On November 5, 2024 Black Diamond Therapeutics, Inc. (Nasdaq: BDTX), a clinical-stage oncology company developing MasterKey therapies that target families of oncogenic mutations in patients with cancer, reported financial results for the third quarter ended September 30, 2024, and provided a corporate update (Press release, Black Diamond Therapeutics, NOV 5, 2024, View Source [SID1234647706]).

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"We are focused on the advancement of BDTX-1535 for the treatment of patients with EGFRm NSCLC and look forward to providing clinical updates on our Phase 2 trial for both newly diagnosed patients and patients with relapsed/refractory EGFRm NSCLC in the first quarter of 2025," said Mark Velleca, M.D., Ph.D., Chief Executive Officer of Black Diamond Therapeutics. "We also look forward to sharing feedback on a registrational path in relapsed/refractory EGFRm NSCLC following a meeting planned with the FDA in the first quarter of 2025."

Recent Developments & Upcoming Milestones:

BDTX-1535:

In September 2024, Black Diamond announced initial Phase 2 data demonstrating encouraging clinical responses and durability of BDTX-1535 in patients with relapsed/refractory epidermal growth factor receptor (EGFR) mutant (EGFRm) non-small cell lung cancer (NSCLC). The 200 mg daily dose of BDTX-1535 was selected for pivotal development, showing robust EGFRm target coverage and a favorable tolerability profile with no new safety signals observed. A preliminary overall response rate (ORR) of 42% was seen in 19 patients with known osimertinib resistance EGFR mutations (either C797S or PACC "P-loop αC-helix compressing" mutations). Encouraging durability was noted with a duration of response (DOR) of approximately eight months or more in the first three patients who achieved a partial response (PR), while 14 of the 19 patients remained on treatment.
In September 2024, Black Diamond presented a poster analyzing real-world treatment outcomes for newly diagnosed NSCLC patients with non-classical EGFR mutations (NCMs) at the 2024 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress. The analyses revealed the presence of a broad spectrum of NCMs, including PACC mutations, and allowed association with real-world treatment practices and therapeutic outcomes. Findings further demonstrated that current treatment practices for patients with NCMs are heterogenous: 36% of patients received osimertinib or afatinib and 60% of patients received chemotherapy and/or immunotherapy.
In October 2024, the Ivy Brain Tumor Center, which is sponsoring a "window of opportunity" (also known as Phase 0/1 "Trigger") trial of BDTX-1535 in patients with recurrent high-grade glioma (HGG), presented updated study results demonstrating that BDTX-1535 effectively penetrates rarely accessible regions of glioblastoma and suppresses EGFR signaling in patient tumors at the 19th Meeting of the European Association of Neuro-Oncology. These encouraging data provide rationale for the program’s expansion into newly diagnosed glioblastoma patients with EGFR aberrations.
In the first quarter of 2025, Black Diamond expects to disclose initial Phase 2 data in first-line EGFRm NSCLC patients with non-classical mutations as well as updated Phase 2 results in the recurrent EGFRm NSCLC setting (NCT05256290) together with an update on a potential registrational path for the recurrent setting.
Corporate

In October 2024, Black Diamond announced a corporate restructuring plan to prioritize its resources on advancing and optimizing development plans for its lead program BDTX-1535, strengthen operational efficiencies and extend the Company’s expected cash runway into the second quarter of 2026. As part of the restructuring, Black Diamond also deprioritized its Phase 1 RAS/RAF inhibitor, BDTX-4933, and is actively seeking partnerships for the program.
Financial Highlights

Cash Position: Black Diamond ended the third quarter of 2024 with approximately $112.7 million in cash, cash equivalents, and investments compared to $131.4 million as of December 31, 2023. Net cash used in operations was $11.3 million for the third quarter of 2024 compared to $18.4 million for the third quarter of 2023.
Research and Development Expenses: Research and development (R&D) expenses were $12.9 million for the third quarter of 2024, compared to $16.2 million for the same period in 2023. The decrease in R&D expenses was primarily due to workforce efficiencies and reduced spending on early discovery projects.
General and Administrative Expenses: General and administrative (G&A) expenses were $5.2 million for the third quarter of 2024, compared to $7.9 million for the same period in 2023. The decrease in G&A expenses was primarily due to a decrease in consulting and other professional fees.
Net Loss: Net loss for the third quarter of 2024 was $15.6 million, as compared to $23.0 million for the same period in 2023.
Financial Guidance

Black Diamond ended the third quarter of 2024 with approximately $112.7 million in cash, cash equivalents and investments which the Company believes is sufficient to fund its anticipated operating expenses and capital expenditure requirements into the second quarter of 2026.

On November 5, 2024 BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX), a commercial stage biopharmaceutical company pursuing life-changing therapies in oncology and rare diseases, reported that an abstract including the initial results from a Phase 1 clinical trial evaluating motixafortide as monotherapy and in combination with natalizumab for CD34+ hematopoietic stem cell (HSC) mobilization for gene therapies in sickle cell disease (SCD) was accepted for oral presentation at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition taking place December 7-10, 2024 in San Diego, California (Press release, BioLineRx, NOV 5, 2024, View Source [SID1234647707]). The proof-of-concept study, conducted in collaboration with Washington University School of Medicine in St. Louis, is exploring alternative HSC mobilization strategies that could significantly improve the treatment journey of patients with sickle cell disease seeking gene therapy.

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"Currently available gene therapies for sickle cell disease rely on the collection of significant quantities of CD34+ hematopoietic stem cells, posing challenges for many patients," said Zachary Crees, MD, principal investigator for the trial, Division of Oncology, Washington University School of Medicine. "The findings in this trial suggest that patients with sickle cell disease given motixafortide alone, or in combination with natalizumab, could mobilize and potentially collect the number of stem cells required for approved gene therapies in a single apheresis cycle. These are encouraging findings that we look forward to presenting in greater detail at ASH (Free ASH Whitepaper) 2024."

"We are encouraged by the initial findings in this Phase 1 study showing that motixafortide is safe and well-tolerated and may hold potential to improve the overall treatment process and access to gene therapy for more people with SCD," said Philip Serlin, Chief Executive Officer of BioLineRx. "We look forward to continued collaboration with Washington University on this important research and our ongoing work to develop motixafortide for the potential benefit of patients with sickle cell disease."

The Phase 1 safety and feasibility study is evaluating motixafortide (CXCR4 inhibitor) as monotherapy and in combination with natalizumab (VLA-4 inhibitor) as novel regimens to mobilize CD34+ hematopoietic stem cells for gene therapies in SCD. As reported in the abstract, five patients completed mobilization and apheresis with motixafortide alone, and four of five with motixafortide in combination with natalizumab.

Motixafortide alone, and in combination with natalizumab, were safe and well-tolerated in the trial. Common adverse events (AEs) were transient and included Grade 1-2 injection site (pruritis, tingling/pain) and systemic reactions (pruritis, hives). No Grade 4 AEs or vaso-occlusive events occurred.

Motixafortide alone, and in combination with natalizumab, resulted in robust CD34+ HSC mobilization to peripheral blood (PB). Motixafortide alone mobilized a median of 198 CD34+ cells/μl (range 77-690) to PB with median 3.49×10 CD34+ cells/kg as part of a single blood volume collection, projecting the collection of 13.9×106 HSCs in a normal, single-day four blood volume apheresis collection session. Motixafortide in combination with natalizumab mobilized a median of 231 CD34+ cells/μl (range 117-408), with median 4.64×10 CD34+ cells/kg collected as part of a single blood volume collection, projecting the collection of 18.6×106 CD34+ HSCs in a single day four blood volume apheresis collection session.

The two approved gene therapies for sickle cell disease in the U.S. require 16.5 million, and 22 million, total CD34+ HSCs, respectively.i,ii Unfortunately, granulocyte colony-stimulating factor (G-CSF), the most commonly used drug to support the collection of stem cells, is contraindicated in patients with SCD. The use of the mobilization agent plerixafor is the current standard of care for collecting HSCs for SCD gene therapies; however, plerixafor alone requires multiple mobilization attempts and often yields suboptimal HSC numbers. For some, gene therapy may be prohibitive due to the failure to obtain adequate numbers of HSCs.

In the trial, patients who underwent prior mobilization with plerixafor, experienced 2.8- fold greater HSC mobilization with motixafortide alone, and 3.2-fold greater HSC mobilization with motixafortide in combination with natalizumab compared to plerixafor.

Oral Presentation at ASH (Free ASH Whitepaper) 2024
San Diego Convention Center, San Diego, California
Oral Presentation Details

Session Name: 711. Cell Collection and Manufacturing of HSPCs, CAR-T Cells, and Other Cellular Therapy Products: Innovations in Mobilization, Collection, and Manufacturing for Cellular Therapies

Title: Motixafortide (CXCR4 Inhibition) Alone and in Combination with Natalizumab (VLA-4 Inhibition) As a Novel Regimen to Mobilize Hematopoietic Stem Cells for Gene Therapies in Sickle Cell Disease: A First-in-Human, Proof-of-Principle Safety and Feasibility Study

Presenter: Zachary D. Crees, MD, Division of Oncology, Washington University School of Medicine, Saint Louis, MO

Abstract ID#: 193210

Date: Saturday, December 7, 2024

Time: 12:00 PM

Location: San Diego Convention Center, Room 25

About the Clinical Trial of Motixafortide in Sickle Cell Disease (SCD)
The trial (ClinicalTrials.gov Identifier: NCT05618301) is a safety and feasibility study to evaluate motixafortide (CXCR4 inhibitor) as monotherapy and in combination with natalizumab (VLA-4 inhibitor) as novel regimens to mobilize CD34+ hematopoietic stem cells for gene therapies in SCD. The study enrolled five adults with a diagnosis of SCD who are receiving automated red blood cell exchanges via apheresis. The trial’s primary objective is to assess the safety and tolerability of motixafortide alone and the combination of motixafortide + natalizumab in SCD patients, defined by dose-limiting toxicities. Secondary objectives include determining the number of CD34+ hematopoietic stem and progenitor cells (HSPCs) mobilized via apheresis; and determining the kinetics of CD34+ HSPC mobilization to peripheral blood in response to motixafortide alone and motixafortide + natalizumab in SCD patients.

About Sickle Cell Disease
Sickle cell disease (SCD) is one of the most common genetic diseases globally, affecting millions of people throughout the world and disproportionately impacting persons of color. Sickle cell disease arises from mutations in the hemoglobin gene, ultimately leading to the production of abnormally shaped (sickle) red blood cells that tend to stick within blood vessels causing their occlusion. The clinical manifestations of SCD include anemia and blood vessel occlusion which can lead to both acute and chronic pain, as well as tissue ischemia across multiple organ systems (e.g., stroke, heart attack, respiratory failure), ultimately compromising end organ function. The cumulative impact of these complications significantly impacts morbidity and mortality for patients with SCD.

On November 5, 2024 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global oncology company, reported it will share new data across a range of B-cell malignancies and assets, including best-in-class Bruton’s tyrosine kinase (BTK) inhibitor BRUKINSA (zanubrutinib), at the 66th ASH (Free ASH Whitepaper) Annual Meeting and Exposition in San Diego, December 7-10 (Press release, BeiGene, NOV 5, 2024, View Source [SID1234647709]). BeiGene has 21 abstracts accepted at ASH (Free ASH Whitepaper) 2024, with four selected for oral presentation.

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"In the five years since its initial approval, BRUKINSA has become a standard of care for patients facing many B-cell malignancies, and our data featured at ASH (Free ASH Whitepaper) demonstrated how long-term follow-up of treatment with BRUKINSA elicited deep and durable responses, including in patients with chronic lymphocytic leukemia and Waldenström’s macroglobulinemia," said Mehrdad Mobasher, M.D., M.P.H., Chief Medical Officer, Hematology at BeiGene. "BRUKINSA is just the starting point – pipeline data for our BTK degrader BGB-16673 and BCL2 inhibitor sonrotoclax showcase our continued leadership across the hematology landscape and our commitment to bringing innovative medicines to as many people with cancer as possible."

Presentations Highlight Sustained Progression-Free Survival and Deepening Durable Responses for Patients Treated with BRUKINSA in Treatment-Naïve and Relapsed/Refractory (R/R) Settings

Five-year follow-up results from Cohort 1 of the Phase 3 SEQUOIA study showed sustained progression-free survival (PFS) benefit with BRUKINSA in patients with treatment-naïve chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), with no new safety signals observed.
Results from the LTE (long-term extension rollover) study of patients with treatment-naïve and R/R CLL also showed that treatment with BRUKINSA as a single agent or as an investigational treatment in combination with obinutuzumab achieved high overall and complete response rates. With a median follow-up of up to 6.5 years, the responses were sustained, and no new safety signals were observed.
Results from an LTE study of patients with Waldenström macroglobulinemia (WM) from the Phase 3 ASPEN study, with a median follow-up of up to 5.8 years, demonstrated that treatment with BRUKINSA monotherapy remained durable and the safety/tolerability profile remained favorable.
Data from a Phase 2 study showed patients with prior intolerance to acalabrutinib were able to safely and effectively switch to BRUKINSA, with the majority of patients not experiencing recurrence of prior acalabrutinib-intolerance events while maintaining or deepening responses.
Pipeline Data Show Early Safety and Efficacy Across Multiple B-cell Malignancies

First-in-human Phase 1/2 CaDAnCe-101 presentations (two oral, one poster) highlighted generally manageable safety and promising efficacy results for BTK degrader, BGB-16673, in patients with R/R CLL/SLL, WM, and R/R indolent non-Hodgkin’s lymphoma. BGB-16673, which induces BTK degradation, is the first and most advanced asset from BeiGene’s chimeric degradation activation compound (CDAC) platform.
Oral presentation of the BGB-11417-101 Phase 1 study demonstrated B-cell lymphoma 2 (BCL2) inhibitor sonrotoclax in combination with BRUKINSA continued to show promising efficacy and was generally well-tolerated in patients with treatment-naïve CLL/SLL; this combination is being evaluated in the Phase 3 CELESTIAL-TNCLL study (NCT06073821).
BeiGene Presentations During ASH (Free ASH Whitepaper) 2024

Abstract Title

Presentation Details

Lead Author

BRUKINSA

Prospective patient preference study for Bruton tyrosine kinase inhibitor (BTKi) treatment attributes and factors affecting patient shared decision-making CLL/SLL in the USA

Publication #2265

Poster

Dec. 7, 5:30-7:30 p.m.

S. Ailawadhi

Real-world Bruton tyrosine kinase inhibitor (BTKi) utilization and clinical outcomes among patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL)

Publication #2353

Poster

Dec. 7, 5:30-7:30 p.m.

J. Hou

Long-term clinical outcomes in patients with Waldenström macroglobulinemia (WM) who received zanubrutinib in the phase 3 ASPEN study: A report from the zanubrutinib extension study

Publication #3031

Poster

Dec. 8, 6-8 p.m.

S. D’Sa

Patient medication preferences in follicular lymphoma (FL) in the United States (USA): A discrete choice experiment (DCE)

Publication #3655

Poster

Dec. 8, 6-8 p.m.

S. Gaballa

Evaluating reasons for differences in real-world (RW) clinical outcomes among patients with R/R MCL on covalent BTKis

Publication #3732

Poster

Dec. 8, 6-8 p.m.

T. Phillips

Sustained superiority of zanubrutinib vs bendamustine + rituximab in treatment-naive chronic lymphocytic leukemia/small lymphocytic lymphoma (TN CLL): 5-year follow-up of cohort 1 from the SEQUOIA study

Publication #3249

Poster

Dec. 8, 6-8 p.m.

M. Shadman

Deep and sustained responses in patients with CLL treated with zanubrutinib or zanubrutinib + obinutuzumab in phase 1/2 AU-003 and phase 1b GA-101 studies: A report from the zanubrutinib extension study

Publication #3255

Poster

Dec. 8, 6-8 p.m.

C. Tam

Comparative efficacy of zanubrutinib plus obinutuzumab versus last prior treatment in relapsed/refractory follicular lymphoma: Growth modulation index analysis from ROSEWOOD study

Publication #3029

Poster

Dec. 8, 6-8 p.m.

J. Trotman

Impact of novel therapies (NTs) on real-world (RW) clinical outcomes of patients (pts) with relapsed/refractory (R/R) mantle-cell lymphoma (MCL) by race/ethnicity and TP53 mutation status

Publication #5097

Poster

Dec. 9, 6-8 p.m.

T. Phillips

Zanubrutinib is well tolerated and effective in acalabrutinib-intolerant patients with B-cell malignancies

Publication #4632

Poster

Dec. 9, 6-8 p.m.

M. Shadman

Long-term impact of dose interruptions (DIs) of Bruton tyrosine kinase inhibitors (BTKis) on change in IgM levels and clinical outcomes in Waldenström macroglobulinemia (WM)

Publication #4412

Poster

Dec. 9, 6-8 p.m.

J. Trotman

Final analysis of a phase 1 study of zanubrutinib plus lenalidomide in patients with relapsed/refractory diffuse large B-cell lymphoma

Publication #986

Oral

Dec. 9, 4:45 p.m.

Z. Song

Treatment with zanubrutinib in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma who were previously treated with another Bruton tyrosine kinase inhibitor in a US community oncology setting

Publication #7763

Online

D. Andorsky

BGB-16673 (BTK CDAC)

Preliminary efficacy and safety of the Bruton tyrosine kinase degrader BGB-16673 in patients with relapsed or refractory (R/R) indolent NHL: Results from the phase 1 CaDAnCe-101 study

Publication #1649

Poster

Dec. 7, 5:30-7:30 p.m.

C. Tam

Preliminary efficacy and safety of the Bruton tyrosine kinase degrader BGB-16673 in patients with relapsed or refractory Waldenström macroglobulinemia: Results from the phase 1 CaDAnCe-101 study

Publication #860

Oral

Dec. 9, 3 p.m.

J. Seymour

Preliminary efficacy and safety of the Bruton tyrosine kinase degrader BGB-16673 in patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma: Results from the phase 1 CaDAnCe-101 study

Publication #885

Oral

Dec. 9, 3:15 p.m.

M. Thompson

BGB-16673, a selective BTK degrader, exhibits deeper inhibition of cancer cell signaling pathways and better efficacy in MCL models

Publication #5833

Online

H. Wang

Sonrotoclax (BCL2 Inhibitor)

Sonrotoclax and zanubrutinib as frontline treatment for CLL demonstrates high MRD clearance rates with good tolerability: Data from an ongoing phase 1/1b study BGB-11417-101

Publication #1012

Oral

Dec. 9, 5:15 p.m.

J. Soumerai

CELESTIAL-TNCLL: An ongoing, open-label, multiregional, phase 3 study of sonrotoclax (BGB-11417) + zanubrutinib vs venetoclax + obinutuzumab for treatment-naive CLL

Publication #6807

Online

P. Patten

BGB-11417-203, an ongoing, phase 2 study of sonrotoclax (BGB-11417), a next-generation BCL2 inhibitor, in patients with Waldenström macroglobulinemia

Publication #6289

Online

H. Lee

Cell Therapy Research

iPSC-derived CAR-γδT with SOCS1/CISH/BIM/FAS combinatorial KO demonstrated extended longevity and profound anti-tumor efficacy without cytokine support in preclinical studies

Publication #4790

Poster

Dec. 7, 5:30-7:30 p.m.

J. Yu

Select Investigator-Initiated Trial

Multicenter Phase II trial of zanubrutinib, obinutuzumab, and venetoclax (BOVen) in treatment-naïve chronic lymphocytic leukemia: 5-year follow up, retreatment outcomes, and impact of MRD kinetics (ΔMRD400)

Publication #1867

Poster

Dec. 7, 5:30-7:30 p.m.

J. Soumerai

About BRUKINSA (zanubrutinib)

BRUKINSA is an orally available, small molecule inhibitor of Bruton’s tyrosine kinase (BTK) designed to deliver complete and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. With differentiated pharmacokinetics compared with other approved BTK inhibitors, BRUKINSA has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease-relevant tissues.

BRUKINSA has the broadest label globally of any BTK inhibitor and is the only BTK inhibitor to provide the flexibility of once or twice daily dosing. The global BRUKINSA clinical development program includes about 6,000 patients enrolled in 30 countries and regions across more than 35 trials. BRUKINSA is approved in more than 70 markets, and more than 100,000 patients have been treated globally.

U.S. Indications and Important Safety Information for BRUKINSA (zanubrutinib)

INDICATIONS

BRUKINSA is a kinase inhibitor indicated for the treatment of adult patients with:

Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
Waldenström’s macroglobulinemia (WM).
Mantle cell lymphoma (MCL) who have received at least one prior therapy.
Relapsed or refractory marginal zone lymphoma (MZL) who have received at least one anti-CD20-based regimen.
Relapsed or refractory follicular lymphoma (FL), in combination with obinutuzumab, after two or more lines of systemic therapy.
The MCL, MZL and FL indications are approved under accelerated approval based on overall response rate and durability of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Hemorrhage

Fatal and serious hemorrhage has occurred in patients with hematological malignancies treated with BRUKINSA. Grade 3 or higher hemorrhage including intracranial and gastrointestinal hemorrhage, hematuria, and hemothorax was reported in 3.8% of patients treated with BRUKINSA in clinical trials, with fatalities occurring in 0.2% of patients. Bleeding of any grade, excluding purpura and petechiae, occurred in 32% of patients.

Bleeding has occurred in patients with and without concomitant antiplatelet or anticoagulation therapy. Coadministration of BRUKINSA with antiplatelet or anticoagulant medications may further increase the risk of hemorrhage.

Monitor for signs and symptoms of bleeding. Discontinue BRUKINSA if intracranial hemorrhage of any grade occurs. Consider the benefit-risk of withholding BRUKINSA for 3-7 days before and after surgery depending upon the type of surgery and the risk of bleeding.

Infections

Fatal and serious infections (including bacterial, viral, or fungal infections) and opportunistic infections have occurred in patients with hematological malignancies treated with BRUKINSA. Grade 3 or higher infections occurred in 26% of patients, most commonly pneumonia (7.9%), with fatal infections occurring in 3.2% of patients. Infections due to hepatitis B virus (HBV) reactivation have occurred.

Consider prophylaxis for herpes simplex virus, pneumocystis jirovecii pneumonia, and other infections according to standard of care in patients who are at increased risk for infections. Monitor and evaluate patients for fever or other signs and symptoms of infection and treat appropriately.

Cytopenias

Grade 3 or 4 cytopenias, including neutropenia (21%), thrombocytopenia (8%) and anemia (8%) based on laboratory measurements, developed in patients treated with BRUKINSA. Grade 4 neutropenia occurred in 10% of patients, and Grade 4 thrombocytopenia occurred in 2.5% of patients.

Monitor complete blood counts regularly during treatment and interrupt treatment, reduce the dose, or discontinue treatment as warranted. Treat using growth factor or transfusions, as needed.

Second Primary Malignancies

Second primary malignancies, including non-skin carcinoma, have occurred in 14% of patients treated with BRUKINSA. The most frequent second primary malignancy was non-melanoma skin cancers (8%), followed by other solid tumors in 7% of the patients (including melanoma in 1% of patients) and hematologic malignancies (0.7%). Advise patients to use sun protection and monitor patients for the development of second primary malignancies.

Cardiac Arrhythmias

Serious cardiac arrhythmias have occurred in patients treated with BRUKINSA. Atrial fibrillation and atrial flutter were reported in 4.4% patients treated with BRUKINSA, including Grade 3 or higher cases in 1.9% of patients. Patients with cardiac risk factors, hypertension, and acute infections may be at increased risk. Grade 3 or higher ventricular arrhythmias were reported in 0.3% of patients.

Monitor for signs and symptoms of cardiac arrhythmias (e.g., palpitations, dizziness, syncope, dyspnea, chest discomfort), manage appropriately, and consider the risks and benefits of continued BRUKINSA treatment.

Hepatotoxicity, Including Drug-Induced Liver Injury

Hepatotoxicity, including severe, life-threatening, and potentially fatal cases of drug-induced liver injury (DILI), has occurred in patients treated with Bruton tyrosine kinase inhibitors, including BRUKINSA.

Evaluate bilirubin and transaminases at baseline and throughout treatment with BRUKINSA. For patients who develop abnormal liver tests after BRUKINSA, monitor more frequently for liver test abnormalities and clinical signs and symptoms of hepatic toxicity. If DILI is suspected, withhold BRUKINSA. Upon confirmation of DILI, discontinue BRUKINSA.

Embryo-Fetal Toxicity

Based on findings in animals, BRUKINSA can cause fetal harm when administered to a pregnant woman. Administration of zanubrutinib to pregnant rats during the period of organogenesis caused embryo-fetal toxicity, including malformations at exposures that were 5 times higher than those reported in patients at the recommended dose of 160 mg twice daily. Advise women to avoid becoming pregnant while taking BRUKINSA and for 1 week after the last dose. Advise men to avoid fathering a child during treatment and for 1 week after the last dose. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.

Adverse Reactions

The most common adverse reactions (≥30%), including laboratory abnormalities, in patients who received BRUKINSA (N=1729) are decreased neutrophil count (51%), decreased platelet count (41%), upper respiratory tract infection (38%), hemorrhage (32%), and musculoskeletal pain (31%).

Drug Interactions

CYP3A Inhibitors: When BRUKINSA is co-administered with a strong CYP3A inhibitor, reduce BRUKINSA dose to 80 mg once daily. For coadministration with a moderate CYP3A inhibitor, reduce BRUKINSA dose to 80 mg twice daily.

CYP3A Inducers: Avoid coadministration with strong or moderate CYP3A inducers. Dose adjustment may be recommended with moderate CYP3A inducers.

Specific Populations

Hepatic Impairment: The recommended dose of BRUKINSA for patients with severe hepatic impairment is 80 mg orally twice daily.

Please see full U.S. Prescribing Information including U.S. Patient Information.

On November 5, 2024 Beam Therapeutics Inc. (Nasdaq: BEAM), a biotechnology company developing precision genetic medicines through base editing, reported the acceptance of multiple oral and poster presentations, including the first clinical data from a Beam program, at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, taking place December 7-10, 2024, in San Diego (Press release, Beam Therapeutics, NOV 5, 2024, View Source [SID1234647704]).

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"For people living with severe sickle cell disease, a serious medical condition with reduced life expectancy, stem cell transplant with genotoxic chemotherapy is the only currently available curative option. At Beam, we have a long-term commitment to delivering better treatments for these patients, first with BEAM-101 as a potentially superior autologous cell product, followed by ESCAPE, which seeks to eliminate chemotherapy from the transplant process altogether," said John Evans, chief executive officer of Beam. "Today represents an important milestone toward this vision as we unveil data with our base editing technology across both approaches to treating sickle cell disease. The initial results for BEAM-101 provide emerging clinical validation of base editing and of our preclinical hypothesis that more precise and efficient editing, without double-stranded DNA breaks, can lead to a differentiated product profile, with greater and more uniform induction of fetal hemoglobin, deeper reduction of sickle hemoglobin, and potentially faster engraftment."

"Our proof-of-concept data for ESCAPE in non-human primates demonstrate that base editing could enable antibody conditioning and engraftment for stem cell transplant without chemotherapy, a potential breakthrough in the field of hematology and for patients," said Giuseppe Ciaramella, Ph.D., president of Beam. "Along with the strong translation from preclinical to clinical of our BEAM-101 program, these data reflect the potential of base editing to enable new therapeutic possibilities for people suffering from serious diseases."

BEAM-101 Oral and Poster Presentations

Title: Initial Results from the BEACON Clinical Study: A Phase 1/2 Study Evaluating the Safety and Efficacy of a Single Dose of Autologous CD34+ Base Edited Hematopoietic Stem Cells (BEAM-101) in Patients with Sickle Cell Disease with Severe Vaso-Occlusive Crises

Abstract: 513

Oral Session: 801. Gene Therapies: Gene Editing and Replacement Therapies for Hemoglobinopathies: From Bench to Bedside

Presentation Time: Sunday, Dec. 8, 2024, at 10 a.m. PT

Location: San Diego Convention Center, Room 30

Presenter: Matthew M. Heeney, M.D., Dana-Farber/Boston Children’s Cancer and Blood Disorders Center

Key Highlights:

•
Preliminary data as of a July 2, 2024, data cut from BEACON, a Phase 1/2 single-arm, open-label clinical trial evaluating the safety and efficacy of a single dose of BEAM-101 in patients with sickle cell disease (SCD) with severe vaso-occlusive crises (VOCs).
•
Initial safety profile was consistent with busulfan conditioning and autologous hematopoietic stem cell transplantation (HSCT).
o
In all patients dosed (n=6), there were no ≥Grade 3 adverse events (AEs) or serious AEs related to treatment with BEAM-101.
o
One patient died four months after BEAM-101 infusion due to respiratory failure that was determined by the investigator to be likely related to busulfan conditioning and deemed unrelated to BEAM-101. The case was reviewed by the Data Safety Monitoring Committee and the U.S. Food and Drug Administration. Pulmonary complications are a known cause of morbidity and, in rare cases, mortality in patients undergoing myeloablation with chemotherapy, such as busulfan, and stem cell transplantation.
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All patients dosed achieved their target cell dose with either 1 or 2 mobilization cycles (mean: 1.5).
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All 4 patients with ≥1 month of follow-up achieved neutrophil and platelet engraftment at a median of 17 (15–19) and 20 (11–34) days, respectively.
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All 4 patients experienced rapid and robust fetal hemoglobin (HbF) induction by Month 1 (>60%) and corresponding sickle hemoglobin (HbS) reduction (≤36%) in non-transfused blood, which was sustained over time.
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Markers of hemolysis normalized or improved for all 4 patients.
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No VOCs were reported by investigators post-treatment.
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These data support base editing of the HBG1/2 promoters as a therapeutic modality for the treatment of SCD and the ongoing development of BEAM-101.
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The presentation at ASH (Free ASH Whitepaper) will include additional data with more patients and longer follow-up.

Title: Impact of BEAM-101 Treatment on Red Blood Cell Hemoglobin Expression, Rheology and Sickling Properties: Initial data from the BEACON Phase 1/2 study of Autologous CD34+ Base Edited Hematopoietic Stem Cells in Sickle Cell Disease

Abstract: 4957
Poster Session: 801. Gene Therapies: Poster III

Session Time: Monday, Dec. 9, 2024, from 6-8 p.m. PT

Location: San Diego Convention Center, Halls G-H

Presenter: Priya S. Chockalingam, Ph.D., Beam Therapeutics

Key Highlights:

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Preliminary data as of a July 2, 2024, data cut includes exploratory biomarker assessments of red blood cell (RBC) hemoglobin expression, health and function in 3 patients for two or more of the following visits: screening, Month 1, 2, 3 and 6.
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Initial results demonstrated 98-99% of RBCs expressing HbF as early as Month 1, with near complete elimination of RBCs expressing solely HbS post-treatment with BEAM-101.
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The data showed reduction in RBC sickling, comparable to sickle cell trait, reduced cell adhesion and improved hemorheological properties of blood post-treatment with BEAM-101.
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The presentation at ASH (Free ASH Whitepaper) will include additional data with more patients and longer follow-up.

ESCAPE Oral Presentation:

Title: CD117 Antibody Conditioning and Multiplex Base Editing Enable Rapid and Robust Fetal Hemoglobin Reactivation in a Rhesus Autologous Transplantation Model

Abstract: 516

Oral Session: 801. Gene Therapies: Gene Editing and Replacement Therapies for Hemoglobinopathies: From Bench to Bedside

Presentation Time: Sunday, Dec. 8, 2024, at 10:45 a.m. PT

Location: San Diego Convention Center, Room 30

Presenter: Selami Demirci, Ph.D., National Institutes of Health

Key Highlights:

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Study investigated whether Beam’s Engineered Stem Cell Antibody Evasion (ESCAPE) approach, using CD117 monoclonal antibody (mAb) conditioning, could successfully achieve long-term engraftment and induce robust levels of HbF in an immunocompetent host. Researchers used a non-human primate (NHP) model where autologous CD34+ hematopoietic stem and progenitor cells were multiplex edited to target a single epitope on CD117 and the promoter regions of HBG1/2, allowing cells to avoid detection by the conditioning mAb while upregulating HbF.
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Two NHPs were conditioned with different doses (10 mg/kg and 25 mg/kg) of CD117 mAb, instead of busulfan, 7 days prior to transplantation. Post-transplant, further mAb treatments were administered to maintain competitive advantage for the edited cells.
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mAb-based conditioning was well tolerated, with no need for NHP supportive care.
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Both NHPs showed rapid and significant induction of HbF. The percentage of red blood cells expressing HbF (F-cells) reached 61% as early as 8 weeks post-transplant in one NHP and stabilized at ~85% by 35 weeks in both animals. Concurrently, levels of HbF increased rapidly, reaching ~55% at 35 weeks post-transplant in both animals.

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Data suggest that ESCAPE, combined with CD117 mAb conditioning and selection, can achieve long-term engraftment and induce high levels of HbF, offering a promising alternative to traditional genotoxic conditioning in autologous HSCT.
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The presentation at ASH (Free ASH Whitepaper) will include additional data.

BEAM-201 Poster Presentation:

Title: BEAM-201 for the Treatment of Relapsed and/or Refractory (R/R) T-Cell Acute Lymphoblastic Leukemia (T-ALL) or T-Cell Lymphoblastic Lymphoma (T-LL): Initial Data from the Phase (Ph) 1/2 Dose-Exploration, Dose-Expansion, Safety, and Efficacy Study of Multiplex Base-Edited Allogeneic Anti CD7 CAR-T-Cells

Abstract: 4838

Poster Session: 704. Cellular Immunotherapies: Early Phase Clinical Trials and Toxicities: Poster III

Session Time: Monday, Dec. 9, 2024, from 6-8 p.m. PT

Location: San Diego Convention Center, Halls G-H

Presenter: Caroline Diorio, M.D., FRCPC, FAAP, Children’s Hospital of Philadelphia

Key Highlights:

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Initial data as of a June 11, 2024, data cut in 3 patients treated with BEAM-201 show a safety profile consistent with underlying disease, lymphodepletion and AEs associated with CAR-T therapy.
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A complete response (CRi/CR) was demonstrated in 2 of 3 patients at CAR-T cell doses <200 million. Both patients achieving a CRi/CR were deemed suitable for stem cell transplant following therapy.
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The presentation at ASH (Free ASH Whitepaper) will include additional data with more patients and longer follow-up.

ASH Investor Event Information

Beam will host a live and webcast investor event on Dec. 8, 2024, at 8:00 p.m. PT in San Diego to review the key presentations from this year’s ASH (Free ASH Whitepaper) meeting. The event will be webcast live and can be accessed under "Events & Presentations" in the Investors section of the company’s website at www.beamtx.com. The archived webcast will be available on the company’s website beginning approximately two hours after the event.

On November 5, 2024 AnaptysBio, Inc. (Nasdaq: ANAB), a clinical-stage biotechnology company focused on delivering innovative immunology therapeutics, reported that Daniel Faga, president and chief executive officer of Anaptys, and/or other members of its senior management team, are scheduled to participate in multiple upcoming investor conferences (Press release, AnaptysBio, NOV 5, 2024, View Source [SID1234647703]):

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Guggenheim’s Inaugural Healthcare Innovation Conference, Boston, MA

Format – Fireside chat and one-on-one investor meetings
Date and Time – Wednesday, Nov. 13, 2024 at 1:30pm ET / 10:30am PT

Stifel 2024 Healthcare Conference, New York, NY

Format – Fireside chat and one-on-one investor meetings
Date and Time – Tuesday, Nov. 19, 2024 at 1:50pm ET / 10:50am PT

Piper Sandler 36th Annual Healthcare Conference, New York, NY

Format – Fireside chat and one-on-one investor meetings
Date and Time – Tuesday, Dec. 3, 2024 at 2:30pm ET / 11:30am PT

7th Annual Evercore HealthCONx Conference, Coral Gables, FL

Format – Fireside chat and one-on-one investor meetings
Date and Time – Wednesday, Dec. 4, 2024 at 1:45pm ET / 10:45am PT
Live webcasts of the fireside chats will be available on the investor section of the Anaptys website at View Source Replays of the webcasts will be available for at least 30 days following the events.