On November 16, 2020, Pfizer Inc. ("Pfizer") reported that it completed the previously disclosed transactions (the "Transactions") contemplated by (i) the Business Combination Agreement, dated as of July 29, 2019, as amended (the "Business Combination Agreement"), by and among Pfizer, Viatris Inc., formerly known as Upjohn Inc. ("Viatris"), Utah Acquisition Sub Inc., a wholly owned subsidiary of Viatris, Mylan N.V. ("Mylan"), Mylan I B.V., a wholly owned subsidiary of Mylan ("Mylan Newco"), and Mylan II B.V., a wholly owned subsidiary of Mylan Newco; and (ii) the Separation and Distribution Agreement, dated as of July 29, 2019, as amended (the "Separation and Distribution Agreement"), by and between Pfizer and Viatris. Specifically, (1) Pfizer contributed its global, primarily off-patent branded and generic established medicines business (the "Upjohn Business") to Viatris, so that the Upjohn Business was separated from the remainder of Pfizer’s businesses (the "Separation"), (2) following the Separation, Pfizer distributed, on a pro rata basis (based on the number of shares of Pfizer common stock held by holders of Pfizer common stock as of the record date of November 13, 2020), all of the shares of Viatris common stock held by Pfizer to Pfizer stockholders as of the record date (the "Distribution"); and (3) immediately after the Distribution, the Upjohn Business combined with Mylan in a series of transactions in which Mylan shareholders received one share of Viatris common stock for each Mylan ordinary share held by such shareholder, subject to any applicable withholding taxes (the "Combination") (Press release, Pfizer, NOV 19, 2020, View Source [SID1234571516]). Prior to the Distribution, Viatris made a cash payment to Pfizer equal to $12 billion as partial consideration for the contribution of the Upjohn Business from Pfizer to Viatris. As of the closing of the Combination, Pfizer stockholders owned approximately 57% of the outstanding shares of Viatris common stock, and Mylan shareholders owned approximately 43% of the outstanding shares of Viatris common stock, in each case on a fully diluted, as-converted and as-exercised basis. The Transactions are generally expected to be tax free to Pfizer and Pfizer stockholders. Effective as of the closing date of the Transactions, Viatris operates both Mylan and the Upjohn Business as an independent publicly traded company under the symbol "VTRS" on the NASDAQ.

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The following unaudited pro forma condensed consolidated financial statements were derived from Pfizer’s historical consolidated financial statements. Prior to the Separation, the Upjohn Business, and beginning in 2020, Pfizer’s Meridian Medical Technologies business ("Meridian"), the manufacturer of EpiPen and other auto-injector products, and a pre-existing strategic collaboration between Pfizer and Mylan for generic drugs in Japan (the "Mylan-Japan collaboration") were managed as part of Pfizer’s Upjohn operating segment. Revenues and expenses associated with Meridian and the Mylan-Japan collaboration were included in Pfizer’s Upjohn operating segment results along with the results of operations of the Upjohn Business in Pfizer’s historical consolidated financial statements.

Meridian supplies EpiPen Auto-Injectors to Mylan under a supply agreement expiring December 31, 2024, with an option for Viatris to further extend the term for an additional one-year period thereafter. Meridian will remain with Pfizer.

On November 13, 2020, subsidiaries of Pfizer and Mylan entered into a definitive agreement under which Pfizer will transfer certain assets, liabilities and operations that currently form part of the Mylan-Japan collaboration to Viatris. The transfer of the Mylan-Japan collaboration to Viatris is subject to the completion of customary closing conditions, including but not limited to, receipt of any necessary regulatory approvals.

The unaudited pro forma condensed consolidated financial statements of Pfizer are prepared in accordance with the Securities and Exchange Commission ("SEC") Regulation S-X Article 11 and are presented to illustrate the estimated effects of (i) the Distribution and the related $12 billion cash payment received by Pfizer from Viatris; and (ii) the planned transfer of the Mylan-Japan collaboration to Viatris (collectively, the "Upjohn Separation"). On November 18, 2020, Pfizer issued redemption notices for the full redemption of all $342,004,000 aggregate principal amount outstanding of its 5.80% Notes due August 12, 2023 (the "2023 Notes") and the full redemption of all $1,150,000,000 aggregate principal amount outstanding of its 1.950% Notes due June 3, 2021 (the "2021 Notes" and, together with the 2023 Notes, the "Notes"). The following unaudited pro forma condensed consolidated financial statements of Pfizer do not give effect to the redemption of the Notes. For additional information, see the notes to unaudited pro forma condensed consolidated financial statements, note 3.c.

The unaudited pro forma condensed consolidated statements of income for the nine months ended September 27, 2020 and the years ended December 31, 2019, 2018 and 2017 give effect to the Upjohn Separation as if it had occurred on January 1, 2017. The unaudited pro forma condensed consolidated balance sheet as of September 27, 2020 gives effect to the Upjohn Separation as if it had occurred on September 27, 2020. Beginning in the fourth quarter of 2020, financial results of the Upjohn Business for periods prior to November 16, 2020 and the Mylan-Japan collaboration will be reflected as discontinued operations in Pfizer’s consolidated financial statements. The financial results of the Mylan-Japan collaboration will continue to be reported in Pfizer’s consolidated financial statements until the transfer of the Mylan-Japan collaboration to Viatris closes.

The unaudited pro forma condensed consolidated financial statements are for illustrative and informational purposes only and are not intended to represent what Pfizer’s results of operations or financial position would have been had it operated without the Upjohn Business and the Mylan-Japan collaboration during the periods presented or if the Upjohn Separation described above had actually occurred as of the dates indicated. The unaudited pro forma condensed consolidated financial statements should not be considered indicative of Pfizer’s future results of operations or financial position without the Upjohn Business and the Mylan-Japan collaboration.

Pro forma adjustments give effect to events that are (i) directly attributable to the Upjohn Separation; (ii) factually supportable; and (iii) with respect to the statements of income, expected to have a continuing impact. The unaudited pro forma condensed consolidated statements of income do not reflect pro forma adjustments related to the effects of transition services arrangements or transitional manufacturing and supply arrangements between Pfizer and Viatris or the impact of any future events that may occur after the Upjohn Separation, including, but not limited to, potential reductions in interest expense as a result of repayment or redemption of Pfizer’s third-party debt or the expected realization of any cost savings or other restructuring actions after the Upjohn Separation.

The unaudited pro forma condensed consolidated financial statements are subject to the assumptions and adjustments described in the accompanying notes, which should be read together with the unaudited pro forma condensed consolidated financial statements. Management believes that these assumptions and adjustments are reasonable given the best information available at this time.

The following unaudited pro forma condensed consolidated financial statements should be read in conjunction with the following:

the section entitled "Management’s Discussion and Analysis of Financial Condition and Results of Operations" within Pfizer’s 2019 Financial Report, which was filed as Exhibit 13 to Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2019, and Pfizer’s Quarterly Report on Form 10-Q for the quarterly period ended September 27, 2020; and

Pfizer’s audited consolidated annual financial statements and accompanying notes in Pfizer’s 2019 Financial Report, which was filed as Exhibit 13 to Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2019 and Pfizer’s unaudited condensed consolidated interim financial statements and accompanying notes in Pfizer’s Quarterly Report on Form 10-Q for the quarterly period ended September 27, 2020.

The Historical Pfizer column in the unaudited pro forma condensed consolidated financial statements represents Pfizer’s historical financial statements for the periods presented and does not reflect any adjustments related to the Upjohn Separation.

The Upjohn Separation column in the unaudited pro forma condensed consolidated statements of income reflects the revenues and expenses directly associated with the results of operations of the Upjohn Business and the Mylan-Japan collaboration, which were derived from the financial information of Pfizer and the Upjohn Business identified below, adjusted to exclude previously allocated corporate overhead costs and to include separation costs that are directly related to the separation of the Upjohn Business from Pfizer. Separation costs included in this column are $176 million and $83 million for the nine months ended September 27, 2020 and the year ended December 31, 2019, respectively, and include transaction costs and external costs directly related to the operational separation of the Upjohn Business from Pfizer that will be reclassified to discontinued operations.

Included in the Upjohn Separation column in the unaudited pro forma condensed consolidated statements of income are the following Revenues and Income from continuing operations before provision/(benefit) for taxes on income associated with the Mylan-Japan collaboration:

The Upjohn Separation column in the unaudited pro forma condensed consolidated balance sheet includes the assets and liabilities of the Upjohn Business transferred to Viatris and the assets of the Mylan-Japan collaboration expected to transfer to Viatris. The Upjohn Separation column reflects, among other assets and liabilities, the elimination of goodwill attributed to the Upjohn operating segment and long-term debt and related accrued interest and restricted short-term investments identified with the Upjohn Business from Pfizer’s historical unaudited condensed consolidated balance sheet as of September 27, 2020. The Upjohn Separation column in the unaudited pro forma condensed consolidated balance sheet does not include assets and liabilities retained by Pfizer, which were not transferred to Viatris pursuant to the terms of the Business Combination Agreement, the Separation and Distribution Agreement and related ancillary agreements (collectively, the "Transaction Agreements").

Included in the Upjohn Separation column in the unaudited pro forma condensed consolidated balance sheet are total assets of the Mylan-Japan collaboration of approximately $154 million, consisting primarily of Trade accounts receivable, less allowance for doubtful accounts (approximately $61 million) and Inventories (approximately $94 million).

The historical financial results of the Upjohn Business and the Mylan-Japan collaboration in the Upjohn Separation column were derived from the following, adjusted for certain items, which are associated with the continuing operations of Pfizer:

Pfizer’s audited consolidated financial statements for the years ended December 31, 2019, 2018 and 2017, Pfizer’s unaudited condensed consolidated interim financial statements for the nine months ended September 27, 2020, and Pfizer’s related accounting records;

the Upjohn Business’s audited combined financial statements for the years ended December 31, 2019, 2018 and 2017 included in Upjohn Inc.’s registration statement on Form 10 (File No. 000-56114) filed with the SEC; and

the terms of the Transaction Agreements.

Pfizer believes that the adjustments included within the Upjohn Separation column of the unaudited pro forma condensed consolidated financial statements are consistent with the guidance under U.S. GAAP for discontinued operations in Accounting Standards Codification 205, "Presentation of Financial Statements." Pfizer’s current estimates of the discontinued operations amounts are preliminary and could change as Pfizer finalizes the discontinued operations accounting to be reported in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2020.

The Pro Forma Adjustments column in the unaudited pro forma condensed consolidated statements of income for the nine months ended September 27, 2020 and for the year ended December 31, 2019 and the unaudited pro forma condensed consolidated balance sheet as of September 27, 2020 includes the following pro forma adjustments:

Reflects adjustments for an intercompany lease entered into prior to the Upjohn Separation between Pfizer (as lessee) and the Upjohn Business (as lessor) that became a third-party lease between Pfizer and Viatris as of the closing date of the Transactions. The activity associated with this lease was eliminated in Pfizer’s consolidated financial statements prior to the Upjohn Separation but is no longer eliminated after the Upjohn Separation (see adjustment 3.d.).

CONDENSED CONSOLIDATED FINANCIAL STATEMENTS

Represents the tax impact of amounts in the Pro Forma Adjustments column impacting Income from continuing operations before provision/(benefit) for taxes on income at the applicable statutory income tax rates.

In order for the Transactions to be generally tax free to Pfizer and Pfizer stockholders, within thirty days of the closing date of the Transactions (the "Cash Disbursement Period"), Pfizer can only use the $12 billion proceeds to (i) repurchase Pfizer common stock, (ii) make pro rata special cash distributions to its stockholders, (iii) repay or repurchase certain debt (including principal, interest and associated premiums and fees) held by third-party lenders, and/or (iv) make contributions to one or more single-employer defined benefit plans for Pfizer’s employees and retirees.

Part of the $12 billion proceeds will be used by Pfizer for the: (i) full redemption of all $342,004,000 aggregate principal amount outstanding of its 5.80% Notes due August 12, 2023 (the "2023 Notes") and (ii) full redemption of all $1,150,000,000 aggregate principal amount outstanding of its 1.950% Notes due June 3, 2021 (the "2021 Notes" and, together with the 2023 Notes, the "Notes"). The redemption date of the Notes is November 28, 2020. On November 30, 2020, Pfizer will pay the applicable "make-whole" redemption prices as set forth in the indentures, as supplemented, pursuant to which the Notes were issued. The 2021 Notes are included in the Historical Pfizer column in the unaudited pro forma condensed consolidated balance sheet in Short-term borrowings, including current portion of long-term debt at a carrying value of approximately $1.15 billion and the 2023 Notes are included in Long-term debt at a carrying value of approximately $364 million. Also included in the Historical Pfizer column in the unaudited pro forma condensed consolidated balance sheet in Other current liabilities is accrued interest payable related to the Notes of approximately $10 million. The Historical Pfizer column in the unaudited pro forma condensed consolidated statements of income includes in Other (income)/deductions––net interest expense associated with the Notes of approximately $32 million for the nine months ended September 27, 2020, and approximately $45 million for the year ended December 31, 2019, which includes stated interest expense and amortization of bond discount and issuance costs. The Historical Pfizer column in the unaudited pro forma condensed consolidated statements of income includes in Other (income)/deductions––net amortization income related to purchase accounting adjustments associated with the 2023 Notes of approximately $5 million for the nine months ended September 27, 2020, and approximately $7 million for the year ended December 31, 2019. Pfizer expects it may incur a loss on the redemption date from the early extinguishment of the Notes, but the amount of such potential loss is not known at this time. The redemption of the Notes reflects only the partial use of the $12 billion proceeds. Pfizer’s expectation is to use the remaining proceeds to repay some of its third-party debt, in particular outstanding commercial paper borrowings, but that expectation may change before the Cash Disbursement Period expires. Accordingly, no pro forma adjustment for Pfizer’s use of the $12 billion proceeds has been made in the unaudited pro forma condensed consolidated financial statements.

On November 19, 2020 MercachemSyncom reported that it will change its name and operate under the registered trade name of Symeres (Press release, Mercachem, NOV 19, 2020, View Source [SID1234584204]).

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The new name reflects the strategic evolution of the company, with the growth of integrated drug discovery and development services, which complement the company’s strong reputation in synthetic discovery and development chemistry. Recent examples of this evolution include the acquisition of ADME-Tox provider Admescope in November 2020 and strategic alliances integrating our services with high-quality CROs in the fields of in vitro biology, biophysics, and structural biology.

The name Symeres (derived from Sy-ncom Me-rcachem res-research) and accompanying tagline "making molecules matter" are derived from the experience and success of the Syncom and Mercachem legacy organizations and their core strengths in innovative research.

Dr. Eelco Ebbers, CEO of Symeres, added, "The evolution of MercachemSyncom into Symeres is representative of the continuing expansion of the organization and our move into integrated solutions for drug discovery and development services, alongside our strong chemistry-centric services. The most recent example being our acquisition of Admescope. We look forward to continuing our journey with our clients around the world under our new identity, without forgetting the core values of quality, integrity, transparency, and innovation that got us to where we are today."

On November 19, 2020 Y-mAbs Therapeutics, Inc. (the "Company" or "Y-mAbs") (Nasdaq: YMAB) a late-stage clinical biopharmaceutical company focused on the development and commercialization of novel, antibody-based therapeutic products for the treatment of cancer, reported a clinical update on omburtamab for the treatment of diffuse intrinsic pontine glioma ("DIPG") (Press release, Y-mAbs Therapeutics, NOV 19, 2020, View Source [SID1234571422]). Data was presented at the Society for Neuro-Oncology ("SNO") Virtual Annual Meeting held November 19 through November 21, 2020. The omburtamab data was presented by Dr. Evan Bander from Weill Cornell Medicine.

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In a poster presentation, Dr. Bander presented infusion related data from the ongoing Phase 1 study in DIPG. The study showed the possibility of repeated convection enhanced delivery ("CED") infusions into the pediatric brainstem. Past CED treatments did not negatively influence the procedural workflow, technical application of the targeted interface, accuracy of catheter placement or distribution capacity. In the study, seven patients underwent two or more sequential CED infusions.

"The potential to retreat DIPG patients with multiple doses of omburtamab is truly exciting. We are planning for a multicenter Phase 2 study in DIPG, and hope to utilize this new insight to optimize the outcome for DIPG patients, who represent a significant unmet medical need," said Thomas Gad, founder, Chairman and President.

Researchers at Memorial Sloan Kettering Cancer Center ("MSK") developed omburtamab, which is exclusively licensed by MSK to Y-mAbs. As a result of this licensing arrangement, MSK has institutional financial interests related to the compound and Y-mAbs.

On November 19, 2020 AstraZeneca reported that it will present new research aimed at addressing key unmet needs facing patients with blood cancers at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, held virtually from 5 to 8 December 2020 (Press release, AstraZeneca, NOV 19, 2020, View Source [SID1234571438]).

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The Company will present 27 abstracts spanning five medicines and potential new medicines and eight different hematology conditions that demonstrate the Company’s commitment to advancing hematology research and treatments for patients living with hematologic malignancies.

Key data presentations include:

A pooled analysis of data from four trials – ELEVATE TN, ASCEND, ACE-CL-001 and 15-H-0016 – expanding on the cardiovascular safety profile of CALQUENCE (acalabrutinib) monotherapy treatment for patients with chronic lymphocytic leukemia (CLL)
Extended follow-up data from the pivotal Phase II ACE-LY-004 trial that support long-term treatment with CALQUENCE in adult patients with relapsed or refractory mantle cell lymphoma (MCL)
Data on CALQUENCE in combination with venetoclax and either obinutuzumab or rituximab in patients with CLL, showing a safety profile consistent with previous trials with high complete responses and undetectable minimal residual disease rates after a median follow-up of 26.9 months, with minimal to no drug-drug interactions in the Phase Ib ACE-CL-003 trial
First-in-human data from the potential new medicine B-cell maturation antigen (BCMA)-targeted antibody drug conjugate, MEDI2228, presenting data on safety and efficacy at all dose levels in relapsed or refractory multiple myeloma
Data showing pre-clinical evidence of overcoming resistance in relapsed or refractory MCL from the dual BCL2/XL inhibitor, AZD4320, which blocks the anti-apoptotic effect of BCL2 and BCLXL
Phase I data from the anti-inducible co-stimulator anti-ICOS monoclonal antibody, MEDI-570, demonstrating promising early clinical activity in poor-risk refractory and heavily pretreated patients with angioimmunoblastic T-cell lymphoma
Multiple studies on roxadustat, the first in a new class of medicines evaluating its clinical effectiveness and safety profile in both the dialysis dependent and non-dialysis dependent anemia of CKD patient populations
Data on roxadustat assessing efficacy in anemia secondary to lower-risk myelodysplastic syndrome (MDS) regardless of baseline factors. In approximately one in three patients MDS leads to acute myeloid leukemia1
Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: "Our data at ASH (Free ASH Whitepaper) this year continue to support CALQUENCE as a well-tolerated treatment with impressive efficacy and safety across multiple blood cancers, reinforcing physicians’ confidence in treating patients with CALQUENCE over the long term. Data at the meeting will also explore CALQUENCE combinations with commonly used therapies, showing potential across a variety of regimens in chronic lymphocytic leukemia to best suit the unique needs of each patient."

José Baselga, Executive Vice President, Oncology R&D, said: "As we rapidly expand our presence in hematology, we are focused on identifying novel targets and mechanisms of action that can address the most urgent unmet needs across various hematological malignancies. Our early portfolio at this year’s ASH (Free ASH Whitepaper) clearly demonstrates our commitment to following the science in combating treatment-resistant and rare blood cancers."

Key AstraZeneca presentations during the 62nd ASH (Free ASH Whitepaper) Annual Meeting and Exposition

Lead author

Abstract title

Presentation details

CALQUENCE (acalabrutinib)

Brown, JR

Pooled Analysis of Cardiovascular Events from Clinical Trials Evaluating Acalabrutinib Monotherapy in Patients with CLL

Abstract #3146

Oral and Poster Abstracts

Monday, 7 December

7am–3:30pm PST

Wang, M

Acalabrutinib Monotherapy in Patients with Relapsed/Refractory MCL: Long-Term Efficacy and Safety Results from a Phase 2 Study

Abstract #2040

Oral and Poster Abstracts

Mantle Cell, Follicular, and Other Indolent B-Cell Lymphoma

Sunday, 6 December

7am– 3:30pm PST

Woyach, JA

Acalabrutinib in Combination with Venetoclax and Obinutuzumab or Rituximab in Patients with Treatment-Naïve or Relapsed/Refractory CLL

Abstract #1312

Oral and Poster Abstracts

CLL: Therapy, excluding Transplantation

Saturday, 5 December
7am – 3:30pm PST

Davids, MS

Updated Safety and Efficacy Results from a Phase 2 Study of Acalabrutinib, Venetoclax and Obinutuzumab for Frontline Treatment of CLL

Abstract #3141

Oral and Poster Abstracts

CLL: Therapy, excluding Transplantation

Monday, 7 December
7am – 3:30pm PST

Munir, T

Cost-effectiveness of Acalabrutinib Monotherapy Compared with Chlorambucil Plus Obinutuzumab for Previously Untreated CLL

Abstract #2510

Oral and Poster Abstracts

Health Services Research—Malignant Conditions

Sunday, 6 December
7am – 3:30pm PST

Roxadustat

Henry, D

Oral Roxadustat Efficacy in Anemia Secondary to Lower-risk MDS Irrespective of Ring Sideroblasts and Baseline Erythropoietin Levels

Abstract #1277

Oral and Poster Abstracts

MDS — Clinical Studies

Saturday, 5 December
7am – 3:30pm PST

Provenzano, R

Pooled Efficacy and Cardiovascular Analysis of Roxadustat Compared with Placebo in Anemia Correction in Chronic Kidney Disease Patients Not on Dialysis

Abstract #1671

Oral and Poster Abstracts

Red Cells and Erythropoiesis, Structure and Function, Metabolism, and Survival, Excluding Iron

Sunday, 6 December
7am – 3:30pm PST

Fishbane, S

Pooled Efficacy and Cardiovascular Safety Results of Roxadustat Compared with Epoetin Alfa in the Treatment of Anemia in Chronic Kidney Disease Patients on Dialysis

Abstract #749

Oral and Poster Abstracts

Red Cells and Erythropoiesis, Structure and Function, Metabolism, and Survival, Excluding Iron

Saturday, 5 December
7am – 3:30pm PST

Early Stage Pipeline

Kumar, S

Phase 1, First-in-Human Study of MEDI2228, a BCMA-Targeted ADC in Patients with Relapsed/Refractory Multiple Myeloma

Abstract #179

Oral and Poster Abstracts

Myeloma/Amyloidosis: Therapy, excluding Transplantation

Saturday, 5 December
12–1:30pm PST

Li, Y

AZD4320 is a Novel and Potent BCL-2/XL Dual Inhibitor in Targeting Aggressive MCL

Abstract #2094

Oral and Poster Abstracts

Lymphoma: Pre-Clinical—Chemotherapy and Biologic Agents

Sunday, 6 December
7am – 3:30pm PST

Chavez, J

A Phase I Study of Anti-ICOS Antibody MEDI-570 for Relapsed/Refractory (R/R) Peripheral T-cell Lymphoma (PTCL) and Angioimmunoblastic T-cell Lymphoma (AITL) (NCI-9930)

Abstract #1151

Oral and Poster Abstracts

Hodgkin Lymphoma and T/NK Cell Lymphoma

Saturday, 5 December
7am – 3:30pm PST

INDICATION AND USAGE

CALQUENCE is a Bruton tyrosine kinase (BTK) inhibitor indicated for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.

This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

CALQUENCE is also indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

IMPORTANT SAFETY INFORMATION ABOUT CALQUENCE (acalabrutinib) capsules

Serious and Opportunistic Infections

Fatal and serious infections, including opportunistic infections, have occurred in patients with hematologic malignancies treated with CALQUENCE.

Serious or Grade 3 or higher infections (bacterial, viral, or fungal) occurred in 19% of 1029 patients exposed to CALQUENCE in clinical trials, most often due to respiratory tract infections (11% of all patients, including pneumonia in 6%). These infections predominantly occurred in the absence of Grade 3 or 4 neutropenia, with neutropenic infection reported in 1.9% of all patients. Opportunistic infections in recipients of CALQUENCE have included, but are not limited to, hepatitis B virus reactivation, fungal pneumonia, Pneumocystis jiroveci pneumonia, Epstein-Barr virus reactivation, cytomegalovirus, and progressive multifocal leukoencephalopathy (PML). Consider prophylaxis in patients who are at increased risk for opportunistic infections. Monitor patients for signs and symptoms of infection and treat promptly.

Hemorrhage

Fatal and serious hemorrhagic events have occurred in patients with hematologic malignancies treated with CALQUENCE. Major hemorrhage (serious or Grade 3 or higher bleeding or any central nervous system bleeding) occurred in 3.0% of patients, with fatal hemorrhage occurring in 0.1% of 1029 patients exposed to CALQUENCE in clinical trials. Bleeding events of any grade, excluding bruising and petechiae, occurred in 22% of patients.

Use of antithrombotic agents concomitantly with CALQUENCE may further increase the risk of hemorrhage. In clinical trials, major hemorrhage occurred in 2.7% of patients taking CALQUENCE without antithrombotic agents and 3.6% of patients taking CALQUENCE with antithrombotic agents. Consider the risks and benefits of antithrombotic agents when co-administered with CALQUENCE. Monitor patients for signs of bleeding.

Consider the benefit-risk of withholding CALQUENCE for 3-7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding.

Cytopenias

Grade 3 or 4 cytopenias, including neutropenia (23%), anemia (8%), thrombocytopenia (7%), and lymphopenia (7%), developed in patients with hematologic malignancies treated with CALQUENCE. Grade 4 neutropenia developed in 12% of patients. Monitor complete blood counts regularly during treatment. Interrupt treatment, reduce the dose, or discontinue treatment as warranted.

Second Primary Malignancies

Second primary malignancies, including skin cancers and other solid tumors, occurred in 12% of 1029 patients exposed to CALQUENCE in clinical trials. The most frequent second primary malignancy was skin cancer, reported in 6% of patients. Monitor patients for skin cancers and advise protection from sun exposure.

Atrial Fibrillation and Flutter

Grade 3 atrial fibrillation or flutter occurred in 1.1% of 1029 patients treated with CALQUENCE, with all grades of atrial fibrillation or flutter reported in 4.1% of all patients. The risk may be increased in patients with cardiac risk factors, hypertension, previous arrhythmias, and acute infection. Monitor for symptoms of arrhythmia (e.g., palpitations, dizziness, syncope, dyspnea) and manage as appropriate.

ADVERSE REACTIONS

The most common adverse reactions (≥ 20%) of any grade in patients with relapsed or refractory MCL were anemia,* thrombocytopenia,* headache (39%), neutropenia,* diarrhea (31%), fatigue (28%), myalgia (21%), and bruising (21%). The most common Grade ≥ 3 non-hematological adverse reaction (reported in at least 2% of patients) was diarrhea (3.2%).

*Treatment-emergent decreases (all grades) of hemoglobin (46%), platelets (44%), and neutrophils (36%) were based on laboratory measurements and adverse reactions.

Dose reductions or discontinuations due to any adverse reaction were reported in 1.6% and 6.5% of patients, respectively. Increases in creatinine 1.5 to 3 times the upper limit of normal occurred in 4.8% of patients.

The most common adverse reactions (≥ 30%) of any grade in patients with CLL were anemia,* neutropenia,* thrombocytopenia,* headache, upper respiratory tract infection, and diarrhea.

*Treatment-emergent decreases (all grades) of hemoglobin, platelets, and neutrophils were based on laboratory measurements and adverse reactions.

In patients with previously untreated CLL exposed to CALQUENCE, fatal adverse reactions that occurred in the absence of disease progression and with onset within 30 days of the last study treatment were reported in 2% for each treatment arm, most often from infection. Serious adverse reactions were reported in 39% of patients in the CALQUENCE plus obinutuzumab arm and 32% in the CALQUENCE monotherapy arm, most often due to events of pneumonia (7% and 2.8%, respectively).

Adverse reactions led to CALQUENCE dose reduction in 7% and 4% of patients in the CALQUENCE plus obinutuzumab arm (N=178) and CALQUENCE monotherapy arm (N=179), respectively. Adverse events led to discontinuation in 11% and 10% of patients, respectively. Increases in creatinine 1.5 to 3 times the upper limit of normal occurred in 3.9% and 2.8% of patients in the CALQUENCE combination arm and monotherapy arm, respectively.

In patients with relapsed/refractory CLL exposed to CALQUENCE, serious adverse reactions occurred in 29% of patients. Serious adverse reactions in > 5% of patients who received CALQUENCE included lower respiratory tract infection (6%). Fatal adverse reactions within 30 days of the last dose of CALQUENCE occurred in 2.6% of patients, including from second primary malignancies and infection.

Adverse reactions led to CALQUENCE dose reduction in 3.9% of patients (N=154), dose interruptions in 34% of patients, most often due to respiratory tract infections followed by neutropenia, and discontinuation in 10% of patients, most frequently due to second primary malignancies followed by infection. Increases in creatinine 1.5 to 3 times the upper limit of normal occurred in 1.3% of patients who received CALQUENCE.

DRUG INTERACTIONS

Strong CYP3A Inhibitors: Avoid co-administration with a strong CYP3A inhibitor. If a strong CYP3A inhibitor will be used short-term, interrupt CALQUENCE.

Moderate CYP3A Inhibitors: When CALQUENCE is co-administered with a moderate CYP3A inhibitor, reduce CALQUENCE dose to 100 mg once daily.

Strong CYP3A Inducers: Avoid co-administration with a strong CYP3A inducer. If a strong CYP3A inducer cannot be avoided, increase the CALQUENCE dose to 200 mg approximately every 12 hours.

Gastric Acid Reducing Agents: If treatment with a gastric acid reducing agent is required, consider using an H2-receptor antagonist or an antacid. Take CALQUENCE 2 hours before taking an H2-receptor antagonist. Separate dosing with an antacid by at least 2 hours.

Avoid co-administration with proton pump inhibitors. Due to the long-lasting effect of proton pump inhibitors, separation of doses may not eliminate the interaction with CALQUENCE.

SPECIFIC POPULATIONS

Based on findings in animals, CALQUENCE may cause fetal harm and dystocia when administered to a pregnant woman. There are no available data in pregnant women to inform the drug-associated risk. Advise pregnant women of the potential risk to a fetus.

Pregnancy testing is recommended for females of reproductive potential prior to initiating CALQUENCE therapy. Advise female patients of reproductive potential to use effective contraception during treatment with CALQUENCE and for at least 1 week following the last dose of CALQUENCE.

It is not known if CALQUENCE is present in human milk. Advise lactating women not to breastfeed while taking CALQUENCE and for at least 2 weeks after the final dose.

Avoid administration of CALQUENCE in patients with severe hepatic impairment. Dose modifications are not required for patients with mild or moderate hepatic impairment.

Please see full Prescribing Information, including Patient Information.

CALQUENCE
CALQUENCE (acalabrutinib) is a next-generation, selective inhibitor of Bruton’s tyrosine kinase (BTK). CALQUENCE binds covalently to BTK, thereby inhibiting its activity.2,3 In B-cells, BTK signaling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion.2

As part of an extensive clinical development program, AstraZeneca and Acerta Pharma are currently evaluating CALQUENCE in more than 20 company-sponsored clinical trials. CALQUENCE is being developed for the treatment of multiple B-cell blood cancers including CLL, MCL, diffuse large B-cell lymphoma, Waldenström macroglobulinemia, follicular lymphoma, and other hematologic malignancies.

Roxadustat
Roxadustat is a first in a new class of investigational medications that has the potential to promote erythropoiesis through increased endogenous production of erythropoietin; improved iron absorption, transport and mobilization; and downregulation of hepcidin, which helps to overcome the negative impact of inflammation on hemoglobin synthesis and red blood cell production. The roxadustat NDA for the treatment of anemia in CKD in both NDD and DD is under review by the US Food and Drug Administration with a decision expected in Q4 2020. Roxadustat is also in clinical development for anemia associated with myelodysplastic syndromes (MDS) and for chemotherapy-induced anemia (CIA).

AstraZeneca and FibroGen Inc. (FibroGen) are collaborating on the development and commercialization of roxadustat for the potential treatment of anemia in the US, China and other markets in the Americas and in Australia/New Zealand, as well as Southeast Asia. Astellas and FibroGen are collaborating on the development and commercialization of roxadustat for the potential treatment of anemia in territories including Japan, Europe, the Commonwealth of Independent States, the Middle East and South Africa.

AstraZeneca in hematology
Leveraging its strength in oncology, AstraZeneca has established hematology as one of four key oncology disease areas of focus. The Company’s hematology franchise includes two medicines approved by the US Food and Drug Administration and a robust global development program for a broad portfolio of potential blood cancer treatments. Acerta Pharma serves as AstraZeneca’s hematology research and development arm. AstraZeneca partners with like-minded science-led companies to advance the discovery and development of therapies to address unmet need.

AstraZeneca in oncology
AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With seven new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers.

By harnessing the power of six scientific platforms – Immuno-Oncology, Tumor Drivers and Resistance, DNA Damage Response, Antibody Drug Conjugates, Epigenetics, and Cell Therapies – and by championing the development of personalized combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

On November 19, 2020 IntraOp Medical Corporation and the University of Verona in Italy reported the enrollment of the first patient in the PancFORT Trial: A phase II study of primary chemotherapy, stereotactic body radiation therapy, and intraoperative radiation therapy in borderline resectable pancreatic adenocarcinoma (Press release, IntraOp Medical, NOV 19, 2020, View Source [SID1234571454]).

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Globally, over 460,000 patients are diagnosed with pancreatic cancer every year. Approximately 30% of those patients are diagnosed as having borderline resectable disease with an expected five-year survival rate of less than 15%.

The Pancreas Institute of the University of Verona is a world-renowned center of excellence for the treatment of pancreatic cancer with a dedicated multidisciplinary team that includes Gastroenterologists, Radiologists, Pathologists, and Oncologists. The General and Pancreatic Surgery Unit is led by Professor Claudio Bassi, MD, FRCS, FACS, FEBS, FASA (Hon.) and comprises a team of surgeons highly experienced in the treatment of all the inflammatory and neoplastic diseases of the pancreas, with a yearly operative caseload exceeding 400 pancreatic resections.

The PancFORT Trial is a prospective clinical trial led by principle investigators Salvatore Paiella, MD, PhD and Giuseppe Malleo, MD, PhD, that will explore the clinical benefits of delivering IORT in patients who’ve been diagnosed with borderline resectable pancreatic cancer and have undergone "total neoadjuvant" treatment including FOLFIRNOX and SBRT with a primary endpoint of three-year disease-specific survival. With the addition of electron beam IORT, the researchers anticipate the escalated dose will potentially improve survival with reduced likelihood of local recurrences and minimal side effects to the patients.

"Despite recent improvements in oncologic treatments, the prognosis for patients diagnosed with borderline resectable pancreatic cancer remains quite poor." stated Professor Claudio Bassi, MD, Chairman of the Surgery Unit of the Pancreas Institute of the University of Verona in Italy. "However, based on early results from PREOPANC trial, we see a promising opportunity to further improve clinical outcomes by combining a total neoadjuvant approach with an ablative dose of electron IORT delivered after resection or as an in situ treatment."

"The overall radiotherapy dose administered in this study corresponds to an ablative biologically effective dose, which could significantly increase the tumor local control rate and finally improve patients’ survival." stated Renzo Mazzarotto, MD, PhD, Chairman of the Radiation Oncology Department at the University Hospital of Verona, "Moreover, for patients whose tumors are determined to be not operable at the time of surgery, delivering IORT as in situ treatment could prevent possible disorders related to tumor progression, such as pain, duodenal/stomach infiltration and bleeding, thus improving patient’s quality of life."

"We are honored to be joining forces with Professor Bassi, Dr Mazzarotto, Drs Paiella and Malleo, and the rest of the team at the University Hospital of Verona to bring new treatment options to patients suffering from pancreatic cancer," said Derek T. DeScioli, Chief Executive Officer of IntraOp Medical Corporation. "As one of the most experienced and innovative pancreatic centers in Europe, they are a perfect partner for advancing the science and clinical evidence supporting the role of IORT in treating this dreadful disease. We look forward to the ongoing collaboration."