On November 5, 2024 Carisma Therapeutics Inc. (Nasdaq: CARM) ("Carisma" or the "Company"), a clinical-stage biopharmaceutical company focused on discovering and developing innovative immunotherapies, reported the upcoming presentation of new pre-clinical data on its anti-GPC3 in vivo chimeric antigen receptor macrophage and monocyte (together, "CAR-M") therapy for the treatment of hepatocellular carcinoma ("HCC"), developed in collaboration with Moderna, Inc. (Nasdaq: MRNA) (Press release, Carisma Therapeutics, NOV 5, 2024, View Source [SID1234647760]). The data will be presented in a poster session at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) ("SITC") Annual Meeting in Houston, Texas, on November 8, 2024.

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The abstract, titled "Pre-Clinical Efficacy of a Novel Anti-GPC3 In Vivo CAR-M for Hepatocellular Carcinoma," presents the first pre-clinical data on the development candidate targeting Glypican-3 ("GPC3"), a tumor-associated antigen commonly expressed in HCC. This novel off-the-shelf approach reprograms endogenous myeloid cells in vivo using lipid nanoparticles ("LNP") to deliver mRNA encoding CARs. The data show that this in vivo CAR-M therapy has significant potential as a treatment for GPC3+ solid tumors, including HCC.

"Our data at SITC (Free SITC Whitepaper) this year highlights the groundbreaking potential of the in vivo CAR-M platform," said Steven Kelly, President and Chief Executive Officer of Carisma. "The pre-clinical results demonstrate robust anti-tumor activity and pave the way for an off-the-shelf therapy for hard-to-treat cancers like hepatocellular carcinoma. This data underscores the progress we’ve made, and we’re eager to advance this promising therapy into clinical development."

SITC Presentations Details:

Title: Pre-clinical efficacy of a novel anti-GPC3 in vivo CAR-M for hepatocellular carcinoma
Publication Number: 329
Session Date & Time: Friday, Nov. 8, 2024
Location: Exhibit Halls A B George R. Brown Convention Center

Title: A Phase 1, First-in-Human study of autologous monocytes engineered to express an anti-HER2 chimeric antigen receptor (CAR) in participants with HER2 overexpressing solid tumors
Publication Number: 659
Session Date & Time: Friday, Nov. 8, 2024
Location: Exhibit Halls A B George R. Brown Convention Center

The poster presented at SITC (Free SITC Whitepaper) 2024 will be available online in the "Publications" section of Carisma’s website at View Source following the start of the poster session.

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 Syndax Pharmaceuticals (Nasdaq: SNDX), a commercial-stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported its financial results for the quarter ended September 30, 2024, and provided a business update (Press release, Syndax, NOV 5, 2024, View Source [SID1234647745]).

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"This has been a historic period for Syndax as we transitioned to a commercial-stage company with the approval of Niktimvo. With the recently completed royalty financing, we expect to be funded through profitability and we are well positioned to maximize the potential of our pipeline," said Michael A. Metzger, Chief Executive Officer. "We have a very exciting quarter ahead with the anticipated FDA approval and U.S. launch of revumenib for adults and pediatrics with R/R KMT2Ar acute leukemia, as well as the expected readout of topline pivotal data from patients with R/R mNPM1 AML. Our commercial organization is well-prepared to launch revumenib and leverage our first-to-market position to drive long-term value creation."

Recent Pipeline Progress and Anticipated Milestones

Revumenib

The New Drug Application (NDA) for revumenib, an oral menin inhibitor, for the treatment of adult and pediatric relapsed or refractory (R/R) KMT2A-rearranged (KMT2Ar) acute leukemia was granted Priority Review and is being reviewed under the U.S. FDA’s Real-Time Oncology Review (RTOR) Program with a Prescription Drug User Fee Act (PDUFA) target action date of December 26, 2024.
The Company expects to report topline data from the AUGMENT-101 pivotal trial cohort of patients with R/R mutant nucleophosmin (mNPM1) acute myeloid leukemia (AML) in the fourth quarter of 2024. Positive data could support a supplemental NDA (sNDA) filing for revumenib in R/R mNPM1 AML in the first half of 2025.
The Company announced that data from the pivotal Phase 2 portion of the AUGMENT-101 trial of revumenib in adult and pediatric patients with R/R KMT2Ar AML and acute lymphoid leukemia (ALL) have been published in the Journal of Clinical Oncology.
The Company announced that a larger data set and longer follow-up from the pivotal Phase 2 portion of the AUGMENT-101 trial of revumenib in R/R KMT2Ar acute leukemia will be presented at the upcoming 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. The larger efficacy population (n=97) includes the 57 patients from the previously reported interim efficacy analysis plus an additional 40 patients. Consistent with previously reported data, the updated analysis shows that revumenib provides durable responses and robust rates of overall response, minimal residual disease (MRD) negativity, and hematopoietic stem cell transplantation (HSTC). With seven months of additional follow-up, the median duration of CR/CRh extended to 13 months among the 13 CR/CRh responders included in the interim analysis presented at ASH (Free ASH Whitepaper) 2023.
Multiple trials evaluating the potential to expand revumenib use across the mNPM1 and KMT2Ar acute leukemia treatment landscape are ongoing. These trials include:
BEAT AML: A Phase 1 trial evaluating the combination of revumenib with venetoclax and azacitidine in front-line AML patients. The trial is being conducted as part of the Leukemia & Lymphoma Society’s Beat AML Master Clinical Trial. The Company presented updated positive data from the trial at the European Hematology Association (EHA) (Free EHA Whitepaper) 2024 Congress, showing a 96% (23 of 24 pts) composite complete remission (CRc) rate in patients with newly diagnosed mNPM1 or KMT2Ar AML. The BEAT AML trial is expanding to validate the recommended Phase 2 dose of the combination of revumenib with venetoclax and azacitidine. The company anticipates that an update on the trial will be available in the fourth quarter of 2024.
SAVE: A Phase 1 trial evaluating the all-oral combination of revumenib with venetoclax and decitabine/cedazuridine in R/R AML or mixed phenotype acute leukemias. The trial is being conducted by investigators from MD Anderson Cancer Center. The Company announced that updated data showing an 88% ORR (23 of 26 pts) in R/R patients with KMT2Ar, mNPM1, or NUP98r leukemias will be presented at the upcoming 66th ASH (Free ASH Whitepaper) Annual Meeting. In addition to the R/R cohort, a frontline cohort is now enrolling patients.
INTERCEPT: A Phase 1 trial evaluating the use of novel therapies, including revumenib, to target MRD and early relapse in AML. The trial is being conducted by the Australasian Leukaemia and Lymphoma Group as part of the INTERCEPT AML master clinical trial. Preliminary results from the first eight mNPM1 patients treated with revumenib will be presented at the upcoming 66th ASH (Free ASH Whitepaper) Annual Meeting.
Intensive chemotherapy: A Phase 1 trial evaluating the combination of revumenib with intensive chemotherapy (7+3) followed by revumenib maintenance treatment in newly diagnosed patients with mNPM1 or KMT2Ar acute leukemias. The trial is designed to identify the recommended Phase 2 dose for this combination to support further development.
Break Through Cancer: A Phase 2 trial studying whether the combination of revumenib and venetoclax can eliminate MRD in patients with AML and extend progression-free survival. The trial is being conducted by Break Through Cancer, a collaboration between leading U.S. cancer research centers.
The Company plans to initiate a pivotal trial of revumenib in combination with venetoclax and azacitidine in newly diagnosed mNPM1 or KMT2Ar acute leukemia patients unfit to receive intensive chemotherapy by year-end 2024.
The Company is evaluating revumenib in patients with R/R metastatic microsatellite stable (MSS) colorectal cancer (CRC). The trial is currently enrolling patients in the Phase 1b portion of its Phase 1/2 proof-of-concept trial.

Niktimvo (axatilimab-csfr)

Niktimvo received U.S. Food and Drug Administration (FDA) approval for the treatment of chronic graft-versus-host disease (GVHD) after failure of at least two prior lines of systemic therapy in adult and pediatric patients weighing at least 40 kg (88.2 lbs). The Company anticipates that Niktimvo will be launched in the U.S. no later than early first quarter 2025. In the U.S., Niktimvo will be co-commercialized by Syndax and Incyte.
The Company announced Niktimvo was added to the latest NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) as a category 2A recommendation for the treatment of GVHD after the failure of at least two prior lines of systemic therapy in adult and pediatric patients weighing at least 40 kg. Treatments are classified as category 2A when there is uniform NCCN consensus that the intervention is appropriate, based on lower level evidence.
The Company announced that results from the pivotal Phase 2 AGAVE-201 trial of Niktimvo in adult and pediatric patients with recurrent/refractory active chronic GVHD who had received at least two prior lines of systemic therapy were published in the New England Journal of Medicine.
The Company announced a secondary analysis of overall and organ-specific responses from the pivotal Phase 2 AGAVE-201 trial of Niktimvo in adult and pediatric patients with recurrent/refractory active chronic GVHD who had received at least two prior lines of systemic therapy will be presented at the 66th ASH (Free ASH Whitepaper) Annual Meeting. The data demonstrated rapid responses and symptom improvement in inflammatory and fibrotic manifestations of chronic GVHD in heavily pretreated patients.
Enrollment is ongoing in a 26-week randomized, double-blinded, placebo-controlled Phase 2 trial of axatilimab on top of standard of care in patients with idiopathic pulmonary fibrosis (IPF), now referred to as the MAXPIRe trial (NCT06132256). The Company expects to report topline data from the trial in 2026.
The Company’s partner, Incyte, is now recruiting patients for a Phase 2, open-label, randomized, multicenter trial of axatilimab in combination with ruxolitinib in patients ≥12 years of age with newly diagnosed chronic GVHD (NCT06388564). A Phase 3 trial of axatilimab in combination with steroids for the treatment of chronic GVHD is currently in preparation.
Corporate Update

The Company announced a $350 million royalty funding agreement with Royalty Pharma based on U.S. net sales of Niktimvo. Under the agreement, Syndax received $350 million in exchange for a 13.8% royalty on U.S. net sales of Niktimvo. Royalty payments to Royalty Pharma will cease upon reaching a multiple of 2.35x.

Third Quarter 2024 Financial Results

As of September 30, 2024, Syndax had cash, cash equivalents, and short- and long-term investments of $399.6 million and 85.6 million common shares and prefunded warrants outstanding.

Third quarter 2024 research and development expenses increased to $71.0 million from $39.1 million for the comparable prior year period. The increase was primarily due to greater clinical development expenses, higher pre-commercial manufacturing costs, and increased employee-related expenses and professional fees.

Third quarter 2024 selling, general and administrative expenses increased to $31.1 million from $17.3 million for the comparable prior year period. The increase was driven by a greater level of commercial readiness activities for revumenib and axatilimab as well as higher employee-related expenses and professional fees.

For the three months ended September 30, 2024, Syndax reported a net loss attributable to common stockholders of $84.1 million, or $0.98 per share, compared to a net loss attributable to common stockholders of $51.1 million, or $0.73 per share, for the comparable prior year period.

Financial Guidance

For the full year of 2024, the Company expects research and development expenses to be $245 to $250 million (prior guidance $240 million to $260 million) and total operating expenses to be $365 to $370 million (prior guidance $355 million to $375 million), which includes milestone payments that the Company expects to become due as well as an estimated $41 million (prior guidance $43 million) in non-cash stock compensation expense.

Syndax expects that its cash, cash equivalents and marketable securities, together with the $350 million from the sale of a portion of the Niktimvo royalty and anticipated product revenue and interest income, enables the company to reach profitability.

Conference Call and Webcast

In connection with the earnings release, Syndax’s management team will host a conference call and live audio webcast at 4:30 p.m. ET today, Tuesday, November 5, 2024.

The live audio webcast and accompanying slides may be accessed through the Events & Presentations page in the Investors section of the Company’s website. Alternatively, the conference call may be accessed through the following:

Conference ID: Syndax3Q24
Domestic Dial-in Number: 800-590-8290
International Dial-in Number: 240-690-8800
Live webcast: https://www.veracast.com/webcasts/syndax/events/SNDX3Q24.cfm

For those unable to participate in the conference call or webcast, a replay will be available on the Investors section of the Company’s website at www.syndax.com approximately 24 hours after the conference call and will be available for 90 days following the call.

About Revumenib

Revumenib is an oral, small molecule inhibitor of the menin-KMT2A binding interaction that is being developed for the treatment of KMT2A-rearranged (KMT2Ar), also known as mixed lineage leukemia rearranged or MLLr, acute leukemias including acute lymphoid leukemia (ALL) and acute myeloid leukemia (AML), and mNPM1 AML. The Journal of Clinical Oncology published results from the Phase 2 AUGMENT-101 trial of revumenib in R/R KMT2Ar acute leukemia showing the trial met its primary endpoint.

Revumenib was previously granted Orphan Drug Designation for the treatment of AML, ALL and acute leukemias of ambiguous lineage (ALAL) by the U.S. FDA and for the treatment of AML by the European Commission. The U.S. FDA also granted Fast Track designation to revumenib for the treatment of adult and pediatric patients with R/R acute leukemias harboring a KMT2A rearrangement or NPM1 mutation and Breakthrough Therapy Designation for the treatment of adult and pediatric patients with R/R acute leukemia harboring a KMT2A rearrangement.

About Niktimvo (axatilimab-csfr)

Niktimvo (axatilimab-csfr) is a first-in-class anti-CSF-1R antibody approved for use in the U.S. for the treatment of chronic graft-versus-host disease (GVHD) after failure of at least two prior lines of systemic therapy in adult and pediatric patients weighing at least 40 kg (88.2 lbs).

In the U.S., Niktimvo will be co-commercialized by Syndax and Incyte. Incyte has exclusive commercialization rights for Niktimvo outside of the U.S.

In 2016, Syndax licensed exclusive worldwide rights to develop and commercialize axatilimab from UCB. In September 2021, Syndax and Incyte entered into an exclusive worldwide co-development and co-commercialization license agreement for axatilimab in chronic GVHD and any future indications.

Axatilimab is being studied in frontline combination trials in chronic GVHD – a Phase 2 combination trial with ruxolitinib (NCT06388564) is underway and a Phase 3 combination trial with steroids is in preparation. Axatilimab is also being studied in an ongoing Phase 2 trial in patients with idiopathic pulmonary fibrosis (NCT06132256).

About the Real-Time Oncology Review Program (RTOR)

RTOR provides a more efficient review process for oncology drugs to ensure that safe and effective treatments are available to patients as early as possible, while improving review quality and engaging in early iterative communication with the applicant. Specifically, it allows for close engagement between the sponsor and the FDA throughout the submission process and it enables the FDA to review individual sections of modules of a drug application rather than requiring the submission of complete modules or a complete application prior to initiating review. Additional information about RTOR can be found at: View Source

On November 5, 2024 Genmab A/S (Nasdaq: GMAB) reported more than 20 abstracts evaluating epcoritamab-bysp (EPKINLY), a T-cell engaging bispecific antibody administered subcutaneously, across lines of therapy and B-cell non-Hodgkin’s lymphoma (NHL) subtypes, will be presented at the 66th Annual Meeting and Exposition of the American Society of Hematology (ASH) (Free ASH Whitepaper), being held at the San Diego Convention Center in San Diego, California, and online, December 7-10 (Press release, Genmab, NOV 5, 2024, View Source [SID1234647761]).

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The breadth of the epcoritamab development program will be featured at this year’s ASH (Free ASH Whitepaper) in four oral presentations. Three of the oral presentations will highlight data evaluating fixed-duration subcutaneous epcoritamab in patients with previously untreated diffuse large B-cell lymphoma (DLBCL), large B-cell lymphoma (LBCL), and relapsed/refractory (R/R) follicular lymphoma (FL). The fourth oral presentation will feature the results of a study evaluating epcoritamab monotherapy in patients with R/R chronic lymphocytic leukemia (CLL). Additionally, three-year efficacy and safety data for subcutaneous epcoritamab in patients with R/R DLBCL from the EPCORE NHL-1 trial will be presented.

"The data evaluating epcoritamab being presented at this year’s ASH (Free ASH Whitepaper) highlight the encouraging clinical results we have seen across epcoritamab clinical trials and demonstrate its potential as a core therapy for B-cell malignancies," said Dr. Judith Klimovsky, Executive Vice President and Chief Development Officer of Genmab. "This has been a pivotal year for epcoritamab, and alongside our partner AbbVie, we are committed to progressing the comprehensive epcoritamab development program with the goal of potentially providing additional therapeutic options to patients in need of treatments."

All abstracts accepted for presentation have been published on the ASH (Free ASH Whitepaper) Website.

2024 R&D Update and ASH (Free ASH Whitepaper) Data Review

On Wednesday, December 11, at 11:00 AM EST (5:00 PM CET/4:00 PM GMT), Genmab will host its 2024 R&D Update and ASH (Free ASH Whitepaper) Data Review. The event will be virtual and webcast live. Details, including the webcast link and registration will be available on www.genmab.com. This meeting is not an official program of the ASH (Free ASH Whitepaper) Annual Meeting.

Abstracts accepted for presentation at ASH (Free ASH Whitepaper) include:

Oral Presentations

Abstract Number

Abstract Title

Type of Presentation

Date/Time of Presentation

342

Fixed-Duration Epcoritamab + R2 Drives Deep and Durable Responses in Patients with Relapsed or Refractory Follicular Lymphoma: 2-Year Follow-Up from Arm 2 of the EPCORE NHL-2 Trial

Oral

Saturday, December 7, 4:00 – 5:30 PM PT

581

Fixed-Duration Epcoritamab + R-CHOP Induces High Complete Response Rates in Patients with Previously Untreated Diffuse Large B-Cell Lymphoma with High-Risk Features: Long-Term Results from the EPCORE NHL-2 Trial

Oral

Sunday, December 8, 12:00 – 1:30 PM PT

867

EPCORE DLBCL-3 First Disclosure: Fixed-Duration Epcoritamab Monotherapy in Older (≥75 y), Anthracycline-Ineligible Patients with Previously Untreated Large B-Cell Lymphoma

Oral

Monday, December 9, 2:45 – 4:15 PM PT

883

Epcoritamab Monotherapy in Patients (Pts) with Relapsed or Refractory (R/R) Chronic Lymphocytic Leukemia (CLL): Results from CLL Expansion and Optimization Cohorts of EPCORE CLL-1

Oral

Monday, December 9, 2:45 – 4:15 PM PT

Poster Presentations

Abstract Number

Abstract Title

Type of Presentation

Date/Time of Presentation

1414

Exposure-Response Analyses Supporting Optimal Epcoritamab 48 mg Full Dose and Dosing Schedule in Relapsed or Refractory Follicular Lymphoma

Poster

Saturday, December 7, 5:30 – 7:30 PM PT

1622

Epcoritamab with R-CHOP Overcomes Poor Risk Features of High Metabolic Tumor Volume in High-Risk Large B-Cell Lymphoma

Poster

Saturday, December 7, 5:30 – 7:30 PM PT

1627

Fixed-Duration Epcoritamab in Combination with Bendamustine + Rituximab for First-Line Treatment of Follicular Lymphoma: Initial Results from EPCORE NHL-2 Arm 3

Poster

Saturday, December 7, 5:30 – 7:30 PM PT

1703

Trends in All-Cause Mortality Rates in Patients with Follicular Lymphoma in the US before and during the COVID-19 Pandemic: A Retrospective Observational Study

Poster

Saturday, December 7, 5:30 – 7:30 PM PT

1734

Immune Biomarkers of Mechanism of Action of Epcoritamab (Epcor) Plus Polatuzumab Vedotin, Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (pola-R-CHP) in Frontline DLBCL

Poster

Saturday, December 7, 5:30 – 7:30 PM PT

1737

Efficacy and Safety of Epcoritamab Monotherapy in Patients with Relapsed or Refractory LBCL Not Previously Exposed to CAR T: Subanalysis of the EPCORE NHL-1 Trial

Poster

Saturday December 7, 5:30 – 7:30 PM PT

2349

Indirect Comparisons of the Efficacy of Epcoritamab Vs Glofitamab in Patients (Pts) with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL)

Poster

Saturday, December 7, 5:30 – 7:30 PM PT

2998

Epcoritamab Induces in vitro-derived Terminally Differentiated Exhausted T Cells to Kill B Cells

Poster

Saturday, December 7, 5:30 – 7:30 PM PT

3106

Fixed-Duration Epcoritamab + R-Mini-CHOP in Patients with Previously Untreated Diffuse Large B-Cell Lymphoma Ineligible for Full-Dose R-CHOP: Updated Results from Arm 8 of the EPCORE NHL-2 Trial

Poster

Sunday, December 8, 6:00 – 8:00 PM PT

3110

Fixed-Duration Epcoritamab Plus Lenalidomide in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL): Updated Results from Arm 1 of the Epcore NHL-5 Trial

Poster

Sunday, December 8, 6:00 – 8:00 PM PT

3115

Prior Bendamustine (Benda) Exposure Did Not Impact Clinical Outcomes and Decreased CD4+ but Not CD8+ T-Cells in Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Treated with the Bispecific Antibody Epcoritamab (Epcor)

Poster

Sunday, December 8, 6:00 – 8:00 PM PT

3231

T cells from CLL patients on venetoclax mount potent cytotoxic responses in combination with epcoritamab, a CD20/CD3 bispecific antibody.

Poster

Sunday, December 8, 6:00 – 8:00 PM PT

3723

Patient Characteristics and Treatment Patterns for Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) By CAR T Eligibility and Treatment Status in France, Germany, Italy, Spain, the UK, and Japan

Poster

Sunday, December 8, 6:00 – 8:00 PM PT

4480

3-Year Update from the EPCORE NHL-1 Trial: Epcoritamab Leads to Deep and Durable Responses in Relapsed or Refractory Large B-Cell Lymphoma

Poster

Monday, December 9, 6:00 – 8:00 PM PT

4491

Three-Factor Prediction Model for Grade 2+Cytokine Release Syndrome in Large B-Cell Lymphoma Patients Receiving Epcoritamab Monotherapy

Poster

Monday, December 9, 6:00 – 8:00 PM PT

5124

Epcoritamab for Relapsed/ Refractory B cell Lymphoma – the Israeli Real-World Experience

Poster

Monday, December 9, 6:00 – 8:00 PM PT

E-publications

Abstract Number

Abstract Title

Type of Presentation

Date/Time of Presentation

7614

Cost-Effectiveness of Epcoritamab Versus Glofitamab in Relapsed or Refractory Large B-Cell Lymphoma after at Least Two Lines of Therapy in the United States

E-publication

N/A

7617

A Canadian Cost-Utility Analysis of Epcoritamab Versus Current Therapies in Third-Line or Later Large B-Cell Lymphoma

E-publication

N/A

7757

Epcoritamab plus Gemcitabine and Oxaliplatin versus Glofitamab or Rituximab plus Gemcitabine and Oxaliplatin in Transplant-Ineligible Relapsed/Refractory Diffuse Large B-Cell Lymphoma Patients: A Match-Adjusted Comparative Analysis

E-publication

N/A

7760

Epcoritamab plus Gemcitabine and Oxaliplatin versus Rituximab, Gemcitabine, and Oxaliplatin in Transplant-Ineligible Relapsed/Refractory Diffuse Large B-Cell Lymphoma Patients: A Match-Adjusted Comparative Analysis

E-publication

N/A

7802

Matching-Adjusted Indirect Treatment Comparison of Epcoritamab versus Zanubrutinib Plus Obinutuzumab in Relapsed or Refractory Follicular Lymphoma

E-publication

N/A

The safety and efficacy of epcoritamab has not been established for these investigational uses.

About Epcoritamab

Epcoritamab is an IgG1-bispecific antibody created using Genmab’s proprietary DuoBody technology and administered subcutaneously. Genmab’s DuoBody-CD3 technology is designed to direct cytotoxic T cells selectively to elicit an immune response toward target cell types. Epcoritamab is designed to simultaneously bind to CD3 on T cells and CD20 on B cells and induces T-cell-mediated killing of CD20+ cells.i

Epcoritamab (approved under the brand name EPKINLY in the U.S. and Japan, and TEPKINLY in the EU) has received regulatory approval in certain lymphoma indications in several territories. Epcoritamab is being co-developed by Genmab and AbbVie as part of the companies’ oncology collaboration. The companies will share commercial responsibilities in the U.S. and Japan, with AbbVie responsible for further global commercialization. Both companies will pursue additional international regulatory approvals for the investigational R/R FL indication and additional approvals for the R/R DLBCL indication.

Genmab and AbbVie continue to evaluate the use of epcoritamab as a monotherapy, and in combination, across lines of therapy in a range of hematologic malignancies. This includes four ongoing Phase 3, open-label, randomized trials including a trial evaluating epcoritamab as a monotherapy in patients with R/R DLBCL compared to investigators choice chemotherapy (NCT04628494), a trial evaluating epcoritamab in combination with R-CHOP in adult participants with newly diagnosed DLBCL (NCT05578976), a trial evaluating epcoritamab in combination with rituximab and lenalidomide (R2) in patients with R/R FL (NCT05409066), and a trial evaluating epcoritamab in combination with rituximab and lenalidomide (R2) compared to chemoimmunotherapy in patients with previously untreated FL (NCT06191744). The safety and efficacy of epcoritamab has not been established for these investigational uses. Please visit www.clinicaltrials.gov for more information.

EPKINLY (epcoritamab-bysp) U.S. IMPORTANT SAFETY INFORMATION

Important Warnings—EPKINLY can cause serious side effects, including:

Cytokine release syndrome (CRS), which is common during treatment with EPKINLY and can be serious or life-threatening. To help reduce your risk of CRS, you will receive EPKINLY on a step-up dosing schedule (when you receive 2 or 3 smaller step-up doses of EPKINLY before your first full dose during your first cycle of treatment), and you may also receive other medicines before and for 3 days after receiving EPKINLY. If your dose of EPKINLY is delayed for any reason, you may need to repeat the step-up dosing schedule.
Neurologic problems that can be life-threatening and lead to death. Neurologic problems may happen days or weeks after you receive EPKINLY.
People with DLBCL or high-grade B-cell lymphoma should be hospitalized for 24 hours after receiving their first full dose of EPKINLY on day 15 of cycle 1 due to the risk of CRS and neurologic problems.

Tell your healthcare provider or get medical help right away if you develop a fever of 100.4°F (38°C) or higher; dizziness or lightheadedness; trouble breathing; chills; fast heartbeat; feeling anxious; headache; confusion; shaking (tremors); problems with balance and movement, such as trouble walking; trouble speaking or writing; confusion and disorientation; drowsiness, tiredness or lack of energy; muscle weakness; seizures; or memory loss. These may be symptoms of CRS or neurologic problems. If you have any symptoms that impair consciousness, do not drive or use heavy machinery or do other dangerous activities until your symptoms go away.

EPKINLY can cause other serious side effects, including:

Infections that may lead to death. Your healthcare provider will check you for signs and symptoms of infection before and during treatment and treat you as needed if you develop an infection. You should receive medicines from your healthcare provider before you start treatment to help prevent infection. Tell your healthcare provider right away if you develop any symptoms of infection during treatment, including fever of 100.4°F (38°C) or higher, cough, chest pain, tiredness, shortness of breath, painful rash, sore throat, pain during urination, or feeling weak or generally unwell.
Low blood cell counts, which can be serious or severe. Your healthcare provider will check your blood cell counts during treatment. EPKINLY may cause low blood cell counts, including low white blood cells (neutropenia), which can increase your risk for infection; low red blood cells (anemia), which can cause tiredness and shortness of breath; and low platelets (thrombocytopenia), which can cause bruising or bleeding problems.
Your healthcare provider will monitor you for symptoms of CRS, neurologic problems, infections, and low blood cell counts during treatment with EPKINLY. Your healthcare provider may temporarily stop or completely stop treatment with EPKINLY if you develop certain side effects.

Before you receive EPKINLY, tell your healthcare provider about all your medical conditions, including if you have an infection, are pregnant or plan to become pregnant, or are breastfeeding or plan to breastfeed. If you receive EPKINLY while pregnant, it may harm your unborn baby. If you are a female who can become pregnant, your healthcare provider should do a pregnancy test before you start treatment with EPKINLY and you should use effective birth control (contraception) during treatment and for 4 months after your last dose of EPKINLY. Tell your healthcare provider if you become pregnant or think that you may be pregnant during treatment with EPKINLY. Do not breastfeed during treatment with EPKINLY and for 4 months after your last dose of EPKINLY.

In DLBCL or high-grade B-cell lymphoma, the most common side effects of EPKINLY include CRS, tiredness, muscle and bone pain, injection site reactions, fever, stomach-area (abdominal) pain, nausea, and diarrhea. The most common severe abnormal laboratory test results include decreased white blood cells, decreased red blood cells, and decreased platelets.

In follicular lymphoma the most common side effects of EPKINLY include injection site reactions, CRS, COVID-19, tiredness, upper respiratory tract infections, muscle and bone pain, rash, diarrhea, fever, cough, and headache. The most common severe abnormal laboratory test results include decreased white blood cells and decreased red blood cells.

These are not all of the possible side effects of EPKINLY. Call your doctor for medical advice about side effects. You are encouraged to report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch or to Genmab US, Inc. at 1-855-4GENMAB (1-855-443-6622).

Please see Medication Guide, including Important Warnings.

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.