Aeglea BioTherapeutics Appoints Jeffrey M. Goldberg as Chief Executive Officer

On November 30, 2022 Aeglea BioTherapeutics, Inc. (NASDAQ:AGLE), a clinical-stage biotechnology company developing a new generation of human enzyme therapeutics as innovative solutions for rare metabolic diseases, reported the appointment of Jeffrey M. Goldberg as president, chief executive officer and member of the board of directors effective November 29, 2022 (Press release, Aeglea BioTherapeutics, NOV 30, 2022, View Source [SID1234624635]). Mr. Goldberg is an accomplished biotech executive with over 25 years of experience leading teams from preclinical discovery through commercialization and previously served as president and chief executive officer of Immunitas Therapeutics.

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"Jeff has successfully built and managed teams across a wide variety of functions, providing strong leadership and strategic direction. His breadth of experience spans from the founding of companies to overseeing successful global launches of rare disease therapies," said Russell J. Cox, chair of the board of directors of Aeglea. "His proven ability to match business capabilities to unmet patient needs and then drive the strategy and execution needed to achieve those goals will be an important asset to Aeglea. I look forward to working closely with Jeff and welcome him to the Aeglea team."

"To me, the most important and fulfilling part of my job has been being able to bring therapies forward that have had significant impact on patients’ lives. Aeglea shares that mission and has built world-class programs in Homocystinuria and Arginase 1 Deficiency with the potential to benefit all the key stakeholders, including employees, shareholders, physicians, and most importantly patients and their families," said Mr. Goldberg. "I’m incredibly excited to be joining the team and helping to facilitate the mission of developing novel medicines for patients battling devastating diseases."

Mr. Goldberg served as president and chief executive officer at Immunitas from 2019-2021. Under his leadership, Immunitas grew significantly, raised additional capital, and is now in the clinic with its first asset. Prior to joining Immunitas, Mr. Goldberg served as the founding chief operating officer at Akcea where he was responsible for building functions and leading teams across all aspects of the business and eventually grew the team from two employees to over 250 in multiple geographies. Mr. Goldberg played a significant role in the company’s initial public offering and fundraising activities, business development and the global launch of two rare disease drugs. Prior to Akcea, he was the vice president of business operations at Proteostasis Therapeutics, a rare disease company. He also held roles of increasing responsibility at Genzyme, where he led teams through product development and global launches across multiple therapeutic areas. Mr. Goldberg has an MBA and a MS in Chemical Engineering from the Massachusetts Institute of Technology, and a B.S. in Chemical Engineering from Cornell University.

Jim Kastenmayer, JD, PhD, will step down as interim chief executive officer and retain his position as Aeglea’s general counsel. "On behalf of the entire board of directors, I want to thank Jim for his service and commitment to Aeglea and its mission. Jim has provided exceptional leadership during a period of critical execution and has kept the team focused on advancing the Homocystinuria program," said Mr. Cox.

Following the leadership transition and as part of the related evaluation of near-term corporate and clinical development strategy, Aeglea no longer plans to announce interim clinical data from the ongoing Phase 1/2 clinical trial of pegtarviliase in Classical Homocystinuria in the fourth quarter of 2022. Enrollment in the third cohort of the Phase 1/2 trial is ongoing with two patients having completed dosing in the cohort. Additionally, the company has decided not to participate in the Piper Sandler 34th Annual Healthcare Conference and 5th Annual Evercore ISI HealthCONx Conference, both being held November 29-December 1, 2022. Aeglea looks forward to delivering a clinical update on the pegtarviliase program when more comprehensive data from the third cohort becomes available.

Liminatus Pharma LLC and Iris Acquisition Corp to combine to incorporate and accelerate much-needed cancer treatments

On November 30, 2022 Liminatus Pharma LLC ("Liminatus"), a clinical-stage biopharmaceutical company developing novel, immune-modulating cancer therapies and Iris Acquisition Corp ("Iris") (Nasdaq: IRAA), a publicly traded special purpose acquisition company ("SPAC") formed for the purpose of acquiring or merging with one or more businesses, reported they have entered into a definitive business combination agreement (Press release, Liminatus Pharma, NOV 30, 2022, View Source [SID1234624633]). Upon closing of the transaction, the combined company will be renamed "Liminatus Pharma, Inc.". The combined company’s common stock is expected to be listed on the Nasdaq Capital Market. The transaction funding includes commitments for a $15 million common stock PIPE financing and a $25 million convertible note financing to further support Liminatus’ business growth strategy.

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As part of the agreement the new entity is expected to develop three much-needed cancer treatments which have originated from the Thomas Jefferson University (TJU) in the US and a South Korean biotech firm, Innobation Bio Ltd. ("Innobation"). The lead product candidate, the GCC Vaccine is currently in Phase II clinical trials and is designed to elicit immune responses against colorectal, pancreatic, gastric, and esophageal cancers that express Guanylyl Cyclase C ("GCC"). Further to the work in this area, Liminatus expects to use the increased capital from this agreement to progress its GCC CAR-T therapy to a first in human clinical trial, and complete IND enabling studies for its next generation CD47 immune checkpoint inhibitor.

About the Transaction

The business combination implies a pro forma enterprise value of the combined company of approximately $334 million. The combined company is expected to receive gross cash proceeds of up to $316 million, comprising the $276 million held in Iris’ trust account (assuming no redemptions by public shareholders of Iris) and a concurrent, committed $15 million equity PIPE financing of common stock issued at $10.00 per share and $25 million convertible note financing with an initial conversion rate of $11.50 per share of common stock, subject to future adjustments based upon the price of Iris’ publicly traded common stock. The combined company will bear deferred underwriting commissions and transaction expenses out of the gross proceeds.

The transaction, which has been approved by Liminatus’s and Iris’ boards of directors, is expected to close in the first half of 2023, subject to review by the Securities and Exchange Commission ("SEC") and effectiveness of the registration statement on Form S-4 to be filed with the SEC, approval by Iris’ shareholders, and satisfaction of the closing conditions set forth in the business combination agreement, including any applicable regulatory approvals.

"The agreement with Iris and the treatments we are now set to develop which have originated from leading global cancer scientists at the Thomas Jefferson University in the US and from Innobation in South Korea, will be a game changer for this area of the healthcare market. There is a significant unmet need for improved treatment for the cancer indications we are targeting, and with the increased capital, we are hopeful that the timelines for getting these potentially life-saving medicines to market have been accelerated", said Chris Kim, CEO Liminatus.

Sumit Metha, CEO of Iris, commented, "Immuno-therapies are much in-demand and we believe they are one of the most promising medical treatments for cancer. This deal presents a good opportunity for our company to tap into a rapidly growing global cancer immunotherapy market, expected to hit around $262 billion dollars by 2030. We are very confident that our investors will be excited for this deal because of the position of these treatments in their development cycle, the global demand and the excellent team of scientific advisors and executives at Liminatus.

Nimble Therapeutics names Pete Gough as Chief Scientific Officer

On November 30, 2022 Nimble Therapeutics, an industry-leading peptide therapeutics company, reported the appointment of Pete Gough, D. Phil. as Chief Scientific Officer (CSO) (Press release, Nimble Therapeutics, NOV 30, 2022, View Source [SID1234624632]). In this newly created role, Dr. Gough will spearhead the expansion of Nimble’s internal drug discovery capabilities that will enable further development of its own pipeline of proprietary therapeutics and drive Nimble towards becoming a fully integrated biotechnology company.

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Dr. Gough has more than 25 years of experience in discovery research, both in academic settings as well as in the life sciences industry, and a track record of success in drug discovery and development, driving research programs into clinical study by building and leading high-performance teams. Prior to joining Nimble, Pete served as the CSO for Inzen Therapeutics, a Flagship company pioneering the newly discovered science of Thanokine Biology. At Inzen, he helped advance the company from seed stage to a successful Series B through the development of their pipeline of potentially transformational Immuno-Oncology therapeutics. Previously, Pete spent 15 years at GSK in roles of increasing responsibility. He served as Head of the Hepatitis B Virus Discovery Performance Unit (DPU) where he led GSK’s efforts to develop a functional cure for HBV including proof of concept studies for bepirovirsen. He also served as Head of the Host Defense DPU, and prior to that was Head of Biology and DMPK in the Pattern Recognition Receptor DPU. Pete led, and oversaw, the discovery and development of a number of clinical assets across multiple therapeutic areas including RIP1 kinase inhibitor GSK2982772 and STING agonist GSK3745417.

"We’re excited to welcome Pete to our management team at Nimble," said Jigar Patel, PhD, Founder and CEO of Nimble Therapeutics. "Since our formation in 2019, Nimble has worked diligently to optimize and validate our peptide discovery platform. Pete brings invaluable experience in drug discovery and development across multiple therapeutic areas that will enable Nimble to deliver on the promise of peptide therapeutics through progressing and expanding our own internal pipeline."

"Nimble has built the industry leading platform for discovering peptide therapeutics that solves for the challenges that everyone else in the field is struggling with," said Dr. Gough. "I’m very excited to be part of the team and to help realize the truly transformative nature of the Nimble platform by advancing novel medicines into the clinic."

Earlier in his career, Pete was a Research Assistant Professor in the Department of Pathology at the University of Washington. He received his D. Phil. and M. A. from the University of Oxford. Pete has authored/co-authored over 100 scientific papers in peer-reviewed journals and has been an invited speaker at numerous academic institutions and scientific conferences.

AstraZeneca Showcases Strength of Hematology Portfolio and Pipeline Across Multiple Hard-to-Treat Conditions at ASH 2022

On November 30, 2022 AstraZeneca reported that it will present 47 abstracts showcasing new data from across its hematology portfolio and clinical pipeline, demonstrating its commitment to redefining care for hard-to-treat blood diseases at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, December 10 to 13, 2022 (Press release, AstraZeneca, NOV 30, 2022, View Source [SID1234624631]).

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A total of eight approved and potential new medicines will be featured across more than 10 types of blood cancers and rare diseases, including data in chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS) and amyloid light chain (AL) amyloidosis.

Anas Younes, Senior Vice President, Oncology R&D, AstraZeneca, said: "At this year’s ASH (Free ASH Whitepaper) Annual Meeting, our data demonstrate the broad potential of our hematology pipeline and the continued strength of our approved medicines. Data are being highlighted from many of our early-stage molecules, including clinical trials of TNB-486 (AZD0486), a B-cell targeting T-cell engager, and presentations of long-term follow-up data will show the consistent safety and efficacy profile of CALQUENCE."

Gianluca Pirozzi, Senior Vice President, Head of Development and Safety, Alexion, AstraZeneca Rare Disease said: "The depth and breadth of Alexion data at this year’s ASH (Free ASH Whitepaper) Annual Meeting reinforce the importance of earlier diagnosis and disease management for rare diseases that are often not well-understood. We will share research across several therapy areas – including an oral presentation demonstrating the potential of vemircopan, an investigational, second-generation factor D inhibitor as monotherapy treatment of paroxysmal nocturnal hemoglobinuria – underscoring our leadership and unwavering commitment to driving critical innovations in rare disease."

CALQUENCE (acalabrutinib) real-world evidence and long-term follow-up data support consistent efficacy and safety profile

A post-hoc safety analysis from the head-to-head ELEVATE-RR Phase III trial of CALQUENCE versus ibrutinib will further support tolerability differences of CALQUENCE in relapsed or refractory CLL.1
Final long-term follow-up results of the Phase I/II trials evaluating CALQUENCE monotherapy in front-line and relapsed or refractory CLL will further support the continued efficacy and safety CALQUENCE demonstrated in both settings.2,3
An oral presentation of Phase II research sponsored by the Dana-Farber Cancer Institute will show the efficacy and tolerability of CALQUENCE combined with venetoclax and obinutuzumab in a front-line, high-risk CLL population.4
A retrospective pooled analysis will show the benefit of adding obinutuzumab to CALQUENCE in the front-line CLL setting in patients with select genomic characteristics.5
An oral presentation of preliminary Phase II results sponsored by Weill Cornell Medicine will show that CALQUENCE combined with lenalidomide and rituximab is generally well-tolerated, highly effective and produces high rates of minimal residual disease-negative complete remission in front-line MCL.6
Novel treatment strategies with emerging pipeline molecules exhibit therapeutic potential

An oral presentation of interim Phase I results evaluating TNB-486 (AZD0486), a CD19/CD3 next generation bispecific T-cell engager, will show the potential of targeting CD19/CD3, leading to an increase in anti-cancer activity in heavily pretreated patients with B-cell non-Hodgkin lymphoma (NHL).7
Results from Phase I and II trials of CDK9 inhibitor AZD4573 alone and with CALQUENCE will exhibit data on tolerability across a broad range of hematologic malignancies, including relapsed or refractory DLBCL.8,9
Preliminary results from an ongoing Phase I trial will demonstrate that Bcl-2/Bcl-xl inhibitor AZD0466 has been well-tolerated in patients with advanced hematologic malignancies.10
Innovating to help address the treatment needs of all patients with PNH

An oral presentation detailing interim results from a Phase II open-label trial of vemircopan (ALXN2050) will highlight efficacy and safety data from the treatment-naïve patient group, establishing proof-of-concept as a monotherapy for PNH.11
An interim analysis from an ongoing Phase IV trial assessing the impact of switching to standard, weight-based intravenous (i.v.) ULTOMIRIS (ravulizumab-cwvz) from high-dose i.v. SOLIRIS (eculizumab) in adults with PNH will be presented.12
Improving diagnosis and management of life-threatening rare diseases

An analysis of data from the Global aHUS Registry, which contains information on patients across more than 100 sites in more than 20 countries, will highlight the importance of considering aHUS as a diagnosis even in the presence of a triggering condition or associated event.13
An analysis of real-world patient data from the US Premier Healthcare Database will expand on the potential of the PLASMIC scoring system to aid in identifying people with aHUS and making earlier treatment decisions.14
An analysis of pediatric patients with hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA) will provide insights on the correlation between complement activation and endothelial damage in HSCT-TMA and the potential for useful biomarkers indicative of this damage to inform diagnosis.15
Results through one year on safety, tolerability and biomarker data will be presented from a Phase II trial evaluating CAEL-101, a potentially first-in-class monoclonal antibody, in adults with AL amyloidosis.16
A real-world analysis in a current population with AL amyloidosis using Komodo Health US claims data will highlight the need for greater awareness and understanding to accelerate time to diagnosis.17
Key presentations during the 64th ASH (Free ASH Whitepaper) Annual Meeting and Exposition

Lead author

Abstract title

Presentation details

CALQUENCE (acalabrutinib)

Byrd, J

Final Results of the Phase 1/2 Study of Acalabrutinib Monotherapy in Treatment-Naive Chronic Lymphocytic Leukemia with >6 Years of Follow-Up

Abstract # 4431

Poster Session: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster III

December 12, 2022

18:00-20:00 CST

Location: Hall D (Ernest N. Morial Convention Center)

Davids, MS

Contribution of Obinutuzumab to Acalabrutinib Therapy in Patients with Treatment-Naive Chronic Lymphocytic Leukemia: Analysis of Survival Outcomes by Genomic Features

Abstract # 1815

Poster Session: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster I

December 10, 2022

17:30-19:30 CST

Location: Hall D (Ernest N. Morial Convention Center)

Davies, AJ

Durable Responses from Acalabrutinib in Combination with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisolone (R-CHOP) as First Line Therapy for Patients with Diffuse Large B-Cell Lymphoma (DLBCL): The ACCEPT Phase Ib/II Single Arm Study

Abstract # 4265

Poster Session: 626. Aggressive Lymphomas: Prospective Therapeutic Trials: Poster III

December 12, 2022

18:00-20:00 CST

Location: Hall D (Ernest N. Morial Convention Center)

Furman, R

Phase 1/2 Study of Acalabrutinib Monotherapy in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia: Final Results with >4 Years of Follow-Up

Abstract # 4434

Poster Session: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster III

December 12, 2022

18:00-20:00 CST

Location: Hall D (Ernest N. Morial Convention Center)

Ruan, J

Phase 2 Trial of Acalabrutinib-Lenalidomide-Rituximab (ALR) with Real-Time Monitoring of MRD in Patients with Treatment-Naïve Mantle Cell Lymphoma

Abstract # 73

Oral Session: 623. Mantle Cell, Follicular, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological I

December 10, 2022

9:30 CST

Location: La Nouvelle Orleans Ballroom C (Ernest N. Morial Convention Center)

Ryan, CE

Updated Results from a Multicenter, Phase 2 Study of Acalabrutinib, Venetoclax, Obinutuzumab (AVO) in a Population of Previously Untreated Patients with CLL Enriched for High-Risk Disease

Abstract # 344

Oral Session: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Targeted Triplet Combinations and Richter’s Transformation

December 10, 2022

16:15 CST

Location: R06-R09 (Ernest N. Morial Convention Center)

Seymour, JF

Assessing the Burden of Adverse Events in a Head-to-Head Trial of Acalabrutinib Versus Ibrutinib in Previously Treated Chronic Lymphocytic Leukemia (CLL)

Abstract # 3133

Poster Session: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster II

December 11, 2022

18:00-20:00 CST

Location: Hall D (Ernest N. Morial Convention Center)

AZD0486 (CD19/CD3 T-cell engager)

Hou, JZ

Interim Results of the Phase 1 Study of Tnb-486, a Novel CD19xCD3 T-Cell Engager, in Patients with Relapsed/Refractory (R/R) B-NHL

Abstract # 612

Oral Session: 623. Mantle Cell, Follicular, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological IV

December 11, 2022

17:45 CST

Location: 278-282 (Ernest N. Morial Convention Center)

AZD0466 (Bcl-2/Bcl-xL inhibitor)

Arslan, S

Safety and Tolerability of AZD0466 as Monotherapy for Patients with Advanced Hematological Malignancies. Preliminary Results from an Ongoing Phase I/II Trial

Abstract # 4094

Poster Session: 616. Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster III

December 12, 2022

18:00-20:00 CST

Location: Hall D (Ernest N. Morial Convention Center)

AZD4573 (CDK9 inhibitor)

Brümmendorf, T

Safety, Tolerability, Pharmacokinetics (PK) and Preliminary Antitumor Activity of the Cyclin-Dependent Kinase-9 (CDK9) Inhibitor AZD4573 in Relapsed/Refractory Hematological Malignancies: A Phase 1 First-in-Human Study

Abstract # 1353

Poster Session: 605. Molecular Pharmacology and Drug Resistance: Lymphoid Neoplasms: Poster I

December 10, 2022

17:30-19:30 CST

Location: Hall D (Ernest N. Morial Convention Center)

Strati, P

Phase 1b/2a Study of AZD4573 (CDK9i) and Acalabrutinib in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (r/r DLBCL): Results from Dose-Escalation

Abstract # 2962

Poster Session: 627. Aggressive Lymphomas: Clinical and Epidemiological: Poster II

December 11, 2022

18:00-20:00 CST

Location: Hall D (Ernest N. Morial Convention Center)

VEMIRCOPAN (ALXN2050)

Browett, P

Vemircopan (ALXN2050) Monotherapy in Paroxysmal Nocturnal Hemoglobinuria: Interim Data from a Phase 2 Open-Label Proof-of-Concept Study

Abstract # 294

Oral Session: 508. Bone Marrow Failure: Acquired: Clinical Studies

December 10, 2022

17:15 CST

Location: 260-262 (Ernest N. Morial Convention Center)

ULTOMIRIS (ravulizumab-cwvz)

Griffin, M

Terminal Complement Inhibition and Control of Hemolysis in Paroxysmal Nocturnal Hemoglobinuria Following Switching from High-Dose Eculizumab to Ravulizumab: An Interim Analysis

Abstract # 1251

Poster Session: 508. Bone Marrow Failure: Acquired: Poster I

December 10, 2022

17:30-19:30 CST

Location: Hall D (Ernest N. Morial Convention Center)

ALXN1820

Dai, Y

A Phase 2a, Randomized, Open-Label Study to Evaluate Multiple Dosing Regimens of Subcutaneous ALXN1820 in Adult Patients with Sickle Cell Disease

Abstract # 3713

Poster Session: 114. Hemoglobinopathies, Excluding Thalassemia: Clinical and Epidemiological: Poster III

December 12, 2022

18:00-20:00 CST

Location: Hall D (Ernest N. Morial Convention Center)

CAEL-101

Valent, J

1-Year Results from a Phase 2 Study to Determine Safety and Tolerability of Treating Patients with Light-Chain (AL) Amyloidosis with CAEL-101, an Anti-Amyloid Monoclonal Antibody, Combined with Anti-Plasma Cell Dyscrasia

Abstract # 4550

Poster Session: 653. Myeloma and Plasma Cell Dyscrasias: Prospective Therapeutic Trials: Poster III

December 12, 2022

18:00-20:00 CST

Location: Hall D (Ernest N. Morial Convention Center)

AL Amyloidosis

Catini, J

Evaluation of the Path to Diagnosis and Time to Treatment in Patients with Light-Chain Amyloidosis Using the Komodo Claims Database

Abstract # 1887

Poster Session: 652. Multiple Myeloma and Plasma Cell Dyscrasias: Clinical and Epidemiological: Poster I

December 10, 2022

17:30-19:30 CST

Location: Hall D (Ernest N. Morial Convention Center)

HSCT-TMA

Jacobi, P

Complement Activation is Associated

with Endothelial Damage in

Hematopoietic Stem Cell Transplant

Associated-Thrombotic Microangiopathy

Abstract # 2431

Poster Session: 301. Vasculature, Endothelium, Thrombosis and Platelets: Basic and Translational: Poster II

December 11, 2022

18:00-20:00 CST

Location: Hall D (Ernest N. Morial Convention Center)

aHUS

Gasteyger, C

Use of PLASMIC Scores to Aid Diagnosis of aHUS: A Real-World Analysis of Hospitalized Patients from the Premier Healthcare Database

Abstract # 1178

Poster Session: 331. Thrombotic Microangiopathies/Thrombocytopenias and COVID-19-related Thrombotic/Vascular Disorders: Clinical and Epidemiological: Poster I

December 10, 2022

17:30-19:30 CST

Location: Hall D (Ernest N. Morial Convention Center)

Siedlecki, A

Characterization of Patients with aHUS and Triggering/Associated Events, with and without Complement Pathogenic Variants or anti-CFH Antibodies: A Global aHUS Registry Analysis

Abstract # 1173

Poster Session: 331. Thrombotic Microangiopathies/Thrombocytopenias and COVID-19-related Thrombotic/Vascular Disorders: Clinical and Epidemiological: Poster I

December 10, 2022

17:30-19:30 CST

Location: Hall D (Ernest N. Morial Convention Center)

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) tablets

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 (eg, 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 to 1.5 to 3 times the upper limit of normal (ULN) 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 to 1.5 to 3 times ULN 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 to 1.5 to 3 times ULN occurred in 1.3% of patients who received CALQUENCE.

DRUG INTERACTIONS

Strong CYP3A Inhibitors: Avoid co-administration of CALQUENCE with a strong CYP3A inhibitor. If these inhibitors will be used short-term, interrupt CALQUENCE. After discontinuation of strong CYP3A inhibitor for at least 24 hours, resume previous dosage of CALQUENCE.

Moderate CYP3A Inhibitors: Reduce the dosage of CALQUENCE to 100 mg once daily when co-administered with a moderate CYP3A inhibitor.

Strong CYP3A Inducers: Avoid co-administration of CALQUENCE with a strong CYP3A inducer. If co-administration is unavoidable, increase the dosage of CALQUENCE to 200 mg approximately every 12 hours.

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 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 2 weeks after the last dose.

Avoid use of CALQUENCE in patients with severe hepatic impairment (Child-Pugh class C). No dosage adjustment of CALQUENCE is recommended in patients with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment.

Please see full Prescribing Information, including Patient Information.

INDICATION(S) & IMPORTANT SAFETY INFORMATION for ULTOMIRIS

INDICATION(S)

Paroxysmal Nocturnal Hemoglobinuria (PNH)

ULTOMIRIS is indicated for the treatment of adult and pediatric patients one month of age and older with paroxysmal nocturnal hemoglobinuria (PNH).

Atypical Hemolytic Uremic Syndrome (aHUS)

ULTOMIRIS is indicated for the treatment of adult and pediatric patients one month of age and older with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy (TMA).

Limitation of Use:

ULTOMIRIS is not indicated for the treatment of patients with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS).

Subcutaneous Use in Adult Patients with PNH or aHUS

Subcutaneous administration of ULTOMIRIS is not approved for use in pediatric patients.

IMPORTANT SAFETY INFORMATION

WARNING: SERIOUS MENINGOCOCCAL INFECTIONS

Life-threatening meningococcal infections/sepsis have occurred in patients treated with ULTOMIRIS. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early.

Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccination in patients with complement deficiencies.
Immunize patients with meningococcal vaccines at least 2 weeks prior to administering the first dose of ULTOMIRIS, unless the risks of delaying ULTOMIRIS therapy outweigh the risk of developing a meningococcal infection. See Warnings and Precautions for additional guidance on the management of the risk of meningococcal infection.
Vaccination reduces, but does not eliminate, the risk of meningococcal infections. Monitor patients for early signs of meningococcal infections and evaluate immediately if infection is suspected.
Because of the risk of serious meningococcal infections, ULTOMIRIS is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called ULTOMIRIS REMS.

CONTRAINDICATIONS

Patients with unresolved Neisseria meningitidis infection.
Patients who are not currently vaccinated against Neisseria meningitidis, unless the risks of delaying ULTOMIRIS treatment outweigh the risks of developing a meningococcal infection.
WARNINGS AND PRECAUTIONS

Serious Meningococcal Infections

Life-threatening meningococcal infections have occurred in patients treated with ULTOMIRIS. The use of ULTOMIRIS increases a patient’s susceptibility to serious meningococcal infections (septicemia and/or meningitis). Meningococcal disease due to any serogroup may occur.

Vaccinate or revaccinate for meningococcal disease according to the most current ACIP recommendations for patients with complement deficiencies. Immunize patients without history of meningococcal vaccination at least 2 weeks prior to the first dose of ULTOMIRIS. Patients who initiate ULTOMIRIS treatment less than 2 weeks after receiving meningococcal vaccine(s) must receive appropriate prophylactic antibiotics until 2 weeks after vaccination.

In clinical studies, 59 adult patients with PNH and 2 adult patients with gMG were treated with ULTOMIRIS less than 2 weeks after meningococcal vaccination. All of these patients received antibiotics for prophylaxis of meningococcal infection until at least 2 weeks after meningococcal vaccination. The benefits and risks of antibiotic prophylaxis for prevention of meningococcal infections in patients receiving ULTOMIRIS have not been established. In clinical studies with ULTOMIRIS, <1% of patients developed serious meningococcal infections/sepsis while receiving treatment with ULTOMIRIS. All were adult patients with PNH who had been vaccinated. These patients recovered while continuing treatment with ULTOMIRIS. Consider discontinuation of ULTOMIRIS in patients who are undergoing treatment for serious meningococcal infection.

ULTOMIRIS REMS

Due to the risk of meningococcal infections, ULTOMIRIS is available only through a restricted program under a REMS called ULTOMIRIS REMS.

Under the ULTOMIRIS REMS, prescribers must enroll in the program. Prescribers must counsel patients about the risk of meningococcal infection/sepsis, provide the patients with the REMS educational materials, and ensure patients are vaccinated with meningococcal vaccines.

Additional information on the REMS requirements is available at www.ultomirisrems.com or 1-888-765-4747.

Other Infections

Patients may have increased susceptibility to infections, especially with encapsulated bacteria, such as infections caused by Neisseria meningitidis but also Streptococcus pneumoniae, Haemophilus influenzae, and to a lesser extent, Neisseria gonorrhoeae. Children treated with ULTOMIRIS may be at increased risk of developing serious infections due to Streptococcus pneumoniae and Haemophilus influenzae type b (Hib). Administer vaccinations for the prevention of Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) infections according to ACIP guidelines. If ULTOMIRIS is administered to patients with active systemic infections, monitor closely for worsening infection.

Monitoring Disease Manifestations after ULTOMIRIS Discontinuation

Treatment Discontinuation for PNH

After discontinuing treatment with ULTOMIRIS, closely monitor for signs and symptoms of hemolysis, identified by elevated LDH along with sudden decrease in PNH clone size or hemoglobin, or re-appearance of symptoms such as fatigue, hemoglobinuria, abdominal pain, shortness of breath (dyspnea), major adverse vascular event (including thrombosis), dysphagia, or erectile dysfunction. Monitor any patient who discontinues ULTOMIRIS for at least 16 weeks to detect hemolysis and other reactions. If signs and symptoms of hemolysis occur after discontinuation, including elevated LDH, consider restarting treatment with ULTOMIRIS.

Treatment Discontinuation for aHUS

ULTOMIRIS treatment of aHUS should be a minimum duration of 6 months. Due to heterogeneous nature of aHUS events and patient-specific risk factors, treatment duration beyond the initial 6 months should be individualized. There are no specific data on ULTOMIRIS discontinuation. After discontinuing treatment with ULTOMIRIS, patients should be monitored for clinical symptoms and laboratory signs of TMA complications for at least 12 months.

TMA complications post-discontinuation can be identified if any of the following is observed: Clinical symptoms of TMA include changes in mental status, seizures, angina, dyspnea, thrombosis or increasing blood pressure. In addition, at least two of the following laboratory signs observed concurrently and results should be confirmed by a second measurement 28 days apart with no interruption: a decrease in platelet count of 25% or more as compared to either baseline or to peak platelet count during ULTOMIRIS treatment; an increase in serum creatinine of 25% or more as compared to baseline or to nadir during ULTOMIRIS treatment; or, an increase in serum LDH of 25% or more as compared to baseline or to nadir during ULTOMIRIS treatment. If TMA complications occur after discontinuation, consider reinitiation of ULTOMIRIS treatment or appropriate organ-specific supportive measures.

Thromboembolic Event Management

The effect of withdrawal of anticoagulant therapy during treatment with ULTOMIRIS has not been established. Treatment should not alter anticoagulant management.

Infusion-Related Reactions

Intravenous or subcutaneous administration of ULTOMIRIS may result in systemic infusion-related reactions, including anaphylaxis and hypersensitivity reactions. In clinical trials, infusion-related reactions occurred in approximately 1% of patients treated with ULTOMIRIS. These events included lower back pain, drop in blood pressure, elevation in blood pressure, limb discomfort, drug hypersensitivity (allergic reaction), dysgeusia (bad taste), and drowsiness. These reactions did not require discontinuation of ULTOMIRIS. If signs of cardiovascular instability or respiratory compromise occur, interrupt ULTOMIRIS infusion and institute appropriate supportive measures.

Injection Site Reactions- Subcutaneous administration

27% (23/84) of patients treated with subcutaneous administration of ULTOMIRIS experienced injection site reactions which included application site rash, device allergy, infusion site pain, infusion site reaction, injection site bruising, injection site erythema, injection site hematoma, injection site induration, injection site inflammation, injection site pain, injection site pruritus, injection site rash, injection site reaction, injection site swelling, injection site urticaria, medical device site bruise, medical device site erythema, medical device site hematoma, medical device site induration, medical device site pruritus, medical device site rash, and medical device site reaction.

Allergies to Acrylic Adhesives

The on-body injector of ULTOMIRIS uses acrylic adhesive. For patients with a known allergy to acrylic adhesive, use of this product may result in an allergic reaction. Premedication can be considered, and supportive measures should be instituted if signs of allergy appear.

ADVERSE REACTIONS

Adverse Reactions for PNH

Adverse reactions reported in 5% or more of patients treated with ULTOMIRIS vs. Eculizumab was Upper respiratory tract infection (39% vs. 39%), Headache (32% vs. 26%), Diarrhea (9% vs. 5%), Nausea (9% vs. 9%), Pyrexia (7% vs. 8%), Pain in extremity (6% vs. 5%), Abdominal pain (6% vs. 7%), Dizziness (5% vs. 6%), Arthralgia (5% vs. 5%). Serious adverse reactions were reported in 15 (6.8%) patients receiving ULTOMIRIS. The serious adverse reactions in patients treated with ULTOMIRIS included hyperthermia and pyrexia. No serious adverse reaction was reported in more than 1 patient treated with ULTOMIRIS. One fatal case of sepsis was identified in a patient treated with ULTOMIRIS. In clinical studies, clinically relevant adverse reactions in 1% of adult patients include infusion-related reactions.

Adverse reactions reported in 10% or more of pediatric patients treated with ULTOMIRIS who were treatment-naïve vs. Eculizumab-experienced was Anemia (20% vs. 25%), Abdominal pain (0% vs. 38%), Constipation (0% vs. 25%), Pyrexia (20% vs. 13%), Upper respiratory tract infection (20% vs. 75%), Pain in extremity (0% vs. 25%), Headache (20% vs. 25%).

Adverse Reactions for aHUS

Most common adverse reactions in patients with aHUS (incidence ≥20%) were upper respiratory tract infection, diarrhea, nausea, vomiting, headache, hypertension and pyrexia. Serious adverse reactions were reported in 42 (57%) patients with aHUS receiving ULTOMIRIS. The most frequent serious adverse reactions reported in more than 2 patients (2.7%) treated with ULTOMIRIS were hypertension, pneumonia and abdominal pain. In clinical studies, clinically relevant adverse reactions in <10% of patients include viral tonsillitis in adults and viral infection in pediatric patients and in 3% of adult patients include infusion-related reactions.

Adverse Reactions for Subcutaneous Administration of ULTOMIRIS

Most common adverse reactions (≥10%) with ULTOMIRIS subcutaneous administration via On Body Injector in adult patients with PNH were local injection site reactions, diarrhea, and headache.

DRUG INTERACTIONS

Plasma Exchange, Plasmapheresis, and Intravenous Immunoglobulins

Concomitant use of ULTOMIRIS with plasma exchange (PE), plasmapheresis (PP), or intravenous immunoglobulin (IVIg) treatment can reduce serum ravulizumab concentrations and requires a supplemental dose of ULTOMIRIS.

Neonatal Fc Receptor Blockers

Concomitant use of ULTOMIRIS with neonatal Fc receptor (FcRn) blockers (e.g., efgartigimod) may lower systemic exposures and reduce effectiveness of ULTOMIRIS. Closely monitor for reduced effectiveness of ULTOMIRIS.

Please see accompanying full Prescribing Information for ULTOMIRIS, including Boxed WARNING regarding serious and life-threatening meningococcal infections/sepsis.

INDICATIONS & IMPORTANT SAFETY INFORMATION FOR SOLIRIS (eculizumab)

INDICATIONS

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Soliris is indicated for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis.

Atypical Hemolytic Uremic Syndrome (aHUS)

Soliris is indicated for the treatment of patients with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy.

Limitation of Use

Soliris is not indicated for the treatment of patients with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS).

IMPORTANT SAFETY INFORMATION

WARNING: SERIOUS MENINGOCOCCAL INFECTIONS
Life-threatening and fatal meningococcal infections have occurred in patients treated with Soliris and may become rapidly life-threatening or fatal if not recognized and treated early.

Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccination in patients with complement deficiencies.
Immunize patients with meningococcal vaccines at least 2 weeks prior to administering the first dose of Soliris, unless the risks of delaying Soliris therapy outweigh the risk of developing a meningococcal infection. (See Serious Meningococcal Infections for additional guidance on the management of the risk of meningococcal infection).
Vaccination reduces, but does not eliminate, the risk of meningococcal infections. Monitor patients for early signs of meningococcal infections and evaluate immediately if infection is suspected.
Soliris is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). Under the Soliris REMS, prescribers must enroll in the program. Enrollment in the Soliris REMS program and additional information are available by telephone: 1-888-SOLIRIS (1-888-765-4747) or at www.solirisrems.com.

Contraindications

Patients with unresolved serious Neisseria meningitidis infection
Patients who are not currently vaccinated against Neisseria meningitidis, unless the risks of delaying Soliris treatment outweigh the risks of developing a meningococcal infection
Warnings and Precautions

Serious Meningococcal Infections

Risk and Prevention

The use of Soliris increases a patient’s susceptibility to serious meningococcal infections (septicemia and/or meningitis).

Vaccinate or revaccinate for meningococcal disease according to the most current ACIP recommendations for patients with complement deficiencies. Immunize patients without a history of meningococcal vaccination at least 2 weeks prior to receiving the first dose of Soliris. If Soliris must be initiated immediately in an unvaccinated patient, administer meningococcal vaccine(s) as soon as possible and provide 2 weeks of antibacterial drug prophylaxis. Discontinue Soliris in patients who are undergoing treatment for serious meningococcal infections.

REMS

Prescribers must counsel patients about the risk of meningococcal infection, provide the patients with the REMS educational materials, and ensure patients are vaccinated with meningococcal vaccine(s).

Other Infections

Serious infections with Neisseria species (other than N. meningitidis), including disseminated gonococcal infections, have been reported.

Patients may have increased susceptibility to infections, especially with encapsulated bacteria. Additionally, Aspergillus infections have occurred in immunocompromised and neutropenic patients. Children treated with Soliris may be at increased risk of developing serious infections due to Streptococcus pneumoniae and Haemophilus influenzae type b (Hib). Administer vaccinations for the prevention of Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) infections according to ACIP guidelines. Use caution when administering Soliris to patients with any systemic infection.

Monitoring Disease Manifestations After Soliris Discontinuation

Treatment Discontinuation for PNH

Monitor patients after discontinuing Soliris for at least 8 weeks to detect hemolysis.

Treatment Discontinuation for aHUS

After discontinuing Soliris, monitor patients with aHUS for signs and symptoms of thrombotic microangiopathy (TMA) complications for at least 12 weeks. In aHUS clinical trials, 18 patients (5 in the prospective studies) discontinued Soliris treatment. TMA complications occurred following a missed dose in 5 patients, and Soliris was reinitiated in 4 of these 5 patients.

Clinical signs and symptoms of TMA include changes in mental status, seizures, angina, dyspnea, or thrombosis. In addition, the following changes in laboratory parameters may identify a TMA complication: occurrence of 2, or repeated measurement of any one of the following: a decrease in platelet count by 25% or more compared to baseline or the peak platelet count during Soliris treatment; an increase in serum creatinine by 25% or more compared to baseline or nadir during Soliris treatment; or, an increase in serum LDH by 25% or more over baseline or nadir during Soliris treatment.

If TMA complications occur after Soliris discontinuation, consider reinstitution of Soliris treatment, plasma therapy [plasmapheresis, plasma exchange, or fresh frozen plasma infusion (PE/PI)], or appropriate organ-specific supportive measures.

Thrombosis Prevention and Management

The effect of withdrawal of anticoagulant therapy during Soliris treatment has not been established. Therefore, treatment with Soliris should not alter anticoagulant management.

Infusion-Related Reactions

Administration of Soliris may result in infusion-related reactions, including anaphylaxis or other hypersensitivity reactions. Interrupt Soliris infusion and institute appropriate supportive measures if signs of cardiovascular instability or respiratory compromise occur.

Adverse Reactions

The most frequently reported adverse reactions in the PNH randomized trial (≥10% overall and greater than placebo) are: headache, nasopharyngitis, back pain, and nausea.

The most frequently reported adverse reactions in aHUS single arm prospective trials (≥20%) are: headache, diarrhea, hypertension, upper respiratory infection, abdominal pain, vomiting, nasopharyngitis, anemia, cough, peripheral edema, nausea, urinary tract infections, pyrexia.

Please see accompanying full prescribing information for Soliris, including Boxed WARNING regarding serious meningococcal infections.

Notes

CALQUENCE

CALQUENCE (acalabrutinib) is a next-generation, selective inhibitor of Bruton’s tyrosine kinase (BTK). CALQUENCE binds covalently to BTK, thereby inhibiting its activity.18,19 In B cells, BTK signaling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis and adhesion.18

CALQUENCE is available for prescribing in capsule and tablet formulations in the US. CALQUENCE tablets and capsules are approved in the US for the treatment of CLL and SLL, and for the treatment of adult patients with MCL who have received at least one prior therapy.18,20 Capsules have restrictions in relation to use with gastric acid-reducing agents. The tablets are not licensed in the European Union.

CALQUENCE capsules are approved for CLL in the EU and many other countries worldwide and approved in Japan for relapsed or refractory CLL and SLL. A Phase I trial is currently underway in Japan for the treatment of front-line CLL.

In the US and several other countries, CALQUENCE capsules are also approved for the treatment of adult patients with MCL who have received at least one prior therapy. The US MCL 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 not currently approved for the treatment of MCL in Europe or Japan.

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 evaluated for the treatment of multiple B-cell blood cancers, including CLL, MCL, diffuse large B-cell lymphoma, Waldenström’s macroglobulinemia, follicular lymphoma and marginal zone lymphoma.

ULTOMIRIS

ULTOMIRIS (ravulizumab-cwvz), the first and only long-acting C5 complement inhibitor, provides immediate, complete and sustained complement inhibition. The medication works by inhibiting the C5 protein in the terminal complement cascade, a part of the body’s immune system. When activated in an uncontrolled manner, the complement cascade over-responds, leading the body to attack its own healthy cells. ULTOMIRIS is administered intravenously every eight weeks in adult patients, following a loading dose.

ULTOMIRIS is approved in the US, EU and Japan for the treatment of certain adults with gMG.

ULTOMIRIS is also approved in the US, EU and Japan for the treatment of certain adults with PNH and for certain children with PNH in the US and EU.

Additionally, ULTOMIRIS is approved in the US, EU and Japan for certain adults and children with aHUS to inhibit complement-mediated thrombotic microangiopathy.

As part of a broad development program, ULTOMIRIS is being assessed for the treatment of additional hematology and neurology indications.

SOLIRIS

SOLIRIS (eculizumab) is a first-in-class C5 complement inhibitor. The medication works by inhibiting the C5 protein in the terminal complement cascade, a part of the body’s immune system. When activated in an uncontrolled manner, the terminal complement cascade over-responds, leading the body to attack its own healthy cells. SOLIRIS is administered intravenously every two weeks, following an introductory dosing period.

SOLIRIS is approved in the US, EU and Japan for the treatment of PNH, aHUS, certain adults with gMG and certain adults with NMOSD.

SOLIRIS is not indicated for the treatment of patients with STEC-HUS.

Memgen Reports Results From Its First-In-Human Clinical Trial of MEM-288 in Solid Tumors Refractory to Checkpoint Inhibitors at SITC 2022

On November 30, 2022 Memgen, Inc., a biopharmaceutical company developing potentially life-saving cancer immunotherapies, reported the first clinical data for MEM-288, its oncolytic viral therapy, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 37th Annual Meeting in Boston, MA (Press release, Memgen, NOV 30, 2022, View Source [SID1234624630]).

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The interim results from this ongoing first-in-human Phase 1 trial indicate that MEM-288 is well tolerated and expands tumor-fighting T cells. Seven patients with solid tumors received at least one intratumoral injection of MEM-288 with no dose-limiting toxicity or discontinuation due to toxicity. The only reported adverse event in more than one patient was grade 1 injection site tenderness. The 7 patients included 6 with non-small cell lung cancer (NSCLC) and 1 with pancreatic cancer. All 6 NSCLC patients had already received 2 to 4 lines of therapy including one or more lines with checkpoint inhibitors before enrollment.

Two of five NSCLC patients evaluable for RECIST response in non-injected, distant tumors exhibited best response of stable disease. This "abscopal effect" suggests that local administration of MEM-288 could stimulate immune system reactivity to tumors elsewhere in the body without corresponding systemic toxicity. The remaining three NSCLC patients evaluable for RECIST response had progressive disease.

One of the NSCLC patients with progressive disease had already had three lines of prior treatment, including osimertinib, carboplatin/paclitaxel/bevacizumab/atezolizumab, and radiation therapy for brain metastasis. This patient achieved a complete response after treatment with MEM-288 and then docetaxel and ramucirumab.

"We’re encouraged by the initial safety, tumor shrinkage, and immune responses seen so far in metastatic NSCLC with MEM-288 as a monotherapy," said Mark Cantwell, Ph.D., Chief Scientific Officer of Memgen. "We look forward to completing this part of the trial and starting on our study of MEM-288 in combination with an anti-PD-1 antibody for relapsed/refractory metastatic NSCLC."

About MEM-288

MEM-288 is an oncolytic adenovirus uniquely engineered to express two immune modulators: MEM40, Memgen’s proprietary recombinant membrane-stable form of CD40 ligand, and the cytokine interferon beta (IFNβ). MEM-288 selectively targets cancer cells and boosts the anti-tumor immune response. MEM-288 leverages validated targets that are potent activators of the immune system. Based on the early results presented at SITC (Free SITC Whitepaper), MEM-288 may successfully deploy the CD40 pathway to stimulate immune responses directed against tumors.

For more information about the ongoing Phase 1 study of MEM-288, visit: View Source