Biotech Values

[WorstLuck]

The HBV program ? Well, a hit and a miss. The miss never made it out of phase 1- discontinued quickly and cheaply. Their antiviral got a 4 log drop but is still lacking (in theory) one more antiviral to combine. I've almost stopped following HBV, but it seems to be a tough nut to crack- not an error or failure per se that other companies also didn't make. The fact that Enanta stopped developing seems a conscious risk/reward decision. I have no issue with that.

It got 4 log in mice?

https://www.enanta.com/pipeline/hepatitis-b-virus/

Results demonstrated that EDP-514 was safe and well-tolerated through 28 days of treatment, displayed pharmacokinetics supportive of once-daily dosing, and resulted in mean HBV DNA reductions of 2.9, 3.3, and 3.5 logs at 28 days for the 200 mg, 400 mg, and 800 mg cohorts, respectively, compared to 0.2 log in placebo. HBV RNA was undetectable at Day 28 in 11 patients in the three EDP-514 cohorts as compared to none in placebo. Mean HBV RNA reductions were 2.9, 2.4, and 2.0 logs for the 200 mg, 400 mg, and 800 mg cohorts, respectively, compared to 0.02 log in placebo.

The miss in 721 had the effect of making the whole program a miss.

https://www.biospace.com/enanta-pharmaceuticals-doses-first-subject-in-a-phase-1-clinical-study-of-edp-721-its-oral-hepatitis-b-virus-rna-destabilizer

“We are pleased to advance our HBV program by dosing the first subject in our Phase 1 clinical study of EDP-721, an orally administered HBV RNA destabilizer that has the potential to reduce S antigen. As we believe that achieving a functional cure for HBV will involve a combination approach, this milestone brings us closer to our vision of developing an all-oral regimen for HBV,” said Jay R. Luly, Ph.D., President and Chief Executive Officer of Enanta Pharmaceuticals. “The current standard of care for chronic HBV involves nucleoside reverse transcriptase inhibitors, or NUCs, which can suppress HBV replication. In addition, EDP-514, our potent core inhibitor inhibits several stages of HBV replication, from uncoating and nuclear import of the virus, to capsid assembly and recycling. Now, with EDP-721, we have an oral compound that has demonstrated preclinically the ability to destabilize HBV RNAs, leading to a reduction in viral proteins, including S antigen, which we believe is essential for the treatment of HBV. With this triple combination of a NUC, EDP-514, and EDP-721, we see the potential for an all-oral functional cure and look forward to progressing this study.”

So, they wanted to do HBV on their own. The P1b in 514 was already running when they killed 721, stopping further development after that trial was easy. Was 514 a hit? I think that is the wrong question. They killed the program once they could no longer advance it on their own. Producing a core inhibitor that can't be marketed might be a success of some kind I suppose.

Bottom line is yes, they efficiently killed the program (pretty much forced into it.)