10108718Investigation of CreaTap Antibody Penetration in Ovarian, Gastric and Breast CancersClosedCollaborative R&DInnovate UKMonoclonal antibodies offer a successful targeted approach for cancer treatment due to their high specificity. Several efficacious drugs have come to market such as trastuzumab, ipilimimab, cetuximab, bevacizumab and pembroluzimab. However, these therapies benefit only a few. Limited penetrability of antibodies into the tumour have lead to high drug toxicities, and in many cases patients cease treatment to manage these side effects. Improving accessibility of antibody drugs into the tumour would not only leverage improving existing drugs, but would also allow the re-visitation of excellent pre-clinical drugs that were halted in the clinical stages due to toxicity. It would also open avenues to go after great research targets that again have shown limited efficacy due to a high number of side effects giving rise to novel therapeutics. Significant strides have been made in the treatment of blood-based cancers, but solid tumours remain a challenge for the industry. Creasallis has focused on solid tumour penetration though CreaTap -- a novel mechanism of action that allows antibody-based drugs to penetrate tumours. CreaTap is a discrete set of mutations in the constant region of an antibody. For this reason, we refer to the technology as plug-and-play due to its applicability to all antibodies. CreaTap does not impact the expression, activity and stability of the antibody. In our In vivo proof of concept work, we have found that it only impacts tumour penetration by more than 2-fold. Our studies focused around an anti-Her2 antibody in ovarian cancer, but there is evidence that Her2 expression is much higher in breast and gastric cancers from the literature, and these may give a larger therapeutic index. So the aims of this study are to investigate this and to narrow down our disease indication for pursing a clinical candidate. The monoclonal antibody market is currently worth ~$300 billion, and rising. The antibody-drug conjugate market has gained traction in the last 18 months currently a $8 billion dollar market. Both these markets are open to Creasallis as avenues to exploit for CreaTap improved penetration. Our value proposition is that increased tumour penetration would reduce off target antibody accumulation, resulting improved safety profiles. Improved tumour penetration would benefit the treatment of patients with larger tumours, opening up new patient populations not previously accessible for treatment. Finally, improved tumour penetration can lead to the administration of lower doses giving a better price per dose for healthcare providers and patients.