Co-development agreement will see invention of new class of drug conjugate

Developer of Affimer biotherapeutics and reagents, Avacta Group, has agreed to a co-development partnership with Bach BioSciences — a company that commercialises the research of William Bachovchin from Tufts University School of Medicine.

This collaboration will see the development of a new class of Affimer drug conjugate therapies with a novel mode of action that combines Affimer technology with drug conjugates that have been developed at Tufts.

Earlier collaborative work by Avacta and Tufts saw the invention of a new class of drug conjugate that selectively releases a potent drug in the tumour microenvironment (TME) without requiring cellular internalisation of the conjugate, as is the case with traditional antibody drug-conjugates.

A joint filing for broad patent protection for this unique concept has been undertaken by the company and the university. This patent covers Affimers, and a wide range of other binders, against oncology, viral and inflammatory targets that are not internalised rapidly enough to be useful in traditional antibody-drug conjugates. It also covers a wide range of drugs to which the binders can be conjugated.

This latest drug development partnership that Avacta has initiated with Bachovchin — Professor of Developmental, Chemical and Molecular Biology at Tufts University School of Medicine, Boston — will involve the development of the first example of this new class of drug conjugate based on the combination of Affimer PDL1 inhibitors and an I-DASH small molecule inhibitor. Considerable clinical data for this has already been generated by the laboratory at Tufts. Avacta will have exclusive rights to commercialise these novel drug conjugates.

“We are very excited indeed by this highly novel Affimer drug conjugate concept, the first example of which builds on our own PD-L1 programme and the world-class research of Professor Bachovchin at Tufts University School of Medicine, one of the top US medical schools and research institutes,” commented Dr Alastair Smith, chief executive officer of Avacta Group. “We believe that this new drug conjugate platform is transformational for the business. From our initial discussions with several large pharmaceutical companies, it is clear that there is significant interest and there is certainly the potential for partnering at an early stage once we have the appropriate supporting data from the collaboration with Professor Bachovchin.

“Broad patent protection for this dual mode of action therapy would be extremely valuable because it could be applied to a wide range of cancers for which patient response to checkpoint inhibitors alone is not high.

“The initial embodiment of the concept, which uses a PD-L1 Affimer, becomes Avacta’s second major drug development programme alongside the PD-L1/LAG-3 bispecific blockade. This will maximise the value we deliver to shareholders from the investment in the PD-L1 programme since 2015 and we very much look forward to updating the market on the progress made in the coming months.”

“Cancer immunotherapy can be an effective treatment strategy, but pharmaceutical companies’ early enthusiasm has given way to the reality of limited patient responses that the industry is now trying to address,” added Dr Amrik Basran, chief scientific officer of Avacta Group. “In particular, while patients that do respond to current checkpoint inhibitors do so with significant and durable benefits, the unfortunate reality is that for most major tumours only about 20–30% of patients actually respond to the use of checkpoint inhibitors, leaving a substantial number of patients unable to realize the full therapeutic benefit.

“Development of bispecifics, such as our PD-L1/LAG-3 programme, is one way to address this, but inducers of innate immune responses have also garnered considerable attention. In this new class of drug conjugate that we are developing with Professor Bachovchin, this innate immune response will be combined with check-point inhibition and we expect to see significant improvements in efficacy and safety.

“The Affimer-drug conjugate circulates as a single molecule, in which the conjugated drug is inert, until it encounters enzymes selectively expressed in tumours, where the drug is released, and through its mechanism of action is designed to turn immunologically ‘cold’ tumours ‘hot’ and receptive to immunotherapy. It is our expectation that this will increase the percentage of responsive patients dramatically and, in doing so, it will make a meaningful difference to the lives of a great many cancer patients.”