Research for a cureAvacta Group, the developer of Affimer biotherapeutics and research reagents, and Glythera Limited, the developer of advanced, stable conjugation chemistries and novel, ultra-potent toxin payloads, have established a collaboration to evaluate the use of Glythera’s PermaLink conjugation chemistry in combination with Avacta’s Affimer technology with the aim of developing a new class of highly targeted biotherapeutics as a superior alternative to the established class of antibody drug conjugates (ADCs).

ADCs use an antibody to which a toxin/chemotherapy payload is chemically attached for targeted delivery to a tumour. More than 50 ADCs are currently in clinical development; of these, approximately a quarter are in Phase II or Phase III. The market is estimated to be worth around $1 billion today from two approved compounds and is expected to be worth $10 billion annually by 2024.

The combined potential benefits of the Affimer and PermaLink technologies have the potential to create an analogous leading protein drug conjugate platform with a number of benefits compared with current ADC offerings. Use of Avacta’s Affimer technology (i) provides the ability to closely control the position and number of toxins in the payload; (ii) has the benefit of much shorter development times (iii) has the flexibility to “design-in” the required pharmacokinetics (the time the drug spends in the blood stream), and (iv) is much easier, more consistent and has lower cost production. The small size of the Affimer molecule is likely to also improve tumour penetration compared with antibodies that are ten times larger in size.

Another major issue facing ADCs is the limited stability of chemical linkages currently used to attach the toxin to the antibody resulting in the toxin coming off the antibody and causing “off-target” and often  severe, side-effects. Glythera’s PermaLink chemical linkers provide much more stable attachment of the toxin/chemotherapy and can potentially reduce such off-target toxicity effects.

Under the terms of the agreement, the companies will develop materials and methods to be used in the generation of Affimer-drug conjugates. The proof of concept study aims to demonstrate the key technical and commercial benefits of the combination over traditional antibody and linker approaches. The two companies will partner to offer Affimer-drug conjugate development services, and licensing of the combined platform, to pharmaceutical developers.

Dr Alastair Smith, Chief Executive Officer, Avacta, commented: “At the half year we set out a detailed commercial strategy for Affimer reagents and therapeutics. We highlighted the importance of commercial partnerships to make rapid progress in the areas of strategic focus. In that context, we recently announced a collaboration with Mologic to develop Affimer based lateral flow devices that would open up the rapid diagnostics market opportunity and, today, we are very pleased to report the establishment of this collaboration with Glythera in the area of ADCs, another important application area for Affimer technology.”

“Avacta’s Affimer technology has significant benefits for drug conjugate development, and the combination of the two companies’ technologies has the potential to deliver a best-in-class solution for those wishing to access such a platform. We are therefore confident that this partnership with Glythera will further demonstrate the utility of the Affimer platform as a powerful approach to generating a broad range of biotherapeutics, creating opportunities for third party licensing of the platform with the potential to generate long-term value for both companies. We continue to make good progress across all aspects of the strategy that we set out and I look forward to further updating the market in due course,” he added.

Dr Dave Simpson, Chief Executive Officer, Glythera, said: “Combining Glythera’s PermaLink conjugation chemistry with Avacta’s Affimer technology will demonstrate the benefits of PermaLink across a new targeting molecule class, opening additional avenues for bringing novel therapeutic assets to market. This is an exciting step forward in biotherapeutic development, and could lead to improved patient outcomes.”