On November 3, 2022 Arcellx, Inc. (NASDAQ: ACLX), a biotechnology company reimagining cell therapy through the development of innovative immunotherapies for patients with cancer and other incurable diseases, reported that new clinical data from its Phase 1 study of CART-ddBCMA in patients with relapsed or refractory multiple myeloma will be presented at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition taking place December 10-13, 2022, in New Orleans, Louisiana (Press release, Arcellx, NOV 3, 2022, View Source [SID1234623056]). The data in the ASH (Free ASH Whitepaper) abstract contains previously presented data from a May 3, 2022, data cut. The presentation at ASH (Free ASH Whitepaper) will include new data with longer follow-up period and additional patients from a recent data cut.

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Presentation Details:

Arcellx will host a live webcast event with an expert panel of clinicians to discuss the clinical results on Sunday, December 11, 2022, at 11:00 a.m. CT. The event will be accessible from Arcellx’s website at www.arcellx.com in the Investors section. A replay of the webcast will be archived and available for 30 days following the event.

On November 3, 2022 Poseida Therapeutics, Inc. (Nasdaq: PSTX), a clinical-stage biopharmaceutical company utilizing proprietary genetic engineering platform technologies to create cell and gene therapeutics with the capacity to cure, reported that preclinical data from its P-FVIII-101 program, partnered with Takeda, has been selected for an oral presentation at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition, being held in New Orleans and virtually December 10–13, 2022 (Press release, Poseida Therapeutics, NOV 3, 2022, View Source;exposition-301667029.html [SID1234623055]).

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P-FVIII-101 is a liver-directed gene therapy product candidate for the in vivo treatment of Hemophilia A utilizing the Company’s non-viral piggyBac DNA Delivery System combined with its nanoparticle delivery technology. Compared to current generation gene therapy approaches that use traditional adeno-associated virus (AAV), the Company’s non-viral gene delivery strategy is designed to enable potential single treatment cures with lower toxicity to mitigate safety issues, allow for re-dosing if needed and deliver optimized FVIII transgenes without cargo size limitations.

The oral presentation will highlight preclinical data from initial proof-of-concept studies, which demonstrated that a single administration of P-FVIII-101 resulted in durable expression of the Factor VIII protein at therapeutic levels in a dose-responsive manner. Expression of Factor VIII was shown to be sustained over six months in mouse models. These data illustrate the potential of P-FVIII-101 utilizing piggyBac to provide a long-term durable response for the treatment of Hemophilia A, early in life, with stable integration.

On November 3, 2022 I-Mab (the "Company") (Nasdaq: IMAB), a clinical-stage biopharmaceutical company committed to the discovery, development, and commercialization of novel biologics, reported that two poster presentations featuring preclinical and translational research data of lemzoparlimab, will be presented at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, taking place December 10-13, 2022, in New Orleans, Louisiana (Press release, I-Mab Biopharma, NOV 3, 2022, View Source [SID1234623054]).

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"While rapidly advancing the clinical development of lemzoparlimab, we continue to pursue the full clinical potential of lemzoparlimab and validating its combination strategies through preclinical and translational research," said Dr. Andrew Zhu, President and acting CEO of I-Mab. "The data being presented at ASH (Free ASH Whitepaper) will feature the results of biomarker analysis from a phase 2 study of lemzoparlimab and azacitidine in myelodysplastic syndrome, as well as highlight preclinical evidence of the exploration of two promising immuno-oncology targets, CD47 and CD38, in combination therapy in multiple myeloma."

The accepted abstracts are currently available on the ASH (Free ASH Whitepaper) website:

Title:

Molecular Biomarker Analyses for Exploring the Therapeutic Mechanism of Lemzoparlimab and Azacitidine (AZA) in Newly Diagnosed Higher Risk Myelodysplastic Syndrome (HR-MDS)

Abstract ID:

3974

Presenter:

Prof. Chunkang Chang, Shanghai Sixth People’s Hospital

Session:

604. Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms: Poster III

Location:

Ernest N. Morial Convention Center, Hall D

Date/Time:

Monday, December 12, 2022, 6:00 p.m. – 8:00 p.m. ET

Abstract synopsis: The data show an increased calreticulin (CALR) expression in CD33+ blasts after lemzoparlimab and AZA combination treatment and higher immune infiltrates including total, CD91+ macrophages and CD8/Treg ratio in bone marrow at baseline is associated with better clinical response, suggesting the important role of activation of tumor derived pro-phagocytic signal and effector immune cells in the anti-tumor activity mediated by combination treatment. In addition, patients whose malignancy harbors a TP53 mutation showed a higher CALR expression and immune infiltrates in bone marrow, which may be related with the observed better clinical response than those with wild type (WT) TP53. Our results pinpoint the potential mechanism of clinical benefits from lemzoparlimab and AZA treatment in HR-MDS.

Title:

Exploration of the Therapeutic Effects of CD47 and CD38 Antibody Combination in Relapsed or Refractory Multiple Myeloma

Abstract ID:

4462

Presenter:

Dr. Fanny Zhang, I-Mab

Session:

651. Multiple Myeloma and Plasma Cell Dyscrasias: Basic and Translational: Poster III

Location:

Ernest N. Morial Convention Center, Hall D

Date/Time:

Monday, December 12, 2022, 6:00 p.m. – 8:00 p.m. ET

Abstract synopsis: In this research we found that high CD47 and low CD38 expression was related with poor clinical outcome in relapsed or refractory multiple myeloma (rrMM) patients especially those high-risk populations. Combination of lemzoparlimab and felzartamab showed enhanced in vitro antibody-dependent cellular phagocytosis (ADCP) and in vivo anti-tumor efficacy in these CD47-high and CD38-low high-risk MM which was resistant to felzartamab or daratumumab mono-treatment. Our study provides preclinical evidence to explore the combination of lemzoparlimab and felzartamab in the treatment of high-risk MM patients.

Additional data collected will be included in final meeting presentations. Both posters will be made available on the Company’s website following the close of ASH (Free ASH Whitepaper) annual meeting on December 13, 2022.

About CD47 and Lemzoparlimab

CD47 is a cell surface protein over-expressed in a wide variety of cancers and can act to protect tumors by delivering a "don’t eat me" signal to otherwise tumor-engulfing macrophages. CD47 antibody blocks this signal and enables macrophages to attack tumor cells. However, development of CD47 antibody as a cancer therapy has been hampered by its hematologic side effects, such as severe anemia, caused by natural binding of CD47 antibody to red blood cells. Scientists at I-Mab discovered a novel CD47 antibody, lemzoparlimab, that is designed to target tumor cells while exerting a minimal untoward effect on red blood cells.

Multiple clinical studies of lemzoparlimab are ongoing to explore indications in treating patients with myelodysplastic syndrome (MDS), acute myelocytic leukemia (AML), non-Hodgkin’s lymphoma (NHL), and advanced solid tumors in combination with chemotherapy and immune checkpoint inhibitors.

About Felzartamab

Felzartamab (TJ202/MOR202) is an investigational human monoclonal antibody derived from MorphoSys’ HuCAL antibody technology. The antibody is directed against CD38 on the surface of multiple myeloma cells, which has been characterized as one of the most strongly and uniformly expressed antigens on the surface of malignant plasma cells. According to its suggested mode of action, the antibody recruits cells of the body’s immune system to kill the tumor through antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). The antibody does not involve complement dependent cytotoxicity, or CDC, an additional immune mechanism involved in tumor cell killing. Scientific research suggests that an anti-CD38 antibody may have therapeutic potential also in other cancers as well as autoimmune diseases. Based on a licensing agreement between MorphoSys and I-Mab signed in November 2017, I-Mab owns the exclusive rights for development and commercialization of TJ202/MOR202 in mainland China, Taiwan, Hong Kong and Macao.

HuCAL is a registered trademark of MorphoSys AG.

On November 3, 2022 Gracell Biotechnologies Inc. ("Gracell" or the "Company", NASDAQ: GRCL), a global clinical-stage biopharmaceutical company dedicated to developing highly efficacious and affordable cell therapies for the treatment of cancer, reported the first clinical data of its ongoing Phase 1, investigator-initiated study in China evaluating FasTCAR-enabled GC012F in newly diagnosed, transplant-eligible, high-risk multiple myeloma (NDMM) patients (Press release, Gracell Biotechnologies, NOV 3, 2022, View Source;exposition-301667106.html [SID1234623053]). The findings will be presented during an oral session at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition, at 5:15pm CT on Dec. 10, 2022, in New Orleans, Louisiana.

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GC012F is an autologous CAR-T therapeutic candidate dual-targeting B cell maturation antigen (BCMA) and CD19 and is developed using Gracell’s proprietary FasTCAR next-day manufacturing platform.

As of the ASH (Free ASH Whitepaper) abstract data cutoff date July 25, 2022, 13 transplant-eligible, NDMM patients had received GC012F infusion. All patients had one or more high-risk features. After receiving a conditioning chemotherapy of cyclophosphamide and fludarabine, patients were treated with GC012F as a single infusion of one of three dose levels: 1×105 cells/kg (DL1), 2×105 cells/kg (DL2) and 3×105 cells/kg (DL3).

The study is ongoing. As of the ASH (Free ASH Whitepaper) abstract data cutoff date, among the 13 efficacy-evaluable patients with a median follow-up time of 5.3 months (range 2.3-12.5 months):

Overall response rate was 100%
69% of patients had achieved stringent complete response (sCR). Patients continue to be followed for deepening responses
All patients had achieved minimal residual disease (MRD) negativity
In the MRD assessment with EuroFlow for landmark analysis at month 1 and month 6, all evaluable patients were MRD negative at both timepoints
All patients had experienced robust CAR-T cell expansion
The preliminary clinical data is also demonstrating an excellent safety profile:

Only 23% (3/13) patients experienced Grade 1-2 cytokine release syndrome (CRS)
No Grade 3 or higher CRS, and no immune effector cell-associated neurotoxicity syndrome (ICANS) of any grade had been observed
Presentation details:

Abstract title: Phase I Open-Label Single-Arm Study of BCMA/CD19 Dual-Targeting FasTCAR-T Cells (GC012F) As First-Line Therapy for Transplant-Eligible Newly Diagnosed High-Risk Multiple Myeloma
Abstract ID: 162295
Session Name: 704. Cellular Immunotherapies: Early Phase and Investigational Therapies: CAR T in Multiple Myeloma and T-cell Therapies After Allo-HCT
Session Date: Saturday, Dec. 10, 2022 from 4-5:30 p.m. CT
Presentation Time: 5:15 p.m. CT
Location: Ernest N. Morial Convention Center, Great Hall A/D
The abstract is now available online on the ASH (Free ASH Whitepaper) website.

"We are excited to present the first clinical data evaluating GC012F as a first-line therapy for multiple myeloma at ASH (Free ASH Whitepaper) 2022, a premier gathering of leading minds in hematology and oncology from around the world. We are thrilled to report that BCMA/CD19 dual targeting FasTCAR-T GC012F is showing a very favorable safety profile and encouraging efficacy in newly-diagnosed multiple myeloma patients," said Dr. Wendy Li, Gracell’s Chief Medical Officer. "We believe the data further validates our proprietary FasTCAR next-day manufacturing platform and the potential of GC012F in treatment for multiple myeloma. Treating newly diagnosed patients will be a new frontier for CAR-T, and we are committed to bringing paradigm-shifting innovation to patients in need."

About GC012F

GC012F is a FasTCAR-enabled BCMA/CD19 dual-targeting CAR-T product candidate that is currently being evaluated in IIT studies in China for the treatment of multiple myeloma and B-cell non-Hodgkin’s lymphoma. GC012F simultaneously targets CD19 and BCMA to drive fast, deep and durable responses, which can potentially improve efficacy and reduce relapse in multiple myeloma and B-NHL patients.

About FasTCAR

CAR-T cells manufactured on Gracell’s proprietary FasTCAR platform appear younger, less exhausted and show enhanced proliferation, persistence, bone marrow migration and tumor cell clearance activities as demonstrated in preclinical studies. With next-day manufacturing, FasTCAR is able to significantly improve cell production efficiency which may result in meaningful cost savings, and, together with fast release time, enables enhanced accessibility of cell therapies for cancer patients.

On November 3, 2022 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company) a leader in the development of targeted radiotherapies, reported that positive results from the Phase 1 trial evaluating Actimab-A with salvage chemotherapy regimen CLAG-M in fit patients with relapsed or refractory acute myeloid leukemia (AML) that is being conducted at the Medical College of Wisconsin as investigator sponsored study (Press release, Actinium Pharmaceuticals, NOV 3, 2022, View Source [SID1234623052]). These data were detailed in an abstract accepted for oral presentation at the 64th Annual ASH (Free ASH Whitepaper) Meeting & Symposium being held December 10-13, 2022 in New Orleans, Louisiana.

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Survival, Response and MRD Negativity Findings
Median Overall Survival (OS) of 12 months amongst all patients (n=21)
1-year OS of 53% and 2-year OS of 32%
Overall Response Rate (ORR) of 67% across all dose cohorts
72% MRD negativity rate in patients achieving CRc
ORR of 83% at the recommended Phase 2 dose of 0.75uCi/kg of Actimab-A with CLAG-M
Actimab-A CLAG-M combo was active in patients with TP53 mutations with an ORR of 73% and an ORR of 55% in patients previously treated with venetoclax
Dr. Sameem Abedin, Assistant Professor at Froedtert & Medical College Wisconsin and Principal Investigator of the Study, commented, "The median overall survival of 12 months and 2-year overall survival of 32% is highly impressive in these relapsed or refractory patients, where a majority of treated patients have adverse cytogenetics including TP53 mutations and received prior venetoclax therapy. These are extremely difficult to treat patients with very limited treatment options and their expected median overall survival is approximately 2 to 3 months."

"These data strongly support the further clinical development of this novel targeted radiotherapy-based combination. We are excited that our hypothesis of adding Actimab-A to CLAG-M to eliminate residual leukemia cells, resulting in deeper remissions and survival with acceptable tolerability given targeted nature of Actimab-A is strongly supported by these findings," concluded Dr. Abedin.

Patient Characteristics
Patients had relapsed or refractory AML and deemed fit with adequate organ function
Patients received a median of two lines of prior therapy
57% received prior venetoclax therapy
67% of patients had adverse cytogenetics, 52% had TP53 mutations
Median age was 63 years
Patients had median blast CD33 expression of 77% (>25% required for enrollment)
52% of patients had secondary AML or treatment related AML
Dr. Avinash Desai, Actinium’s Chief Medical Officer, commented, "Improvements in overall survival have been difficult to achieve in relapsed or refractory AML patients, particularly for those with TP53 mutations. Additionally, as venetoclax-based treatments have become a standard of care, physicians need better treatment options to then manage the significant number of patients that do not respond, stop treatment due to toxicities or relapse and who have a median overall survival of just 2.4 months. We are incredibly excited by these data that clearly show Actimab-A’s potential to improve patient outcomes when combined with CLAG-M. Further, it shows how Actimab-A can be utilized in combination with other therapies and add potency, which supports our strategy to establish it as a backbone therapy for AML with other therapies. With our recommended phase 2 dose finalized and these strong rates of MRD negativity and overall survival, we look forward to providing updates on our development and regulatory strategy as we work to bring this important combination to patients."

ASH Oral Presentation Details
Title: Lintuzumab-Ac225 with Combination with Intensive Chemotherapy Yields High Response Rate and MRD Negativity in R/R AML with Adverse Features

Maiti et al. Outcomes of relapsed or refractory acute myeloid leukemia after front-line hypomethylating agent and venetoclax regimens. Hematoligica 2021 Mar 1; 894-898
Ganzel et al. Very poor long-term survival in past and more recent studies for relapsed AML patients: The ECOG-ACRIN experience. American Journal of Hematology. 2018 Aug; 93(8): 1074–1081