Jennifer Buell: Mostly checkpoint refractory for a few reasons. This — we have been able to demonstrate that we can dose monotherapy iNKT in patients who have failed prior IO therapy, and we have been able to dose in combination. We could do so tolerably to 1 billion cells. and we’ll be sharing the data from those signals. I think importantly, one thing that is commonly observed in patients who are PD-1 refractory is the exhausted CD8+ T cells for those cells that actually cannot enter the trauma and do the past November, we presented data demonstrating that our iNKTs can actually reverse the CD8 exhaustion signature and also kill M2 suppressive immuno-suppressive macrophages. Both of those, we believe, set us up for bringing benefits in patients who have actually failed anti-PD-1 therapy because of the translational data that we’ve been able to generate and present.
IO-naive patients in — with non-small cell lung cancer are very far fewer of the population. So, we’re really focused on the refractory patients.
Kalpit Patel: Okay. Make sense. Thanks, very much for taking my question.
Operator: Our next question comes from the line of Jack Allen from Baird. Please proceed.
Jack Allen: Great. Thank you so much, and congratulations on the progress. I guess my first question was around the decision to move forward with the PD-1 inhibitors. I was wondering if you had any comments about the thoughts that you had previously had around genesis proprietary CTLA-4 inhibitor, Botensilimab and any potential combination use there?
Jennifer Buell: Jack, I’m still glad you asked. We will be making some announcements at AACR about the combination, which we did not elucidate in our — about different combinations that we’ll be advancing both in our hands as well as in combination with some of the agents from Genesis portfolio. I think really importantly; Genesis most recent data presentation was at ASCO GI and Botensilimab. And for those who may be less aware, the product appears to be bringing extraordinary benefit to a host of solid tumor cancers that have failed prior therapies. So that includes MA SS, colorectal cancer as well as PD-1 refractory non-small cell lung cancer. At the most recent earnings call, they shared the response rates that are really exceeding, I think, 50% in that cohort of patients with non-small cell lung cancer.
And what we had previously collaborated on were preclinical studies that actually demonstrated the synergy and complementarity of agenT-797 or iNKT cells in combination with both version and Botensilimab. So, in the model, it was the B15 OVA model with metastatic lung disease, and we saw that the combination of CTLA-4, PD-1 eliminated about 30% to 40% of the disease. The cells alone did about that same reduction and liver mess when you put the three or two together, so the cells in combination with Botensilimab or the cells in combination with Botensilimab and Beltsville and that we set saw near complete to our eradication. So, it sets us up for a few really important opportunities that could be expanding the benefit of what we see with Botensilimab because of the complementarity of the mechanisms that I mentioned before.
We have some additional preclinical data that we will also be releasing in other indications where the combination may productive. One of the areas that we believe the cells can expand the benefit of Botensilimab is in patients with metastatic liver disease. What we see — and we’ve shared a bit about is it in a patient in our study with metastatic liver disease. We had the cells not only home delivery disease, but also modulate the disease and eliminate the disease in some settings in those liver mets. So, we do believe that there’s an enormous opportunity to expand the benefit of Botensilimab by adding the iNKT cells agenT-797 to this combination, and we’ll be talking more about that at AACR.
