On February 17, 2022 Lunaphore, a Swiss life sciences company developing technology to enable spatial biology in every laboratory, reported it has entered a collaboration with the Pathology Department at Massachusetts General Hospital to develop an in vitro diagnostic (IVD) that evaluates sensitivity of solid tumors to poly-ADP ribose polymerase (PARP) inhibitors, with an initial focus on ovarian, breast and prostate cancers (Press release, Lunaphore Technologies, FEB 17, 2022, View Source [SID1234608247]). The project will be led by Markus D. Herrmann, M.D., Ph.D., Director of Computational Pathology at Massachusetts General Hospital, who is also Assistant Professor of Pathology at Harvard Medical School. Lunaphore and Dr. Herrmann will collaborate to develop a multiplexed immunofluorescence assay that can measure the expression of multiple proteins using the COMET platform currently installed at Massachusetts General Hospital.

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"Spatial biology tools enhance the visualization and quantification of the expression of multiple proteins at once, providing valuable information for treatment decisions," said Diego G. Dupouy, Ph.D., Chief Technology Officer of Lunaphore. "This partnership will further solidify spatial biology’s role in both improved diagnostics and treatment selection with targeted therapies."

PARP inhibitors are targeted therapies that are designed to kill cancer cells by preventing them from repairing their damaged DNA. The DNA repair pathway called homologous recombination is of clinical interest as tumors with homologous recombination deficiency (HRD) have been found to be sensitive to PARP inhibitors. However, current methods of identifying HRD in tumors have been varied and imperfect. For example, current biomarker assays are not able to identify epigenetic changes in HRD genes with traditional genotyping assays.

"We look forward to developing a quantitative image-based proteomic assay to comprehensively assess DNA repair at the single-cell level in spatial tissue context and to better predict response to PARP inhibitor therapy," said Dr. Herrmann. "Adopting spatial biology methods can help us gain pathophysiological insight into the biological processes involved in DNA repair in tumor tissue that may yield clinically actionable biomarkers to improve treatment selection and patient outcomes."

On February 17, 2022 Exelixis, Inc. (Nasdaq: EXEL) reported financial results for the fourth quarter and full year 2021 and provided an update on progress toward achieving key corporate objectives, as well as commercial, clinical and pipeline development milestones (Press release, Exelixis, FEB 17, 2022, View Source [SID1234608246]).

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"The Exelixis team made significant progress across our entire business in the fourth quarter and throughout 2021"

"The Exelixis team made significant progress across our entire business in the fourth quarter and throughout 2021," said Michael M. Morrissey, Ph.D., President and Chief Executive Officer, Exelixis. "With strong performance from CABOMETYX in the fourth quarter, the cabozantinib franchise achieved two significant commercial milestones in 2021 with Exelixis full year U.S. net product revenues exceeding $1 billion and global net product revenues generated by Exelixis and its partners of more than $1.5 billion. These major milestones reflect the importance of our flagship product not only as a treatment for multiple serious cancers, but as the foundation for our company’s growth, enabling the buildout of our clinical pipeline and fueling our ambition to become a global, multiproduct oncology company."

Dr. Morrissey continued: "In late 2021 and early 2022, we achieved multiple key pipeline and discovery milestones, including expanding the phase 1b clinical program for XL092, advancing the phase 1 development of XB002 and XL102, in-licensing and progressing XL114 toward the clinic, and expanding our portfolio through new business development agreements. Collectively, our four clinical compounds and more than 10 discovery programs represent an exciting, diverse portfolio of therapeutic candidates with the potential to improve outcomes for patients with cancer. I’m grateful to the Exelixis team for their continued focus, commitment and hard work as we advance our mission to help cancer patients recover stronger and live longer."

Fourth Quarter and Full Year 2021 Financial Results

Total revenues for the quarter and year ended December 31, 2021 were $451.1 million and $1,435.0 million, respectively, compared to $270.1 million and $987.5 million for the comparable periods in 2020.

Total revenues for the quarter and year ended December 31, 2021 included net product revenues of $302.7 million and $1,077.3 million, respectively, compared to $200.4 million and $741.6 million for the comparable periods in 2020. The increases in net product revenues were primarily related to increases in sales volume driven by the strong uptake for the combination therapy of CABOMETYX (cabozantinib) and OPDIVO (nivolumab) following approval by the U.S. Food and Drug Administration (FDA) in January 2021.

Collaboration revenues, composed of license revenues and collaboration services revenues, were $148.5 million and $357.7 million for the quarter and year ended December 31, 2021, respectively, compared to $69.7 million and $246.0 million for the comparable periods in 2020. The increases in collaboration revenues were primarily related to increases in the recognition of milestone-related revenues, increases in development cost reimbursements earned, and higher royalty revenues for the sales of cabozantinib outside of the U.S. generated by Exelixis’ collaboration partners, Ipsen Pharma SAS (Ipsen) and Takeda Pharmaceutical Company Limited (Takeda).

Research and development expenses for the quarter and year ended December 31, 2021 were $222.3 million and $693.7 million, respectively, compared to $154.3 million and $547.9 million for the comparable periods in 2020. The increases in research and development expenses were primarily related to increases in license and other collaboration costs, personnel expenses and stock-based compensation expense, which were partially offset by decreases in clinical trial costs.

Selling, general and administrative expenses for the quarter and year ended December 31, 2021 were $99.3 million and $401.7 million, respectively, compared to $82.4 million and $293.4 million for the comparable periods in 2020. The increases in selling, general and administrative expenses were primarily related to increases in personnel expenses, marketing costs, legal costs, corporate giving and stock-based compensation expense.

Provision for (benefit from) income taxes for the quarter and year ended December 31, 2021 was $22.9 million and $63.1 million, respectively, compared to $(0.3) million and $19.1 million for the comparable periods in 2020, primarily due to an increase in pre-tax income.

GAAP net income for the quarter ended December 31, 2021 was $95.2 million, or $0.30 per share, basic and $0.29 per share, diluted, compared to GAAP net income of $28.4 million, or $0.09 per share, basic and diluted, for the comparable period in 2020. GAAP net income for the year ended December 31, 2021 was $231.1 million, or $0.73 per share, basic and $0.72 per share, diluted, compared to GAAP net income of $111.8 million, or $0.36 per share, basic and $0.35 per share, diluted, for the comparable period in 2020.

Non-GAAP net income for the quarter ended December 31, 2021 was $113.3 million, or $0.36 per share, basic and $0.35 per share, diluted, compared to non-GAAP net income of $43.3 million, or $0.14 per share, basic and diluted, for the comparable period in 2020. Non-GAAP net income for the year ended December 31, 2021 was $324.2 million, or $1.03 per share, basic and $1.01 per share, diluted, compared to non-GAAP net income of $193.3 million, or $0.63 per share, basic and $0.61 per share, diluted, for the comparable period in 2020. Non-GAAP net income excludes stock-based compensation, adjusted for the related income tax effect.

Cash, cash equivalents, restricted cash equivalents and investments were $1.9 billion at December 31, 2021, compared to $1.5 billion at December 31, 2020.

Non-GAAP Financial Measures

To supplement Exelixis’ financial results presented in accordance with U.S. Generally Accepted Accounting Principles (GAAP), Exelixis presents non-GAAP net income (and the related per share measures), which excludes from GAAP net income (and the related per share measures) stock-based compensation expense, adjusted for the related income tax effect for all periods presented.

Exelixis believes that the presentation of these non-GAAP financial measures provides useful supplementary information to, and facilitates additional analysis by, investors. In particular, Exelixis believes that these non-GAAP financial measures, when considered together with its financial information prepared in accordance with GAAP, can enhance investors’ and analysts’ ability to meaningfully compare Exelixis’ results from period to period, and to identify operating trends in Exelixis’ business. Exelixis has excluded stock-based compensation expense, adjusted for the related income tax effect, because it is a non-cash item that may vary significantly from period to period as a result of changes not directly or immediately related to the operational performance for the periods presented. Exelixis also regularly uses these non-GAAP financial measures internally to understand, manage and evaluate its business and to make operating decisions.

These non-GAAP financial measures are in addition to, not a substitute for, or superior to, measures of financial performance prepared in accordance with GAAP. Exelixis encourages investors to carefully consider its results under GAAP, as well as its supplemental non-GAAP financial information and the reconciliation between these presentations, to more fully understand Exelixis’ business. Reconciliations between GAAP and non-GAAP results are presented in the tables of this release.

2022 Financial Guidance

Exelixis is providing the following financial guidance for fiscal year 2022:

Total revenues

$1.525 billion – $1.625 billion

Net product revenues

$1.325 billion – $1.425 billion

Cost of goods sold

5% – 6% of net product revenues

Research and development expenses (1)

$725 million – $775 million

Selling, general and administrative expenses (2)

$400 million – $450 million

Effective tax rate

20% – 22%

____________________
(1) Includes $45 million of non-cash stock-based compensation expense.

(2) Includes $50 million of non-cash stock-based compensation expense.

Cabozantinib Highlights

Cabozantinib Franchise Net Product Revenues and Royalties. Net product revenues generated by the cabozantinib franchise in the U.S. were $302.7 million during the fourth quarter of 2021, with net product revenues of $295.1 million from CABOMETYX and $7.6 million from COMETRIQ (cabozantinib). For the year ended December 31, 2021, net product revenues generated by the cabozantinib franchise in the U.S. were $1,077.3 million, with net product revenues of $1,054.1 million from CABOMETYX and $23.2 million from COMETRIQ. In 2021, global cabozantinib franchise net product revenues generated by Exelixis and its partners exceeded $1.5 billion. Based upon cabozantinib-related net product revenues generated by Exelixis’ collaboration partners during the quarter and year ended December 31, 2021, Exelixis earned $29.3 million and $105.1 million, respectively, in royalty revenues.

Achievement of Cabozantinib Sales-Based Milestone from Ipsen. In the fourth quarter of 2021, Exelixis recorded in license revenues a $100.0 million milestone from Ipsen in connection with the achievement of $400.0 million in net sales in its related license territory over four consecutive quarters. Exelixis expects to receive this payment in the first quarter of 2022.

Completion of Enrollment in CONTACT-01 Pivotal Trial of Cabozantinib in Combination with an Immune Checkpoint Inhibitor (ICI) in Previously Treated Metastatic Non-Small Cell Lung Cancer (NSCLC). In November 2021, Exelixis announced that enrollment was completed for CONTACT-01, the global phase 3 pivotal trial evaluating cabozantinib in combination with atezolizumab versus docetaxel in patients with metastatic NSCLC who have been previously treated with an ICI and platinum-containing chemotherapy. CONTACT-01 enrolled 366 patients who were randomized 1:1 to the experimental arm of cabozantinib in combination with atezolizumab and the control arm of docetaxel. The primary endpoint of the trial is overall survival (OS). Secondary endpoints include progression-free survival (PFS), objective response rate (ORR) and duration of response (DOR). CONTACT-01 is sponsored by F. Hoffmann-La Roche Ltd. (Roche) and co-funded by Exelixis. Interim data from the trial are anticipated in the second half of 2022.

Presentation of Detailed Results from Phase 3 COSMIC-312 Pivotal Trial of Cabozantinib in Combination with Atezolizumab in Previously Untreated Advanced Hepatocellular Carcinoma (HCC) at the European Society for Medical Oncology Asia Virtual Oncology Week 2021 (ESMO Asia 2021). In November 2021, Exelixis presented detailed results from the first planned analysis of COSMIC-312, the ongoing phase 3 pivotal trial evaluating cabozantinib in combination with atezolizumab versus sorafenib in patients with previously untreated advanced HCC, at ESMO (Free ESMO Whitepaper) Asia 2021. Exelixis expects the final OS data to be available in early 2022.

Completion of Enrollment in CONTACT-03 Pivotal Trial of Cabozantinib in Combination with Atezolizumab in Previously Treated Metastatic Renal Cell Carcinoma (RCC). In January 2022, Exelixis announced that enrollment was complete for CONTACT-03, the global phase 3 pivotal trial evaluating cabozantinib in combination with atezolizumab versus cabozantinib alone in patients with locally advanced or metastatic clear cell or non-clear cell RCC who progressed during or following treatment with an ICI. CONTACT-03 enrolled 523 patients who were randomized 1:1 to the experimental arm of cabozantinib in combination with atezolizumab and the control arm of cabozantinib alone. The primary endpoints of the trial are PFS per Response Evaluation Criteria in Solid Tumors v. 1.1 as assessed by independent radiology review and OS. Secondary endpoints include PFS, ORR and DOR as assessed by study investigators. CONTACT-03 is sponsored by Roche and co-funded by Exelixis. Interim data from the trial are anticipated in the second half of 2022.

Cabozantinib Data at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO GI 2022). In January 2022, investigators presented encouraging data from two trials of cabozantinib in combination with ICIs for the treatment of advanced colorectal cancer (CRC). The results reinforce Exelixis’ decision to pursue clinical development of XL092, which pairs a target profile similar to cabozantinib with a potentially significantly improved safety profile, in advanced CRC through the STELLAR-303 global phase 3 pivotal trial expected to initiate in the first half of 2022.

Cabozantinib Data at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium (ASCO GU 2022). Later this week, cabozantinib will be the subject of multiple data presentations at ASCO (Free ASCO Whitepaper) GU 2022, which is being held in a hybrid virtual/in-person format from February 17-19. Notable presentations include two additional data sets from the phase 3 pivotal CheckMate -9ER study providing final OS analysis and organ-specific target lesion assessments with two-year follow-up, and updated health-related quality of life results.

Pipeline Highlights

In-Licensing of Second Anti-Cancer Compound from Aurigene Discovery Technologies Limited (Aurigene) Following FDA Acceptance of Investigational New Drug (IND) Application. In October 2021, Exelixis and Aurigene announced that Exelixis exercised its exclusive option to in-license XL114 (formerly AUR104) under the companies’ July 2019 collaboration, option and license agreement. As a result, Exelixis assumed responsibility for all subsequent clinical development, manufacturing and commercialization of the novel anti-cancer compound that inhibits the CARD11-BCL10-MALT1 (CBM) complex, a key component of signaling downstream of B- and T-cell receptors, which promotes B- and T-cell lymphoma survival and proliferation. Following the FDA’s recent acceptance of Exelixis’ IND, the company plans to initiate a phase 1 trial of XL114 as a monotherapy in patients with non-Hodgkin’s lymphoma (NHL) in the first half of 2022.

Initiation of STELLAR-002 Phase 1b Trial Evaluating XL092 in Combination with Immuno-Oncology (IO) Therapies in Patients with Advanced Solid Tumors. In December 2021, Exelixis announced the initiation of the dose-escalation stage of STELLAR-002, a phase 1b trial evaluating XL092 in combination with IO therapies in advanced solid tumors. The objective of the study is to evaluate the safety, tolerability and efficacy of XL092, Exelixis’ novel next-generation tyrosine kinase inhibitor, in combination with: nivolumab; nivolumab and ipilimumab; and nivolumab and bempegaldesleukin. Exelixis expects to expand the STELLAR-002 study, as well as the ongoing phase 1b STELLAR-001 study, which are evaluating XL092 in combination with several IO therapies, into potential new tumor types, and IO and other targeted therapy combination regimens throughout 2022. Clinical updates are expected in 2022.

Amendment of Option and License Agreement for XB002, an Antibody-Drug Conjugate (ADC) Targeting Tissue Factor (TF). In January 2022, Exelixis and Iconic Therapeutics, Inc. (Iconic) announced amended terms to their May 2019 exclusive option and license agreement for XB002, a next-generation TF-targeting ADC. Under the amended agreement, Exelixis acquired broad rights to use the anti-TF antibody incorporated into XB002 for any application, including conjugated to other payloads, as well as rights within oncology to a number of other anti-TF antibodies developed by Iconic, including for use in ADCs and multispecific biotherapeutics. The single-agent dose escalation cohort for Exelixis’ ongoing phase 1 trial of XB002 continues enrolling, with the study moving into its cohort expansion and combination phase as the next step. Based on early clinical data supportive of a potentially differentiated and best-in-class profile, Exelixis intends to aggressively expand development of XB002, both as a monotherapy and in combination with ICIs and other targeted therapies, across a wide range of tumor types, including indications other than those currently addressed by commercially available TF-targeted therapies. Exelixis expects to provide clinical updates from the ongoing phase 1 study of XB002 in 2022.

Corporate Updates

Exclusive Collaboration and License Agreement with STORM Therapeutics LTD (STORM) to Discover and Develop Inhibitors of Novel RNA Modifying Enzymes. In October 2021, Exelixis and STORM entered into an exclusive collaboration and license agreement under which the companies will discover and advance novel drug leads intended for the treatment of cancer. The collaboration will focus initially on ADAR1, advancing early work by STORM applying its proprietary RNA epigenetic platform, as well as explore an additional undisclosed target.

Appointment of Jacqueline Wright to the Exelixis Board of Directors. In December 2021, Exelixis announced that Jacqueline (Jacky) Wright was appointed to the company’s Board of Directors. The appointment took effect on December 16, 2021. Ms. Wright is an accomplished technology executive with decades of technology experience and is widely recognized for her expertise in digital transformation, both in the public and private sectors. She currently serves as Corporate Vice President & Chief Digital Officer, U.S. Business at Microsoft Corporation.

Appointment of Vicki L. Goodman, M.D., as Executive Vice President, Product Development & Medical Affairs and Chief Medical Officer (CMO). In January 2022, Exelixis announced the appointment of Vicki L. Goodman, M.D., as Executive Vice President, Product Development & Medical Affairs and CMO. Dr. Goodman has more than 20 years of oncology experience as a drug development leader at global biopharmaceutical organizations, regulator and clinician. She joined from Merck & Co., where she served as Vice President, Clinical Research and Therapeutic Area Head, Late Stage Oncology. Dr. Goodman will be based in the Greater Philadelphia area. As part of her role overseeing the company’s product development operations, she will play a leadership role in building a new Exelixis team that will expand the company’s development activities on the East Coast. Exelixis’ East Coast presence will complement the company’s growing West Coast development team and enable the company to lay additional groundwork for potential future growth outside the U.S.

Announcement of Key Priorities and Anticipated Milestones for 2022. In January 2022, Exelixis announced its key priorities and anticipated milestones for 2022, including: multiple pivotal clinical trial readouts for cabozantinib across the COSMIC and CONTACT clinical studies; the launch of the XL092 phase 3 pivotal trial program; the expansion of the ongoing phase 1b STELLAR-001/-002 clinical trials of XL092, with plans to provide clinical updates; accelerated development and expansion of the XB002 clinical program, with plans to provide clinical updates from the ongoing phase 1 study; expansion of the XL102 phase 1 clinical program into the cohort expansion phase, with plans to provide clinical updates; initiation of the phase 1 trial for XL114, an inhibitor of the CBM complex, in patients with NHL; plans to expand development operations to the East Coast under the leadership of Dr. Goodman, the company’s newly hired CMO; and the progression of up to five new development candidates into preclinical development from the company’s more than 10 discovery programs currently advancing through internal and collaborative efforts. Exelixis presented the details of its key priorities and anticipated milestones at the 40th Annual J.P. Morgan Healthcare Conference.

Basis of Presentation

Exelixis has adopted a 52- or 53-week fiscal year policy that ends on the Friday closest to December 31st. For convenience, references in this press release as of and for the fiscal periods ended January 1, 2021 are indicated as being as of and for the periods ended December 31, 2020.

Conference Call and Webcast

Exelixis management will discuss the company’s financial results for the fourth quarter and full year of 2021 and provide a general business update during a conference call beginning at 5:00 p.m. ET / 2:00 p.m. PT today, Thursday, February 17, 2022.

To access the webcast link, log onto www.exelixis.com and proceed to the News & Events / Event Calendar page under the Investors & Media heading. Please connect to the company’s website at least 15 minutes prior to the conference call to ensure adequate time for any software download that may be required to listen to the webcast. Alternatively, please call 855-793-2457 (domestic) or 631-485-4921 (international) and provide the conference call passcode 8647777 to join by phone.

A telephone replay will be available until 8:00 p.m. ET on Saturday, February 19, 2022. Access numbers for the telephone replay are: 855-859-2056 (domestic) and 404-537-3406 (international); the passcode is 8647777. A webcast replay will also be archived on www.exelixis.com for one year.

On February 17, 2022 Bayer reported that Results from the investigational Phase III ARASENS trial have shown that the use of oral androgen receptor inhibitor (ARi) NUBEQA (darolutamide) plus androgen deprivation therapy (ADT) and docetaxel significantly increased overall survival (OS) in patients with metastatic hormone-sensitive prostate cancer (mHSPC) compared to ADT plus docetaxel (Press release, Bayer, FEB 17, 2022, View Source [SID1234608245]). NUBEQA plus ADT and docetaxel significantly reduced the risk of death by 32.5% compared to ADT plus docetaxel (HR=0.68, 95% CI 0.57-0.80; P<0.001). At the data cutoff date for the primary analysis (October 25, 2021), the median treatment duration was longer for NUBEQA plus ADT and docetaxel (41.0 months) versus ADT plus docetaxel (16.7 months).1 NUBEQA is currently indicated for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC).

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These results were presented at the 2022 ASCO (Free ASCO Whitepaper) GU Cancers Symposium and simultaneously published in The New England Journal of Medicine.1

"Metastatic prostate cancer is a uniformly fatal disease and despite progress in recent years, only 30% of these men will survive beyond five years. ARASENS demonstrated that the addition of NUBEQA, an androgen receptor inhibitor, significantly increased overall survival for patients receiving standard androgen deprivation therapy and docetaxel as initial treatment for metastatic hormone-sensitive prostate cancer. NUBEQA also improved time to castration-resistant prostate cancer and other key secondary endpoints," said Matthew Smith, M.D., Ph.D., Director of the Genitourinary Malignancies Program, Massachusetts General Hospital Cancer Center. "These results are an important step forward for the treatment of patients with metastatic hormone-sensitive prostate cancer."

"With the ARASENS results in mHSPC adding to the existing Phase III ARAMIS data in nmCRPC, NUBEQA has now shown positive data in two pivotal clinical trials for patients across these key disease stages in prostate cancer," said Robert LaCaze, Member of the Executive Committee of Bayer’s Pharmaceutical Division and Head of the Oncology SBU at Bayer. "We believe NUBEQA has the potential to become a foundational drug for appropriate prostate cancer patients. We are committed to making this potential new treatment option in mHSPC available to patients and their treating physicians, and therefore are pursuing the fastest possible regulatory timelines."

ARASENS is the only randomized, double-blind pivotal study prospectively designed to compare the use of a second-generation ARi plus ADT and docetaxel to ADT plus docetaxel (a guideline recommended standard-of-care) in mHSPC.2

Detailed results from ARASENS

The significant improvement in OS was observed despite substantially higher use of subsequent systemic antineoplastic therapies (such as abiraterone, enzalutamide, cabazitaxel, docetaxel, radium-223 dichloride, sipuleucel-T, lutetium-177 PSMA, or apalutamide) among patients receiving ADT plus docetaxel who entered follow-up (75.6%) compared with the group who received NUBEQA plus ADT and docetaxel (56.8%).1

NUBEQA plus ADT and docetaxel demonstrated statistically significant benefits across multiple secondary endpoints compared to ADT plus docetaxel, including delaying the time to castration-resistant prostate cancer (CRPC) (HR=0.36, 95% CI 0.30-0.42; P<0.001), time to pain progression (HR=0.79, 95% CI 0.66-0.95; P=0.01), time to first symptomatic skeletal event (SSE) (HR=0.71, 95% CI 0.54-0.94; P=0.02) and time to initiation of subsequent systemic antineoplastic therapy (HR=0.39, 95% CI 0.33-0.46; P<0.001).1

Treatment-emergent adverse events (TEAEs) were similar between treatment arms. The most common TEAEs (≥10%) were highest during the overlapping docetaxel treatment period for both arms and decreased progressively thereafter. The most frequently reported AEs in the treatment arms (NUBEQA plus ADT and docetaxel versus ADT plus docetaxel) were alopecia (40.5% and 40.6%, respectively), neutropenia (39.3% and 38.8%, respectively), fatigue (33.1% and 32.9%, respectively) and anemia (27.8% and 25.1%, respectively). Grade 3 or 4 AEs reported in 66.1% versus 63.5% of patients were mainly due to neutropenia (33.7% versus 34.2%, respectively). Serious AEs occurred in 44.8% versus 42.3% of patients, and TEAEs leading to treatment discontinuation occurred in 13.5% versus 10.6% of patients.1

AEs of special interest in patients treated with AR pathway inhibitors for prostate cancer such as fatigue, falls, fractures, mental impairment and cardiovascular events were similar between study arms.1

About the ARASENS Trial2

The ARASENS trial (NCT02799602) is a randomized, Phase III, multi-center, double-blind, placebo-controlled trial which was prospectively designed to investigate the efficacy and safety of oral NUBEQA, an androgen receptor inhibitor (ARi), plus androgen deprivation therapy (ADT) and the chemotherapy docetaxel in patients with metastatic hormone-sensitive prostate cancer (mHSPC). A total of 1,306 newly diagnosed patients were randomized in a 1:1 ratio to receive 600 mg of NUBEQA twice a day or matching placebo, plus ADT and docetaxel.

The primary endpoint of this trial was overall survival (OS). Secondary endpoints included time to castration-resistant prostate cancer (CRPC), time to pain progression, time to first symptomatic skeletal event (SSE), time to initiation of subsequent anticancer therapy, all measured at 12‐week intervals, as well as adverse events (AEs) as a measure of safety and tolerability.

About NUBEQA (darolutamide)3

NUBEQA is an androgen receptor inhibitor (ARi) with a distinct chemical structure that competitively inhibits androgen binding, AR nuclear translocation, and AR-mediated transcription.3

On July 30, 2019, the FDA approved NUBEQA (darolutamide) based on the ARAMIS trial, a randomized, double-blind, placebo-controlled, multi-center Phase III study, which evaluated the safety and efficacy of oral NUBEQA in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) who were receiving a concomitant gonadotropin-releasing hormone (GnRH) analog or had a bilateral orchiectomy. In the clinical study, 1,509 patients were randomized in a 2:1 ratio to receive 600 mg of NUBEQA orally twice daily or androgen deprivation therapy (ADT) alone. The primary efficacy endpoint was metastasis-free survival (MFS). NUBEQA is also being investigated in further studies across various stages of prostate cancer, including another Phase III trial in metastatic hormone-sensitive prostate cancer (mHSPC) (ARANOTE) as well as a Phase III trial evaluating NUBEQA as an adjuvant treatment for localized prostate cancer with very high risk of recurrence (DASL-HiCaP). Information about these trials can be found at www.clinicaltrials.gov.

Developed jointly by Bayer and Orion Corporation, a globally operating Finnish pharmaceutical company, NUBEQA is currently indicated for the treatment of men with nmCRPC.3 The approvals of NUBEQA in the U.S., European Union (EU), and other global markets have been based on the pivotal Phase III ARAMIS trial data evaluating the efficacy and safety of NUBEQA plus ADT compared to ADT alone.3 Filings in other regions are underway or planned.

INDICATION FOR NUBEQA (darolutamide)

NUBEQA (darolutamide) is an androgen receptor inhibitor indicated for the treatment of patients with non-metastatic castration-resistant prostate cancer.

IMPORTANT SAFETY INFORMATION FOR NUBEQA (darolutamide)

Embryo-Fetal Toxicity: Safety and efficacy of NUBEQA have not been established in females. NUBEQA can cause fetal harm and loss of pregnancy. Advise males with female partners of reproductive potential to use effective contraception during treatment with NUBEQA and for 1 week after the last dose.

Adverse Reactions

Serious adverse reactions occurred in 25% of patients receiving NUBEQA and in 20% of patients receiving placebo. Serious adverse reactions in ≥1% of patients who received NUBEQA were urinary retention, pneumonia, and hematuria. Overall, 3.9% of patients receiving NUBEQA and 3.2% of patients receiving placebo died from adverse reactions, which included death (0.4%), cardiac failure (0.3%), cardiac arrest (0.2%), general physical health deterioration (0.2%), and pulmonary embolism (0.2%) for NUBEQA.

Adverse reactions occurring more frequently in the NUBEQA arm (≥2% over placebo) were fatigue (16% vs 11%), pain in extremity (6% vs 3%) and rash (3% vs 1%).

Clinically significant adverse reactions occurring in ≥2% of patients treated with NUBEQA included ischemic heart disease (4.0% vs 3.4% on placebo) and heart failure (2.1% vs 0.9% on placebo).

Drug Interactions

Effect of Other Drugs on NUBEQA – Combined P-gp and strong or moderate CYP3A4 inducers decrease NUBEQA exposure, which may decrease NUBEQA activity. Avoid concomitant use.

Combined P-gp and strong CYP3A4 inhibitors increase NUBEQA exposure, which may increase the risk of NUBEQA adverse reactions. Monitor more frequently and modify NUBEQA dose as needed.

Effects of NUBEQA on Other Drugs – NUBEQA inhibits breast cancer resistance protein (BCRP) transporter. Concomitant use increases exposure (AUC) and maximal concentration of BCRP substrates, which may increase the risk of BCRP substrate-related toxicities. Avoid concomitant use where possible. If used together, monitor more frequently for adverse reactions, and consider dose reduction of the BCRP substrate.

NUBEQA inhibits OATP1B1 and OATP1B3 transporters. Concomitant use may increase plasma concentrations of OATP1B1 or OATP1B3 substrates. Monitor more frequently for adverse reactions and consider dose reduction of these substrates.

Review the prescribing information of drugs that are BCRP, OATP1B1, and OATP1B3 substrates when used concomitantly with NUBEQA.

For important risk and use information about NUBEQA, please see the accompanying full Prescribing Information.

About Metastatic Hormone-Sensitive Prostate Cancer

Prostate cancer is the second most commonly diagnosed malignancy in men worldwide. In 2020, an estimated 1.4 million men were diagnosed with prostate cancer, and about 375,000 died from the disease worldwide.4

At the time of diagnosis, most men have localized prostate cancer, meaning their cancer is confined to the prostate gland and can be treated with curative surgery or radiotherapy.5,6 Upon relapse when the disease will metastasize or spread, androgen deprivation therapy (ADT) is the cornerstone of treatment for this hormone-sensitive disease. Approximately 5% of men will already suffer from prostate cancer with distant metastases when first diagnosed. Current treatment options for men with metastatic hormone-sensitive prostate cancer (mHSPC) include hormone therapy, such as ADT, androgen receptor pathway inhibitors plus ADT or a combination of the chemotherapy docetaxel and ADT. Despite these treatments, most men with mHSPC will eventually progress to metastatic castration-resistant prostate cancer (mCRPC), a condition with limited survival.7,8

About Oncology at Bayer

Bayer is committed to delivering science for a better life by advancing a portfolio of innovative treatments. The oncology franchise at Bayer includes six marketed products and several other assets in various stages of clinical development. Together, these products reflect the company’s approach to research, which prioritizes targets and pathways with the potential to impact the way that cancer is treated.

On February 17, 2022 Immune-Onc Therapeutics, Inc. ("Immune-Onc"), a clinical-stage cancer immunotherapy company developing novel biotherapeutics targeting immunosuppressive myeloid checkpoints, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for IO-202, a first-in-class myeloid checkpoint inhibitor targeting leukocyte immunoglobulin-like receptor B4 (LILRB4, also known as ILT3) for the treatment of patients with relapsed or refractory acute myeloid leukemia (AML) (Press release, Immune-Onc Therapeutics, FEB 17, 2022, View Source [SID1234608244]). The Company received Orphan Drug Designation for IO-202 for the treatment of AML in 2020.

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"We are pleased that the FDA has granted IO-202 Fast Track designation in recognition of its potential to improve outcomes for people with relapsed or refractory AML," said Paul Woodard, Ph.D., chief medical officer of Immune-Onc. "We look forward to working closely with the FDA to accelerate the clinical development of IO-202, which is currently being evaluated as a monotherapy and in combination with other agents in a Phase 1 dose escalation and expansion trial in patients with AML with monocytic differentiation and in chronic myelomonocytic leukemia (CMML)."

The FDA’s Fast Track designation is designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need to get important new medicines to patients earlier. Drugs that receive Fast Track designation may be eligible for more frequent interactions and written communications with the FDA to discuss the development plan and data collection to support an approval pathway. The designation also supports the eligibility for Accelerated Approval and Priority Review if relevant criteria are met.

ABOUT LILRB4 (also known as ILT3)

LILRB4, also known as ILT3, is an immune inhibitory transmembrane protein found on monocytic myeloid cells, including dendritic cells. LILRB4 inhibits antigen-presenting cell activation, resulting in immune tolerance. LILRB4 is also expressed on certain hematologic cancer cells and monocytic myeloid cells in the solid tumor microenvironment. Immune-Onc and The University of Texas published pioneering research in Nature illuminating the role of LILRB4 in immune suppression and tumor infiltration in AML and presented the rationale for targeting LILRB4 in solid tumors at the AACR (Free AACR Whitepaper) Annual Meeting 2021.

ABOUT IO-202

IO-202 is a first-in-class LILRB4 antagonist antibody with broad potential as an immunotherapy in both blood cancers and solid tumors. In hematologic malignancies, preclinical studies showed that IO-202 converts a "don’t kill me" to a "kill me" signal by activating T cell killing and converts a "don’t find me" to a "find me" signal by inhibiting infiltration of blood cancer cells. In solid tumors, preclinical data showed that IO-202 enhances dendritic cell function and T cell activation in vitro and inhibits tumor growth in a solid tumor model in vivo.

IO-202 is currently in Phase 1 clinical development for the treatment of AML and CMML. The U.S. Food and Drug Administration granted IO-202 Orphan Drug Designations for treatment of AML in 2020. The company has received IND clearance to evaluate IO-202 in solid tumors in January 2022.

On February 17, 2022 BeiGene (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global, science-driven biotechnology company focused on developing innovative and affordable medicines, reported that BeiGene’s BTK inhibitor BRUKINSA (zanubrutinib) received approval from Swissmedic for the treatment of adult patients with Waldenström’s macroglobulinemia (WM) who have received at least one prior line of therapy, or for treatment-naïve patients who are not suited for standard chemo-immunotherapy (Press release, BeiGene, FEB 17, 2022, View Source [SID1234608243]). BRUKINSA had previously been granted orphan drug status.

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"The authorization of BRUKINSA will bring a new option and an innovative medicine that has potential to offer deep and durable response for eligible patients with WM in Switzerland," said Pr. Davide Rossi, Deputy Head of the Division of Hematology of the Oncology Institute of Southern Switzerland IOSI. "BRUKINSA is a next-generation BTK inhibitor which has also provided meaningful improvements in tolerability for some patients with WM compared to ibrutinib, as treatment discontinuation remains a concern."

Reto Kessler, Country Manager, Switzerland at BeiGene added, "This approval is a significant development for people living with WM in Switzerland and for BeiGene’s expansion in Europe. Our teams are committed to collaborating with the Federal Office of Public Health and healthcare professionals to ensure access to BRUKINSA for patients in Switzerland."

The Marketing Authorization Application (MAA) is supported by data from the global Phase 3 ASPEN clinical trial, a Phase 3 randomized, open-label, multicenter trial (NCT03053440) that evaluated BRUKINSA compared to ibrutinib in patients with relapsed/refractory (R/R) or treatment-naïve (TN) WM who harbor a MYD88 mutation (MYD88MUT). In the ASPEN trial, BRUKINSA demonstrated a numerically higher very good partial response (VGPR) rate and a favorable safety profile over ibrutinib, although the primary endpoint of statistical superiority related to deep response (VGPR or better) was not met. As assessed by independent review committee (IRC) per adaptation of the response criteria updated at the Sixth International Workshop on Waldenström’s Macroglobulinemia (IWWM), the combined complete response (CR) + VGPR rate in the overall intention-to-treat (ITT) population was 29% with BRUKINSA (95% CI: 20, 40), compared to 19% with ibrutinib (95% CI: 12, 30).

In the ASPEN trial, of the 101 patients with WM randomized and treated with BRUKINSA, four percent of patients discontinued due to adverse events, including cardiomegaly, neutropenia, plasma cell myeloma, and subdural hemorrhage. Adverse events leading to dose reduction occurred in 14% of patients, with the most common being neutropenia (3%) and diarrhea (2%).

The recommended dose of BRUKINSA is either 160 mg twice daily or 320 mg once daily, taken orally with or without food. The dose may be adjusted for adverse reactions and reduced for patients with severe hepatic impairment and certain drug interactions.

About Waldenström’s Macroglobulinemia

WM is a rare B-cell lymphoma that occurs in less than two percent of patients with non-Hodgkin lymphomas.2 The disease usually affects older adults and is primarily found in bone marrow, although lymph nodes and the spleen may be involved.1 Throughout Europe, the estimated incidence rate of WM is approximately seven for every one million men and four for every one million women.2

About BRUKINSA

BRUKINSA is a small molecule inhibitor of Bruton’s tyrosine kinase (BTK) discovered by BeiGene scientists that is currently being evaluated globally in a broad clinical program as a monotherapy and in combination with other therapies to treat various B-cell malignancies. Because new BTK is continuously synthesized, BRUKINSA was specifically designed to deliver complete and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. With differentiated pharmacokinetics compared to other approved BTK inhibitors, BRUKINSA has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease relevant tissues.

BRUKINSA is supported by a broad clinical program which includes more than 3,900 subjects in 35 trials across 28 markets. To date, BRUKINSA has received more than 20 approvals covering more than 40 countries and regions, including the U.S., European Union, China, Australia, Great Britain and Switzerland. Currently, more than 40 additional regulatory submissions are in review around the world.

BeiGene Oncology

BeiGene is committed to advancing best- and first-in-class clinical candidates internally or with like-minded partners to develop impactful and affordable medicines for patients across the globe. We have a growing R&D and medical affairs team of approximately 2,900 colleagues dedicated to advancing more than 100 clinical trials that have involved more than 14,500 subjects. Our expansive portfolio is directed predominantly by our internal colleagues supporting clinical trials in more than 45 countries and regions. Hematology-oncology and solid tumor targeted therapies and immuno-oncology are key focus areas for the Company, with both mono- and combination therapies prioritized in our research and development. BeiGene currently has three approved medicines discovered and developed in our own labs: BTK inhibitor BRUKINSA in the United States, China, the EU and U.K., Canada, Australia and additional international markets; and the non-FC-gamma receptor binding anti-PD-1 antibody tislelizumab as well as the PARP inhibitor pamiparib in China.

BeiGene also partners with innovative companies who share our goal of developing therapies to address global health needs. We commercialize a range of oncology medicines in China licensed from Amgen, Bristol Myers Squibb, EUSA Pharma and Bio-Thera. We also plan to address greater areas of unmet need globally through our other collaborations including with Mirati Therapeutics, Seagen, and Zymeworks.

In January 2021 BeiGene and Novartis announced a collaboration granting Novartis rights to co-develop, manufacture, and commercialize BeiGene’s anti-PD1 antibody tislelizumab in North America, Europe, and Japan. Building upon this productive collaboration, including a biologics license application (BLA) under FDA review, BeiGene and Novartis announced an option, collaboration and license agreement in December 2021 for BeiGene’s TIGIT inhibitor ociperlimab that is in Phase 3 development. Novartis and BeiGene also entered into a strategic commercial agreement through which BeiGene will promote five approved Novartis Oncology products across designated regions of China.