On December 26, 2019 Acorda Therapeutics, Inc. (Nasdaq: ACOR) ("Acorda" or the "Company") reported it has successfully completed its previously announced private exchange of $276 million aggregate principal amount of its 1.75% Convertible Senior Notes due June 2021 (the "Existing Convertible Notes") for a combination of approximately $207 million aggregate principal amount of newly issued 6.00% Convertible Senior Secured Notes due 2024 (the "New Convertible Secured Notes ") and $55.2 million in cash (Press release, Acorda Therapeutics, DEC 26, 2019, View Source [SID1234552607]). The initial conversion rate for the New Convertible Secured Notes is 285.7142 shares of the Company’s common stock per $1,000 principal amount of New Convertible Secured Notes, which is equivalent to an initial conversion price of approximately $3.50 per share, which represents a premium of approximately 97% above the Company’s closing stock price on December 20, 2019.

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"We have taken a significant step to strengthen our capital structure by refinancing approximately $276 million of our debt that matures in 2021 and replacing it with indebtedness that will not mature until December 2024," said Ron Cohen, M.D., Acorda’s President and Chief Executive Officer. "We structured the exchange to both address our near-term obligation and to preserve shareholder value through a substantial conversion premium. This now affords us the runway needed to drive the commercial success of INBRIJA, which addresses the critical unmet need of OFF periods in people living with Parkinson’s."

The Existing Convertible Notes received by the Company in the Exchange were cancelled in accordance with their terms. Accordingly, upon completion of the exchange, $69 million of Existing Convertible Notes remain outstanding.

The Company previously announced the terms of the New Convertible Secured Notes on December 23, 2019. The Company will file a Current Report on Form 8-K with the U.S. Securities and Exchange Commission on December 26, 2019, which will describe the exchange and the terms of the New Convertible Secured Notes, and include copies of the indenture and security agreement relating to the New Convertible Secured Notes.

This press release does not constitute an offer to sell or the solicitation of an offer to buy any securities of the Company. The offer and sale of the New Convertible Secured Notes or the shares of common stock issuable upon their conversion have not been registered under the Securities Act of 1933 (the "Securities Act") or the securities laws of any other jurisdiction, and these securities may not be offered or sold in the United States absent registration or an applicable exemption from the Securities Act and applicable state laws.

J. Wood Capital Advisors LLC is acting as the Company’s financial advisor for the Exchange and Covington & Burling LLP is acting as the Company’s legal advisor.

On December 26, 2019 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that it obtained an approval for the expanded use of FoundationOne CDx Cancer Genomic Profile as a companion diagnostic for anti-cancer agent/tyrosine kinase inhibitor, Rozlytrek (generic name: entrectinib) for the treatment of ROS1 fusion-positive, locally advanced or metastatic non-small cell lung cancer (NSCLC) from the Ministry of Health, Labour and Welfare on December 25, 2019 (Press release, Chugai, DEC 26, 2019, View Source [SID1234552604]). The approval allows physicians to identify NSCLC patients who could benefit from Rozlytrek by detecting ROS1 fusion genes. Chugai filed an application for this additional indication of Rozlytrek for the treatment of ROS1 fusion-positive, locally advanced or metastatic NSCLC on March 15, 2019.

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"We are pleased that the FoundationOne CDx Cancer Genomic Profile is now approved as a companion diagnostic against ROS1 fusion gene, which is one of the driver mutations in NSCLC. Although the frequency of ROS1 fusion gene expression in NSCLC is only about 1 to 2%1), treatment using ROS1 inhibitors can become one of the important therapeutic options for patients with ROS1-positive cancer," said Dr. Minoru Watanabe, Chugai’s Vice President, Head of Foundation Medicine Unit. "I am convinced that comprehensive cancer genomic profiling can further contribute to patients by enhancing its companion diagnostic functions. We will further expand companion diagnostic functions for both our in-house products and collaborations with biopharma partners."

Developed by Foundation Medicine Inc., FoundationOne CDx Cancer Genomic Profile is a next-generation sequencing based in vitro diagnostic device for the detection of substitutions, insertion and deletion alterations, and copy number alterations in 324 genes and select gene rearrangements, as well as genomic signatures including microsatellite instability (MSI) and tumor mutational burden (TMB) using DNA isolated from formalin-fixed, paraffin-embedded (FFPE) tumor tissue specimens. The program is available as a companion diagnostic for multiple molecular-targeted drugs approved in Japan.

As a leading company in the field of oncology, Chugai is committed to realize advanced personalized oncology care and contribute to patients and healthcare professionals through improving access to comprehensive genomic profiling.

On December 24, 2019 CEL-SCI Corporation (NYSE American: CVM), a Phase 3 cancer immunotherapy company, reported the pricing of an underwritten public offering with gross proceeds to the Company expected to be approximately $5.5 million before deducting underwriting discounts and other estimated offering expenses (Press release, Cel-Sci, DEC 24, 2019, View Source [SID1234552602]). The proposed offering equates to 606,395 shares of the Company’s common stock at a price of $9.07 per share. The Company intends to use the net proceeds from this offering to fund the continued development of Multikine*, LEAPS and for other general corporate purposes.

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The Company has also granted the underwriters a 45-day option to purchase up to 90,959 additional shares of common stock to cover over-allotments at the public offering price. The offering is expected to close on or about December 27, 2019, subject to customary closing conditions.

Aegis Capital Corp. is acting as sole bookrunner for the offering. This offering is being made pursuant to an effective shelf registration statement on Form S-3 (No. 333-226558) previously filed with the U.S. Securities and Exchange Commission (the "SEC") and declared effective by the SEC on August 24, 2018. A final prospectus supplement and accompanying prospectus describing the terms of the proposed offering will be filed with the SEC and will be available on the SEC’s website located at View Source

Electronic copies of the final prospectus supplement and the accompanying prospectus, when available, may be obtained by contacting Aegis Capital Corp., Attention: Syndicate Department, 810 7th Avenue, 18th floor, New York, NY 10019, by email at [email protected], or by telephone at (212) 813-1010. Before investing in this offering, interested parties should read in their entirety the prospectus supplement and the accompanying prospectus and the other documents that the Company has filed with the SEC that are incorporated by reference in such prospectus supplement and the accompanying prospectus, which provide more information about the Company and such offering.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On December 23, 2019 Researchers at The University of Texas MD Anderson Cancer Center reported that have identified a tenacious subset of immune macrophages that thwart treatment of glioblastoma with anti-PD-1 checkpoint blockade, elevating a new potential target for treating the almost uniformly lethal brain tumor (Press release, MD Anderson, DEC 23, 2019, View Source [SID1234553318]).

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Their findings, reported in Nature Medicine, identify macrophages that express high levels of CD73, a surface enzyme that’s a vital piece of an immunosuppressive molecular pathway. The strong presence of the CD73 macrophages was unique to glioblastoma among five tumor types analyzed by the researchers.

"By studying the immune microenvironments across tumor types, we’ve identified a rational combination therapy for glioblastoma," says first author Sangeeta Goswami, M.D., Ph.D., assistant professor of Genitourinary Medical Oncology.

Glioblastoma immunotherapy clinical trial planned

After establishing the cells’ presence in human tumors and correlating them with decreased survival, the researchers took their hypothesis to a mouse model of glioblastoma. They found combining anti-PD-1 and anti-CTLA-4 immunotherapies in CD73 knockout mice stifled tumor growth and increased survival.

"We’re working with pharmaceutical companies that are developing agents to target CD73 to move forward with a glioblastoma clinical trial in combination with anti-PD-1 and anti-CTLA-4 checkpoint inhibitors," says Padmanee Sharma, M.D., Ph.D., professor of Genitourinary Medical Oncology and Immunology.

Sharma and colleagues take an approach they call reverse translation. Instead of developing hypotheses through cell line and animal model experiments that are then translated to human clinical trials, the team starts by analyzing human tumors to generate hypotheses for testing in the lab in hopes of then taking findings to human clinical trials.

To more effectively extend immunotherapy to more cancers, Sharma says, researchers need to realize immune microenvironments differ from cancer to cancer. "Understanding what’s different in immune niches across cancers provides clues and targets for treating tumors," Sharma says. "That’s why we did this study."

The team tracked down the population of CD73-positive macrophages through a project to characterize immune cells found in five tumor types using CyTOF mass cytometry and single-cell RNA sequencing. They analyzed 94 human tumors across glioblastoma, non-small cell lung cancer and kidney, prostate and colorectal cancers to characterize clusters of immune cells.

CD73 cells associated with shorter survival

The most surprising finding was a metacluster of immune cells found predominantly among the 13 glioblastoma tumors. Cells in the cluster expressed CD68, a marker for macrophages, immune system cells that either aid or suppress immune response. The CD68 metacluster also expressed high levels of CD73 as well as other immune-inhibiting molecules. The team confirmed these findings in nine additional glioblastomas.

Single-cell RNA sequencing identified an immunosuppressive gene expression signature associated with the high-CD73-expressing macrophages. A refined gene signature for the cells was evaluated against 525 glioblastoma samples from The Cancer Genome Atlas and was correlated with decreased survival.

The team conducted CyTOF mass cytometry cluster analysis on five glioblastoma tumors treated with the PD-1 checkpoint inhibitor pembrolizumab and seven untreated tumors. They identified three CD73-expressing macrophage clusters that persisted despite pembrolizumab treatment.

Sharma and colleagues note the prevalence of CD73-expressing macrophages likely contributed to lack of tumor-killing T cell responses and poor clinical outcome.

Combination extends survival in mice

A mouse model of glioblastoma showed that knocking out CD73 alone slowed tumor growth and increased survival.

The team treated mice with either PD-1 inhibitors or a combination of PD-1 and CTLA-4 immune checkpoint inhibitors. Mice with intact CD73 treated with the combination had increased survival over untreated mice, while mice with CD73 knocked out lived even longer after combination therapy. There was no survival benefit from anti-PD-1 alone.

"Based on our data and earlier studies, we propose a combination therapy strategy to target CD73 plus dual blockade of PD-1 and CTLA-4," the team concludes in the paper, noting that anti-CD73 antibodies have yielded promising results in early studies.

Co-authors with Goswami and Sharma are Swetha Anandhan of Genitourinary Medical Oncology; Sreyashi Basu, Ph.D., Irina Fernandez, Ph.D., Luis Vence, Ph.D, Jorge Blando, Ph.D., Hao Zhao, Ph.D., Shalini Singh Yadav, Ph.D., and Jim Allison, Ph.D., of MD Anderson’s Immunotherapy Platform; Martina Ott, Ph.D., Ling Kong, Ph.D., and Amy Heimberger, M.D., of Neurosurgery; John de Groot, M.D., of Neuro-Oncology; Boris Sepesi, M.D., of Thoracic and Cardiovascular Surgery: Michael Overman, M.D., and Scott Kopetz, M.D., Ph.D., of GI Medical Oncology; Thomas Walle, Ph.D., of the National Center for Tumor Diseases in Heidelberg, Germany; and Andrew Cornish and Dana Pe’er, Ph.D., of the Computational and Systems Biology Program, Sloan-Kettering Institute, New York. Anandhan is a graduate student in the MD Anderson/UTHealth Graduate School of Biomedical Sciences.

This research was supported by the Immunotherapy Platform of MD Anderson’s Moon Shots Program and funded by MD Anderson’s Glioblastoma Moon Shot and Lung Cancer Moon Shot and by grants from the National Cancer Institute of the National Institutes of Health (CA1208113, P30CA016672) and NCI Cancer Center Support Grant (CA016672). Sharma and Allison are members of the Parker Institute for Cancer Immunotherapy.

On December 23, 2019 EpiVax ("EpiVax, Inc.") reported its record-breaking performance and growth in personnel in 2019 while identifying new milestones to aspire to in 2020 (Press release, EpiVax, DEC 23, 2019, View Source [SID1234552616]).

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The Business Development team closed 15% more contracts over 2018 and acquired two new clients for ISPRI, the in silico immunogenicity screening and protein re-engineering interface, bringing the total number of licenses to 14. Over one million sequences were screened in ISPRI for both academic and commercial clients this year.

The Immunoinformatics team upgraded all in silico platforms and developed new strategies for analyzing highly complex biologics, including those containing unnatural amino acids. These improvements have enabled the Protein Therapeutics team to address the growing peptide therapeutics industry.

EpiVax’s Tregitope and Vaccine Development teams pushed science forward in the fields of autoimmune therapy, infectious disease, and animal health. Notably, data highlighting the potential for Tregitopes, an EpiVax discovery, to treat Type I Diabetes was featured in Nature Scientific Reports. The number of funded collaborations also increased by 15%, contributing to the list of joint publications. A total of nine publications appeared in highly-ranked scientific journals.

Team members attended over 50 conferences around the globe, in locations such as Bern, Bamako, Lisbon, Hamburg, Paris, Edinburgh, the United States and beyond. EpiVax also hosted five scientific seminars, bringing "Science without Fear" concepts in the fields of immunogenicity and vaccine development to contacts in Cambridge, Seoul, Tokyo, Amsterdam and Ghent.

The company also expanded personnel by 15%, welcoming new Epi-Team members to the Tregitope, Immunoinformatics, Protein Therapeutics, Vaccine Development and Laboratory staff. EpiVax maintains its tradition of workplace diversity with a scientific team composed of greater than 50% women and women leading four out of seven departments.

EpiVax looks forward to exceeding these milestones in 2020 and is already looking forward to a new multi-institutional collaboration in the European Union researching an improved flu vaccine starting in January 2020.