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Barr Ellison Solicitors – commercial property
6 June, 2019 - 13:08 By Tony Quested

Avacta shows human touch with cancer breakthrough

Dr Alastair Smith Avacta

A Cambridge company tilting at a $120 billion global market hopes to trial a new cancer drug in humans for the first time early in 2020 – well ahead of its plans.

Avacta’s tumour microenvironment activated drug conjugates (TMAC) are a ground-breaking new form of cancer immunotherapy.

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. 

The company intends to submit an Investigational New Drug (IND) Application with the FDA early next year to test the TMAC™ linker in a phase I study in patients with selected solid tumours. This is a major de-risking milestone for the programme.

Avacta’s conjugates are a ground-breaking new form of cancer immunotherapy, co-invented with Tufts University Medical School. They combine 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.

To test the TMAC linker in humans 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’s planned 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.

CEO Dr Alastair Smith said: “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. It is a hugely exciting period for Avacta.”

Avacta’s chief medical officer, Dr Jose Saro, added: “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 tumour microenvironment to be maintained for a longer period with reduced systemic toxicity.

“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.”

Antibodies dominate markets worth in excess of $100bn despite their shortcomings. Affimer technology has been designed to address many of these negative performance issues, principally; the time taken to generate new antibodies, the reliance on an animal’s immune response, poor specificity in many cases, and batch to batch variability.

Affimer technology is based on a small protein that can be quickly generated to bind with high specificity and affinity to a wide range of protein targets.

Avacta has a pre-clinical biotech development programme with an in-house focus on immuno-oncology as well as partnered development programmes. It is commercialising non-therapeutic Affimer reagents through licensing to developers of life sciences research tools and diagnostics.

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