On December 9, 2024 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global oncology company that plans to change its name to BeOne Medicines Ltd., reported the presentation of new clinical data at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, underscoring its leadership in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) through continued clinical success with BRUKINSA (zanubrutinib) and promising advancements in its pipeline assets (Press release, BeiGene, DEC 9, 2024, View Source [SID1234648931]).

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"The breadth of data we’re presenting at ASH (Free ASH Whitepaper) underscores BRUKINSA’s role as a best-in-class treatment for CLL and highlights BeiGene’s leadership in advancing the treatment landscape for B-cell malignancies," said Mehrdad Mobasher, M.D., M.P.H., Chief Medical Officer, Hematology at BeiGene. "BRUKINSA shows tremendous promise for patients as a monotherapy and as a backbone for best-in-class combinations. The combination of BRUKINSA and our investigational BCL2 inhibitor, sonrotoclax, demonstrated significant potential as a first-line therapy in CLL, with a 99% overall response rate, best uMRD rate of 92%, and was generally well-tolerated at a median follow-up of 19.4 months; this combination is expected to offer better efficacy than a fixed-dose V-O regimen. Additionally, our investigational BTK degrader could become a first-in-class treatment option for patients with CLL and other BTK-driven B-cell malignancies based on the results of data presented at ASH (Free ASH Whitepaper). BeiGene is primed to shape the future of CLL treatment and aims to meet the needs of CLL patients globally."

Long-term follow-up results from the ongoing Phase 3 SEQUOIA study presented during ASH (Free ASH Whitepaper), which were simultaneously published in the Journal of Clinical Oncology, reaffirm BRUKINSA’s durable efficacy and differentiated safety profile across diverse CLL patient populations, including those with high-risk features. Additional findings spotlight the promising potential of BeiGene’s BTK-targeted chimeric degradation activation compound (CDAC), BGB-16673, which has shown rapid and deep responses in B-cell malignancies in phase 1/2 clinical trials. BeiGene is also developing a next-generation BCL2 inhibitor, sonrotoclax, aiming to improve the safety profile and feasibility of use for this class of drugs and deliver deeper and more durable responses. Together, these advancements reflect BeiGene’s comprehensive approach to addressing the complexities of CLL and its commitment to reshaping the treatment landscape for B-cell malignancies.

With a median follow-up of 61.2 months, data from the SEQUOIA study of patients with treatment-naïve CLL/SLL demonstrated that treatment with BRUKINSA reduced the risk of progression or death by 71% (HR, 0.29; 95% CI, 0.21-0.40; P<.0001*) compared to bendamustine-rituximab (BR). At 54 months, 80.1% of patients who received BRUKINSA remained progression-free (95% CI, 74.3, 84.7) while only 44.6% of patients who received BR remained progression-free (95% CI, 37.6, 51.3). At 60 months, PFS rates were 75.8% (95% CI, 69.0, 81.3) and 40.1% (95% CI, 32.7, 47.3) for BRUKINSA and BR, respectively. Notably, for patients in the study with unmutated IGHV, a prognostic biomarker that indicates a patient’s CLL may be more aggressive, treatment with BRUKINSA reduced the risk of progression or death by 79% compared to BR (HR, 0.21; 95% CI, 0.14-0.33; P<.0001*). The safety profile of BRUKINSA was consistent with the results of prior studies, and no new safety signals were identified. Grade ≥3 treatment-emergent adverse events of interest (AEIs) with BRUKINSA and BR included infection (30.0% and 22.5%, respectively), neutropenia (12.5%; 51.1%), bleeding (7.5%; 1.8%), thrombocytopenia (2.5%; 8.4%), and anemia (0.8%; 2.6%). Rates of atrial fibrillation were 7.1% with BRUKINSA and 3.5% with BR. The rate of discontinuation due to AEs was 20% in the BRUKINSA arm; 13% of patients discontinued BR early due AEs.(Abstract 3249)

"The long-term follow-up of SEQUOIA confirms the sustained efficacy of zanubrutinib over chemotherapy, regardless of IGHV status, in patients with treatment-naïve CLL," said Mazyar Shadman, M.D. M.P.H., Associate Professor and Innovators Network Endowed Chair, Medical Director, Cellular Immunotherapy and the Bezos Family Immunotherapy Clinic at Fred Hutch Cancer Center. He also holds the Innovators Network Endowed Chair at Fred Hutch and is Associate Professor at Fred Hutch and University of Washington. "Notably, there is a deepening of responses, with a complete remission/complete remission with incomplete count recovery rate in the range of 20%, which, based on cross-trial comparison is higher than a typical BTK inhibitor used as monotherapy. Additionally, the incidence of adverse events of interest, such as atrial fibrillation and hypertension, appears comparable to the background risk of this patient population."

In addition to BRUKINSA, BeiGene is advancing a robust pipeline to address the needs of CLL patients, including:

Sonrotoclax (BCL2 Inhibitor): Presented data from the Phase 1/1b study (NCT04277637) demonstrated sonrotoclax, in combination with BRUKINSA, was generally well-tolerated and no cases of tumor lysis syndrome (TLS) were reported in patients with treatment-naïve CLL/SLL. Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 49.6% of patients, with the most common (≥20%) being neutropenia (24% in 160mg cohort; 23% in 320mg cohort). With a median follow-up of 19.4 months (0.4–33.3 months), the combination achieved a 99% overall response rate (ORR), including in patients with high-risk features (51% had unmutated IGHV, 20% had TP53 mutation, and 9% had del(17p)). High and early rates of undetectable minimal residual disease (uMRD) were seen by week 24 of combination therapy, with responses continuing to deepen with time through week 48. Best uMRD rate was achieved in 92% of patients (n=112). At a median follow-up of over a year and a half, no progression has been observed in the 320 mg dose cohort. These data support continued evaluation of this combination in the ongoing registrational Phase 3 fixed-duration CELESTIAL-TNCLL study (NCT06073821) (Abstract 1012)
BGB-16673 (BTK CDAC): Data from the Phase 1/2 CaDAnCe-101 CLL study (NCT05006716) demonstrated that treatment with BGB-16673 was generally well tolerated in this heavily pretreated population of patients. Promising antitumor activity was observed in patients with high-risk features, including in patients with BTK inhibitor-resistant mutations and those previously exposed to covalent BTK inhibitors, noncovalent BTK inhibitors, and BCL2 inhibitors. No atrial fibrillation was observed in either the CLL/SLL or WM cohorts.
From the cohort of CLL/SLL patients, BGB-16673 demonstrated an ORR of 94% at the 200mg dose. Furthermore, amongst all doses delivered, 2 patients achieved a complete remission/complete remission with incomplete count recovery (CR/CRi). Grade ≥3 TEAEs were reported in 57% of patients. The most common grade ≥3 TEAEs (≥10%) were neutropenia/neutrophil count decreased (20%) and pneumonia (10%). (Abstract 885)
From the cohort of Waldenström’s macroglobulinemia patients, BGB-16673 demonstrated a 93% disease control rate (DCR) and 26% very good partial response (VGPR). Grade ≥3 TEAEs were reported in 45% of patients. The most common grade ≥3 TEAE (≥20%) was neutropenia/neutrophil count decreased. (Abstract 860)
For additional information about BeiGene’s presence at ASH (Free ASH Whitepaper) 2024, please visit our meeting hub: congress.beigene.com.

The Company recently announced its intent to change its name to BeOne Medicines, reaffirming its commitment to develop innovative medicines to eliminate cancer by partnering with the global community to serve as many patients as possible.

*P-value was one-sided and descriptive.

About Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL) is a life-threatening cancer of adults. It is a type of mature B-cell malignancy in which abnormal leukemic B lymphocytes (a type of white blood cells) arise from the bone marrow and flood peripheral blood, bone marrow, and lymphoid tissues.1,2 CLL is the most common type of leukemia in adults, accounting for about one-third of new cases.2,3 Approximately 20,700 new cases of CLL will be diagnosed in the U.S. in 2024.3

About Sonrotoclax (BGB-11417)

Sonrotoclax is designed to block the B-cell lymphoma 2 (BCL2) protein, which helps cancer cells survive. It is part of a group of drugs called BH3 mimetics, which mimic natural cell death signals. Studies in the lab and during early drug development have shown that sonrotoclax is a potent and specific inhibitor of BCL2 with a short half-life and no accumulation. Sonrotoclax has shown promising clinical activity across a range of B-cell malignancies, and more than 1,300 patients have been enrolled to date across the global development program. The U.S. Food and Drug Administration (FDA) granted sonrotoclax Fast Track Designation for the treatment of patients with mantle cell lymphoma (MCL) and Waldenström macroglobulinemia (WM).

About BGB‑16673

BGB‑16673 is an orally available, brain-penetrating Bruton’s tyrosine kinase (BTK) targeting chimeric degradation activation compound (CDAC) designed to promote the degradation, or breakdown, of both wildtype and mutant forms of BTK, including those that commonly result in resistance to BTK inhibitors in patients who experience progressive disease. BGB-16673 is the most advanced BTK degrader in the clinic, with more than 350 patients treated to date across the global clinical development program. The U.S. Food and Drug Administration (FDA) granted Fast Track Designation to BGB-16673 for the treatment of adult patients with relapsed or refractory (R/R) chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have been previously treated with at least two prior lines of therapy, including BTK inhibitor (BTKi) and B-cell lymphoma 2 (BCL2) inhibitor, and adult patients with R/R mantle cell lymphoma (MCL).

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 December 9, 2024 Lantern Pharma Inc. (NASDAQ: LTRN), an artificial intelligence (AI) company developing targeted cancer therapies using its proprietary RADR AI platform, reported that the first patient has been enrolled and dosed in Taiwan for its Phase 2 HARMONIC clinical trial evaluating LP-300 in never-smoker patients with non-small cell lung cancer (NSCLC) who have progressed after receiving treatment with tyrosine kinase inhibitors (TKIs) (Press release, Lantern Pharma, DEC 9, 2024, View Source [SID1234648930]).

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The enrollment of the first patient in Taiwan extends the recent expansion of the HARMONIC trial into Asia, where there is a notably higher prevalence of never-smoker NSCLC patients compared to Western populations. Taiwan represents a particularly important region for the trial, as more than half of all new lung cancer diagnoses in Taiwan occur in people who are classified as never-smokers. Never-smokers in the context of lung cancer have been commonly defined, by the CDC and other health agencies, as people who have smoked less than 100 cigarettes in their lifetime.

"The enrollment of our first patient in Taiwan marks another important milestone in the expansion of our HARMONIC trial," said Panna Sharma, President and CEO of Lantern Pharma. "The extremely high proportion of never-smoker lung cancer patients in Taiwan makes this region important for accelerating our enrollment with the objective of addressing a critical unmet need in a population where this disease has an outsized impact."

The scientific and clinical community is increasingly recognizing that lung cancers in nonsmokers and never-smokers represent a distinct disease entity with unique clinical, genomic, pathological, and biological characteristics. Lantern believes that this has particular importance for the Harmonic trial, as it underscores the need of targeted, precision therapy approaches for this unique patient population. Lung cancer in never-smokers constitutes one of the top 10 causes of cancer-related deaths globally, making it a crucial focus for therapeutic innovation.

The expansion into Asia follows encouraging preliminary results from the trial’s initial safety lead-in cohort, which demonstrated an 86% clinical benefit rate and 43% objective response rate among the first seven patients. The HARMONIC trial is evaluating LP-300 in combination with carboplatin and pemetrexed in never-smoker NSCLC patients that have relapsed following treatment with TKIs.

Dr. Reggie Ewesuedo, VP of Clinical Development at Lantern Pharma commented, "The initiation of patient dosing in Taiwan demonstrates the continued momentum of our Asia expansion strategy. With active screening now occurring at multiple sites across both Japan and Taiwan, we expect to see accelerated enrollment in the trial. The enthusiasm we’ve seen from clinical collaborators in Taiwan reflects the significant need for new therapeutic options for never-smoker NSCLC patients in this region."

The Phase 2 HARMONIC trial is actively screening in multiple cancer centers in the US, Japan and Taiwan and is expected to enroll up to 90 patients across two treatment arms. The two treatment arms are randomized, at a ratio of 2 to 1, and will compare the co-primary endpoints of PFS (progression free survival) and OS (median overall survival) of:

– the LP-300 arm which is expected to enroll 60 patients (LP-300 which will be given in combination with the standard of care chemotherapy doublet)
– the SOC arm which is expected to enroll 30 patients (the standard of care arm will only dose patients with the chemotherapy doublet alone).

Initial results from the Phase 2 clinical trial from the lead-in patient cohort can be reviewed in an earlier press release issued by Lantern Pharma. Lantern plans to review, and share the interim data from, the Phase 2 trial for PFS and OS (co-primary endpoints) after 30 clinical events have been observed.

About LP-300

LP-300 is a disulfide small molecule and an investigational new drug candidate. It has been well characterized to have a multimodal mechanism of action directed towards tyrosine kinase receptors and cell redox enzymes. It is believed to modulate cellular redox in key signaling pathways in NSCLC and directly engage with TKI receptors via cysteine modification.

It is known that lung carcinomas in never smoker patients have a much higher percentage of mutations in certain tyrosine kinase (TK) oncogenes such as EGFR, ALK, ROS, and MET-1, contributing to tumor formation and growth, while lung carcinomas in smokers are much more likely to have growth-driver mutations in oncogenes such as RAS, and much lower percentages of mutations in TK oncogenes. Both published (Parker 2015) and unpublished studies have shown that LP-300 covalently binds to and/or inhibits the kinase activity of each of these TK oncogenes (EGFR, ALK, ROS, and MET-1), suggesting that a greater number of lung adenocarcinomas in never smokers, compared to smokers, could be susceptible to the inhibitory effects of LP-300.

LP-300 has been evaluated in 5 Phase 1 and 5 Phase 2 or 3 clinical trials in over 1,000 subjects. In a retrospective subgroup analysis from a prior Phase 3 trial, never smoker lung adenocarcinoma patients receiving the combination of LP-300 with cisplatin and paclitaxel chemotherapy were observed to have significant survival benefit compared to the never smoker patients receiving cisplatin and paclitaxel without LP-300.

On December 9, 2024 Poseida Therapeutics, Inc. (Nasdaq: PSTX), a clinical-stage allogeneic cell therapy and genetic medicines company advancing differentiated non-viral treatments for patients with cancer, autoimmune and rare diseases, reported interim clinical data from its Phase 1 trial of P-BCMA-ALLO1 in patients with relapsed/refractory multiple myeloma (RRMM), including new profiling of patient responses from Arm C, an optimized lymphodepletion arm (Press release, Poseida Therapeutics, DEC 9, 2024, View Source [SID1234648929]). The P-BCMA-ALLO1 data are being presented, along with two additional Company poster presentations covering new preclinical data for P-CD19CD20-ALLO1 and a patient case study demonstrating the reactivation of a Poseida autologous CAR-T therapy with a T-cell engager, at the 66th ASH (Free ASH Whitepaper) Annual Meeting and Exposition being held in San Diego on December 7-10, 2024.

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P-BCMA-ALLO1 is an investigational non-viral, stem cell memory T cell (TSCM)-rich allogeneic CAR-T cell therapy in Phase 1/1b clinical development for the treatment of patients with RRMM. P-CD19CD20-ALLO1 is an investigational, non-viral TSCM-rich allogeneic CAR-T cell therapy in Phase 1 clinical development for the treatment of patients with B-cell malignancies and is the Company’s first dual CAR-T program. P-BCMA-ALLO1 and P-CD19CD20-ALLO1 are being developed in collaboration with Roche.

"We continue to gain confidence in the potential for P-BCMA-ALLO1 in multiple myeloma, including from the additional sub-analysis of the Phase 1 data presented at ASH (Free ASH Whitepaper)," said Kristin Yarema, Ph.D., President and Chief Executive Officer of Poseida Therapeutics. "We believe the data to-date provide strong validation for our allogeneic cell therapy platform, laying the groundwork for us to extend our non-viral, TSCM-rich approach and drive value with additional clinical programs. This includes P-CD19CD20-ALLO1, our first dual CAR-T supported by preclinical data presented at ASH (Free ASH Whitepaper), and with clinical data anticipated in 2025."

P-BCMA-ALLO1 Phase 1 Data
The poster presentation will highlight Phase 1 clinical data first presented at the 21st International Myeloma Society (IMS) Annual Meeting in September 2024. The data showed a 91% overall response rate (ORR) in Arm C (an optimized lymphodepletion arm), including a 100% ORR in B-cell maturation antigen (BCMA)-naïve patients, and an 86% ORR in those who had received at least one prior BCMA- and/or G protein-coupled receptor class C group 5 member D (GPRC5D)-targeting treatment modality, along with differentiated safety results with no dose-limiting toxicities, low rates of cytokine release syndrome (CRS) and immune effector cell neurotoxicity syndrome (ICANS), all Grade 2 or less, and no graft vs. host disease or Parkinsonism. No patients required anti-myeloma bridging therapy or prophylaxis with steroids or tocilizumab, and there was no invasive apheresis; an average manufacturing wait time, from treatment decision to clinical response, was only 3.5 weeks1 (with a median time to response of 16 days post initial P-BCMA-ALLO1 therapy). The patients in this study had more advanced disease than the myeloma patients studied in clinical trials of approved autologous CAR-T therapies2, and in the intent-to-treat population, 100% of patients were infused with P-BCMA-ALLO1.

New profiling of patient responses from Arm C are included in the ASH (Free ASH Whitepaper) poster presentation. The data from this analysis show consistent P-BCMA-ALLO1 cellular expansion and persistence across different subgroups, including patients that are typically more challenging to treat. Key highlights suggest that P-BCMA-ALLO1:

Cellular kinetics were not impacted by prior BCMA/GPRC5D-targeted therapy
Expands and persists in patients with extramedullary disease (EMD)
P-CD19CD20-ALLO1 Preclinical Data
Preclinical data has demonstrated that P-CD19CD20-ALLO1 delivers high in vitro potency and strong in vivo antitumor activity for either CD19 or CD20 single-positive target cells, as well as double-positive targets. New preclinical data included in the poster presentation show that compared to CD19-single targeting or CD20-single targeting CAR-T cells, P-CD19CD20-ALLO1:

Achieved higher and more durable killing of tumor cells over three rechallenges, even in the presence of only one tumor antigen
Exhibited higher cytotoxicity
Produced higher and more sustained levels of effector cytokines (IL-2, IFN-γ, sFasL, Granzyme A and Granulysin) that play an important role mediating the immune system response to cancers
Showed higher in vivo antitumor efficacy than the CD19-single targeting CAR-T cells
The Company’s P-CD19CD20-ALLO1 Phase 1 clinical trial is enrolling patients with selected B-cell malignancies, with initial clinical data anticipated in 2025.

CAR-T Reactivation with T-cell Engager Case Study
The case study highlights the reactivation of an autologous Poseida CAR-T therapy with a T-cell engager in a patient with relapsed multiple myeloma. The patient attained and remained in stringent complete response over 12 months after CAR-T reactivation. This case highlights the potential of Poseida’s TSCM-based CAR-T therapies to deliver a strong anti-myeloma response with long-term remission and CAR-T cell persistence. The Company believes this is the first time that a T-cell engager has been seen to reactivate a CAR-T therapy.

ASH 2024 Poster Presentations

Title: Late Polyclonal P-BCMA-101 CAR-T Cell Re-expansion and Rapid Complete Response in a Patient with Relapsed Multiple Myeloma Treated with One Cycle of Talquetamab, More Than 3 Years After CAR-T Infusion

Presenting Author: Anupama Kumar, M.D., Assistant Professor, Hematology, Blood & Marrow Transplant, and Cellular Therapy (HBC) Program, University of California, San Francisco (UCSF)
Session: 704. Cellular Immunotherapies: Early Phase Clinical Trials and Toxicities: Poster I
Presentation Date/Time: Saturday, December 7, 2024, 5:30-7:30 p.m. PT (8:30-10:30 p.m. ET)
Room: Halls G-H, San Diego Convention Center
Abstract Number: 2083
Title: P-CD19CD20-ALLO1: Potent Fully Allogeneic CAR-T Therapy Targeting CD19 and CD20 with Superior Efficacy Over Single-Target Products

Presenting Author: Samy Jambon, Ph.D., Poseida Therapeutics
Session: 702. CAR-T Cell Therapies: Basic and Translational: Poster III
Presentation Date/Time: Monday, December 9, 2024, 6:00-8:00 p.m. PT (9:00-11:00 p.m. ET)
Room: Halls G-H, San Diego Convention Center
Abstract Number: 4805
Title: A Phase 1 Study of P-BCMA-ALLO1, a Non-viral, Allogeneic BCMA Directed CAR-T in Relapsed/Refractory Multiple Myeloma (RRMM): Results from Optimized Lymphodepletion Cohort

Presenting Author: Caitlin Costello, M.D., Professor of Medicine, Director of Multiple Myeloma Program, Division of Blood and Marrow Transplant, Moores Cancer Center, University of California, San Diego (UCSD)
Session: 704. Cellular Immunotherapies: Early Phase Clinical Trials and Toxicities: Poster III
Presentation Date/Time: Monday, December 9, 2024, 6:00-8:00 p.m. PT (9:00-11:00 p.m. ET)
Room: Halls G-H, San Diego Convention Center
Abstract Number: 4828
About P-BCMA-ALLO1
P-BCMA-ALLO1 is an allogeneic CAR-T product candidate licensed to Roche targeting B-cell maturation antigen (BCMA) for the treatment of relapsed/refractory multiple myeloma. This allogeneic program includes a VH-based binder that targets BCMA, and interim clinical data presented at IMS in September 2024 support the Company’s belief that T stem cell (TSCM)-rich allogeneic CAR-Ts have the potential to offer effective, safe and reliable treatment addressing unmet needs in multiple myeloma. The FDA has granted P-BCMA-ALLO1 Orphan Drug designation for multiple myeloma and Regenerative Medicine Advanced Therapy (RMAT) designation for adult patients with relapsed/refractory multiple myeloma after three or more prior lines of therapies including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody.

P-BCMA-ALLO1 is currently being evaluated in a Phase 1/1b trial in patients with multiple myeloma. Additional information about the trial is available at www.clinicaltrials.gov using identifier: NCT04960579.

About P-CD19CD20-ALLO1
P-CD19CD20-ALLO1 is an allogeneic CAR-T cell therapy product candidate being developed for relapsed or refractory B-cell malignancies in partnership with Roche. P-CD19CD20-ALLO1 expresses two fully functional CAR molecules to target cells that express either CD19 or CD20. The dual targeting approach employed in P-CD19CD20-ALLO1 aims to overcome the antigen escape limitations of CD19-only targeted CAR-T therapies by simultaneously targeting both CD19 and CD20. In addition to the dual targeting, P-CD19CD20-ALLO1 uses a novel CD19 binder that showed greater potency in in vivo preclinical models when compared to the canonical FMC63 Single-chain variable fragment (scFv) binder. P-CD19CD20-ALLO1 is an off-the-shelf CAR-T therapy for which patients do not have to undergo apheresis and wait for cells to be manufactured, which can potentially overcome the limitation of autologous CAR-T therapies associated with significant manufacturing times. P-CD19CD20-ALLO1 is being studied in a Phase 1 study in B-cell malignancies (www.clinicaltrials.gov using identifier: NCT06014762). Building on the transformative potential of the CAR-T modality beyond oncology, the Company has recently submitted investigational new drug (IND) applications to the U.S. Food and Drug Administration (FDA) to investigate this program’s potential for patients with multiple sclerosis and systemic lupus erythematosus.

On December 09, 2024 Affimed N.V. (Nasdaq: AFMD) ("Affimed", or the "Company"), a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, reported the oral presentation of data on AFM28 at the 66th ASH (Free ASH Whitepaper) Annual Meeting and Exposition (Press release, Affimed, DEC 9, 2024, View Source [SID1234648928]). The data, derived from the first-in-human Phase 1 study of AFM28, showed promising results in R/R AML, with signs of clinical efficacy and a well-managed safety profile at doses up to 300 mg weekly.

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The study included 29 heavily pretreated R/R AML patients across six AFM28 dose levels. The median number of prior treatment lines was two and 86% of patients had an adverse risk profile according to the 2022 guidelines from the European LeukemiaNet (ELN2022). AFM28 was administered intravenously once a week across six dose levels, ranging from 25 mg to 300 mg. AFM28 was well tolerated, and the most common treatment-emergent adverse events were IRRs, observed in 45% of patients. All IRRs were mild to moderate (Grade 1 or 2). One patient demonstrated grade 1 cytokine release syndrome (CRS). No neurotoxicity or signs for immune-effector related side effects were seen.

One of six patients treated at 250 mg showed a CR and stayed on treatment for 6.5 months. At the 300 mg dose level, 1 CR and 3 CRi were seen in 10 evaluable patients for a CRcR of 40%. Four of 10 patients are still on treatment with the option to deepen responses.

"Achieving a 40% composite complete remission rate with AFM28 in R/R AML is a significant milestone, especially in this difficult-to-treat patient population. Importantly, we see activity independent of mutational status, including patients with negative prognostic molecular profiles. Safety has been manageable which provides the basis for further development of AFM28 either as single agent or in combination regimens," said Dr. Andreas Harstrick, MD, Chief Medical Officer at Affimed.

The AFM28 Phase 1 study is on-going.

About AFM28

AFM28, a tetravalent, bispecific CD123- and CD16A-binding ICE, is designed to bring our immunotherapeutic approach to patients with acute myeloid leukemia (AML). It engages NK cells to initiate leukemic cell killing via antibody-dependent cellular cytotoxicity, even at low CD123 expression levels. AFM28 is currently in clinical development as monotherapy in patients with R/R AML (NCT05817058).

On December 9, 2024 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to bringing a first-in-class pipeline of induced pluripotent stem cell (iPSC)-derived cellular immunotherapies to patients with cancer and autoimmune disorders, reported new clinical and translational data from the Company’s FT819 Phase 1 Autoimmunity study for moderate-to-severe systemic lupus erythematosus (SLE) at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting being held in San Diego, CA (Press release, Fate Therapeutics, DEC 9, 2024, View Source [SID1234648927]). The first three study patients, each of whom presented with active lupus nephritis (LN) despite having been treated with multiple standard-of-care therapies, received fludarabine-free conditioning followed by a single dose of FT819 at 360 million cells. There were no dose-limiting toxicities (DLTs), no events of any grade of cytokine release syndrome (CRS), immune effector-cell associated neurotoxicity syndrome (ICANS), or graft-versus-host disease (GvHD), and rapid, deep, and sustained elimination of CD19+ B cells in the periphery was observed during the first month of treatment. FT819 is the Company’s off-the-shelf, CD19-targeted, 1XX CAR T-cell product candidate comprised of CD8αβ+ T cells with a memory phenotype and high CXCR4 expression to promote tissue trafficking.

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"We continue to be very pleased with early clinical observations of fludarabine-free conditioning and FT819 off-the-shelf, CAR T-cell therapy in patients with moderate-to-severe SLE. The remarkable experience of the first patient treated in April is ongoing, as the patient remains on-study in drug-free clinical remission. In addition, the initial clinical and translational data from the two additional patients treated at the first dose level continue to support the potential for disease transformation," said Bob Valamehr, President of Research and Development of Fate Therapeutics. "We are now initiating dose expansion at this first dose level to accelerate development, and are also escalating dose based on the favorable safety profile observed. In addition, I am pleased to announce that the first patient has now been treated with FT819 as an add-on to maintenance therapy without conditioning chemotherapy. We believe our therapeutic approach is highly-differentiated and has the potential to transform disease outcomes without requiring patient apheresis, discontinuation of maintenance therapy, intense conditioning chemotherapy, and extended hospitalization."

FT819 Phase 1 Autoimmunity Study

The ongoing multi-center, Phase 1 clinical trial for patients with moderate-to-severe SLE is designed to evaluate the safety, pharmacokinetics, and anti-B cell activity of FT819 (NCT06308978). The first three patients, all of whom presented with active LN despite having been treated with multiple standard-of-care therapies, received fludarabine-free conditioning consisting of either cyclophosphamide alone or bendamustine alone, followed by a single dose of FT819 at 360 million cells. In all three patients, FT819 was detected in the peripheral blood and rapid, deep, and sustained elimination of CD19+ B cells in the periphery was observed during the first month of treatment. All three patients remain on-study, and there have been no DLTs and no events of any grade of CRS, ICANS, or GvHD. Based on these clinical observations, the Company is initiating dose expansion in up to 10 patients at this first dose level, and is also escalating dose to 720 million cells.

The Company’s FT819 Phase 1 Autoimmunity study also includes a second treatment arm to assess the safety, pharmacokinetics, and anti-B cell activity of a single dose of FT819 as an add-on to maintenance therapy without conditioning chemotherapy in patients with SLE. The first patient has now been treated in this second arm, which is being conducted in parallel with the study’s conditioning arm.

FT819 Patient 1 Case Study

The first patient treated in the Phase 1 Autoimmunity study presented with active LN and severe disease, which was marked by renal BILAG A (British Isles Lupus Assessment Group) disease activity score based on biopsy, SLEDAI-2K (Systemic Lupus Erythematosus Disease Activity Index) score of 20, FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) score of 33 (range 0-52, where a score of 52 indicates no fatigue) and PGA (Physician Global Assessment) score of 2.5 (where a score of 3 indicates most severe activity). Following administration of fludarabine-free conditioning and treatment with a single dose of FT819 at 360 million cells, the patient was discharged from the hospital without notable adverse events (AEs) after a protocol-required three-day stay. Rapid elimination of CD19+ B cells in the periphery was observed following treatment, and B-cell recovery by Month 3 was predominantly comprised of naïve, non-class switched B cells with near-complete elimination of switched memory B cells and deep depletion of plasmablasts, indicative of an immune reset. The patient reported that her debilitating fatigue had entirely resolved without further treatment, and treatment with methylprednisolone was discontinued at Month 3. The patient achieved DORIS (definition of remission in SLE) clinical remission, including with resolution of arthritis and active urinary sediment and with a substantial reduction in proteinuria, as of Month 6 follow-up. The patient continues on-study, in DORIS clinical remission, and remains free of all immunosuppressive therapy.

iPSC-derived CAR T-cell Product Platform

The Company also highlighted the scientific progress of its proprietary iPSC-derived CAR T-cell product platform at the ASH (Free ASH Whitepaper) Annual Meeting. In an oral presentation entitled "Off-the-shelf Product Candidate Incorporates Novel Sword & Shield Technology Designed to Promote Functional Persistence without Conditioning Chemotherapy", the Company compared its novel Sword & Shield technology, which utilizes a 4-1BB-targeted CAR (ADR) alongside the complete knock-out of CD58 (CD58KO) to both target and evade host alloreactive immune cells, to other host immune evasion strategies. In preclinical studies of allogeneic models, the Company showed that its Sword and Shield Technology specifically engaged with alloreactive T cells and supported functional persistence while avoiding the killing of general host T cells and activated anti-tumor T cells. This unique observation was not seen with other approaches that are either too broad and undesirably eliminate most of the host immune system or have limited coverage and cannot adequately protect the allogeneic cell product. In a second presentation entitled "Development of Induced Pluripotent Stem Cell-Derived T Cells Exhibiting Phenotypic and Functional Attributes of Primary CAR T Cells", the Company conducted a series of high-resolution analyses to show stimulated iPSC-derived T cells elicit primary T-cell like activation, proliferation, transcriptional and functional program engagement, and iPSC-derived CAR T cells uniquely emulate antigen-mediated response similar to primary-derived autologous CAR T cells.

About Fate Therapeutics’ iPSC Product Platform

Human induced pluripotent stem cells (iPSCs) possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s proprietary iPSC product platform combines multiplexed-engineering of human iPSCs with single-cell selection to create clonal master iPSC lines. Analogous to master cell lines used to mass produce biopharmaceutical drug products such as monoclonal antibodies, the Company utilizes its clonal master iPSC lines as a starting cell source to manufacture engineered cell products which are well-defined and uniform in composition, can be stored in inventory for off-the-shelf availability, can be combined and administered with other therapies, and can potentially reach a broad patient population. As a result, the Company’s platform is uniquely designed to overcome numerous limitations associated with the manufacture of cell therapies using patient- or donor-sourced cells. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 500 issued patents and 500 pending patent applications.