On November 3, 2022 Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) reported the upcoming presentation of five posters highlighting data from the Company’s commercial and clinical-stage hematology-oncology portfolio at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition being held December 10-13, 2022, in New Orleans, LA, and virtually (Press release, Rigel, NOV 3, 2022, View Source [SID1234622937]).

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The abstract titled "Olutasidenib (FT-2102) induces durable complete remissions in patients with relapsed/refractory mIDH1 acute myeloid leukemia: Results from a planned interim analysis of a phase 2 pivotal clinical trial" provides an updated interim analysis from the open-label Phase 2 registrational study of olutasidenib, an investigational, oral, small molecule inhibitor of mutant isocitrate dehydrogenase-1 (mIDH1), in patients with relapsed/refractory acute myeloid leukemia (R/R AML). The registrational cohort of the Phase 2 study enrolled 153 patients with mIDH1 R/R AML who received olutasidenib monotherapy 150 mg twice daily. The efficacy evaluable population was 147 patients who received their first dose at least six months prior to the interim analysis cutoff date of June 18, 2021. The primary endpoint was a composite of complete remission (CR) plus complete remission with partial hematological recovery (CRh). CRh is defined as less than 5% blasts in the bone marrow, no evidence of disease, and partial recovery of peripheral blood counts (platelets >50,000/microliter and absolute neutrophil count >500/microliter).

Results from the updated interim analysis of patients with mIDH1 R/R AML demonstrated a 35% CR+CRh rate with a median duration of 25.9 months. The observed activity is clinically meaningful and potentially represents a new therapeutic option in the treatment of this poor prognosis patient population. In this cohort, olutasidenib was well tolerated with an adverse event profile largely characteristic of symptoms or conditions experienced by patients with AML undergoing treatment. Differentiation syndrome was observed and manageable in most cases with dose interruption and corticosteroids. Increases in liver function parameters were manageable with dose modifications and concomitant medications.

"We are thrilled with these updated results from the olutasidenib registrational trial, which demonstrate a median duration of CR+CRh of 25.9 months, and potentially represents an improvement for patients with mIDH1 R/R AML. The totality of these efficacy and safety data underscore the potential for olutasidenib to be a meaningful new treatment option for these patients who are currently underserved," said Raul Rodriguez, Rigel’s president and CEO. "In addition to the olutasidenib data, we are pleased to see data presented from across our hematology-oncology portfolio, demonstrating our strength in this space."

A New Drug Application (NDA) for olutasidenib for the treatment of mIDH1 R/R AML is currently under review by the U.S. Food and Drug Administration (FDA) with a Prescription Drug User Fee Act (PDUFA) target action date of February 15, 2023.

Poster Presentations

Abstract #: 2757
Title: Olutasidenib (FT-2102) induces durable complete remissions in patients with relapsed/refractory mIDH1 acute myeloid leukemia: Results from a planned interim analysis of a phase 2 pivotal clinical trial
Presenter: Jorge E. Cortes, M.D., Director, Georgia Cancer Center, Cecil F. Whitaker Jr., GRA Eminent Scholar Chair in Cancer, and Phase 2 Trial Investigator
Session Name: 616. Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster II
Date: Sunday, December 11, 2022
Presentation Time: 6:00-8:00 PM CT
Location: Ernest N. Morial Convention Center, Hall D

Abstract #: 2250
Title: The safety and efficacy of fostamatinib in patients with chronic immune thrombocytopenic purpura treated in a real-world community hematology setting
Presenter: Mehdi M. Moezi, MD, Cancer Specialists of North Florida
Session Name: 904. Outcomes Research—Non-Malignant Conditions: Poster I
Date: Saturday, December 10, 2022
Presentation Time: 5:30-7:30 PM CT
Location: Ernest N. Morial Convention Center, Hall D

Abstract #: 1011
Title: Phase 3, randomized, double-blind, placebo-controlled, global study (FORWARD) of fostamatinib for the treatment of warm antibody autoimmune hemolytic anemia
Presenter: David J. Kuter, M.D., DPhil, Director of Clinical Hematology at Massachusetts General Hospital, Professor of Medicine at Harvard Medical School, FORWARD Trial Lead Investigator
Session Name: 101. Red Cells and Erythropoiesis, Excluding Iron: Poster I
Date: Saturday, December 10, 2022
Presentation Time: 5:30-7:30 PM CT
Location: Ernest N. Morial Convention Center, Hall D

Abstract #: 3724
Title: SYK kinase as a master regulator of NETosis
Presenter: Vadim V. Markovtsov, PhD, MS, Rigel Pharmaceuticals, Inc.
Session Name: 201. Granulocytes, Monocytes, and Macrophages: Poster III
Date: Monday, December 12, 2022
Presentation Time: 6:00-8:00 PM CT
Location: Ernest N. Morial Convention Center, Hall D

Abstract #: 1132
Title: Comparative Effectiveness of Fostamatinib Vs. Rituximab in Refractory Chronic Immune Thrombocytopenia: A Network Meta-Analysis
Presenter: Vickie McDonald, MD, Consultant Haematologist at Barts Health NHS Trust
Session Name: 311. Disorders of Platelet Number or Function: Clinical and Epidemiological: Poster I
Date: Saturday, December 10, 2022
Presentation Time: 5:30-7:30 PM CT
Location: Ernest N. Morial Convention Center, Hall D

The conference abstracts can be accessed here.

To learn more about Rigel Pharmaceuticals and the Company’s clinical and commercial heme-onc portfolio visit booth #2815 during ASH (Free ASH Whitepaper) 2022.

About Olutasidenib & AML
Olutasidenib is an oral, small molecule investigational agent designed to selectively bind to and inhibit mutated IDH1 enzymes. This targeted agent has the potential to provide therapeutic benefit by reducing 2-HG levels and restoring normal cellular differentiation. IDH1 is a natural enzyme that is part of the normal metabolism of all cells. When mutated, IDH1 activity can promote blood malignancies and solid tumors. IDH1 mutations are present in 6 to 9 percent of patients with AML.1

Acute myeloid leukemia (AML) is a rapidly progressing cancer of the blood and bone marrow that affects myeloid cells, which normally develop into various types of mature blood cells. AML occurs primarily in adults and accounts for about 1 percent of all adult cancers. The American Cancer Society estimates that in the United States alone, there will be about 20,050 new cases, most in adults, in 2022.2 Relapsed AML affects about half of all patients who, following treatment and remission, experience a return of leukemia cells in the bone marrow.3 Refractory AML, which affects between 10 and 40 percent of newly diagnosed patients, occurs when a patient fails to achieve remission even after intensive treatment.4 Quality of life declines for patients with each successive line of treatment for AML, and well tolerated treatments in relapsed and refractory disease remain an unmet need.

About ITP
In patients with ITP (immune thrombocytopenia), the immune system attacks and destroys the body’s own blood platelets, which play an active role in blood clotting and healing. Common symptoms of ITP are excessive bruising and bleeding. People suffering with chronic ITP may live with an increased risk of severe bleeding events that can result in serious medical complications or even death. Current therapies for ITP include steroids, blood platelet production boosters (TPO-RAs), and splenectomy. However, not all patients respond to existing therapies. As a result, there remains a significant medical need for additional treatment options for patients with ITP.

About AIHA
Autoimmune hemolytic anemia (AIHA) is a rare, serious blood disorder in which the immune system produces antibodies that lead to the destruction of the body’s own red blood cells. Warm antibody AIHA (wAIHA), which is the most common form of AIHA, is characterized by the presence of antibodies that react with the red blood cell surface at body temperature. wAIHA affects approximately 36,000 adult patients in the U.S.5 and can be a severe, debilitating disease. To date, there are no disease-targeted therapies approved for wAIHA, despite the unmet medical need that exists for these patients.

About TAVALISSE
Indication
TAVALISSE (fostamatinib disodium hexahydrate) tablets is indicated for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment.

Important Safety Information

Warnings and Precautions

Hypertension can occur with TAVALISSE treatment. Patients with pre-existing hypertension may be more susceptible to the hypertensive effects. Monitor blood pressure every 2 weeks until stable, then monthly, and adjust or initiate antihypertensive therapy for blood pressure control maintenance during therapy. If increased blood pressure persists, TAVALISSE interruption, reduction, or discontinuation may be required.
Elevated liver function tests (LFTs), mainly ALT and AST, can occur with TAVALISSE. Monitor LFTs monthly during treatment. If ALT or AST increase to ≥3 x upper limit of normal, manage hepatotoxicity using TAVALISSE interruption, reduction, or discontinuation.
Diarrhea occurred in 31% of patients and severe diarrhea occurred in 1% of patients treated with TAVALISSE. Monitor patients for the development of diarrhea and manage using supportive care measures early after the onset of symptoms. If diarrhea becomes severe (≥Grade 3), interrupt, reduce dose or discontinue TAVALISSE.
Neutropenia occurred in 6% of patients treated with TAVALISSE; febrile neutropenia occurred in 1% of patients. Monitor the ANC monthly and for infection during treatment. Manage toxicity with TAVALISSE interruption, reduction, or discontinuation.
TAVALISSE can cause fetal harm when administered to pregnant women. Advise pregnant women the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the last dose. Verify pregnancy status prior to initiating TAVALISSE. It is unknown if TAVALISSE or its metabolite is present in human milk. Because of the potential for serious adverse reactions in a breastfed child, advise a lactating woman not to breastfeed during TAVALISSE treatment and for at least 1 month after the last dose.
Drug Interactions

Concomitant use of TAVALISSE with strong CYP3A4 inhibitors increases exposure to the major active metabolite of TAVALISSE (R406), which may increase the risk of adverse reactions. Monitor for toxicities that may require a reduction in TAVALISSE dose.
It is not recommended to use TAVALISSE with strong CYP3A4 inducers, as concomitant use reduces exposure to R406.
Concomitant use of TAVALISSE may increase concentrations of some CYP3A4 substrate drugs and may require a dose reduction of the CYP3A4 substrate drug.
Concomitant use of TAVALISSE may increase concentrations of BCRP substrate drugs (eg, rosuvastatin) and P-Glycoprotein (P-gp) substrate drugs (eg, digoxin), which may require a dose reduction of the BCRP and P-gp substrate drug.
Adverse Reactions

Serious adverse drug reactions in the ITP double-blind studies were febrile neutropenia, diarrhea, pneumonia, and hypertensive crisis, which occurred in 1% of TAVALISSE patients. In addition, severe adverse reactions occurred including dyspnea and hypertension (both 2%), neutropenia, arthralgia, chest pain, diarrhea, dizziness, nephrolithiasis, pain in extremity, toothache, syncope, and hypoxia (all 1%).
Common adverse reactions (≥5% and more common than placebo) from FIT-1 and FIT-2 included: diarrhea, hypertension, nausea, dizziness, ALT and AST increased, respiratory infection, rash, abdominal pain, fatigue, chest pain, and neutropenia.

On November 3, 2022 Biomea Fusion, Inc. (Nasdaq: BMEA), a clinical-stage biopharmaceutical company dedicated to discovering and developing novel covalent small molecules to treat and improve the lives of patients with genetically defined cancers and metabolic diseases, reported it will present preclinical data of investigational covalent FLT3 inhibitor, BMF-500, at the 64th ASH (Free ASH Whitepaper) Annual Meeting, which will be held from December 10-13, 2022, at the Ernest N. Morial Convention Center in New Orleans, Louisiana (Press release, Biomea Fusion, NOV 3, 2022, View Source [SID1234622936]).

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BMF-500 was discovered and developed in-house at Biomea using the company’s proprietary FUSION System and designed to have a therapeutic profile to allow for combinations with standard of care and/or novel targeted agents like BMF-219, Biomea’s investigational covalent menin inhibitor. The company is on track to submit an investigational new drug (IND) application for BMF-500 in the first half of 2023 and, subject to the successful clearance of an investigational new drug (IND) application, plans to initiate clinical trials evaluating BMF-500 as a single agent and in novel combinations.

"We believe the preclinical data we will present at ASH (Free ASH Whitepaper) has the potential to establish BMF-500 as the most potent and selective FLT3 inhibitor reported to date. BMF-500’s unique profile and robust preclinical data demonstrate our growing expertise in developing next-generation covalently binding small molecules through our FUSIONTM System," said Dr. Steve Morris, Biomea’s CMO. "Given the picomolar activity against key isoforms of FLT3, high specificity to FLT3, and the potential to combine with other agents, including our own novel menin inhibitor, BMF-219, we believe BMF-500 has the potential to produce deep and durable remissions in patients with FLT3 mutant AML."

Presentation Details

Session Name: 616. Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster II
Session Date: Sunday, December 11, 2022
Presentation Time: 6:00 PM – 8:00 PM (CST)
Publication Number: 2756
Title: BMF-500: An Orally Bioavailable Covalent Inhibitor of FLT3 with High Selectivity and Potent Antileukemic Activity in FLT3-Mutated AML

Full Text of Abstract:
Activating mutations of the FMS-like tyrosine kinase 3 (FLT3) are the most frequent genetic alteration in AML and are associated with poor prognosis. Though several FLT3 inhibitors have entered clinical trials and reached commercialization, adverse events and dose-limiting toxicities often restrict the therapeutic window and limit their long-term use. Such limitations impact the ability to achieve long-lasting response in patients and ultimately result in therapy-induced resistance. Exquisite potency combined with high selectivity and improved safety profile is expected to help improve tolerance and overall treatment outcomes of FLT3-targeted therapy.

BMF-500 was designed as a highly potent and selective, covalent, small molecule inhibitor of FLT3, that binds irreversibly to a reactive cysteine in the kinase active site. BMF-500 is a picomolar inhibitor with markedly improved potency over gilteritinib, a reversible inhibitor of FLT3. BMF-500 selectively killed AML cells harboring FLT3 activating mutations, including MV4-11 and MOLM-13, and engineered cells expressing FLT3 internal tandem duplications (FLT3-ITD) and/or FLT3 tyrosine kinase domain (TKD) mutations. In ex vivo cultures, BMF-500 as a single agent induced potent growth inhibition of patient-derived AML cells harboring either FLT3-ITD or FLT3 non-ITD mutations.

The potent covalent inhibition of FLT3 by BMF-500 manifested in effective and durable cellular response that was improved over gilteritinib. For example, a 3-hour exposure followed by wash-out of BMF-500 outperformed 4 days of continuous exposure to gilteritinib, at all concentrations tested. In cells harboring FLT3 activating mutations, BMF-500 induced dose-dependent inhibition of FLT3 phosphorylation and downstream signaling, including phospho-STAT5 and phospho-ERK. A 1-hour pulse treatment with BMF-500 was sufficient to achieve deep and durable target inhibition for greater than 24 hours, an effect not observed with gilteritinib under similar conditions. Profiling BMF-500 across a broad panel of kinases and key cell-surface receptors revealed high selectivity for FLT3 mutants and selectivity against cKit.

Potent FLT3 inhibition and high selectivity of BMF-500 translated to sustained tumor regression and improved survival in both subcutaneous and disseminated xenograft models of mutant FLT3-driven AML. Orally administered BMF-500 was well tolerated over 4 weeks of dosing. Study results including efficacy and PD response will be presented.

Collectively these data demonstrate BMF-500 to be a novel FLT3 inhibitor with best-in-class potential, given its efficacy, durability, and selectivity in comparison to existing FLT3 inhibitors.

About FLT3 (fms-like tyrosine kinase 3)

FLT3 is a tyrosine kinase receptor that plays a central role in the survival, proliferation, and differentiation of immature blood cells. Notably, FLT3 gene mutations are common in patients with AML and are associated with a poor prognosis. Nearly 30% of AML patients have a FLT3 mutation, representing more than 6,000 incident patients in the United States each year. While FLT3-specific and pan-tyrosine kinase inhibitors are approved by the FDA across various lines of therapy in AML, these agents have produced relatively low rates of durable responses and overall survival remains an unmet need.

On November 3, 2022 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported that two abstracts detailing new selinexor data have been selected for poster presentation at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition taking place December 10-13, 2022 (Press release, Karyopharm, NOV 3, 2022, View Source [SID1234622935]). The presentations include results from the Phase 1 open-label, dose-escalation study of selinexor in combination with ruxolitinib in patients with treatment-naïve myelofibrosis (MF) and data from a subset analysis of the STOMP study in patients with triple-class refractory MM.

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Results from Phase 1 Study Evaluating Selinexor in Combination with Ruxolitinib in Patients with Treatment-Naïve Myelofibrosis

The data included in the abstract for ASH (Free ASH Whitepaper) 2022 were based on the Phase 1 portion of the Phase 1/2 study evaluating the safety and preliminary efficacy of once-weekly selinexor in combination with standard dose ruxolitinib in patients with treatment-naïve myelofibrosis (NCT04562389). As of July 2022, 19 patients had been assigned to either selinexor 40 mg or 60 mg, in combination with ruxolitinib 15/20 mg BID.

Seventy-nine percent of efficacy evaluable patients (11 out of 14) demonstrated ≥35% reduction in spleen volume (SVR35) at week 12 and 86% (6 out of 7) achieved SVR35 at week 24. Thirteen patients who had received at least 12 weeks of treatment experienced rapid improvements in their symptom scores, with 69% (9 out of 13) of efficacy evaluable patients having ≥50% reduction (TSS50). Eleven out of 17 transfusion-independent patients (65%) who had at least eight weeks of treatment maintained stable hemoglobin (± 2g/dL) or improved hemoglobin level (>2g/dL increase) at last follow up.

"We remain very encouraged by the notable activity across three clinically meaningful efficacy endpoints relevant to patients with MF including spleen volume reduction, improvement in symptom score and hemoglobin stabilization," said Reshma Rangwala, MD, PhD, Chief Medical Officer of Karyopharm. "We look forward to observing how the efficacy and safety evolve across the two doses and engaging with the FDA on the registrational portion of this trial."

The data observed across both the 40mg and 60mg assigned groups demonstrate a generally manageable side effect profile with no dose-limiting toxicities observed at either dose level in the Phase 1a dose escalation portion of the study. The most common adverse events (AEs) were nausea (58%), anemia (42%) and vomiting (42%), the majority of which were grades 1-2. The most common reported grade 3-4 treatment-emergent AEs were thrombocytopenia (26%) and anemia (21%), both of which were reversible. Updated data from this study, including results from additional patients, will be presented at the ASH (Free ASH Whitepaper) meeting in December 2022.

"The addition of novel agents to JAK inhibitors is an intriguing approach to improve depth and duration of responses compared to JAK inhibition alone," said Dr. Haris Ali, City of Hope Comprehensive Cancer Center. "The introduction of a novel mechanism of SINE inhibition, in combination with a JAK inhibitor, may provide patients an upfront treatment option that could improve clinical outcomes with a manageable safety profile."

Details for the ASH (Free ASH Whitepaper) 2022 abstracts are as follows:

Poster Presentations

Title: A Phase 1, Open-Label, Dose-Escalation Study of Selinexor Plus Ruxolitinib in Patients with Treatment-Naïve Myelofibrosis
Presenter: Dr. Ali, City of Hope Comprehensive Cancer Center
Abstract #: 1734
Session Type: Poster Presentation
Session: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Poster I
Date and Time: Saturday, December 10, 2022, 5:30 PM – 7:30 PM CT

Title: Once Weekly Selinexor, Carfilzomib and Dexamethasone (XKd) in Triple Class Refractory Multiple Myeloma
Presenter: Dr. Schiller, David Geffen School of Medicine at UCLA
Abstract #: 4516
Session Type: Poster Presentation
Session: 652. Multiple Myeloma and Plasma Cell Dyscrasias: Clinical and Epidemiological: Poster III
Date and Time: Monday, December 12, 2022, 6:00 PM – 8:00 PM CT

Online Publication

Title: Real-World Safety and Effectiveness of Selinexor-Based Regimens in Patients with Relapsed or Refractory Multiple Myeloma and Dialysis-Dependent Renal Impairment
Presenter: Dr. Niblock, Karyopharm Therapeutics
Abstract #: 5773
Session Type: Online publication
Date and Time: Available in the November supplemental issue of Blood

About XPOVIO (selinexor)

XPOVIO is a first-in-class, oral exportin 1 (XPO1) inhibitor and the first of Karyopharm’s Selective Inhibitor of Nuclear Export (SINE) compounds to be approved for the treatment of cancer. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein XPO1. XPOVIO is approved in the U.S. and marketed by Karyopharm in multiple oncology indications, including: (i) in combination with Velcade (bortezomib) and dexamethasone (XVd) in patients with multiple myeloma after at least one prior therapy; (ii) in combination with dexamethasone in patients with heavily pre-treated multiple myeloma; and (iii) in patients with diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. XPOVIO (also known as NEXPOVIO in certain countries) has received regulatory approvals in various indications in a growing number of ex-U.S. territories and countries, including but not limited to the European Union, the United Kingdom, China, South Korea, Canada, Israel and Taiwan. XPOVIO and NEXPOVIO is marketed by Karyopharm’s partners, Antengene, Menarini, Neopharm and FORUS in China, South Korea, Singapore, Australia, Hong Kong, Germany, Austria, Israel and Canada.

Please refer to the local Prescribing Information for full details.

Selinexor is also being investigated in several other mid- and late-stage clinical trials across multiple high unmet need cancer indications, including in endometrial cancer and myelofibrosis.

For more information about Karyopharm’s products or clinical trials, please contact the Medical Information department at:

Tel: +1 (888) 209-9326
Email: [email protected]

SELECT IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Thrombocytopenia: Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care.
Neutropenia: Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony–stimulating factors.
Gastrointestinal Toxicity: Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care.
Hyponatremia: Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care.
Serious Infection: Monitor for infection and treat promptly.
Neurological Toxicity: Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes.
Embryo–Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception.
Cataract: Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract.
Adverse Reactions

The most common adverse reactions (≥20%) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting. Grade 3–4 laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia. In the BOSTON trial, fatal adverse reactions occurred in 6% of patients within 30 days of last treatment. Serious adverse reactions occurred in 52% of patients. Treatment discontinuation rate due to adverse reactions was 19%.
The most common adverse reactions (≥20%) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%.
The most common adverse reactions (incidence ≥20%) in patients with DLBCL, excluding laboratory abnormalities, are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3–4 laboratory abnormalities (≥15%) are thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. In the SADAL trial, fatal adverse reactions occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal adverse reactions was infection (4.5% of patients). Serious adverse reactions occurred in 46% of patients; the most frequent serious adverse reaction was infection (21% of patients). Discontinuation due to adverse reactions occurred in 17% of patients.
Use In Specific Populations

On November 3, 2022 Affimed N.V. (Nasdaq: AFMD) ("Affimed"), and Artiva Biotherapeutics Inc. ("Artiva"), both immune-oncology companies focused on developing and commercializing therapies utilizing the innate immune system, reported a new strategic partnership to jointly develop, manufacture, and commercialize a combination therapy comprised of Affimed’s Innate Cell Engager (ICE) AFM13 and Artiva’s cord blood-derived, cryopreserved off-the-shelf allogeneic NK cell product candidate, AB-101 (Press release, Artiva Biotherapeutics, NOV 3, 2022, View Source [SID1234622934]).

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Affimed submitted a pre-IND meeting request for the AFM13 and AB-101 co-administered combination therapy to the FDA requesting feedback on the clinical trial design in relapsed/refractory (r/r) Hodgkin lymphoma (HL) with an exploratory arm evaluating the combination in r/r CD30-positive peripheral T-cell lymphoma (PTCL) and potential path to registration. FDA responded to this request and guided to providing feedback by Q1 2023.

This clinical agreement follows the parties’ existing two-year preclinical collaboration to assess combining elements of the companies’ respective platforms in the generation of targeted, off-the-shelf allogeneic NK cell therapies. As part of the collaboration, the companies evaluated the combination of AFM13 and AB101 in various preclinical models and generated data that supports development of a co-administered combination therapy.

"Based on the compelling clinical data we have generated for AFM13 in combination with NK cells, we are committed to finding the fastest path to bringing this potentially life-changing treatment to lymphoma patients," said Dr. Adi Hoess, CEO of Affimed. "The allogeneic NK field is still at a nascent stage, and we selected Artiva because of their commercially-viable production process that can support a multicenter clinical trial and potentially enable a path to registration."

"We are developing AB-101 as a universal ADCC enhancer when combined with monoclonal antibodies and NK cell engagers," said Dr. Fred Aslan, CEO of Artiva. "The data Affimed has generated to date with AFM13 in combination with cord blood-derived NK cells in a patient population with great unmet need is very compelling, and we are excited to partner with Affimed on what could become one of the first approvals for an allogeneic NK cell therapy-based regimen."

AFM13 is currently being investigated in combination with allogeneic cord blood-derived NK cells (CBNK) from The University of Texas MD Anderson Cancer Center. In this investigator sponsored study, data published earlier today for presentation at the 64th ASH (Free ASH Whitepaper) Annual Meeting and Exposition demonstrated that all 24 patients in the recommended Phase 2 dose cohort responded (overall response rate of 100%) and showed a complete response rate of 70.8%. The combination was well tolerated with few infusion-related reactions and without cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or graft versus host disease.

The Affimed-Artiva partnership aims to expedite further development of the combination therapy in CD30-positive lymphoma patients who have exhausted other treatment options. AB-101 has already completed a monotherapy safety cohort in an initial Phase 1 trial and is currently being assessed in combination with the anti-CD20 monoclonal antibody, rituximab, in patients with relapsed or refractory non-Hodgkin lymphoma (NHL). Preclinical results investigating the combination of AFM13 and AB-101 have further demonstrated enhanced anti-tumor activity. The companies plan to file an IND for the program in relapsed/refractory CD30-positive lymphoma patients during the first half of 2023.

Under the terms of the agreement, Affimed and Artiva will pursue the development of the AFM13/AB-101 combination treatment in the United States on a co-exclusive basis. Affimed will lead regulatory activities through Phase 2 and any confirmatory studies. Affimed will be responsible for funding clinical study costs through Phase 2, while Artiva will be responsible for the costs of supplying AB-101 and IL-2 for such studies. If accelerated approval is obtained, the companies will share confirmatory study costs on a 50/50 basis.

Both companies will retain commercialization and distribution rights and book sales for their respective products. Affimed will be responsible for promotional activities and expenses of the combination therapy. Pursuant to the agreement, revenues from the combination will be shared, with Affimed receiving 67% of the combination therapy revenue and Artiva receiving 33%.

CONFERENCE CALL AND WEBCAST INFORMATION

Affimed and Artiva will host a conference and webcast on November 3, 2022, at 10:30 a.m. EDT / 15:30 CEST to discuss this partnership and next steps in the development of AFM13 in combination with AB-101. The conference call will be available via phone and webcast. A live audio webcast of the conference call will be available in the "Webcasts" section on the "Investors" page of the Affimed website at View Source

To access the call by phone, please use link https://register.vevent.com/register/BIca92c598dd7a41319b8a09f5f7ce08bf, and you will be provided with dial in details and a pin number.

To avoid delays, we encourage participants to dial into the conference call fifteen minutes ahead of the scheduled start time.

A replay of the webcast will be accessible at the same link for 30 days following the call.

About AFM13

AFM13 is a first-in-class innate cell engager (ICE) that uniquely activates the innate immune system to destroy CD30-positive hematologic tumors. AFM13 induces specific and selective killing of CD30-positive tumor cells, leveraging the power of the innate immune system by engaging and activating natural killer (NK) cells and macrophages. AFM13 is Affimed’s most advanced ICE clinical program and is currently being evaluated as a monotherapy in a registration-directed trial in patients with relapsed/refractory peripheral T-cell lymphoma (REDIRECT). Additional details can be found at www.clinicaltrials.gov (NCT04101331).

About AB-101

AB-101 is a cord blood-derived, allogeneic, cryopreserved, ADCC-enhancing NK cell therapy candidate for use in combination with monoclonal antibodies or innate-cell engagers. Artiva selects cord blood units with the high affinity variant of the receptor CD16 and a KIR-B haplotype for enhanced product activity. Artiva can generate thousands of doses of pure, cryopreserved, infusion-ready NK cells from a single umbilical cord blood unit while retaining the high and consistent expression of CD16 without the need for engineering. Artiva is conducting a Phase 1/2 multicenter clinical trial (ClinicalTrials.gov Identifier: NCT04673617) to assess the safety and clinical activity of AB-101 alone and in combination with the anti-CD20 monoclonal antibody, rituximab, in patients with relapsed or refractory B-cell-non-Hodgkin lymphoma (NHL) who have progressed beyond two or more prior lines of therapy.

On November 3, 2022 Allergan Aesthetics, an AbbVie company (NYSE: ABBV), reported that it is continuing its commitment to provide education and support for breast health, restoration, and research through its Pink Ribbon Strong 365 campaign (Press release, AbbVie, NOV 3, 2022, View Source [SID1234622933]). Mindful that breast cancer affects people of all races, ethnicities, and socioeconomic status and does not limit its impact to a specific time of the year, Pink Ribbon Strong 365 is a year-round program advocating for awareness, empowering confidence, and supporting those organizations creating an impact in the fight against breast cancer.

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"Whether you’ve received a recent diagnosis, are currently going through treatment, or are in remission, we understand that each woman’s journey is deeply personal," said Carrie Strom, Senior Vice President, AbbVie, and President, Global Allergan Aesthetics. "The fight against breast cancer doesn’t stop because Breast Cancer Awareness month is over, which is why the Pink Ribbon Strong 365 campaign is focused on supporting organizations that help women year-round."

Pink Ribbon Strong 365 strives to help women on their unique journeys in a multitude of ways:

Natrelle Cares Package: a thoughtfully curated collection of items created by breast cancer survivors and other resources provided to breast cancer patients, survivors, and previvors. The package includes educational resources to support and empower women to make the right choices for themselves and useful items such as SkinMedica skincare products.
Natrelle Inspires Bra, a Natrelle x AnaOno Collaboration: a partnership with AnaOno to sponsor the creation of a purposefully designed bralette for breast cancer patients that gives back. For every bra sold, one is donated to a breast cancer patient in need.
"Not Just One," Award-Winning Documentary: a powerful documentary that featured women impacted by breast cancer who walked in the New York Fashion Week to raise awareness and funds for METAvivor, a nonprofit organization dedicated to funding metastatic breast cancer (MBC) research. Watch now on Amazon Prime. Proceeds from each purchase go to METAvivor.
Inspiring Patient Stories Shed Light on Reconstruction Journey: featured on Lifetime TV to share the story of a woman who went through implant-based breast reconstruction after being treated for breast cancer. The segment will be available to view on Natrelle’s YouTube channel.
Additional Partnerships: working with like-minded organizations who share the same goals, such as METAvivor, Young Survival Coalition, Adelphi NY Statewide Breast Cancer Hotline & Support Program, Sisters Network, ALAS Wings, Pink Lemonade Project, Living Beyond Breast Cancer, Breast Cancer Resource Center, AiRS Alliance in Reconstructive Surgery, and Susan Komen in Orange County, Calif., Austin, San Francisco, New Jersey, and Chicago.
For more information on each of these initiatives, follow the conversation on Instagram @NatrelleBreastReconstruction, #ThePowerOfYou, #MyReconReason.

Natrelle Breast Implants IMPORTANT SAFETY INFORMATION

Breast implants are not lifetime devices. The longer patients have them, the greater the chance they will develop complications, which may require more surgery. Breast implants have been associated with a cancer of the immune system called breast implant–associated anaplastic large cell lymphoma (BIA-ALCL). Some patients have died from BIA-ALCL. Patients have also reported a variety of systemic symptoms such as joint pain, muscle aches, confusion, chronic fatigue, autoimmune diseases, and others.

Natrelle Breast Implants are for breast reconstruction to replace breast tissue that was removed due to cancer or trauma or that failed to develop properly due to severe breast abnormality, and for revision surgery to improve primary breast reconstruction.

You should not get breast implants if you currently have an active infection, untreated breast cancer or precancer, or are pregnant or nursing. Tell your doctor about any conditions you have, any medications you are taking, and any planned cancer treatments. Breast implantation is likely not a one-time surgery. Having implants removed and not replaced may lead to permanent cosmetic changes of the breasts. Breast implants may affect breastfeeding. Gel implants may rupture without symptoms, so periodic imaging after surgery is recommended.

Key complications are reoperation, implant removal, implant rupture, implant deflation with saline-filled implants, and severe capsular contracture.

Talk to your doctor for more information.

The use of Natrelle Breast Implants is restricted to licensed physicians who provide information to patients about the risks and benefits of breast implant surgery.