BioSight developing non-toxic drug against leukemia

Dr. Ruth Ben Yakar

Dr. Ruth Ben Yakar

Closely-held BioSight is in clinical development with its lead chemotherapy drug, Astarabine, as a non-toxic treatment for hematologic malignancies, including acute myeloid leukemia (AML).

“Treatment and outcomes in AML patients have not changed much in decades,” CEO, Dr. Ruth Ben Yakar, says in an interview with, pointing to high toxicity and treatment limitations for a growing population of older patients.

“AML is the most common of all adult leukemias and is the last major hematologic indication with hardly any therapeutic improvement since the 1970s,” she adds.

If left untreated, AML patients will die within a few months. In addition, a majority of patients treated with front-line induction chemotherapy progress to relapsed/refractory AML, where the five-year survival remains at about 20% and about 5% in patients over the age of 65.

While the median age of AML patients is almost 70, Dr. Ben Yakar points out that the median survival rate for newly-diagnosed patients aged 75 and older is extremely poor, largely because of the dose-limiting toxicity of the standard of care, cytarabine, in patients with AML, relapsed/refractory chronic myeloid leukemia (CML), and acute lymphocytic leukemia (ALL).

“Cytarabine is an effective chemotherapy drug, but it is highly toxic, with severe side effects, such as cerebellar toxicity and bone marrow suppression, which significantly limit its use, especially in older patients and those with liver or renal dysfunction,” Dr. Ben Yakar says.

“For decades, and still today, many clinical trials have focused on optimizing the dosage of cytarabine, mainly in older patients,” she adds.

BioSight’s Astarabine is designed as a non-toxic “pro-drug” conjugate of cytarabine and the amino acid, asparagine.

BioSight’s data suggests that as a pro-drug, Astarabine is not active on its own. However, inside a leukemia cell, Astarabine is cleaved into its components, allowing cytarabine’s cancer killing activity to target the leukemia cell, Dr. Ben Yakar contends.

Inside a leukemia cell, Astarabine is cleaved into its components, allowing cytarabine’s cancer killing activity to target the leukemia cell

Inside a leukemia cell, Astarabine is cleaved into its components, allowing cytarabine’s cancer killing activity to target the leukemia cell

She explains that compared to normal cells, cancer cells often require higher amounts of amino acids, including asparagine, to support their metabolism and proliferation. Moreover, certain leukemia cells lack the enzyme, asparagine synthetase, and completely depend on an external source of asparagine.

Hence, leukemia cells have developed transporters to actively take up amino acids from their environment. Part of the company’s technology involves benefiting from these existing mechanisms so that leukemia cells take up Astarabine via its asparagine component and get it into the cells, like a Trojan horse.

“We believe Astarabine may potentially replace cytarabine in all of its clinical indications,” she suggests.

Israel-based BioSight has four worldwide patent families granted and pending that protect Astarabine and its technology, including pharmaceutical composition, uses and methods.

“In preclinical studies with a leukemia mouse model, the maximal tolerated dose of Astarabine was found to be 10-to-15 fold higher than cytarabine,” Dr. Ben Yakar points out.

In terms of efficacy, she says preclinical studies demonstrated that Astarabine can be used at high doses to eliminate tumors, with minimal toxicity to the animals.

BioSight is currently conducting a Phase 1/2a, open-label study in Israel to evaluate safety and efficacy of escalating doses of Astarabine as single agent in 15 refractory/relapsed and newly diagnosed adult patients with AML or ALL.

The primary endpoint is safety; secondary endpoints include efficacy at 90 days.

The trial is scheduled to complete enrollment and treatment during the first quarter this year, with final data available during the first half.

In an abstract presented at ASH last month, interim results from the first nine patients in the study were reported, demonstrating no significant drug-related toxicity or adverse events with high doses of Astarabine, including in patients over 80 years of age.

A response and increased survival was also observed in newly diagnosed patients, with three of the four patients in remission after several months.

Dr. Ben Yakar says BioSight is planning a Phase 2 trial this year in the U.S., Israel and possibly Europe to further investigate the use of Astarabine for patients otherwise unable to receive high doses of cytarabine.

“The response from clinicians who have seen our data has been overwhelmingly positive in terms of Astarabine’s lack of toxicity and potential to treat patients,” she adds.

BioSight Product Pipeline

BioSight Product Pipeline