Therapeutic Pipeline
Partnering Organization: Children's Hospital of Pennsylvania
CD4+CD25+ T-regulatory (Treg) cells inhibit the body’s immune responses and thereby prevent autoimmune diseases, but they can also limit the body’s immune response to cancer. As a result, they are considered one of the key factors limiting current efforts at improving the outcomes of immunotherapy in patients with a wide variety of different types of cancers.
Treg cells are recognized by their nuclear expression of a unique protein, FOXP3, that unfortunately cannot be directly targeted by drugs or antibodies.
We have developed next generation self-delivering anitisense oligonucleotides (ASO) that specifically decrease FOXP3 expression in vitro and in vivo in the Tregs of mice and of humans and thereby help activate conventional T cells. These anti-FOXP3 ASO promote antitumor immunity in mouse and impair human Treg function in humanized mice.
We are currently undertaking preclinical studies and further evaluating our identified anti-FOXP3 ASO lead compounds in preparation for IND-enabling studies and application in patients with cancer.
TARGET: FOXP3
Partnering Organization: University of Pennsylvania
Parkinson's Disease (PD) is the second most common neurodegenerative disorder, affecting ~1 million individuals in the US alone. There is no current disease modifying therapy for PD. In virtually all PD patients, as well as those with dementia with Lewy bodies (DLB) and ~50% of Alzheimer’s disease (AD) patients, neurons accumulate misfolded forms of alpha-synuclein (aSyn) while mutations in the SNCA gene cause familial PD, suggesting that aSyn is central to pathogenesis. Thus, histological and genetic evidence strongly point to the accumulation of abnormal aSyn as a central step in the pathogenesis of Parkinson's Disease. These data also make aSyn a high priority target for novel therapies for not only PD but for related synucleinopathies like PD with dementia (PDD), DLB, multiple system atrophy (MSA), and AD. However, current therapies in clinical trials for PD include antibodies and small molecules that target both toxic and non-toxic forms aSyn. Such approaches mainly target aSyn at the extracellular level and thus may have limited therapeutic benefits.
We have developed a next-generation gene silencing approach that can selectively knockdown our identified target gene and inhibit production of aSyn in neurons, using our self-deliverable FANA antisense oligonucleotides (FANA ASOs). We are currently conducting preclinical studies and further evaluating our identified lead compounds.
TARGET: Undisclosed