On December 30, 2019 OncoImmune, Inc. reported that its Investigational New Drug ("IND") application for ONC-392, its novel, next generation anti-CTLA-4 antibody, has been approved by the U.S. Food and Drug Administration ("FDA") (Press release, ONCOIMMUNE, DEC 30, 2019, View Source [SID1234552635]). The IND approval enables OncoImmune to begin a Phase 1A/1B clinical trial of ONC-392 that is designed to assess the safety, pharmacokinetics, and efficacy of ONC-392 as a single agent in advanced solid tumors and in combination with anti-PD(L)1 standard of care in Non- Small Cell Lung Cancer. This open label trial is expected to begin in early 2020.

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ONC-392 was developed based on the research of OncoImmune’s Founders, Drs. Yang Liu and Pan Zheng, who proposed a new theory to improve both the efficacy and safety of immunotherapy drugs. The theory calls for preservation of the CTLA-4 immune checkpoint for safer and more effective immunotherapy. (https://www.sciencedirect.com/science/article/pii/S0165614719302639). This groundbreaking research was published in three papers in Cell Research in 2018 and 2019. The two 2018 papers were recognized with the Sanofi-Cell Research Outstanding Paper Award of 2018 (View Source).

"ONC-392 is OncoImmune’s second drug product candidate and the approval of this IND is an important milestone for OncoImmune," said Yang Liu, President and CEO of OncoImmune. "Unlike other anti-CTLA-4 antibodies that cause lysosomal degradation of CTLA-4, ONC-392 preserves CTLA-4 recycling and thus maintains CTLA-4 function outside of the tumor microenvironment while allowing more effective CTLA-4-targeted depletion of regulatory T cells within the tumor. The truly novel and differentiated mechanism of action of this drug has the potential to improve therapeutic outcomes while significantly reducing toxicity."

"We are very excited to test the potential of this novel antibody in cancer patients," said Pan Zheng, Chief Medical Officer of OncoImmune, Inc.

The CMC development and GMP manufacturing of the drug substance and drug product were performed by WuXi Biologics, a leading global open-access biologics technology platform for the ONC-392 program. "Throughout the development program from DNA to IND, we were very impressed by WuXi Biologics’ expertise and professionalism, and we could not have picked a better partner for this project," said Martin Devenport, OncoImmune’s Chief Operating Officer.

On December 30, 2019 X4 Pharmaceuticals, Inc. (Nasdaq: XFOR), a clinical-stage biopharmaceutical company focused on the development of novel therapeutics for the treatment of rare diseases, reported the initiation of a Phase 1b clinical trial of mavorixafor (X4P-001) in combination with ibrutinib (Imbruvica) for the treatment of Waldenström’s macroglobulinemia (WM), a rare form of non-Hodgkin’s lymphoma (Press release, X4 Pharmaceuticals, DEC 30, 2019, View Source [SID1234552634]). Mavorixafor, X4’s lead therapeutic candidate, is a potential first-in-class, once-daily, oral, small molecule antagonist of chemokine receptor CXCR4.

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"There is a significant unmet medical need for patients living with WM who have CXCR4 mutations. The development of a therapeutic CXCR4 antagonist such as mavorixafor represents a very important advance for targeted therapy of this disease," said Steven Treon, M.D., Ph.D., FACP, FRCP, Director of the Bing Center for Waldenström’s Macroglobulinemia and Professor of Medicine at Harvard Medical School.

"The CXCR4 mutation, which is present in approximately 30 to 40 percent of patients with WM, is known to play an important role in treatment resistance, and is associated with higher rates of disease burden, making the CXCR4 pathway a critical therapeutic target for patients with WM," said Christian Buske, M.D., Director of the Institute of Experimental Cancer Research and Attending Physician and Professor of Medicine at the University of Ulm.

The Phase 1b multi-center, open-label, dose-escalation, clinical trial is designed to assess the safety and tolerability of mavorixafor in combination with ibrutinib in patients with WM who have acquired a "gain of function" mutation in CXCR4 in addition to the MYD88 mutation, which is a hallmark of WM diagnosis.1 In addition, the trial is designed to measure changes in serum immunoglobulin M (IgM) and hemoglobin (Hgb) from baseline, both biomarkers are key elements of clinical response in WM patients.2,3 The clinical trial is expected to enroll approximately 12-18 patients.

"Having established proof of concept for mavorixafor in WHIM patients, we believe that there is a compelling case to evaluate mavorixafor’s same mechanism of action in WM patients who have acquired gain-of-function mutations in the CXCR4 receptor, which is known to result in treatment-resistant cancer," said Lynne Kelley, M.D., FACS, Chief Medical Officer of X4 Pharmaceuticals. "We are excited to initiate our first clinical trial in WM and look forward to providing initial results in the second half of 2020 as we continue to advance our pipeline as rapidly as possible for patients in need."

This trial is being conducted as part of a collaboration with The Leukemia & Lymphoma Society (LLS) to accelerate the development of mavorixafor for the treatment of WM. Mavorixafor was selected for LLS’s Therapy Acceleration Program (TAP), a strategic initiative where LLS builds business alliances and collaborations with biotechnology companies and academic researchers to speed the development of new therapies for blood cancers.

About Waldenström’s Macroglobulinemia (WM)

Waldenström’s macroglobulinemia is a rare form of non-Hodgkin’s lymphoma in which abnormal white blood cells produce an excess of monoclonal immunoglobulin M (IgM) which can result in symptoms of anemia, hyper viscosity, neuropathy or other complications. Recent advancements in whole-genome sequencing have enabled the characterization of genetic mutations in the disease. WM is the result of a somatic mutation in the MYD88 gene, which is present in 90% of patients, with a subset of these patients having an additional mutation in the CXCR4 gene.4,5 Mutations of the CXCR4 gene in WM patients are associated with active tumor cells and possible drug resistance to Burton tyrosine kinase (BTK) inhibitors, such as ibrutinib,6 significantly longer median time to major response and substantially shorter median progression free survival.7

About Mavorixafor

X4 Pharmaceuticals’ lead product candidate, mavorixafor (X4P-001), is a potential first-in-class, once-daily, oral inhibitor of CXCR4, currently in a Phase 3 clinical trial for the treatment of WHIM syndrome, a rare, inherited, primary immunodeficiency disease caused by genetic mutations in the CXCR4 receptor gene. Mavorixafor has demonstrated proof-of-concept in WHIM syndrome in a Phase 2 clinical trial, including clinically meaningful increases in neutrophil and lymphocyte biomarker counts, as well as a trend of reduction in infection rates and wart burden, and a favorable safety profile. Mavorixafor was recently granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with WHIM syndrome, and was granted orphan drug status by the FDA in 2018 and by the European Commission in 2019 for the treatment of WHIM syndrome. Mavorixafor is also being developed by X4 to treat Severe Congenital Neutropenia (SCN), Waldenström’s macroglobulinemia (WM), and clear cell renal cell carcinoma (ccRCC).

On December 30, 2019 Castle Biosciences, Inc. (Nasdaq: CSTL) reported that results from a study designed to perform a systematic review of the literature and establish the level of evidence for the Company’s DecisionDx-Melanoma gene expression profile test were published in the December 2019 issue of the American Journal of Clinical Dermatology (Press release, Castle Biosciences, DEC 30, 2019, View Source [SID1234552633]). The results show that the DecisionDx-Melanoma test achieves a higher level of evidence than determined by major organizations that publish guidelines on melanoma management.

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DecisionDx-Melanoma is a gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous melanoma metastasis or recurrence, as well as sentinel lymph node positivity, independent of traditional staging factors. In this independent study by Dubin, et al. titled, "Level of Evidence Review for a Gene Expression Profile Test for Cutaneous Melanoma," the researchers conducted a review of seven development and validation studies for the DecisionDx-Melanoma test. They then applied attributes of each study to the level of evidence criteria for the American Joint Committee on Cancer (AJCC), National Comprehensive Cancer Network (NCCN) and American Academy of Dermatology (AAD). The AJCC, NCCN and AAD are considered major authoritative organizations that many dermatologists rely upon to provide skin cancer guidelines, and each employs a unique ranking system to assign a level of evidence to the management of melanoma.

Key Findings:

The evaluation of seven development and validation studies led the authors to classify DecisionDx-Melanoma as level I/II, I–IIIB and IIA according to AJCC, NCCN and AAD criteria, respectively, which are higher than the official unrated status conferred by the AJCC and NCCN and the II/IIIC rating designated by the AAD in the latest version of their melanoma guidelines.
The authors note that the differences between the study’s findings and official published ratings may be attributed to chronological issues, as many of the studies were not yet published when the organizations conducted their reviews. There was also difficulty in applying the National Comprehensive Cancer Network criteria to this prognostic test, as their guidelines were intended for evaluation of therapeutic response markers.
Based on current published data, the authors find integration of the DecisionDx-Melanoma test to be useful for patients with invasive melanoma, particularly older patients with T1/T2 (tumor depth of 2 mm or less) melanomas:
For patients with invasive melanoma, DecisionDx-Melanoma may help guide the frequency of skin examinations and utilization of a sentinel lymph node biopsy (SLNB) surgical procedure or imaging following diagnosis of melanoma.
DecisionDx-Melanoma may benefit patients aged older than 65 years diagnosed with T1/T2 melanomas in the assessment of the risks and benefits of a SLNB surgical procedure.
Three additional prospective peer-reviewed clinical validity studies published in 2019 were not included in the Dubin study, due to publication after the systematic review was completed.

The full published study can be accessed at the journal’s website.

About DecisionDx-Melanoma

DecisionDx-Melanoma is a gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous melanoma metastasis or recurrence, as well as sentinel lymph node positivity, independent of traditional staging factors, and has been studied in more than 3,900 patient samples. Using tissue from the primary melanoma, the test measures the expression of 31 genes. The test has been validated in four archival risk of recurrence studies of 901 patients and five prospective risk of recurrence studies including more than 780 patients. Prediction of the likelihood of sentinel lymph node positivity has also been validated in two prospective multicenter study cohorts that included more than 2,000 patients. Impact on patient management plans for one of every two patients tested has been demonstrated in four multicenter and single-center studies including more than 560 patients. The consistent performance and accuracy demonstrated in these studies provides confidence in disease management plans that incorporate DecisionDx-Melanoma test results.

On December 30, 2019 Five Prime Therapeutics, Inc. (NASDAQ: FPRX), a clinical-stage biotechnology company focused on developing immune modulators and precision therapies for solid tumor cancers, reported that it will participate in the 38TH Annual J.P. Morgan Healthcare Conference on Thursday, January 16, 2020 (Press release, Five Prime Therapeutics, DEC 30, 2019, View Source [SID1234552632]). William Ringo, who is Five Prime’s Chairman and interim Chief Executive Officer, will represent the company and respond to questions from investors. He is scheduled to present at 7:30 a.m. PT (10:30 a.m. ET).

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Investors and other interested parties will be able to access a live audio webcast of the presentation by visiting View Source A replay of the presentation will also be available on the Five Prime website for 30 days after the conference.

On December 30, 2019 Myovant Sciences (NYSE: MYOV), a healthcare company focused on developing innovative treatments for women’s health and prostate cancer, reported the closing of the previously announced landmark, low-interest (3-month LIBOR plus 3%) loan facility from Sumitomo Dainippon Pharma Co., Ltd. (TSE: 4506), now increased to $400 million (Press release, Myovant Sciences, DEC 30, 2019, https://investors.myovant.com/news-releases/news-release-details/myovant-sciences-announces-closing-400-million-loan-facility [SID1234552631]). The closing of the loan facility is concurrent with the transfer by Roivant Sciences of a majority of Myovant’s shares and four additional biopharmaceutical "Vant" companies to Sumitovant Biopharma Ltd. ("Sumitovant"), a newly-formed subsidiary of Sumitomo Dainippon Pharma as a result of the completion of their transaction for the creation of a significant multi-national Sumitomo Dainippon Pharma-Roivant Alliance. With the increase in its loan facility with Sumitomo Dainippon Pharma, Myovant will repay its pre-existing loans from NovaQuest Capital Management and Hercules Capital (NYSE: HTGC). Concurrent with the transfer of Myovant’s shares, Hiroshi Nomura and Adele Gulfo have joined Myovant’s Board of Directors, while Vivek Ramaswamy and Frank Torti, M.D., have transitioned off.

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"It is with great pleasure that we welcome Hiroshi Nomura and Adele Gulfo to join our Board of Directors. They will bring valuable financial, strategic, and commercial expertise as Myovant approaches multiple potential commercial launches," said Lynn Seely, M.D., CEO of Myovant Sciences. "I sincerely thank Vivek Ramaswamy for his role in the formation and launch of Myovant, and both Vivek and Frank Torti for their contributions to Myovant’s success. Myovant is now in a much stronger financial position with the increased, low-interest loan facility from Sumitomo Dainippon Pharma, which enables us to repay the NovaQuest and Hercules loans and thereby substantially lower our cost of capital and reset our debt maturities to 5 years."

Mr. Nomura has been President, CEO, and Representative Director of Sumitomo Dainippon Pharma since April 2018. Prior to his current role, Mr. Nomura served in a number of executive leadership roles at Sumitomo Dainippon Pharma, including Board of Directors, Senior Executive Officer, and Chief Financial Officer from 2014 to 2018. From 2003 to 2014, he held various other positions with increasing responsibilities at Sumitomo Dainippon Pharma. He also served on the Board of Directors and as Vice Chairman, Executive Vice President, and Chief Financial Officer of Sunovion Pharmaceuticals Inc. from 2012 to 2014. Mr. Nomura received a Bachelor of economics from the University of Tokyo.

Ms. Gulfo serves as the Chief Business and Commercial Development Officer at Sumitovant. Prior to joining Sumitovant, from May 2018 to December 2019, Ms. Gulfo served as Chief of Commercial Development at Roivant Sciences. Previously, from 2014 to 2018, she was Chief Strategy Officer, Executive Vice President, and Head of Global Commercial Development at Mylan. From 2009 to 2014, she served in a number of executive leadership roles at Pfizer, including President and General Manager of the U.S. primary care business and President of Latin America. She also currently serves on the Board of Directors of EnPro Industries and Medexus Pharma. Ms. Gulfo received a B.S. from Seton Hall University and a M.B.A. from Fairleigh Dickinson University.

Myovant also announced the promotions of Frank Karbe to President and Chief Financial Officer and Matthew Lang to Chief Administrative and Legal Officer and Corporate Secretary.

Mr. Karbe joined Myovant in 2017 as Chief Financial Officer. He previously served as Executive Vice President and Chief Financial Officer for Exelixis from 2004 to 2014. Earlier in his career, he worked as an investment banker for Goldman Sachs & Co. Frank currently serves on the Board of Directors of Aduro Biotech. He received his Diplom-Kaufmann from the WHU-Otto Beisheim Graduate School of Management, Koblenz, Germany.

Mr. Lang joined Myovant in 2017 as General Counsel and Corporate Secretary. Previously, from 2009 to 2017, he worked at Gilead Sciences where he served most recently as Vice President, Head of Global Litigation, Investigations, Employment Law and Information Governance. Prior to Gilead, he practiced law at Dechert LLP in New York City. Mr. Lang received his B.A. in classical studies from Queen’s University at Kingston, Canada and his J.D. from the University of Pennsylvania Law School.