On December 7, 2020 ERYTECH Pharma (Nasdaq & Euronext: ERYP), a clinical-stage biopharmaceutical company developing innovative therapies by encapsulating therapeutic drug substances inside red blood cells, reported that results from the NOPHO sponsored Phase 2 trial of eryaspase in ALL patients, which were presented by Dr. Line Stensig Lynggaard at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting yesterday (Press release, ERYtech Pharma, DEC 7, 2020, View Source [SID1234572280]). In a webcast later today, Dr. Birgitte Klug Albertsen, Associate Professor at Aarhus University Hospital, Denmark, and Principal Investigator of the trial, will comment on the data and be available for Q&A.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The Phase 2 NOR-GRASPALL-2016 trial evaluated the safety and pharmacological profile of eryaspase in ALL patients who had previously experienced hypersensitivity reactions to pegylated asparaginase therapy. The trial was conducted by the Nordic Society of Pediatric Hematology and Oncology (NOPHO) at 21 clinical sites in the Nordic and Baltic countries of Europe and enrolled 55 patients. Primary objectives of the trial were asparaginase enzyme activity and safety. Both endpoints were met.

Eryaspase demonstrated sustained asparaginase enzyme activity above the threshold of >100 U/L at trough levels, 14 days after first infusion in 54 of the 55 patients treated.

Eryaspase was generally well tolerated when added to chemotherapy and almost all patients were able to receive the intended courses of asparaginase (median of 5 doses per patient). Of the 55 patients, only 2 patients had severe allergic reaction and withdrew eryaspase treatment.

Dr Line Stensig Lynggaard, the study leader for NOPHO, commented: "Maintaining adequate asparaginase treatment following hypersensitivity to PEG-asparaginase remains an important goal when treating patients with ALL. A global shortage of supply Erwinia-derived asparaginase, which is the current alternative treatment option to PEG-asparaginase, highlights the need for new alternative treatment options. Our study has demonstrated that eryaspase, given as a convenient schedule every two weeks, provides a sustained asparaginase enzyme activity level, few hypersentivity reactions and is generally well tolerated in combination with chemotherapy. We conclude that eryaspase is an attractive treatment alternative for ALL patients with hypersensitivity to PEG-asparaginase."

"We are proud to be working with the NOPHO group in conducting this study in ALL and very grateful to them for presenting the findings at ASH (Free ASH Whitepaper) this year. The full study results provide the possibility of an alternative treatment for ALL patients with hypersensitivity to PEG-asparaginase" said Dr. Iman El-Hariry, ERYTECH’s Chief Medical Officer. "We look forward to discussing further the potential path forward for eryaspase in ALL with regulatory authorities, including the FDA".

A related eryaspase poster will be presented by Dr. Frank Hoke (ERYTECH’s Head of Clinical Pharmacology) on Monday 7th December 2020 from 8am PST / 11am EST / 5pm CET.

Abstract #2799: Population Pharmacokinetics of Eryaspase in Patients with Acute Lymphoblastic Leukemia or Pancreatic Adenocarcinoma

The analysis shows the extended circulation time of eryaspase, provides information on patient factors that influence the exposure of eryaspase, and evaluates patient population (pancreatic cancer vs ALL) and formulation (native vs recombinant asparaginase). Specifically, the simulations demonstrate that 100 U/kg dosed every two weeks would achieve the clinical AEA target levels of 100 U/L at trough in approximately 95% of patients.

The abstract (#2799) can be found at: View Source

Webcast Details

ERYTECH will hold a webcast later today, Monday, December 7, at 4:00 pm CET / 10:00am ET.

Dr. Birgitte Klug Albertsen, Associate Professor at Aarhus University Hospital, Denmark, and Principal Investigator of the trial, Dr. Iman El-Hariry, Chief Medical Officier of ERYTECH Pharma, and Gil Beyen, Chief Executive Officer of ERYTECH Pharma, will comment on the data and be available for Q&A.

The webcast can be followed live online via the link: View Source

Conference ID#: 2272914#

About Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia (ALL) is a cancer of the blood and bone marrow that is the most common type of cancer in children in the US and Europe. More than 13,000 cases are diagnosed in the US and Europe each year with the majority of patients diagnosed before age 20. Asparaginase has been an integral component of ALL treatment for several years but is associated with treatment-limiting hypersensitivity in up to 30% of patients. Discontinuation of asparaginase therapy in ALL patients has been associated with inferior event free survival highlighting the need for additional asparaginase based treatment options.

On December 6, 2020 Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T) therapies for cancer, reported preclinical findings of ALLO-316, an AlloCAR T therapy targeting CD70, in models of acute myeloid leukemia (AML) (Press release, Allogene, DEC 6, 2020, View Source [SID1234572473]). Data were presented in a poster session today at the 62nd Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The Company also announced that the U.S. Food and Drug Administration (FDA) has cleared an Investigational New Drug (IND) application for a Phase 1 trial of ALLO-316 for patients with advanced or metastatic clear cell renal cell carcinoma (RCC). The Company’s first solid tumor trial is expected to begin enrolling patients in 2021.

"We are very excited about the potential of ALLO-316, our fourth AlloCAR T investigational therapy, to treat patients with CD70 expressing malignancies across both hematologic and solid tumor indications," said Rafael Amado, M.D., Executive Vice President of Research & Development and Chief Medical Officer of Allogene. "These preclinical results in AML, coupled with previous findings of ALLO-316 in RCC presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in 2019, reinforce our belief that CD70 may become one of the more important targets across a broad spectrum of cancers."

CD70 is expressed in a number of malignancies ranging from solid tumors such as RCC, lung cancer and glioblastoma to hematologic cancers including AML, diffuse large B-cell lymphoma, multiple myeloma, and chronic lymphocytic leukemia.

In the preclinical studies presented at ASH (Free ASH Whitepaper), CD70 expression was detected on AML cell lines and primary AML samples from patients. No expression of CD70 was identified in hematopoietic stem cells. ALLO-316 demonstrated the ability to mediate efficient killing of leukemic cells in multiple models. This killing activity was specific to CD70 expression on the target cells as ALLO-316 did not kill AML cell lines in which CD70 was knocked out. The preclinical studies also showed that ALLO-316 can mask CD70 on the surface of CAR T cells thereby preventing fratercide and allowing scaled manufacturing of AlloCAR T cells.

On December 6, 2020 Aptose Biosciences Inc. ("Aptose") (NASDAQ: APTO, TSX: APS) reported that highlights from a corporate update event held on Sunday, December 6th, in conjunction with participation at the 2020 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Aptose Biosciences, DEC 6, 2020, View Source [SID1234572343]). The Aptose management team reviewed the current clinical status of CG-806, Aptose’s oral, first-in-class FLT3 and BTK cluster selective kinase inhibitor currently in two Phase 1 a/b trials, one trial in patients with relapsed or refractory acute myeloid leukemia (AML), and the other trial in patients with relapsed or refractory B cell malignancies; and the team also reviewed the clinical status of APTO-253, a first-in-class small molecule MYC inhibitor in a Phase 1 a/b trial in patients with relapsed or refractory AML or high risk myelodysplastic syndrome (MDS).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The webcast of the presentation is available on Aptose’s website here.

Aptose provided a recap on CG-806 and included the following key highlights:

B-cell malignancy trial

Increasing plasma exposure with increased dose levels, with sustained steady state concentration (trough level) above 2M in the latest cohort (750mg)
Progressive accrual of leading indicators of pharmacologic and clinical activity to date, including robust inhibition of multiple key oncogenic target pathways (including BTK) on target lymphocytosis in classic CLL patients, and modest tumor reductions in different tumor types
Latest cohort (750mg) currently under expansion following a possibly drug-related DLT, however subsequent data and analyses suggest this event is unlikely related to study drug
Generally well tolerated with no toxicity trends to date that would prevent dose escalation
Based on clinical observations to date, study enrollment now focused on certain types of CLL patients
AML trial

Initiated dosing with 450mg BID as potentially active dose based on target engagement analyses
Rapidly enrolled four patients on study drug, including both FLT3-ITD and FLT3-WT
Initial PK data consistent with exposures observed with 450mg dose level in CLL/NHL patients
Observed potential anti-leukemic activity in one heavily pretreated FLT3+ AML patient, including reduction in the percentage of peripheral blood blast count from 93% to 10% in cycle one
Generally well tolerated with no toxicity trends to date that would prevent dose escalation
Aptose also reviewed the current status of APTO-253:

Continued favorable safety and tolerability in heavily pretreated patients with relapsed or refractory AML and MDS
Continued dose-related exposure, with sustained active drug species in the 2-3µM range at the fourth dose level of 100mg/m2
Observed reductions in MYC expression in PBMCs in 24 hours following dosing in most patients
Continuing dosing of patients at the fifth dose level of 150mg/m2
"The on-target lymphocytosis and modest nodal reductions we have observed in CLL patients being treated with CG-806 may be leading indicators of potential eventual responses, similar to what has been observed in the development of other successful BTK inhibitors," said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer. "We are encouraged by the continued increase in plasma exposure, and we hope the current and future dose levels will deliver formal responses to these deeply relapsed or refractory CLL patients. In AML, we are pleased by the observation of an anti-leukemic blast reduction from 93% to 10% in one of our first patients who was heavily pretreated with several consecutive FLT3 inhibitors. For APTO-253, we continue to escalate the dose and observe MYC repression, suggesting future potential for broad anti-cancer activity. We are pleased by such indicators of activity from both CG-806 and APTO-253, and we look forward to providing further updates in the first half of 2021 and at the Annual EHA (Free EHA Whitepaper) Meeting 2021."

In addition, early clinical data, along with certain preclinical data for CG-806 and APTO-253, were presented at the ASH (Free ASH Whitepaper) Annual Meeting and Exposition. The posters are now available on the presentations page of Aptose website here.

On December 6, 2020 CARsgen Therapeutics, a clinical-stage biopharmaceutical company, reported updated safety and efficacy results from its ongoing global clinical studies of CT053, an investigational chimeric antigen receptor (CAR) T-cell therapy for patients with relapsed and/or refractory multiple myeloma (RRMM) (Press release, Carsgen Therapeutics, DEC 6, 2020, View Source [SID1234572262]). The data were presented virtually in two oral sessions and one poster session at the 62nd Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) held December 5-8, 2020.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

CT053 is a CAR T-cell therapy that targets B-cell maturation antigen (BCMA), a protein expressed on the surface of malignant plasma cells in multiple myeloma. CT053 notably uses a fully human anti-BCMA scFv domain, hypothesized to reduce immunogenicity and improve safety. The results for a total of 58 patients treated with CT053 CAR T cells in three studies were presented at the ASH (Free ASH Whitepaper) meeting.

Two years of follow-up data for 24 patients with RRMM in poor clinical condition who received CT053 in three parallel investigator-initiated studies were shown in the oral presentation given by Siguo Hao, MD PhD, from Xinhua Hospital affiliated with Shanghai Jiao Tong University School of Medicine.1 Data from these studies in China demonstrated an overall response rate (ORR) of 87.5%, with a median duration of response of 21.8 months, and median progression-free survival reached 18.8 months. The complete response/stringent complete response (CR/sCR) rate was 79.2% as defined by the International Myeloma Working Group Uniform Response Criteria for multiple myeloma. As of the June 30,2020 cutoff date, a total of 9 patients who had no evidence of myeloma in the bone marrow, known as minimal residual disease, continued to maintain CR/sCR. No grade 3 or higher cytokine release syndrome (CRS) events occurred, indicating the safety and tolerability of CT053 CAR T cells.

"We are encouraged by CT053’s remarkable duration of response given that response times to new multiple myeloma treatments generally shorten with each successive therapy. The treatment of CT053 was generally well tolerated in patients with refractory/relapsed multiple myeloma," shared Dr. Hao.

In the United States, 20 patients with RRMM have received CT053 in the ongoing Phase 1b single-arm, open, multicenter study (LUMMICAR STUDY 2).2 Shaji Kumar, MD, Professor of Medicine, Division of Hematology, Department of Internal Medicine, Mayo Clinic, gave the oral presentation reporting on these early data. As of the November 11, 2020 cutoff date, 20 heavily pretreated patients with RRMM [median 5 prior lines (range 3–11 lines); 25% extramedullary disease; 55% high-risk cytogenetics; 85% triple-refractory; 50% penta-refractory] received CT053: 14 patients received 1.5–1.8×108 cells and 6 patients received 2.5–3.0×108 cells. The patients tolerated treatment well with no grade 3 or higher CRS. No dose-limiting toxicities were observed, and the safety profile corresponded with that observed in the China studies. The first 18 patients who completed at least 8 weeks of efficacy follow-up experienced an ORR of 94% with a time to response of 1–3 months. Responses deepened after longer follow-up. The CAR T cells expanded well in vivo, and CAR copies were detected for at least 6 months.

"The CT053 data in the U.S. provide additional support that the fully human BCMA-specific scFv with fine-tuned binding affinity could be beneficial in managing patients with relapsed and refractory multiple myeloma," summarized Hong Ma, MD, Senior Vice President Clinical Development, CARsgen Therapeutics. "We have observed early and deep responses with CT053 in the study."

Wenming Chen, MD PhD, from Beijing Chaoyang Hospital, presented a poster reporting results from the ongoing a single-arm, open, multicenter Phase 1 clinical trial in China (LUMMICAR STUDY 1).3 As of the September 28, 2020 cutoff date, a total of 14 heavily pretreated patients with RRMM received CT053: 3 patients received 1.0×108 cells and 11 patients received 1.5×108 cells. The 14 patients tolerated treatment well. No dose-limiting toxicities occurred, no grade 3 or higher events of CRS or CRS-related encephalopathy were observed, and no anti-CT053 antibodies were detected. All 14 patients responded, resulting in an ORR of 100%.

"Our data showed that CT053 was well tolerated in patients with relapsed and refractory multiple myeloma and that significant and long-lasting responses were observed in patients despite heavy prior treatment," said Zonghai Li, Founder, President, CEO, and CSO of CARsgen Therapeutics. "The cells expanded well in vivo, and anti-CT053 immunogenicity was not detected. CT053 cells have the potential to be a breakthrough product for the treatment of relapsed and refractory multiple myeloma."

About CT053 and LUMMICAR
CT053 is a CAR T-cell therapy that targets B-cell maturation antigen (BCMA), a protein expressed on the surface of malignant and normal plasma cells in the blood. The CT053 construct utilizes a fully human anti-BCMA scFv domain, hypothesized to reduce immunogenicity and improve safety. CT053 T cells are proposed to recognize, bind, and eradicate multiple myeloma cells that express BCMA.

CT053 has received regenerative medicine advanced therapy (RMAT) and orphan drug designations from the U.S. Food and Drug Administration and PRIority MEdicines (PRIME) and orphan drug designations from the European Medicines Agency.

CARsgen Therapeutics’ clinical development program for CT053 includes the clinical studies: LUMMICAR STUDY 1 (NCT03975907 Phase 1, China) and LUMMICAR STUDY 2 (NCT03915184 Phase 1b/2, United States and Canada). These are open-label, multicenter studies evaluating the safety and efficacy of CT053 in adult patients with RRMM. CT053 studies also include three investigator-initiated trials (NCT03380039; NCT03716856; NCT03302403 Phase 1, China). For more information, visit clinicaltrials.gov.

References:

Hao S, Jin J, Jiang S, et al. Two-year follow-up of investigator-initiated Phase 1 trials of the safety and efficacy of fully human anti-BCMA CAR T cells (CT053) in relapsed/refractory multiple myeloma. Blood. 2020;136(suppl 1):27–28. View Source
Kumar SK, Baz RC, Orlowski RZ, et al. Results from LUMMICAR–2: a Phase 1b/2 study of fully human B-cell maturation antigen-specific CAR T cells (CT053) in patients with relapsed and/or refractory multiple myeloma. Blood. 2020;136(suppl 1):28–29. View Source
Chen W, Fu C, Cai Z, et al. Results from LUMMICAR-1: a Phase 1 study of fully human B-cell maturation antigen-specific CAR T cells (CT053) in Chinese subjects with relapsed and/or refractory multiple myeloma. Blood. 2020;136(suppl 1):49–50. View Source

On December 6, 2020 Amphivena Therapeutics, a clinical-stage oncology company focused on developing immunotherapeutics that restore anti-cancer immunity in patients, reported that data on a novel assay for selection of acute myeloid leukemia (AML) patients for treatment with AMV564, at the 62nd Annual American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting and Exposition (ASH 2020), taking place virtually from December 5-8, 2020 (Press release, Amphivena Therapeutics, DEC 6, 2020, View Source [SID1234572261]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

AMV564 is the lead candidate from the AMPHIVENA ReSTORETM (Relieve Suppression of T cells in Oncology and Reinvigorate Effectors) platform of bivalent T-cell engagers, and has been studied in 2 Ph1 clinical studies in relapsed/refractory AML (NCT03144245) and in patients with advanced solid tumor malignancies (NCT04128423). AMV564 selectively depletes both myeloid derived suppressor cells (MDSC) and leukemic blasts via avid binding to clustered CD33, has been well tolerated with no dose-limiting toxicities reported and has shown single-agent activity across both R/R AML and solid tumors.

This novel assay could identify patients most likely to experience deeper and more durable responses with AMV564 therapy

The assay leverages the selectivity of AMV564 in a screening format to identify AML patients in whom leukemic blasts are expressing CD33 in a predominantly clustered configuration. "While AMV564 has demonstrated early signs of efficacy and anti-leukemic blast activity across an unselected relapsed/refractory AML population, this novel assay could identify patients most likely to experience deeper and more durable responses with AMV564 monotherapy", said Curtis Ruegg, Ph.D., President and CEO of Amphivena.

Details of the Presentation:

Title:

Selectivity of T Cell Engager AMV564 Against Different Leukemic Blast Populations and Potential Application for Patient Selection

Authors:

Sarde, A. et al.

Abstract Number:

1976

Session:

Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Poster II

Poster Viewing:

Sunday, December 6, 2020: 7:00 AM-3:30 PM EST

The abstract and presentation are available on the ASH (Free ASH Whitepaper) Annual Meeting, and Amphivena websites.

About AMV564

AMV564 relieves immune suppression via targeted depletion of immunosuppressive myeloid derived suppressor cells (MDSC) and drives T cell activation and polarization to restore anti-cancer immunity. To date, over 95 patients have received AMV564 across three Phase 1 clinical trials for patients with solid tumors, acute myeloid leukemia (AML), and myelodysplastic syndromes (MDS).