On May 1, 2019 Nektar Therapeutics (Nasdaq: NKTR) reported that it will announce its financial results for the first quarter 2019 on Wednesday, May 8, 2019, after the close of U.S.-based financial markets (Press release, Nektar Therapeutics, MAY 1, 2019, View Source [SID1234535512]). Howard Robin, President and Chief Executive Officer, will host a conference call to review the results beginning at 5:00 p.m. Eastern Daylight Time/2:00 p.m. Pacific Daylight Time.

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The press release and live audio-only 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, June 10, 2019.

To access the conference call, follow these instructions:

Dial: (877) 881-2183 (U.S.); (970) 315-0453 (international)
Conference ID: 8249707 (Nektar Therapeutics is the host)

On May 1, 2019 CStone Pharmaceuticals ("CStone"; HKEX: 2616) and Numab Therapeutics AG ("Numab") reported that they have entered into an exclusive regional licensing agreement for the development and commercialization of ND021, a potential best-in-class monovalent, tri-specific antibody-based molecule targeting PD-L1, 4-1BB, and human serum albumin (HSA) (Press release, CStone Pharmaceauticals, MAY 1, 2019, View Source [SID1234535511]).

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Pursuant to the terms of the licensing agreement, CStone will fund the research and development of ND021 up to completion of an initial Phase Ib clinical trial. In exchange, CStone obtains exclusive rights from Numab to develop and commercialize ND021 in Greater China (including Mainland China, Hong Kong, Macau and Taiwan), South Korea and Singapore. Numab retains all ND021 rights for the rest of the world. Upon completion of CStone’s funding period, no further financial obligations will be owed by either party. This collaboration provides CStone with its first access to Numab’s novel multi-specific technology platform and Numab the opportunity to bring this innovative drug candidate into this region.

Discovered and engineered using Numab’s proprietary λcap technology and MATCH platform, ND021 is a late-preclinical-stage, monovalent, tri-specific antibody-based molecule (scMATCH3) that simultaneously targets PD-L1, 4-1BB, and HSA. ND021 is designed to bind to 4-1BB and activate T cells only when engaging with PD-L1 on the surface of tumor cells, potentially preventing liver toxicities observed in patients treated with conventional 4-1BB-agonistic antibodies.

Compared to other PD-L1/4-1BB bispecific antibody candidates, ND021’s unique monovalent structure and ultra-high-affinity PD-L1-binding is expected to lead to a significantly broader safety window and higher efficacy. Furthermore, half-life extension via the HSA-binding motif in ND021 enables convenient dosing schedules for patients. ND021 is anticipated to be effective against tumors with a wide range of PD-L1 expression-levels and may overcome primary and/or acquired resistance to anti-PD-1/PD-L1 therapies. Therefore, ND021 represents a leading class of next-generation cancer immunotherapies and a new backbone molecule for combinations.

CStone Chairman and CEO, Dr. Frank Jiang, commented: "This collaboration with Numab further strengthens our position as a leading immuno-oncology player in China and commitment to our IO combination strategy. We look forward to joining global simultaneous development to bring this novel therapy to patients in China and beyond as soon as possible."

Dr. David Urech, CEO of Numab, said: "We are very happy to join forces with CStone to accelerate the progress of ND021 in the clinic. In addition to blocking PD-L1-mediated immune-suppression, ND021 has a novel design that tethers potent T cell co-stimulation to the engagement of PD-L1-positive cancer cells, in order to generate focused anti-cancer immune-responses and a favorable risk/benefit profile. We believe this drug candidate has the potential to become an important treatment option for cancer patients around the world."

About ND021

ND021 is a next-generation PD-L1/4-1BB/HSA monovalent, tri-specific scMATCH3 that potently blocks PD-L1/PD-1 signaling while eliciting tumor-restricted co-stimulation of 4-1BB+ cells. In preclinical models, ND021 was well tolerated and induced exquisite antitumoral effects. Its unique, rationally designed molecular architecture and binding properties endow ND021 with several advantageous features that may translate into significant clinical benefit in a broad population of cancer patients.

On May 1, 2019 Celgene Corporation (Nasdaq: CELG) and bluebird bio, Inc. (Nasdaq: BLUE) reported that the New England Journal of Medicine (NEJM) has published interim results from CRB-401, the ongoing phase 1 study of bb2121, the companies’ lead investigational BCMA-targeted chimeric antigen receptor (CAR) T-cell therapy candidate for patients with relapsed and refractory multiple myeloma (Press release, Celgene, MAY 1, 2019, View Source [SID1234535510]).

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The manuscript, "Anti-BCMA CAR T Cell Therapy bb2121 in Relapsed/Refractory Multiple Myeloma", published in NEJM includes key safety and efficacy results from the dose escalation and first expansion cohort, including a minimum of six months follow up on all subjects. As of the data cut-off date of April 30, 2018, manageable safety and deep and durable responses were reported in the first 33 patients infused with bb2121 BCMA-targeted CAR T-cells. Patients in the study were heavily pre-treated, with a median of seven prior multiple myeloma treatment regimens (range, 3 to 23), which included prior treatment with immunomodulatory drugs, proteasome inhibitors and daratumumab in the majority of patients. All but one patient had previously received an autologous stem cell transplant.

"CAR T-cell therapy is an important area of research for relapsed/refractory multiple myeloma patients where there remains a need for new options. We are encouraged by the expansion and persistence of the CAR T-cells, as well as the deep and durable responses with a manageable safety profile we’ve seen for bb2121 to date," said senior author and principal investigator James N. Kochenderfer, M.D., Experimental Transplantation and Immunology Branch, National Cancer Institute Center for Cancer Research.

For the first 33 patients, the most common grade ≥3 events were hematologic toxicities, including neutropenia (85%), leukopenia (58%), anemia (45%) and thrombocytopenia (45%). Neurotoxicity all-grades occurred in 14 (42%) patients; 13 (39%) were grade ≤2 and one patient (3%) had grade 4 neurotoxicity which resolved within one month. Twenty-five (76%) patients experienced cytokine release syndrome; 23 (70%) were grade ≤2 events and two (6%) were grade 3 events; all events were reversible. Infection occurred in 14 (42%) patients; two were grade 3 (6%) and there were no grade 4 events. Peak CAR T cell expansion was higher in patients with cytokine release syndrome and CAR T-cells remained detectable in the blood in 57% of patients at six months following infusion.

Treatment with bb2121 resulted in an 85% objective response rate (ORR) with 45% of patients achieving a complete response (CR) (n=15) and an additional 27% of patients (n=9) achieving a very good partial response (VGPR) to yield a ≥ VGPR rate of 73%. Sixteen responding patients were evaluable for assessment of minimal residual disease (MRD) and all tested MRD negative at one or more time points.

Responses to bb2121 CAR T-cell infusion occurred early, with a median time to first partial response or better of 1.0 month (range, 0.5 to 3.0), and responses were durable, with a median duration of response of 10.9 months (95% CI, 7.2 to not estimable). Researchers observed that greater CAR T-cell expansion occurred in responding patients. Responses were observed independent of tumor or serum BCMA levels. Median progression-free survival among all 33 patients was 11.8 months (95% CI, 6.2–17.8).

"These data from CRB-401 demonstrate that BCMA is a promising target in the treatment of patients with multiple myeloma. We continue to be encouraged by the potential of bb2121 as a first-in-class BCMA-targeted CAR T-cell therapy," said Alise Reicin, M.D., President, Global Clinical Development for Celgene. "The compelling data in these heavily pre-treated relapsed/refractory patients has provided important insights in the development of bb2121 as we continue the follow up of patients in our recently fully enrolled pivotal KarMMa trial. We are also evaluating the potential for bb2121 in earlier lines of multiple myeloma treatment in the other KarMMa trials."

"The data published in NEJM from CRB-401 provide the foundation for advancing the development of bb2121, which is currently being assessed in multiple clinical studies across different patient populations within multiple myeloma," said Dave Davidson, M.D., chief medical officer, bluebird bio. "We hope that this potentially first-in-class BCMA-targeted CAR T-cell therapy may provide a new treatment option for patients living with multiple myeloma."

In November 2017, bb2121 was granted Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration and PRIority Medicines (PRIME) eligibility by the European Medicines Agency based on preliminary clinical data from the phase 1 CRB-401 study.

bb2121 is being developed as part of a Co-Development, Co-Promote and Profit Share Agreement between Celgene and bluebird bio.

Potential approval of bb2121 in the U.S. is anticipated in the second half of 2020. bb2121 is an investigational therapy; safety and efficacy have not yet been established. bb2121 has not been approved for use by any health authority.

About CRB-401

The open-label phase 1 CRB-401 study (NCT02658929) is evaluating the preliminary safety and efficacy of bb2121 BCMA-targeted CAR T-cell therapy in patients with relapsed/refractory multiple myeloma. The primary endpoint of the study is safety. The first portion of the study included a dose-escalation phase in which cohorts of patients received ascending doses of bb2121 to determine the maximum tolerated dose; these findings established the recommended dose of the phase 2 KarMMa trial. The second portion of the study was a dose expansion phase where patients received bb2121 to further evaluate the safety, tolerability and clinical activity at the recommended phase 2 dose. All patients have been treated in the study and follow-up is ongoing. Complete data from the additional expansion cohorts will be published at a later date.

Patients in the dose escalation cohort and first expansion cohort of the study were heavily pre-treated, with a median of seven prior multiple myeloma treatment regimens (range: 3-14) in the dose escalation cohort (n=21) and eight prior regimens (range: 3-23) in the dose expansion cohort (n=12). Patients in the dose escalation phase had received at least three previous lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or were refractory to both drug classes. In addition, patients in the expansion cohorts had received a CD38 antibody and were refractory to their last regimen. All but one patient had previously received an autologous stem cell transplant. As of the data cut-off, patients had at least six months of follow-up or had disease progression, and there was one patient death unrelated to study treatment.

Patients received a lymphodepleting conditioning regimen of fludarabine and cyclophosphamide, followed by an infusion of bb2121 anti-BCMA CAR T-cells. The CAR T-cells were produced from each patient’s own blood cells, which were modified using a proprietary lentiviral vector encoding the anti-BCMA CAR.

Patients were enrolled and dosed in either the dose-escalation cohort of the study, at four target dose levels (50 x 106, 150 x 106, 450 x 106 and 800 x 106 CAR+ T cells), or in the dose expansion cohort in a target dose range between 150-450 x 106 CAR+ T cells.

On May 1, 2019 Physicians’ Education Resource (PER), a worldwide leading resource for continuing medical education (CME), reported that it will present an in-studio video broadcast titled, "Rapid Reviews in Oncology from Chicago: Practice-Changing Data in Breast Cancer" on Wednesday, June 19 at 8 p.m. EDT (Press release, Physicians’ Education Resource, MAY 1, 2019, View Source [SID1234535509]).

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The live activity will be chaired by renowned breast cancer expert and leading clinical researcher Dr. Joyce O’Shaughnessy, who is the Celebrating Women Chair in Breast Cancer Research at Texas Oncology-Baylor Charles A. Sammons Cancer Center, and co-chair of the breast cancer research program at The US Oncology Network.

"We look forward to presenting this live-stream interactive broadcast to physicians after this year’s ASCO (Free ASCO Whitepaper) Annual Meeting to cover recent data in breast cancer," said Phil Talamo, president of PER. "PER’s Rapid Reviews in Oncology legacy program features highlights of practice-changing data in breast cancer, with expert faculty interpretation, along with audience Q&A sessions immediately following the Annual Meeting."

This live CME-certified interactive webcast is designed to rapidly update medical oncologists and fellows who treat patients with breast cancer with emerging data that has recently been presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. O’Shaughnessy will be joined by a panel of experts who will highlight the implications and applications of these data for physicians’ practice, helping them optimize care for their patients with breast cancer. Attendees will also have the opportunity to learn how experts in breast cancer research place emerging data into clinical context for the treatment and management of patients with breast cancer and stay up-to-date on the latest data pertaining to treatment and management of breast cancer across the spectrum of disease.

This live webcast is accredited by the Accreditation Council for Continuing Medical Education for 2.0 AMA PRA Category 1 Credits for physicians. For more information and to register, click here.

On May 1, 2019 Exelixis, Inc. (NASDAQ: EXEL) reported that it is initiating COSMIC-313, a phase 3 pivotal trial of cabozantinib (CABOMETYX) in combination with nivolumab (Opdivo) and ipilimumab (Yervoy) versus nivolumab and ipilimumab in patients with previously untreated advanced renal cell carcinoma (RCC) with intermediate- or poor-risk disease per the International Metastatic Renal Cell Carcinoma Database Consortium (Press release, Exelixis, MAY 1, 2019, View Source [SID1234535508]). The primary endpoint of the trial is progression-free survival, and the secondary endpoints are overall survival and objective response rate.

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"Clinical observations suggest cabozantinib promotes an immune-permissive environment, which could present an opportunity for additive or synergistic effects with immune checkpoint inhibitors," said Gisela Schwab, M.D., President, Product Development and Medical Affairs and Chief Medical Officer, Exelixis. "The mechanisms of action of single agent cabozantinib and the combination of nivolumab and ipilimumab are complementary, and each has demonstrated efficacy in advanced renal cell carcinoma. The further combination of these agents as a triplet regimen may offer promise to previously untreated patients with intermediate- or poor-risk disease, who are known to have poor treatment outcomes."

COSMIC-313 is a multicenter, randomized, double-blinded, controlled phase 3 pivotal trial that aims to enroll approximately 676 patients at 150 sites globally. Patients will be randomized 1:1 to the experimental arm of cabozantinib in combination with nivolumab and ipilimumab and to the control arm of nivolumab and ipilimumab in combination with matched placebo.

Design of this phase 3 pivotal trial was informed by results from the ongoing phase 1b study of cabozantinib plus nivolumab with or without ipilimumab in patients with previously treated advanced genitourinary cancers, including RCC. The phase 1b trial is being conducted by the U.S. National Cancer Institute and includes centers from its Experimental Therapeutics Clinical Trials Network.

Bristol-Myers Squibb is providing nivolumab and ipilimumab for use in this trial.

Please see Important Safety Information below and full U.S. prescribing information at View Source

About RCC

The American Cancer Society’s 2019 statistics cite kidney cancer as among the top ten most commonly diagnosed forms of cancer among both men and women in the U.S.1 Clear cell RCC is the most common type of kidney cancer in adults.2 If detected in its early stages, the five-year survival rate for RCC is high; for patients with advanced or late-stage metastatic RCC, however, the five-year survival rate is only 12 percent, with no identified cure for the disease.1 Approximately 32,000 patients in the U.S. and 70,000 globally require treatment, and an estimated 15,000 patients in the U.S. each year are in need of a first-line treatment for advanced kidney cancer.3

The majority of clear cell RCC tumors have lower than normal levels of a protein called von Hippel-Lindau, which leads to higher levels of MET, AXL and VEGF.4,5 These proteins promote tumor angiogenesis (blood vessel growth), growth, invasiveness and metastasis.6,7,8,9 MET and AXL may provide escape pathways that drive resistance to VEGF receptor inhibitors.5,6

About CABOMETYX (cabozantinib)

In the U.S., CABOMETYX tablets are approved for the treatment of patients with advanced RCC and for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. CABOMETYX tablets have also received regulatory approvals in the European Union and additional countries and regions worldwide. In 2016, Exelixis granted Ipsen exclusive rights for the commercialization and further clinical development of cabozantinib outside of the United States and Japan. In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited for the commercialization and further clinical development of cabozantinib for all future indications in Japan.

The combination of CABOMETYX with nivolumab and ipilimumab is not indicated for previously untreated advanced RCC.

U.S. Important Safety Information

Hemorrhage: Severe and fatal hemorrhages occurred with CABOMETYX. The incidence of Grade 3 to 5 hemorrhagic events was 5% in CABOMETYX patients. Discontinue CABOMETYX for Grade 3 or 4 hemorrhage. Do not administer CABOMETYX to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena.
Perforations and Fistulas: GastrointestinaI (GI) perforations, including fatal cases, occurred in 1% of CABOMETYX patients. Fistulas, including fatal cases, occurred in 1% of CABOMETYX patients. Monitor patients for signs and symptoms of perforations and fistulas, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a fistula that cannot be appropriately managed or a GI perforation.
Thrombotic Events: CABOMETYX increased the risk of thrombotic events. Venous thromboembolism occurred in 7% (including 4% pulmonary embolism) and arterial thromboembolism in 2% of CABOMETYX patients. Fatal thrombotic events occurred in CABOMETYX patients. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or serious arterial or venous thromboembolic event requiring medical intervention.
Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension, including hypertensive crisis. Hypertension occurred in 36% (17% Grade 3 and <1% Grade 4) of CABOMETYX patients. Do not initiate CABOMETYX in patients with uncontrolled hypertension. Monitor blood pressure regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume at a reduced dose. Discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy or for hypertensive crisis.
Diarrhea: Diarrhea occurred in 63% of CABOMETYX patients. Grade 3 diarrhea occurred in 11% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 diarrhea, Grade 3 diarrhea that cannot be managed with standard antidiarrheal treatments, or Grade 4 diarrhea.
Palmar-Plantar Erythrodysesthesia (PPE): PPE occurred in 44% of CABOMETYX patients. Grade 3 PPE occurred in 13% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 PPE or Grade 3 PPE.
Proteinuria: Proteinuria occurred in 7% of CABOMETYX patients. Monitor urine protein regularly during CABOMETYX treatment. Discontinue CABOMETYX in patients who develop nephrotic syndrome.
Osteonecrosis of the Jaw (ONJ): ONJ occurred in <1% of CABOMETYX patients. ONJ can manifest as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration or erosion, persistent jaw pain, or slow healing of the mouth or jaw after dental surgery. Perform an oral examination prior to CABOMETYX initiation and periodically during treatment. Advise patients regarding good oral hygiene practices. Withhold CABOMETYX for at least 28 days prior to scheduled dental surgery or invasive dental procedures. Withhold CABOMETYX for development of ONJ until complete resolution.
Wound Complications: Wound complications were reported with CABOMETYX. Stop CABOMETYX at least 28 days prior to scheduled surgery. Resume CABOMETYX after surgery based on clinical judgment of adequate wound healing. Withhold CABOMETYX in patients with dehiscence or wound healing complications requiring medical intervention.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS, a syndrome of subcortical vasogenic edema diagnosed by characteristic finding on MRI, can occur with CABOMETYX. Evaluate for RPLS in patients presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.
Embryo-Fetal Toxicity: CABOMETYX can cause fetal harm. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to initiating CABOMETYX and advise them to use effective contraception during treatment and for 4 months after the last dose.
Adverse Reactions: The most commonly reported (≥25%) adverse reactions are: diarrhea, fatigue, decreased appetite, PPE, nausea, hypertension, and vomiting.
Strong CYP3A4 Inhibitors: If coadministration with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage. Avoid grapefruit or grapefruit juice.
Strong CYP3A4 Inducers: If coadministration with strong CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage. Avoid St. John’s wort.
Lactation: Advise women not to breastfeed during CABOMETYX treatment and for 4 months after the final dose.
Hepatic Impairment: In patients with moderate hepatic impairment, reduce the CABOMETYX dosage. CABOMETYX is not recommended for use in patients with severe hepatic impairment.