Replies to post #209443 on Biotech Values

[DewDiligence]

CEMP drops NASH program (buried in 4Q16 PR in #msg-129069897):

Nonalcoholic steatohepatitis (NASH)

• In September 2016, Cempra announced interim results from an exploratory trial showing anti-NASH effects in the first six NASH patients dosed with solithromycin. Based on the safety profile and activity seen in the first six patients, Cempra continued this study to obtain data from up to 15 NASH patients. In the first quarter of 2017, four additional patients had completed treatment and undergone end-of-treatment liver biopsies, and the company has evaluated the data from the cohort of 10 patients.

• While data from the initial six patients were promising, the overall efficacy from patients receiving a reduced dose of 200 mg three times a week (after a 200 mg loading dose), including the second cohort of four patients, is unclear. Therefore, Cempra has elected to suspend the NASH development program for solithromycin at this time.

They could have omitted the rejoinder, “at this time.” This program will not be restarted.

[DewDiligence]

Imaging endpoints for NASH are being tested—but it’s too soon to say which ones will make the cut:

https://www.biocentury.com/biocentury/product-development/2017-04-14/new-nash-data-show-companies-testing-non-invasive-imaging-

Data on mid-stage NASH candidates to be presented at the…International Liver Congress this month…raise the possibility that, before long, imaging-based endpoints could replace biopsies in clinical trials.

In abstracts released ahead of the International Liver Congress, NGM Biopharmaceuticals Inc., Bristol-Myers Squibb Co. and Gilead Sciences Inc. reported Phase II data demonstrating their non-alcoholic steatohepatitis (NASH) agents led to reductions in liver fat content measured by MRI-proton density fat fraction (MRI-PDFF).

BMS and Gilead also showed reductions in liver stiffness, a measure of fibrosis, as determined by magnetic resonance elastography (MRE).

The imaging-based endpoints are not yet validated, and do not permit comparison with Phase III compounds that have used only the biopsy-based histological endpoints required by FDA and EMA for approval.

…But imaging-based endpoints have the potential to provide more accurate data, as well as reduce burden and risks to patients. As a result, many companies working in NASH are incorporating both imaging and biopsy in ongoing and planned studies.

Please see #msg-129038646 for related discussion.

[DewDiligence]

BMY presents positive phase-2 data on NASH compound, BMS-986036:

http://finance.yahoo.com/news/bristol-myers-squibb-bms-986036-050100126.html

The study achieved its primary endpoint of significant reduction in liver fat versus placebo. Statistically significant improvements were also seen in prespecified exploratory endpoints including biomarkers of fibrosis, metabolic parameters and markers of liver injury.

The obvious question is: What does BMY do next? Do they proceed to a phase-2b monotherapy trial or pair BMS-986036 with a NASH drug that employs a different MoA? My expectation is the latter.

BMY licensed BMS-986036, a PEGylated form of FGF-21, from Ambrx in 2011 (http://ambrx.com/bristol-myers-squibb-and-ambrx-announce-collaboration-for-novel-biologics-programs-in-diabetes-and-heart-failure/ ). Ambrx is private, although it attempted to IPO in 2014 (#msg-103867664).

[DewDiligence]

GILD's CEO at JPM—(NASH) patients with F4 fibrosis have median survival of only 5 years.