On February 17, 2022 Coherus BioSciences, Inc. ("Coherus" or the "Company", Nasdaq: CHRS), reported financial results for the quarter and full year ended December 31, 2021 and highlighted recent achievement of important milestones toward the Company’s key strategic initiatives (Press release, Coherus Biosciences, FEB 17, 2022, View Source [SID1234608226]):

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RECENT EXECUTION ON KEY STRATEGIC INITIATIVES
Building an innovative immuno-oncology company:

U.S. Food and Drug Administration ("FDA") granted toripalimab BLA priority review for nasopharyngeal carcinoma ("NPC") and assigned a target action date of April 30, 2022.
Toripalimab in combination with chemotherapy demonstrated a statistically significant overall survival benefit in prespecified interim analysis of Phase 3 clinical trial in patients with non-small cell lung cancer.
Initiated process to exercise option to license JS006, a TIGIT targeted antibody being evaluated in combination with toripalimab in an ongoing Phase 1/2 clinical trial.
Advancing internal immuno-oncology antibody into IND enabling studies.
Diversifying and growing the commercial product portfolio:

FDA approved YUSIMRY (adalimumab-aqvh), a Humira biosimilar, on December 17, 2021.
FDA accepted for review the BLA for CIMERLI (ranibizumab-ranq), a Lucentis biosimilar, and assigned a target action date in August 2022.
UDENYCA (pegfilgrastim-cbqv) on-body injector ("OBI") achieved both pharmacokinetic and pharmacodynamic bioequivalence in randomized clinical trial, enabling prior approval supplement filing with FDA in 2022; if approved, a UDENYCA OBI would compete directly with Neulasta Onpro which retains approximately 50% share of the overall pegfilgrastim market.
"We have made rapid progress transforming Coherus into an innovative immuno-oncology company supported by income from a diversified portfolio of FDA-approved products. In 2022, we expect to launch two new products, if approved, including our first immuno-oncology antibody, toripalimab, addressing an unmet need in nasopharyngeal carcinoma, as well as CIMERLI. We also plan to initiate a clinical trial in North America evaluating toripalimab in combination with JS006, a TIGIT-targeted antibody," said Denny Lanfear, CEO of Coherus. "Looking ahead to 2023, we project accelerating revenue growth with the planned launch of FDA-approved YUSIMRY into the $17 billion Humira market and the introduction of the UDENYCA on-body injector, if approved, a new presentation that would enable us to address the remaining $1.2 billion Neulasta Onpro segment of the pegfilgrastim market where there is currently no biosimilar competition."

Fourth Quarter and Full Year 2021 Financial Results

Net revenue, consisting of net sales of UDENYCA, was $73.4 million for the fourth quarter of 2021 compared to $110.4 million for the same period in 2020. Net revenue for 2021 was $326.6 million compared to $475.8 million for 2020. The declines for the fourth quarter and full year 2021 were primarily due to a decrease in the number of units of UDENYCA sold as well as a decline in net realized price due to increased competition and COVID-19 impacts.

Cost of goods sold ("COGS") was $12.1 million and $11.7 million during the three months ended December 31, 2021 and 2020, respectively, and $57.6 million and $37.7 million for the full years 2021 and 2020, respectively. Through the first quarter of 2021, Coherus sold inventory that was manufactured and expensed prior to the approval of UDENYCA in late 2018. This inventory was depleted in the first quarter of 2021, and since then COGS fully reflects per unit acquisition cost of UDENYCA. UDENYCA COGS also includes a mid single digit royalty on net sales payable through the first half of 2024.

Research and development ("R&D") expenses for the fourth quarter of 2021 were $50.8 million, compared to $44.6 million for the same period in 2020. The increase was mainly due to higher regulatory and development costs in support of the advancement of multiple pipeline product candidates. R&D expense for 2021 was $363.1 million compared to $142.8 million for 2020. The increase of $220.3 million was primarily due to the $136.0 million upfront license fee paid to Junshi Biosciences and also due to costs incurred in the development of YUSIMRY, toripalimab and additional presentations of UDENYCA.

Selling, general and administrative ("SG&A") expenses were $50.1 million for the fourth quarter of 2021, compared to $37.7 million for the same period in 2020. The increase was driven primarily by increased commercialization expense to support UDENYCA sales. For the full year 2021, SG&A expenses were $169.7 million, compared to $139.1 million for the prior year. The year-over-year increase is primarily due to costs incurred in support of UDENYCA commercial activities, as well as an increase in stock-based compensation expense.

Cash and cash equivalents were $417.2 million as of December 31, 2021, compared to $541.2 million as of December 31, 2020. During 2021, Coherus used $37.4 million in operating activities and $138.4 million in investing activities, including $136.0 million in an upfront payment to Junshi Biosciences. The Company received net cash proceeds of $51.9 million from financing activities related to the issuance of common stock to Junshi Biosciences, as well as proceeds from the exercise of stock options and from purchases under the employee stock purchase plan.

Net loss for the fourth quarter of 2021 was $45.7 million, or $(0.60) per share on a diluted basis, compared to net income of $9.7 million, or $0.12 per share on a diluted basis for the same period in 2020. Net loss for 2021 was $287.1 million, or $(3.81) per share on a diluted basis, compared to net income of $132.2 million, or $1.62 per share on a diluted basis for 2020.

Non-GAAP net loss for the fourth quarter of 2021 was $35.1 million, or $(0.46) per share on a diluted basis, compared to non-GAAP income of $18.6 million, or $0.23 per share on a diluted basis for the same period in 2020. Non-GAAP net loss for 2021 was $88.5 million, or $(1.17) per share on a diluted basis, compared to non-GAAP income of $176.7 million, or $2.16 per share on a diluted basis for 2020. See "Non-GAAP Financial Measures" below for a discussion on how Coherus calculates non-GAAP net income (loss) and a reconciliation to the most directly comparable GAAP measures.

2022 Guidance

Coherus projects combined R&D and SG&A expenses in 2022 to be in the range of $415 million to $450 million, excluding a potential $25 million milestone payable upon FDA approval of the toripalimab BLA for nasopharyngeal carcinoma and the $35 million fee to exercise the option for the license to JS006, which is expected to close in the first quarter of 2022. The projected increase compared to 2021 is driven primarily by costs the Company expects to incur with the anticipated launches of two new products, toripalimab and CIMERLI, as well as manufacturing and development costs for additional presentations of UDENYCA and for FDA-approved YUSIMRY, which Coherus is planning to launch in 2023.

This financial guidance excludes the effects of any potential future strategic acquisitions, collaborations or investments, the exercise of rights or options related to collaboration programs, and any other transactions or items not yet identified or quantified. This guidance is subject to a number of risks and uncertainties. See Forward-Looking Statements described in the section below.

Conference Call Information
When: Thursday, Feb. 17, 2022, starting at 5 p.m. ET
Dial-in: (844) 452-6826 (Toll-Free U.S. and Canada) or (765) 507-2587 (International)
Conference ID: 3677018

Webcast: View Source
Please dial-in 15 minutes early to ensure a timely connection to the call.
Fourth quarter and full year 2021 financial results are posted on the Coherus website at View Source

On February 17, 2022 Celsion Corporation (NASDAQ: CLSN), a clinical-stage company focused on DNA-based immunotherapy and next-generation vaccines, reported that following a pre-planned interim safety review of 81 as treated patients randomized in the Phase I/II OVATION 2 Study with GEN-1 in advanced (Stage III/IV) ovarian cancer, the Data Safety Monitoring Board (DSMB) has unanimously recommended that the OVATION 2 Study continue treating patients with the dose of 100 mg/m2 (Press release, Celsion, FEB 17, 2022, View Source [SID1234608224]). The DSMB also determined that safety is satisfactory with an acceptable risk/benefit, and that patients tolerate up to 17 doses of GEN-1 during a course of treatment that lasts up to six months. No dose-limiting toxicities were reported.

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The OVATION 2 Study combines GEN-1, the Company’s IL-12 gene-mediated immunotherapy, with standard-of-care neoadjuvant chemotherapy (NACT) in patients newly diagnosed with Stage III/IV ovarian cancer. NACT is designed to shrink the cancer as much as possible for optimal surgical removal after three cycles of chemotherapy. Following NACT, patients undergo interval debulking surgery, followed by three additional cycles of chemotherapy to treat any residual tumor.

The OVATION 2 Study is designed with an 80% confidence interval for an observed Progression Free Survival (PFS) Hazard Ratio of 0.75, which would mean an approximate 33% improvement in risk for cancer progression when comparing the treatment arm (NACT + GEN-1) with the control arm (NACT only). GEN-1 is an immunotherapy that produces safe and durable local levels of IL-12, a pluripotent cytokine associated with the stimulation of innate and adaptive immune response against cancer. The GEN-1 nanoparticle comprises a DNA plasmid encoding IL-12 gene and a synthetic polymer facilitating plasmid delivery vector. Cell transfection is followed by persistent, local secretion of the IL-12 protein at therapeutic levels.

The Company also announced that more than 75% of the projected 110 patients have been enrolled in the OVATION 2 Study. Interim clinical data from the first 39 patients who have undergone interval debulking surgery showed that the GEN-1 treatment arm is showing a 27% improvement in R0 surgical resection rate over the control arm. A complete tumor resection (R0) is a microscopically margin-negative resection in which no gross or microscopic tumor remains in the tumor bed.

"Findings from our OVATION I and OVATION 2 studies show a consistent dose-dependent clinical response in both surgical outcome and tumor response, which is further supported by translational data of the tumor microenvironment," noted Nicholas Borys, M.D., Celsion’s executive vice president and chief medical officer. "We are encouraged by the current rate of patient recruitment and expect to complete enrollment by mid-2022. The primary endpoint for the study is progression-free survival (PFS) which we expect to report approximately 12 months after patient enrollment is completed."

In February 2021, the Company announced that GEN-1 received FDA Fast Track Designation in advanced ovarian cancer. Celsion plans to request FDA Breakthrough Therapy Designation for GEN-1 based on the encouraging clinical data.

"We thank the DSMB members for their work and advice," said Michael H. Tardugno, Celsion’s chairman, president and chief executive officer. "FDA Fast Track and Orphan Drug Designations for GEN-1 in advanced ovarian cancer are important for our future commercialization efforts. In addition, under the Biologics Price Competition and Innovation Act of 2009, sponsors of new, licensed biological products like GEN-1 that are approved through a Biologics License Application receive 12 years of market exclusivity. The FDA cannot license any 351(k) application for a biosimilar or interchangeable product that relies on the previously approved product as a reference for biosimilarity during this 12-year period."

About GEN-1 Immunotherapy

GEN-1, designed using Celsion’s proprietary TheraPlas platform technology, is an IL-12 DNA plasmid vector encased in a nanoparticle delivery system, which enables cell transfection followed by persistent, local secretion of the IL-12 protein. IL-12 is one of the most active cytokines for the induction of potent anti-cancer immunity acting through the induction of T-lymphocyte and natural killer (NK) cell proliferation. The Company previously reported positive safety and encouraging Phase I results with GEN-1 given as monotherapy or a combination therapy in patients with advanced peritoneally metastasized primary or recurrent ovarian cancer, and recently completed a Phase Ib dose-escalation trial (OVATION 1 Study) of GEN-1 in combination with carboplatin and paclitaxel in patients with newly diagnosed ovarian cancer.

About Epithelial Ovarian Cancer

Epithelial ovarian cancer (EOC) is the fifth deadliest malignancy among women in the United States. There are approximately 22,000 new cases of ovarian cancer every year and the majority (approximately 70%) are diagnosed in advanced stages III and IV. EOC is characterized by dissemination of tumor in the peritoneal cavity with a high risk of recurrence (75%, stage III and IV) after surgery and chemotherapy. Since the five-year survival rates of patients with stages III and IV disease at diagnosis are poor (41% and 20%, respectively), there remains a need for a therapy that not only reduces the recurrence rate but also improves overall survival. The peritoneal cavity of advanced ovarian cancer patients contains the primary tumor environment and is an attractive target for regional approach to immune modulation.

On February 17, 2022 Bristol Myers Squibb (NYSE: BMY) reported that the U.S. Food and Drug Administration (FDA) has accepted its supplemental Biologics License Application (sBLA) for Breyanzi (lisocabtagene maraleucel), a CD19-directed chimeric antigen receptor (CAR) T cell therapy, to expand its current indication to include earlier use of Breyanzi for the treatment of adults with relapsed or refractory large B-cell lymphoma (LBCL) after failure of first-line therapy (Press release, Bristol-Myers Squibb, FEB 17, 2022, View Source [SID1234608222]). The FDA has granted the application Priority Review and assigned a Prescription Drug User Fee Act (PDUFA) goal date of June 24, 2022.

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"Breyanzi as a differentiated CD19-directed CAR T cell therapyhas already proven to be an important treatment option for patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy and nowhas the potential to be a new standard of care for patients after failure of first-line therapy, offering significantly improved outcomes beyond the current mainstay of care," said Anne Kerber, senior vice president, Cell Therapy Development, Bristol Myers Squibb. "This acceptance from the FDA brings us one step closer to delivering a practice-changing treatment for primary refractory or relapsed large B-cell lymphoma, making Breyanzi available to more patients in need, and underscores the advancements we’re making in cell therapy research to transform the lives of patients with difficult-to-treat blood cancers, including lymphoma."

The sBLA is based on results from the Phase 3 TRANSFORM trial, a global, randomized, multicenter study evaluating Breyanzi as a second-line treatment in adults with relapsed or refractory LBCL compared to the standard of care consisting of salvage chemotherapy followed by high-dose chemotherapy plus autologous hematopoietic stem cell transplant. Results showed Breyanzi provided highly statistically significant and clinically meaningful improvements in event-free survival, complete responses and progression-free survival, and a positive trend in overall survival in patients with LBCL whose disease was primary refractory or relapsed within 12 months after first-line therapy compared to standard of care. Results were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in December 2021.

About TRANSFORM

TRANSFORM (NCT03575351) is a pivotal, global, randomized, multicenter Phase 3 trial evaluating Breyanzi compared to current standard of care regimens in adults with large B-cell lymphoma that is primary refractory or relapsed within 12 months after first-line therapy and who are intended for stem cell transplant. Patients were randomized to receive Breyanzi or standard of care salvage chemotherapy, including rituximab plus dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP), rituximab plus ifosfamide, carboplatin and etoposide (R-ICE), or rituximab plus gemcitabine, dexamethasone and cisplatin (R-GDP) per the investigators’ choice before proceeding to high-dose chemotherapy (HDCT) and hematopoietic stem cell transplant (HSCT). The primary endpoint of the study is event-free survival, defined as time from randomization to death from any cause, progressive disease, failure to achieve complete response or partial response, or start of new antineoplastic therapy due to efficacy concerns, whichever occurs first. Key secondary endpoints include complete response rate, progression-free survival, and overall survival. Overall response rate and duration of response are additional secondary endpoints.

About Breyanzi

Breyanzi is a CD-19 directed chimeric antigen receptor (CAR) T cell therapy with a defined and purified composition and 4-1BB costimulatory domain. Breyanzi is administered as a defined composition to reduce variability of the CD8 and CD4 component dose. The 4-1BB signaling domain enhances the expansion and persistence of the CAR T cells. Breyanzi is approved by the U.S. Food and Drug Administration for the treatment of adult patients with relapsed or refractory LBCL after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B. Breyanzi is not indicated for the treatment of patients with primary central nervous system lymphoma. The U.S. Prescribing Information for Breyanzi has a BOXED WARNING for the risks of cytokine release syndrome (CRS) and neurologic toxicities (NT). Breyanzi is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the BREYANZI REMS.

Breyanzi is also approved in Japan for relapsed and refractory LBCL after two or more lines of systemic therapy, and Marketing Authorization Applications for Breyanzi for this indicationare currently under review in the European Union, Switzerland and Canada. Bristol Myers Squibb’s clinical development program for Breyanzi includes clinical studies in earlier lines of treatment for patients with relapsed or refractory LBCL and other types of lymphoma. For more information, visit clinicaltrials.gov.

Important Safety Information

BOXED WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITIES

Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients receiving BREYANZI. Do not administer BREYANZI to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab with or without corticosteroids.
Neurologic toxicities, including fatal or life-threatening reactions, occurred in patients receiving BREYANZI, including concurrently with CRS, after CRS resolution or in the absence of CRS. Monitor for neurologic events after treatment with BREYANZI. Provide supportive care and/or corticosteroids as needed.
BREYANZI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the BREYANZI REMS.
Cytokine Release Syndrome (CRS)

CRS, including fatal or life-threatening reactions, occurred following treatment with BREYANZI. CRS occurred in 46% (122/268) of patients receiving BREYANZI, including ≥ Grade 3 (Lee grading system) CRS in 4% (11/268) of patients. One patient had fatal CRS and 2 had ongoing CRS at time of death. The median time to onset was 5 days (range: 1 to 15 days). CRS resolved in 119 of 122 patients (98%) with a median duration of 5 days (range: 1 to 17 days). Median duration of CRS was 5 days (range 1 to 30 days) in all patients, including those who died or had CRS ongoing at time of death.

Among patients with CRS, the most common manifestations of CRS include fever (93%), hypotension (49%), tachycardia (39%), chills (28%), and hypoxia (21%). Serious events that may be associated with CRS include cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), cardiac arrest, cardiac failure, diffuse alveolar damage, renal insufficiency, capillary leak syndrome, hypotension, hypoxia, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS).

Ensure that 2 doses of tocilizumab are available prior to infusion of BREYANZI. Sixty-one of 268 (23%) patients received tocilizumab and/or a corticosteroid for CRS after infusion of BREYANZI. Twenty-seven (10%) patients received tocilizumab only, 25 (9%) received tocilizumab and a corticosteroid, and 9 (3%) received corticosteroids only.

Neurologic Toxicities

Neurologic toxicities that were fatal or life-threatening, occurred following treatment with BREYANZI. CAR T cell-associated neurologic toxicities occurred in 35% (95/268) of patients receiving BREYANZI, including ≥ Grade 3 in 12% (31/268) of patients. Three patients had fatal neurologic toxicity and 7 had ongoing neurologic toxicity at time of death. The median time to onset of the first event was 8 days (range: 1 to 46 days). The onset of all neurologic events occurred within the first 8 weeks following BREYANZI infusion. Neurologic toxicities resolved in 81 of 95 patients (85%) with a median duration of 12 days (range: 1 to 87 days). Three of four patients with ongoing neurologic toxicity at data cutoff had tremor and one subject had encephalopathy. Median duration of neurologic toxicity was 15 days (range: 1 to 785 days) in all patients, including those with ongoing neurologic events at the time of death or at data cutoff.

Seventy-eight (78) of 95 (82%) patients with neurologic toxicity experienced CRS. Neurologic toxicity overlapped with CRS in 57 patients. The onset of neurologic toxicity was after onset of CRS in 30 patients, before CRS onset in 13 patients, same day as CRS onset in 7 patients, and same day as CRS resolution in 7 patients.

Neurologic toxicity resolved in three patients before the onset of CRS. Eighteen patients experienced neurologic toxicity after resolution of CRS.

The most common neurologic toxicities included encephalopathy (24%), tremor (14%), aphasia (9%), delirium (7%), headache (7%), dizziness (6%), and ataxia (6%). Serious events including cerebral edema and seizures occurred with BREYANZI. Fatal and serious cases of leukoencephalopathy, some attributable to fludarabine, have occurred in patients treated with BREYANZI.

CRS and Neurologic Toxicities Monitoring

Monitor patients daily at a certified healthcare facility during the first week following infusion, for signs and symptoms of CRS and neurologic toxicities. Monitor patients for signs and symptoms of CRS and neurologic toxicities for at least 4 weeks after infusion; evaluate and treat promptly. Counsel patients to seek immediate medical attention should signs or symptoms of CRS or neurologic toxicity occur at any time. At the first sign of CRS, institute treatment with supportive care, tocilizumab or tocilizumab and corticosteroids as indicated.

BREYANZI REMS

Because of the risk of CRS and neurologic toxicities, BREYANZI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the BREYANZI REMS. The required components of the BREYANZI REMS are:

Healthcare facilities that dispense and administer BREYANZI must be enrolled and comply with the REMS requirements.
Certified healthcare facilities must have on-site, immediate access to tocilizumab.
Ensure that a minimum of 2 doses of tocilizumab are available for each patient for infusion within 2 hours after BREYANZI infusion, if needed for treatment of CRS.
Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense, or administer BREYANZI are trained on the management of CRS and neurologic toxicities.
Further information is available at www.BreyanziREMS.com, or contact Bristol Myers Squibb at 1-888-423-5436.

Hypersensitivity Reactions

Allergic reactions may occur with the infusion of BREYANZI. Serious hypersensitivity reactions, including anaphylaxis, may be due to dimethyl sulfoxide (DMSO).

Serious Infections

Severe infections, including life-threatening or fatal infections, have occurred in patients after BREYANZI infusion. Infections (all grades) occurred in 45% (121/268) of patients. Grade 3 or higher infections occurred in 19% of patients. Grade 3 or higher infections with an unspecified pathogen occurred in 16% of patients, bacterial infections occurred in 5%, and viral and fungal infections occurred in 1.5% and 0.4% of patients, respectively. Monitor patients for signs and symptoms of infection before and after BREYANZI administration and treat appropriately. Administer prophylactic antimicrobials according to standard institutional guidelines.

Febrile neutropenia has been observed in 9% (24/268) of patients after BREYANZI infusion and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad spectrum antibiotics, fluids, and other supportive care as medically indicated.

Avoid administration of BREYANZI in patients with clinically significant active systemic infections.

Viral reactivation: Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with drugs directed against B cells. Ten of the 11 patients in the TRANSCEND study with a prior history of HBV were treated with concurrent antiviral suppressive therapy to prevent HBV reactivation during and after treatment with BREYANZI. Perform screening for HBV, HCV, and HIV in accordance with clinical guidelines before collection of cells for manufacturing.

Prolonged Cytopenias

Patients may exhibit cytopenias not resolved for several weeks following lymphodepleting chemotherapy and BREYANZI infusion. Grade 3 or higher cytopenias persisted at Day 29 following BREYANZI infusion in 31% (84/268) of patients, and included thrombocytopenia (26%), neutropenia (14%), and anemia (3%). Monitor complete blood counts prior to and after BREYANZI administration.

Hypogammaglobulinemia

B-cell aplasia and hypogammaglobulinemia can occur in patients receiving treatment with BREYANZI. The adverse event of hypogammaglobulinemia was reported as an adverse reaction in 14% (37/268) of patients; laboratory IgG levels fell below 500 mg/dL after infusion in 21% (56/268) of patients. Hypogammaglobulinemia, either as an adverse reaction or laboratory IgG level below 500 mg/dL after infusion, was reported in 32% (85/268) of patients. Monitor immunoglobulin levels after treatment with BREYANZI and manage using infection precautions, antibiotic prophylaxis, and immunoglobulin replacement as clinically indicated.

Live vaccines: The safety of immunization with live viral vaccines during or following BREYANZI treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during BREYANZI treatment, and until immune recovery following treatment with BREYANZI.

Secondary Malignancies

Patients treated with BREYANZI may develop secondary malignancies. Monitor lifelong for secondary malignancies. In the event that a secondary malignancy occurs, contact Bristol Myers Squibb at 1-888-805-4555 for reporting and to obtain instructions on collection of patient samples for testing.

Effects on Ability to Drive and Use Machines

Due to the potential for neurologic events, including altered mental status or seizures, patients receiving BREYANZI are at risk for altered or decreased consciousness or impaired coordination in the 8 weeks following BREYANZI administration. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, during this initial period.

Adverse Reactions

Serious adverse reactions occurred in 46% of patients. The most common nonlaboratory, serious adverse reactions (> 2%) were CRS, encephalopathy, sepsis, febrile neutropenia, aphasia, pneumonia, fever, hypotension, dizziness, and delirium. Fatal adverse reactions occurred in 4% of patients.

The most common nonlaboratory adverse reactions of any grade (≥ 20%) were fatigue, CRS, musculoskeletal pain, nausea, headache, encephalopathy, infections (pathogen unspecified), decreased appetite, diarrhea, hypotension, tachycardia, dizziness, cough, constipation, abdominal pain, vomiting, and edema.

Please see full Prescribing Information, including Boxed WARNINGS and Medication Guide.

Bristol Myers Squibb: Creating a Better Future for People with Cancer

Bristol Myers Squibb is inspired by a single vision—transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine, and through innovative digital platforms, are turning data into insights that sharpen their focus. Deep scientific expertise, cutting-edge capabilities and discovery platforms enable the company to look at cancer from every angle. Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. Because as a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.

Learn more about the science behind cell therapy and ongoing research at Bristol Myers Squibb here.

On February 17, 2022 Atara Biotherapeutics, Inc. (Nasdaq: ATRA), a leader in T-cell immunotherapy, leveraging its novel allogeneic Epstein-Barr virus (EBV) T-cell platform to develop transformative therapies for patients with cancer and autoimmune diseases, reported the Company will release fourth quarter and full year 2021 financial results after market close on Monday, February 28, 2022 (Press release, Atara Biotherapeutics, FEB 17, 2022, View Source [SID1234608221]). Following the release, the Company will host a live conference call and webcast at 4:30 p.m. EST to discuss the Company’s financial results and provide a corporate update.

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Analysts and investors can participate in the conference call by dialing 877-407-8291 for domestic callers and 201-689-8345 for international callers, using the conference ID 13725930. A live audio webcast can be accessed by visiting the Investors & Media – News & Events section of atarabio.com. An archived replay will be available on the Company’s website for 30 days following the live webcast.

On February 17, 2022 Arvinas, Inc. (Nasdaq: ARVN), a clinical-stage biotechnology company creating a new class of drugs based on targeted protein degradation, reported completed Phase 1 and interim Phase 2 ARDENT data for bavdegalutamide (ARV-110), a novel PROTAC degrader targeting the androgen receptor (AR) (Press release, Arvinas, FEB 17, 2022, View Source [SID1234608220]). These data continue to provide evidence of anti-tumor activity and clinical benefit in patients with metastatic castration-resistant prostate cancer (mCRPC). Bavdegalutamide reduced prostate-specific antigen (PSA) levels greater than or equal to 50% (PSA50) in 46% of patients with tumors harboring AR T878X and/ or H875Y (T878X = T878A or T878S) mutations, and two of the seven Response Evaluation Criteria in Solid Tumors (RECIST)-evaluable patients in this group also had confirmed tumor responses. These results also demonstrated PSA declines and tumor regressions in patients without tumors harboring AR T878X/H875Y mutations, suggesting an opportunity to develop bavdegalutamide more broadly in prostate cancer. Data from these trials will be presented in both a rapid abstract session and a poster session on February 17, 2022, at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary (ASCO GU) Cancers Symposium.

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"These results reinforce our belief that bavdegalutamide has the potential to provide meaningful clinical benefits to a patient population for which few options exist after progression of their mCRPC," said John Houston, Ph.D., president and chief executive officer of Arvinas. "In addition to a PSA50 response rate of 46% in tumors harboring T875X and/or H878Y mutations, we also saw durable confirmed responses in 2 of the 7 evaluable patients in this group. Overall, these data give us confidence that there is a clear path forward to accelerating the potential development of this novel treatment as a precision medicine option for patients."

Highlights from the Phase 1 and interim Phase 2 ARDENT data (data cut-off date, December 20, 2021):

PSA50 rate of 46% in patients with AR T878X/H875Y tumor mutations (n=28)
Two durable confirmed RECIST (Response Evaluation Criteria in Solid Tumors) partial responses out of seven RECIST-evaluable patients with AR T878X/H875Y tumor mutations
PSA reductions and evidence of anti-tumor activity as measured by RECIST were observed across all subgroups regardless of mutation status, including in patients with tumors not harboring AR T878X/875Y mutations
PSA50 rate of 22% (six of 27) in evaluable patients in the subgroup defined as "less pretreated" (having received only one prior novel hormonal agent and no prior chemotherapy). A majority of patients with PSA50 declines in this group had tumors with the AR T878X/H875Y mutations.
Bavdegalutamide had a manageable tolerability profile at the recommended Phase 2 dose (RP2D) of 420 mg oral, once daily. Most treatment-related adverse events (TRAEs) were Grade 1/2 and there were no Grade ≥4 TRAEs in the 138 patients treated at the RP2D
Arvinas intends to initiate discussions with the U.S. Food and Drug Administration (FDA) about the potential for an accelerated approval pathway with bavdegalutamide in a molecularly defined mCRPC population. The Company also plans to initiate a pivotal trial by year end. Future studies will be planned to explore the potential to treat earlier-line patients who may benefit from bavdegalutamide therapy.

Bavdegalutamide Clinical Update

Enrollment

As of the data cut-off date of December 20, 2021, 195 patients were enrolled across the Phase 1/2 clinical trial (71 in Phase 1; 124 in Phase 2).

The Phase 1 dose escalation trial evaluated bavdegalutamide at doses ranging from 35–700 mg, orally, once-daily (QD), or 210–420 mg twice-daily (BID) in patients with mCRPC and ≥2 prior therapies (including abiraterone and/or enzalutamide or other AR antagonist).

The ARDENT Phase 2 dose expansion trial was administered at a starting dose of 420 mg QD. Patients in the ARDENT trial received a median of four prior lines of therapy with 100% receiving at least one novel hormonal therapy (NHA; 64% abiraterone, 75% enzalutamide or other AR inhibitor, 39% both abiraterone and an AR inhibitor) and 31% receiving at least one chemotherapy regimen.

Patients in ARDENT were enrolled in one of four subgroups:

Tumors with AR T878X and/or H875Y mutations and excluding AR L702H mutations and AR-V7 splice variants
Tumors with wild-type AR or AR alterations other than T878X, H875Y, L702H, AR-V7
Tumors with AR L702H mutations or AR-V7 splice variants, which are variants of AR that bavdegalutamide does not degrade preclinically
Biomarker agnostic tumors with only one prior NHA and no prior chemotherapy
The biomarker-agnostic subgroup is referred to as "less pretreated;" the three biomarker-defined subgroups are referred to collectively as "more pretreated" and received 1-2 prior NHA and no more than two regimens of chemotherapy.

Efficacy Measures

Efficacy measures are presented on a combined basis for patients in both the completed Phase 1 dose escalation trial and the interim analysis from the ongoing ARDENT Phase 2 dose expansion trial.

Biomarker defined ("more pretreated"):
In patients with:

Tumors with AR T878X and/or H875Y mutations but excluding L702H and AR-V7 (n=8)
PSA50=75%; PSA30=75%
Tumors with wild-type AR or AR alterations other than T878X, H875Y, L702H, or AR-V7 (n=44)
PSA50=11%; PSA30=20%
Tumors with AR L702H or AR-V7 (n=25)
PSA50=4%; PSA30=20%
Biomarker agnostic ("less pretreated"):

No more than one prior NHA and no prior chemotherapy (n=27)
PSA50=22%; PSA30=26%
In biomarker-evaluable patients treated at or above the RP2D and with tumors harboring AR T878X/H875Y mutations (across all subgroups and thus regardless of prior therapy regimens or other mutations; n=28), the PSA50 response rate was 46% and the PSA decline of more than 30% (PSA30) response rate was 57%.

Of seven RECIST-evaluable patients across the Phase 1/Phase 2 trial having tumors harboring AR T878X/H875Y mutations, two had confirmed durable confirmed partial responses. These patients were on treatment for approximately nine months (ongoing as of the data cut-off) and 10 months; the duration of treatment ranged from eight weeks to 44 weeks, with three of the seven patients continuing on treatment as of the data cutoff of December 20, 2021.

Twelve (43%) of the 28 patients with AR T878X/H875Y-positive tumors received bavdegalutamide for ≥24 weeks, with nine patients ongoing as of the data cutoff.

One confirmed and three unconfirmed RECIST responses were seen in patients with tumors lacking AR T878X/H875Y mutations. The "less pretreated" subgroup (n=27) had a similar molecular profile – as assessed by circulating tumor DNA analysis – to the more pretreated, biomarker-defined subgroups in the ARDENT trial. These similarities included both AR variations (point mutations and AR-V7 splice variants) and non-AR mutations frequently associated with poor outcomes (e.g., TP53, BRCA1). Six of the 27 patients (22%) had PSA50 reductions, and this PSA50 rate was similar to that observed collectively in the "more pretreated" subgroups (16%; n=77). Four of the six "less pretreated" patients with PSA50 declines had tumors with AR T878X/H875Y mutations.

Safety

Bavdegalutamide had a manageable tolerability profile at the RP2D of 420 mg QD. The majority of treatment-related adverse events (TRAEs) were Grade 1/2 and there were no Grade ≥4 TRAEs in the 138 patients treated at the RP2D.

TRAEs that occurred in ≥10% of patients treated at the RP2D were nausea (Gr 1: 30%; Gr 2: 16%; Gr 3: 1%), fatigue (Gr 1: 23%; Gr 2: 12%; Gr 3: 1%), vomiting (Gr 1: 20%; Gr 2: 5%; Gr 3: 1%), decreased appetite (Gr 1: 14%; Gr 2: 11%; Gr 3: 1%), diarrhea (Gr 1: 14%; Gr 2: 4%; Gr 3: 2%), alopecia (Gr 1: 13%; Gr 2: 1%; Gr 3: N/A), AST increased (Gr 1: 9%; Gr 2: 3%; Gr 3: 1%), weight decreased (Gr 1: 7%; Gr 2: 5%; Gr 3: 0%), and anemia (Gr 1: 4%; Gr 2: 1%; Gr 3: 5%).

TRAEs at the RP2D led to dose reduction in 11 (8%) patients and discontinuation in 12 (9%) patients.

Anticipated 2022 Milestones for Bavdegalutamide

Discuss the potential accelerated approval path with the FDA (1H 2022)
Finalize partnership for companion diagnostic (1H 2022)
Initiate planned pivotal trial for patients with AR T878/H875 tumor mutations (2H 2022)
About Bavdegalutamide (ARV-110)
Bavdegalutamide is an investigational orally bioavailable PROTAC protein degrader designed to selectively target and degrade the androgen receptor (AR). Bavdegalutamide is being developed as a potential treatment for men with metastatic castration-resistant prostate cancer.

Bavdegalutamide has demonstrated activity in preclinical models of AR mutation or overexpression, both common mechanisms of resistance to currently available AR-targeted therapies.