dumbcritic
A Disturbance in the Force
dumbcritic said:
Some info from LinkedIn and a patent that they have shared. It seems the lead compound (EF-022) is a lectin-receptor activator that modulates suppressor macrophages and tolerogenic dendritic cells.
In 25% of patients (n=24) with refractory tumours then it lead to stabilized disease. This was the fourth line of treatment for over a third of them. To be eligible they had to have failed standard of care (chemo, PD-1 inhibitor and/or a EGFR inhibitor). In patients whose disease progressed after treatment with PD-1 inhibitors then 40% (2 out of 5) showed stable disease (SD) after treatment with EF-022.
EF-022 has also shown encouraging results in a compassionate use case. A patient with pulmonary metastatic sarcoma received weekly injections (100 ng/each injection) intramuscularly (IM) for one year. As a result, disease stabilization was achieved for 6 months. Thereafter, relapse accompanied with new lesions in the lungs occurred. At that stage, the patient received a combination therapy of it and the anti-PD-1 drug Keytruda which was administered by intravenous (IV) injection every three weeks. The combination was continued for an additional 6 months. This resulted in disease stabilization and complete disappearance of one of the lung metastases (FIGs. IB and 1C). Thus, the combination therapy was found to be more efficacious than either treatment alone.
https://s27.postimg.org/ufgn75r43/WO_id00000035251162_10951756_200_0_000038.jpg
Then a patient with oral cavity squamous cell carcinoma (SCC) who after failing SOC (chemotherapy and Keytruda) showed stable disease (SD) after treatment with EF-022. It was shown that it unexpectedly increased the number of cytotoxic T cells and macrophages in the tumour site, leading to disease stabilization despite the extremely high increase in PD-L1 expression on the tumour cells and/or adjacent cells during the EF-022 treatment course.
This shows the number of cells expressing PD-L1 from tumour biopsies collected from the patient prior to treatment (baseline) and after 57 days
https://s28.postimg.org/j8h1q67q5/WO_id00000035251162_10951756_200_0_000039.jpg
https://s4.postimg.org/4dev4z12l/WO_id00000035251162_10951756_200_0_000040.jpg
It should be noted that high expression of PD-L1 on tumour cells and/or adjacent cells is typically linked with immune suppression and poor prognosis. Yet, treating this patient for four months resulted in disease stabilization and then tumour shrinkage. This result indicates that in spite of the high expression of PD-L1 EF-022 was capable of arresting tumour growth.
This shows staining of CD8+ T cells in biopsies collected from the same patient. They show a significant increase (115% compared to baseline) in the level of these
https://s28.postimg.org/uz7oz39d9/WO_id00000035251162_10951756_200_0_000041.jpg
