On May 13, 2021 Applied DNA Sciences, Inc. (NASDAQ: APDN) (the "Company"), a leader in Polymerase Chain Reaction (PCR)-based DNA manufacturing, reported consolidated financial results for the three and six months ended March 31, 2021 (Press release, Applied DNA Sciences, MAY 13, 2021, View Source [SID1234579927]).

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"We are pleased to deliver a strong fiscal second quarter with year-over-year revenue growth of 384%, capping an impressive first half of the fiscal year distinguished by demand for our COVID-19 diagnostics and surveillance testing offerings (cumulatively "COVID-19 testing business")," said Dr. James A. Hayward, president and CEO, Applied DNA. "Our strategic and operational execution across non-COVID-19 testing initiatives was also notable: we launched our first-ever clinical trial for a therapeutic candidate in the form of a LinearDNA COVID-19 vaccine candidate for the veterinary market; advanced our cGMP capabilities and compliance roadmap that is a precursor to securing more lucrative CMO relationships and lays the foundation potentially to disrupt the market for the manufacturing of nucleic acid-based therapies; established a recurring revenue stream from the dietary supplements industry via Nutrition21’s use of our CertainT platform; strengthened our capital position, and deepened the management team to support our growth goals."

Continued Dr. Hayward, "Our COVID-19 testing strategy is increasingly informed by the acceleration in vaccine distribution. While traditional positive/negative testing remains a component of our go-to-market strategy, we believe that we are well-positioned despite increasing vaccination rates given our ability to detect SARS-COV-2 mutations. The expansion of our COVID-19 product portfolio with our Selective Genomic Surveillance (SGS) Panel and expanded intended use of our EUA for our LineaTM COVID-19 Assay Kit to include asymptomatic serial screening testing reflects a differentiated capability that expands our addressable market to include populations that can serve as a nexus for vaccinated and under-vaccinated populations coming together with increasing frequency, such as skilled nursing facilities, and supports the reopening of schools and workplaces. With our newly expanded intended use, together with the receipt of a New York clinical laboratory permit and CLIA certification for COVID-19 testing using EUA-authorized methods and devices by our Applied DNA Clinical Labs, LLC subsidiary, we believe our COVID-19 testing business presents a compelling opportunity for continued top-line growth.

"During the second half of the fiscal year, we will focus on positioning our COVID-19 testing business for the expected ongoing need for tests and services to support clients’ reopening strategies. While today our SGS Panel is available on a research use only (RUO) basis, our logical next step would be to seek an EUA to bring this critical tool out from the lab and to every Emergency Room and other healthcare providers that serve as the first line of defense against coronavirus variants to potentially inform their use of monoclonal antibody and convalescent plasma therapies. Concurrently and in line with our phased approach to cGMP that is further bolstered by preliminary positive neutralizing antibody results in domestic felines in our LinearDNA COVID-19 vaccine candidate clinical trial, we intend to explore an expansion of our LinearDNA-based therapeutic pipeline into classes of therapies that will best utilize the many benefits of our LinearDNA platform.

"While the speed and shape of the global recovery and timing of its impact on our supply chain security business remain uncertain, over the past year, we have seen brands and their supply chains put more emphasis on supply chain security and transparency to enhance their market position exiting the pandemic. We continue to position our CertainT platform as an enabler of the trust that both brands and consumers seek in a post-pandemic world, which, following the passage of the Uyghur Forced Labor Prevention Act, has further catalyzed our interest in leveraging our deep expertise in cotton genotyping and new next-generation sequencing capability to support brands’ regulatory requirements and ethical responsibilities."

Concluded Dr. Hayward, "Our strong balance sheet affords us substantial strategic and operational flexibility, as well as the ability to make both short- and longer-term investments in our businesses. We believe these investments in R&D and pre-commercial and commercial initiatives further enhance our growth profile."

Fiscal Second Quarter 2021 Financial Highlights:

Revenues increased 384% for the second quarter of fiscal 2021 to $2.7 million, compared with $552 thousand reported in the same period of the prior fiscal year and increased 65% from $1.6 million for the first quarter of fiscal 2021. The increase in revenues year over year was due primarily to an increase in service revenues of approximately $1.4 million and an increase of $767 thousand in product revenues. The increase in service revenue was primarily from revenues derived from our safeCircle COVID-19 surveillance testing. The increase in product revenue was mainly attributable to an increase in sales of our Linea COVID-19 Assay Kit.
Total operating expenses increased to $4.6 million for the second fiscal quarter of 2021, compared with $3.0 million in the prior fiscal year’s second quarter. This increase is primarily attributable to an increase in payroll of $315 thousand for staffing of Applied DNA Clinical Labs, LLC (ADCL), as well as an increase of $277 thousand for supplies and equipment to operate the ADCL laboratory. The increase in operating expenses also related to an increase in stock-based compensation expense of $422 thousand relating to officer stock option grants that vested immediately. The increase is also the result of increases in research and development expenses of $171 thousand and depreciation and amortization of $133 thousand.
Net loss applicable to common stockholders for the quarter ended March 31, 2021 was $1.5 million, or $0.21 per share, compared with a net loss of $3.0 million, or $0.79 per share, for the quarter ended March 31, 2020.
Excluding non-cash expenses, Adjusted EBITDA was negative $1.5 million and negative $2.6 million for the quarters ended March 31, 2021 and 2020, respectively. See below for information regarding non-GAAP measures.
Cash and cash equivalents stood at $13.9 million on March 31, 2021, compared to $7.8 million as of September 30, 2020.
Six-Month Financial Highlights:

Revenues increased 262% for the first six months of fiscal 2021 to $4.3 million, compared with $1.2 million reported in the same period of the prior fiscal year. The increase in revenues year over year was due primarily to an increase in service revenues of approximately $2.0 million and an increase of $1.1 million in product revenues. The increase in service revenue was primarily from revenues derived from our safeCircle COVID-19 surveillance testing. The increase in product revenue was mainly attributable to an increase in sales of our Linea Assay Kit.
Total operating expenses increased to $9.0 million for the first six months of fiscal 2021, compared with $6.1 million in the same period of the prior fiscal year. This increase is primarily attributable to an increase in payroll of $1 million. The increase in payroll relates to additional headcount to staff at ADCL, as well as an increase for officer bonuses. The increase in operating expenses also related to an increase in stock-based compensation expense of $725 thousand primarily relating to officer stock option grants that vested immediately.
Net loss applicable to common stockholders for the six-months ended March 31, 2021 was $6.3 million, or $1.00 per share, compared with a net loss of $5.6 million, or $1.76 per share, for the first six months of fiscal 2020.
Excluding non-cash expenses, Adjusted EBITDA was negative $3.9 million for the first six months of fiscal 2021, compared to negative $5.0 million for the same period in the prior fiscal year. See below for information regarding non-GAAP measures.
Fiscal Second Quarter 2021 Conference Call Information

The Company will hold a conference call and webcast to discuss its fiscal second quarter-end 2021 results on Thursday, May 13, 2021 at 4:30 PM ET. To participate on the conference call, please follow the instructions below. While every attempt will be made to answer investors’ questions on the Q&A portion of the call, not all questions may be answered.

Webcast replay: View Source
For those unable to attend the live call, a copy of management’s PowerPoint presentation will be available for review under the ‘IR Calendar’ section of the company’s Investor Relations web site: View Source

Information about Non-GAAP Financial Measures

As used herein, "GAAP" refers to accounting principles generally accepted in the United States of America. To supplement our condensed consolidated financial statements prepared and presented in accordance with GAAP, this earnings release includes Adjusted EBITDA, which is a non-GAAP financial measure as defined in Rule 101 of Regulation G promulgated by the Securities and Exchange Commission. Generally, a non-GAAP financial measure is a numerical measure of a company’s historical or future performance, financial position, or cash flows that either excludes or includes amounts that are not normally excluded or included in the most directly comparable measure calculated and presented in accordance with GAAP. The presentation of this non-GAAP financial information is not intended to be considered in isolation or as a substitute for, or superior to, the financial information presented in accordance with GAAP. We use this non-GAAP financial measure for internal financial and operational decision-making purposes and as a means to evaluate period-to-period comparisons of the performance and results of operations of our core business. Our management believes that these non-GAAP financial measures provide meaningful supplemental information regarding the performance of our business by excluding non-cash expenses that may not be indicative of our recurring operating results. We believe this non-GAAP financial measure is useful to investors as they allow for greater transparency with respect to key metrics used by management in its financial and operational decision making.

"EBITDA"- is defined as earnings (loss) before interest expense, income tax expense and depreciation and amortization expense.

"Adjusted EBITDA"- is defined as EBITDA adjusted to exclude (i) stock-based compensation and (ii) other non-cash expenses.

On May 13, 2021 Anavex Life Sciences Corp. ("Anavex" or the "Company") (Nasdaq: AVXL), a clinical-stage biopharmaceutical company developing differentiated therapeutics for the treatment of neurodegenerative and neurodevelopmental disorders including Alzheimer’s disease, Parkinson’s disease, Rett syndrome and other central nervous system (CNS) diseases, reported financial results for its fiscal quarter ended March 31, 2021 (Press release, Anavex Life Sciences, MAY 13, 2021, View Source [SID1234579943]).

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"Positive momentum continues to build this quarter and affirms the strength of our pipeline and execution capabilities," said Christopher U Missling, PhD, President and Chief Executive Officer of Anavex. "For our lead drug candidate, ANAVEX2-73 in Alzheimer’s disease, we are close to complete enrollment for our Phase 2b/3 study, and we expect a very data-rich current quarter with data readouts from multiple clinical trials and the remainder of 2021 to be a catalyst-rich year for Anavex. This is an exciting time for Anavex and I look forward to advancing our impressive pipeline of mid- and late-stage clinical trials with a commitment to bringing innovative therapies to patients in need around the globe."

Anavex Life Sciences’ Business and Near-Term Clinical Outlook:

ANAVEX2-73 Program and other Near-Term Pipeline Data Updates:

Complete data ANAVEX2-73 U.S. Rett syndrome Phase 2 study.
Complete data ANAVEX2-73 Parkinson’s disease dementia (PDD) Phase 2 study.
Top-line data AVATAR: Potentially pivotal Phase 2/3 ANAVEX2-73 adult Rett syndrome clinical trial.
Top-line data Phase 1 ANAVEX3-71 clinical trial.
Complete enrollment of Phase 2b/3 ANAVEX2-73 Alzheimer’s disease clinical trial.
Recent Business Highlights:

In March 2021, Anavex announced that the Independent Data Safety Monitoring Board (DSMB) for the Company’s Phase 2b/3 Alzheimer’s disease study of its investigational compound ANAVEX2-73 (blarcamesine) has completed its recent pre-planned review of the preliminary Phase 2b/3 study data. As specified in the protocol, the DSMB reviewed the interim safety data for the ANAVEX2-73 Phase 2b/3 Alzheimer’s disease clinical study ANAVEX2-73-AD-004 and its Open Label Extension (OLE) ANAVEX2-73-AD-EP-004 ATTENTION-AD study. Upon review of the interim safety data, the DSMB made the following recommendation: The DSMB recommendation is to continue the studies without modification.
In April 2021, Anavex announced that the Independent Data Safety Monitoring Board (DSMB) for the Company’s ongoing clinical trial program, including the late-stage AVATAR (ANAVEX2-73-RS-002), EXCELLENCE (ANAVEX2-73-RS-003) and the U.S. Rett syndrome extension study (ANAVEX2-73-RS-EP-001) of its investigational compound ANAVEX2-73 (blarcamesine) has completed its recent pre-planned review of the respective interim safety data for these three separate clinical studies. Upon review of the interim safety data, the DSMB made the following recommendation for each of the three studies: The DSMB recommendation is to continue the studies without modification.
In March 2021, Anavex announced that ANAVEX2-73 (blarcamesine) is featured in a recent peer-reviewed publication in the journal of Neuropharmacology, titled "Future avenues for Alzheimer’s disease detection and therapy: liquid biopsy, intracellular signaling modulation, systems pharmacology drug discovery" from the series of the special issue on ‘The Quest for Disease-Modifying Therapies for Neurodegenerative Disorders’.
In May 2021, Anavex announced the appointment of former FDA officer as Senior Vice President for Nonclinical Development.
Further clinical milestones are provided in Anavex Life Sciences’ latest corporate presentation, available on anavex.com.
Financial Highlights:

Continued fiscal responsible management of cash utilization.
Cash and cash equivalents at March 31, 2021 of approximately $75.9 million, sufficient cash runway for up to three (3) years.
Net loss of $8.2 million, or $0.12 per share for the quarter, compared to net loss of $7.2 million, or $0.12 per share in comparative quarter of fiscal 2020.
Research and development expenses of $6.7 million for the quarter, compared to $6.1 million for comparable quarter of fiscal 2020.
General and administrative expenses were $2.2 million for the quarter, as compared to $1.7 million for the prior year period.
The financial information for the fiscal quarter ended March 31, 2021 should be read in conjunction with the Company’s interim condensed consolidated financial statements, which will appear on EDGAR, www.sec.gov and will be available on the Anavex website at www.anavex.com.

Conference Call / Webcast Information:

The live webcast of the conference call can be accessed online at View Source

To join the conference call, live via telephone, interested parties within the U.S. should dial, toll-free, 1 (866) 866-1333 and international callers should dial 1 (404) 260-1421. Please use confirmation number 50162864, followed by the pound sign (#).

A replay of the conference call will also be available on www.anavex.com.

On May 13, 2021 Osmol Therapeutics reported that it has initiated Investigational New Drug (IND) enabling studies to develop a therapy to prevent chemotherapy-induced peripheral neuropathy (CIPN) (Press release, Osmol Therapeutics, MAY 13, 2021, View Source [SID1234579961]). A phase 1 clinical study is projected to begin in 2022 . There are currently no Food and Drug Administration (FDA) approved therapies for the prevention or treatment of CIPN, a debilitating condition resulting from the off-target toxicity of many chemotherapy treatments.

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Osmol was founded by Dr. Barbara Ehrlich, Professor of Pharmacology and of Cellular and Molecular Physiology, Yale School of Medicine. Her research on neuronal calcium sensor-1 (NCS1), a critical calcium binding protein that regulates intracellular calcium levels, forms the basis of Osmol’s CIPN treatment, OSM-0205 and future potential NCS1 therapeutics. OSM-0205’s mechanism addresses the off-target toxicity of microtubule-based chemotherapy agents that results in a calcium surge leading to CIPN. OSM-0205 modulates NCS1 to prevent the calcium surge and maintain neuronal integrity.

The company’s initial focus is CIPN in breast cancer patients resulting from taxane-based chemotherapy treatment. Taxanes are the most widely used chemotherapy treatment for breast cancer and can lead to CIPN in up to 80% of patients. Independent market research conducted with breast cancer oncologists at leading US cancer centers confirmed that CIPN is the most significant toxicity issue facing clinicians and patients when treating breast cancer.

"Chemotherapy-induced peripheral neuropathy is a devastating adverse event that can leave patients and their treating physicians with a very difficult choice – reduce taxane therapy with the possibility of negatively impacting patient outcomes or continue therapy at the recommended dose with the potential of causing increased and possibly permanent, disabling CIPN," said Dr. Ehrlich. "OSM-0205 is being developed with the goal of preventing CIPN before it occurs. By blocking the calcium surge that causes neuropathy, optimal treatment with taxanes can continue. This is particularly important in the treatment of breast cancer where taxanes remain the foundation of most therapeutic regimens."

"There are currently no FDA-approved therapies to avoid or reduce CIPN, creating an urgent need for patients being treated with chemotherapy," said Robert Berman, M.D., Executive Chairman of Osmol Therapeutics and co-founder and former Chief Medical Officer at Biohaven Pharmaceuticals. "Over 225,000 patients in the U.S. and the European Union with early stage or metastatic breast cancer are treated with taxanes each year. We have recruited an experienced and capable executive team, led by Bob Linke, Osmol’s Chief Executive Officer, to advance OSM-0205 to address this need as well as explore the potential use of neuronal calcium sensor-1 (NCS1) in other indications. We are excited by the potential of OSM-0205 and expect to begin clinical development as early as next year."

Bob Linke, MBA, is an experienced biopharma entrepreneur, who is also Executive Chairman of Embera NeuroTherapeutics and IonSense. He has an established track record developing strategies, building and leading emerging companies through all phases of growth – from research, product development and clinical studies to successful commercialization, partnership and acquisitions. Bob brings an open management style to create cohesive, high-functioning teams. He has raised over $70 million in private equity and non-dilutive financing to fund these companies’ development and commercialization efforts. His early career was spent at Baxter, developing and commercializing pharmaceuticals and drug delivery systems.

About OSM-0205 and CIPN

Osmol’s lead drug, OSM-0205, is based on Dr. Barbara Ehrlich’s research in neuronal calcium sensor-1 (NCS1) at Yale University and is designed to prevent the off-target calcium surge caused by taxanes and potentially other chemotherapy treatments associated with peripheral nerve damage. Data from preclinical studies conducted by Osmol show that pre-treatment with OSM-0205 prevents neuronal damage from taxanes in mice by preventing the off-target intracellular calcium surge caused by these chemotherapy agents. It is hypothesized that OSM-0205 modulates NCS1 in patients to protect neurons from damage leading to a reduction of CIPN. CIPN affects hundreds of thousands of cancer patients every year and can compromise optimum chemotherapy dosing. There are no effective treatments for CIPN, a condition which can diminish quality of life and lead to lifelong disability.

On May 13, 2021 Insmed Incorporated (Nasdaq: INSM) reported the closing of the previously announced registered underwritten public offering (the "Equity Offering") of 11,500,000 shares of its common stock (the "Shares"), including 1,500,000 Shares issued pursuant to the exercise in full of the underwriters’ option to purchase additional Shares, at a price to the public of $25.00 per share before deducting underwriting discounts and commissions, and the previously announced registered underwritten public offering (the "Notes Offering") of $575 million aggregate principal amount of its 0.75% convertible senior notes due 2028 (the "Notes"), including $75 million aggregate principal amount of Notes purchased pursuant to the exercise in full of the underwriters’ option to purchase additional Notes, solely to cover over-allotments (Press release, Insmed, MAY 13, 2021, View Source [SID1234580031]). A portion of the net proceeds from the offering of the Notes will be used to repurchase $225 million in aggregate principal amount of Insmed’s existing outstanding 1.75% Convertible Senior Notes due 2025 (the "2025 Notes"). The gross proceeds to Insmed from the offerings, before deducting underwriting discounts and commissions and other offering expenses payable by Insmed, were $287.5 million and $575 million, respectively.

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The Notes are senior unsecured obligations of Insmed and rank senior in right of payment to any of Insmed’s future indebtedness that is expressly subordinated in right of payment to the Notes and rank equally in right of payment with all of Insmed’s existing and future liabilities that are not so subordinated, including the existing 2025 Notes. The Notes will accrue interest payable semiannually in arrears on June 1 and December 1 of each year at the rate of 0.75% per year, beginning on December 1, 2021. The Notes will mature on June 1, 2028, unless earlier repurchased, redeemed or converted in accordance with their terms prior to such date. Prior to June 6, 2025, Insmed will not have the right to redeem the Notes. Subject to certain conditions, on or after June 6, 2025, Insmed may redeem for cash all or a part of the Notes. Prior to March 1, 2028, the Notes will be convertible at the option of holders of the Notes only upon satisfaction of certain conditions and during certain periods, and thereafter, will be convertible at any time until the close of business on the second scheduled trading day immediately preceding the maturity date. Upon conversion, holders of the Notes will receive shares of Insmed common stock, cash or a combination thereof, at Insmed’s election. The conversion rate for the Notes is initially 30.7692 shares of Insmed common stock per $1,000 principal amount of Notes, which is equivalent to an initial conversion price of approximately $32.50 per share, and is subject to adjustment under the terms of the Notes. Insmed may be obligated to increase the conversion rate for any conversion that occurs in connection with certain corporate events or a redemption of the Notes by Insmed. The initial conversion price represents a premium of approximately 30% over the public offering price per share of the Shares in the Equity Offering.

Concurrently with the offerings, Insmed entered into separate and privately negotiated repurchase transactions with certain holders of a portion of the 2025 Notes. In these transactions, Insmed will repurchase 2025 Notes with an aggregate principal amount of $225 million for an aggregate repurchase price of approximately $238.9 million, using a portion of the net proceeds from the Notes Offering. Insmed intends to use the remaining net proceeds from the Notes Offering and the net proceeds from the Equity Offering to fund activities related to the commercialization and development of ARIKAYCE, further research and development of brensocatib, TPIP or any of its product candidates, and for other general corporate purposes, including business expansion activities.

J.P. Morgan Securities LLC and SVB Leerink LLC acted as book-running managers for the offerings. Morgan Stanley & Co. LLC also acted as a book-running manager for the offerings. Credit Suisse Securities (USA) LLC and Stifel, Nicolaus & Company, Incorporated acted as co-lead managers for the Equity Offering. Cantor Fitzgerald & Co. and H.C. Wainwright & Co., LLC acted as co-managers for the Equity Offering.

A shelf registration statement on Form S-3 (File No. 333-238560) relating to the Equity Offering and the Notes Offering as described above has been filed with the Securities and Exchange Commission ("SEC"), and became automatically effective upon filing on May 21, 2020. A final prospectus supplement relating to and describing the terms of each offering was filed with the SEC and is available on the SEC’s website at www.sec.gov. Alternatively, copies may be obtained from: J.P. Morgan Securities LLC, Attention: Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, by telephone at (866) 803-9204 or by email at [email protected]; or SVB Leerink LLC, Attention: Syndicate Department, One Federal Street, 37th Floor, Boston, MA 02110, by telephone at (800) 808-7525, ext. 6105 or by email at [email protected].

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

On May 13, 2021 bluebird bio, Inc. (Nasdaq: BLUE) reported that data from its gene therapy programs for transfusion-dependent β-thalassemia (TDT) and sickle cell disease (SCD) and its cell therapy program for relapsed or refractory multiple myeloma (R/RMM) will be presented during EHA (Free EHA Whitepaper)2021 Virtual, the 26th Annual Congress of the European Hematology Association (EHA) (Free EHA Whitepaper), taking place June 9-17, 2021 (Press release, bluebird bio, MAY 13, 2021, View Source [SID1234579846]).

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bluebird bio will present data from its ongoing clinical studies of betibeglogene autotemcel (beti-cel), including updated results from the Phase 3 Northstar-2 (HGB-207) and the Phase 3 Northstar-3 (HGB-212) studies, as well as long-term efficacy and safety results from the LTF-303 follow-up study. Additionally, data from the company’s Phase 1/2 HGB-206 study of LentiGlobin for SCD (bb1111) will be shared.

Data from the pivotal Phase 2 KarMMa study of ABECMA (idecabtagene vicleucel; ide-cel) in R/RMM will also be presented in encore presentations, in partnership with Bristol Myers Squibb, including long-term results and a sub-analysis of characteristics of treatment-associated neurotoxicity.

Transfusion-Dependent β-Thalassemia Data at EHA (Free EHA Whitepaper)2021

Oral Presentation [S266]: Betibeglogene autotemcel in Patients With Transfusion-Dependent β-Thalassemia: Updated Results From HGB-207 (Northstar-2) and HGB-212 (Northstar-3)
Presenting Author: Professor Franco Locatelli, Director, Department of Pediatric Hematology and Oncology, Ospedale Pediatrico Bambino Gesù, Rome, Italy
Session Title: Changing the Scene on Thalassemias
Date & Time: Available on Demand, Friday, June 11; Live Q&A Session

Oral Presentation [S257]: Betibeglogene autotemcel Gene Therapy for the Treatment of Transfusion-Dependent β-Thalassemia: Updated Long-Term Efficacy and Safety Results
Presenting Author: Dr. Evangelia Yannaki, Director, Gene and Cell Therapy Center, Hematology Department, George Papanicolaou Hospital, Thessaloniki, Greece
Session Title: Cellular Immunotherapy and Gene Therapy – Clinical
Date & Time: Available on Demand, Friday, June 11; Live Q&A Session

ePoster [EP1301]: Interim Results of Betibeglogene autotemcel Gene Therapy in Pediatric Patients with Transfusion-Dependent β-thalassemia (TDT) Treated in the Phase 3 Northstar-2 (HGB-207) and Northstar-3 (HGB-212) Studies
Presenting Author: Dr. Andreas E. Kulozik, Chairman, Department of Pediatric Oncology, Hematology and Immunology, and Director, Hopp Children’s Cancer Center, University of Heidelberg, Heidelberg, Germany

ePoster [EP1309]: A Retrospective Database Study of Disease Course and Clinical Outcomes in Patients with Transfusion-dependent Thalassemia (TDT) in Italy
Presenting Author: Dr. Angela Vitrano, Campus of Hematology Franco and Piera Cutino, AOOR Villa Sofia-V. Cervello, Palermo, Italy

Sickle Cell Disease Data at EHA (Free EHA Whitepaper)2021

Oral Presentation [S261]: Complete Resolution of Severe Vaso-Occlusive Events and Improved Pathophysiology with LentiGlobin Gene Therapy in Sickle Cell Disease (SCD): Ongoing Phase 1/2 HGB-206 Group C Study
Presenting Author: Dr. Janet L. Kwiatkowski, Director, Thalassemia Center at Children’s Hospital of Philadelphia, Philadelphia, PA
Session Title: Changing the Scene on Sickle Cell Disease
Date & Time: Available on Demand, Friday, June 11; Live Q&A Session

ePoster [EP1212]: Complications of Sickle Cell Disease in East London Newborn Cohort Patients Over the Years 2015-2018
Presenting Author: Muriel Soriano, Centre of Genomics and Child Health, Queen Mary University of London, London, United Kingdom

Multiple Myeloma Data at EHA (Free EHA Whitepaper)2021

ePoster [EP984]: Characteristics of Neurotoxicity Associated with Idecabtagene Vicleucel (ide-cel, bb2121) in Patients with Relapsed and Refractory Multiple Myeloma in the Pivotal Phase II KarMMa Study
Presenting Author: Dr. Salomon Manier, Department of Hematology, Lille University Hospital, Lille, France

ePoster [EP1009]: Idecabtagene Vicleucel (ide-cel, bb2121), a BCMA-Directed CAR T Cell Therapy, in Patients with Relapsed and Refractory Multiple Myeloma: Updated KarMMa Results
Presenting Author: Dr. Albert Oriol, Institut Josep Carreras and Institut Catala d’Oncologia, Hospital Germans Trias i Pujol, Badalona, Spain

Abstracts are available on the EHA (Free EHA Whitepaper)2021 conference website.

About betibeglogene autotemcel (beti-cel)

Betibeglogene autotemcel (beti-cel) is a one-time gene therapy that adds functional copies of a modified form of the β-globin gene (βA-T87Q-globin gene) into a patient’s own hematopoietic (blood) stem cells (HSCs). Once a patient has the βA-T87Q-globin gene, they have the potential to produce HbAT87Q, which is gene therapy-derived adult hemoglobin (Hb), at levels that may eliminate or significantly reduce the need for transfusions. In studies of beti-cel, transfusion independence (TI) is defined as no longer needing red blood cell transfusions for at least 12 months while maintaining a weighted average Hb of at least 9 g/dL.

The European Commission granted conditional marketing authorization (CMA) for beti-cel, marketed as ZYNTEGLO gene therapy, for patients 12 years and older with TDT who do not have a β0/β0 genotype, for whom hematopoietic stem cell (HSC) transplantation is appropriate, but a human leukocyte antigen (HLA)-matched related HSC donor is not available. Non-serious adverse events (AEs) observed during clinical studies that were attributed to beti-cel included abdominal pain, thrombocytopenia, leukopenia, neutropenia, hot flush, dyspnea, pain in extremity, tachycardia and non-cardiac chest pain. One serious adverse event (SAE) of thrombocytopenia was considered possibly related to beti-cel.

Additional AEs observed in clinical studies were consistent with the known side effects of HSC collection and bone marrow ablation with busulfan, including SAEs of veno-occlusive disease. For details, please see the Summary of Product Characteristics (SmPC).

On April 28, 2020, the European Medicines Agency (EMA) renewed the CMA for beti-cel. The CMA for beti-cel is valid in the 27 member states of the EU as well as the UK, Iceland, Liechtenstein and Norway. In November 2020, bluebird bio submitted to the EMA an application for the second renewal of the CMA. This procedure is currently on hold while the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) reviews the safety of ZYNTEGLO. The CMA is valid while the renewal application review is ongoing and while it is on hold by the regulatory agency. The U.S. Food and Drug Administration (FDA) granted beti-cel Orphan Drug status and Breakthrough Therapy designation for the treatment of TDT. Beti-cel is not approved in the U.S.

Beti-cel continues to be evaluated in the ongoing Phase 3 Northstar-2 (HGB-207) and Northstar-3 (HGB-212) studies, which are on clinical hold. bluebird bio is conducting a long-term safety and efficacy follow-up study, LTF-303, for people who have participated in bluebird bio-sponsored clinical studies of beti-cel.

About LentiGlobin for SCD (bb1111)

LentiGlobin gene therapy for sickle cell disease (bb1111) is an investigational treatment being studied as a potential treatment for SCD. bluebird bio’s clinical development program for LentiGlobin for SCD includes the completed Phase 1/2 HGB-205 study. It also includes the Phase 1/2 HGB-206 and the Phase 3 HGB-210 studies, which are on clinical hold.

The U.S. FDA granted orphan drug designation, fast track designation, regenerative medicine advanced therapy (RMAT) designation and rare pediatric disease designation for LentiGlobin for SCD.

LentiGlobin for SCD received orphan medicinal product designation from the European Commission for the treatment of SCD, and Priority Medicines (PRIME) eligibility by the EMA in September 2020.

bluebird bio is conducting a long-term safety and efficacy follow-up study (LTF-307) for people who have participated in bluebird bio-sponsored clinical studies of LentiGlobin for SCD. For more information visit: View Source or clinicaltrials.gov and use identifier NCT04628585 for LTF-307.

LentiGlobin for SCD is investigational and has not been approved in any geography.

About ABECMA

ABECMA is the first-in-class B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell immunotherapy approved in the U.S. for the treatment of adult patients with relapsed and refractory multiple myeloma after four or more prior lines of therapy, including and immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. ABECMA recognizes and binds to BCMA on the surface of multiple myeloma cells leading to CAR T cell proliferation, cytokine secretion, and subsequent cytolytic killing of BCMA-expressing cells. ABECMA is being jointly developed and commercialized in the U.S. as part of a Co-Development, Co-Promotion, and Profit Share Agreement with Bristol Myers Squibb and bluebird bio.

Bristol Myers Squibb and bluebird bio’s broad clinical development program for ABECMA includes clinical studies (KarMMa-2, KarMMa-3, KarMMa-4, KarMMa-7) in earlier lines of treatment for patients with multiple myeloma, including newly diagnosed multiple myeloma. For more information visit clinicaltrials.gov.

Indication

ABECMA (idecabtagene vicleucel) is a B-cell maturation antigen (BCMA)-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody.

Important Safety Information

BOXED WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, HLH/MAS, AND PROLONGED CYTOPENIA

Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients following treatment with ABECMA. Do not administer ABECMA to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.
Neurologic Toxicities, which may be severe or life-threatening, occurred following treatment with ABECMA, including concurrently with CRS, after CRS resolution, or in the absence of CRS. Monitor for neurologic events after treatment with ABECMA. Provide supportive care and/or corticosteroids as needed.
Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS) including fatal and life-threatening reactions, occurred in patients following treatment with ABECMA. HLH/MAS can occur with CRS or neurologic toxicities.
Prolonged Cytopenia with bleeding and infection, including fatal outcomes following stem cell transplantation for hematopoietic recovery, occurred following treatment with ABECMA.
ABECMA is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the ABECMA REMS.
Cytokine Release Syndrome (CRS): CRS, including fatal or life-threatening reactions, occurred following treatment with ABECMA. CRS occurred in 85% (108/127) of patients receiving ABECMA. Grade 3 or higher CRS (Lee grading system) occurred in 9% (12/127) of patients, with Grade 5 CRS reported in one (0.8%) patient. The median time to onset of CRS, any grade, was 1 day (range: 1 – 23 days) and the median duration of CRS was 7 days (range: 1 – 63 days) in all patients including the patient who died. The most common manifestations of CRS included pyrexia (98%), hypotension (41%), tachycardia (35%), chills (31%), hypoxia (20%), fatigue (12%), and headache (10%). Grade 3 or higher events that may be associated with CRS include hypotension, hypoxia, hyperbilirubinemia, hypofibrinogenemia, acute respiratory distress syndrome (ARDS), atrial fibrillation, hepatocellular injury, metabolic acidosis, pulmonary edema, multiple organ dysfunction syndrome and HLH/MAS.

Identify CRS based on clinical presentation. Evaluate for and treat other causes of fever, hypoxia, and hypotension. CRS has been reported to be associated with findings of HLH/MAS, and the physiology of the syndromes may overlap. HLH/MAS is a potentially life-threatening condition. In patients with progressive symptoms of CRS or refractory CRS despite treatment, evaluate for evidence of HLH/MAS.

Fifty four percent (68/127) of patients received tocilizumab; 35% (45/127) received a single dose while 18% (23/127) received more than 1 dose of tocilizumab. Overall, across the dose levels, 15% (19/127) of patients received at least 1 dose of corticosteroids for treatment of CRS. All patients that received corticosteroids for CRS received tocilizumab.

Overall rate of CRS was 79% and rate of Grade 2 CRS was 23% in patients treated in the 300 x 106 CAR+ T cell dose cohort. For patients treated in the 450 x 106 CAR+ T cell dose cohort, the overall rate of CRS was 96% and rate of Grade 2 CRS was 40%. Rate of Grade 3 or higher CRS was similar across the dose range. The median duration of CRS for the 450 x 106 CAR+ T cell dose cohort was 7 days (range: 1-63 days) and for the 300 x 106 CAR+ T cell dose cohort was 6 days (range: 2-28 days). In the 450 x 106 CAR+ T cell dose cohort, 68% (36/53) of patients received tocilizumab and 23% (12/53) received at least 1 dose of corticosteroids for treatment of CRS. In the 300 x 106 CAR+ T cell dose cohort, 44% (31/70) of patients received tocilizumab and 10% (7/70) received corticosteroids. All patients that received corticosteroids for CRS also received tocilizumab. Ensure that a minimum of 2 doses of tocilizumab are available prior to infusion of ABECMA.

Monitor patients at least daily for 7 days following ABECMA infusion at the REMS-certified healthcare facility for signs and symptoms of CRS. Monitor patients for signs or symptoms of CRS for at least 4 weeks after infusion. At the first sign of CRS, institute treatment with supportive care, tocilizumab and/or corticosteroids as indicated.

Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time.

Neurologic Toxicities: Neurologic toxicities, which may be severe or life-threatening, occurred following treatment with ABECMA, including concurrently with CRS, after CRS resolution, or in the absence of CRS. CAR T cell-associated neurotoxicity occurred in 28% (36/127) of patients receiving ABECMA, including Grade 3 in 4% (5/127) of patients. One patient had ongoing Grade 2 neurotoxicity at the time of death. Two patients had ongoing Grade 1 tremor at the time of data cutoff. The median time to onset of neurotoxicity was 2 days (range: 1 – 42 days). CAR T cell-associated neurotoxicity resolved in 92% (33/36) of patients with a median duration of neurotoxicity was 5 days (range: 1 – 61 days). The median duration of neurotoxicity was 6 days (range: 1 – 578) in all patients including those with ongoing neurotoxicity at the time of death or data cut off. Thirty-four patients with neurotoxicity had CRS. Neurotoxicity had onset in 3 patients before, 29 patients during, and 2 patients after CRS. The rate of Grade 3 neurotoxicity was 8% in the 450 x 106 CAR+ T cell dose cohort and 1.4% in the 300 x 106 CAR+ T cell dose cohort. The most frequently reported (greater than or equal to 5%) manifestations of CAR T cell-associated neurotoxicity include encephalopathy (20%), tremor (9%), aphasia (7%), and delirium (6%). Grade 4 neurotoxicity and cerebral edema in 1 patient has been reported with ABECMA in another study in multiple myeloma. Grade 3 myelitis and Grade 3 parkinsonism have been reported after treatment with ABECMA in another study in multiple myeloma.

Monitor patients at least daily for 7 days following ABECMA infusion at the REMS-certified healthcare facility for signs and symptoms of neurologic toxicities. Rule out other causes of neurologic symptoms. Monitor patients for signs or symptoms of neurologic toxicities for at least 4 weeks after infusion and treat promptly. Neurologic toxicity should be managed with supportive care and/or corticosteroids as needed.

Counsel patients to seek immediate medical attention should signs or symptoms of neurologic toxicity occur at any time.

Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS): HLH/MAS occurred in 4% (5/127) of patients receiving ABECMA. One patient treated in the 300 x 106 CAR+ T cell dose cohort developed fatal multi-organ HLH/MAS with CRS. In another patient with fatal bronchopulmonary aspergillosis, HLH/MAS was contributory to the fatal outcome. Three cases of Grade 2 HLH/MAS resolved. The rate of HLH/MAS was 8% in the 450 x 106 CAR+ T cell dose cohort and 1% in the 300 x 106 CAR+ T cell dose cohort. All events of HLH/MAS had onset within 10 days of receiving ABECMA with a median onset of 7 days (range: 4-9 days) and occurred in the setting of ongoing or worsening CRS. Two patients with HLH/MAS had overlapping neurotoxicity. The manifestations of HLH/MAS include hypotension, hypoxia, multiple organ dysfunction, renal dysfunction, and cytopenia. HLH/MAS is a potentially life-threatening condition with a high mortality rate if not recognized early and treated. Treatment of HLH/MAS should be administered per institutional standards.

ABECMA REMS: Due to the risk of CRS and neurologic toxicities, ABECMA is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the ABECMA REMS. Further information is available at www.AbecmaREMS.com or 1‑888‑423‑5436.

Hypersensitivity Reactions: Allergic reactions may occur with the infusion of ABECMA. Serious hypersensitivity reactions, including anaphylaxis, may be due to dimethyl sulfoxide (DMSO) in ABECMA.

Infections: ABECMA should not be administered to patients with active infections or inflammatory disorders. Severe, life-threatening, or fatal infections occurred in patients after ABECMA infusion. Infections (all grades) occurred in 70% of patients. Grade 3 or 4 infections occurred in 23% of patients. Overall, 4 patients had Grade 5 infections (3%); 2 patients (1.6%) had Grade 5 events of pneumonia, 1 patient (0.8%) had Grade 5 bronchopulmonary aspergillosis, and 1 patient (0.8%) had cytomegalovirus (CMV) pneumonia associated with Pneumocystis jirovecii. Monitor patients for signs and symptoms of infection before and after ABECMA infusion and treat appropriately. Administer prophylactic, preemptive, and/or therapeutic antimicrobials according to standard institutional guidelines. Febrile neutropenia was observed in 16% (20/127) of patients after ABECMA infusion and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad spectrum antibiotics, fluids, and other supportive care as medically indicated.

Viral Reactivation: Cytomegalovirus (CMV) infection resulting in pneumonia and death has occurred following ABECMA administration. Monitor and treat for CMV reactivation in accordance with clinical guidelines. Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with drugs directed against plasma cells. Perform screening for CMV, HBV, hepatitis C virus (HCV), and human immunodeficiency virus (HIV) in accordance with clinical guidelines before collection of cells for manufacturing.

Prolonged Cytopenias: Patients may exhibit prolonged cytopenias following lymphodepleting chemotherapy and ABECMA infusion. In the KarMMa study, 41% of patients (52/127) experienced prolonged Grade 3 or 4 neutropenia and 49% (62/127) experienced prolonged Grade 3 or 4 thrombocytopenia that had not resolved by Month 1 following ABECMA infusion. Rate of prolonged neutropenia was 49% in the 450 x 106 CAR+ T cell dose cohort and 34% in the 300 x 106 CAR+ T cell dose cohort. In 83% (43/52) of patients who recovered from Grade 3 or 4 neutropenia after Month 1, the median time to recovery from ABECMA infusion was 1.9 months. In 65% (40/62) of patients who recovered from Grade 3 or 4 thrombocytopenia, the median time to recovery was 2.1 months. Median time to cytopenia recovery was similar across the 300 and 450 x 106 dose cohort.

Three patients underwent stem cell therapy for hematopoietic reconstitution due to prolonged cytopenia. Two of the three patients died from complications of prolonged cytopenia. Monitor blood counts prior to and after ABECMA infusion. Manage cytopenia with myeloid growth factor and blood product transfusion support according to institutional guidelines.

Hypogammaglobulinemia: Plasma cell aplasia and hypogammaglobulinemia can occur in patients receiving treatment with ABECMA. Hypogammaglobulinemia was reported as an adverse event in 21% (27/127) of patients; laboratory IgG levels fell below 500 mg/dl after infusion in 25% (32/127) of patients treated with ABECMA.

Monitor immunoglobulin levels after treatment with ABECMA and administer IVIG for IgG <400 mg/dl. Manage per local institutional guidelines, including infection precautions and antibiotic or antiviral prophylaxis.

The safety of immunization with live viral vaccines during or following ABECMA treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during ABECMA treatment, and until immune recovery following treatment with ABECMA.

Secondary Malignancies: Patients treated with ABECMA may develop secondary malignancies. Monitor life-long for secondary malignancies. If a secondary malignancy occurs, contact Bristol Myers Squibb at 1-888-805-4555 to obtain instructions on patient samples to collect for testing of secondary malignancy of T cell origin.

Effects on Ability to Drive and Operate Machinery: Due to the potential for neurologic events, including altered mental status or seizures, patients receiving ABECMA are at risk for altered or decreased consciousness or coordination in the 8 weeks following ABECMA infusion. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, during this initial period.

Adverse Reactions: The most common nonlaboratory adverse reactions (incidence greater than or equal to 20%) include CRS, infections – pathogen unspecified, fatigue, musculoskeletal pain, hypogammaglobulinemia, diarrhea, upper respiratory tract infection, nausea, viral infections, encephalopathy, edema, pyrexia, cough, headache, and decreased appetite.