PIPELINE — Collaborations Pharmaceuticals, Inc.

Our Pipeline

Our work using machine learning for bacteria, viruses, parasites and rare diseases has demonstrated that we can identify molecules with potential in vivo activity that can lead to NIH funding to build our pipeline of drug candidates.

Our Work

Ebola

We have identified 3 molecules (pyronaridine, tilorone and quinacrine) with in vitro activity against three strains of Ebola virus. These three molecules were also active in vivo in a mouse adapted virus model. One molecule Pyronaridine, has to date, shown activity in a guinea pig adapted virus model and is ready to go into a non-human primate model.

We have 3 orphan drug designations for this disease.

Enteroviruses

An analog of a clinical stage compound pleconaril, with potent activity across these enteroviruses in vitro was identified. We have demonstrated EV68, EV71, Polio, CVB3, CVB5 and Echovirus activities. We have also generated in vivo data for EV68 and CVB5. Our lead candidate is 10x more potent than pleconaril vs EV68 in vitro with no apparent CYP3A4 induction. This compound has demonstrated in vivo efficacy in a 5 day mouse model provided by NIAID.

Recent studies by several research groups have demonstrated enterovirus infection in the pancreas of newly diagnosed type I diabetes (T1D) patients and therefore a strong association with this disease. A clinical trial recently showed that pleconaril and ribavirin can significantly increase serum C-peptide versus placebo, suggesting the potential to preserve insulin production in patients with T1D. Our lead candidate may have applications for T1D and other diseases.

Covid-19

We have leveraged multiple collaborators to pursue small molecule inhibitors. We identified pyronaridine, quinacrine, tilorone and vandetanib as well as many other compounds as active in vitro. Pyronaridine demonstrated efficacy in a mouse model and vandetanib demonstrated activity against the cytokine storm in vitro and in vivo.

Batten Disease (CLN1)

Batten Disease is a genetic disease caused by an autosomal recessive mutation. The infantile onset form termed CLN1 disease is characterized by progressive intellectual and motor deterioration, seizures, loss of vision, and early death. There is currently no treatment for CLN1.

We are developing a recombinant human enzyme replacement therapy for CLN1. A recent paper from our collaborators described the efficacy of this protein in mice and sheep. We are currently manufacturing the protein in preparation for IND enabling toxicity testing. This protein will be delivered ICV. We have had our preIND meeting with the FDA (May 2023).

We have an orphan drug designation and rare pediatric disease designation for this treatment for this disease.

We have also identified several novel small molecules as potential chaperones being tested in vitro.

If you are a CLN1 family and want to hear more about what we are doing please contact us. You can also learn more in our recent presentation below.These foundations also have useful information:

https://bdsra.org/

https://taylorstale.org/

https://haleysheroesfoundation.org

https://beyondbatten.org

http://www.bdfa-uk.org.uk

Cancer

We have developed a novel series of FLT3 inhibitors with activity against several cell lines when tested at the NCI. These molecules are undergoing in vivo testing against models for glioblastoma.

In partnership with the NIH National Cancer Institute (NCI), we have tested over 250 novel small molecules against 60 different cancer cell types to identify lead molecules against 9 different types of cancer. Our small library of compounds represents an unexplored chemical space of potent therapeutics which are under active development as potential new anticancer drugs.

Our most potent therapeutic leads display up to 85% growth inhibition against melanoma and CNS cancer cells in vitro. Other compounds in our library inhibit the growth of colon, renal, lung, prostate, breast, and ovarian cancers between 60 and 80%. We hypothesize that these compounds are a novel class of kinase inhibitors, and current work with this library involves discerning the specific biological mode of action.

Neuroblastoma

We have identified several novel molecules with in vitro activity in neuroblastoma cells.

Chordoma

Along with collaborators in the UNC Catalyst group we determined that a combination of 2 kinase inhibitors appears to demonstrate synergy in vitro and initial in vivo studies appear promising. Animal studies have been performed by the Chrodoma Foundation. We have also used our machine learning models to identify a kinase inhibitor that appears just as active (nM) as the most potent molecules in clinical trials. We have an orphan drug designation for this disease.