EDO-S101 combines the active structures of bendamustine and vorinostat, two molecules that are well established in the treatment of haematological malignancies, to produce a novel single agent with efficacy characteristics superior to those of the parent compounds when given in combination.
It is a representative of the A-DAC principle, a new approach in chemotherapy that uses fusion technology to combine an alkylating agent with a pan-histone deacetylase inhibitor (HDAC) to simultaneously damage DNA and block damage repair. 1,2
The combination of the two different modes of action has the potential to overcome resistance towards other conventional chemotherapies. 3
In pre-clinical studies, EDO-S101 administered as monotherapy has been demonstrated to show response, slow disease progression in myeloid and lymphoid malignancies and solid tumours. 1
Initial work suggests that EDO-S101 may: 3,4
- Overcome resistance to some chemotherapy agents, while potentiating the effect of others.
- Offer a more sustained anti-tumour effect than bendamustine and vorinostat either individually or administered concomitantly.
The first clinical study with EDO-S101 is ongoing in patients with relapsed refractory haematological malignancies.
1. López-Iglesias, AA. Blood 2014;124(21):2100.
2. López-Iglesias, AA. Preclinical antimyeloma activity of EDO-S101 (bendamustine-vorinostat fusion molecule) through DNA-damaging and HDACi effects. 15th International Myeloma Workshop. 23−26 September 2015. Rome, Italy.
3. Yan S, Xu K, Lin J, et al. Cancer Research 2012;72(8 Supplement):Abstract 2741.
Rationale for development
Improved chemotherapy with a favourable risk/benefit profile is still needed for most cancer treatments either alone or as part of combination therapy with other chemotherapy agents or targeted therapies such as small molecules and biologics.