Gemphire Therapeutics provides overview of gemcabene and its clinical trials.

- Gemphire Therapeutics Inc. has announced that the FDA has requested that the Company produce data from a sub-chronic toxicology study to provide information to support lifting the partial clinical hold on gemcabene with respect to clinical trials of longer than six months in duration. The FDA also informed the Company that the End of Phase II meeting, and consequently the initiation of Phase III trials investigating gemcabene in dyslipidemia indications and long-term safety exposure trials needed for registration, will not take place until the partial hold has been lifted.

Gemphire�s ongoing Phase IIa proof-of-concept (POC) studies investigating gemcabene as a treatment for familial partial lipodystrophy (FPL) and for pediatric NAFLD are not affected by the FDA�s request for additional data and the Company continues to expect that these studies will produce top-line interim data in late 2018 and in the first half of 2019, respectively. In addition, the Company continues to be free to conduct clinical trials that do not extend beyond six months in duration.

Beginning in 2004, the FDA began issuing partial clinical holds to all sponsors of PPAR agonists or agents deemed to have PPAR-like properties from preclinical studies. The FDA takes the position that PPAR agonists are potential liver toxins, but recognizes that rodent observations are often not relevant to humans. In 2004, the FDA determined that gemcabene has PPAR agonist properties and issued a partial clinical hold. The partial clinical hold permits clinical trials of up to six months for gemcabene and also required the Company to conduct two-year rat and mouse carcinogenicity studies that are reviewed by the agency in view of all other preclinical data and completed clinical trials before allowing clinical trials of longer than six months.

As previously disclosed, Gemphire believse gemcabene acts through PPAR alpha to cause peroxisome proliferation and tumor formation in rodents and these effects are likely rodent-specific phenomena. Based on historical nonclinical and clinical experience on these type of compounds, the company believes rodents share little apparent relevance for human risk assessment. In recently completed PPAR agonist receptor binding assays, the company observed weak or no gemcabene direct binding to the mouse, rat, or human PPAR alpha, PPAR beta/d, or PPARy receptors. The company has also observed that gemcabene induces markers of peroxisome proliferation in wild-type mice but not in PPAR alpha knockout mice. The company believes the PPAR alpha responses in rats and mice are secondary and perhaps related to the mobilization or formation of a naturally occurring molecule that binds to PPAR alpha in response to gemcabene administration.The Company recently submitted the results of the two-year rat and mouse carcinogenicity studies to the FDA. As would be expected for an activator of PPAR alpha the results showed the presence of liver tumors. The Company also provided results from a short-term, 8 day study demonstrating that in PPAR alpha knockout mice, gemcabene did not induce known markers of peroxisome proliferation, providing evidence that gemcabene works through PPAR alpha. Similar observations in PPAR alpha knockout mice have been seen with other agents, such as gemfibrozil, that cause tumors in rodents but not in humans.

In response the FDA has requested that, as part of a complete response, Gemphire must provide additional data including a subchronic (13 week) study in PPAR alpha knock-out mice and PPAR transactivation assays using monkey and canine PPAR isoforms, to further understand the human relevance of the preclinical findings. The Company has initiated plans to conduct these required studies and expects to submit the additional results to the FDA in the second quarter of 2019.

�We are working closely with the FDA to release the partial clinical hold on gemcabene, with the goal of proceeding to an End of Phase II meeting and reaching agreement on the design of a Phase III clinical program,� said Dr. Steven Gullans, CEO of Gemphire. �Our confidence in gemcabene�s safety profile is supported by the fact that it has been observed to be safe in nearly 1,200 human subjects in 24 Phase 1 and II clinical trials. In fact, gemcabene�s safety performance in previous human clinical provided the basis for the FDA to allow the agent to be evaluated in a multi-center, investigator-led ongoing NAFLD trial in pediatric patients. �In the meantime, we are continuing to execute on our ongoing Phase IIa POC clinical trials of gemcabene in NAFLD/NASH. Gemphire is well capitalized, with $28 million cash on hand as of June 30 2018. Based on current projections, taking into account the delay of significant cash expenditures for clinical trials and manufacturing and the amended terms of the loan agreement with SVB, we believe we have sufficient resources to fund operations into the fourth quarter of 2019.�