In an acceleration of the TMAC programme, Avacta is now in a position to test this critical TMAC linker in humans, a major de-risking milestone for the programme, early in 2020 and well ahead of its original plans.
Avacta’s tumour microenvironment activated drug conjugates (TMAC) are a ground-breaking new form of cancer immunotherapy, co-invented with Tufts University Medical School, combining Affimers with chemotherapies in a single drug using a linker that is designed to only release the chemotherapy in the tumour microenvironment. This allows extremely potent chemotherapies, too potent to be given to patients systemically, to be combined with Affimer immune-checkpoint therapies.
In order to test the TMAC linker in humans for the first time, a standard-of-care chemotherapy called doxorubicin has been modified with the linker rendering it inactive and harmless until the linker is cleaved in the tumour releasing active doxorubicin. Doxorubicin has well documented safety issues limiting its dosing, and also limiting the patient sub-group that can be treated. Despite these issues, the global doxorubicin market is valued at $910m and is expected to reach $1.4bn by the end of 2025. Avacta’s TMAC linker has been shown to increase the maximum tolerated dose of doxorubicin by a factor of six in a pre-clinical study in mice.
Avacta plans to submit an IND/CTA application for a phase I clinical study of the TMAC linker-doxorubicin early in 2020. The phase I trial will comprise a dose escalation study in patients with selected solid tumours including advanced and metastatic high-grade soft tissue sarcoma. Successful functioning of the TMAC linker will be reflected in tumour shrinkage as a result of the release of doxorubicin. Potentially the study will also demonstrate improved tolerability over standard doxorubicin.
The cancer immunotherapy market is currently worth $60bn and is predicted to double by 2025. Avacta’s TMAC and bispecific cancer immunotherapies are designed not only to compete strongly in this market through improved clinical benefit to patients but also to expand the market to patients who do not respond to single checkpoint inhibitors. Avacta has exclusive rights to commercialise TMAC drug conjugates.
“What is so attractive about Avacta’s Affimer TMAC programme is that it offers a way to combine chemotherapy with immune checkpoint inhibitors without exposing the whole body to the same level of the chemo-toxin.
Whilst immunotherapies offer great promise for cancer patients, it is well established that only a relatively small sub-group of patients see durable responses to single immune checkpoint therapies. Avacta is directly addressing this urgent clinical need with its novel Affimer TMAC and bispecific programmes.
The function of the linker in the TMAC is critical and I am delighted that the planned phase I study will allow us to test it well ahead of our original schedule. This is an important de-risking step for the TMAC programme and could be a catalyst for spin-off licensing opportunities for a range of chemotherapies with improved tolerability. The testing of an Affimer PD-L1 inhbitor, which will form part of the first full TMAC drug and be the foundation for bispecific Affimer immunotherapies, will be the subject of an IND application later in 2020.
It is a hugely exciting period for Avacta and I look forward to keeping the market updated on our progress.”
Dr Jose Saro MD, Chief Medical Officer, commented: “The TMAC linker is a key element of this ground breaking technology and we are excited to have the opportunity to test it in the clinic very soon. If successful, not only does it de-risk the TMAC platform, but it has the potential to significantly increase any chemotherapy therapeutic index allowing higher chemotherapy exposure in the tumor microenvironment to be maintained for a longer period with reduced systemic toxicity.
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This could be one of the most important current advances in developing safer combinations of immunotherapies with chemotherapies and help Avacta to define a new Affimer-based standard of care in several solid tumours.”
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