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.

On November 3, 2022 BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX), a pre-commercial-stage biopharmaceutical company focused on oncology, reported that its full pharmacoeconomic study that indirectly evaluated the cost-effectiveness of using the investigational drug motixafortide as a primary stem cell mobilization (SCM) agent in combination with granulocyte colony stimulating factor (G-CSF), against plerixafor in combination with G-CSF, in multiple myeloma (MM) patients undergoing autologous stem cell transplantation, will be presented at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting held from December 10-13 in New Orleans, LA (Press release, BioLineRx, NOV 3, 2022, View Source [SID1234622932]). The analysis demonstrated significant net cost savings with motixafortide plus G-CSF and a greater proportion of patients achieving successful mobilization of optimal amounts of stem cells in a single apheresis day. The company has submitted a new drug application to the FDA for motixafortide in this indication.

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Collaborating investigators will also present a Phase 1 trial design of a novel mobilization regimen combining motixafortide and a VLA-4 inhibitor. The clinical trial will evaluate the regimen’s ability to safely produce the significant quantity of hematopoietic stem cells (HSC) required for the genetic manipulation processes used in gene therapy development in patients with sickle cell disease (SCD). Sickle cell disease is one of the most common inherited genetic diseases globally and HSC -based gene therapies now offer curative potential; however, effective HSC-based gene therapy depends on the collection of sufficient HSCs. Currently, the most widely used mobilization strategies include G-CSF and CXCR4 inhibition with plerixafor. However, G-CSF is contra-indicated in SCD and short-acting CXCR4 inhibition with plerixafor alone does not reliably yield optimal HSC numbers for SCD gene therapy applications. Developing novel HSC mobilization regimens to rapidly and reliably mobilize optimal CD34+ HSCs for gene therapy in SCD represents an unmet need.

"We are pleased to publish our full pharmacoeconomic data at ASH (Free ASH Whitepaper) which demonstrates that the combination of motixafortide plus G-CSF significantly lowers healthcare resource utilization in patients with multiple myeloma in the U.S. undergoing autologous stem cell transplantation," said Philip Serlin, Chief Executive Officer of BioLineRx. "Importantly, motixafortide plus G-CSF had significantly greater successful mobilization of the optimal number of cells following a single administration of motixafortide and in only one apheresis session, improving the patient journey. If approved, we believe motixafortide has the potential to become the new standard of care for all patients with multiple myeloma undergoing autologous stem cell transplantation. We are also excited to introduce the design of a Phase 1 study by investigators who are targeting unmet needs in both quantity and quality of cells harvested for cell engineering and administration. Our team is working diligently to develop motixafortide in different areas of stem cell mobilization with the objective of becoming the standard of care in these settings."

Major Findings of Cost-Effectiveness Analysis

The study was performed by the Global Health Economics and Outcomes Research (HEOR) team of IQVIA. For this study, an adjusted indirect comparison was undertaken, using data from the relevant phase 3 trials. This included finding and extracting efficacy data for both motixafortide (from GENESIS Phase 3 trial patient-level data) and plerixafor (aggregate data from literature), estimating plerixafor efficacy as if it had been one arm of the GENESIS trial (Bucher method), and implementing the results in the cost-effectiveness model.

Healthcare resource utilization (HRU) outcomes significantly favored motixafortide plus G-CSF during primary mobilization, including less frequent administration of G-CSF, lower G-CSF doses, and fewer apheresis sessions
The proportion of patients with successful mobilization of≥6×106 CD34+ cells/kg within 1 apheresis day was significantly greater with motixafortide plus G-CSF than with plerixafor plus G-CSF
Motixafortide plus G-CSF was dominant to plerixafor plus G-CSF over a lifetime horizon, resulting in additional QALYs and lower total costs as per base case deterministic results. The key cost drivers were the probability of successful transplantation, long-term maintenance costs, and the time to engraftment in poor mobilizers
PRESENTATIONS AT ASH (Free ASH Whitepaper)

Title: Cost-Effectiveness Analysis of Motixafortide Versus Plerixafor in Stem Cell Mobilization for Autologous Transplantation in Patients with Multiple Myeloma
Presenting Author: Mark Lamotte, MD, Global Health Economics & Outcomes Research, IQVIA
Date/Time: Poster 4848, Monday, December 12, 2022, 6:00 PM – 8:00 PM

Title: A Phase I Safety and Feasibility Study to Evaluate Motixafortide (CXCR4/SDF-1 Inhibition) and Natalizumab (VLA-4/VCAM-1 Inhibition) As a Novel Regimen to Mobilize CD34+ Hematopoietic Stem Cells for Gene Therapy in Sickle Cell Disease
Presenting Author: Zachary Crees, MD, Division of Oncology, Washington University School of Medicine, St. Louis, MO
Date/Time: Poster 4679, Monday, December 12, 2022, 6:00 PM – 8:00 PM

About the GENESIS Trial
The GENESIS trial (NCT03246529) was initiated in December 2017. GENESIS was a randomized, placebo-controlled, multicenter study, evaluating the safety, tolerability and efficacy of motixafortide and G-CSF, compared to placebo and G-CSF, for the mobilization of hematopoietic stem cells for autologous transplantation in multiple myeloma patients. The primary objective of the study was to demonstrate that only one dose of motixafortide on top of G-CSF is superior to G-CSF alone in the ability to mobilize ≥ 6 million CD34+ cells in up to two apheresis sessions. A key secondary objective of the study was to demonstrate that only one dose of motixafortide on top of G-CSF is superior to G-CSF alone in the ability to mobilize ≥ 6 million CD34+ cells in only one apheresis session. In this regard, ~90% of patients in the GENESIS study went directly to transplantation after mobilizing the optimal number of stem cells following only one administration of motixafortide on top of G-CSF and in only one apheresis session, compared to less than 10% of those receiving G-CSF alone. Additional objectives included time to engraftment of neutrophils and platelets and durability of engraftment, as well as other efficacy and safety parameters.

About Multiple Myeloma
Multiple myeloma is an incurable blood cancer that affects some white blood cells called plasma cells, which are found in the bone marrow. When damaged, these plasma cells rapidly spread and replace normal cells in the bone marrow with tumors. In 2022, it is estimated that more than 34,000 people will be diagnosed with multiple myeloma, and more than 12,000 people will die from the disease in the U.S. While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems or infections.

About Autologous Stem Cell Transplantation
Autologous stem cell transplantation (ASCT) is part of the standard treatment paradigm for a number of blood cancers, including multiple myeloma. In the U.S., nearly 15,000 ASCTs are performed each year with the majority in patients with multiple myeloma. The current standard of care includes the administration of 5-8 daily doses of granulocyte colony stimulating factor (G-CSF), with or without 1-4 doses of plerixafor, and the performance of 1-4 apheresis sessions. For patients unable to mobilize sufficient numbers of cells for harvesting during this primary mobilization phase, rescue therapy is carried out, consisting of 1-4 additional doses of plerixafor on top of G-CSF, and the performance of an additional number of apheresis sessions as necessary. In light of this, an agent with superior mobilization activity may significantly reduce the mobilization and harvesting burden and associated risks of the ASCT process and lead to significant clinical and resource benefits.