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.

On November 6, 2019 Nektar Therapeutics (Nasdaq: NKTR) reported its financial results for the third quarter ended September 30, 2019 (Press release, Nektar Therapeutics, NOV 6, 2019, View Source [SID1234550481]).

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Cash and investments in marketable securities at September 30, 2019 were approximately $1.7 billion as compared to $1.9 billion at December 31, 2018.

"We continue to make steady progress with our diverse portfolio of immuno-oncology and immunology programs," said Howard W. Robin, President and CEO of Nektar. "With our partner Bristol-Myers Squibb, we are conducting registrational trials evaluating the combination of bempegaldesleukin with nivolumab in melanoma, urothelial cancer and renal cell carcinoma. We are also working collaboratively with BMS to finalize the next set of registrational studies. This weekend at the SITC (Free SITC Whitepaper) Annual Meeting, we are excited to present an 18-month follow-up for patients with metastatic melanoma enrolled in our PIVOT-02 study. This follows the recent announcement of our Breakthrough Therapy Designation for the doublet which was granted by FDA in August for patients with previously untreated metastatic melanoma. For NKTR-358, we now have three separate Phase 1b clinical trials ongoing in lupus, psoriasis and atopic dermatitis with our partner Eli Lilly, with plans to add an additional autoimmune indication to the development program in 2020. And importantly, we initiated our first clinical trial for NKTR-255, our novel IL-15 agonist, in patients with non-Hodgkin lymphoma and multiple myeloma."

Revenue in the third quarter of 2019 was $29.2 million as compared to $27.8 million in the third quarter of 2018. Year-to-date revenue for 2019 was $80.8 million as compared to $1.15 billion in the first nine months of 2018. Revenue was higher in the third quarter of 2019 as compared to the same period in 2018 primarily due to non-cash royalty revenue and an increase in product sales. Revenue was lower in the first nine months of 2019 as compared to the same period in 2018 primarily because of the recognition of $1.06 billion of license revenue from the Bristol-Myers Squibb collaboration agreement in the second quarter of 2018.

Total operating costs and expenses in the third quarter of 2019 were $128.0 million as compared to $126.4 million in the third quarter of 2018. Total operating costs and expenses in the first nine months of 2019 were $411.2 million as compared to $365.3 million in the same period of 2018. Total operating costs and expenses increased marginally in the third quarter of 2019 as compared to the third quarter of 2018 due to a decrease in research and development (R&D) expense, offset by an increase in general and administrative (G&A) expense. Total operating costs and expenses increased in the first nine months of 2019 as compared to the same period in 2018 due to increases in both R&D and G&A expense.

R&D expense in the third quarter of 2019 was $99.0 million as compared to $102.9 million for the third quarter of 2018. For the first nine months of 2019, R&D expense was $324.2 million as compared to $290.7 million in the first nine months of 2018. R&D expense was lower in the third quarter of 2019 as compared to the same period in 2018 due to decreased expense for the bempegaldesleukin program. R&D expense was higher in the first nine months as compared to the same period in 2018 primarily because of expenses for our pipeline programs, including the continued development of bempegaldesleukin in Phase 2 and registrational studies and related manufacturing costs, costs related to Phase 1 clinical studies of NKTR-358 and IND-enabling activities for NKTR-255.

G&A expense was $24.0 million in the third quarter of 2019 as compared to $18.7 million in the third quarter of 2018. G&A expense in the first nine months of 2019 was $71.6 million as compared to $57.7 million in the first nine months of 2018. G&A expense was higher in the third quarter and first nine months of 2019 as compared to the same periods in 2018 due to costs related to commercialization readiness activities for NKTR-181 and bempegaldesleukin, and increased non-cash stock-based compensation.

Net loss in the third quarter of 2019 was $98.8 million or $0.56 basic and diluted loss per share as compared to net loss of $96.1 million or $0.56 basic and diluted loss per share in the third quarter of 2018. Net loss in the first nine months of 2019 was $327.2 million or $1.87 basic and diluted loss per share as compared to net income of $779.5 million or $4.34 diluted income per share in the first nine months of 2018.

Third Quarter 2019 and Recent Business Highlights

·In September, Nektar presented clinical data from its PIVOT-02 study for bempegaldesleukin in combination with Opdivo (nivolumab) at the 2019 CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper) demonstrating the promising clinical activity of the combination in patients with advanced or metastatic triple-negative breast cancer, particularly in patients with PD-L1 negative baseline tumors.

·In October, Nektar announced that its partner Eli Lilly initiated two Phase 1b studies of NKTR-358, a novel T regulatory (Treg) cell stimulator, one in patients with psoriasis and one in patients with atopic dermatitis. NKTR-358 is designed to treat autoimmune and inflammatory conditions by correcting the immune system imbalance that results from reduced numbers and impaired function of immune regulating Treg cells.

·In October, Nektar announced the initiation of a first-in-human, Phase 1 clinical study evaluating NKTR-255, an interleukin-15 (IL-15) receptor agonist, as monotherapy for patients with relapsed or refractory non-Hodgkin lymphoma or multiple myeloma (MM). The study will also combine NKTR-255 with multiple targeted antibodies that function through an antibody-dependent cell-mediated cytotoxicity mechanism to evaluate the safety and efficacy in adults with relapsed or refractory MM.

The company also announced upcoming presentations at the following scientific congresses:

2019 Society for Immunotherapy and Cancer (SITC) (Free SITC Whitepaper) Annual Meeting, National Harbor, MD:

·Oral Presentation: "Clinical activity of BEMPEG plus NIVO in previously untreated patients with metastatic melanoma: updated results from the phase 1/2 PIVOT-02 study"
oPresenter: Dr. Adi Diab, MD Anderson Cancer Center
oSession: Concurrent Session 310: Combination Phase 1-2 Clinical Trials
oDate: Saturday, November 9, 2019, 5:15 p.m. – 5:30 p.m. Eastern Standard Time

·Poster: "NKTR-255, a polymer-conjugated IL-15 receptor agonist, enhances efficacy of therapeutic monoclonal antibodies with ADCC activity in solid tumor models", Kivimäe, S., et al.
oSession Date and Time: Friday, November 8, 2019, 7:00 a.m. – 8:00 p.m. Eastern Standard Time

·Poster: "Bempegaldesleukin in combination with local radiation and systemic checkpoint blockade induces a robust systemic anti-tumor immunity", Pieper, A., et al.
oSession Date and Time: Friday, November 8, 2019, 7:00 a.m. – 8:00 p.m. Eastern Standard Time

·Poster: "Characterization and comparison of NKTR-255, a polymer-conjugated IL-15 versus IL-15 superagonist", Miyazaki, T., et al.
oSession Date and Time: Saturday, November 9, 2019, 7:00 a.m. – 8:00 p.m. Eastern Standard Time

·Trials in Progress Poster: "A multicenter, open-label, exploratory platform study to evaluate biomarkers and immunotherapy combinations for the treatment of patients with metastatic castration-resistant prostate cancer (PORTER)", Nissola, L., et al.
oSession Date and Time: Friday, November 8, 2019, 7:00 a.m. – 8:00 p.m. Eastern Standard Time

ACR 2019 American College of Rheumatology Annual Meeting, Atlanta, GA:

·Poster: "Selective induction of functional regulatory T-cells in healthy volunteers by NKTR-358, a novel IL-2 conjugate Treg stimulator, in development for the treatment of autoimmune diseases", Fanton, C., et al.
oSession: T Cell Biology & Targets in Autoimmune & Inflammatory Disease Poster
oDate: Sunday, November 10, 2019, 9:00 a.m. – 11:00 a.m. Eastern Standard Time

The Promise of Interleukin-2 Therapy 2019, Paris, France:

·Presentation: "NKTR-358: A polymer-conjugated IL-2 that drives the selective expansion of endogenous Tregs for the treatment of autoimmune diseases"
oPresenter: Christine Fanton, Ph.D., Nektar Therapeutics
oSession: Session V.a – Novel IL-2s
oDate: Friday, November 15, 2019, 2:00 p.m. Central European Time

·Presentation: "Bempegaldesleukin: A polymer-conjugated IL-2 prodrug for multiple immune oncology applications"
oPresenter: Loui Madakamutil, Ph.D., Nektar Therapeutics
oSession: Session VI – IL-2 in cancer therapy
oDate: Friday, November 15, 2019, 4:30 p.m. Central European Time

11th Annual PEGs Europe, Lisbon, Portugal:

·Presentation: "TLR Agonist NKTR-262 Immunotherapy Combination with Bempegaldesleukin (NKTR-214) Harnessing Innate and Adaptive Immune System for the Treatment of Solid Tumors"
oPresenter: Saul Kivimäe, Ph.D., Nektar Therapeutics
oSession: Reprogramming the Microenvironment/The Innate Immune System/Glyco-immune Checkpoints
oDate: Tuesday, November 19, 2019, 5:30 p.m. Western European Time

·Presentation: "NKTR-255: A Polymer-Conjugated IL-15 that Enhances CAR T Efficacy in Murine Models"
oPresenter: Loui Madakamutil, Ph.D., Nektar Therapeutics
oSession: TILs and Gamma Delta Therapy
oDate: Thursday, November 21, 2019, 11:15 a.m. Western European Time

Melanoma Bridge 2019, Naples, Italy:

·Presentation: "Clinical activity of BEMPEG plus NIVO in previously untreated patients with metastatic melanoma: updated results from the phase 1/2 PIVOT-02 study"- [Encore Presentation]
oPresenter: Igor Puzanov, M.D., Roswell Park Comprehensive Cancer Center, Melanoma Bridge Co-chair
oSession: Emergent Strategies Session
oDate: Saturday, December 7, 2019, 12:00 p.m. – 12:15 p.m. Central European Time

61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition, Orlando, FL:

·Poster: "Combination of NKTR-255, a Polymer Conjugated Human IL-15, with CD19 CAR T Cell Immunotherapy in a Preclinical Lymphoma Model", Chou, C., et al.
oSession: 625. Lymphoma: Pre-Clinical—Chemotherapy and Biologic Agents: Poster II
oDate: Sunday, December 8, 2019, 6:00 p.m. – 8:00 p.m. Eastern Standard Time

·Poster: "Restoring Innate and Adaptive Immune Repertoire in Multiple Myeloma for Therapeutic Application", Fernandez, R., et al.
oSession: 652. Myeloma: Pathophysiology and Pre-Clinical Studies, Excluding Therapy: Poster III
oDate: Monday, December 9, 2019, 6:00 p.m. – 8:00 p.m. Eastern Standard Time

·Trials in Progress Poster: "A Phase 1, Open-Label, Multi-Center, Dose Escalation and Dose Expansion Study of NKTR-255 As a Single Agent in Relapsed or Refractory Hematologic Malignancies and in Combination with Daratumumab As a Salvage Regimen for Multiple Myeloma", Shah, N. et al.
oSession: 704. Immunotherapies: Poster III
oDate: Monday, December 9, 2019, 6:00 p.m. – 8:00 p.m. Eastern Standard Time

Conference Call to Discuss First Quarter 2019 Financial Results

Nektar management will host a conference call to review the results beginning at 5:00 p.m. Eastern Standard Time/2:00 p.m. Pacific Standard Time, Wednesday, November 6, 2019.

This press release and a Webcast of the conference call can be accessed through a link that is posted on the home page and Investors section of the Nektar website: View Source The web broadcast of the conference call will be available for replay through Monday, December 9, 2019.

To access the conference call, follow these instructions:

Dial: (877) 881-2183 (U.S.); (970) 315-0453 (international)

Conference ID: 3079832 (Nektar Therapeutics is the host)

In the event that any non-GAAP financial measure is discussed on the conference call that is not described in the press release, or explained on the conference call, related information will be made available on the Investors page at the Nektar website as soon as practical after the conclusion of the conference call.

On November 6, 2019 Artios Pharma Limited (Artios), The University of Texas MD Anderson Cancer Center (MD Anderson) and ShangPharma Innovation (ShangPharma) reported the in-licensing by Artios of a small-molecule ATR inhibitor programme, developed jointly by MD Anderson and ShangPharma (Press release, Artios Pharma, NOV 6, 2019, View Source [SID1234550506]).

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Under the agreement, Artios has exclusive rights to research, develop, manufacture and commercialize products globally. The lead candidate is expected to be ready for Investigational New Drug (IND) application by the second half of 2020.

"This programme has the potential to be a highly effective DNA damage response (DDR) targeted treatment in cancer. We look forward to advancing the work done by MD Anderson and ShangPharma for the benefit of cancer patients," said Dr. Niall Martin, Chief Executive Officer at Artios Pharma. "The addition of the ATR programme further supports our position as a leader in the DDR space and strengthens our growing portfolio of assets, which includes a leading Polθ programme, currently in candidate IND evaluation, and a large discovery stage platform of novel DNA repair nuclease inhibitors."

The ATR inhibitor programme is the result of an extensive collaboration between MD Anderson’s Therapeutics Discovery team and ShangPharma. Therapeutics Discovery is a multidisciplinary team created within MD Anderson to advance the next generation of cancer therapies to answer unmet oncology needs.

"Targeting DNA damage repair has the potential to provide an important therapeutic option for many patients in need of new treatments," said Philip Jones, Ph.D., vice president of Therapeutics Discovery at MD Anderson. "We are pleased Artios will leverage its unique expertise in this field to advance this novel therapy toward the clinic to improve outcomes for cancer patients."

ATR[1] is an important signalling protein in DNA double strand break repair and replication stress. Through inhibition of ATR, tumours bearing an ATM[2] deficiency can be selectively killed through a concept known as synthetic lethality. High levels of ATM mutations and protein loss have been characterised across many different tumour types, creating a significant opportunity for ATR inhibitors clinically. Based on clinical observations at MD Anderson, Therapeutics Discovery engaged with ShangPharma and its affiliate, ChemPartner, to develop small-molecule inhibitors of the DDR that could benefit patients across multiple cancer types.

"We are proud of the entire collaboration team, including ChemPartner, led by Sarah Lively, Ph.D., vice president of Innovation and New Technologies, for advancing the programme from early-stage research to formal drug discovery and development," said Walter Moos, Ph.D., CEO of ShangPharma Innovation. "We are pleased to transition this important programme to the capable development team at Artios, and we hope this ultimately provides an impactful therapy for those afflicted with cancer."