Date: 2018-01-15
Type of information: Licensing agreement
Compound: highly targeted bio-therapeutics
Company: Avacta (UK) Glythera (UK)
Therapeutic area: Technology - Services
Type agreement: collaboration
Action mechanism:
- antibody drug conjugate (ADC). Antibody drug conjugates use an antibody to which a toxin/chemotherapy payload is chemically attached for targeted delivery to a tumour. 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 over current ADC offerings.
- The Affimer® scaffold is based on the cystatin protein fold. Affimer reagents are selected from libraries in which 12 – 36 amino acids are diversified giving a predicted total binding surface area of 650-1000 Å2. The Affimer scaffold has been engineered so that it no longer binds to proteins found in human cells, serum or plasma so that an Affimer molecule’s interactions are specifically defined by the engineered peptide loops made up of 19 naturally occurring amino acid side chain. They can distinguish between proteins that differ by only a single amino acid, can detect subtle changes in protein expression levels even in a multiplexed format, can distinguish between multiple closely related protein domains, can be generated against targets which are intractable for antibodies and can even detect whether a protein is in an active or inactive conformation. Use of this technology provides the ability to closely control the position and number of toxins in the payload. It has the benefit of much shorter development times and has the flexibility to “design-in” the required pharmacokinetics (the time the drug spends in the blood stream). The small size of the Affimer molecule is likely to also improve tumour penetration compared with antibodies which 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.
Disease:
Details:
- • On July 14, 2016, Avacta, the developer of Affimer® biotherapeutics and research reagents, and Glythera, the developer of advanced, stable conjugation chemistries and novel, ultra-potent toxin payloads, announced that they 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 bio-therapeutics as a superior alternative to the established class of antibody drug conjugates (ADCs).
- 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.
Financial terms:
Latest news:
- • On January 15, 2018, Avacta Group announcee that its initial study with Glythera has concluded successfully. Following this study the two companies have agreed the terms of a licensing deal which will allow them to develop drug conjugates using the combined technologies. The detailed terms of the license have not been disclosed but Avacta would receive development milestone payments and royalties on sales of an approved drug developed by Glythera.
- Avacta and Glythera have carried out a proof-of-concept study designed to demonstrate that Avacta’s Affimer® technology could be combined with Glythera’s Permalink® conjugation chemistry to provide a technically superior drug conjugate platform with shorter development times, simpler, more consistent production and greater chemical stability. An Affimer, compared with a much larger antibody, potentially also allows greater control over the time the drug spends in the blood stream and deeper tumor penetration producing a more effective medicine with fewer toxic side effects.
- Importantly, the initial trial has also shown that the Affimer remains functional when the toxic payload has been added indicating that the combination of the two technologies has the potential to develop drug conjugate therapies.
Is general: Yes
