Astarabine (asparagine cytarabine conjugate) / Ayala Pharma - LARVOL DELTA

BST-236 as a Single Agent in Adults With Relapsed or Refractory AML or HR-MDS (clinicaltrials.gov) - P2 | N=40 | Active, not recruiting | Sponsor: Groupe Francophone des Myelodysplasies | Recruiting ➔ Active, not recruiting

Enrollment closed • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Frontline Aspacytarabine with Venetoclax for Older/Unfit Patients with Acute Myeloid Leukemia: Preliminary Results of a Phase 1 Study (ASH 2023) - "The combination induction regimen of ASPA and VEN followed by consolidation with ASPA alone, is a promising therapy. The regimen is tolerable, and all patients in cohort 2 have attained a CR with 2/3 MRDneg and the third with treatment ongoing. This treatment may overcome the limitations of prolonged cytopenia and indefinite therapy with HMA/VEN along with a high CR rate."

Clinical • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Infectious Disease • Otorhinolaryngology • Pneumonia • Respiratory Diseases • Septic Shock

A Phase II Study of Single Agent Aspacytarabine (BST-236) in Adults Unfit for Intensive Chemotherapy with Relapsed or Refractory Acute Myeloid Leukemia (R/R AML) or Higher Risk Myelodysplastic Syndromes (R/R HR MDS) (ASH 2023) - P2 | "MDS pts were refractory or had relapsed to azacytidine (AZA), and AML pts to AZA, low-dose cytarabine (LDAC) or AZA -venetoclax (VEN), given as a first line regimen. Conclusion— Response rates with BST-236, in this pretreated older frail R/R AML and MDS population, were modest. Toxicity, including myelosuppression, however appears lower than with conventional intensive chemotherapy, suggesting this treatment could be interesting earlier in the disease course."

Clinical • P2 data • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Hepatology • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • Septic Shock

Aspacytarabine for the treatment of patients with AML unfit for intensive chemotherapy: a phase 2 study. (PubMed, Blood Adv) - P2b | "Adverse events typically precluding the use of high-dose cytarabine in older or unfit patients were not observed. Aspacytarabine appears to be an effective regimen, with a reduction in the attendant toxicities associated with high-dose cytarabine, an important consideration when treating AML and other hematologic disorders that use high-dose cytarabine."

Journal • P2 data • Acute Myelogenous Leukemia • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • TP53

Ayala Pharmaceuticals Announces Closing of Merger with Biosight (GlobeNewswire) - "Ayala Pharmaceuticals, Inc...today announced the closing of its merger with Biosight, Ltd...pursuant to which Ayala acquired Biosight. The combined company will operate under the name Ayala Pharmaceuticals, Inc., and its shares will continue to trade on the OTCQX under Ayala’s current ticker symbol ('ADXS')....'We have added aspacytarabine (BST-236), a novel antimetabolite, which is in clinical development for AML and could potentially serve as a superior backbone therapy for unfit AML as part of combination treatment regimens. Our primary focus continues to be completing the ongoing Phase 3 RINGSIDE study evaluating AL102 in desmoid tumors and we look forward to continuing our mission of bringing innovative therapies to people with rare tumors and aggressive cancers.'"

M&A • Acute Myelogenous Leukemia • Desmoid Tumors • Hematological Malignancies • Leukemia • Oncology • Solid Tumor

ELPIS: Efficacy and Safety of BST-236 in Newly Diagnosed Acute Myeloid Leukemia Patients, Unfit for Standard Induction Therapy (clinicaltrials.gov) - P2b | N=66 | Completed | Sponsor: BioSight Ltd. | Active, not recruiting ➔ Completed | Trial primary completion date: Dec 2022 ➔ Mar 2023

Trial completion • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Ayala Pharmaceuticals and Biosight Enter into Definitive Merger Agreement (GlobeNewswire) - "Ayala Pharmaceuticals, Inc...today announced they have entered into a definitive merger agreement pursuant to which Ayala will combine with Biosight in an all-stock transaction. Upon completion of the merger, the combined company will operate under the name Ayala Pharmaceuticals, Inc., and will continue to trade on the OTCQX under Ayala’s current ticker symbol ('ADXS'). Certain of the current Biosight shareholders have agreed to support the proposed transaction. The combined company will work to advance a portfolio of oncology assets, with a primary focus on Ayala’s AL102, a once-daily, potent, selective, oral gamma-secretase inhibitor (GSI) and Biosight’s Aspacytarabine (BST-236)."

M&A • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Desmoid Tumors • Hematological Malignancies • Leukemia • Multiple Myeloma • Myelodysplastic Syndrome • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Phase 2, Open-Label, Single Arm Study, With BST-236 in Adults With R/R AML or Higher-Risk MDS (clinicaltrials.gov) - P2 | N=40 | Active, not recruiting | Sponsor: BioSight Ltd. | Recruiting ➔ Active, not recruiting

Enrollment closed • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

BST 236, A NOVEL CYTARABINE PRO-DRUG ALLOW, FOR THE FIRST TIME, THE DELIVERY OF HIGH CYTARABINE DOSES FOR OLDER OR UNFIT PATIENTS WITH ACUTE LEUKEMIA. RESULTS OF AN ONGOING PHASE I/IIA STUDY (EHA 2017) - "BST-236 (Astarabine) is a new compound of cytarabine covalently bound to asparagine. BST-236 is safe and very well tolerated, enabling delivery of high dose cytarabine to older and unfit patients, resulting in overall response and CR rates of 50% and 33%, respectively, and a 3-fold increase in median OS of the responding compared to the non-responding newly-diagnosed patients. Notably, 67% of the responding patients had secondary AML, refractory to hypomethylating agents. To the best of our knowledge, this is the only experimental drug permitting high-dose cytarabine, considered a cornerstone of leukemia therapy, to be given to a population of patients that currently do not have this option."

Adverse events • Clinical • P1/2 data • Acute Myelogenous Leukemia • Biosimilar • Immunology

ELPIS: Efficacy and Safety of BST-236 in Newly Diagnosed Acute Myeloid Leukemia Patients, Unfit for Standard Induction Therapy (clinicaltrials.gov) - P2b | N=65 | Active, not recruiting | Sponsor: BioSight Ltd. | Trial completion date: Dec 2022 ➔ May 2023

Trial completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Biosight Launches a Phase 1/2 Clinical Trial of Aspacytarabine in Combination with Venetoclax for First-Line AML Induction Therapy, Followed by Aspacytarabine Consolidation (PRNewswire) - "Biosight...announced enrollment of a first patient to a phase 1/2 clinical trial designed to evaluate the safety and efficacy of its lead asset aspacytarabine (BST-236) in combination with the BCL2 inhibitor venetoclax for induction therapy of newly-diagnosed Acute Myeloid Leukemia (AML), followed by aspacytarabine single-agent consolidation therapy. The trial, conducted in leading clinical centers in the United States, enrolls newly-diagnosed AML patients who are unfit for standard induction chemotherapy due to age or comorbidities."

Trial status • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Aspacytarabine (BST-236) As Monotherapy Is Safe, Well-Tolerated and Effective for the Treatment of Adults with Newly Diagnosed Acute Myeloid Leukemia Unfit for Intensive Therapy. Results of a Phase 2 Study (ASH 2021) - P2b | "Patients with secondary or therapy related AML, and patients who received prior hypomethylating agents (HMA) ± venetoclax therapy for a preceding condition were eligible. The results of the phase 2b study are consistent with the previously completed phase 1/2a study, which demonstrated safety and a 36% CR rate in a similar population, suggest that aspacytarabine, given as monotherapy, is generally safe and effective as a first-line therapy for AML patients who are unfit for intensive chemotherapy These data support a role for aspacytarabine as a new treatment option for older patients with AML. Furthermore, this agent may serve as a backbone for combination therapy with targeted or other chemotherapy agents, as well as in younger patients with AML."

Clinical • Monotherapy • P2 data • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Oncology

BST-236 (ASCO 2017) - P1/2; "BST-236 is safe and very well tolerated, enabling delivery of high dose cytarabine to old patients, resulting in overall response and CR rates of 50% and 33%, respectively and increased OS. Notably, 67% of the responding patients had secondary AML, refractory to hypomethylating agents. A phase II study is planned to confirm these encouraging results."

Adverse events • Clinical • Acute Myelogenous Leukemia • Biosimilar • Hematological Malignancies • Immunology • Leukemia • Oncology

A Phase I/II Dose Escalation and Expansion Study of BST-236 Plus Venetoclax in Patients With Unfit Newly Diagnosed AML (clinicaltrials.gov) - P1/2 | N=80 | Recruiting | Sponsor: BioSight Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

A Phase I/II Dose Escalation and Expansion Study of BST-236 Plus Venetoclax in Patients With Unfit Newly Diagnosed AML (clinicaltrials.gov) - P1/2 | N=80 | Not yet recruiting | Sponsor: BioSight Ltd.

New P1/2 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Biosight Granted Orphan Drug Designation from the FDA for Aspacytarabine for the Treatment of Myelodysplastic Syndromes (PRNewswire) - "Biosight Ltd...announced today that the United States Food & Drug Administration (FDA) has granted Orphan Drug Designation to aspacytarabine (BST-236), an investigational novel antimetabolite, for the treatment of myelodysplastic syndromes..."

Orphan drug • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

[VIRTUAL] Efficacy and safety of aspacytarabine (BST-236) as a single-agent, first-line therapy for patients with acute myeloid leukemia unfit for standard chemotherapy. (ASCO 2021) - P2b | "The cumulative clinical data suggest that aspacytarabine, a time-limited single-agent treatment, is safe and efficacious as a first-line therapy for patients who are unfit for intensive chemotherapy, which may establish it as a new tolerable AML chemotherapy backbone."

Clinical • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Oncology

Phase 2, Open-Label, Single Arm Study, With BST-236 in Adults With R/R AML or Higher-Risk MDS (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: BioSight Ltd. | Not yet recruiting ➔ Recruiting | Trial primary completion date: Aug 2023 ➔ Dec 2023

Enrollment open • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Aspacytarabine Shows Promise in Newly-Diagnosed Acute Myeloid Leukemia (Targeted Oncology) - "'These final complete remission data are extremely encouraging and strengthen our conviction in the potential of aspacytarabine as a potential standard-of-care treatment option for AML patients,' said Jessica Altman MD....'Notably, a complete remission rate of 37% was achieved in a challenging patient population, including patients with secondary AML, prior hypomethylating agent treatment, and older age. While follow-up is still ongoing, the efficacy data across key measures, including duration of response and overall survival, combined with a favorable safety profile and a time-limited treatment of up to 4 courses, all form the basis for my confidence in aspacytarabine as a novel therapy for the treatment of patients with AML.'"

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Aspacytarabine May Be Viable Option for Patients with AML Who Are Unfit for Intensive Therapy (Oncology Nursing News) - "'These final CR data are extremely encouraging and strengthen our conviction in the potential of aspacytarabine as a potential standard-of-care treatment option for [patients with] AML,' Jessica Altman, MD...stated in a press release. 'Notably, a CR rate of 37% was achieved in a challenging patient population, including [those] with secondary AML, prior HMA treatment, and older age.'"

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Biosight Reports Final Primary Endpoint Data from Phase 2b Study of Aspacytarabine (BST-236) for First-Line Acute Myeloid Leukemia Therapy (GlobeNewswire) - P2b, N=65; ELPIS (NCT03435848); Sponsor: BioSight Ltd.; "These results, presented at the 2021 American Society of Hematology (ASH) Annual Meeting held in December, 2021, demonstrated efficacy, safety, and tolerability of BST-236 as a monotherapy in treatment of newly-diagnosed AML patients unfit for standard induction therapy....Patients were treated with up to four 6-day courses of aspacytarabine at a dose of 4.5 g/m2/d; aspacytarabine was well-tolerated, CR rates were 37% across all evaluable patients (n=65), 27% in patients with prior HMA ± venetoclax therapy (n=11), 44% in de novo AML patients (n=39), 27% in secondary AML patients (n=26), 35% in patients ≥ 75 years old (n=34), and 32% in patients with adverse ELN risk scores (n=34)."

P2b data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Aspacytarabine Yields Reduced Toxicity as a First-Line Regimen in AML (HMP Global) - "'Due to the pharmacokinetics and metabolism of aspacytarabine, the peak toxic systemic exposure to cytarabine is decreased, resulting in reduced systemic toxicity with relative sparing of normal tissues, thus enabling delivery of high cytarabine doses to patients with AML otherwise unfit to receive intensive cytarabine therapy,' explained Jessica Altman, MD...and co-researchers."

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Biosight Announces Initiation of Phase 2 Clinical Trial of Aspacytarabine for MDS and AML (Yahoo Finance) - "Eytan Stein, M.D...and lead investigator of the study said 'I'm encouraged by the results from Biosight’s Phase 2b trial to be presented at the 63rd American Society of Hematology (ASH) Annual Meeting. The efficacy achieved in a challenging population, across key measures including complete remission and MRD (-) rates, duration of response and overall survival, are noteworthy. Furthermore, these results were particularly impressive as they were achieved with a favorable safety and tolerability profile in patients who are unfit for intensive chemotherapy. Patients with relapsed or refractory AML and MDS have limited treatment options and poor prognoses, with many patients unable to tolerate intensive chemotherapy. I look forward to leading this new Phase 2 study to evaluate the potential of aspacytarabine which may ultimately become the standard of care for relapsed or refractory MDS and AML patients for whom currently there are no effective treatments.'"

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Biosight Announces Initiation of Phase 2 Clinical Trial of Aspacytarabine for MDS and AML (GlobeNewswire) - "Biosight Ltd....announced the initiation of a Phase 2 trial to evaluate aspacytarabine (BST-236), Biosight’s proprietary antimetabolite, as a second line treatment for patients with relapsed or refractory myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). The multi-center study will be conducted across 18 leading U.S. and Israeli sites including Memorial Sloan Kettering Cancer Center and The University of Texas MD Anderson Cancer Center."

Trial status • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

[VIRTUAL] EFFICACY AND SAFETY OF ASPACYTARABINE (BST-236) AS A FIRST-LINE MONOTHERAPY FOR PATIENTS WITH ACUTE MYELOID LEUKEMIA UNFIT FOR STANDARD CHEMOTHERAPY (EHA 2021) - "Conclusion The cumulative clinical data suggest that aspacytarabine monotherapy is safe and efficacious as a first-line therapy for patients who are unfit for intensive chemotherapy, including patients with adverse cytogenetics and patients ≥75 year of age. The data may establish aspacytarabine, already granted Fast Track designation from the FDA, as a new intensive therapy backbone of AML and may, for the first time, allow older adults benefit from standard intensive therapy."

Clinical • Monotherapy • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Oncology