On November 3, 2022 Adicet Bio, Inc. (Nasdaq: ACET), a clinical stage biotechnology company discovering and developing allogeneic gamma delta T cell therapies for cancer, reported that an abstract detailing updated safety and efficacy data from the Company’s Phase 1 study of ADI-001 for the potential treatment of relapsed or refractory B-cell Non-Hodgkin’s lymphoma (NHL) was made available as part of the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, which is being held December 10-13, 2022 in New Orleans, Louisiana (Press release, Adicet Bio, NOV 3, 2022, View Source [SID1234623038]). The abstract outlines a summary of clinical data as of a July 15, 2022 data-cut date. Clinical data will be provided during a poster presentation by Sattva Neelapu, M.D., from the MD Anderson Cancer Center at the ASH (Free ASH Whitepaper) Annual Meeting on Saturday, December 10, 2022.

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"The latest data-cut from our ongoing study of ADI-001 is extremely encouraging, as we continue to see complete responses and preliminary durability coupled with a benign safety profile in heavily pre-treated patients with aggressive NHL. We look forward to providing additional clinical data from a later data-cut date during the ASH (Free ASH Whitepaper) Annual Meeting," said Francesco Galimi, M.D., Ph.D., Chief Medical Officer of Adicet Bio. "With the data generated to date coupled with the pace of enrollment in dose level 4, we remain on track to initiate a potentially pivotal program for ADI-001 in the first half of 2023."

Data highlights as of the July 15, 2022 data-cut date included in the ASH (Free ASH Whitepaper) abstract were as follows:

Of the nine evaluable patients, three patients were treated at each of the three dose levels: dose level 1 (DL1; 30 million CAR+ cells), dose level 2 (DL2; 100 million CAR+ cells), and dose level 3 (DL3; 300 million CAR+ cells). Two patients at DL3 were re-dosed with a second course of ADI-001, per protocol. Six of nine were male (67%) and the median age was 62 years (range 45-75). There were eight patients with large B-cell lymphoma (LBCL) and one with mantle cell lymphoma. Of the eight patients with LBCL, five had diffuse-large B-cell lymphoma (DLBCL), two had high-grade B-cell lymphoma (HGBCL) with double/triple hit, and one had HGBCL not otherwise specified. Indolent lymphomas, such as follicular lymphoma, are currently excluded from the study.
Overall, the patients were heavily pretreated with a median number of prior therapies of four (range 2-5), and had a poor prognostic outlook as indicated by the median International Prognostic Index (IPI) score of four (range 2-4); the median tumor burden was 2,974 (150-7,919) mm2, and 89% (8/9) had stage III/IV disease.
The best overall response rate (ORR) and complete response rate (CR) was 78% (7/9). For the four patients who had prior autologous CD19 CAR T therapies, the ORR and CR rate was 100% (4/4). As of the data-cut date, of the seven patients who had achieved CR, two patients progressed, one died of unrelated causes while in complete remission and four were still in CR and in active follow up, with a range of follow-up time between 1.2 and 8.8 months.
CAR+ gamma delta T cell kinetics in the peripheral blood increased in a dose-dependent manner with peak cell expansion occurring between Days seven and 10 at DL3 based on flow cytometry.
Of the nine patients, there were no ≥ Grade 3 Cytokine Release Syndrome (CRS) or Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) events. Two patients developed CRS: one Grade 1 and one Grade 2. At the time of the ASH (Free ASH Whitepaper) abstract submission, there were three reported related serious adverse events: Grade 2 CRS, Grade 1 ICANS and Grade 3 adenoviraemia. There was no reported graft versus host disease or protocol-defined dose-limiting toxicity events.
Response data were evaluated per Lugano 2014 criteria by independent radiographic review.
The full abstract is available online on the ASH (Free ASH Whitepaper) website.

Clinical data will be presented during a poster presentation by Sattva Neelapu, M.D. at the ASH (Free ASH Whitepaper) Annual Meeting on Saturday, December 10, 2022 from 5:30 – 7:30 p.m. CT. Adicet will provide data from a more recent data-cut date from the Phase 1 study in a press release and company webcast on Sunday, December 11, 2022 at 8:00 a.m. CT/ 9:00 a.m. ET.

Details of the poster presentation are as follows:

Session Title: 704. Cellular Immunotherapies: Early Phase and Investigational Therapies: Poster I
Title: A Phase 1 Study of ADI-001: Anti-CD20 CAR-Engineered Allogeneic Gamma Delta1 (γδ) T Cells in Adults with B-Cell Malignancies
Presenting Author: Sattva Neelapu, M.D., MD Anderson Cancer Center
Date/Time: Saturday, December 10, 2022 from 5:30 – 7:30 p.m. CT.

Adicet ADI-001 Webcast Information

The Company will host a webcast event on Sunday, December 11, 2022, at 8:00 a.m. CT/ 9:00 a.m. ET to discuss recent data from its ongoing Phase 1 clinical study of ADI-001 in relapsed or refractory aggressive B-cell NHL.

About ADI-001

ADI-001 is an investigational allogeneic gamma delta CAR T cell therapy being developed as a potential treatment for relapsed or refractory B-cell NHL. ADI-001 targets malignant B-cells via an anti-CD20 CAR and via the gamma delta innate and T cell endogenous cytotoxicity receptors. Gamma delta T cells engineered with an anti-CD20 CAR have demonstrated potent antitumor activity in preclinical models, leading to long-term control of tumor growth. In April 2022, ADI-001 was granted Fast Track Designation by the U.S. Food and Drug Administration (FDA) for the potential treatment of relapsed or refractory B-cell NHL.

About the GLEAN Study

This Phase 1 study is an open-label, multi-center study of ADI-001 enrolling adults diagnosed with B-cell malignancies who have either relapsed, or are refractory to at least two prior regimens. The primary objectives of the study are to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of ADI-001, and to determine optimal dosing as a monotherapy. The study is expected to enroll approximately 75 patients. For more information about the clinical study design, please visit www.clinicaltrials.gov (NCT04735471).

On November 3, 2022 Ajax Therapeutics, Inc., a biopharmaceutical company applying computational chemistry and structure-based technologies to develop novel, selective small molecules for myeloproliferative neoplasms (MPNs), reported two abstracts have been accepted for oral and poster presentations at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, to be held December 10-13, 2022 in New Orleans (Press release, Ajax Therapeutics, NOV 3, 2022, View Source [SID1234623037]). The presentations highlight preclinical data on Ajax’s next-generation JAK2 inhibitors for the treatment of MPNs.

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On November 3, 2022 Asher Biotherapeutics, Inc. (Asher Bio), a biotechnology company focused on developing therapies to precisely engage specific immune cells to fight cancer, chronic viral infection and autoimmune disease, reported that it will present preclinical data showing that cis-targeted IL-2 or IL-21 cytokine fusion molecules selectively augment CAR-Ts in vitro and enhance in vivo anti-tumor activity and survival at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting being held in New Orleans, Louisiana, December 10-13, 2022 (Press release, Asher Biotherapeutics, NOV 3, 2022, View Source [SID1234623036]).

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Asher Bio’s cis-targeted cytokine fusions consist of a targeting antibody directed against a tag expressed on the CAR-T surface that is co-expressed with the CAR and a cytokine mutein with attenuated binding to its cognate cytokine receptor.

On November 3, 2022 Gamida Cell Ltd. (Nasdaq: GMDA), the leader in the development of NAM-enabled cell therapy candidates for patients with hematological and solid cancers and other serious diseases, reported an oral presentation of a real-world analysis comparing the effectiveness of omidubicel to other allo-HCT donor sources from the Center for International Blood and Marrow Transplant Research (CIBMTR) database (Press release, Gamida Cell, NOV 3, 2022, View Source [SID1234623035]). These data are being presented at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, which is being held in New Orleans from December 10-13, 2022.

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"These data reinforce the clinical relevance of the rapid time to neutrophil engraftment observed in patients transplanted with omidubicel, and support the potential use of omidubicel in patients with hematologic malignancies requiring transplant. We are diligently preparing to bring this important therapy to patients upon potential FDA approval."

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"Data from our phase 3 study compared the safety and efficacy of omidubicel to standard cord blood. We are delighted to have the opportunity, in a podium presentation at ASH (Free ASH Whitepaper), to share the work we have done with CIBMTR, exploring their expansive real-world database and performing the first comparative efficacy analyses between omidubicel and other donor sources for patients undergoing allogeneic stem cell transplant," said Ronit Simantov, M.D., Chief Medical and Scientific Officer of Gamida Cell. "These data reinforce the clinical relevance of the rapid time to neutrophil engraftment observed in patients transplanted with omidubicel, and support the potential use of omidubicel in patients with hematologic malignancies requiring transplant. We are diligently preparing to bring this important therapy to patients upon potential FDA approval."

Details about the ASH (Free ASH Whitepaper) presentation are as follows:

Title: Clinical Outcomes Following Allogeneic Hematopoietic Cell Transplantation with Omidubicel or Other Donor Sources in Patients with Hematologic Malignancies: Comparison of Clinical Trial Results to Center for International Blood and Marrow Transplant Research Database Controls
Session Title: 732. Allogeneic Transplantation: Disease Response and Comparative Treatment Studies: Clinical Outcome: Real World Studies Based on Database Analyses
Lead Author: Smitha Sivaraman, PhD.
Time: Saturday, December 10, 2022, 2:00 p.m. – 3:30 p.m. EST (session time) and 2:30 p.m. EST (presentation time)
Location: Ernest N. Morial Convention Center, 391 – 392

A prospective cohort analysis study to compare the effectiveness of omidubicel versus other allo-HCT donor sources (MUD, MMUD and haploidentical) used in clinical practice is being presented. The study compared data from the omidubicel (n=52) and control arms (n=56) of the phase 3 study with a cohort of similar patients derived from the CIBMTR database (n = 807) who had undergone transplant with matched unrelated donors, mismatched unrelated donors, or haploidentical donors. The analysis showed that omidubicel was associated with more rapid neutrophil recovery (median: 10 days) compared to all other donor sources (median 15-20 days; p<0.001). While platelet recovery took longer in the omidubicel cohort, rates of severe acute and chronic graft versus host disease (GVHD) were comparable. Importantly, analyses of non-relapse mortality, disease-free survival, and overall survival showed similar results among all donor sources. While the phase 3 study compared omidubicel to standard cord blood, these real-world data reinforce the clinical utility of omidubicel as a graft source in patients in need of an allogeneic stem cell transplant.

About Omidubicel

Omidubicel is an advanced cell therapy candidate developed as a potential life-saving allogeneic hematopoietic stem cell (bone marrow) transplant for patients with blood cancers. Omidubicel demonstrated a statistically significant reduction in time to neutrophil engraftment in comparison to standard umbilical cord blood in an international, multi-center, randomized Phase 3 study (NCT0273029) in patients with hematologic malignancies undergoing allogeneic bone marrow transplant. The Phase 3 study also showed reduced time to platelet engraftment, reduced infections, and fewer days of hospitalization. One-year post-transplant data showed sustained clinical benefits with omidubicel as demonstrated by significant reduction in infectious complications as well as reduced non-relapse mortality and no significant increase in relapse rates nor increases in graft-versus-host-disease (GvHD) rates. Omidubicel is the first stem cell transplant donor source to receive Breakthrough Therapy Designation from the FDA and has also received Orphan Drug Designation in the US and EU.

The BLA for omidubicel has been assigned a Prescription Drug User Fee Act (PDUFA) target action date of January 30, 2023. If approved, omidubicel will be the first allogeneic advanced stem cell therapy donor source for patients with blood cancers in need of a stem cell transplant.

Omidubicel is an investigational stem cell therapy candidate, and its safety and efficacy have not been established by the FDA or any other health authority. For more information about omidubicel, please visit View Source

About NAM Technology

Our NAM-enabling technology is designed to enhance the number and functionality of targeted cells, enabling us to pursue a curative approach that moves beyond what is possible with existing therapies. Leveraging the unique properties of NAM (nicotinamide), we can expand and metabolically modulate multiple cell types — including stem cells and natural killer cells — with appropriate growth factors to maintain the cells’ active phenotype and enhance potency. Additionally, our NAM technology improves the metabolic fitness of cells, allowing for continued activity throughout the expansion process.

On November 3, 2022 Pfizer Inc. (NYSE:PFE) reported its investigational cancer immunotherapy, elranatamab, received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for the treatment of people with relapsed or refractory multiple myeloma (RRMM) (Press release, Pfizer, NOV 3, 2022, View Source [SID1234623033]). Elranatamab is a B-cell maturation antigen (BCMA)-CD3-targeted bispecific antibody (BsAb).

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"The FDA’s Breakthrough Designation recognizes the potential of elranatamab as an innovative medicine for people with multiple myeloma whose disease has relapsed or is refractory to existing treatments, which at present leaves very few avenues for staving off this currently incurable cancer," said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology and Rare Disease, Pfizer Global Product Development. "This marks Pfizer’s twelfth FDA Breakthrough Therapy Designation in Oncology, a testament to our relentless commitment to developing transformational cancer medicines in areas of high unmet need. We look forward to working with the FDA to accelerate the development of this therapy."

The FDA’s Breakthrough Therapy Designation is intended to expedite the development and review of a medicine that is intended to treat a serious or life-threatening disease and preliminary clinical evidence indicates the drug may demonstrate substantial improvement over existing therapies.1

BsAbs are a novel form of cancer immunotherapy that bind to and engage two different targets at once. One arm binds directly to specific antigens on cancer cells and the other arm binds to T-cells, bringing both cell types together. Elranatamab is designed to bind to BCMA, which is highly expressed on the surface of multiple myeloma (MM) cells, and the CD3 receptor found on the surface of T-cells, bridging them together and activating the T-cells to kill the myeloma cells. The binding affinity of elranatamab for BCMA and CD3 has been engineered to elicit potent T-cell mediated anti-myeloma activity. Elranatamab is administered subcutaneously, which offers more convenience over intravenous administration, and may mitigate the risk of potential adverse events, such as cytokine release syndrome (CRS).

The Breakthrough Therapy Designation is based on six-month follow-up data from cohort A (n=123) of MagnetisMM-3, an open-label, multicenter, single arm, Phase 2 study evaluating the safety and efficacy of elranatamab monotherapy in patients with RRMM. Patients received subcutaneous (SC) elranatamab 76 mg weekly (QW) with a 2-step-up priming dose regimen administered during the first week. The study showed elranatamab demonstrated a manageable safety profile, and at a median follow-up of 6.8 months, patients achieved an overall response rate (ORR) of 61.0%. Among responders, there was 90.4% probability of maintaining a response ≥6 months. The most common treatment-emergent adverse event (TEAE) regardless of causality was CRS (57.9%), with the majority of events reported being either Grade 1 (43.2%) or Grade 2 (14.2%). Updated data from MagnetisMM-3 will be presented at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition 2022 (ASH 2022), taking place December 10-13, 2022, in New Orleans.

MagnetisMM-3 is part of the robust MagnetisMM clinical research program, which has registration-intent trials planned or ongoing that explore elranatamab both as monotherapy and in combination with standard or novel therapies, spanning multiple patient populations from newly diagnosed multiple myeloma (NDMM), double-class exposed disease and RRMM.

In addition to the Breakthrough Therapy Designation, elranatamab has been granted Orphan Drug Designation by the FDA and the European Medicines Agency (EMA) for the treatment of MM. The FDA and EMA have granted elranatamab Fast Track Designation and the PRIME scheme, respectively, for the treatment of patients with RRMM. The UK Medicines and Healthcare Products Regulatory Agency (MHRA) has also granted elranatamab Innovative Medicine Designation and the Innovation Passport, for the treatment of MM.

About Multiple Myeloma

MM is a blood cancer that affects plasma cells made in the bone marrow. Healthy plasma cells make antibodies that help the body fight infection. According to the latest figures available, there are over 34,000 new cases of MM diagnosed annually in the U.S. and 176,000 globally.2, 3 Despite treatment advances, MM remains incurable. The median overall survival is just over five years, and most patients receive four or more lines of therapy.4

About Pfizer Oncology

At Pfizer Oncology, we are committed to advancing medicines wherever we believe we can make a meaningful difference in the lives of people living with cancer. Today, we have an industry-leading portfolio of 24 approved innovative cancer medicines and biosimilars across more than 30 indications, including breast, genitourinary, colorectal, blood and lung cancers, as well as melanoma.