Cambridge, UK—Avacta Group plc, the developer of Affimer biotherapeutics and research reagents, announced today that the company is planning to submit an IND/CTA application early in 2020 to test the TMAC linker in a Phase 1 study in patients with selected solid tumors. Avacta is now in a position to test this critical TMAC linker in humans, a major de-risking milestone for the program, early in 2020 and well ahead of the original plans.
Avacta’s tumor microenvironment activated drug conjugates (TMAC) are a new form of cancer immunotherapy, co-invented with Tufts University Medical School, that combine Affimers with chemotherapies in a single drug. The technology uses a linker designed to only release the chemotherapy in the tumor microenvironment. This allows extremely potent chemotherapies, ones that are 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 tumor, releasing active doxorubicin. Doxorubicin has well documented safety issues limiting its dosing, which limits the patient sub-group that can be treated. Despite these issues, the global doxorubicin market is valued at $910 million, and is expected to reach $1.4 billion 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 preclinical study in mice.
“What is so attractive about Avacta’s Affimer TMAC program 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,” noted Dr. Alastair Smith, chief executive officer, Avacta. “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 programs.”
“The function of the linker in the TMAC is critical and I am delighted that the planned Phase 1 study will allow us to test it well ahead of our original schedule. This is an important de-risking step for the TMAC program 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 inhibitor, 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,” Smith continued.
The planned Phase 1 trial will comprise a dose escalation study in patients with selected solid tumors, including advanced and metastatic high-grade soft tissue sarcoma. Successful functioning of the TMAC linker will be reflected in tumor shrinkage, as a result of the release of doxorubicin. The study may also potentially demonstrate improved tolerability over standard doxorubicin.
The cancer immunotherapy market is currently worth $60 billion, and is predicted to double by 2025. Avacta’s TMAC and bispecific cancer immunotherapies are designed to not only compete strongly in this market through improved clinical benefit to patients, but to also expand the market to patients who do not respond to single checkpoint inhibitors. Avacta has exclusive rights to commercialize TMAC drug conjugates.
“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,” said Dr. Jose Saro M.D., chief medical officer, Avacta. “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 tumors.”