Use these links to rapidly review the document TABLE OF CONTENTS Index to The Financial Statements Table of Contents Filed Pursuant to Rule 424(b)(4) Registration No.: 333-210815 PROSPECTUS 3,000,000 Shares Gemphire Therapeutics Inc. Common Stock We are offering 3,000,000 shares of our common stock. This is our initial public offering and no public market currently exists for our common stock. The initial public offering price of our common stock is $10.00 per share. Our common stock has been approved for listing on the NASDAQ Global Market under the symbol "GEMP". We are an emerging growth company as that term is used in the Jumpstart Our Business Startups Act of 2012 and, as such, have elected to comply with certain reduced public company reporting requirements for this prospectus and future filings. Investing in our common stock involves a high degree of risk. See "Risk Factors" beginning on page 12 of this prospectus. Neither the Securities and Exchange Commission nor any state securities commission has approved or disapproved of these securities, or determined if this prospectus is truthful or complete. Any representation to the contrary is a criminal offense. PER SHARE TOTAL Public Offering Price $ 10.00 $ 30,000,000 Underwriting Discounts and Commissions(1) $ 0.70 $ 2,100,000 Proceeds to Gemphire, before expenses $ 9.30 $ 27,900,000 (1) We have agreed to reimburse the underwriters for certain expenses. See "Underwriting." Certain of our existing security holders and their affiliated entities, and other entities and individuals associated with us and them have indicated an interest in purchasing approximately $10 million of shares (or 1,000,000 shares) in the aggregate of our common stock in this offering at the initial public offering price. The underwriters will receive the same underwriting discount on any shares purchased by these entities as they will on any other shares sold to the public in this offering. We have granted the underwriters an option for a period of 30 days to purchase up to an additional 450,000 shares of common stock. If the underwriters exercise the option in full, the total underwriting discounts and commissions payable by us will be $2.4 million, and the total proceeds to us, before expenses will be $32.1 million. The underwriters expect to deliver the shares of common stock to purchasers on or about August 10, 2016. Joint Book-Running Managers Jefferies RBC Capital Markets Co-Lead Manager Canaccord Genuity Co-Managers Laidlaw & Company (UK) Ltd. LifeSci Capital Prospectus dated August 4, 2016 Table of Contents TABLE OF CONTENTS PAGE Prospectus Summary 1 Risk Factors 12 Special Note Regarding Forward-Looking Statements 55 Statistical Data and Market Information 57 Use of Proceeds 58 Dividend Policy 59 Capitalization 60 Dilution 63 Selected Financial Data 65 Management's Discussion and Analysis of Financial Condition and Results of Operations 68 Business 85 Management 132 Executive Officer and Director Compensation 139 Certain Relationships and Related Party Transactions 152 Principal Stockholders 157 Description of Capital Stock 160 Shares Eligible for Future Sale 165 Material U.S. Federal Income Tax Consequences to Non-U.S. Holders of Our Common Stock 167 Underwriting 171 Legal Matters 180 Experts 180 Where You Can Find Additional Information 180 Index to the Financial Statements F-1 We have not authorized anyone to provide you with information that is different from that contained in this prospectus or in any free writing prospectus prepared by or on behalf of us or to which we have referred you. We take no responsibility for, and can provide no assurance as to the reliability of, any other information that others may give you. We and the underwriters are offering to sell our common stock, and seeking offers to buy our common stock, only in jurisdictions where such offers and sales are permitted. You should assume that the information in this prospectus is accurate only as of the date of this prospectus, regardless of the time of delivery of this prospectus or any sale of our common stock. Our business, financial condition, results of operations and prospects may have changed since that date. For investors outside the United States: We have not and the underwriters have not done anything that would permit this offering or possession or distribution of this prospectus in any jurisdiction where action for that purpose is required, other than in the United States. Persons outside the United States who come into possession of this prospectus must inform themselves about, and observe any restrictions relating to, the offering of the shares of common stock and the distribution of this prospectus outside the United States. Through and including August 29, 2016 (25 days after the date of this prospectus), all dealers effecting transactions in these securities, whether or not participating in this offering, may be required to deliver a prospectus. This delivery requirement is in addition to the obligation of dealers to deliver a prospectus when acting as underwriters and with respect to their unsold allotments or subscriptions. i Table of Contents PROSPECTUS SUMMARY This summary highlights information contained in other parts of this prospectus. Because it is only a summary, it does not contain all of the information that you should consider before investing in shares of our common stock and it is qualified in its entirety by, and should be read in conjunction with, the more detailed information appearing elsewhere in this prospectus. You should read the entire prospectus carefully, especially "Risk Factors," "Management's Discussion and Analysis of Financial Condition and Results of Operations" and our financial statements, related notes and other financial information elsewhere in this prospectus, before deciding to buy shares of our common stock. Unless the context requires otherwise, references in this prospectus to "we," "us," "the Company" and "our" refer to Gemphire Therapeutics Inc. Overview We are a clinical-stage biopharmaceutical company focused on developing and commercializing therapies for the treatment of dyslipidemia, a serious medical condition that increases the risk of life threatening cardiovascular disease. Dyslipidemia is generally characterized by an elevation of low- density lipoprotein cholesterol (LDL-C), or bad cholesterol, triglycerides, or fat in the blood, or both. We are developing our product candidate gemcabene (CI-1027), a novel, once-daily, oral therapy, for patients who are unable to achieve normal levels of LDL-C or triglycerides with currently approved therapies, primarily statin therapy. Gemcabene's mechanism of action is designed to enhance the clearance of very low-density lipoproteins (VLDLs) in the plasma and inhibit the production of fatty acids and cholesterol in the liver. Gemcabene is liver-directed and inhibits apolipoprotein C-III (apoC-III) protein in the liver and may inhibit acetyl-CoA carboxylase (ACC) in the liver. Gemcabene has been tested as monotherapy and in combination with statins and other drugs in 895 subjects, which we define as healthy volunteers and patients, across 18 Phase 1 and Phase 2 clinical trials and has demonstrated promising evidence of efficacy, safety and tolerability. Cardiovascular disease is a major health concern, causing more deaths globally than any other disease. Dyslipidemia is generally viewed as an important predictor of cardiovascular events including heart attack and stroke, and a cause of cardiovascular disease. It comprises one of the largest therapeutic areas with annual worldwide drug sales of approximately $22 billion in 2013. We estimate more than 40% of Americans have LDL-C or triglycerides, or both, above a normal range. Statins, such as Lipitor, marketed by Pfizer Inc. (Pfizer), and Crestor, marketed by AstraZeneca Pharmaceuticals LP (AstraZeneca), among others, are standard of care for LDL-C lowering, while fibrates, prescription fish oils and niacin are standar of care for triglyceride lowering. Although these drugs are highly prescribed and capable of reducing LDL-C and triglyceride levels, many patients are unable to effectively manage their dyslipidemia with currently approved therapies and are in need of better treatment alternatives. For example, approximately 40% of patients on statins are unable to meet their LDL-C lowering goal, and doubling a statin dose has shown to incrementally lower LDL-C levels by a nominal percentage (approximately 6% based on historical evidence), while increasing safety and tolerability concerns. An even higher percentage of patients with severe hypertriglyceridemia do not achieve triglyceride levels low enough to reduce the risk of developing co- morbidities such as pancreatitis. We believe gemcabene possesses a differentiated product profile compared to other therapies in the market and in clinical development. Key attribute of our product candidate include the following: § Cost-effective, once-daily, oral therapy. Gemcabene is a small molecule formulated as a tablet and is cost effective to manufacture. As a once-daily, oral therapy, gemcabene, if approved, would be more convenient than other non-statin therapies, many of which require frequent injections or multiple daily doses. We expect to take a value-based approach to pricing across the target indications. § Promising safety and tolerability. Gemcabene was observed to be well tolerated in 895 subjects across 18 Phase 1 and Phase 2 trial both as monotherapy and in combination with statins. No subjects died