Therapeutic Pipeline 

Read More

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

Read More

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

Read More

Partnering Organization: City of Hope

 

Human immunodeficiency virus 1 (HIV-1) is the primary cause of acquired immune deficiency syndrome (AIDS) that affects over a million people in the United States alone. Advances in treatment have significantly prolonged the lives of those infected with HIV-1, with combinatorial antiretroviral therapy (cART) being the current standard in therapeutic care. However, cART alone cannot achieve complete eradication of the virus. Besides, drawbacks such as drug resistance development and severe side effects (e.g. premature aging, cancer, and cardiovascular disease) remain critical issues in cART therapy. Therefore, there is a need for a treatment, with efficient delivery and a favorable safety profile, that can reduce the HIV-1 viral load to undetectable levels.

 

A promising approach is to utilize RNA silencing to treat HIV-1 infection by targeting the dimerization initiation site (DIS), a replication signal in the 5’ untranslated region (5’-UTR). Dimerization is initiated when the 5'-UTR undergoes a conformational change, allowing the DIS loops of two RNA genomes to base pair. This forms a kissing-loop (KL) dimer, which then leads to the subsequent packaging of the viral RNA. It is known that mutation or inhibition of the DIS severely restricts viral infectivity.  We have developed self-delivering FANA ASOs that can effectively target these regions. We are currently conducting preclinical studies to further evaluate the efficacy of our identified lead compounds. This work is funded by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) under Award Number R43AI152774.

 

TARGET: Multiple