NeuroPhage Pharmaceuticals hopes to reinvent itself a bit with a new name, Proclara Biosciences, and a cash infusion of $47 million. The Series E financing brings the total raised by the company to more than $110 million.
The Cambridge, MA-based startup plans to use the funds to support a recently started proof-of-activity Phase Ib trial for its lead candidate, NPT088, to treat Alzheimer’s disease and to advance another molecule, likely NPT289, to IND potentially in transthyretin-related amyloidosis.
The company is pursuing a strategy with a pipeline of molecules aimed specifically at simultaneously correcting multiple misfolded proteins that are implicated in neurodegenerative diseases including amyloid beta, tau and alpha-synuclein.
Proclara expects that its ability to address several forms of protein misfolding simultaneously will be a significant advantage over other neurodegenerative approaches that are in the clinic, like Biogen’s high-profile aducanumab, that target only a single type.
“Both amyloid beta and tau tangles are involved, so for Biogen we are disruptive because we can do with a single molecule what they will ultimately need to do with a combination. That’s really our claim to fame is that we have the only molecule able to target these multiple amyloid aggregates in the brain,” Proclara President and CEO Franz Hefti told FierceBiotech.
“About 95% of experts agree that Alzheimer’s involves amyloid beta and tau aggregation. The fight on which is most important is no longer really important. Amyloid beta is earlier, a predictor of bad things to come. Tau correlates with cognitive decline. Experts agree that an optimal therapy will counteract both of these main events in the Alzheimer’s mechanism,” he concluded.
Helping to drive the company's name change is the fact that it is no longer working on a bacteriophage, as it was for the first 5 years or so after its 2008 inception. Now the focus is on taking a fragment of that and engineering it as part of an antibody. The advantage is expected to be that, unlike the very large molecule bacteriophage that would need to be physically delivered into the brain, the antibody is slated to be a monthly intravenous infusion.
Unlike in most neurodegenerative diseases, Proclara targets multiple misfolded proteins via its general amyloid interaction motif (GAIM) approach. The idea is to target amyloid protein conformation, thereby preventing the misfolded protein assemblies associated with these disorders and the cell-to-cell transmission of toxic aggregates.
NPT088 is a GAIM-Ig fusion protein that’s being initially developed in Alzheimer’s disease and is expected to selectively bind to amyloid beta and tau aggregates. In preclinical testing in Alzheimer’s disease mouse models, NPT088 resulted in improvements in functional endpoints including cognition.
In research supported by the Michael J. Fox Foundation, Proclara also found that NPT088 reduced levels of alpha-synuclein aggregates in an animal model of Parkinson’s disease.
It has tested NPT088 in a Phase Ia study in healthy volunteers in which it was found to be well-tolerated at multiple dose levels. The Phase Ib trial will enroll up to 66 patients with probable Alzheimer’s disease. The randomized, double-blind, placebo-controlled study will measure amyloid beta and tau via PET scan.
The Phase Ib top-line imaging data for NPT088 is due around the end of next year or early 2018. If the candidate is successful in this Phase Ib trial, Proclara expects to advance it directly into Phase II/III trials in Alzheimer’s disease and Parkinson’s disease.
Third Rock Ventures partner Daniel Lynch is joining the Proclara board, although his firm is not an investor in Proclara, as is Nick Leschly, CEO of gene therapy player bluebird bio. The financing was led by undisclosed existing investors, including private investors and Merieux Developpement. Shire previously invested in the company.
Lynch cited the enormous unmet need, the talented team and compelling science as igniting his interest in the company. “The approach of going after amyloid beta and tau--we won’t know until we see the results of this clinical trial--but I’m impressed with the novel approach relative to other drugs in the clinic for Alzheimer’s,” he said.