On February 5, 2020 The University of Texas MD Anderson Cancer Center reported that results from a Phase I/IIa trial treatment with cord blood-derived chimeric antigen receptor (CAR) natural killer (NK)-cell therapy targeting CD19 resulted in clinical responses in a majority of patients with relapsed or refractory non-Hodgkin’s lymphoma (NHL) and chronic lymphocytic leukemia (CLL), with no major toxicities observed (Press release, MD Anderson, FEB 5, 2020, View Source [SID1234553885]).

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The trial results were published today in the New England Journal of Medicine. Of the 11 patients participating in the study, eight (73%) responded to therapy and seven of those achieved a complete response, meaning they no longer showed evidence of disease at a median follow-up of 13.8 months. Post-remission therapy was administered to five of the responding patients. No patients experienced cytokine release syndrome or neurotoxicity.

Responses to the CD19 CAR NK cell therapy were evident within one month following infusion, and persistence of these cells was confirmed out to one year post-infusion.

"We are encouraged by the results of the clinical trial, which will launch further clinical studies to investigate allogeneic cord blood-derived CAR NK cells as a potential treatment option for patients in need," said corresponding author Katy Rezvani, M.D., Ph.D., professor of Stem Cell Transplantation & Cellular Therapy.

Rezvani led the development of MD Anderson’s CAR NK platform with the support of the adoptive cell therapy (ACT) platform, Chronic Lymphocytic Leukemia Moon Shot and B-Cell Lymphoma Moon Shot, all part of the institution’s Moon Shots Program, a collaborative effort to rapidly develop scientific discoveries into meaningful clinical advances that save patients’ lives.

CAR NK cells are allogeneic, meaning the cells are taken from a non-related healthy donor rather than the patient themselves. Thus, CAR NK cells have the potential to be manufactured in advance and stored for off-the-shelf immediate use. In contrast, currently commercially available CAR T cells require the use of a patient’s own genetically modified T cells, created through a multi-week manufacturing process.

At MD Anderson, NK cells are isolated from donated umbilical cord blood and genetically engineered to express the desired CAR, which recognizes cancer-specific targets. The CAR NK cells also are ‘armored’ with IL-15, an immune signaling molecule that is designed to enhance proliferation and survival of the cells. The CD19 CAR NK cells used in this study were designed to target B-cell malignancies.

On the clinical trial, 11 patients received a single dose of cord blood-derived CD19 CAR NK cells, administered at one of three dose levels. Five patients had CLL and six had NHL. All patients were treated with a minimum of three and maximum of 11 lines of prior therapy. The first nine patients treated received CD19 CAR NK cells that were partially matched according to the individual’s human leukocyte antigen (HLA) type, but the protocol allowed the final two patients to be treated with no HLA matching.

Side effects experienced by participants were primarily related to the conditioning chemotherapy given before cell infusion and were resolved within one to two weeks, said Rezvani. No patient required admission to an intensive care unit for management of treatment side effects.

"Due to the nature of the therapy, we’ve actually been able to administer it in an outpatient setting," said Rezvani. "We look forward to building upon these results in larger multi-center trials as we work with Takeda to make this therapy available more broadly."

MD Anderson’s CAR NK cell therapy platform was licensed to Takeda Pharmaceutical Company Limited in 2019. As part of the license agreement and research agreement, Takeda has exclusive rights to develop and commercialize up to four CAR NK programs, including the CD19 CAR NK cell therapy (TAK-007) and B-cell maturation antigen (BCMA)-targeted CAR NK cells.

With continued support from the ACT platform, the Department of Lymphoma and Myeloma, and MD Anderson’s Therapeutics Discovery division, Takeda and MD Anderson are collaborating to initiate a pivotal clinical trial for the CD19 CAR NK-cell therapy TAK-007 in 2021. MD Anderson will implement an Institutional Conflict of Interest Management and Monitoring Plan for this research.

On February 5, 2020 Lannett Company, Inc. (NYSE: LCI) reported financial results for its fiscal 2020 second quarter ended December 31, 2019 (Press release, Lannett, FEB 5, 2020, View Source [SID1234553901]).

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"For our fiscal 2020 second quarter, strong sales across multiple product categories drove solid increases to our net sales and net income over our fiscal 2020 first-quarter results," said Tim Crew, chief executive officer of Lannett. "Our improved topline was due in part to the introduction of seven new products in the second quarter of fiscal 2020, as well as a full quarter of sales of Posaconazole. We plan to commence marketing an additional 10 or so products in the second half of the year, including Numbrino, our recently approved, branded topical anesthetic product.

"We remain on track for launching a substantial number of new products in fiscal 2020. At the same time, we are making excellent progress advancing multiple products in our pipeline that have significant upside, as evidenced by the recent human pharmacokinetics and pharmacodynamics clinical trial that met all primary endpoints for our insulin glargine product."

For the fiscal 2020 second quarter on a GAAP basis, net sales were $136.1 million compared with $193.7 million for the second quarter of fiscal 2019. Gross profit was $41.3 million, or 30% of net sales, compared with $69.8 million, or 36% of net sales. Net income was $5.1 million, or $0.13 per diluted share, compared with $12.4 million, or $0.32 per diluted share.

For the fiscal 2020 second quarter reported on a Non-GAAP basis, net sales were $136.1 million compared with $193.7 million for the second quarter of fiscal 2019. Adjusted gross profit was $50.2 million, or 37% of net sales, compared with $86.0 million, or 44% of net sales, for the prior-year second quarter. Adjusted interest expense was $13.1 million compared with $17.1 million for the second quarter of fiscal 2019. Adjusted net income was $11.7 million, or $0.27 per diluted share, compared with $33.6 million, or $0.86 per diluted share, for the fiscal 2019 second quarter. Adjusted EBITDA for the fiscal 2020 second quarter was $35.8 million.

Guidance for Fiscal 2020
Based on its current outlook, the company revised certain items in its GAAP guidance and adjusted guidance for fiscal year 2020, the net effect of which is not expected to have an impact on adjusted EBITDA. The full guidance is as follows:

**A reconciliation of Adjusted amounts to most directly comparable GAAP amounts can be found in the attached financial tables.

Conference Call Information and Forward-Looking Statements
Later today, the company will host a conference call at 4:30 p.m. ET to review its results of operations for its fiscal 2020 second quarter ended December 31, 2019. The conference call will be available to interested parties by dialing 800-447-0521 from the U.S. or Canada, or 847-413-3238 from international locations, passcode 49357861. The call will be broadcast via the Internet at www.lannett.com. Listeners are encouraged to visit the website at least 10 minutes prior to the start of the scheduled presentation to register, download and install any necessary audio software. A playback of the call will be archived and accessible on the same website for at least three months.

Discussion during the conference call may include forward-looking statements regarding such topics as, but not limited to, the company’s financial status and performance, regulatory and operational developments, and any comments the company may make about its future plans or prospects in response to questions from participants on the conference call.

Use of Non-GAAP Financial Measures
This news release contains references to Non-GAAP financial measures, including Adjusted EBITDA, which are financial measures that are not prepared in conformity with United States generally accepted accounting principles (U.S. GAAP). Management uses these measures internally for evaluating its operating performance. The Company’s management believes that the presentation of Non-GAAP financial measures provides useful supplementary information regarding operational performance, because it enhances an investor’s overall understanding of the financial results for the Company’s core business. Additionally, it provides a basis for the comparison of the financial results for the Company’s core business between current, past and future periods. The company also believes that including Adjusted EBITDA, as defined in the company’s existing Credit Agreement, is appropriate to provide additional information to investors to demonstrate the company’s ability to comply with financial debt covenants. Non-GAAP financial measures should be considered only as a supplement to, and not as a substitute for or as a superior measure to, financial measures prepared in accordance with U.S. GAAP.

Detailed reconciliations of non-GAAP financial measures to the most directly comparable GAAP financial measures are included with this release.

Non-GAAP financial measures exclude, among others, the effects of (1) amortization of purchased intangibles and other purchase accounting entries, (2) restructuring expenses, (3) non-cash interest expense, as well as (4) certain other items considered unusual or non-recurring in nature.

*Adjusted EBITDA excludes the same adjustments discussed above, as well as additional adjustments permitted under the company’s existing Credit Agreement.

On February 5, 2020 bluebird bio, Inc. (NASDAQ: BLUE) reported that members of the management team will present at the following upcoming investor conferences (Press release, bluebird bio, FEB 5, 2020, View Source [SID1234553868]):

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9th Annual SVB Leerink Global Healthcare Conference, Wednesday, February 26, at 2:30 p.m. ET at the Lotte New York Palace, New York, NY
Cowen 40th Annual Health Care Conference, Tuesday, March 3, at 8:00 a.m. ET at the Boston Marriott Copley Place, Boston, MA
To access the live webcasts of bluebird bio’s presentations, please visit the "Events & Presentations" page within the Investors & Media section of the bluebird bio website at View Source Replays of the webcasts will be available on the bluebird bio website for 90 days following the events.

On February 5, 2020 MaaT Pharma announced today an €18 million Series B financing round including a microbiome-focused US investor, SymBiosis, LLC, and support from its existing investors Seventure Partners, Crédit Mutuel Innovation, and Biocodex (Press release, MaaT Pharma, FEB 5, 2020, View Source [SID1234553886]). The funding will enable the continued clinical development of the company’s current pipeline, as well as the expansion into additional oncological indications where restoring a functional microbiome could provide significant therapeutic benefit when combined with other cancer treatments such as immune checkpoint inhibitors.

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"We are excited to have added a US-based investor to our syndicate based on the strategic importance of the US market for our future development. I would like to thank our existing investors and our network of scientific advisors for their continued support as we enter into this next development phase for the company," said Hervé Affagard, co-founder and CEO of MaaT Pharma. "A growing body of evidence suggests that a functional microbiome can improve cancer outcomes, and we look forward to continue building on our initial proof of concept by going beyond hematological malignancies into solid tumors."

The proceeds will be used to complete the ongoing HERACLES Phase II clinical trial (NCT03359980) of MaaT’s lead compound, MaaT013, in patients that developed steroid-refractory, gastrointestinal-predominant, acute Graft-versus-Host-Disease (SR aGvHD) following allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT). In addition, the company will accelerate the development of a capsule formulation of MaaT013, MaaT033, which will ease administration and facilitate the expansion of the company’s pipeline into new oncological indications, including the initiation of a Phase 1b clinical trial with MaaT033. Recent studies demonstrated that restoring a balanced microbiome can significantly improve the clinical outcomes of checkpoint inhibitors, and MaaT Pharma will investigate this potential in a combination trial in solid tumors. Preliminary data from the safety and dose-finding Phase 1b trial of MaaT033 is expected in H2 2020.

MaaT Pharma’s product candidates are based on the company’s proprietary MaaT Microbiome Restoration Biotherapeutics (MMRB) platform. MaaT Pharma’s lead product candidate, MaaT013, is an enema formulation characterized by a high consistent richness of microbial species, whose specific bacteria are protected thanks to a proprietary formulation, derived from pooling the full intestinal ecosystems of stringently vetted, healthy donors. The product is manufactured at MaaT’s centralized European cGMP production facility. Apart from the ongoing HERACLES Phase II trial, from which results are expected in 2020, MaaT has provided MaaT013 to a compassionate use program for patients who had failed to respond to previous treatments for SR aGvHD. In total, over 50 patients with severe hematological malignancies have been treated with the company’s product candidate. The data collected up to date demonstrate that reintroduction of a full-ecosystem microbiota is well tolerated in these patients and provides initial signs of therapeutic benefit. Initial results from the company’s compassionate use program were presented at the 2019 ASH (Free ASH Whitepaper) conference in Orlando, Florida.

On February 5, 2020 CytoSorbents Corporation (NASDAQ:CTSO), a critical care immunotherapy leader commercializing its CytoSorb blood purification technology to treat deadly inflammation in critically-ill and cardiac surgery patients around the world, reported the first published case report detailing the successful use of CytoSorb to help treat cytokine release syndrome (CRS) following the administration of CAR T-cell immunotherapy (Press release, Cytosorbents, FEB 5, 2020, View Source [SID1234553902]). In a recent publication entitled, "Multimodal Therapeutic Approach of Cytokine Release Syndrome Developing in a Child Given Chimeric Antigen Receptor-Modified T Cell Infusion", in the journal, Critical Care Explorations, a publication of the Society of Critical Care Medicine, Bottari and colleagues highlight the use of CytoSorb, in conjunction with continuous renal replacement and tocilizumab, to help treat a 14-year old boy with refractory acute lymphoblastic leukemia (ALL), who developed Grade 4 cytokine release syndrome (CRS) with progressive respiratory failure and severe acute respiratory distress syndrome (ARDS) following the administration of CAR T-cell immunotherapy.

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Dr. Joerg Scheier, Senior European Medical Director of CytoSorbents stated, "We are pleased to report the first published use of CytoSorb to assist in the rescue of a patient suffering from life-threatening cytokine release syndrome due to CAR T-cell immunotherapy. The combination of CytoSorb with continuous renal replacement therapy, and tocilizumab, was simple and safe to implement. More importantly, it led to a dramatic reversal of acute respiratory distress syndrome, one of the most deadly forms of lung injury that is a root cause of death in the Wuhan coronavirus outbreak, with a corresponding profound drop in cytokine storm and circulating inflammatory mediators. We believe this successful proof-of-concept treatment supports the consideration of this treatment regimen in future cases of CRS triggered by CAR T-cell immunotherapy."

This patient had previously failed treatment of his ALL with both chemotherapy and immunotherapy, and was enrolled into an academic CAR T-cell immunotherapy trial. However, 7 days after the CAR T-cell therapy infusion, he developed severe cytokine release syndrome (a form of cytokine storm), and the rapid progression of respiratory failure that did not respond to an initial dose of tocilizumab and low dose steroids. The patient was admitted to the pediatric intensive care unit (PICU) and placed on mechanical ventilation for profound ARDS with a PaO2/FiO2 (P/F) ratio of 45 mm Hg, and hemodynamic instability requiring vasopressors. His Grade 4 cytokine release syndrome (CRS) exhibited extremely high cytokine and inflammatory marker levels, including an IL-6 of 4,048 pg/mL and a ferritin of 146,095 ng/mL. The patient underwent five blood purification treatments with CytoSorb, changed every 12 hours for the first day, and then every 24 hours for the next 3 days, in conjunction with continuous renal replacement therapy (CRRT), with tocilizumab administered on the last 2 days of CytoSorb treatment. In the first 3 days of CytoSorb treatment, the ferritin levels dramatically decreased to normal, and the IL-6 dropped to 248 pg/mL. This improvement in control of CRS was mirrored by a gradual and progressive improvement in lung function, as measured by P/F ratio and chest X-rays. On day 12 of admission to the PICU, he was weaned off of mechanical ventilation and was discharged from the ICU a week later.

CAR T-cell immunotherapy (Kymriah – Novartis; Yescarta – Gilead) represents a breakthrough in cancer treatment of acute lymphocytic leukemia (ALL; also called acute lymphocytic leukemia) and Diffuse large B-cell lymphoma (DLBCL) that are refractory to standard biologic therapy and chemotherapy, and has great potential in other blood cancers and solid tumors in the future. The therapy takes a patient’s own immune T-cells, genetically modifies them outside of the body with a chimeric antigen receptor (CAR) to be able to recognize and kill the cancer cells, and reinfuses these CAR T-cells back into the body where they have led to dramatic cures of what were considered irreversibly fatal cancers. However, in doing so the activated cells often trigger an inflammatory response in the patient caused by the production of high levels of inflammatory mediators called cytokines. In some patients, the levels of these cytokines can spiral upwards, creating a "cytokine storm" or cytokine release syndrome (CRS) that can rapidly cause multi-organ failure, inflammation of the brain, and potentially death if left untreated. Tocilizumab (an IL-6 receptor antagonist) and intravenous steroids are the current approved treatments for CRS but are not always successful in controlling CRS or CRES, and have the potential to immune suppress the patient, increasing the risk of serious infection. CytoSorb has the potential to fill this gap. There are currently two approved CAR T-cell immunotherapies in both the United States and European Union. According to Market Research Future, the global CAR T-cell immunotherapy market is expected to approach $9 billion in revenue by 2025.