of a patient’s own immune system. BCMA is a protein that is highly expressed on myeloma cells. By targeting BCMA via a CAR-T approach, CAR-T therapies may have the potential to redefine the treatment paradigm for multiple myeloma and potentially advance towards cures for patients with the disease.

About Multiple Myeloma
Multiple myeloma is an incurable blood cancer that occurs when malignant plasma cells grow uncontrollably in the bone marrow.1,2 While some patients with myeloma have no symptoms at all, most patients are diagnosed due to symptoms, which can include bone fracture or pain, low red blood counts, fatigue, calcium elevation, kidney problems or infections.3 Despite significant treatment advances in the past 10 years, many myeloma patients relapse after initial or secondary treatment and/or become resistant to therapies. There is a significant unmet medical need for more efficacious treatments that can overcome resistance associated with standard of care based on an immunomodulatory agent and/or a proteasome inhibitor to induce deeper and durable responses.1,4 Globally, it is estimated that 124,225 people were diagnosed and 87,084 died from multiple myeloma in 2015.5,6

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Janssen in Oncology
In oncology, our goal is to fundamentally alter the way cancer is understood, diagnosed and managed, reinforcing our commitment to the patients who inspire us. In looking to find innovative ways to address the cancer challenge, our primary efforts focus on several treatment and prevention solutions. These include a focus on hematologic malignancies, prostate cancer and lung cancer; cancer interception with the goal of developing products that interrupt the carcinogenic process; biomarkers that may help guide targeted, individualized use of our therapies; as well as safe and effective identification and treatment of early changes in the tumor microenvironment. Please visit www.janssen.com/oncology.

On December 21, 2017 MEI Pharma, Inc. (Nasdaq: MEIP), an oncology company focused on the clinical development of novel therapies for cancer, reported that a study of voruciclib, an orally available CDK9 inhibitor, was published in the journal Nature Scientific Reports (Press release, MEI Pharma, DEC 21, 2017, View Source [SID1234522756]). Researchers found that voruciclib when combined with the BCL-2 inhibitor Venclexta (venetoclax) was capable of inhibiting two master regulators of drug resistance, MCL-1 and BCL-2, and achieved synergistic antitumor efficacy in an aggressive subset of Diffuse Large B-cell Lymphoma (DLBCL). A phase 1 study of voruciclib in relapsed/refractory B-cell malignancies is planned to begin in the first half of 2018.

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"As an orally available CDK9 inhibitor with a favorable pharmacokinetic profile and the ability to regulate MCL-1 expression, voruciclib is an ideal candidate to test in combination with a BCL-2 inhibitor such as venetoclax in patients with high risk hematological malignancies," said Daniel P. Gold, Ph.D., President and Chief Executive Officer of MEI Pharma. "The fact that overexpression of MCL-1 is a known mechanism of resistance to venetoclax suggests that the combination of MCL-1 and BCL-2 inhibitors may pave the way for a novel treatment strategy for high-risk DLBCL."

Approximately 40% of patients with DLBCL do not respond or relapse following standard chemotherapy. The evasion of apoptosis is primarily due to over expression of BCL-2, a pro-survival protein, in response to chemotherapy. The selective inhibition of BCL-2 has been achieved with the BH3 mimetic, venetoclax, resulting in high response rates in certain malignancies. However, exclusive targeting of BCL-2 with venetoclax in relapsed or refractory DLBCL has yielded only a modest 18% response rate with a one-month median progression free survival1. A primary mechanism of resistance to venetoclax is overexpression of MCL-1 which compensates for loss of BCL-2 functionality. The combined targeting of BCL-2 and MCL-1 is a potential treatment strategy for lymphomas that are refractory to standard chemotherapy.

Key findings reported in the study:

Differentiated structure of voruciclib confers greater selectively for CDK9 compared to other CDK9 inhibitors, with less off-target liability
Voruciclib significantly decreased MCL-1 expression in a dose dependent manner at concentrations achievable with doses that appeared to be generally well tolerated in Phase 1 solid tumor studies
The combination of voruciclib and venetoclax was more effective than either drug alone, with the best responses in the more aggressive subtypes of DLBCL
The published study is available online at View Source

Voruciclib (formerly P1446A) has been tested in more than 70 patients with solid tumors 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) samples2.

On December 21, 2017 Moleculin Biotech, Inc., (NASDAQ: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company focused on the development of anti-cancer drug candidates, some of which are based on license agreements with The University of Texas System on behalf of the MD Anderson Cancer Center ("MD Anderson"), reported that the Ethics Committee in Poland has approved the Company’s Phase I/II clinical trial of Annamycin for the treatment of relapsed or refractory acute myeloid leukemia ("AML") (Press release, Moleculin, DEC 21, 2017, View Source [SID1234522757]).

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"We have been highly focused on accelerating our clinical development of Annamycin," commented Walter Klemp, Chairman and CEO of Moleculin. "The protocol approved in Poland allows us to move more aggressively in identifying the optimum dosing for AML patients, which in turn should allow us to move into Phase II data generation more expeditiously."

Mr. Klemp added, "This approval should also increase our ability to recruit patients into our AML trial, which we expect to begin in a matter of weeks. Importantly, we believe the clinical data produced in Poland will be useful in our interactions with both the U.S. Food and Drug Administration ("FDA"), as well as with the European Medicines Agency ("EMA"), as we seek regulatory approval for Annamycin."

A site initiation visit for the first treatment site was completed this week and treatment of patients in Poland is now subject only to confirmation by the Polish National Office that all necessary forms have been properly filed. The Company expects the first patient to be enrolled in first quarter 2018.