Gritstone bio Inc (GRTS)

[jondoeuk]

Based on my own DD (some of which is below) I have a small position. Currently, I think they are one of the leaders in the space. Whether this will change is going to be based on the webcast and data presented next month.

Neoantigens, are derived from random somatic mutations in cancer cells and are not present in healthy cells. Therefore, not only can you target them due to there being no pre-existing tolerance, but also there is very little risk of inducing autoimmunity [1-3].

In humans, there is a large amount of evidence showing that T-cells, which target these serve an important role in mediating clinical responses to a range of different immunotherapies such as anti-PD-1 mAbs [4].

However, two of the biggest challenges are identification and delivery. When it comes to the latter, the company is using a heterologous prime-boost regime [5]. The hope is by using this they are able to generate enough T-cells to impact the cancer. For the former they have their own platform (EDGE). It was tested against public methods as well as how both compared to another approach used by Dr. Rosenberg/NCI. The majority (19/26, 73%) of MHC Class I restricted neoantigens would be included with EDGE vs. only 9/26 (35%) with public tools [6]. They will try to prioritise clonal over subclonal neoantigens [7]. Last year a collaboration with BLUE happened and this somewhat helps with validation in my view [8].

Refs:
1 https://www.cell.com/trends/molecular-medicine/fulltext/S1471-4914(17)30147-8
2 https://science.sciencemag.org/content/348/6230/69.long
3 https://www.nature.com/articles/nature13988
4 https://www.nature.com/articles/nature13954
5 http://cancerres.aacrjournals.org/content/78/13_Supplement/724
6 https://www.nature.com/articles/nbt.4313
7 https://science.sciencemag.org/content/351/6280/1463
8 https://www.businesswire.com/news/home/20180823005039/en/bluebird-bio-Gritstone-Oncology-Announce-Strategic-Collaboration