On November 6, 2019 LIDDS AB (publ) reported that it has received approval from authorities in Lithuania to conduct its Phase I study, NZ-DTX-001 (Press release, Lidds, NOV 6, 2019, View Source [SID1234555903]). Previously the phase I study is approved in Sweden and Denmark .

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The aim of the phase I dose escalation clinical trial is to assess the tolerability and safety of intratumoral injections of NanoZolid with docetaxel, a well-established cytostatic used in the treatment of cancer with an estimated global market of over USD 1 billion.

LIDDS enrolled the first patient in spring and further patients are planned to be treated in Q4, 2019.

– This is very exciting as we hope that NanoZolid combined with docetaxel will decrease the tumor size and improve surgery and radiation therapy outcomes. In the Phase I study, LIDDS aims to demonstrate that intratumoral injections with cytostatics are safe and we expect that following this study a wide range of different indications and NanoZolid combinations using chemotherapy drugs will emerge, says Monica Wallter, CEO.

– Our goal is to deliver drugs directly into the cancer tumor and thereby limit the severe side effects for cancer sufferers receiving systemic chemotherapy treatments which affect all cells in the body including the immune system, says Monica Wallter.

NZ-DTX-001 study description:
A phase Ia/Ib, first-in-human, open label, multicenter, dose-escalation and dose-expansion study of a novel NanoZolid-docetaxel depot formulation (NZ-DTX Depot) given as an intratumoral injection in patients with advanced solid tumors.

On November 6, 2019 NewLink Genetics Corporation (NASDAQ:NLNK) reported financial results for the third quarter ended September 30, 2019 and provided an update on corporate activities (Press release, NewLink Genetics, NOV 6, 2019, View Source [SID1234550399]).

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"We are excited about the proposed merger with Lumos Pharma that we announced at the close of the third quarter and continue to advance the process required to close the transaction," commented Brad Powers, General Counsel and member of NewLink’s Office of the CEO. "We believe this merger positions the company to improve therapeutic options for patients with pediatric growth hormone deficiency and other rare and neglected diseases, and to bring greater value to our shareholders."

Eugene Kennedy, MD, Chief Medical Officer and member of NewLink’s Office of the CEO added, "We are also pleased by the FDA’s recent acceptance of the biologic licensing application for priority review of our partnered investigational Ebola vaccine, which we licensed to Merck in 2014. We are encouraged, as well, that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending a conditional marketing authorization for V920 Ebola Zaire vaccine. We believe these actions demonstrate the urgency with which regulatory bodies are addressing this deadly disease in order to help the affected individuals and communities."

Proposed Merger and Related Milestones

On September 30, 2019, NewLink announced its intent to merge with Lumos Pharma, a private clinical-stage biopharmaceutical company targeting rare and neglected diseases. Under the terms of the merger agreement, Lumos and NewLink stockholders will each own approximately 50% of the combined company which will be renamed "Lumos Pharma" at the close of the transaction. Rick Hawkins, current CEO of Lumos Pharma, is expected to become CEO of the combined company. The proposed merger has been approved by the Boards of both companies and the major stockholders of Lumos Pharma and NewLink’s largest stockholder has entered into a support agreement with NewLink to vote in favor of various proposals relating to the Merger.

The combined company would focus initially on the development of Lumos Pharma’s lead product candidate, LUM-201 (ibutamoren), an oral growth hormone (GH) secretagogue targeting pediatric growth hormone deficiency (PGHD) and other rare endocrine disorders. If approved, LUM-201 has the potential to be the first orally administered growth hormone stimulating therapy for PGHD, a well-established and sizable market where daily recombinant human growth hormone injections represent current standard-of-care therapy.

The initiation of a Phase 2b trial for LUM-201 in a subset of PGHD patients meeting certain predictive enrichment markers (PEMs) is anticipated in mid-2020. The combined company is expected to have resources sufficient to support clinical development through the readout of this planned Phase 2b trial. Additional target indications are being evaluated for LUM-201 clinical development, including Turner Syndrome and children born Small for Gestational Age (SGA).

NewLink will file a proxy statement with the Securities and Exchange Commission (SEC) providing additional information about the proposed merger. The transaction is expected to close in the first quarter of 2020, subject to the satisfaction of customary closing conditions, including approval of certain proposals by the stockholders of NewLink.

Additional Updates

The combined company may receive additional, non-dilutive financing should the U.S. Food and Drug Administration (FDA) approve NewLink’s Ebola vaccine V920 partnered with Merck Sharp & Dohme Corp. (Merck). On September 17, 2019, Merck announced that the FDA has accepted its biologics license application (BLA) and granted priority review for the investigational Ebola vaccine V920 and the Prescription Drug User Fee Act (PDUFA), or target action date, is set for March 14, 2020. If the vaccine receives approval by the FDA, a priority review voucher will be issued, in which the Company owns a substantial interest and which the Company plans to monetize.

On October 18, 2019, the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use(CHMP) adopted a positive opinion recommending a conditional marketing authorization for investigational V920 Ebola Zaire vaccine (rVSV∆G-ZEBOV-GP), as confirmed by our partner, Merck (NYSE:MRK). This Committee’s recommendation will now be reviewed by the European Commission (EC) for a centralized marketing authorization of the vaccine (brand name ERVEBO) across EU member countries.

Updated Phase 1b results for indoximod for the cohort of pediatric patients with newly diagnosed treatment-naïve diffuse intrinsic pontine glioma (DIPG) has been accepted for presentation at the upcoming ESMO (Free ESMO Whitepaper) Immuno-Oncology Congress 2019, 11-14 December 2019, Geneva, Switzerland. NewLink expects to continue to evaluate its oncology portfolio to determine value creation opportunities.

Financial Results for the Three-Month Period Ended September 30, 2019

Restructuring: On September 30, 2019, NewLink Genetics announced it had adopted a restructuring plan to reduce its headcount by approximately 60% to align with future priorities and to conserve resources. In conjunction with the restructuring and the departures of our former CEO and President, the company recorded restructuring and severance charges of $4.5 million during the third quarter.

Cash Position: NewLink Genetics ended the quarter on September 30, 2019, with cash and cash equivalents totaling $98.5 million compared to $120.7 millionDecember 31, 2018.

R&D Expenses: Research and development expenses for the third quarter of 2019 were $7.0 million, a decrease of $546,000 from $7.6 million for the same period in 2018. The decrease was primarily due to reductions of $1.1 million in personnel-related and stock compensation expense, $255,000 in contract research and manufacturing spend, and $333,000 in legal and consulting and supplies expense, offset by increases of $1.1 million in restructuring costs and $87,000 in clinical trial and licensing expense.

G&A Expenses: General and administrative expenses in the third quarter of 2019 were $8.3 million, an increase of $691,000 from $7.6 million for the same period in 2018. The increase was due primarily to increases of $2.0 million in restructuring and severance expense, and $1.2 million in legal and consulting expense, offset by decreases of $1.7 million in stock compensation expense, $431,000 in personnel-related expense, and $353,000 in supplies.

Net Loss: NewLink Genetics reported a net loss of $14.5 million or ($0.39) per diluted share for the third quarter of 2019 compared to a net loss of $7.4 million or ($0.20) per diluted share for the third quarter of 2018.

NewLink Genetics ended Q3 2019 with 37,314,076 shares outstanding.

Conference Call and Webcast Details

The Company has scheduled a conference call and webcast for 8:30 a.m. ET today to discuss its financial results and to give an update on clinical and business development activities.

Access to the live conference call is available five minutes prior to the start of the call by dialing (855) 469-0612 (U.S.) or (484) 756-4268 (international). The conference call will be webcast live and a link to the webcast can be accessed through the NewLink Genetics website at www.NewLinkGenetics.com in the "Investors & Media" section under "Events and Presentations" or through the link View Source To ensure a timely connection, it is recommended that users register at least 10 minutes prior to the scheduled webcast. A replay of the call will be available approximately two hours after the completion of the call and can be accessed by dialing (855) 859-2056 (U.S.) or (404) 537-3406 (international) and using the passcode 3794399. The replay will be available for two weeks from the date of the call.

On November 6, 2019 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium") reported that new findings from its pivotal Phase 3 SIERRA trial for Iomab-B (Iodine-131 apamistamab) that support its Iomab-ACT program for lymphodepletion for CAR-T and adoptive cell therapies has been accepted for presentation at the 2019 American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting that is being held December 7-10, 2019 in Orlando, FL (Press release, Actinium Pharmaceuticals, NOV 6, 2019, View Source [SID1234550431]). Lymphodepletion is a necessary step that creates space for the CAR-T cells to be infused and promotes expansion of cells in vivo by creating a favorable homeostatic cytokine environment. Actinium is advancing the development of low dose Iomab-B (Iodine-131 apamistamab), a CD45 targeting antibody radiation-conjugate (ARC), as an alternative to today’s standard practice of chemotherapy-based lymphodepletion regimens like fludarabine/cyclophosphamide (Flu/Cy), which have been implicated in CAR-T toxicities including cytokine release syndrome (CRS) and neurotoxicity.

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Title: Sierra Clinical Trial Dosimetry Results Support Low Dose Anti-CD45 Iodine (131I) Apamistamab [Iomab-B] for Targeted Lymphodepletion Prior to Adoptive Cell Therapy

An analysis was performed on blood samples from 57 patients enrolled in the ongoing pivotal Phase 3 SIERRA trial for Iomab-B to demonstrate the effectiveness of low dose Iomab-B as a modality for targeted transient lymphodepletion. On the SIERRA trial, patients receive a low dosimetry dose of Iomab-B (median dose of 10 mCi with a range of 7-20 mCi) in an outpatient setting per study protocol. The analysis presented in the poster evaluated blood samples at various time points including pre-dosimetric infusion, post-dosimetric infusion, day 1 post-dosimetric infusion, and pre-therapeutic infusion (range 6-14 days post-dosimetry) to assess the impact of low dose Iomab-B on immune cell lymphodepletion and its anti-tumor effect on circulating blasts, as well as to determine its clearance profile from circulation.

Key Highlights:

– A significant but transient reduction in lymphocytes and white blood cells was observed compared to pre-dosimetry infusion levels
– 85% reduction in lymphocytes was observed at the post-dosimetry infusion time point, a 67% decrease at day 1 post-dosimetric infusion, and a 43% decrease one week later just prior to the Iomab-B therapeutic infusion
– 35% reduction in peripheral leukemic blasts was observed at the post-dosimetry infusion time point, suggesting a rapid anti-leukemic effect with single-agent Iomab-B consistent with findings from SIERRA presented at ASCO (Free ASCO Whitepaper) 2019
– The levels of platelets, red blood cells, and neutrophils were unchanged between pre-infusion and post-dosimetry infusion, potentially reflecting the comparatively lower surface antigen levels of CD45 on these cell types
– Based on an analysis of 25 treated patients, a non-myeloablative dose of 75 mCi has been proposed as a starting dose for human clinical testing
– Analysis of the proposed 75 mCi dose of Iomab-B would be sufficiently cleared in 136 hours (5.7 days) to allow for CAR-T administration

Poster Details:

Publication Number: 1958
Session Name: 704. Immunotherapies: Poster I
Date: Saturday, December 7, 2019
Presentation Time: 5:30 PM – 7:30 PM
Location: Orange County Convention Center, Hall B

Dale Ludwig, Ph.D., Actinium’s Chief Scientific Officer, said, "These promising findings from the analysis of clinical data from the SIERRA trial confirm our excitement and support the potential of our Iomab-ACT program as a chemotherapy-free alternative for lymphodepletion. While significant efforts have gone towards innovating CAR-T and cellular therapies, there has been little innovation in the lymphodepletion regimens that they rely on. These results show that the multi-modal mechanism of our CD45 targeting ARC can selectively deplete immune cells and exert an anti-leukemic effect while sparing red blood cells and platelets through a single-dose outpatient administration. It is exciting to see human clinical data produce these promising results and demonstrate that our Iomab-ACT program will fit well within the vein-to-vein time of CAR-T. We look forward to beginning a first-in-man clinical trial that will explore our Iomab-ACT program in conjunction with a CAR-T therapy and we have great confidence in continued positive results."

About the Iomab-ACT program

Iomab-ACT is a lower dose of Actinium’s lead program Iomab-B, which has been studied in over 300 patients and is currently being investigated in a pivotal Phase 3 trial for targeted conditioning prior to a Bone Marrow Transplant (BMT). Iomab-ACT targets CD45, an antigen expressed on many of the cells that are relevant to CAR-T including lymphocytes, macrophages and regulatory T-cells and that have been associated with CAR-T challenges such as durability of response, cytokine release syndrome (CRS) and neurotoxicity. Actinium has generated preclinical data that targeted lymphodepletion via Iomab-ACT has the potential to improve tumor control, selectively deplete necessary cells and be highly differentiated in terms of tolerability compared to chemotherapy-based lymphodepletion regimens, namely fludarabine/cyclophosphamide (Flu/Cy). The Iomab-ACT program may enable lymphodepletion through a single-dose outpatient administration versus Flu/Cy or other chemo-based lymphodepletion regimens that require multiple infusions in an inpatient setting over several days.

On November 6, 2019 bluebird bio, Inc. (Nasdaq: BLUE) reported that new and updated data from its investigational gene and cell therapy programs for multiple myeloma, sickle cell disease (SCD) and transfusion-dependent β-thalassemia (TDT) will be presented at the 61stAmerican Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in Orlando, Florida, December 7 – 10 (Press release, bluebird bio, NOV 6, 2019, View Source [SID1234550447]).

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bluebird bio will present updated safety and efficacy data from the ongoing Phase 1 clinical study (CRB-402) of bb21217. bb21217 is an investigational BCMA-targeted chimeric antigen receptor (CAR) T cell therapy being studied, in partnership with Celgene, in patients with relapsed/refractory multiple myeloma (RRMM).

In addition, data from clinical studies of LentiGlobin gene therapy for β-thalassemia, including results up to 61 months from the long-term follow-up study (LTF-303) and updated results from the completed Phase 1/2 Northstar (HGB-204) study, will be presented at ASH (Free ASH Whitepaper). The company will also present new data from the ongoing Phase 3 Northstar-2 (HGB-207) study in pediatric, adolescent and adult patients who do not have a β0/β0 genotype and from the ongoing Phase 3 Northstar-3 (HGB-212) study in pediatric, adolescent and adult patients who have β0/β0 genotype or an IVS-I-110 mutation at both alleles of the β-globin gene.

New data from the company’s Phase 1/2 HGB-206 study of LentiGlobin gene therapy for SCD will include additional patients treated in the study and updated data for those previously reported. The company will also present data from exploratory assays designed to assess the relationship between drug product characteristics and red blood cell physiology in patients treated with LentiGlobin for SCD.

Updated Data from Ongoing Phase 1 Clinical Study (CRB-402) of bb21217

Updated Results from an Ongoing Phase 1 Clinical Study of bb21217 Anti-BCMA CAR T Cell Therapy
Presenting Author: Jesus G. Berdeja, M.D., Sarah Cannon Center for Blood Cancers, Nashville, Tenn.
Date & Time: Oral #927, Monday, December 9, 2019, 6:45 p.m. ET

bb21217, an investigational BCMA-targeted CAR T cell therapy being developed in partnership with Celgene, is one of bluebird bio’s lead oncology programs. bb21217 uses the idecabtagene vicleucel CAR molecule (formerly referred to as bb2121) and is manufactured with a process intended to increase the in vivo persistence of CAR T cells.

This presentation will include updated data from the Phase 1 CRB-402 study, the first-in-human study of bb21217 in patients with RRMM, designed to assess the primary endpoint of safety as well as other pre-defined endpoints including efficacy and pharmacokinetics measurements. CRB-402 is a two-part (dose escalation and dose expansion), open-label, multi-site Phase 1 study of bb21217 in adults with RRMM with a projected final enrollment of 74 patients.

Data in the abstract include results as of the data cutoff date of April 20, 2019 for 22 patients who have received bb21217 at three dose levels (12 at 150 x 106 CAR+ T cells; six at 300 x 106 CAR+ T cells; and four at 450 x 106 CAR+ T cells). These patients had a median of seven prior lines of therapy (min-max: 4 – 17 lines), 18 patients had a prior autologous stem cell transplant, 19 patients received daratumumab and 13 patients received prior treatment with bortezomib, lenalidomide, carfilzomib, pomalidomide and daratumumab.

As of the data cutoff, the adverse events observed were consistent with known toxicities of CAR T therapies. Thirteen of 22 patients developed cytokine release syndrome (CRS); five Grade 1, seven Grade 2, and one Grade 3 case. All 13 patients responded to supportive care, tocilizumab and/or corticosteroids. Five of 22 patients developed neurotoxicity; one Grade 1, two Grade 2, one Grade 3 (vertigo/dizziness), and one Grade 4 (encephalopathy, previously reported). For the one patient previously reported with Grade 4 neurotoxicity, Grade 3 CRS was also reported, and both have resolved.

Eighteen patients were evaluable for clinical response with > two months of follow-up or progressive disease within two months. Eighty-three percent (n=15/18) of evaluable patients demonstrated clinical response per the International Myeloma Working Group Uniform Response Criteria for multiple myeloma. As of the data cutoff, with the median follow-up after bb21217 infusion of five months (min-max: <1 – 18 months), nine patients remained in response, including two patients with ongoing response at 15 and 18 months.

Evidence of myeloma in the bone marrow, known as minimal residual disease, was undetectable by next-generation sequencing at a sensitivity level of 10-5 or better in all responders who had evaluable bone marrow samples (n=10) at Month 1. CAR T cell persistence was observed in six of eight patients evaluable at six months and in two of two patients evaluable at 12 months.

This study is ongoing to evaluate the potential safety and efficacy of treatment with bb21217, and updated results, including early clinical and CAR T cell persistence data, will be shared at the ASH (Free ASH Whitepaper) conference.

Multiple Myeloma Presentations at ASH (Free ASH Whitepaper)

Markers of Initial and Long-Term Responses to Idecabtagene Vicleucel (Ide-Cel; bb2121) in the CRB-401 Study in Relapsed/Refractory Multiple Myeloma
Presenting Author: Ethan G. Thompson, Ph.D., Celgene, Seattle, Wash.
Date & Time: Poster #4328, Monday, December 9, 2019, 6:00 – 8:00 p.m. ET

Updated Results from an Ongoing Phase 1 Clinical Study of bb21217 anti-BCMA CAR T Cell Therapy
Presenting Author: Jesus G. Berdeja, M.D., Sarah Cannon Center for Blood Cancers, Nashville, Tenn.
Date & Time: Oral #927, Monday, December 9, 2019, 6:45 p.m. ET

SCD Presentations at ASH (Free ASH Whitepaper)

The Relationships Between Target Gene Transduction, Engraftment of HSCs and RBC Physiology in Sickle Cell Disease Gene Therapy
Presenting Author: Melissa Bonner, Ph.D., bluebird bio, Cambridge, Mass.
Date & Time: Oral #206, Saturday, December 7, 2019, 2:15 p.m.

Exploring the Drivers of Clinical Benefit in Initial Patients Treated in the HGB-206 Study of LentiGlobin for Sickle Cell Disease (SCD) Gene Therapy
Presenting Author: Mark Walters, M.D., Benioff Children’s Hospital, Oakland, Calif.
Date & Time: Poster #2061, Saturday, December 7, 2019, 5:30 – 7:30 p.m.

Resolution of Sickle Cell Disease Manifestations in Patients Treated with LentiGlobin Gene Therapy: Updated Results from the Phase 1/2 HGB-206 Group C Study
Presenting Author: Julie Kanter, M.D., University of Alabama at Birmingham, Birmingham, Ala.
Date & Time: Poster #990, Saturday, December 7, 2019, 5:30 – 7:30 p.m.

TDT Presentations at ASH (Free ASH Whitepaper)

Clinical Outcomes after Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Transfusion-Dependent β-Thalassemia Treated at the Bambino Gesù Children’s Hospital, Rome, Italy
Presenting Author: Pietro Merli, M.D., IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy
Date & Time: Poster #969, Saturday, December 7, 2019, 5:30 – 7:30 p.m.

Northstar-3: Interim Results from a Phase 3 Study Evaluating LentiGlobin Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia and Either a β0 or IVS-I-110 Mutation at Both Alleles of the HBB Gene
Presenting Author: Ashutosh Lal, M.D., UCSF Benioff Children’s Hospital, Oakland, Calif.
Date & Time: Oral #815, Monday, December 9, 2019, 5:30 p.m.

Northstar-2: Updated Safety and Efficacy Analysis of LentiGlobin Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia and Non-β0/β0Genotypes
Presenting Author: Alexis Thompson, M.D., MPH, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, Ill.
Date & Time: Poster #3543, Monday, December 9, 2019, 6:00 – 8:00 p.m.

Long-Term Clinical Outcomes of LentiGlobin Gene Therapy for Transfusion-Dependent β-Thalassemia in the Northstar (HGB-204) Study
Presenting Author: Janet Kwiatkowski, M.D., MSCE, Children’s Hospital of Philadelphia, Philadelphia, Pa.
Date & Time: Poster #4628, Monday, December 9, 2019, 6:00 – 8:00 p.m.

Routine Management, Healthcare Resource Use and Patient/Caregiver-Reported Outcomes of Patients with Transfusion-Dependent β-Thalassaemia in the United Kingdom: A Mixed Methods Observational Study
Presenting Author: Farrukh Shah, MBBS, FRCP, FRCPath, M.D., Whittington Hospital, London, U.K.
Date & Time: Poster #3550, Monday, December 9, 2019, 6:00 – 8:00 p.m.

SCD and TDT Presentation at ASH (Free ASH Whitepaper)

Results from the Completed HGB-205 Trial of LentiGlobin for β-Thalassemia and LentiGlobin for Sickle Cell Disease Gene Therapy
Presenting Author: Elisa Magrin, Ph.D., Necker Children’s Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
Date & Time: Poster #3358, Sunday, December 8, 2019, 6:00 – 8:00 p.m.

Abstracts outlining bluebird bio’s accepted data at ASH (Free ASH Whitepaper) will be available on the ASH (Free ASH Whitepaper) conference website at 9 a.m. EST today.

About ide-cel and bb21217 for Multiple Myeloma

bluebird bio’s lead oncology programs, idecabtagene vicleucel (ide-cel, formerly referred to as bb2121) and bb21217, are investigational BCMA-targeted chimeric antigen receptor (CAR) T cell therapies being studied in a broad clinical development program for patients with multiple myeloma. ide-cel and bb21217 are being developed in partnership with Celgene.

KarMMa is a registration-enabling, open-label, single-arm, multi-center Phase 2 study evaluating the efficacy and safety of ide-cel in patients with relapsed/refractory multiple myeloma. In November 2018, bluebird bio announced completion of enrollment in the trial. ide-cel was granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration and Priority Medicines (PRIME) eligibility by the European Medicines Agency in November 2017 based on preliminary clinical data from the Phase 1 CRB-401 study.

bluebird bio’s clinical development program for bb21217 includes the ongoing Phase 1 CRB-402 study. CRB-402 is the first-in-human study of bb21217 in patients with RRMM, designed to assess safety, pharmacokinetics, efficacy and duration of effect. CRB-402 is a two-part (dose escalation and dose expansion), open-label, multi-site Phase 1 study of bb21217 in adults with RRMM with a projected final enrollment of 74 patients. For more information visit: clinicaltrials.gov using identifier NCT03274219.

ide-cel and bb21217 are not approved for any indication in any geography.

About LentiGlobin for Sickle Cell Disease

LentiGlobin for sickle cell disease is an investigational gene therapy being studied as a potential treatment for SCD. bluebird bio’s clinical development program for LentiGlobin for SCD includes the ongoing Phase 1/2 HGB-206 study.

SCD is a serious, progressive and debilitating genetic disease caused by a mutation in the β-globin gene that leads to the production of abnormal sickle hemoglobin (HbS), causing red blood cells (RBCs) to become sickled and fragile, resulting in chronic hemolytic anemia, vasculopathy and painful vaso-occlusive events (VOEs). For adults and children living with SCD, this means unpredictable episodes of excruciating pain due to vaso-occlusion as well as other acute complications—such as acute chest syndrome (ACS), stroke, and infections, which can contribute to early mortality in these patients.

LentiGlobin for SCD received Orphan Medicinal Product designation from the European Commission for the treatment of SCD.

The U.S. Food and Drug Administration granted Orphan Drug status and Regenerative Medicine Advanced Therapy designation for LentiGlobin for the treatment of SCD.

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 LentiGlobin for SCD. For more information visit: View Source or clinicaltrials.gov and use identifier NCT02633943 for LTF-303.

About LentiGlobin for β-Thalassemia

The European Commission granted conditional marketing authorization for LentiGlobin for TDT, to be marketed as ZYNTEGLO (autologous CD34+ cells encoding βA-T87Q-globin gene) 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.

TDT is a severe genetic disease caused by mutations in the β-globin gene that result in reduced or absent hemoglobin (Hb). In order to survive, people with TDT maintain Hb levels through lifelong chronic blood transfusions. These transfusions carry the risk of progressive multi-organ damage due to unavoidable iron overload.

LentiGlobin 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-hemoglobin, at levels that may eliminate or significantly reduce the need for transfusions.

Non-serious adverse events (AEs) observed during clinical studies that were attributed to LentiGlobin for TDT were hot flush, dyspnoea, abdominal pain, pain in extremities and non-cardiac chest pain. One serious adverse event (SAE) of thrombocytopenia was considered possibly related to LentiGlobin for TDT.

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.

The conditional marketing authorization for ZYNTEGLO is only valid in the 28 member states of the EU as well as Iceland, Liechtenstein and Norway. For details, please see the Summary of Product Characteristics (SmPC).

The U.S. Food and Drug Administration granted LentiGlobin for β-thalassemia Orphan Drug status and Breakthrough Therapy designation for the treatment of TDT.

LentiGlobin for β-thalassemia continues to be evaluated in the ongoing Phase 3 Northstar-2 and Northstar-3 studies. For more information about the ongoing clinical studies, visit www.northstarclinicalstudies.com or clinicaltrials.gov and use identifier NCT02906202 for Northstar-2 (HGB-207), NCT03207009 for Northstar-3 (HGB-212).

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 LentiGlobin for TDT. For more information visit: View Source or clinicaltrials.gov and use identifier NCT02633943 for LTF-303.

On November 6, 2019 Genmab reported that Interim Report for the First Nine Months Ended September 30, 2019 (Press release, Genmab, NOV 6, 2019, View Source [SID1234550465]).

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Highlights

Completion of public offering and listing of American Depository Shares (ADSs) on Nasdaq Global Select Market under the symbol "GMAB." Total gross proceeds from the issuance of new shares amounted to USD 582 million (DKK 3,873 million) with a corresponding increase in share capital of 3,277,500 ordinary shares or 32,775,000 ADSs
Positive data reported by Novartis for the Phase III ASCLEPIOS I & II studies of subcutaneous ofatumumab in relapsing multiple sclerosis (RMS)
DARZALEX (daratumumab) approved in the U.S. in combination with bortezomib, thalidomide and dexamethasone (VTd) and in Japan in combination with bortezomib, melphalan and prednisone (VMP) in various multiple myeloma frontline settings
Positive topline results for daratumumab in both the Phase III CANDOR and Phase II GRIFFIN studies in various multiple myeloma settings
Biologics License Application (BLA) submitted to U.S. Food and Drug Administration (U.S. FDA) for the subcutaneous formulation of daratumumab; standard review received. An extension of marketing authorization for this formulation was also submitted to the European Medicines Agency (EMA)
DARZALEX net sales increased 50% compared to the first nine months of 2018 to USD 2,168 million, resulting in royalty income of DKK 2,033 million

Genmab is improving its 2019 financial guidance mainly due to positive foreign exchange movements between the USD and DKK resulting in increased milestone income and royalties on sales of DARZALEX
"Genmab made excellent progress across many areas of the business during the third quarter of 2019. Of key significance was the completion of our public offering of American Depositary Shares and listing on the Nasdaq Global Select Market in the U.S. Genmab’s status as a dual listed company both increases our visibility as an innovation powerhouse and provides additional support for the development of our exciting pipeline of antibody product candidates," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. "Over the past three months advances to this pipeline included positive data readouts for ofatumumab in relapsing multiple sclerosis and daratumumab in multiple myeloma, regulatory submissions for daratumumab and teprotumumab and additional approvals for daratumumab in the U.S. and Asia. In addition, we entered into new strategic collaborations with companies such as Tempus and BliNK Biomedical, which will allow us to expand our pipeline in new directions as Genmab continues to move towards our goal of transforming cancer treatment."

Financial Performance First Nine Months of 2019

Revenue was DKK 2,405 million in the first nine months of 2019 compared to DKK 1,789 million in the first nine months of 2018. The increase of DKK 616 million, or 34%, was mainly driven by higher DARZALEX royalties and reimbursement income from our collaborations with Seattle Genetics and BioNTech, partly offset by the one-time payment from Novartis of USD 50 million (DKK 304 million) during the first nine months of 2018 for lost potential milestones and royalties following announcement of Novartis’ intention to transition Arzerra (ofatumumab) to limited availability via compassionate use programs for chronic lymphocytic leukemia (CLL) in non-U.S. markets.
Net sales of DARZALEX by Janssen were USD 2,168 million in the first nine months of 2019 compared to USD 1,441 million in the first nine months of 2018, an increase of USD 727 million, or 50%.
Operating expenses were DKK 1,943 million in the first nine months of 2019 compared to DKK 1,130 million in the first nine months of 2018. The increase of DKK 813 million, or 72%, was driven by the advancement of tisotumab vedotin and enapotamab vedotin, additional investments in our product pipeline, and the increase in new employees to support the expansion of our product pipeline.
Operating income was DKK 462 million in the first nine months of 2019 compared to DKK 659 million in the first nine months of 2018. As anticipated, the decrease of DKK 197 million, or 30%, was driven primarily by increased operating expenses and the one-time payment from Novartis in 2018.
Outlook
Genmab is improving its 2019 financial guidance published on August 14, 2019 mainly due to positive foreign exchange movements between the USD and DKK resulting in increased milestone income and royalties on sales of DARZALEX.

MDKK Revised Guidance Previous
Guidance
Revenue 5,100 4,800
Operating expenses (2,750) (2,750)
Operating income 2,350 2,050
Conference Call
Genmab will hold a conference call in English to discuss the results for the first nine months of 2019 today, Wednesday, November 6, at 6:00 pm CET, 5:00 pm GMT or 12:00 pm EST. To join the call dial
+1 631 510 7495 (U.S. participants) or +44 2071 928000 (international participants) and provide conference code 7996106.

A live and archived webcast of the call and relevant slides will be available at www.genmab.com.