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Blood Health 2019

Removing the toxicity from bone marrow transplant conditioning

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Vladislav Sandler

Co-founder and CEO, HemoGenyx

A new method of non-toxic bone marrow transplant conditioning promises to transform the treatment of haematological cancers and autoimmune diseases.

Blood cancers affect more than 1.1 million people annually in the United States alone. More than 150,000 new cases are expected to be diagnosed this year. Unfortunately, some blood cancers, such as acute myeloid leukaemia (AML), are extremely difficult to treat.

In fact, first-round treatments fail in about 70% of all AML cases, and a bone marrow/haematopoietic stem cell transplant (BMT) is the only remaining option. Yet many people can’t tolerate the BMT conditioning process, which carries a high level of toxicity and danger, and are therefore not able to obtain a BMT.

However, newly developed antibodies, currently in pre-clinical trials, could offer a solution — and new hope for blood cancer patients.

Traditional BMT involves a toxic procedure

For nearly half a century, bone marrow transplants have been demonstrated to successfully treat blood cancers and prolong life.

“For many people with leukemia, lymphoma or multiple myeloma, who have failed front line therapy, a BMT is their only viable option,” says Vladislav Sandler, Co-founder and CEO of Hemogenyx, a Brooklyn-based biotechnology company listed on the London Stock Exchange (LSE:HEMO).

Nevertheless, cautions Sandler: “It’s a very difficult procedure that often fails.” That’s because preparing the patient for the procedure involves first administering maximally tolerated doses of a cocktail of chemotherapeutic agents with or without radiation.

These preparative regimes are toxic and can have severe side effects including radiation damage to the heart or lungs, thyroid problems, fertility problems, bone damage, and development of other cancers years later. It is also difficult to eliminate cancer cells that have possibly already developed resistance to drugs during the initial treatment.

“In one sense, you could say that conditioning nearly kills the patient before the BMT tries to save them,” says Sandler. Indeed, between 2-4% of people who undergo a BMT die during the conditioning stage.

‘A walking skeleton’

Sandler knows about the horrors of BMT conditioning first-hand. When Sandler’s father was 63 years old, he was diagnosed with lymphoma.

His doctors started him on an aggressive round of chemotherapy combined with the first generation of immunotherapy and radiation. Almost immediately, he relapsed. That’s when he began the preparation treatment for a BMT.

“He was tortured by the first chemo. Then he was tortured again,” says Sandler. “He was like a walking skeleton.” 

Unfortunately, the conditioning failed to kill the lymphoma. The transplant ultimately failed, and just seven months after his initial diagnosis, Sandler’s father passed away.

A ‘transformative’ approach

Having witnessed his father suffer in his final year of life, Sandler was inspired to found Hemogenyx, which is developing an antibody, code-named CDX, that has the potential to completely reinvent BMT conditioning as well as the treatment of relapsed/refractory AML, increasing the chances of patient survival.

CDX is a bi-specific antibody that works by instructing the patient’s own T-cells to rid the body of unwanted cells, eliminating the need for chemotherapy or radiation and their toxic side effects.

“People won’t lose their hair, their bowels won’t be destroyed, and young women won’t have to freeze their eggs over fertility concerns,” says Sandler. “The difference, potentially, is absolutely transformative.”

Moreover, this approach could make BMTs available to a range of previously ineligible patients, such as those considered too old or weak to contend with the toxicity of conditioning.

Potential for autoimmune diseases

In addition to transforming the treatment of blood cancers, Hemogenyx’s antibodies could expand the use of BMT treatments for patients suffering from severe autoimmune diseases such as lupus, multiple sclerosis and possibly others. 

Evidence points to the efficacy of BMT as a treatment for these diseases, but typically these patients aren’t candidates for BMTs because the chemotherapy and radiation that are currently part of the conditioning stage are too dangerous and the risk/reward profile of the treatment is unfavorable.

Hemogenyx recently created a first generation, humanised mouse-based model of human lupus, which the company is using to better understand the disease. Sandler says two new treatment approaches have been identified. However, he adds, Hemogenyx’s research is “still in the early stages.”

In the meantime, Hemogenyx continues to race toward full development of its CDX antibodies, with a view toward expanding the use of bone marrow transplants in the treatment of blood diseases and other disorders. “It’s a very exciting time in science and research,” says Sandler. “Every day we’re opening up new opportunities for the future.”

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