The Client looks for proposals from companies that develop antibodies for cancer treatment and wish to engage in either of the following:
- In-house assessment of the Client's AiADC technology
- Joint research/development with the Client
Sumitomo Dainippon Presents Preclinical Key Data on AiADC technology at the AACR2019 Annual Meeting on March 31, 2019 1:00PM-5:00PM:
- #1663: Antibody intracellular activated drug conjugate (AiADC) as novel ADC technology
- Georgia World Congress Center (Atlanta, Georgia, USA), Exhibit Hall B, Poster Section 9 – Poster Board 14
The Client would like to discuss the detail with the candidates who will apply in this project at the AACR2019.
Overview and characteristics of the newly developed AiADC technology
- Applicable to various antibodies
The Client's AiADC technology can be applied to various antibodies and has shown high levels of in vitro activity in application to not only anti-CD30 antibodies but other antibodies such as anti-HER2 antibodies. This demonstrates the great versatility and high efficacy of the technology.The data when using AiADC for anti-CD30 antibody is described below.
- A highly novel payload
The payload on the Client's AiADC is a microtubule destabilizer, which has activity equal to or more potent than that of monomethyl auristatin E (MMAE).
May be used in combination with immunotherapy
DSP payload is highly hydrophilic and has low cell membrane permeability, which means that the payload will not be delivered into cells on its own, and has no effect on anything other than the target cells (Figure 1, Table 1). Because the AiADC has little effect on immune cells, it may be used in combination with immunotherapy, which is intended to activate immune cells.
Figure 1. Overview of AiADC technology
The specificity of the anti-CD30 antibody-drug conjugate created by the AiADC technology (anti-CD30 AiADC) depending on the expression of CD30 was analyzed. The results showed efficacy with high selectivity only to CD30 expressing cells.
Table 1. Efficacy in CD30-positive cells (Karpas-299) and CD30-negative cells (SK-BR-3)
- High levels of efficacy
Tumor-bearing mice were given a single dose of anti-CD30 AiADC created using the AiADC technology with a drug-to-antibody ratio (DAR) of 8, or anti-CD30 Vedotin created using conventional ADCs with an average DAR of 4. A comparison of changes in the tumor volume in the mice found that anti-CD30 AiADC showed high levels of antitumor activity.
Figure 2. In vivo evaluation of drug efficacy in cell-derived tumor xenograft murine models
(Left: Anti-CD30 AiADC created using AiADC technology; Right: anti-CD30 Vedotin based on conventional ADC)
- High levels of safety and reduced adverse reactions
The results of toxicity studies in rats confirmed a favorable safety profile for the anti-CD30 AiADC, which did not show toxicity even when given in a dose ten times higher than that of anti-CD30 Vedotin (created using conventional ADCs).
Table 2. Toxicity studies in rats
- Able to produce homogenous ADCs
The Client's AiADC technology enables the ratio of antibody to drug to be kept constant, which makes it possible to produce homogenous ADCs. This makes it a beneficial technology from the GMP perspective, among others.