Avacta’s Proprietary TMAC Cancer Therapy Platform Demonstrates Successful Proof-of-Concept
Avacta Group plc recently announced it has demonstrated initial proof-of-concept for its proprietary new class of drug conjugate, TMAC, in a preclinical animal model of cancer. The study showed that AVA04-VbP outperformed Bavencio (Avelumab), a marketed anti-PD-L1 immunotherapy.
Avacta’s tumour microenvironment activated drug conjugates (TMAC) are a groundbreaking new form of cancer immunotherapy, combining its Affimer biotherapeutics with chemotherapies in a single drug, using a linker (incorporating its proprietary pre|CISION substrate) that is designed to only release the chemotherapy in the tumour microenvironment through the action of an extracellular enzyme called FAPa. This mechanism overcomes the need to target an internalising cancer marker, as with conventional antibody drug conjugates (ADCs), and allows extremely potent chemotherapies to be combined with Affimer immune-checkpoint therapies. Combining pre|CISION technology with the Affimer platform is enabling Avacta to build a pipeline of novel and safe cancer therapies applicable to a broader range of cancer patients, including those who do not respond to existing immunotherapies.
AVA04-VbP combines an Affimer PD-L1 checkpoint inhibitor with an I-DASH chemotherapy warhead, addressing the acute systemic toxicity associated with I-DASH inhibitors by targeting the release of the drug warhead in the tumour microenvironment. The drug warhead induces a highly pro-inflammatory cell death, which in turn stimulates an immune response in the tumour, which is supported by the Affimer PD-L1/PD-1 signalling pathway blockade.
In a mouse syngeneic tumour model study, Avacta has shown that AVA04-VbP outperforms Bavencio; animals treated with AVA04-VbP showed a significant reduction in the rate of tumour growth with respect to those treated with Bavencio. A considerably higher level of the released I-DASH warhead was measured in the tumours compared with very low levels in the blood, indicating that healthy tissues are less exposed to the highly toxic warhead. This tumour targeting is central to the TMAC mechanism of action, and permits the use of the highly potent cancer-killing warheads.
Dr Alastair Smith, Chief Executive Officer of Avacta Group, said “These in vivo efficacy and pharmacokinetic data demonstrate initial proof-of-concept for TMAC drug conjugates and represent an important milestone for the Company. We have received significant commercial interest in the TMAC concept, so I am delighted that we have been able to demonstrate superior efficacy and targeting of the warhead to the tumour with the first TMAC to be have tested in animals. This is hugely encouraging for the TMAC programme and I look forward to keeping the market updated on future developments.”
Avacta is developing novel cancer immunotherapies combining its two proprietary platforms – Affimer biotherapeutics and pre|CISION tumour targeted chemotherapy. With this approach, the Company aims to address the lack of a durable response to current immunotherapies experienced by most patients. The Company’s therapeutics development activities are based in Cambridge, UK. The company benefits from near-term revenues generated from Affimer reagents for diagnostics, bioprocessing and research, through a separate business unit based in Wetherby, UK. The Affimer platform is an alternative to antibodies derived from a small human protein. Despite their shortcomings, antibodies currently dominate markets worth in excess of $100 billion.
Affimer technology has been designed to address many of these negative performance issues, principally: the time taken, and the reliance on an animal’s immune response, to generate new antibodies; poor specificity in many cases; large size and cost. Avacta’s pre|CISION platform, activates chemotherapy only in the tumour, thereby limiting systemic exposure and damage to healthy tissues, and thus improving the overall safety and therapeutic potential of these powerful anti-cancer treatments. By combining these two platforms the Company is building a wholly owned pipeline of novel cancer therapies with the aim of creating effective treatments for all cancer patients including those who do not respond to existing immunotherapies. Avacta expects to take its first drug, a pre|CISION targeted form of the standard-of-care Doxorubicin, into the clinic in the middle of 2020.
Avacta has established drug development partnerships with pharma and biotech, including with Moderna Therapeutics Inc., a collaboration with LG Chem to develop treatments for autoimmune and inflammatory diseases worth up to $310 million, a partnership with ADC Therapeutics to develop Affimer drug conjugates and a joint venture in South Korea with Daewoong Pharmaceuticals to develop the next generation of stem cell therapies that incorporate Affimer immuno-modulators. Avacta actively seeks to license its proprietary platforms in a range of therapeutic areas.
The Avacta diagnostics business unit works with partners world-wide to develop Affimers for evaluation by those third parties with the objective of establishing royalty bearing license deals. The company is also developing a small in-house pipeline of Affimer-based diagnostic assays for licensing. For more information, visit https://www.avacta.com.
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