Scientific Explanations and References

ENV 105

Antibody that targets CD105 (Endoglin) by inhibiting BMP signaling to reverse cancer drug resistance
Papers: Kato et al., Madhav et al. (Science behind ENV105), Smith et al (Phase II trial results)
Other papers not by our group: Schoonderwoerd et al. shows the synergy with checkpoint inhibition of CD105 targeting and Wu et al. discusses synergy of ENV105 with immunotherapy.

Papers:

Kato et al
Madhav et all
Smith et al
Schoonderwoerd et al
Wu et al

KROS 101

Small molecule agonist for GITR ligand
Papers: Zhou et al. (Human) hGITR PNAS paper of Ram Murali showing crystal structure of the human GITR ligand used to develop KROS 101 agonist and KROS 102 antagonist. Zhou et al. (Mouse), PNAS paper showing mouse GITR activation by Ram’s group (our VP of Research and Development) through structural biology.

Papers:

Zhou et al. (Human)
Zhou et al. (Mouse)

KROS 102

Small molecule antagonist for GITR ligand
Papers for KROS101 is relevant but this antagonist prevents GITR ligand from working inhibiting T cell growth

KROS 201

Activated T cells targeting glioblastoma cancer stem cell antigens
Papers: Miyaguchi et al. shows translational development of activated T cell technology, Wen et al., Clin Cancer Research paper is the randomized multi-institutional phase II study showing that a multi-epitope DC vaccine significantly improves progression free survival. We use 6 of the antigens in our activated T cell technology, and also add 3 more CTL antigens and 9 helper epitopes in order to improve the robustness of the immunogenicity, Yuan et al. Oncogene paper is our first report of isolation of cancer stem cells from glioblastoma which is the target cell in KROS 201, Xu et al. Stem Cell paper shows strategy of immunologically targeting cancer stem cells and demonstrates some of the antigens overexpressed on glioblastoma cancer stem cells.

Papers:

Miyaguchi et al
Wen et al
Yuan et al
Xu et al

KROS 301

Small molecule inhibiting relA nuclear translocation in the NF-kB molecular pathway in dependent cancers
Paper: Kanzaki et al., BCTT paper showing KROS 301 in triple negative breast cancer model

Papers:

Kanzaki et al

KROS 401:

Cyclic peptide inhibits IL-4 and and IL-13 receptors on macrophages to reverse M1 to M2 transition
Paper: Xue et al. IL4- IL13 inhibitor paper in Nature Communications showing KROS 401 activity in a chronic pancreatitis model reversing M1 to M2 transition in macrophages

Papers:

Xue et al

ENV 205

Mitochondrial DNA depletion to reverse doxetaxel chemotherapy resistance
Paper: Halder et al., PNAS paper showing mechanism of action of ENV 205

Papers:

Halder et al

Drug	Mechanism of Action	PDF Link
ENV 105	• Antibody that targets CD105 (Endoglin) by inhibiting BMP signaling to reverse cancer drug resistance • Papers: Kato et al., Madhav et al. (Science behind ENV105), Smith et al (Phase II trial results) • Other papers not by our group: Schoonderwoerd et al. shows the synergy with checkpoint inhibition of CD105 targeting and Wu et al. discusses synergy of ENV105 with immunotherapy.	Kato et al Madhav et all Smith et al Schoonderwoerd et al Wu et al
KROS 101	• Small molecule agonist for GITR ligand • Papers: Zhou et al. (Human) hGITR PNAS paper of Ram Murali showing crystal structure of the human GITR ligand used to develop KROS 101 agonist and KROS 102 antagonist. Zhou et al. (Mouse), PNAS paper showing mouse GITR activation by Ram’s group (our VP of Research and Development) through structural biology.	Zhou et al. (Human) Zhou et al. (Mouse)
KROS 102	• Small molecule antagonist for GITR ligand • Papers for KROS101 is relevant but this antagonist prevents GITR ligand from working inhibiting T cell growth
KROS 201	• Activated T cells targeting glioblastoma cancer stem cell antigens • Papers: Miyaguchi et al. shows translational development of activated T cell technology, Wen et al., Clin Cancer Research paper is the randomized multi-institutional phase II study showing that a multi-epitope DC vaccine significantly improves progression free survival. We use 6 of the antigens in our activated T cell technology, and also add 3 more CTL antigens and 9 helper epitopes in order to improve the robustness of the immunogenicity, Yuan et al. Oncogene paper is our first report of isolation of cancer stem cells from glioblastoma which is the target cell in KROS 201, Xu et al. Stem Cell paper shows strategy of immunologically targeting cancer stem cells and demonstrates some of the antigens overexpressed on glioblastoma cancer stem cells.	Miyaguchi et al Wen et al Yuan et al Xu et al
KROS 301	• Small molecule inhibiting relA nuclear translocation in the NF-kB molecular pathway in dependent cancers • Paper: Kanzaki et al., BCTT paper showing KROS 301 in triple negative breast cancer model	Kanzaki et al
KROS 401	• Cyclic peptide inhibits IL-4 and and IL-13 receptors on macrophages to reverse M1 to M2 transition • Paper: Xue et al. IL4- IL13 inhibitor paper in Nature Communications showing KROS 401 activity in a chronic pancreatitis model reversing M1 to M2 transition in macrophages	Xue et al
ENV 205	• Mitochondrial DNA depletion to reverse doxetaxel chemotherapy resistance • Paper: Halder et al., PNAS paper showing mechanism of action of ENV 205	Halder et al