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Entry into a Material Definitive Agreement.

On April 9, 2020, SCYNEXIS, Inc. ("SCYNEXIS") reported that it has entered into a Senior Convertible Note Purchase Agreement (the "Note Purchase Agreement") with Puissance Life Science Opportunities Fund VI (the "Investor") (Filing, 8-K, Scynexis, APR 9, 2020, View Source [SID1234556229]). Pursuant to the Note Purchase Agreement, on April 9, 2020, SCYNEXIS issued and sold to the Investor $10.0 million aggregate principal amount of its 6.0% Senior Convertible Notes due 2026 (the "Notes"). The Notes were issued and sold for cash at a purchase price equal to 100% of their principal amount, in reliance on the exemption from registration provided by Section 4(a)(2) of the Securities Act of 1933, as amended (the "Securities Act"), due to the notes being issued to one financially sophisticated investor.

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The Notes will bear interest at a rate of 6.0% per annum, payable semiannually in arrears on April 15 and October 15 of each year, beginning October 15, 2020. The Notes will mature on April 15, 2026, unless earlier converted, redeemed or repurchased. The Notes constitute general, senior unsecured obligations of SCYNEXIS.

The holders of the Notes may convert their Notes at their option at any time prior to the close of business on the business day immediately preceding April 15, 2026 into shares of SCYNEXIS’s common stock. The initial conversion rate is 1,111.1111 shares of common stock per $1,000 principal amount of Notes, which is equivalent to an initial conversion price of approximately $0.90 per share, and is subject to adjustment in certain events described in the Note Purchase Agreement. Holders who convert may also be entitled to receive, under certain circumstances, an "interest make-whole payment" (as defined in the Note Purchase Agreement) payable in shares of common stock. In addition, following certain corporate events that occur prior to the maturity date, SCYNEXIS will, in certain circumstances, increase the conversion rate for a holder who elects to convert its Notes in connection with such a corporate event. Unless SCYNEXIS seeks and receives stockholder approval, the number of shares that SCYNEXIS may deliver in connection with a conversion of the Notes, including those delivered in connection with an "interest make-whole payment" or a "make-whole fundamental change" (each as defined in the Note Purchase Agreement), will not exceed a cap of 19,386,000 shares of common stock, which is approximately 19.99% of the shares of common stock of SCYNEXIS outstanding on March 1, 2020.

On or after April 15, 2023, SCYNEXIS has the right, at its election, to redeem all or any portion of the Notes not previously converted if the last reported sale price per share of common stock exceeds 130% of the conversion price on each of at least 20 trading days (whether or not consecutive) during the 30 consecutive trading days ending on, and including, the trading day immediately before the date SCYNEXIS sends the related redemption notice. The redemption price will be 100% of the principal amount of the Notes to be redeemed, plus accrued and unpaid interest to, but excluding, the redemption date.

If a "fundamental change" (as defined in the Note Purchase Agreement) occurs, then, subject to certain exceptions, SCYNEXIS must offer to repurchase the Notes for cash at a repurchase price of 100% of the principal amount of the Notes to be repurchased, plus accrued and unpaid interest to, but excluding, the repurchase date. A "fundamental change" includes the failure of SCYNEXIS’s VANISH-306 clinical study of oral ibrexafungerp in vulvovaginal candidiasis to achieve its pre-specified primary endpoint with statistical significance (p ≤ 0.05) superiority over placebo.

If certain bankruptcy and insolvency-related events of default with respect to SCYNEXIS occur, the principal of, and accrued and unpaid interest on, all of the then outstanding Notes shall automatically become due and payable. If any other event of default occurs and is continuing, the holders of at least 25% in principal amount of the outstanding Notes, by notice to SCYNEXIS, may declare the principal of, and accrued and unpaid interest on, all of the then outstanding Notes to be due and payable. Notwithstanding the foregoing, the Note Purchase Agreement provides that, to the extent SCYNEXIS elects, the sole remedy for an event of default relating to certain failures by SCYNEXIS to comply with certain reporting covenants in the Note Purchase Agreement will, for the first 180 days after such event of default, consist exclusively of the right to receive additional interest on the Notes.

Heron Therapeutics to Present at the 19th Annual Needham Virtual Healthcare Conference

On April 9, 2020 Heron Therapeutics, Inc. (Nasdaq: HRTX), a commercial-stage biotechnology company focused on improving the lives of patients by developing best-in-class treatments to address some of the most important unmet patient needs, reported that Barry Quart, Pharm.D., President and Chief Executive Officer of Heron Therapeutics, will present at the 19th Annual Needham Virtual Healthcare Conference on Tuesday, April 14th, 2020 at 2:50 p.m. ET (Press release, Heron Therapeutics, APR 9, 2020, View Source [SID1234556228]). The conference is being held in a virtual format.

A live webcast of the presentation will be available on the Company’s website at www.herontx.com in the Investor Resources section. A replay of the presentation will be archived on the site for 60 days.

Bolt Biotherapeutics Appoints Edith Perez, M.D., as Chief Medical Officer

On April 9, 2020 Bolt Biotherapeutics, Inc., a private clinical-stage biotechnology company developing its Immune-Stimulating Antibody Conjugate (ISAC) platform technology to harness the power of the immune system to treat cancer, reported the appointment of Edith Perez, M.D., as chief medical officer (Press release, Bolt Biotherapeutics, APR 9, 2020, View Source [SID1234556227]).

An internationally recognized translational researcher and cancer specialist, Dr. Perez has extensive experience in medical leadership with oncology drug development, translational clinical trials, biomarkers and precision medicine. Throughout her career, Dr. Perez has developed a wide range of clinical trials exploring the use of new therapeutic agents for the treatment and prevention of breast cancer. She has authored more than 400 peer-reviewed articles and is invited frequently to lecture at national and international meetings. In addition to her work in industry, Dr. Perez has held positions within AACR (Free AACR Whitepaper), ASCO (Free ASCO Whitepaper) and the NCI.

"With our first Boltbody therapeutic program in clinical development, Edith’s contributions as a member of our senior leadership team will have an immediate impact," said Randall Schatzman, Ph.D., chief executive officer of Bolt. "This is one of the most important additions to our company at a time that we are ramping up all of our drug development activities. Bolt is one of the most advanced companies that is focused on the emerging area of ISACs. Edith brings to us the relevant experience and insights to enable us to maintain our leadership position while driving forward clinical development of myeloid-based cancer therapeutics."

Dr. Perez commented, "Bolt’s technology platform has broad promise for the future of cancer therapies and could help a wide range of patients who have limited treatment options with current immunooncology therapeutics. I look forward to leading Bolt’s team in clinical development and strategy. Leveraging Bolt’s unique platform, we will address the unmet need to expand and improve targeted therapies, starting with BDC-1001 in solid tumors that express HER2 and are refractory to or ineligible for current HER2-targeting treatments. Our expanded strategy includes the development of Boltbody ISACs for other oncolytic targets, as well as in additional therapeutic indications."

Dr. Perez will maintain a clinical affiliation as Professor of Medicine at the Mayo Clinic and director of the Mayo Clinic Breast Cancer Translational Genomics Program, where she has practiced for two decades. Prior to joining Bolt, Dr. Perez was the vice president and head of the BioOncology-U.S. medical affairs unit at Genentech for three years. She earned her medical degree from the University of Puerto Rico School of Medicine in San Juan and completed her residency in internal medicine at the Loma Linda University Medical Center in California. In addition, she completed her fellowship training at the University of California, Davis. Dr. Perez is board certified in internal medicine, medical oncology and hematology.

TANGO THERAPEUTICS RAISES $60 MILLION SERIES B FINANCING AND STRENGTHENS EXECUTIVE TEAM

On April 9, 2020 Tango Therapeutics, a biotechnology company focused on discovering and delivering the next generation of targeted cancer therapies, reported the closing of an oversubscribed Series B financing of $60 million led by Boxer Capital of the Tavistock Group (Press release, Tango Therapeutics, APR 9, 2020, View Source [SID1234556226]). Cormorant Asset Management and Casdin Capital are additional new investors in the round.

"We are very fortunate to have the support of this strong syndicate of cross-over investors as we bring our first targeted therapies based on the genetic concept of synthetic lethality to well-defined patient populations," said Barbara Weber, MD, President and Chief Executive Officer of Tango. "This financing will support our lead program into IND-enabling studies early next year as well multiple other ongoing target and drug discovery efforts."

Additionally, Tango announced leadership appointments of Daniella Beckman, Chief Financial Officer, John C. Ross, Vice President of Human Resources and Samy Tadros, Vice President of Business Development.

Daniella Beckman, CPA, brings more than 20 years of strategic, financial and operational experience to her role at Tango overseeing finance, investor relations and business development. She served as interim Chief Financial Officer for Tango since its inception, and prior to that, for other early-stage biotechnology companies, including Neon Therapeutics. Previously, Ms. Beckman was the Chief Financial Officer of Idenix Pharmaceuticals, where she oversaw finance, investor relations and IT until it was acquired by Merck in 2014. Prior to serving as CFO, Ms. Beckman served as corporate controller for Idenix. She previously held finance positions at Coley Pharmaceuticals, Biogen Idec and PricewaterhouseCoopers. Ms. Beckman serves on the board of directors of Translate Bio. Ms. Beckman has a BA in business administration/accounting from Boston University and is a certified public accountant in Massachusetts.

John C. Ross, MS, MHRIR, joins Tango after serving as senior director of human resources for the surgical medical device business at Alcon, formerly a division of Novartis. Mr. Ross helped to facilitate the company’s spinoff from Novartis in 2019. Prior to Alcon, he served in multiple human resources leadership roles in Novartis Oncology and Novartis General Medicines in the U.S. and Europe. Mr. Ross also has held HR leadership roles at Google and Honeywell. Mr. Ross earned a BS in communications from the University of Texas at Austin and an MS in human resources and industrial relations from the University of Illinois.

Samy Tadros, MS, MBA, joins Tango from Celgene, recently acquired by Bristol Myers Squibb, where he served as Executive Director, Business Development and Global Alliances. Mr. Tadros spent more than ten years at Celgene, leading multiple cross-functional teams and closing many important transactions for Celgene. Mr. Tadros’ transactions spanned the spectrum from early research agreements to late stage development and commercialization deals. Before joining Celgene, Mr. Tadros worked at Charles River Labs and Schering-Plough. Mr. Tadros has a BS in biochemistry from Concordia University, an MS from the Temple University School of Pharmacy and an MBA from Fairleigh Dickinson University.

"We’re thrilled Daniella has agreed to join our team as CFO and to welcome John and Samy into these key leadership roles," added Dr. Weber. "Insights from all three industry leaders will be invaluable as we advance our pipeline of next-generation targeted cancer therapies and bring novel therapies to patients."

EMD Serono and Pfizer Receive US FDA Breakthrough Therapy Designation and Submit Application for BAVENCIO® for First-Line Maintenance Treatment of Locally Advanced or Metastatic Urothelial Carcinoma

On April 9, 2020 EMD Serono, the biopharmaceutical business of Merck KGaA, Darmstadt, Germany in the US and Canada, and Pfizer Inc. (NYSE: PFE) reported completion of the submission of a supplemental Biologics License Application (sBLA) to the US Food and Drug Administration (FDA) for BAVENCIO (avelumab)* for first-line maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) (Press release, Pfizer, APR 9, 2020, View Source [SID1234556225]). The FDA granted Breakthrough Therapy Designation to BAVENCIO for this indication, and the sBLA is being reviewed by the FDA under its Real-Time Oncology Review (RTOR) pilot program.

The application is based on positive results from an interim analysis of the Phase III JAVELIN Bladder 100 trial, which met its primary endpoint of overall survival (OS). In this study, BAVENCIO plus best supportive care (BSC) as first-line maintenance therapy significantly extended the survival of patients with previously untreated locally advanced or metastatic UC whose disease did not progress on induction chemotherapy, compared with BSC only. A statistically significant improvement was demonstrated in both co-primary populations: all randomized patients and patients with PD-L1–positive tumors. The safety profile for BAVENCIO in the trial was consistent with that in the JAVELIN monotherapy clinical development program. Detailed results from the JAVELIN Bladder 100 study will be presented at an upcoming medical congress.

"BAVENCIO is the first immunotherapy to demonstrate a statistically significant improvement in overall survival in a Phase III clinical trial in the first-line setting for patients with locally advanced or metastatic urothelial carcinoma," said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global Product Development. "Participation in the Real-Time Oncology Review program, coupled with the Breakthrough Therapy Designation, reflect the potential impact of BAVENCIO in this patient setting and provide the opportunity to work towards bringing this treatment option to patients as quickly as possible."

The RTOR program is intended to create a more efficient review process to bring safe and effective treatments to patients earlier, including drugs that are likely to demonstrate substantial improvements over currently available therapy. It allows the FDA to review clinical trial data from certain applications before the complete application is formally submitted. Review under the program does not guarantee or influence the approvability of the application.1

Breakthrough Therapy Designation is a program created by the FDA to accelerate the development and review of medicines intended to treat serious or life-threatening diseases where the new treatment may be a substantial improvement over available therapy. In order to receive Breakthrough Therapy Designation, preliminary clinical evidence must indicate that the drug may demonstrate a significant improvement over available therapy on a clinically significant endpoint.2

"Given the poor prognosis for patients with advanced urothelial carcinoma, there is an urgent need for additional treatment options that improve overall survival," said Luciano Rossetti, Head of Global R&D for EMD Serono. "Our data highlight the potential for a first-line maintenance treatment approach with BAVENCIO to advance the current standard of care for previously untreated patients, and we are working with urgency toward our goal of bringing this regimen to patients."

"For the past 30 years, chemotherapy has been the first-line standard of care for patients with advanced urothelial carcinoma. While this is an effective short-term option for many patients, most will ultimately experience disease progression, underscoring a need for additional treatment options," said Petros Grivas, M.D., Ph.D., one of the principal investigators in the JAVELIN Bladder 100 trial. "Based on the positive overall survival results from JAVELIN Bladder 100, I believe avelumab has the potential to be practice-changing."

In 2017, the FDA approved BAVENCIO for the treatment of patients with locally advanced or metastatic UC who have disease progression during or following platinum-containing chemotherapy, or who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response and duration of response. JAVELIN Bladder 100 is the confirmatory study for the conversion to full approval.

*BAVENCIO is under clinical investigation for the first-line maintenance treatment of advanced UC. There is no guarantee that BAVENCIO will be approved for first-line maintenance treatment of advanced UC by any health authority worldwide.

About JAVELIN Bladder 100
JAVELIN Bladder 100 (NCT02603432) is a Phase III, multicenter, multinational, randomized, open-label, parallel-arm study investigating first-line maintenance treatment with BAVENCIO plus BSC versus BSC alone in patients with locally advanced or metastatic UC. A total of 700 patients whose disease had not progressed after platinum-based induction chemotherapy as per RECIST v1.1 were randomized to receive either BAVENCIO plus BSC or BSC alone. The study achieved its primary endpoint of OS in each of the co-primary populations of all randomized patients and patients with PD-L1-positive tumors. Secondary endpoints include progression-free survival, anti-tumor activity, safety, pharmacokinetics, immunogenicity, predictive biomarkers and patient-reported outcomes in the co-primary populations. The safety profile for BAVENCIO in the trial was consistent with that in the JAVELIN monotherapy clinical development program.

About Urothelial Carcinoma
Bladder cancer is the tenth most common cancer worldwide.3 In 2018, there were over half a million new cases of bladder cancer diagnosed, with around 200,000 deaths from the disease globally.3 UC accounts for about 90% of all bladder cancers.4 This subtype becomes harder to treat as it advances, spreading through the layers of the bladder wall.5 For patients with metastatic UC, the five-year relative survival rate is 5%.6 Combination chemotherapy is currently the first-line standard of care for patients with advanced disease, and while a majority of patients experience high initial response rates, most patients will ultimately experience disease progression within nine months after initiation of treatment.7,8 Given the poor prognosis for patients with advanced bladder cancer whose disease progresses after first-line chemotherapy, there is an urgent need for additional treatment options that improve overall survival.9

About BAVENCIO (avelumab)
BAVENCIO is a human anti-programmed death ligand-1 (PD-L1) antibody. BAVENCIO has been shown in preclinical models to engage both the adaptive and innate immune functions. By blocking the interaction of PD-L1 with PD-1 receptors, BAVENCIO has been shown to release the suppression of the T cell-mediated antitumor immune response in preclinical models.10-12 In November 2014, Merck KGaA, Darmstadt, Germany and Pfizer announced a strategic alliance to co-develop and co-commercialize BAVENCIO.

BAVENCIO Approved Indications
BAVENCIO (avelumab) in combination with axitinib is indicated in the US for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

In the US, the FDA granted accelerated approval for BAVENCIO for the treatment of (i) adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (mMCC) and (ii) patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy, or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. These indications are approved under accelerated approval based on tumor response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

Avelumab is currently approved for patients with MCC in 50 countries globally, with the majority of these approvals in a broad indication that is not limited to a specific line of treatment.

BAVENCIO Important Safety Information from the US FDA-Approved Label

BAVENCIO can cause immune-mediated pneumonitis, including fatal cases. Monitor patients for signs and symptoms of pneumonitis, and evaluate suspected cases with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold BAVENCIO for moderate (Grade 2) and permanently discontinue for severe (Grade 3), life-threatening (Grade 4), or recurrent moderate (Grade 2) pneumonitis. Pneumonitis occurred in 1.2% of patients, including one (0.1%) patient with Grade 5, one (0.1%) with Grade 4, and five (0.3%) with Grade 3.

BAVENCIO can cause hepatotoxicity and immune-mediated hepatitis, including fatal cases. Monitor patients for abnormal liver tests prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater hepatitis. Withhold BAVENCIO for moderate (Grade 2) immune-mediated hepatitis until resolution and permanently discontinue for severe (Grade 3) or life-threatening (Grade 4) immune-mediated hepatitis. Immune-mediated hepatitis occurred with BAVENCIO as a single agent in 0.9% of patients, including two (0.1%) patients with Grade 5, and 11 (0.6%) with Grade 3.

BAVENCIO in combination with axitinib can cause hepatotoxicity with higher than expected frequencies of Grade 3 and 4 alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevation. Consider more frequent monitoring of liver enzymes as compared to when the drugs are used as monotherapy. Withhold BAVENCIO and axitinib for moderate (Grade 2) hepatotoxicity and permanently discontinue the combination for severe or life-threatening (Grade 3 or 4) hepatotoxicity. Administer corticosteroids as needed. In patients treated with BAVENCIO in combination with axitinib, Grades 3 and 4 increased ALT and AST occurred in 9% and 7% of patients, respectively, and immune-mediated hepatitis occurred in 7% of patients, including 4.9% with Grade 3 or 4.

BAVENCIO can cause immune-mediated colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold BAVENCIO until resolution for moderate or severe (Grade 2 or 3) colitis until resolution. Permanently discontinue for life-threatening (Grade 4) or recurrent (Grade 3) colitis upon reinitiation of BAVENCIO. Immune-mediated colitis occurred in 1.5% of patients, including seven (0.4%) with Grade 3.

BAVENCIO can cause immune-mediated endocrinopathies, including adrenal insufficiency, thyroid disorders, and type 1 diabetes mellitus.

Monitor patients for signs and symptoms of adrenal insufficiency during and after treatment, and administer corticosteroids as appropriate. Withhold BAVENCIO for severe (Grade 3) or life-threatening (Grade 4) adrenal insufficiency. Adrenal insufficiency was reported in 0.5% of patients, including one (0.1%) with Grade 3.

Thyroid disorders can occur at any time during treatment. Monitor patients for changes in thyroid function at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation. Manage hypothyroidism with hormone replacement therapy and hyperthyroidism with medical management. Withhold BAVENCIO for severe (Grade 3) or life-threatening (Grade 4) thyroid disorders. Thyroid disorders, including hypothyroidism, hyperthyroidism, and thyroiditis, were reported in 6% of patients, including three (0.2%) with Grade 3.

Type 1 diabetes mellitus including diabetic ketoacidosis: Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Withhold BAVENCIO and administer antihyperglycemics or insulin in patients with severe or life-threatening (Grade ≥3) hyperglycemia, and resume treatment when metabolic control is achieved. Type 1 diabetes mellitus without an alternative etiology occurred in 0.1% of patients, including two cases of Grade 3 hyperglycemia.

BAVENCIO can cause immune-mediated nephritis and renal dysfunction. Monitor patients for elevated serum creatinine prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater nephritis. Withhold BAVENCIO for moderate (Grade 2) or severe (Grade 3) nephritis until resolution to Grade 1 or lower. Permanently discontinue BAVENCIO for life-threatening (Grade 4) nephritis. Immune-mediated nephritis occurred in 0.1% of patients.

BAVENCIO can result in other severe and fatal immune-mediated adverse reactions involving any organ system during treatment or after treatment discontinuation. For suspected immune-mediated adverse reactions, evaluate to confirm or rule out an immune-mediated adverse reaction and to exclude other causes. Depending on the severity of the adverse reaction, withhold or permanently discontinue BAVENCIO, administer high-dose corticosteroids, and initiate hormone replacement therapy, if appropriate. Resume BAVENCIO when the immune-mediated adverse reaction remains at Grade 1 or lower following a corticosteroid taper. Permanently discontinue BAVENCIO for any severe (Grade 3) immune-mediated adverse reaction that recurs and for any life-threatening (Grade 4) immune-mediated adverse reaction. The following clinically significant immune-mediated adverse reactions occurred in less than 1% of 1738 patients treated with BAVENCIO as a single agent or in 489 patients who received BAVENCIO in combination with axitinib: myocarditis including fatal cases, pancreatitis including fatal cases, myositis, psoriasis, arthritis, exfoliative dermatitis, erythema multiforme, pemphigoid, hypopituitarism, uveitis, Guillain-Barré syndrome, and systemic inflammatory response.

BAVENCIO can cause severe or life-threatening infusion-related reactions. Premedicate patients with an antihistamine and acetaminophen prior to the first 4 infusions and for subsequent infusions based upon clinical judgment and presence/severity of prior infusion reactions. Monitor patients for signs and symptoms of infusion-related reactions, including pyrexia, chills, flushing, hypotension, dyspnea, wheezing, back pain, abdominal pain, and urticaria. Interrupt or slow the rate of infusion for mild (Grade 1) or moderate (Grade 2) infusion-related reactions. Permanently discontinue BAVENCIO for severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions. Infusion-related reactions occurred in 25% of patients, including three (0.2%) patients with Grade 4 and nine (0.5%) with Grade 3.

BAVENCIO in combination with axitinib can cause major adverse cardiovascular events (MACE) including severe and fatal events. Consider baseline and periodic evaluations of left ventricular ejection fraction. Monitor for signs and symptoms of cardiovascular events. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Discontinue BAVENCIO and axitinib for Grade 3-4 cardiovascular events. MACE occurred in 7% of patients with advanced RCC treated with BAVENCIO in combination with axitinib compared to 3.4% treated with sunitinib. These events included death due to cardiac events (1.4%), Grade 3-4 myocardial infarction (2.8%), and Grade 3-4 congestive heart failure (1.8%).

BAVENCIO can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to a fetus including the risk of fetal death. Advise females of childbearing potential to use effective contraception during treatment with BAVENCIO and for at least 1 month after the last dose of BAVENCIO. It is not known whether BAVENCIO is excreted in human milk. Advise a lactating woman not to breastfeed during treatment and for at least 1 month after the last dose of BAVENCIO due to the potential for serious adverse reactions in breastfed infants.

The most common adverse reactions (all grades, ≥ 20%) in patients with metastatic Merkel cell carcinoma (MCC) were fatigue (50%), musculoskeletal pain (32%), diarrhea (23%), nausea (22%), infusion-related reaction (22%), rash (22%), decreased appetite (20%), and peripheral edema (20%).

Selected treatment-emergent laboratory abnormalities (all grades, ≥ 20%) in patients with metastatic MCC were lymphopenia (49%), anemia (35%), increased aspartate aminotransferase (34%), thrombocytopenia (27%), and increased alanine aminotransferase (20%).

The most common adverse reactions (all grades, ≥ 20%) in patients with locally advanced or metastatic urothelial carcinoma (UC) were fatigue (41%), infusion-related reaction (30%), musculoskeletal pain (25%), nausea (24%), decreased appetite/hypophagia (21%), and urinary tract infection (21%).

Selected laboratory abnormalities (Grades 3-4, ≥ 3%) in patients with locally advanced or metastatic UC were hyponatremia (16%), increased gamma-glutamyltransferase (12%), lymphopenia (11%), hyperglycemia (9%), increased alkaline phosphatase (7%), anemia (6%), increased lipase (6%), hyperkalemia (3%), and increased aspartate aminotransferase (3%).

Fatal adverse reactions occurred in 1.8% of patients with advanced renal cell carcinoma (RCC) receiving BAVENCIO in combination with axitinib. These included sudden cardiac death (1.2%), stroke (0.2%), myocarditis (0.2%), and necrotizing pancreatitis (0.2%).

The most common adverse reactions (all grades, ≥20%) in patients with advanced RCC receiving BAVENCIO in combination with axitinib (vs sunitinib) were diarrhea (62% vs 48%), fatigue (53% vs 54%), hypertension (50% vs 36%), musculoskeletal pain (40% vs 33%), nausea (34% vs 39%), mucositis (34% vs 35%), palmar-plantar erythrodysesthesia (33% vs 34%), dysphonia (31% vs 3.2%), decreased appetite (26% vs 29%), hypothyroidism (25% vs 14%), rash (25% vs 16%), hepatotoxicity (24% vs 18%), cough (23% vs 19%), dyspnea (23% vs 16%), abdominal pain (22% vs 19%), and headache (21% vs 16%).

Selected laboratory abnormalities (all grades, ≥20%) worsening from baseline in patients with advanced RCC receiving BAVENCIO in combination with axitinib (vs sunitinib) were blood triglycerides increased (71% vs 48%), blood creatinine increased (62% vs 68%), blood cholesterol increased (57% vs 22%), alanine aminotransferase increased (ALT) (50% vs 46%), aspartate aminotransferase increased (AST) (47% vs 57%), blood sodium decreased (38% vs 37%), lipase increased (37% vs 25%), blood potassium increased (35% vs 28%), platelet count decreased (27% vs 80%), blood bilirubin increased (21% vs 23%), and hemoglobin decreased (21% vs 65.%).