On June 10, 2020 NantKwest, Inc. (Nasdaq: NK), a clinical-stage, natural killer cell-based therapeutics company, reported the publication of two peer-reviewed manuscripts in the Journal of Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (Press release, NantKwest, JUN 10, 2020, https://ir.nantkwest.com/news-releases/news-release-details/nantkwest-announces-studies-collaboration-national-cancer?field_nir_news_date_value[min]= [SID1234560976]). These invitro and in-vivo studies, conducted in collaboration with the National Cancer Institute pursuant to a Cooperative Research and Development Agreement, support the mechanism and functionality of NantKwest’s clinical-stage engineered natural killer (NK) cell lines, haNK and first-in-class PD-L1 t-haNKTM, as effecting anti-tumor activity in treatment-refractory cancer types even in the hypoxemic setting of the solid tumor microenvironment.

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"These published studies provide important insight and validation for the mechanism and activity of our novel first-in-class engineered NK cells for use in notoriously difficult solid tumor types," said Patrick Soon-Shiong, M.D., Chairman and Chief Executive Officer of NantKwest. "NK cells have the potential to kill tumor cells; however, the hypoxic nature of the suppressive tumor environment has been shown to curb primary NK cell function. These published data indicate that our engineered haNK cells remain active in hypoxic conditions, which may be an important new mechanism of its anti-tumor activity. In addition, our NK cells appear to be resistant even to acute hypoxia and are capable of maintaining tumor killing activity in conditions comparable to a suppressive tumor microenvironment."

Dr. Soon-Shiong continued, "In addition, we are encouraged to observe anti-tumor activity in every cancer cell line tested by the investigators at NCI. The positive data in the in-vivo models of solid tumors with PD-L1 t-haNK, our engineered haNK cell line that also expresses a PD-L1 CAR, provides a novel approach to target tumors expressing PD-L1. This highly targeted NK cell therapy has the potential to address the evolution of tumors as they become resistant to chemotherapy, antibody therapy and, ultimately, checkpoint immunotherapy. We have hypothesized that cancer undergoes a quantum change and adapts to the therapy administered, resulting in the selection of resistant, cancer stem-like cells. It is at this stage of evolution where intractable tumors such as in patients with metastatic pancreatic cancer and triple negative breast cancer, are deemed incurable. It is our belief that these cancer "stem" cells, which do not divide and hence are untouchable by chemotherapy, become resistant and render checkpoint therapy futile by not expressing t-cell receptor ligands. In the face of this immunosuppressive milieu, our PD-L1 t-haNK cells can act to kill these otherwise highly resistant cancer cells, as demonstrated by these two important reports by our colleagues at the NCI. Our clinical results in the first patient with advanced metastatic pancreatic cancer to have received PD-L1 t-haNK demonstrated a durable complete response."

Study highlights from the publication titled "Overcoming hypoxia-induced functional suppression of NK cells" include:

NantKwest haNK cells engineered to express a high-affinity CD16 receptor as well as internal interleukin (IL)-2 for increased antibody-dependent cellular cytotoxicity (ADCC) and activation maintained killing activity under hypoxic conditions comparable to those of the suppressive tumor microenvironment, while healthy donor NK cell activity was significantly impaired
NK killing, serial killing and ADCC were maintained under hypoxia in haNK cells
haNK cells’ IL-2 is likely a driver of maintained killing capacity under hypoxic conditions
Study highlights from the article titled "PD-L1-targeting high-affinity NK cells (PD-L1 t-haNK) induce direct antitumor effects and target suppressive MDSC populations" include:

PD-L1.t-haNK cells engineered to express a high-affinity CD16 receptor, an internal interleukin (IL)-2 and PD-L1-specific chimeric antigen receptor (CAR) broke down all 15 human tumor cell lines tested, including those modelling historically treatment-refractory cancers (triple negative breast cancer, lung, and urogenital cancer)
In vitro, the cytotoxicity of PD-L1 t-haNK cells was correlated to the PD-L1 expression of the tumor targets
In mouse models of solid tumors, PD-L1 t-haNK inhibited the growth of engrafted TNBC, lung and bladder tumors in mice without toxicity

On June 10, 2020 Mateon Therapeutics Inc. (OTCQB:MATN) reported the fruition of its licensing of OT-101/IL-2 combination to Autotelic BIO based on an agreement entered into between Oncotelic and Autotelic BIO, a South Korean Company, during 2018 (Press release, Mateon Therapeutics, JUN 10, 2020, View Source [SID1234560975]).

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OT-101 has received orphan drug designation for glioblastoma, melanoma, and pancreatic cancer. Furthermore, FDA recently granted Rare Pediatric Designation for OT-101 against diffuse intrinsic pontine glioma (DIPG). OT-101 is also effective against coronavirus including COVID-19 and being deployed against the COVID-19 epidemic.

OT-101 has demonstrated robust efficacy against pancreatic cancer, glioblastoma, and melanoma during phase 2 clinical trials. The demonstration that OT-101 will synergize with IL-2 further demonstrate its utility as adjunct to other immunotherapies. Interleukin-2 (IL-2, Aldesleukin, PROLEUKIN) Immunotherapy is cancer treatment that stimulates the body’s immune system to fight cancer, such as melanoma.

"In addition to additional milestone payments under said agreement, Mateon also entitled to profit sharing and royalties arising from the commercialization and/or licensing of OT-101/IL-2 by Autotelic BIO," stated Amit Shah, CFO of Mateon Therapeutics. "We look forward to continue our collaboration with Autotelic BIO and to make this unique immunotherapy available to patients."

On June 10, 2020 Can-Fite BioPharma Ltd. (NYSE American: CANF) (TASE:CFBI), a biotechnology company advancing a pipeline of proprietary small molecule drugs that address inflammatory, cancer and liver diseases, reported that it has entered into definitive agreements with several institutional and accredited investors for the purchase and sale of 3,902,440 of the Company’s American Depositary Shares (ADSs), at a purchase price of $2.05 per ADS, in a registered direct offering (Press release, Can-Fite BioPharma, JUN 10, 2020, View Source [SID1234560974]). Can-Fite has also agreed to issue and sell to the investors, in a concurrent private placement, unregistered warrants to purchase up to an aggregate of 1,951,220 ADSs. Each ADS represents thirty (30) ordinary shares, par value NIS 0.25 per share, of Can-Fite. The offering is expected to close on or about June 12, 2020, subject to satisfaction of customary closing conditions.

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H.C. Wainwright & Co. is acting as the exclusive placement agent for the offering.

The warrants will have an exercise price of $2.50 per ADS and will be exercisable at any time upon issuance and will expire four and one-half years from the date of issuance.

The gross proceeds from the offering (without taking into account any proceeds from any future exercises of warrants issued in the concurrent private placement), before deducting the placement agent’s fees and other estimated offering expenses payable by the Company, are expected to be approximately $8.0 million. Can-Fite intends to use the net proceeds for funding research and development and clinical trials, payment of a consulting fee, and for other working capital and general corporate purposes.

The ADSs (but not the warrants or the ADSs underlying the warrants) are being offered by Can-Fite pursuant to a "shelf" registration statement on Form F-3 (File No. 333-220644) originally filed with the U.S. Securities and Exchange Commission (the "SEC") on September 26, 2017 and declared effective by the SEC on October 11, 2017. The offering of the ADSs is being made only by means of a prospectus, including a prospectus supplement, forming a part of the effective registration statement. A final prospectus supplement and the accompanying prospectus relating to the ADSs being offered will be filed with the SEC. Electronic copies of the final prospectus supplement and the accompanying prospectus may be obtained, when available, on the SEC’s website at View Source or by contacting H.C. Wainwright & Co., LLC at 430 Park Avenue, 3rd Floor, New York, NY 10022, by phone at (646) 975-6996 or e-mail at [email protected].

The warrants described above were offered in a private placement under Section 4(a)(2) of the Securities Act of 1933, as amended (the "Act"), and Regulation D promulgated thereunder and, along with the ADSs underlying the warrants, have not been registered under the Act, or applicable state securities laws. Accordingly, the warrants and underlying ADSs may not be offered or sold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Act and such applicable state securities laws.

On June 10, 2020 PharmaCyte Biotech, Inc. (OTCQB: PMCB), a biotechnology company focused on developing cellular therapies for cancer and diabetes using its signature live-cell encapsulation technology, Cell-in-a-Box, reported that it has successfully completed development of the "change history" information and data for CypCaps (2nd generation product) compared to CapCell (1st generation product) (Press release, PharmaCyte Biotech, JUN 10, 2020, View Source [SID1234560973]). The history of the changes to the manufacturing of the two generations of product is a critical component of PharmaCyte’s Investigational New Drug application (IND) and is specifically required by the U.S. Food and Drug Administration (FDA).

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PharmaCyte’s Chief Executive Officer, Kenneth L. Waggoner, stated, "We are very pleased that our partner Austrianova developed the needed information and data to be in a position to satisfy our cGMP consultant and our regulatory consultant that the information and supporting data should be sufficient to meet the FDA comparability requirements of the two generations of encapsulated live human cells.

"The first generation of product was referred to as "CapCell", and the current generation of product is referred to as "CypCaps." Although the cellulose material is basically the same, a material of improved quality is used in the 2nd generation product. The differences relate to control of impurities with heavy metal content and microbial and endotoxin levels being below the limits in the relevant literature for powdered cellulose. In addition, the production process for the cellulose is more closely controlled in the 2nd generation product. The original cell line used is also now better characterized at the genetic level. Lastly, the encapsulated cells undergo a maturation process in the 2nd generation product and are stored frozen for a longer shelf life.

"In short, while both generations of product use the identical cell line, the CypCaps have improved quality and control of the cells, improved encapsulation material reproducibility, better controlled cell filling and a much-improved shelf life, resulting in a more robust product overall."

The FDA requires that all relevant information and data from different generations of the same manufactured medicinal product be compared to one another to ensure that the original manufactured product is essentially the same as the current one. There can be improvements to the product, but to use the data from the two clinical trials in the 1990s to support PharmaCyte’s Phase 2b clinical trial, it was imperative to develop information and data to support that the two generations of the products are essentially the same – the only difference being improvement to the overall product using the same manufacturing process.

Austrianova also had to gather the data for the release specifications for each generation of encapsulated cells and explain why changes were made and how the changes made for an improved product using the same manufacturing process. Information and data about the capsule maturation and storage were also developed.

In addition, the quality control release assay information and supporting data had to be assembled. This involved capsule diameter; viability of encapsulated cells; sterility; pyrogenicity; potency; cell identity; endotoxins; enzymatic activity; capsule count; label check; and pH.

To learn more about PharmaCyte’s pancreatic cancer treatment and how it works inside the body to treat locally advanced inoperable pancreatic cancer, we encourage you to watch the company’s documentary video complete with medical animations at: View Source

On June 10, 2020 Bristol Myers Squibb (NYSE: BMY) reported that Opdivo (nivolumab) was approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy (Press release, Bristol-Myers Squibb, JUN 10, 2020, View Source [SID1234560972]).1 This application was granted Priority Review Designation by the FDA, and the approval is based on the Phase 3 ATTRACTION-3 trial in which Opdivo (n=210) demonstrated superior overall survival (OS) versus taxane chemotherapy (n=209) (investigator’s choice of docetaxel or paclitaxel) (hazard ratio [HR] 0.77; 95% confidence interval [CI]: 0.62 to 0.96; p=0.0189).1,2 The median OS was 10.9 months (95% CI: 9.2 to 13.3) for Opdivo compared to 8.4 months (95% CI: 7.2 to 9.9) for docetaxel or paclitaxel.1 Opdivo is the first approved immunotherapy in this setting regardless of tumor PD-L1 expression level.

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Opdivo is associated with the following Warnings and Precautions including immune-mediated: pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, skin adverse reactions, encephalitis, other adverse reactions; infusion-related reactions; embryo-fetal toxicity; and increased mortality in patients with multiple myeloma when Opdivo is added to a thalidomide analogue and dexamethasone, which is not recommended outside of controlled clinical trials.1 Please see the Important Safety Information section below.

"Many cases of esophageal cancer are diagnosed at the advanced stage, when the disease could have a significant impact on a patient’s health.3 Treatment options can be limited once patients with advanced esophageal squamous cell carcinoma progress,"2,4 said Adam Lenkowsky, general manager and head, U.S., Oncology, Immunology, Cardiovascular, Bristol Myers Squibb. "The approval of Opdivo as a new treatment option for previously treated patients with advanced esophageal squamous cell carcinoma, regardless of PD-L1 expression, highlights our commitment to providing new options to address the unmet needs of patients and brings us another step closer to understanding the full potential of immunotherapy for gastrointestinal cancers."1,2,5,6,7

About ATTRACTION-3

ATTRACTION-3 (NCT02569242) is a Phase 3, multicenter, randomized, active-controlled, open-label global study evaluating Opdivo versus taxane chemotherapy (investigator’s choice of docetaxel or paclitaxel) in patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma, refractory or intolerant to at least one prior fluoropyrimidine- and platinum-based regimen. 1,2 The trial included patients regardless of tumor PD-L1 status, but tumor specimens were evaluated prospectively using the PD-L1 IHC 28-8 pharmDx assay at a central laboratory.1

The trial excluded patients who were refractory or intolerant to taxane therapy, had brain metastases that were symptomatic or required treatment, had autoimmune disease, used systemic corticosteroids or immunosuppressants or had apparent tumor invasion of organs adjacent to the esophageal tumor or had stents in the esophagus or respiratory tract.1 Patients were randomized to receive Opdivo 240 mg by intravenous infusion over 30 minutes every 2 weeks (n=210) or investigator’s choice of taxane chemotherapy (n=209) of either docetaxel 75 mg/m2 intravenously every 3 weeks (n=65), or paclitaxel 100 mg/m2 intravenously once a week for 6 weeks followed by 1 week off (n=144).1,2 Patient enrollment occurred predominantly in Asia, with the United States and Europe accounting for the remainder.2 Patients were treated until disease progression, assessed by the investigator per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), or unacceptable toxicity.1

The major efficacy outcome measure was OS.1 Additional efficacy outcome measures included overall response rate (ORR) and progression-free survival (PFS) as assessed by the investigator using RECIST v1.1 and duration of response (DOR).1 There was no statistically significant difference between the two arms for ORR (19.3% [33/171, 95% CI: 13.7 to 26.0] versus 21.5% [34/158, 95% CI: 15.4 to 28.8] for Opdivo (0.6% complete response [CR] and 18.7% partial response [PR]) and investigator’s choice chemotherapy (1.3% CR and 20.3% PR), respectively; p=0.6323).1 The median PFS was 1.7 months (95% CI: 1.5 to 2.7) for Opdivo versus 3.4 months (95% CI: 3.0 to 4.2) for investigator’s choice chemotherapy (HR 1.1; 95% CI: 0.9 to 1.3), however it was not tested due to the pre-specified hierarchical testing strategy.1 This trial was sponsored by Ono Pharmaceutical Co. Ltd. of Japan, Bristol Myers Squibb’s development partner for Opdivo.8

Select Safety Profile from ATTRACTION-3

The safety of Opdivo was evaluated in ATTRACTION-3 in 209 patients.1 Serious adverse reactions occurred in 38% of patients receiving Opdivo.1 Serious adverse reactions reported in ≥2% of patients who received Opdivo were pneumonia, esophageal fistula, interstitial lung disease and pyrexia. The following fatal adverse reactions occurred in patients who received Opdivo: interstitial lung disease or pneumonitis (1.4%), pneumonia (1.0%), septic shock (0.5%), esophageal fistula (0.5%), gastrointestinal hemorrhage (0.5%), pulmonary embolism (0.5%), and sudden death (0.5%).1 Opdivo was discontinued in 13% of patients and was delayed in 27% of patients for an adverse reaction.1 The most common adverse reactions occurring in ≥20% of Opdivo-treated patients were rash (22%) and decreased appetite (21%).1

About Esophageal Cancer

In the United States, it is estimated that approximately 18,440 new cases of esophageal cancer will be diagnosed and approximately 16,170 deaths will result from the disease this year alone.9 Esophageal cancer is a type of gastrointestinal cancer that starts in the inner layer of the esophagus (the mucosa) and grows.10 The mucosa is normally lined with squamous cells, and cancer starting in these cells is called squamous cell carcinoma, and accounts for less than 30% of esophageal cancers in the United States.10 For about 25% of patients, the disease is diagnosed in the advanced stage, which is typically harder to treat.3,7

Indication

OPDIVO (nivolumab) is indicated for the treatment of patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy.

The recommended dosage of OPDIVO for this indication is 240 mg IV infusion over 30 minutes every 2 weeks or 480 mg IV infusion over 30 minutes every 4 weeks, until disease progression or unacceptable toxicity.1

OPDIVO (10 mg/mL) is an injection for intravenous (IV) use.1

IMPORTANT SAFETY INFORMATION

Immune-Mediated Pneumonitis

OPDIVO can cause immune-mediated pneumonitis. Fatal cases have been reported. Monitor patients for signs with radiographic imaging and for symptoms of pneumonitis. Administer corticosteroids for Grade 2 or more severe pneumonitis. Permanently discontinue for Grade 3 or 4 and withhold until resolution for Grade 2. In patients receiving OPDIVO monotherapy, fatal cases of immune-mediated pneumonitis have occurred. Immune-mediated pneumonitis occurred in 3.1% (61/1994) of patients.

Immune-Mediated Colitis

OPDIVO can cause immune-mediated colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 (of more than 5 days duration), 3, or 4 colitis. Withhold OPDIVO monotherapy for Grade 2 or 3 and permanently discontinue for Grade 4 or recurrent colitis upon re-initiation of OPDIVO. In patients receiving OPDIVO monotherapy, immune-mediated colitis occurred in 2.9% (58/1994) of patients.

Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Addition of an alternative immunosuppressive agent to the corticosteroid therapy, or replacement of the corticosteroid therapy, should be considered in corticosteroid-refractory immune-mediated colitis if other causes are excluded.

Immune-Mediated Hepatitis

OPDIVO can cause immune-mediated hepatitis. Monitor patients for abnormal liver tests prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater transaminase elevations. Withhold OPDIVO for Grade 2 and permanently discontinue OPDIVO for Grade 3 or 4. In patients receiving OPDIVO monotherapy, immune-mediated hepatitis occurred in 1.8% (35/1994) of patients.

Immune-Mediated Endocrinopathies

OPDIVO can cause immune-mediated hypophysitis, immune-mediated adrenal insufficiency, autoimmune thyroid disorders, and Type 1 diabetes mellitus. Monitor patients for signs and symptoms of hypophysitis, signs and symptoms of adrenal insufficiency, thyroid function prior to and periodically during treatment, and hyperglycemia. Administer hormone replacement as clinically indicated and corticosteroids for Grade 2 or greater hypophysitis. Withhold for Grade 2 or 3 and permanently discontinue for Grade 4 hypophysitis. Administer corticosteroids for Grade 3 or 4 adrenal insufficiency. Withhold for Grade 2 and permanently discontinue for Grade 3 or 4 adrenal insufficiency. Administer hormone-replacement therapy for hypothyroidism. Initiate medical management for control of hyperthyroidism. Withhold OPDIVO for Grade 3 and permanently discontinue for Grade 4 hyperglycemia.

In patients receiving OPDIVO monotherapy, hypophysitis occurred in 0.6% (12/1994) of patients. In patients receiving OPDIVO monotherapy, adrenal insufficiency occurred in 1% (20/1994) of patients. In patients receiving OPDIVO monotherapy, hypothyroidism or thyroiditis resulting in hypothyroidism occurred in 9% (171/1994) of patients. Hyperthyroidism occurred in 2.7% (54/1994) of patients receiving OPDIVO monotherapy. In patients receiving OPDIVO monotherapy, diabetes occurred in 0.9% (17/1994) of patients.

Immune-Mediated Nephritis and Renal Dysfunction

OPDIVO can cause immune-mediated nephritis. Monitor patients for elevated serum creatinine prior to and periodically during treatment. Administer corticosteroids for Grades 2-4 increased serum creatinine. Withhold OPDIVO for Grade 2 or 3 and permanently discontinue for Grade 4 increased serum creatinine. In patients receiving OPDIVO monotherapy, immune-mediated nephritis and renal dysfunction occurred in 1.2% (23/1994) of patients.

Immune-Mediated Skin Adverse Reactions

OPDIVO can cause immune-mediated rash, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), some cases with fatal outcome. Administer corticosteroids for Grade 3 or 4 rash. Withhold for Grade 3 and permanently discontinue for Grade 4 rash. For symptoms or signs of SJS or TEN, withhold OPDIVO and refer the patient for specialized care for assessment and treatment; if confirmed, permanently discontinue. In patients receiving OPDIVO monotherapy, immune-mediated rash occurred in 9% (171/1994) of patients.

Immune-Mediated Encephalitis

OPDIVO can cause immune-mediated encephalitis. Evaluation of patients with neurologic symptoms may include, but not be limited to, consultation with a neurologist, brain MRI, and lumbar puncture. Withhold OPDIVO in patients with new-onset moderate to severe neurologic signs or symptoms and evaluate to rule out other causes. If other etiologies are ruled out, administer corticosteroids and permanently discontinue OPDIVO for immune-mediated encephalitis. In patients receiving OPDIVO monotherapy, encephalitis occurred in 0.2% (3/1994) of patients. Fatal limbic encephalitis occurred in one patient after 7.2 months of exposure despite discontinuation of OPDIVO and administration of corticosteroids.

Other Immune-Mediated Adverse Reactions

Based on the severity of the adverse reaction, permanently discontinue or withhold OPDIVO, administer high-dose corticosteroids, and, if appropriate, initiate hormone-replacement therapy. Across clinical trials of OPDIVO monotherapy, the following clinically significant immune-mediated adverse reactions, some with fatal outcome, occurred in <1.0% of patients receiving OPDIVO: myocarditis, rhabdomyolysis, myositis, uveitis, iritis, pancreatitis, facial and abducens nerve paresis, demyelination, polymyalgia rheumatica, autoimmune neuropathy, Guillain-Barré syndrome, hypopituitarism, systemic inflammatory response syndrome, gastritis, duodenitis, sarcoidosis, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), motor dysfunction, vasculitis, aplastic anemia, pericarditis, and myasthenic syndrome.

If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, which has been observed in patients receiving OPDIVO and may require treatment with systemic steroids to reduce the risk of permanent vision loss.

Infusion-Related Reactions

OPDIVO can cause severe infusion-related reactions, which have been reported in <1.0% of patients in clinical trials. Discontinue OPDIVO in patients with Grade 3 or 4 infusion-related reactions. Interrupt or slow the rate of infusion in patients with Grade 1 or 2. In patients receiving OPDIVO monotherapy as a 60-minute infusion, infusion-related reactions occurred in 6.4% (127/1994) of patients. In a separate trial in which patients received OPDIVO monotherapy as a 60-minute infusion or a 30-minute infusion, infusion-related reactions occurred in 2.2% (8/368) and 2.7% (10/369) of patients, respectively. Additionally, 0.5% (2/368) and 1.4% (5/369) of patients, respectively, experienced adverse reactions within 48 hours of infusion that led to dose delay, permanent discontinuation or withholding of OPDIVO.

Embryo-Fetal Toxicity

Based on mechanism of action, OPDIVO can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with OPDIVO and for at least 5 months after the last dose.

Increased Mortality in Patients with Multiple Myeloma when OPDIVO is Added to a Thalidomide Analogue and Dexamethasone

In clinical trials in patients with multiple myeloma, the addition of OPDIVO to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of patients with multiple myeloma with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analogue plus dexamethasone is not recommended outside of controlled clinical trials.

Lactation

It is not known whether OPDIVO is present in human milk. Because many drugs, including antibodies, are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from OPDIVO, advise women not to breastfeed during treatment and for at least 5 months after the last dose.

Serious Adverse Reactions

In Attraction-3, serious adverse reactions occurred in 38% of patients receiving OPDIVO (n=209). Serious adverse reactions reported in ≥2% of patients who received OPDIVO were pneumonia, esophageal fistula, interstitial lung disease and pyrexia. The following fatal adverse reactions occurred in patients who received OPDIVO: interstitial lung disease or pneumonitis (1.4%), pneumonia (1.0%), septic shock (0.5%), esophageal fistula (0.5%), gastrointestinal hemorrhage (0.5%), pulmonary embolism (0.5%), and sudden death (0.5%).

Common Adverse Reactions

In Attraction-3, the most common adverse reactions occurring in ≥20% of OPDIVO-treated patients (n=209) were rash (22%) and decreased appetite (21%).

Please see U.S. Full Prescribing Information for OPDIVO.

Bristol Myers Squibb: Advancing Cancer Research

At Bristol Myers Squibb, patients are at the center of everything we do. The goal of our cancer research is to increase patients’ quality of life, long-term survival and make cure a possibility. We harness our deep scientific experience, cutting-edge technologies and discovery platforms to discover, develop and deliver novel treatments for patients.

Building upon our transformative work and legacy in hematology and Immuno-Oncology that has changed survival expectations for many cancers, our researchers are advancing a deep and diverse pipeline across multiple modalities. In the field of immune cell therapy, this includes registrational CAR T cell agents for numerous diseases, and a growing early-stage pipeline that expands cell and gene therapy targets, and technologies. We are developing cancer treatments directed at key biological pathways using our protein homeostasis platform, a research capability that has been the basis of our approved therapies for multiple myeloma and several promising compounds in early- to mid-stage development. Our scientists are targeting different immune system pathways to address interactions between tumors, the microenvironment and the immune system to further expand upon the progress we have made and help more patients respond to treatment. Combining these approaches is key to delivering potential new options for the treatment of cancer and addressing the growing issue of resistance to immunotherapy. We source innovation internally, and in collaboration with academia, government, advocacy groups and biotechnology companies, to help make the promise of transformational medicines a reality for patients.

About Bristol Myers Squibb’s Patient Access Support

Bristol Myers Squibb remains committed to providing assistance so that cancer patients who need our medicines can access them and expedite time to therapy.

BMS Access Support, the Bristol Myers Squibb patient access and reimbursement program, is designed to help appropriate patients initiate and maintain access to BMS medicines during their treatment journey. BMS Access Support offers benefit investigation, prior authorization assistance, as well as co-pay assistance for eligible, commercially insured patients. More information about our access and reimbursement support can be obtained by calling BMS Access Support at 1-800-861-0048 or by visiting www.bmsaccesssupport.com.

About the Bristol Myers Squibb and Ono Pharmaceutical Collaboration

In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Bristol Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally, except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Ono and Bristol Myers Squibb further expanded the companies’ strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agents and combination regimens – for patients with cancer in Japan, South Korea and Taiwan.