Arrowhead Pharmaceuticals ($ARWR) and Spring Bank Pharmaceuticals ($SBPH) have partnered to test a couple of hepatitis B candidates in combination. After some initial preclinical testing, the Phase II HBV candidates will be tested together as part of a new, additional arm to an ongoing Phase IIb trial by Arrowhead.
This is the first combination study of two completely novel HBV candidates, the partners said. It will enable the testing of Arrowhead's ARC-520 alongside Spring Bank's Phase IIa oral immunomodulatory small molecule SB-9200 and an approved nuc inhibitor.
The deal is built around Arrowhead’s lead candidate ARC-520, which is its first candidate aimed at providing a functional cure for chronic HBV infection. It’s expected to be more active in patients with relatively high levels of antigen expression from covalently closed circular DNA (cccDNA) rather than being integrated into host DNA.
“ARC-520 appears to be maximally active in patients with higher relative levels of antigen expression from HBV cccDNA versus HBV that has integrated into a host DNA. In e-antigen positive NUC-naïve patients, we saw max s-antigen knockdown of almost two logs or 99%, with an extremely long duration of effect,” summed up Arrowhead President and CEO Christopher Anzalone about early clinical and preclinical data on an August earnings call.
“These and other data let us to believe that ARC-520 is doing precisely what it was designed to do. It appears to be highly active against cccDNA-derived mRNA transcripts and thus can reduce the production of HBV proteins and a pre-genomic RNA. Remember that this virus only makes six things and we hit all of them. For those patients with lower relative levels of cccDNA and higher relative levels of integrated DNA, we developed ARC-521,” he added.
The additional cohort will be part of the MONARCH Phase IIb trial, which was designed to introduce additional arms for combinations with ARC-520, Arrowhead said. It expects the candidate could serve as a backbone for combo therapy.
Arrowhead’s follow-up Phase I HBV candidate, ARC-521, is expected to be more useful in patients with relatively lower levels of cccDNA and higher levels of integrated DNA. It expects the first Phase IIb data for ARC-520 around mid-2017—and anticipates the completion of enrollment this year in a pair of trials in Nuc-experienced patients.
ARC-520 is designed to work upstream of the reverse transcription process, where current standard-of-care nucleotide and nucleoside analogs act. It is intended to silence the production of all HBV gene products. The small interfering RNAs (siRNAs) in ARC-520 aim to reduce the levels of HBV proteins and the RNA template used to produce viral DNA.
“We believe combining SB 9200 with Arrowhead’s ARC-520, along with an approved nucleotide(side) polymerase inhibitor, has the potential to lead to a functional cure,” said Spring Bank CMO Dr. Nezam Afdhal in a statement. “Together, we hope to demonstrate in the MONARCH trial that triple therapy can increase HBV functional cure rates with a more favorable tolerability profile and perhaps a shorter duration of treatment relative to current standard of care with interferon-based regimens.”
The Spring Bank deal comes on the heels of big partnership news last week as Arrowhead partnered with Amgen ($AMGN) to develop cardiovascular RNAi candidates. Spring Bank just went public earlier this year in a tiny $11 million IPO.