On May 30, 2019 Myovant Sciences (NYSE: MYOV) ("Myovant"), a clinical-stage healthcare company focused on developing and commercializing innovative therapies for women’s health and prostate cancer, reported the pricing of its underwritten public offering of 15,151,516 of its common shares at a price to the public of $8.25 per share (Press release, Myovant Sciences, MAY 30, 2019, https://investors.myovant.com/news-releases/news-release-details/myovant-sciences-announces-pricing-125-million-public-offering [SID1234536733]). Gross proceeds to Myovant from the offering are expected to be approximately $125.0 million, before deducting underwriting discounts and commissions and estimated offering expenses. All of the common shares are being offered by Myovant. In connection with this offering, Myovant has granted the underwriters a 30-day option to purchase up to an additional 2,272,727 of its common shares on the same terms and conditions. The offering is expected to close on June 4, 2019, subject to the satisfaction of customary closing conditions. Myovant currently intends to use the net proceeds from the offering primarily to fund its clinical development programs, including the Phase 3 LIBERTY 2 trial in uterine fibroids and heavy menstrual bleeding and the Phase 3 HERO trial in advanced prostate cancer, preparations for potential future regulatory approvals and commercialization of relugolix, as well as for working capital and other general corporate purposes.

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J.P. Morgan Securities LLC, Goldman Sachs & Co. LLC, Cowen and Company, LLC and Evercore Group L.L.C. are acting as joint book-running managers for the offering.

A shelf registration statement relating to the offered common shares was filed with the Securities and Exchange Commission (SEC) and became effective upon filing on May 24, 2019. A preliminary prospectus supplement and accompanying prospectus relating to the offering have been filed with the SEC and are available on the SEC’s website, located at www.sec.gov. Copies of the final prospectus supplement and accompanying prospectus related to the offering may be obtained, when available, from J.P. Morgan Securities LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, Attention: Prospectus Department, by email at [email protected] or by phone at (866) 803-9204, Goldman Sachs & Co. LLC, Prospectus Department, 200 West Street, New York, NY 10282, by email at [email protected], by phone at (866) 471-2526 or by facsimile at (212) 902-9316, Cowen and Company, LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, Attn: Prospectus Department, by phone at 1-631-274-2806, or Evercore Group L.L.C., Attention: Equity Capital Markets, 55 East 52nd Street, New York, NY 10055, by phone at (888) 474-0200, or by email at [email protected].

This announcement is neither an offer to sell nor a solicitation of an offer to buy any of these securities, and shall not constitute an offer, solicitation, or sale in any jurisdiction in which such offer, solicitation, or sale is unlawful.

On May 30, 2019 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, reported that the China National Medical Products Administration (NMPA, formerly known as CFDA) has accepted the supplemental import drug application for ABRAXANE (paclitaxel protein-bound particles for injectable suspension) (albumin-bound), in combination with gemcitabine, as a first-line treatment of patients with metastatic adenocarcinoma of the pancreas (mPC) (Press release, BeiGene, MAY 30, 2019, View Source [SID1234536732]). ABRAXANE was first approved in China in 2008 for the treatment of patients with metastatic breast cancer. It is currently marketed in China by BeiGene under an exclusive license from Celgene Corporation.

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"We’re delighted about the NMPA’s acceptance of the supplemental import drug submission of ABRAXANE as a treatment for Chinese patients with metastatic adenocarcinoma of the pancreas," said Dr. Xiaobin Wu, General Manager of China and President of BeiGene. "ABRAXANE has been an important global treatment option for patients with metastatic adenocarcinoma of the pancreas outside of China, and we strive to provide access to ABRAXANE in China to those patients for whom there is great need for additional treatments to combat this deadly disease."

About Pancreatic Cancer
Pancreatic cancer is one of the deadliest cancers, with a nine percent five-year survival rate.i In 2018, there were an estimated 458,918 new cases globally, making it the 12th most common cancer in the world.ii Pancreatic cancer is difficult to detect in early stages, as the disease does not cause obvious symptoms. In addition, the pancreas is located deep in the abdomen, hindering the diagnosis of pancreatic cancer.

About ABRAXANE in Pancreatic Cancer

In September 2013, the U.S. Food and Drug Administration (FDA) approved ABRAXANE in combination with gemcitabine as first-line treatment of patients with metastatic adenocarcinoma of the pancreas.

Clinical trials continue building on the foundation of ABRAXANE in combination with gemcitabine for a new wave of potential treatments, such as an ongoing Phase 2 cooperative group trial with SWOG S1505 (ClinicalTrials.gov, NCT02562716) investigating the safety and effectiveness of ABRAXANE in combination with gemcitabine as neoadjuvant treatment for localized pancreatic head adenocarcinoma.

Indications

ABRAXANE is indicated for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. Prior therapy should have included an anthracycline unless clinically contraindicated.

ABRAXANE is indicated for the first-line treatment of locally advanced or metastatic non– small cell lung cancer, in combination with carboplatin, in patients who are not candidates for curative surgery or radiation therapy.

ABRAXANE is indicated for the first-line treatment of patients with metastatic adenocarcinoma of the pancreas, in combination with gemcitabine.

Important Safety Information

WARNING – NEUTROPENIA

Do not administer ABRAXANE therapy to patients who have baseline neutrophil counts of less than 1500 cells/mm3. In order to monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection, it is recommended that frequent peripheral blood cell counts be performed on all patients receiving ABRAXANE
Note: An albumin form of paclitaxel may substantially affect a drug’s functional properties relative to those of drug in solution. DO NOT SUBSTITUTE FOR OR WITH OTHER PACLITAXEL FORMULATIONS
CONTRAINDICATIONS
Neutrophil Counts

ABRAXANE should not be used in patients who have baseline neutrophil counts of <1500 cells/mm3
Hypersensitivity

Patients who experience a severe hypersensitivity reaction to ABRAXANE should not be rechallenged with the drug
WARNINGS AND PRECAUTIONS
Hematologic Effects

Bone marrow suppression (primarily neutropenia) is dose-dependent and a dose-limiting toxicity of ABRAXANE. In clinical studies, Grade 3-4 neutropenia occurred in 34% of patients with metastatic breast cancer (MBC), 47% of patients with non–small cell lung cancer (NSCLC), and 38% of patients with pancreatic cancer
Monitor for myelotoxicity by performing complete blood cell counts frequently, including prior to dosing on Day 1 (for MBC) and Days 1, 8, and 15 (for NSCLC and for pancreatic cancer)
Do not administer ABRAXANE to patients with baseline absolute neutrophil counts (ANC) of less than 1500 cells/mm3
In the case of severe neutropenia (<500 cells/mm3 for 7 days or more) during a course of ABRAXANE therapy, reduce the dose of ABRAXANE in subsequent courses in patients with either MBC or NSCLC
In patients with MBC, resume treatment with every-3-week cycles of ABRAXANE after ANC recovers to a level >1500 cells/mm3 and platelets recover to a level >100,000 cells/mm3
In patients with NSCLC, resume treatment if recommended at permanently reduced doses for both weekly ABRAXANE and every-3-week carboplatin after ANC recovers to at least 1500 cells/mm3 and platelet count of at least 100,000 cells/mm3 on Day 1 or to an ANC of at least 500 cells/mm3 and platelet count of at least 50,000 cells/mm3 on Days 8 or 15 of the cycle
In patients with adenocarcinoma of the pancreas, withhold ABRAXANE and gemcitabine if the ANC is less than 500 cells/mm3 or platelets are less than 50,000 cells/mm3 and delay initiation of the next cycle if the ANC is less than 1500 cells/mm3 or platelet count is less than 100,000 cells/mm3 on Day 1 of the cycle. Resume treatment with appropriate dose reduction if recommended
Nervous System

Sensory neuropathy is dose- and schedule-dependent
The occurrence of Grade 1 or 2 sensory neuropathy does not generally require dose modification
If ≥ Grade 3 sensory neuropathy develops, withhold ABRAXANE treatment until resolution to Grade 1 or 2 for MBC or until resolution to ≤ Grade 1 for NSCLC and pancreatic cancer followed by a dose reduction for all subsequent courses of ABRAXANE
Sepsis

Sepsis occurred in 5% of patients with or without neutropenia who received ABRAXANE in combination with gemcitabine
Biliary obstruction or presence of biliary stent were risk factors for severe or fatal sepsis
If a patient becomes febrile (regardless of ANC), initiate treatment with broad-spectrum antibiotics
For febrile neutropenia, interrupt ABRAXANE and gemcitabine until fever resolves and ANC ≥1500 cells/mm3, then resume treatment at reduced dose levels
Pneumonitis

Pneumonitis, including some cases that were fatal, occurred in 4% of patients receiving ABRAXANE in combination with gemcitabine
Monitor patients for signs and symptoms and interrupt ABRAXANE and gemcitabine during evaluation of suspected pneumonitis
Permanently discontinue treatment with ABRAXANE and gemcitabine upon making a diagnosis of pneumonitis
Hypersensitivity

Severe and sometimes fatal hypersensitivity reactions, including anaphylactic reactions, have been reported
Patients who experience a severe hypersensitivity reaction to ABRAXANE should not be rechallenged with this drug
Cross-hypersensitivity between ABRAXANE and other taxane products has been reported and may include severe reactions such as anaphylaxis. Patients with a previous history of hypersensitivity to other taxanes should be closely monitored during initiation of ABRAXANE therapy
Hepatic Impairment

Because the exposure and toxicity of paclitaxel can be increased with hepatic impairment, administration of ABRAXANE in patients with hepatic impairment should be performed with caution
Patients with hepatic impairment may be at an increased risk of toxicity, particularly from myelosuppression, and should be monitored for development of profound myelosuppression
For MBC and NSCLC, the starting dose should be reduced for patients with moderate or severe hepatic impairment
For pancreatic adenocarcinoma, ABRAXANE is not recommended for patients with moderate to severe hepatic impairment (total bilirubin >1.5 x ULN and AST ≤10 x ULN)
Albumin (Human)

ABRAXANE contains albumin (human), a derivative of human blood
Embryo Fetal Toxicity

Based on mechanism of action and findings in animals, ABRAXANE can cause fetal harm when administered to a pregnant woman
Advise females of reproductive potential of the potential risk to a fetus.
Advise females of reproductive potential to use effective contraception and avoid becoming pregnant during treatment with ABRAXANE and for at least six months after the last dose of ABRAXANE
Advise male patients with female partners of reproductive potential to use effective contraception and avoid fathering a child during treatment with ABRAXANE and for at least three months after the last dose of ABRAXANE
ADVERSE REACTIONS
Randomized Metastatic Breast Cancer (MBC) Study

The most common adverse reactions (≥20%) with single-agent use of ABRAXANE vs paclitaxel injection in the MBC study are alopecia (90%, 94%), neutropenia (all cases 80%, 82%; severe 9%, 22%), sensory neuropathy (any symptoms 71%, 56%; severe 10%, 2%), abnormal ECG (all patients 60%, 52%; patients with normal baseline 35%, 30%), fatigue/asthenia (any 47%, 39%; severe 8%, 3%), myalgia/arthralgia (any 44%, 49%; severe 8%, 4%), AST elevation (any 39%, 32%), alkaline phosphatase elevation (any 36%, 31%), anemia (any 33%, 25%; severe 1%, <1%), nausea (any 30%, 22%; severe 3%, <1%), diarrhea (any 27%, 15%; severe <1%, 1%) and infections (24%, 20%), respectively
Sensory neuropathy was the cause of ABRAXANE discontinuation in 7/229 (3%) patients
Other adverse reactions of note with the use of ABRAXANE vs paclitaxel injection included vomiting (any 18%, 10%; severe 4%, 1%), fluid retention (any 10%, 8%; severe 0%, <1%), mucositis (any 7%, 6%; severe <1%, 0%), hepatic dysfunction (elevations in bilirubin 7%, 7%), hypersensitivity reactions (any 4%, 12%; severe 0%, 2%), thrombocytopenia (any 2%, 3%; severe <1%, <1%), neutropenic sepsis (<1%, <1%), and injection site reactions (<1%, 1%), respectively. Dehydration and pyrexia were also reported
Renal dysfunction (any 11%, severe 1%) was reported in patients treated with ABRAXANE (n=229)
In all ABRAXANE-treated patients (n=366), ocular/visual disturbances were reported (any 13%; severe 1%)
Severe cardiovascular events possibly related to single-agent ABRAXANE occurred in approximately 3% of patients and included cardiac ischemia/infarction, chest pain, cardiac arrest, supraventricular tachycardia, edema, thrombosis, pulmonary thromboembolism, pulmonary emboli, and hypertension
Cases of cerebrovascular attacks (strokes) and transient ischemic attacks have been reported
Non–Small Cell Lung Cancer (NSCLC) Study

The most common adverse reactions (≥20%) of ABRAXANE in combination with carboplatin are anemia, neutropenia, thrombocytopenia, alopecia, peripheral neuropathy, nausea, and fatigue
The most common serious adverse reactions of ABRAXANE in combination with carboplatin for NSCLC are anemia (4%) and pneumonia (3%)
The most common adverse reactions resulting in permanent discontinuation of ABRAXANE are neutropenia (3%), thrombocytopenia (3%), and peripheral neuropathy (1%)
The most common adverse reactions resulting in dose reduction of ABRAXANE are neutropenia (24%), thrombocytopenia (13%), and anemia (6%)
The most common adverse reactions leading to withholding or delay in ABRAXANE dosing are neutropenia (41%), thrombocytopenia (30%), and anemia (16%)
The following common (≥10% incidence) adverse reactions were observed at a similar incidence in ABRAXANE plus carboplatin–treated and paclitaxel injection plus carboplatin– treated patients: alopecia (56%), nausea (27%), fatigue (25%), decreased appetite (17%), asthenia (16%), constipation (16%), diarrhea (15%), vomiting (12%), dyspnea (12%), and rash (10%); incidence rates are for the ABRAXANE plus carboplatin treatment group
Adverse reactions with a difference of ≥2%, Grade 3 or higher, with combination use of ABRAXANE and carboplatin vs combination use of paclitaxel injection and carboplatin in NSCLC are anemia (28%, 7%), neutropenia (47%, 58%), thrombocytopenia (18%, 9%), and peripheral neuropathy (3%, 12%), respectively
Adverse reactions with a difference of ≥5%, Grades 1-4, with combination use of ABRAXANE and carboplatin vs combination use of paclitaxel injection and carboplatin in NSCLC are anemia (98%, 91%), thrombocytopenia (68%, 55%), peripheral neuropathy (48%, 64%), edema peripheral (10%, 4%), epistaxis (7%, 2%), arthralgia (13%, 25%), and myalgia (10%, 19%), respectively
Neutropenia (all grades) was reported in 85% of patients who received ABRAXANE and carboplatin vs 83% of patients who received paclitaxel injection and carboplatin
Pancreatic Adenocarcinoma Study

Among the most common (≥20%) adverse reactions in the phase III study, those with a ≥5% higher incidence in the ABRAXANE/gemcitabine group compared with the gemcitabine group are neutropenia (73%, 58%), fatigue (59%, 46%), peripheral neuropathy (54%, 13%), nausea (54%, 48%), alopecia (50%, 5%), peripheral edema (46%, 30%), diarrhea (44%, 24%), pyrexia (41%, 28%), vomiting (36%, 28%), decreased appetite (36%, 26%), rash (30%, 11%), and dehydration (21%, 11%)
Of these most common adverse reactions, those with a ≥2% higher incidence of Grade 3-4 toxicity in the ABRAXANE/gemcitabine group compared with the gemcitabine group, respectively, are neutropenia (38%, 27%), fatigue (18%, 9%), peripheral neuropathy (17%, 1%), nausea (6%, 3%), diarrhea (6%, 1%), pyrexia (3%, 1%), vomiting (6%, 4%), decreased appetite (5%, 2%), and dehydration (7%, 2%)
Thrombocytopenia (all grades) was reported in 74% of patients in the ABRAXANE/gemcitabine group vs 70% of patients in the gemcitabine group
The most common serious adverse reactions of ABRAXANE (with a ≥1% higher incidence) are pyrexia (6%), dehydration (5%), pneumonia (4%), and vomiting (4%)
The most common adverse reactions resulting in permanent discontinuation of ABRAXANE were peripheral neuropathy (8%), fatigue (4%), and thrombocytopenia (2%)
The most common adverse reactions resulting in dose reduction of ABRAXANE are neutropenia (10%) and peripheral neuropathy (6%)
The most common adverse reactions leading to withholding or delay in ABRAXANE dosing are neutropenia (16%), thrombocytopenia (12%), fatigue (8%), peripheral neuropathy (15%), anemia (5%), and diarrhea (5%)
Other selected adverse reactions with a ≥5% higher incidence for all-grade toxicity in the ABRAXANE/gemcitabine group compared to the gemcitabine group, respectively, are asthenia (19%, 13%), mucositis (10%, 4%), dysgeusia (16%, 8%), headache (14%, 9%), hypokalemia (12%, 7%), cough (17%, 7%), epistaxis (15%, 3%), urinary tract infection (11%, 5%), pain in extremity (11%, 6%), arthralgia (11%, 3%), myalgia (10%, 4%), and depression (12%, 6%)
Other selected adverse reactions with a ≥2% higher incidence for Grade 3-4 toxicity in the ABRAXANE/gemcitabine group compared to the gemcitabine group are thrombocytopenia (13%, 9%), asthenia (7%, 4%), and hypokalemia (4%, 1%)
Postmarketing Experience With ABRAXANE and Other Paclitaxel Formulations

Severe and sometimes fatal hypersensitivity reactions have been reported with ABRAXANE. The use of ABRAXANE in patients previously exhibiting hypersensitivity to paclitaxel injection or human albumin has not been studied. In postmarketing experience, cross-hypersensitivity between ABRAXANE and other taxanes has been reported
There have been reports of congestive heart failure, left ventricular dysfunction, and atrioventricular block with ABRAXANE, primarily among individuals with underlying cardiac history or prior exposure to cardiotoxic drugs
There have been reports of extravasation of ABRAXANE. Given the possibility of extravasation, it is advisable to monitor closely the ABRAXANE infusion site for possible infiltration during drug administration
DRUG INTERACTIONS

Caution should be exercised when administering ABRAXANE concomitantly with medicines known to inhibit or induce either CYP2C8 or CYP3A4
USE IN SPECIFIC POPULATIONS
Pregnancy

Based on the mechanism of action and findings in animals, ABRAXANE can cause fetal harm when administered to a pregnant woman. Advise females of the potential risk to a fetus and to avoid becoming pregnant while receiving ABRAXANE
Lactation

Paclitaxel and/or its metabolites were excreted into the milk of lactating rats. Nursing must be discontinued when receiving treatment with ABRAXANE and for two weeks after the last dose
Females and Males of Reproductive Potential

Females of reproductive potential should have a pregnancy test prior to starting treatment with ABRAXANE
Advise females of reproductive potential to use effective contraception and avoid becoming pregnant during treatment with and for at least six months after the last dose of ABRAXANE [see Warnings and Precautions]
Advise males with female partners of reproductive potential to use effective contraception and avoid fathering a child during treatment with ABRAXANE and for at least three months after the last dose of ABRAXANE [see Warnings and Precautions]
Based on findings in animals, ABRAXANE may impair fertility in females and males of reproductive potential
Pediatric

The safety and effectiveness of ABRAXANE in pediatric patients have not been evaluated
Geriatric

A higher incidence of epistaxis, diarrhea, dehydration, fatigue, and peripheral edema was found in patients 65 years or older who received ABRAXANE for MBC in a pooled analysis of clinical studies
Myelosuppression, peripheral neuropathy, and arthralgia were more frequent in patients ≥65 years of age treated with ABRAXANE and carboplatin in NSCLC
Diarrhea, decreased appetite, dehydration, and epistaxis were more frequent in patients 65 years or older compared with patients younger than 65 years old who received ABRAXANE and gemcitabine in adenocarcinoma of the pancreas
Renal Impairment

There are insufficient data to permit dosage recommendations in patients with severe renal impairment or end stage renal disease (estimated creatinine clearance <30 mL/min)
DOSAGE AND ADMINISTRATION

Do not administer ABRAXANE to any patient with total bilirubin greater than 5 x ULN or AST greater than 10 x ULN
For MBC and NSCLC, reduce starting dose in patients with moderate to severe hepatic impairment
For adenocarcinoma of the pancreas, do not administer ABRAXANE to patients who have moderate to severe hepatic impairment
Dose reductions or discontinuation may be needed based on severe hematologic, neurologic, cutaneous, or gastrointestinal toxicity
Monitor patients closely

On May 30, 2019 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, reported that the China National Medical Products Administration (NMPA, formerly known as CFDA) has accepted a supplemental new drug application (sNDA) for tislelizumab, an investigational anti-PD-1 antibody, for the treatment of patients with previously treated locally advanced or metastatic urothelial carcinoma (UC) (Press release, BeiGene, MAY 30, 2019, View Source [SID1234536731]).

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"The development program for tislelizumab is achieving its milestones swiftly with our first solid-tumor filing for patients with previously treated urothelial carcinoma following our initial filing last year for patients with relapsed/refractory classical Hodgkin’s lymphoma. We sincerely hope that this submission, if approved, can bring a meaningful treatment option for patients with UC in China," said Dr. Xiaobin Wu, General Manager of China and President of BeiGene. "We believe that the broad development program for this anti-PD1 inhibitor, along with manufacturing capabilities that are nearing completion, and non-clinical data presented earlier this year, reinforce tislelizumab as a potentially differentiated immuno-oncology compound. We are excited by its prospects to improve the way people with cancer are treated around the world."

The sNDA is supported by a clinical, non-clinical, and CMC data package, including the results from a pivotal Phase 2 study of tislelizumab in 113 Chinese and South Korean patients with previously treated PD-L1+ locally advanced or metastatic urothelial carcinoma (chinadrugtrials.org registration number: CTR20170071). A recent independent review of data showed that, with a median follow-up time of 8 months at the data cutoff, overall response rate (ORR) in 104 efficacy-evaluable patients was 23.1 percent, including eight (7.7 percent) confirmed complete responses (CRs) and 16 (15.4 percent) confirmed partial responses (PRs). Frequency and severity of adverse events were generally consistent with the previously reported Phase 1/2 safety and tolerability data for tislelizumab, or, in the case of certain immune-related adverse events, consistent with previous reports of other PD-1 antibodies. Full results of the study are planned to be presented at an upcoming medical conference.

About Urothelial Carcinoma
Urothelial carcinoma (UC), also known as transitional cell carcinoma (TCC), is by far the most common type of bladder cancer.i In 2018, there was an estimated 82,270 incidences of bladder cancer in China, accounting for 27.3 percent of all incidences worldwide.ii Although UC is most common in the bladder, it can occur in other parts of the urinary system.

About Tislelizumab
Tislelizumab (BGB-A317) is an investigational humanized IgG4 anti–PD-1 monoclonal antibody specifically designed to minimize binding to FcγR on macrophages. In pre-clinical studies, binding to FcγR on macrophages has been shown to compromise the anti-tumor activity of PD-1 antibodies through activation of antibody-dependent macrophage-mediated killing of T effector cells. Tislelizumab is the first drug candidate produced from BeiGene’s immuno-oncology biologic program, and is being developed as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers.

In addition to the pivotal Phase 2 trial of tislelizumab in locally advanced or metastatic urothelial cancer mentioned in this release, BeiGene has also completed a pivotal Phase 2 clinical trial in patients with relapsed or refractory classical Hodgkin’s lymphoma (cHL). Ongoing clinical trials of tislelizumab include a Phase 3 clinical trial in patients with second-line or third-line non-small cell lung cancer (NSCLC); a Phase 3 clinical trial in first-line patients with hepatocellular carcinoma (HCC); a Phase 3 clinical trial in second-line patients with esophageal squamous carcinoma (ESCC); a Phase 3 clinical trial in first-line patients with gastric cancer (GC); a Phase 3 clinical trial in first-line patients with ESCC; a Phase 3 trial in patients with Stage III NSCLC; a Phase 2 clinical trial in second- or third-line patients with HCC; and a Phase 1 clinical trial in patients with relapsed/refractory (R/R) NK/T-cell lymphomas. The aforementioned studies are enrolling patients in multiple countries, including the U.S., Europe, and China.

Additionally, BeiGene is conducting a Phase 3 clinical trial in first-line patients with non-squamous NSCLC; a Phase 3 clinical trial in first-line patients with squamous NSCLC; a Phase 3 clinical trial in patients with nasopharyngeal cancer (NPC); a Phase 3 clinical trial in first-line patients with urothelial carcinoma (UC); and a pivotal Phase 2 trial in patients with MSI-H or dMMR solid tumors. These studies are enrolling patients in China.

New drug applications (NDA) for tislelizumab in patients with R/R cHL and in patients with previously treated locally advanced or metastatic UC have been accepted by the China National Medical Products Administration (NMPA, formerly known as CFDA) and the R/R cHL filing has been granted priority review. BeiGene and Celgene Corporation have a global strategic collaboration for the development of tislelizumab in solid tumor cancers outside of Asia (except Japan).

On May 30, 2019 OncBioMune Pharmaceuticals, Inc. (OTCQB:OBMP) ("OncBioMune" or the "Company"), a clinical-stage biopharmaceutical company engaged in the development of a proprietary therapeutic prostate cancer vaccine immunotherapy and a CD71-targeted cancer therapy combining paclitaxel, gallium, and transferrin, otherwise known as PGT, reported the results of initial in vitro data for PGT in a Multi-drug resistant ovarian cancer model (Press release, Oncbiomune, MAY 30, 2019, View Source [SID1234536719]).

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Cell proliferation assays were performed on 2 cell lines, MCF-7 (a breast cancer cell line known to be sensitive to chemotherapy) and NCI/ADR-RES (OVCAR-8 ADR-RES, a multidrug-resistant cell line that is a model for the study of drug resistance in ovarian cancer) grown under hypoxic conditions and treated separately with varying concentrations of either the standard chemotherapy agent paclitaxel or PGT for 72 hours. The IC50 (concentration of drug needed to inhibit the cell growth by 50%) was determined for paclitaxel and PGT, standardized by the concentration of paclitaxel. The IC50s were calculated from growth inhibition curves.

The IC50s for the MCF-7 cells were similar for paclitaxel and PGT (range 0.02 to 0.09 micromolar). However, the IC50 of the NCI/ADR-RES cells for the paclitaxel was 216 micromolar and the IC50 for the PGT was 0.0318 micromolar. This shows that in this experiment, a 6797-fold decrease in the concentration of PGT can obtain the same inhibition of cancer cell growth as the standard chemotherapy paclitaxel in this multidrug-resistant model. Additionally, this concentration of PGT is similar to the IC50 of paclitaxel seen in the chemotherapy sensitive MCF-7 cells. Taken together, this implies that PGT is able to overcome drug resistance mechanisms at play in the NCI/ADR-RES cell line model of chemotherapy resistance and thereby makes these cells sensitive to PGT therapy in an acceptable concentration range.

PGT is designed to deliver the chemotherapeutic agent paclitaxel to cancer cells over-expressing the transferrin receptor (aka CD71). Paclitaxel is currently FDA-approved in two forms: as solvent-based paclitaxel (sb-paclitaxel, Taxol) and protein-based paclitaxel (nab-paclitaxel, ABRAXANE ).

PGT combines paclitaxel to the human protein transferrin as opposed to albumin, which is employed in nab-paclitaxel. This creates the potential to target the paclitaxel to CD71, which has been shown to be highly over-expressed on many different types of cancer cells.

Additionally, PGT takes advantage of the fact that the transferrin protein has binding sites for iron that can also bind gallium, which has anti-cancer activity. In theory, this creates a novel protein drug complex which has the capacity to deliver two, non-cross resistant cancer therapeutics in a targeted fashion.

"This is only one experimental model, but it does suggest that PGT has the potential to show activity in cancer cells that are resistant to standard chemotherapies that are used widely in patients today," commented Dr. Brian Barnett, Chief Executive Officer at OncBioMune. "This experiment utilizes a well characterized ovarian cancer cell line that is multi-drug resistant. In the near future, we plan to perform tests on other models as we are hopeful that this therapy may show broad activity in multiple cancer types with the ultimate goal of developing PGT for patients with refractory cancers, an area of high unmet medical need."

On May 30 2019 Genmab A/S (Nasdaq Copenhagen: GEN) reported that the U.S. Food and Drug Administration (U.S. FDA) granted a Priority Review for the supplemental Biologics License Application (sBLA) for the use of daratumumab (DARZALEX) in combination with bortezomib, thalidomide and dexamethasone (VTd) as treatment for patients newly diagnosed with multiple myeloma who are candidates for autologous stem cell transplant (ASCT) (Press release, Genmab, MAY 30, 2019, View Source [SID1234536715]). The sBLA was submitted by Genmab’s licensing partner, Janssen Biotech, Inc. (Janssen), in March 2019. Priority Review is a U.S. FDA designation for drugs that treat a serious condition and may provide a significant improvement in safety or efficacy. The U.S. FDA assigned a Prescription Drug User Fee Act (PDUFA) target date of September 26, 2019 to take a decision on daratumumab in this indication. In August 2012, Genmab granted Janssen an exclusive worldwide license to develop, manufacture and commercialize daratumumab.

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The sBLA submission is based on data from the Phase III CASSIOPEIA study of daratumumab in combination with VTd as treatment for patients newly diagnosed with multiple myeloma who are candidates for ASCT. The study is sponsored by the French Intergroupe Francophone du Myelome (IFM) in collaboration with the Dutch-Belgian Cooperative Trial Group for Hematology Oncology (HOVON) and Janssen. Genmab announced topline results from the trial in October 2018 and the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) accepted an abstract containing more complete data, submitted by Janssen, for oral presentation at the 2019 ASCO (Free ASCO Whitepaper) Annual meeting in June 2019.

"Thanks to the strong collaborative effort of IFM, HOVON and Janssen, should the U.S. FDA approve this sBLA, patients in the United States newly diagnosed with multiple myeloma who are eligible candidates for ASCT may one day also be able to include DARZALEX in combination with VTd in their treatment regimen," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

About the CASSIOPEIA (MMY3006) study
This Phase III study is a randomized, open-label, multicenter study, run by the French Intergroupe Francophone du Myelome (IFM) in collaboration with the Dutch-Belgian Cooperative Trial Group for Hematology Oncology (HOVON) and Janssen, including 1,085 newly diagnosed patients with previously untreated symptomatic multiple myeloma who are eligible for high dose chemotherapy and stem cell transplant. In the first part of the study, patients were randomized to receive induction and consolidation treatment with daratumumab combined with bortezomib, thalidomide (an immunomodulatory agent) and dexamethasone (a corticosteroid) or bortezomib, thalidomide and dexamethasone alone. The primary endpoint is the proportion of patients that achieve a stringent Complete Response (sCR). In the second part of the study, patients that achieved a response will undergo a second randomization to either receive maintenance treatment of daratumumab 16 mg/kg every 8 weeks for up to 2 years versus no further treatment (observation). The primary endpoint of this part of the study is progression free survival (PFS).

About multiple myeloma
Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excess proliferation of plasma cells.1 Multiple myeloma is the third most common blood cancer in the U.S., after leukemia and lymphoma.2 Approximately 26,000 new patients were expected to be diagnosed with multiple myeloma and approximately 13,650 people were expected to die from the disease in the U.S. in 2018.3 Globally, it was estimated that 160,000 people were diagnosed and 106,000 died from the disease in 2018.4 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms which can include bone problems, low blood counts, calcium elevation, kidney problems or infections.5

About DARZALEX(daratumumab)
DARZALEX (daratumumab) intravenous infusion is indicated in the United States in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy; in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI); and as a monotherapy for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.6 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (U.S. FDA) approval to treat multiple myeloma. DARZALEX is indicated in Europe in combination with bortezomib, melphalan and prednisone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy; and as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy. The option to split the first infusion of DARZALEX over two consecutive days has been approved in both Europe and the U.S. In Japan, DARZALEX is approved in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adults with relapsed or refractory multiple myeloma. DARZALEX is the first human CD38 monoclonal antibody to reach the market in the United Stated, Europe and Japan. For more information, visit www.DARZALEX.com.

Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. Daratumumab triggers a person’s own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death, via apoptosis (programmed cell death).6,7,8,9,10

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. A comprehensive clinical development program for daratumumab is ongoing, including multiple Phase III studies in smoldering, relapsed and frontline multiple myeloma settings and in amyloidosis. Additional studies are ongoing or planned to assess the potential of daratumumab in other malignant and pre-malignant diseases, such as NKT-cell lymphoma, B and T-ALL. Daratumumab has received two Breakthrough Therapy Designations