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As filed with the Securities and Exchange Commission on May 6, 2021November 13, 2023
Registration No. 333-      ​
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UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
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FORM S-3
REGISTRATION STATEMENT
UNDER
THE SECURITIES ACT OF 1933
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VYNE THERAPEUTICS INC.Therapeutics Inc.

(Exact name of registrant as specified in its charter)
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Delaware​
(State or other jurisdiction of
incorporation or
organization)​
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45-3757789​
(I.R.S. Employer
Identification Number)
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520 U.S. Highway 22,685 Route 202/206 N., Suite 204301
Bridgewater, New Jersey 08807
(800) 775-7936
(Address, Including Zip Code,including zip code, and Telephone Number, Including Area Code,telephone number, including area code of Registrant’s Principal Executive Offices)registrant’s principal executive offices)​
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Mutya Harsch
Chief Legal Officer and General Counsel
VYNE Therapeutics Inc.
520 U.S. Highway 22,685 Route 202/206 N., Suite 204301
Bridgewater, New Jersey 08807
(800) 775-7936
(Name, Address, Including Zip Code,address, including zip code, and Telephone Number, Including Area Code,telephone number, including area code, of Agentagent for Service)service)​
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Copies to:
Andrea L. Nicolas, Esq.Brian Leaf
Skadden, Arps, Slate, Meagher & FlomMark Ballantyne
Cooley LLP
One Manhattan WestFreedom Square, Reston Town Center
New York, New York 1000111951 Freedom Drive
Tel: (212) 735-3000Reston, VA 20190
(703) 456-8000
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From time to time after the effective date of this Registration Statement
(Approximate date of commencement of proposed sale to the public:public)
from time to time after this registration statement becomes effective.
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If the only securities being registered on this Form are being offered pursuant to dividend or interest reinvestment plans, please check the following box. ☐
If any of the securities being registered on this Form are to be offered on a delayed or continuous basis pursuant to Rule 415 under the Securities Act of 1933, other than securities offered only in connection with dividend or interest reinvestment plans, check the following box. ☒
If this Form is filed to register additional securities for an offering pursuant to Rule 462(b) under the Securities Act, please check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering. ☐
If this Form is a post-effective amendment filed pursuant to Rule 462(c) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering. ☐
If this Form is a registration statement pursuant to General Instruction I.DI.D. or a post-effective amendment thereto that shall become effective upon filing with the Commission pursuant to Rule 462(e) under the Securities Act, check the following box. ☐
If this Form is a post-effective amendment to a registration statement filed pursuant to General Instruction I.DI.D. filed to register additional securities or additional classes of securities pursuant to Rule 413(b) under the Securities Act, check the following box. ☐
Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company”company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act.
​Large accelerated filer​​☐​​Accelerated filer    ☐​​☐​
​Non-accelerated filer​​☒​​Smaller reporting company​​☒
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​​​​​​​Emerging growth company​​☒​
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 7(a)(2)(B) of the Securities Act. ☐
CALCULATION OF REGISTRATION FEE
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Title of each class of securities
to be registered
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Amount to be
Registered(1)(2)
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Proposed Maximum
Offering Price Per
Share(1)(2)
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Maximum
Aggregate Offering
Price(1)(2)
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Amount of
Registration
Fee(3)(4)
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Common stock, $0.0001 par value per share​​​​​​​​​​​​​​​​​​​​​​
Preferred stock, $0.0001 par value per share​​​​​​​​​​​​​​​​​​​​​​
Warrants​​​​​​​​​​​​​​​​​​​​​​
Total​​​$200,000,000​​​​​​​$200,000,000​​​​$21,570​​
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(1)
An unspecified number of securities or aggregate principal amount, as applicable, is being registered as may from time to time be offered at unspecified prices, which together shall have an aggregate maximum offering price of $200,000,000.
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(2)
Includes rights to acquire common stock or preferred stock of the Company under any shareholder rights plan then in effect, if applicable under the terms of any such plan.
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(3)
The registration fee has been calculated in accordance with Rule 457(o) under the Securities Act of 1933, as amended.
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(4)
Pursuant to Rule 415(a)(6) under the Securities Act of 1933, securities with a maximum aggregate offering price of $2.3 million registered hereunder are unsold securities previously registered on registration statement No. 333-229482 initially filed on February 1, 2019 (the “Prior Registration Statement”). Pursuant to Rule 415(a)(6) under the Securities Act of 1933, the $278.76 filing fee previously paid in connection with such unsold securities will continue to be applied to such unsold securities. The amount of the registration fee in the “Calculation of Registration Fee” table relates to the additional $197,700,000 maximum aggregate offering price being registered hereunder. As a result, a filing fee of $21,570 is being paid herewith. Pursuant to Rule 415(a)(6) under the Securities Act of 1933, the offering of unsold securities under the Prior Registration Statement will be deemed terminated as of the date of effectiveness of this registration statement.
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The Registrantregistrant hereby amends this registration statement on such date or dates as may be necessary to delay its effective date until the Registrantregistrant shall file a further amendment whichthat specifically states that this registration statement shall thereafter become effective in accordance with Section 8(a) of the Securities Act of 1933 or until the registration statement shall become effective on such date as the Securities and Exchange Commission, acting pursuant to said Section 8(a), may determine.
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The information in this prospectus is not complete and may be changed. WeThe selling stockholders may not sell these securities or accept an offer to buy these securities until the registration statement filed with the Securities and Exchange Commission is effective. This prospectus is not an offer to sell these securities and we areit is not soliciting offers to buy these securities in any jurisdictionstate where thesuch offer or sale is not permitted.
Subject to completion, dated May 6, 2021SUBJECT TO COMPLETION, DATED NOVEMBER 13, 2023
PROSPECTUS
[MISSING IMAGE: lg_vynethera-4c.jpg]
VYNE Therapeutics Inc.39,266,980 Shares
$200,000,000[MISSING IMAGE: lg_vynetherapeu-4c.jpg]
Common Stock Preferred Stock, WarrantsOffered by the Selling Stockholders
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This prospectus relates to the proposed resale from time to time of up to 39,266,980 shares, or the Shares, of our common stock, par value $0.0001 per share, or the common stock, by the selling stockholders named herein, together with any additional selling stockholders listed in a prospectus supplement (together with any of such stockholders’ transferees, pledgees, donees or successors), which consist of (i) 10,652,543 shares of our common stock held by the selling stockholders and (ii) 28,614,437 shares of our common stock issuable upon the exercise of outstanding pre-funded warrants, or the Pre-Funded Warrants, to purchase shares of our common stock held by certain of the selling stockholders. We will not receive any proceeds from the sale of the shares offered by this prospectus, except the exercise price of $0.0001 per share of any of the Pre-Funded Warrants exercised for cash.
The selling stockholders acquired the Shares in a private placement transaction that closed on November 1, 2023, or the Private Placement. We are filing this Registration Statement on Form S-3, of which this prospectus forms a part, to fulfill our contractual obligations with the selling stockholders to provide for the resale by the selling stockholders of the Shares. See “Selling Stockholders” beginning on page 10 of this prospectus for more information about the selling stockholders. The registration of the Shares to which this prospectus relates does not require the selling stockholders to sell any of their Shares, including any shares of common stock issuable upon the exercise of Pre-Funded Warrants.
We are not offering any Shares under this prospectus and will not receive any proceeds from the sale or other disposition of the Shares covered hereby; however, we will receive proceeds from the exercise of the Pre-Funded Warrants. See “Use of Proceeds” beginning on page 9 of this prospectus.
The selling stockholders may offer and sell securities identified aboveor otherwise dispose of the Shares described in this prospectus from time to time in onethrough public or more offeringsprivate transactions at prevailing market prices, at prices related to prevailing market prices or at privately negotiated prices. The selling stockholders will bear all selling commissions applicable to the sales of upShares and all fees and expenses of legal counsel for the selling stockholders, subject to $200,000,000. This prospectus describes the general terms of these securities and the general manner in which these securities will be offered.certain specified exceptions. We will providebear all other costs, expenses and fees in connection with the specific termsregistration of these securities in onethe Shares. See the section titled “Plan of Distribution” for more information about how the selling stockholders may sell or more supplements to this prospectus. The prospectus supplements will also describe the specific manner in which these securities will be offered and may also supplement, update or amend information contained in this document. You should read this prospectus and any applicable prospectus supplement before you invest.
We may offer these securities in amounts, at prices and on terms determined at the timedispose of offering. The securities may be sold directly to you, through agents, or through underwriters and dealers. If agents, underwriters or dealers are used to sell the securities, we will name them and describe their compensation in a prospectus supplement.its Shares.
Our common stock is listed on the NASDAQ Global SelectThe Nasdaq Capital Market under the trading symbol “VYNE.” On November 10, 2023, the closing price of our common stock was $3.51 per share.
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Investing in these securitiesshares of our common stock involves certain risks. Seea high degree of risk. You should review carefully the risks and uncertainties described in the section titled “Risk Factors” on page 46 of this prospectus and any similar section includedcontained in any accompanyingthe applicable prospectus supplement and in any free writing prospectuses we have authorized for use in connection with a specific offering, and under similar headings in the documents that are incorporated by reference ininto this prospectus. You should carefully consider these risks before you make your investment decision.
We may offer these securities through underwriting syndicates managed or co-managed by one or more underwriters or dealers, through agents or directly to purchasers. If required, the prospectus supplement for each offering of securities will describe the plan of distribution for that offering. For general information about the distribution of securities offered, please see “Plan of Distribution” in this prospectus.
Neither the Securities and Exchange Commission nor any state securities commission has approved or disapproved of these securities or passed upon the adequacy or accuracy ofdetermined if this prospectus is truthful or any accompanying prospectus supplement.complete. Any representation to the contrary is a criminal offense.
The date of this prospectus is           , 2021.2023.
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ABOUT THIS PROSPECTUS
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PROSPECTUS SUMMARY
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WHERE YOU CAN FIND MORE INFORMATION; INCORPORATION BY REFERENCE
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PROSPECTUS SUMMARYTHE OFFERING
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RISK FACTORS
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FORWARD-LOOKING STATEMENTS
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USE OF PROCEEDS
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PLAN OF DISTRIBUTIONSPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS
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DESCRIPTIONUSE OF CAPITAL STOCKPROCEEDS
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DESCRIPTION OF WARRANTSSELLING STOCKHOLDERS
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PLAN OF DISTRIBUTION
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LEGAL MATTERS
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EXPERTS
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WHERE YOU CAN FIND ADDITIONAL INFORMATION
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INCORPORATION OF CERTAIN INFORMATION BY REFERENCE
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ABOUT THIS PROSPECTUS
This prospectus is part of a registration statement on Form S-3 that we filed with the Securities and Exchange Commission, or the SEC, utilizingusing a “shelf” registration process. Under this shelf registration process, wethe selling stockholders may from time to time sell the securitiesshares of common stock described in this prospectus in one or more offerings for an aggregate initial offering priceor otherwise as described under “Plan of up to $200,000,000.Distribution.”
This prospectus provides you with a general description of the securities we may offer. Eachbe supplemented from time we sell securities, we will provideto time by one or more prospectus supplements that will contain specific information about the terms of the offering, including the specific amounts, prices and terms of the securities offered. Thesupplements. Such prospectus supplement may also add, update or change information contained in this prospectus. If there is any inconsistency between the information in this prospectus and the applicable prospectus supplement, you must rely on the information in the prospectus supplement. You should carefully read both this prospectus the accompanyingand any applicable prospectus supplement and any free writing prospectus prepared by or on behalf of us, together with the additional information described under the heading “Where You Can Find More Information; Incorporation by Reference” beginning on page 1 of this prospectus.Additional Information” before deciding to invest in any shares being offered.
You should rely only onNeither we nor the selling stockholders have authorized anyone to provide any information other than that contained in or incorporated by reference in this prospectus any accompanying prospectus supplement or in any related prospectus supplement or any free writing prospectus filed by us with the SEC. Wethat we have not authorized anyone to provide you with different information.authorized. We take no responsibility for, and can provide no assurance as to the reliability of, any other information that others may give you. This prospectus and any accompanying prospectus supplement do not constitute an offer to sell or the solicitation of an offer to buy any securities other than the securities described in this prospectus or such accompanying prospectus supplement or an offer to sell or the solicitation of an offer to buy such securities in any circumstances in which such offer or solicitation is unlawful. WeThe Shares are not making offers to sell the securitiesbeing offered in any jurisdiction in which anwhere the offer or solicitation is not authorized or in which the person making such offer or solicitation is not qualified to do so or to anyone to whom it is unlawful to make an offer or solicitation.permitted. You should not assume that the information appearingcontained in or incorporated by reference in this prospectus any prospectus supplement, the documents incorporated by reference and any related free writing prospectus is accurate only as of theirany date other than the respective dates.dates of such document. Our business, financial condition, results of operations and prospects may have changed materially since those dates.
Unless the context otherwise indicates,stated, all references in this prospectus to “we,” “us,” “our,” “us”“the company,” “VYNE” and “VYNE”“VYNE Therapeutics,” and similar designations, except where the context requires otherwise, refer collectively to VYNE Therapeutics Inc., a Delaware corporation.
WHERE YOU CAN FIND MORE INFORMATION; INCORPORATION BY REFERENCE
Available Information
We file reports, proxy statements and other informationcorporation, together with the SEC. The SEC maintains a website that contains reports, proxy and information statements and other information about issuers, such as us, who file electronically with the SEC. The address of that website is http://www.sec.gov.
Our website address is www.vynetherapeutics.com. The information on our website, however, is not, and should not be deemed to be, a part of this prospectus. We have included our website address as an inactive textual reference only.
Incorporation by Reference
The SEC’s rules allow us to “incorporate by reference” information into this prospectus, which means that we can disclose important information to you by referring you to another document filed separately with the SEC. The information incorporated by reference is deemed to be part of this prospectus, and subsequent information that we file with the SEC will automatically update and supersede that information. Any statement contained in this prospectus or a previously filed document incorporated by reference will be deemed to be modified or superseded for purposes of this prospectus to the extent that a statement contained in this prospectus or a subsequently filed document incorporated by reference modifies or replaces that statement.
We incorporate by reference our documents listed below and any future filings made by us with the SEC under Sections 13(a), 13(c), 14 or 15(d) of the Securities Exchange Act of 1934, as amended, which we

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refer to as the “Exchange Act” in this prospectus, between the date of this prospectus and the termination of the offering of the securities described in this prospectus. We are not, however, incorporating by reference any documents or portions thereof, whether specifically listed below or filed in the future, that are not deemed “filed” with the SEC, including any information furnished pursuant to Items 2.02 or 7.01 of Form 8-K or related exhibits furnished pursuant to Item 9.01 of Form 8-K.
This prospectus and any accompanying prospectus supplement incorporate by reference the documents set forth below that have previously been filed with the SEC:
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our Annual Report on Form 10-K for the year ended December 31, 2020, filed with the SEC on March 4, 2021, as amended by Amendment No.1 to the Annual Report on Form 10-K, filed with the SEC on April 20, 2021;
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our Quarterly Report on Form 10-Q for the quarter ended March 31, 2021 filed with the SEC on May 6, 2021;
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our Current Reports on Form 8-K filed with the SEC on January 28, 2021 and February 12, 2021; and
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the description of our common stock contained in our registration statement on Form 8-A filed with the SEC on January 19, 2018, including any amendments or reports filed for the purpose of updating such description.
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All reports and other documents we subsequently file pursuant to Section 13(a), 13(c), 14 or 15(d) of the Exchange Act prior to the termination of this offering, including all such documents we may file with the SEC after the date of the initial registration statement and prior to the effectiveness of the registration statement, but excluding any information furnished to, rather than filed with, the SEC, will also be incorporated by reference into this prospectus and deemed to be part of this prospectus from the date of the filing of such reports and documents.
You may request a free copy of any of the documents incorporated by reference in this prospectus (other than exhibits, unless they are specifically incorporated by reference in the documents) by writing or telephoning us at the following address:
VYNE Therapeutics Inc.
520 U.S. Highway 22, Suite 204
Bridgewater, New Jersey 08807
(800) 775-7936
Exhibits to the filings will not be sent, however, unless those exhibits have specifically been incorporated by reference in this prospectus and any accompanying prospectus supplement.its consolidated subsidiaries.
 
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PROSPECTUS SUMMARY
The followingThis summary highlights someselected information about VYNE. It is not completecontained elsewhere in this prospectus and in the documents we incorporate by reference. This summary does not contain all of the information that you should consider before making an investment decision.investing in our common stock. You should read this entire prospectus includingcarefully, especially the risks of investing in our common stock discussed in the section titled “Risk Factors” section on page 4 and under similar headings in our filings with the disclosures toSEC which that section refers you, theare incorporated by reference in this prospectus, along with our consolidated financial statements and related notes to those consolidated financial statements and the other more detailed information appearing elsewhere or incorporated by reference intoin this prospectus, before investing in any of the securities described in this prospectus.making an investment decision.
Company Overview
We are a specialty pharmaceuticalclinical-stage biopharmaceutical company focused on developing proprietary, innovative and differentiated therapies in dermatology and beyond. Our products, AMZEEQ® (minocycline) topical foam, 4% (“AMZEEQ”) for the treatment of inflammatory lesions of moderate-to-severe acne vulgaris in adultsimmuno-inflammatory conditions.
In August 2021, we entered into a transaction with Tay Therapeutics Limited (formerly known as In4Derm Limited, or Tay) providing us with exclusive worldwide rights to research, develop and patients 9 years of agecommercialize products containing bromodomain and older, and ZILXI® (minocycline) topical foam, 1.5% (“ZILXI”)extra-terminal domain, or BET, inhibitors for the treatment of inflammatory lesionsany disease, disorder or condition in humans. Through our access to this library of rosaceanew chemical BET inhibitor compounds, we plan to develop product candidates for a diverse set of indications. Based on preclinical data generated to date, we have chosen to focus our initial efforts for this platform on select therapeutic areas in adults, are the first topical minocycline products to be approved by the FDA. AMZEEQ and ZILXI were commercially launched in January and October of 2020, respectively, and serveimmuno-inflammatory disease.
Our lead program is VYN201, a locally administered pan-BD BET inhibitor designed as a springboard for commercializing additional innovative products. Our product pipeline includes FCD105 (minocycline 3%“soft” drug to address diseases involving multiple, diverse inflammatory cell signaling pathways while providing low systemic exposure. To date, VYN201 has produced consistent reductions in pro-inflammatory and adapalene 0.3%) (“FCD105”), our proprietary noveldisease-related biomarkers, improvements in disease severity and a demonstrated local activity through several preclinical models. In November 2022, we initiated a Phase 1a/b clinical trial evaluating a topical combination foam formulation of minocycline and adapaleneVYN201 for the treatment of moderate-to-severe acne vulgaris. FCD105nonsegmental vitiligo. In February 2023, we announced positive preliminary safety and tolerability data from the Phase 1a portion of the trial. In addition, in March 2023, we announced positive pharmacokinetic and hematology data from the Phase 1a trial. The first nonsegmental vitiligo patient was dosed in the Phase 1b portion of the trial in January 2023, and on October 30, 2023, we announced positive data from the Phase 1b trial noting that significant clinical improvement in facial vitiligo area scoring index (F-VASI) was observed in the 1% and 2% cohorts of participating subjects after 16 weeks of treatment. We have initiated Phase 2b preparatory activities and expect to advance VYN201 into a longer duration Phase 2b trial to evaluate optimal dosing and peak efficacy in patients with active and stable nonsegmental vitiligo in the first half of 2024, with top-line results expected in mid-2025.
Our second program is a Phase 3-ready asset thatVYN202, an oral small molecule BD2-selective BET inhibitor. VYN202 is in preclinical development for the treatment of immuno-inflammatory indications, and has been designed to achieve class-leading selectivity (BD2 vs. BD1), maximum potency on BD2 and optimal oral bioavailability. By maximizing BD2 selectivity, we believe VYN202 has the potential to be a best-in-classmore conveniently-administered non-biologic treatment option for patientsboth acute control and chronic management of immuno-inflammatory indications, where the damaging effects of unrestricted inflammatory signaling activity is common. We expect to submit our IND for VYN202 by year-end 2023 and commence a first-in-human Phase 1a single ascending dose/multiple ascending dose trial in the first quarter of 2024. Upon successful completion of the Phase 1a study, we expect to initiate Phase 1b trials in moderate-to-severe plaque psoriasis and in moderate-to-severe adult-onset rheumatoid arthritis in the second half of 2024, with acne. In addition,top-line results expected in mid-2025.
We intend to advance our product candidates through the clinic toward regulatory approval, and may also partner with leading pharmaceutical companies to expand and accelerate the development of our programs and explore therapeutic areas outside of our core focus in immunology to maximize the value of our pipeline.
Private Placement
On October 27, 2023, we announcedentered into a development program for FMX114,securities purchase agreement, or the Purchase Agreement, with certain institutional and other accredited investors, or the Purchasers, pursuant to which is a combination topical gelwe agreed to

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sell and issue to the Purchasers in the Private Placement (i) 10,652,543 shares of our common stock and (ii) with respect to certain Purchasers, the Pre-Funded Warrants to purchase 28,614,437 shares of common stock in lieu of shares of common stock. The purchase price per share of common stock was $2.245 per share, or the Purchase Price, and the purchase price for the potential treatmentPre-Funded Warrants was the Purchase Price minus $0.0001 per Pre-Funded Warrant. We received gross proceeds of mild-to-moderate atopic dermatitis. We plan$88.2 million from the Private Placement, before deducting fees to conductthe placement agent and offering expenses payable by us. The closing of the Private Placement occurred on November 1, 2023.
The Pre-Funded Warrants have a Phase 2a proof-of-concept study for FMX114per share exercise price of $0.0001, subject to proportional adjustments in the third quarterevent of 2021.
AMZEEQ and ZILXI utilize our proprietary Molecule Stabilizing Technology (MST)™ delivery system that is also being used to develop FCD105. Our MST™ proprietary foam platform is designed to optimizestock splits or combinations or similar events. The Pre-Funded Warrants will not expire until exercised in full. The Pre-Funded Warrants may not be exercised if the topical delivery of minocycline, an active pharmaceutical ingredient (“API”) that was previously available only in oral form despite its prevalent use in dermatology. In addition to the MST platform, we have aaggregate number of proprietary delivery platformsshares of common stock beneficially owned by the holder thereof immediately following such exercise would exceed a specified beneficial ownership limitation; provided, however, that a holder may increase or decrease the beneficial ownership limitation by giving 60 days’ notice to us, but not to any percentage in developmentexcess of 19.99%.
The Shares were not initially registered under the Securities Act of 1933, as amended, or the Securities Act. Based in part upon the representations of the Purchasers in the Purchase Agreement, we relied on the exemption afforded by Regulation D under the Securities Act, and corresponding provisions of state securities or “blue sky” laws. Each of the Purchasers represented in the Purchase Agreement that enable topical delivery of other APIs, each having unique pharmacological features and characteristics designed to keep the API stable when delivered and directed to the target site. We believe our MST vehicles and other topical delivery platforms may offer significant advantages over alternative delivery options and are suitable for multiple application sites across a range of conditions.
We areit was an “emerging growth company,”“accredited investor” as defined in Section 2(a)Regulation D of the Securities Act and as modifiedthat it was acquiring the securities for investment only and not with a view towards, or for resale in connection with, the public sale or distribution thereof, and appropriate legends will be affixed to the securities. The sale of the securities did not involve a public offering and was made without general solicitation or general advertising.
On October 27, 2023, we also entered into a registration rights agreement with the Purchasers, or the Registration Rights Agreement, pursuant to which we agreed to prepare and file, by November 26, 2023, or the Filing Deadline, one or more registration statements with the SEC to register for resale the Shares, and to cause the applicable registration statements to become effective within a specified period after the Filing Deadline, or the Effectiveness Deadline.
In the event (i) the registration statement has not been filed by the JOBS ActFiling Deadline or has not been declared effective by the SEC by the Effectiveness Deadline, subject to certain limited exceptions, or (ii) sales of all the registrable securities required to be included on such registration statement cannot be made for more than ten consecutive calendar days or more than an aggregate of 15 calendar days during any 12-month period pursuant to such registration statement, we have agreed to make pro rata payments to each Purchaser as liquidated damages in an amount equal to 1.0% of the Purchaser’s aggregate amount invested by such Purchaser for the registrable securities until such event is cured, subject to certain caps set forth in the Registration Rights Agreement.
We granted the Purchasers customary indemnification rights in connection with the registration statement. The Purchasers have also granted us customary indemnification rights in connection with the registration statement.
The registration statement of which this prospectus is a part relates to the offer and resale of the Shares issued to the Purchasers pursuant to the Purchase Agreement, including the shares of our common stock issuable upon the exercise of outstanding pre-funded warrants. When we refer to the selling stockholders in this prospectus, we are referring to the Purchasers and, as applicable, any donees, pledgees, assignees, transferees or other successors-in-interest selling the Shares received after the date of this prospectus from the selling stockholders as a gift, pledge, or other non-sale related transfer.
Following the closing of the Private Placement, as of November 3, 2023, we had 13,957,324 shares of common stock outstanding.
Risks Associated with Our Business
Our business is subject to numerous risks and uncertainties that you should be aware of in making an investment decision with respect to our common stock. These risks include, but are not limited to, the following:
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Our business is substantially dependent on the successful development of our BET inhibitor product candidates.
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We may encounter delays in enrolling patients and successfully completing clinical trials for our product candidates, and may even be prevented from commencing such trials due to factors that are largely beyond our control.
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Clinical drug development is very expensive, time-consuming and uncertain. Our clinical trials may fail to adequately demonstrate the safety and efficacy of our current or any future product candidates, which could prevent or delay regulatory approval and commercialization.
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New chemical entities may require more time and resources for development, testing and regulatory approval.
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Our clinical trials may fail to demonstrate the safety and efficacy of our product candidates, or serious adverse or unacceptable side effects may be identified during the development of our product candidates, which could result in the abandonment or limitation of the development of our product candidates or prevent or delay our ability to pursue strategic alternatives for our product candidates.
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Results obtained in non-clinical studies and completed clinical trials may not predict success in later clinical trials.
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Topline and preliminary data from our clinical trials that we announce or publish from time to time may change as additional data become available and are subject to audit and verification procedures that could result in material changes in the final data.
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We have a limited history as a clinical-stage biopharmaceutical company developing product candidates for immuno-inflammatory conditions, which may make it difficult to assess our future viability.
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We may spend our limited resources to pursue a particular product candidate or indication and fail to capitalize on product candidates or indications that may be more profitable or for which there is a greater likelihood of success.
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We are subject to various risks and uncertainties, including litigation, arising out of the completed divestiture of our commercial business.
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We have not obtained regulatory approvals to market our other pipeline product candidates, and we may be delayed in obtaining or fail to obtain such regulatory approvals and to commercialize these product candidates.
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Intellectual property rights that we seek to protect our product candidates, including patent applications, may not be granted, may be narrowed, held to be invalid or unenforceable.
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Our intellectual property rights may be challenged by third parties.
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Our failure to develop and market additional product candidates or successfully out-license, sell or partner any of our product candidates could impair our ability to grow our business. We may engage in strategic partnering transactions, which could impact our liquidity, increase our expenses and present significant distractions to our management.
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We may decide not to continue developing any of our product candidates at any time during development or of any of our products after approval, which would reduce or eliminate our potential return on investment for those product candidates or products.
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We are subject to various U.S. federal, state, local and foreign health care fraud and abuse laws, including anti-kickback, self-referral, false claims and fraud laws, health information privacy and security, and transparency laws, and any violations by us of such laws could result in substantial penalties or other consequences including criminal sanctions, civil penalties, contractual damages, reputational harm, and diminished profits and future earnings. Additionally, any challenge to or investigation into our practices under these laws could cause adverse publicity and be costly to respond to, and thus could harm our business.
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Legislative or regulatory healthcare reforms in the United States may make it more difficult and costly for us to obtain regulatory clearance or approval of our product candidates and to produce, market, and distribute our products after clearance or approval is obtained.
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The trading price of the shares of our common stock is volatile, and stockholders could incur substantial losses.
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Company Information
We were incorporated in October 2011 as a Delaware corporation under the name Tigercat Pharma, Inc. We changed our name to VYNE Therapeutics Inc. in September 2020, following the merger between Foamix Pharmaceuticals Ltd. and Menlo Therapeutics Inc. in March 2020.
Our principal executive offices are located at 685 Route 202/206 N., Suite 301, Bridgewater, New Jersey 08807 and our telephone number is (800) 775-7936. Our website address is www.vynetherapeutics.com. The information contained on, or accessible through, our website is not incorporated by reference into this prospectus. We have included our website in this prospectus solely as an inactive textual reference.
Implications of Being an Emerging Growth Company and a “smaller reporting company,”Smaller Reporting Company
We qualify as an “emerging growth company” as defined in Rule 12b-2the Jumpstart Our Business Startups Act of 2012, or the ExchangeJOBS Act. As such,For so long as we are eligible toremain an emerging growth company, we may take advantage of certain exemptionsrelief from variouscertain reporting requirements such asand other burdens that are otherwise applicable generally to public companies. These provisions include:
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reduced obligations with respect to financial data, including only being required to present two years of audited financial statements, in addition to any required unaudited interim financial statements with correspondingly reduced “Management’s Discussion and Analysis of Financial Condition and Results of Operations” disclosure;
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an exception from compliance with the auditor attestation requirements of Section 404 of the Sarbanes-Oxley Act of 2002, as amended;
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reduced disclosure about our executive compensation arrangements in our periodic reports, proxy statements and registration statements;
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exemptions from the requirements of holding non-binding advisory votes on executive compensation or golden parachute arrangements; and
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an exemption from compliance with the requirements of the Public Company Accounting Oversight Board regarding the communication of critical audit matters in the auditor’s report on financial statements.
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We may take advantage of these provisions until we cease to be an emerging growth company on December 31, 2023. We may choose to take advantage of some but not all of these reduced reporting burdens. We have taken advantage of certain reduced reporting requirements in this prospectus. Accordingly, the information contained herein may be different than you might obtain from other public companies in which you hold equity interests. Under Section 107(b) of the JOBS Act, emerging growth companies can delay adopting new or scaledrevised accounting standards until such time as those standards apply to private companies. We have irrevocably elected not to avail ourselves of this exemption from new or revised accounting standards and, therefore, we will be subject to the same new or revised accounting standards as other public companies that are not emerging growth companies.
We are also a “smaller reporting company,” as defined in Rule 12b-2 of the Securities Exchange Act of 1934, or the Exchange Act, meaning that the market value of our shares held by non-affiliates is less than $700 million and our annual revenue was less than $100 million during the most recently completed fiscal year. We may continue to be a smaller reporting company if either (i) the market value of our shares held by non-affiliates is less than $250 million or (ii) our annual revenue was less than $100 million during the most recently completed fiscal year and the market value of our shares held by non-affiliates is less than $700 million. If we are a smaller reporting company at the time we cease to be an emerging growth company on December 31, 2023, we may continue to rely on exemptions from certain disclosure requirements that are available to smaller reporting companies.
Our principal Specifically, as a smaller reporting company, we may choose to present only the two most recent fiscal years of audited financial statements in our Annual Report on Form 10-K and, similar to emerging growth companies, smaller reporting companies have reduced disclosure obligations regarding executive offices are located at 520 U.S. Highway 22, Suite 204, Bridgewater, NJ 08807. Our website is www.vynetherapeutics.com.compensation. Additionally, as a smaller reporting company, we may continue to take advantage of the exception from compliance with the auditor attestation requirements of Section 404 of the Sarbanes-Oxley Act of 2002, as amended.
 
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THE OFFERING
Common Stock Offered by the Selling Stockholders
39,266,980 Shares (consisting of 10,652,543 outstanding shares of our common stock and 28,614,437 shares of our common stock issuable upon the exercise of the Pre-Funded Warrants).
Use of Proceeds
The selling stockholders will receive all of the proceeds from the sale of the Shares hereunder. Accordingly, we will not receive any of the proceeds from the sale of the Shares in this offering; however, we will receive nominal proceeds from any cash exercise of the Pre-Funded Warrants. See “Use of Proceeds.”
Risk Factors
An investment in our common stock involves a high degree of risk. See the information contained in or incorporated by reference in the section titled “Risk Factors” and under similar headings in the other documents that are incorporated by reference herein, as well as the other information included in or incorporated by reference in this prospectus.
Nasdaq Capital Market
Symbol
Our common stock is listed on The Nasdaq Capital Market under the symbol “VYNE.”

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RISK FACTORS
InvestingAn investment in our securitiescommon stock involves significant risks. Please seea high degree of risk. Prior to making a decision about investing in our common stock, you should consider carefully the specific risk factors underdiscussed in the headingsections titled “Risk Factors” contained in our most recent Annual Report on Form 10-K or Quarterly Report on Form 10-Q, as amended bywell as any amendments thereto and those containedreflected in our othersubsequent filings with the SEC, thatwhich are incorporated by reference into this prospectus in their entirety, together with other information in this prospectus, the documents incorporated by reference, any prospectus supplement and any accompanyingfree writing prospectus supplement. Before making an investment decision, you should carefully consider these risks as well as other informationthat we include or incorporate by reference in this prospectus and any prospectus supplement.may authorize. These risks could materially affect our business, financial condition or results of operations and causeuncertainties are not the value of our securities to decline. Theonly risks and uncertainties we have described are not the only ones facing our company.face. Additional risks and uncertainties not presently known to us, or that we currently deemview as immaterial, may also affectimpair our business. If any of the risks or uncertainties described in our SEC filings or any additional risks and uncertainties actually occur, our business, operations. The occurrencefinancial condition, results of anyoperations and cash flow could be materially and adversely affected. In that case, the trading price of these risksour common stock could decline and you might cause you to lose all or part of your investment in the offered securities. The discussion of risks includes or refers to forward-looking statements. You should read the explanation of the qualifications and limitations on such forward-looking statements discussed elsewhere in this prospectus.investment.

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SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS
This prospectus contains expressand the documents incorporated by reference herein contain forward-looking statements. These are based on our management’s current beliefs, expectations and assumptions about future events, conditions and results and on information currently available to us. Discussions containing these forward-looking statements may be found, among other places, in the sections entitled “Business,” “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” contained in the documents incorporated by reference herein.
Any statements in this prospectus, or implied “forward-looking statements” withinincorporated herein, about our expectations, beliefs, plans, objectives, assumptions or future events or performance are not historical facts and are forward-looking statements. Within the meaning of Section 27A of the Private Securities Litigation Reform Act and Section 21E of 1995 and other U.S. Federal securities laws. Thesethe Exchange Act, these forward-looking statements include but are not limited to, statements regarding the following matters:regarding:
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our ability to successfully commercialize AMZEEQ and ZILXI andexecute our other product candidates, if approved;business strategy, including our ability to successfully develop our BET inhibitor platform for immuno-inflammatory conditions;
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disruptions relatedour ability to COVID-19 or another pandemic, epidemic or outbreak of a contagious disease, on the ability of our suppliers to manufactureenroll patients and provide materialssuccessfully complete, and receive favorable results in, clinical trials for our products and product candidates, initiating and retaining patients in our clinical trials, distribution of our products and business sales execution, operating results, liquidity and financial condition;candidates;
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the regulatory approval processtiming of commencement of future preclinical studies and clinical trials;
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our pursuit of, and ability to successfully identify and execute, strategic transactions;
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estimates of our expenses, capital requirements, our needs for additional financing and our product candidates, including any delayability to obtain additional capital on acceptable terms or failure in obtaining requisite approvals;at all;
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the potential market size of treatments for any diseases and market adoption of our products, if approved or cleared for commercial use, by physicians and patients;
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the timing, cost or other aspectsrisks and uncertainties arising out of the commercializationcompleted divestiture of AMZEEQ, ZILXIour commercial business;
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disruptions related to macroeconomic conditions on our ability to initiate and retain patients in our clinical trials and progress preclinical studies and the ability of our suppliers to manufacture and provide materials for our product candidates, if approved;candidates;
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our ability to achieve favorable pricingcreate or in-license intellectual property and the scope of protection we are able to establish and maintain for AMZEEQ, ZILXI andintellectual property rights covering our product candidates if approved;and programs, including the projected terms of patent protection;
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third-party payor reimbursementthe regulatory approval process for AMZEEQ, ZILXI andour product candidates, including any future products;delay or failure in obtaining requisite approvals;
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developments and projections relating to our competitors and our industry,the markets in which we compete, including competing drugs and therapies, particularly if we are unable to receive exclusivity;
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risks related to our indebtedness, including our ability to comply with the covenants in our loan documents;
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the timing of commencement of future non-clinical studies and clinical trials;
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our ability to successfully complete, and receive favorable results in, clinical trials for our product candidates;
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our intentions and our ability to establish collaborations or obtain additional funding;
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the timing or likelihood of regulatory filings and approvals or clearances for our product candidates;
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our ability to comply with various regulations applicable to our business;
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our expectations regarding the commercial supply of AMZEEQ, ZILXI andability to successfully challenge intellectual property claimed by others or otherwise protect our product candidates;intellectual property;
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our ability to create intellectual property and the scope of protection we are able to establish and maintain for intellectual property rights covering our product candidates, including the projected terms of patent protection;
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the timing, costs or results of litigation, including litigation to protect our intellectual property, including our ability to challenge successfully intellectual property claimed by others;
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estimates of our expenses, future revenue, capital requirements, our needs for additional financingintentions and our ability to establish collaborations or obtain additional capital on acceptable terms or at all;funding;
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our ability to attract and retain key scientific or management personnel;
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our defense of current and any future litigation that may be initiated against us;
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our expectations regarding licensing, business transactions and strategic operations; and
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our future financial performance and liquidity.liquidity; and
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In some cases, forward-looking statements are identified by terminology such as “may,” “will,” “could,” “should,” “expects,” “plans,” “anticipates,” “believes,” “intends,” “estimates,” “predicts,” “potential,” or “continue” or the negative of these terms or •
other comparable terminology. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results or performance to differ materially from those projected. These statements are only current predictions and are subject to known and unknown risks, uncertainties, and other factors that may cause our or our industry’s actual results, levels of activity, performance or achievements to be materially different from those anticipated by the forward-looking statements. In addition, historic results of scientific research and clinical and preclinical trials do not guarantee that the conclusions of future research or trials would not be different, and historic results referred to in our most recent Annual Report on Form 10-K, as amended, may be interpreted differently in light of additional research and clinical and preclinical trials results. The forward-looking statements contained in this prospectus are subject to risks and uncertainties, including those discussedlisted under the headingcaption “Risk Factors” in our most recent Annual Report on Form 10-K, as amended,Quarterly Report on Form 10-Q and in our other filings we make with the SEC. Readers are cautioned not to place undue reliance on these
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In some cases, you can identify forward-looking statements which speak only as ofby the date hereof. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance, or achievements. Except as required by law, we are under no duty to (and expressly disclaim any such obligation to) update or revise any of the forward-looking statements, whether as a result of new information, future events or otherwise, after the date of this prospectus.

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USE OF PROCEEDS
We intend to use the net proceeds from the sale of any securities offered under this prospectus for funding our commercialization and/or research and development activities and for general corporate purposes unless otherwise indicated in the applicable prospectus supplement. General corporate purposes may include the acquisition of companies or businesses, repayment and refinancing of debt, working capital, clinical trial expenditures, commercial expenditures and capital expenditures. We have not determined the amount of net proceeds towords “may,” “might,” “can,” “will,” “to be, used specifically for such purposes. As a result, management will retain broad discretion over the allocation of net proceeds.
PLAN OF DISTRIBUTION
We may sell the securities being offered hereby in one or more of the following ways from time to time:
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through underwriters for resale to purchasers;
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through dealers to purchasers;
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through agents to purchasers;
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directly to one or more purchasers; or
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through a combination of any of these methods of sale.
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We may also sell the securities covered by this registration statement in an “at the market offering” as defined in Rule 415 under the Securities Act. Such offering may be made into an existing trading market for such securities in transactions at other than a fixed price, either:
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on or through the facilities of the NASDAQ Global Market or any other securities exchange or quotation or trading service on which such securities may be listed, quoted or traded at the time of sale; and/or
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to or through a market maker other than on the NASDAQ Global Market or such other securities exchanges or quotation or trading services.
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We may directly solicit offers to purchase securities, or agents may be designated to solicit such offers. We will, in the prospectus supplement relating to such offering, name any agent that could be viewed as an underwriter under the Securities Act, and describe any commissions that we must pay. Any such agent will be acting on a best efforts basis for the period of its appointment or, if indicated in the applicable prospectus supplement, on a firm commitment basis.
The distribution of the securities may be effected from time to time in one or more transactions:
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at a fixed price, or prices, which may be changed from time to time;
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at market prices prevailing at the time of sale; or
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at prices related to such prevailing market prices;
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Each prospectus supplement will describe the method of distribution of the securities and any applicable restrictions.
The prospectus supplement with respect to the securities of a particular series will describe the terms of the offering of the securities, including the following:
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the name of the agent or any underwriters;
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the public offering or purchase price and the proceeds we will receive from the sale of the securities;
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any discounts and commissions to be allowed or re-allowed or paid to the agent or underwriters;
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all other items constituting underwriting compensation;
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any discounts and commissions to be allowed or re-allowed or paid to dealers; and
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any exchanges on which the securities will be listed.
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If any underwriters or agents are utilized in the sale of the securities in respect of which this prospectus is delivered, we will enter into an underwriting agreement or other agreement with them at the time of sale to them, and we will set forth in the prospectus supplement relating to such offering the names of the underwriters or agents and the terms of the related agreement with them.
If a dealer is utilized in the sale of the securities in respect of which this prospectus is delivered, we will sell such securities to the dealer, as principal. The dealer may then resell such securities to the public at varying prices to be determined by such dealer at the time of resale.
If we offer securities in a subscription rights offering to our existing security holders, we may enter into a standby underwriting agreement with dealers, acting as standby underwriters. We may pay the standby underwriters a commitment fee for the securities they commit to purchase on a standby basis. If we do not enter into a standby underwriting arrangement, we may retain a dealer-manager to manage a subscription rights offering for us.
Remarketing firms, agents, underwriters, dealers and other persons may be entitled under agreements which they may enter into with us to indemnification by us against certain civil liabilities, including liabilities under the Securities Act, and may be customers of, engage in transactions with or perform services for us in the ordinary course of business.
If so indicated in the applicable prospectus supplement, we will authorize underwriters or other persons acting as our agents to solicit offers by certain institutions to purchase securities from us pursuant to delayed delivery contracts providing for payment and delivery on the date stated in the prospectus supplement. Each contract will be for an amount not less than, and the aggregate amount of securities sold pursuant to such contracts shall not be less nor more than, the respective amounts stated in the prospectus supplement. Institutions with whom the contracts, when authorized, may be made, include commercial and savings banks, insurance companies, pension funds, investment companies, educational and charitable institutions and other institutions, but shall in all cases be subject to our approval. Delayed delivery contracts will not be subject to any conditions except that:
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the purchase by an institution of the securities covered under that contract shall not, at the time of delivery, be prohibited under the laws of the jurisdiction to which that institution is subject; and
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if the securities are also being sold to underwriters acting as principals for their own account, the underwriters shall have purchased such securities not sold for delayed delivery. The underwriters and other persons acting as our agents will not have any responsibility in respect of the validity or performance of delayed delivery contracts.
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Certain agents, underwriters and dealers, and their associates and affiliates may be customers of, have borrowing relationships with, engage in other transactions with, or perform services (including investment banking services) for us or one or more of our respective affiliates in the ordinary course of business.
In order to facilitate the offering of the securities, any underwriters may engage in transactions that stabilize, maintain or otherwise affect the price of the securities or any other securities the prices of which may be used to determine payments on such securities. Specifically, any underwriters may over-allot in connection with the offering, creating a short position for their own accounts. In addition, to cover overallotments or to stabilize the price of the securities or of any such other securities, the underwriters may bid for, and purchase, the securities or any such other securities in the open market. Finally, in any offering of the securities through a syndicate of underwriters, the underwriting syndicate may reclaim selling concessions allowed to an underwriter or a dealer for distributing the securities in the offering if the syndicate repurchases previously distributed securities in transactions to cover syndicate short positions, in stabilization transactions or otherwise. Any of these activities may stabilize or maintain the market price of the securities above independent market levels. Any such underwriters are not required to engage in these activities and may end any of these activities at any time.
Under Rule 15c6-1 of the Exchange Act, trades in the secondary market generally are required to settle in three business days, unless the parties to any such trade expressly agree otherwise. The applicable prospectus supplement may provide that the original issue date for your securities may be more than three scheduled business days after the trade date for your securities. Accordingly, in such a case, if you wish to trade securities” “could,” “would,” “should,” “expect,” “intend,” “plan,” “objective,” “anticipate,” “believe,” “estimate,”
 
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on any date prior“predict,” “project,” “potential,” “likely,” “continue” and “ongoing,” or the negative of these terms, or other comparable terminology intended to identify statements about the future, although not all forward-looking statements contain these words. These statements involve known and unknown risks, uncertainties and other factors that may cause our actual results, levels of activity, performance or achievements to be materially different from the information expressed or implied by these forward-looking statements.
You should refer to the third business day before“Risk Factors” section below and contained in any applicable prospectus supplement and any related free writing prospectus, and under similar headings in the original issue dateother documents that are incorporated by reference into this prospectus, for your securities,a discussion of important factors that may cause our actual results to differ materially from those expressed or implied by our forward-looking statements. Given these risks, uncertainties and other factors, many of which are beyond our control, we cannot assure you that the forward-looking statements in this prospectus will prove to be accurate, and you should not place undue reliance on these forward-looking statements. Furthermore, if our forward-looking statements prove to be inaccurate, the inaccuracy may be material. In light of the significant uncertainties in these forward-looking statements, you should not regard these statements as a representation or warranty by us or any other person that we will achieve our objectives and plans in any specified time frame, or at all.
Except as required by virtue of the fact that your securities initially are expectedlaw, we assume no obligation to settle more than three scheduled business daysupdate these forward-looking statements publicly, or to revise any forward-looking statements to reflect events or developments occurring after the trade date for your securities, to make alternative settlement arrangements to prevent a failed settlement.of this prospectus, even if new information becomes available in the future.
 
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DESCRIPTIONUSE OF CAPITAL STOCKPROCEEDS
This prospectus contains summary descriptions of the common stock, preferred stock and warrants that may be offered and sold from time to time. These summary descriptions are not meant to be complete descriptions of each security. However, at the time of an offering and sale, this prospectus together with the accompanying prospectus supplementThe selling stockholders will contain the material terms of the securities being offered.
General
Our amended and restated certificate of incorporation authorizes 75,000,000 shares of common stock, $0.0001 par value per share, and 20,000,000 shares of preferred stock, $0.0001 par value per share. As of May 5, 2021, 51,386,596 shares of our common stock were issued and outstanding and held of record by eight holders, and no shares of our preferred stock were issued and outstanding.
Common Stock
Voting Rights
Each holder of our common stock is entitled to one vote for each share on all matters submitted to a vote of the stockholders, including the election of directors. Our stockholders do not have cumulative voting rights in the election of directors. Accordingly, holders of a majority of the voting shares are able to electreceive all of the directors. In addition,proceeds from the affirmative vote of holders of 66-2/3%sale of the voting power of allShares hereunder. Accordingly, we will not receive any of the then outstanding voting stock will be required to take certain actions, including amending certain provisions of our amended and restated certificate of incorporation, such asproceeds from the provisions relating to amending our amended and restated bylaws, procedures for our stockholder meetings, the classified board, director liability, and exclusive forum for proceedings.
Dividends
Subject to preferences that may be applicable to any then outstanding preferred stock, holders of our common stock are entitled to receive dividends, if any, as may be declared from time to time by our board of directors out of legally available funds.
Liquidation
In the event of our liquidation, dissolution or winding up, holders of our common stock will be entitled to share ratably in the net assets legally available for distribution to stockholders after the payment of all of our debts and other liabilities and the satisfaction of any liquidation preference granted to the holders of any then outstanding shares of preferred stock.
Rights and Preferences
Holders of our common stock have no preemptive, conversion, subscription or other rights, and there are no redemption or sinking fund provisions applicable to our common stock. The rights, preferences and privilegessale of the holders of our common stock are subject to, and may be adversely affected by, the rightsShares in this offering; however, we will receive nominal proceeds from any cash exercise of the holders of shares of any series of our preferred stock that we may designate in the future.
Forum for Securities Litigation
Our amended and restated bylaws provide that, unless the Company consents in writing to the selection of an alternative forum, the federal district courts of the United States of America will be the sole and exclusive forum for the resolution of any complaint asserting a cause of action arising under the Securities Act of 1933, as amended.
Preferred Stock
Our board of directors has the authority, without further action by our stockholders, to issue up to 20,000,000 shares of preferred stock in one or more series and to fix the rights, preferences, privileges and restrictions thereof. These rights, preferences and privileges could include dividend rights, conversion rights,Pre-Funded Warrants.
 
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voting rights,SELLING STOCKHOLDERS
We have prepared this prospectus to allow the selling stockholders to offer and sell from time to time up to 39,266,980 shares of our common stock for their own account, consisting of (i) up to 10,652,543 shares of common stock issued to the selling stockholders and (ii) 28,614,437 shares of common stock issuable to certain of the selling stockholders upon the exercise of the Pre-Funded Warrants pursuant to the Purchase Agreement, without giving effect to any beneficial ownership limitation contained in any Pre-Funded Warrant. For additional information regarding the issuances of those shares of our common stock and the Pre-Funded Warrants, see “Prospectus Summary — Private Placement” above.
We are registering the offer and sale of the Shares to satisfy certain registration obligations that we granted the selling stockholders in connection with the purchase of the Shares pursuant to the Registration Rights Agreement. Under the terms of redemption, liquidation preferences, sinking fund termsthe Purchase Agreement, we agreed to prepare and file one or more registration statements with the SEC within 30 calendar days of the date of the Registration Rights Agreement to register the resale of the Shares by the selling stockholders, and to use our best efforts to cause the applicable registration statements to become effective by the Effectiveness Deadline. We also agreed to use our best efforts to keep such registration statement continuously effective under the Securities Act until the earlier of (i) the date on which the securities may be resold by the Selling Stockholders without registration and without regard to any volume or manner-of-sale limitations or current public information requirements by reason of Rule 144, or (ii) all of the securities have been sold pursuant to this prospectus or Rule 144 under the Securities Act or any other rule of similar effect.
The Pre-Funded Warrants may not be exercised if the aggregate number of shares constituting,of common stock beneficially owned by the holder thereof immediately following such exercise would exceed a specified beneficial ownership limitation; provided, however, that a holder may increase or decrease the designationbeneficial ownership limitation by giving 60 days’ notice to us, but not to any percentage in excess of 19.99%.
The following table sets forth, to our knowledge, information concerning the beneficial ownership of shares of our common stock by the selling stockholders as of November 3, 2023. Beneficial ownership is determined in accordance with the rules of the SEC, and includes voting or investment power with respect to our common stock. Except as indicated by the footnotes below, we believe, based on the information furnished to us, that each selling stockholder named in the table below has sole voting and investment power with respect to all shares of common stock that they beneficially own, subject to applicable community property laws.
The number of shares of common stock beneficially owned by each selling stockholder as of November 3, 2023 includes (i) all shares of our common stock purchased by such series,selling stockholder in the Private Placement and (ii) all shares of common stock issuable upon the exercise of Pre-Funded Warrants purchased by such selling stockholder in the Private Placement, giving effect to any orbeneficial ownership limitation contained in any Pre-Funded Warrant. The number of shares of common stock that may be offered under this prospectus, includes (x) all shares of our common stock purchased by such selling stockholder in the Private Placement and (y) all shares of our common stock underlying Pre-Funded Warrants purchased by such selling stockholder in the Private Placement without giving effect to the beneficial ownership limitation. The number of shares of common stock beneficially owned by each selling stockholder following the offering assumes all of the Shares covered hereby are sold and such stockholder does not acquire beneficial ownership of any additional shares of common stock.
The percentage of shares owned before and after the offering are based on 13,957,324 shares of our common stock outstanding as of November 3, 2023, which may be greater thanincludes the rightsoutstanding shares of common stock offered by this prospectus but does not include any shares of common stock offered by this prospectus that are issuable pursuant to the Pre-Funded Warrants, and assumes the selling stockholders dispose of all of the Shares covered by this prospectus and do not acquire beneficial ownership of any additional shares of common stock. The issuanceregistration of our preferred stock could adversely affect the voting powerShares does not necessarily mean that the selling stockholders will sell all or any portion of holders of common stock and the likelihood that such holders will receive dividend payments and payments upon our liquidation. In addition, the issuance of preferred stock could have the effect of delaying, deferring or preventing a change in control of our company or other corporate action.Shares covered by this prospectus.
Anti-Takeover Effects of Provisions of our Amended and Restated Certificate of Incorporation, our Amended and Restated Bylaws and Delaware Law
Some provisions of Delaware law and our amended and restated certificate of incorporation and our amended and restated bylaws contain provisions that could make the following transactions more difficult: acquisition of us by means of a tender offer; acquisition of us by means of a proxy contest or otherwise; or removal of our incumbent officers and directors. It is possible that these provisions could make it more difficult to accomplish or could deter transactions thatThe selling stockholders may otherwise consider to be in their best interestsell some, all or in our best interests, including transactions that might result in a premium over the market price for our shares.
These provisions, summarized below, are expected to discourage coercive takeover practices and inadequate takeover bids. These provisions are also designed to encourage persons seeking to acquire control of us to first negotiate with our board of directors. We believe that the benefits of increased protection of our potential ability to negotiate with the proponent of an unfriendly or unsolicited proposal to acquire or restructure us outweigh the disadvantages of discouraging these proposals because negotiation of these proposals could result in an improvement of their terms.
Delaware Anti-Takeover Statute
We are subject to Section 203none of the Delaware General Corporation Law, which prohibits persons deemed “interested stockholders”Shares offered by this prospectus from engaging in a “business combination” with a publicly-held Delaware corporation for three years followingtime to time. We do not know how long the date these persons become interestedselling stockholders unlesswill hold the business combination is, or the transaction in which the person became an interested stockholder was, approved in a prescribed manner or another prescribed exception applies. Generally, an “interested stockholder” is a person who, together with affiliates and associates, owns, or within three years prior to the determination of interested stockholder status did own, 15% or more of a corporation’s voting stock. Generally, a “business combination” includes a merger, asset or stock sale, or other transaction resulting in a financial benefit to the interested stockholder. The existence of this provision may have an anti-takeover effect with respect to transactions not approved in advance by the board of directors, such as discouraging takeover attempts that might result in a premium over the market price of our common stock.
Undesignated Preferred Stock
The ability to authorize undesignated preferred stock makes it possible for our board of directors to issue preferred stock with voting or other rights or preferences that could impede the success of any attempt to change control of us. These and other provisions may have the effect of deterring hostile takeovers or delaying changes in control or management of our company.
Special Stockholder Meetings
Our amended and restated bylaws provide that a special meeting of stockholders may be called by our board of directors, our President, our Chief Executive Officer, or the Secretary.
Requirements for Advance Notification of Stockholder Nominations and Proposals
Our amended and restated bylaws include advance notice procedures with respect to stockholder proposals and the nomination of candidates for election as directors, other than nominations made by or at the direction of the board of directors or a committee of the board of directors.Shares covered hereby before selling
 
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Eliminationthem and we currently have no agreements, arrangements or understandings with the selling stockholders regarding the sale or other disposition of Stockholder Action by Written Consentany Shares.
Our amendedAs used in this prospectus, the term “selling stockholders” includes the selling stockholders listed in the table below, together with any additional selling stockholders listed in a prospectus supplement, and restated certificatetheir donees, pledgees, assignees, transferees, distributees and successors-in-interest that receive Shares in any non-sale transfer after the date of incorporation and our amended and restated bylaws do not permit stockholders to act by written consent without a meeting.this prospectus.
Except as otherwise noted below, the address for persons listed in the table is c/o VYNE Therapeutics Inc., 685 Route 202/206 N., Suite 301 Bridgewater, New Jersey 08807.
​​​
Beneficial
Ownership Prior to
this Offering
​​
Maximum
Number of
Shares to be Sold
Pursuant to
this Prospectus(2)
​​
Beneficial
Ownership After
this Offering(1)
​
Name of Selling Stockholder​​
Number of
Shares
​​
Percentage of
Outstanding
Common
Stock
​​
Number of
Shares
​​
Percentage of
Outstanding
Common
Stock
​
Eventide Healthcare Innovation Fund I LP(3)
​​​​1,394,336​​​​​9.99%​​​​​6,681,749​​​​​—​​​​​—​​
Cormorant Global Healthcare Master Fund, LP(4)
​​​​1,394,336​​​​​9.99%​​​​​4,454,479​​​​​—​​​​​—​​
AI Biotechnology LLC(5)
​​​​1,394,336​​​​​9.99%​​​​​8,909,033​​​​​—​​​​​—​​
Citadel CEMF Investments Ltd.(6)
​​​​1,181,088​​​​​8.46%​​​​​1,181,088​​​​​—​​​​​—​​
Soleus Capital Master Fund, L.P.(7)
​​​​890,868​​​​​6.38%​​​​​890,868​​​​​—​​​​​—​​
Entities affiliated with Baker Bros. Advisors LP(8)
​​​​696,470​​​​​4.99%​​​​​6,681,813​​​​​—​​​​​—​​
Entities affiliated with Acorn Bioventures(9)
​​​​696,470​​​​​4.99%​​​​​3,118,147​​​​​—​​​​​—​​
Delaware Street Capital Master Fund, L.P.(10)
​​​​696,470​​​​​4.99%​​​​​2,227,244​​​​​115,000​​​​​*​​
Entities affiliated with Parkman(11)
​​​​696,470​​​​​4.99%​​​​​1,781,785​​​​​—​​​​​—​​
Entities affiliated with LifeSci Ventures(12)
​​​​696,467​​​​​4.99%​​​​​1,336,321​​​​​—​​​​​—​​
AlphaCentric LifeSci Healthcare Fund(13)
​​​​668,151​​​​​4.79%​​​​​668,151​​​​​—​​​​​—​​
Lytton-Kambara Foundation(14)
​​​​455,374​​​​​3.26%​​​​​445,434​​​​​9,940​​​​​*​​
Micro Cap Partners, L.P.(15)
​​​​445,434​​​​​3.19%​​​​​445,434​​​​​—​​​​​—​​
Worldwide Healthcare Partners LLC(16)
​​​​445,434​​​​​3.19%​​​​​445,434​​​​​—​​​​​—​​
​
Classified Board; Election and Removal*
Represents beneficial ownership of Directors; Filling Vacanciesless than 1%
Our board​
(1)
Assumes each selling stockholder sells the maximum number of directors is divided into three classes. The directors in each class will serve for a three-year term, one class being elected each year by our stockholders, with staggered three-year terms. Only one class of directors will be elected at each annual meetingshares of our stockholders, with the other classes continuing for the remainder of their respective three-year terms. Because our stockholders do not have cumulative voting rights, our stockholders holding a majoritycommon stock possible in this offering.
​
(2)
Represents all of the shares of common stock outstanding will be able to elect all of our directors. Our amended and restated certificate of incorporation provides for the removal of any of our directors only for cause and requires a stockholder vote by the holders of at least a 66-2/3% of the voting power of the then outstanding voting stock. Furthermore, any vacancy on our board of directors, however occurring, including a vacancy resulting from an increase in the size of the board, may only be filled by a resolution of the board of directors unless the board of directors determines that such vacancies shall be filled by the stockholders. This system of electing and removing directors and filling vacancies may tend to discourage a third party from making a tender offer or otherwise attempting to obtain control of us, because it generally makes it more difficult for stockholders to replace a majority of the directors.
Choice of Forum
Our amended and restated certificate of incorporation provides that, unless we consent in writing to the selection of an alternative forum, the Court of Chancery of the State of Delaware will be the exclusive forum for: any derivative action or proceeding brought on our behalf; any action asserting a breach of fiduciary duty; any action asserting a claim against us arising pursuant to the Delaware General Corporation Law, our amended and restated certificate of incorporation or our amended and restated bylaws; or any action asserting a claim against us that is governed by the internal affairs doctrine. Although our amended and restated certificate of incorporation contains the choice of forum provision described above, it is possible that a court could find that such a provision is inapplicable for a particular claim or action or that such provision is unenforceable.
Amendment of Charter Provisions
The amendment of any of the above provisions, except for the provision making it possible for our board of directors to issue undesignated preferred stock, would require approval by a stockholder vote by the holders of at least a 66-2/3% of the voting power of the then outstanding voting stock.
The provisions of the Delaware General Corporation Law, our amended and restated certificate of incorporation and our amended and restated bylaws could have the effect of discouraging others from attempting hostile takeovers and, as a consequence, they may also inhibit temporary fluctuations in the market price of our common stock that often result from actual or rumored hostile takeover attempts. These provisions may also have the effect of preventing changes in our management. It is possible that these provisions could make it more difficult to accomplish transactions thatselling stockholders may otherwise deemoffer and sell from time to be in their best interests.
Limitations of Liability and Indemnification
Our amended and restated certificate of incorporation contains provisions that limit the liability of our directors for monetary damagestime under this prospectus without giving effect to the fullest extent permitted by Delaware law. Consequently, our directors will not be personally liable to us or our stockholders for monetary damages for any breach of fiduciary duties as directors, except liability for:
•
any breach ofbeneficial ownership limitation in the director’s duty of loyalty to us or our stockholders;Pre-Funded Warrants.
​
•(3)
any act“Beneficial Ownership Prior to this Offering” consists of 1,394,336 shares of common stock issued in the Private Placement to Eventide Healthcare Innovation Fund I LP, or omissionEventide LP. Such amount does not include 5,287,413 shares of common stock issuable upon exercise of Pre-Funded Warrants purchased by Eventide LP in good faiththe Private Placement because they are subject to limitations on exercisability if such exercise would result in entities affiliated with Eventide beneficially owning more than 9.99% of our common stock then issued and outstanding after giving effect to such exercise. Eventide Healthcare Innovation GP LLC, or that involves intentional misconductEventide GP, is the General Partner of Eventide LP. Eventide Asset Management, LLC, or a knowing violationEAM, is the Managing Member of law;Eventide GP. Robin John is the chief executive officer of EAM. Finny Kuruvilla and Kyle Rasbach are members of Eventide LP’s investment committee. By virtue of the foregoing, each of Mr. John, EAM and Eventide GP may be deemed to have, and Mr. Kuruvilla and Mr. Rasbach may be deemed to share, voting and investment power over the Shares held by Eventide LP. The business address of each of Eventide LP, Eventide GP, EAM, Mr. John, Mr. Kuruvilla and Mr. Rasbach is Eventide Healthcare Innovation Fund I LP c/o Eventide Asset Management, LLC, 1 International Place, Suite 4210, Boston, MA 02110.
​
 
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•(4)
unlawful payments“Beneficial Ownership Prior to this Offering” consists of dividends or unlawful stock repurchases or redemptions as provided in Section 1741,394,336 shares of the Delaware General Corporation Law; or
​
•
any transaction from which the director derived an improper personal benefit.
​
Each of our amended and restated certificate of incorporation and amended and restated bylaws provides that we are required to indemnify our directors and officers, in each case, to the fullest extent permitted by Delaware law. Our amended and restated bylaws will also obligate us to advance expenses incurred by a director or officer in advance of the final disposition of any action or proceeding, and permit us to secure insurance on behalf of any officer, director, employee or other agent for any liability arising out of his or her actions in that capacity regardless of whether we would otherwise be permitted to indemnify him or her under Delaware law. We have entered and expect to continue to enter into agreements to indemnify our directors, executive officers and other employees as determined by our board of directors. With specified exceptions, these agreements provide for indemnification for related expenses including, among other things, attorneys’ fees, judgments, fines and settlement amounts incurred by any of these individuals in any action or proceeding. We believe that these bylaw provisions and indemnification agreements are necessary to attract and retain qualified persons as directors and officers. We also maintain directors’ and officers’ liability insurance. The limitation of liability and indemnification provisions in our amended and restated certificate of incorporation and amended and restated bylaws may discourage stockholders from bringing a lawsuit against our directors and officers for breach of their fiduciary duty. They may also reduce the likelihood of derivative litigation against our directors and officers, even though an action, if successful, might benefit us and our stockholders. Further, a stockholder’s investment may be adversely affected to the extent that we pay the costs of settlement and damage.
Listing
Our common stock is listed onissued in the NasdaqPrivate Placement to Cormorant Global Select Market under the trading symbol “VYNE.”
Transfer Agent and Registrar
The transfer agent and registrar for ourHealthcare Master Fund, LP, or Cormorant LP. Such amount does not include 3,060,143 shares of common stock is American Stock Transfer Trust Company, LLC. The transfer agent and registrar’s address is 6201 15th Avenue, Brooklyn, New York 11219.
DESCRIPTION OF WARRANTS
We may issue warrants forissuable upon exercise of Pre-Funded Warrants purchased by Cormorant LP in the purchase of sharesPrivate Placement because they are subject to limitations on exercisability if such exercise would result in entities affiliated with Cormorant LP beneficially owning more than 9.99% of our common stock then issued and outstanding after giving effect to such exercise. Cormorant Global Healthcare GP, LLC, or preferred stock. We may issue warrants independentlyCormorant GP, serves as the General Partner of Cormorant LP. Cormorant Asset Management, LP serves as the investment manager to Cormorant LP. Bihua Chen serves as the Managing Member of Cormorant GP and the General Partner of Cormorant Asset Management, LP, or, together with other securities,Cormorant LP the Cormorant Entities. By virtue of the foregoing, each of Bihua Chen and the warrantsCormorant Entities may be attacheddeemed to or separate from any offered securities. Each serieshave voting and investment power over the Shares held by Cormorant LP. The business address of warrants will be issued under a separate warrant agreement to be entered into between useach of Bihua Chen and the investors or a warrant agent. The following summary of material provisions of the warrants and warrant agreements are subject to, and qualified in their entirety by reference to, all the provisions of the warrant agreement and warrant certificate applicable to a particular series of warrants. The terms of any warrants offered under a prospectus supplement may differ from the terms described below. We urge you to read the applicable prospectus supplement and any related free writing prospectus, as well as the complete warrant agreements and warrant certificates that contain the terms of the warrants.Cormorant Entities is 200 Clarendon St., 52nd Floor, Boston, Massachusetts 02116.
The particular terms of any issue of warrants will be described in the prospectus supplement relating to the issue. Those terms may include:​
•(5)
the number“Beneficial Ownership Prior to this Offering” consists of (i) 1,116,585 shares of common stock or preferredissued in the Private Placement to AI Biotechnology LLC and (ii) 277,751 shares of common stock purchasableissuable upon the exercise of warrantsPre-Funded Warrants purchased by AI Biotechnology LLC in the Private Placement. Such amount does not include 7,514,697 shares of common stock issuable upon exercise of Pre-Funded Warrants purchased by AI Biotechnology LLC in the Private Placement because they are subject to purchaselimitations on exercisability if such sharesexercise would result in entities affiliated with AI Biotechnology LLC beneficially owning more than 9.99% of our common stock then issued and outstanding after giving effect to such exercise. Access Industries Holdings LLC, or AIH, directly controls all of the price at which such numberoutstanding voting interest in AI Biotechnology LLC. Access Industries Management, LLC, or AIM, controls AIH. Len Blavatnik controls AIM and holds a majority of sharesthe outstanding voting interests in AIH. By virtue of the foregoing, each of Len Blavatnik, AIM and AIH may be purchased upon such exercise;deemed to have voting and investment power over the Shares held by AI Biotechnology LLC. The business address of each of AI Biotechnology LLC, AIM, AIH and Len Blavatnik is c/o Access Industries, Inc. 40 West 57th Street, 28th Floor, New York, NY 10019.
​
•(6)
“Beneficial Ownership Prior to this Offering” consists of 1,181,088 shares of common stock issued to Citadel CEMF Investments Ltd. in the designation, stated value and terms (including, without limitation, liquidation, dividend, conversion and voting rights)Private Placement. Citadel Advisors LLC is the portfolio manager of Citadel CEMF Investments Ltd. Citadel Advisors Holdings LP is the sole member of Citadel Advisors LLC. Citadel GP LLC is the General Partner of Citadel Advisors Holdings LP. Kenneth Griffin owns a controlling interest in Citadel GP LLC. Mr. Griffin, as the owner of a controlling interest in Citadel GP LLC, may be deemed to have shared power to vote and/or shared power to dispose of the seriessecurities held by Citadel CEMF Investments Ltd. This disclosure shall not be construed as an admission that Mr. Griffin or any of preferredthe Citadel related entities listed above is the beneficial owner of any securities of the Company other than the securities actually owned by such person (if any). The business address of Citadel CEMF Investments Ltd. is c/o Citadel Enterprise Americas LLC, Southeast Financial Center, 200 S. Biscayne Blvd., Suite 3300, Miami, FL 33131.
​
(7)
“Beneficial Ownership Prior to this Offering” consists of 890,868 shares of common stock purchasableissued to Soleus Capital Master Fund, L.P., or Soleus Master Fund, in the Private Placement. Soleus Capital, LLC, or Soleus Capital, is the sole General Partner of Soleus Master Fund and thus holds voting and dispositive power over the shares held by Soleus Master Fund. Soleus Capital Group, LLC, or SCG, is the sole Managing Member of Soleus Capital. Guy Levy is the sole Managing Member of SCG. By virtue of the foregoing, each of Soleus Capital, SCG and Guy Levy may be deemed to have voting and investment power over the Shares held by Soleus Master Fund. The business address of each of Soleus Master Fund, Soleus Capital, SCG and Guy Levy is 104 Field Point Road, 2nd Floor, Greenwich, CT 06830.
​
(8)
“Beneficial Ownership Prior to this Offering” consists of (i) 55,010 shares of common stock issuable upon exercise of warrants to purchase preferred stock;
​
•
Pre-Funded Warrants purchased by 667, L.P., or 667, in the date, if any, onPrivate Placement and after which the warrants and the related preferred stock or(ii) 641,460 shares of common stock will be separately transferable;issuable upon exercise of Pre-Funded Warrants purchased by Baker Brothers Life Sciences, L.P., or BBLS, in the Private Placement, assuming proportionate exercise of the Pre-Funded Warrants. Such amount does not include (i) 472,748 shares of common stock issuable upon exercise of Pre-Funded Warrants purchased by 667 in the Private Placement and (ii) 5,512,595 shares of common stock issuable upon exercise of Pre-Funded Warrants purchased by BBLS in the Private Placement because they are subject to limitations on exercisability if such exercise would result
​
 
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in entities affiliated with the holder beneficially owning more than 4.99% of our common stock then issued and outstanding after giving effect to such exercise. Baker Bros. Advisors LP, or BBA, is the management company and investment adviser to 667 and BBLS and has sole voting and investment power over the Shares held by 667 and BBLS. Baker Bros. Advisors (GP) LLC, or BBA-GP, is the sole General Partner of BBA. Julian C. Baker and Felix J. Baker are managing members of BBA-GP. BBA-GP, Felix J. Baker, Julian C. Baker and BBA may be deemed to be beneficial owners of the Shares directly held by BBLS and 667. Julian C. Baker, Felix J. Baker, BBA, and BBA-GP disclaim beneficial ownership of all Shares held by BBLS and 667, except to the extent of their indirect pecuniary interest therein. The business address of each of 667, BBLS, BBA, BBA-GP, Julian C. Baker and Felix J. Baker is 860 Washington St., 3rd Floor, New York, NY 10014.
•(9)
“Beneficial Ownership Prior to this Offering” consists of (i) 292,517 shares of common stock issued to Acorn Bioventures, L.P., or Acorn LP, in the termsPrivate Placement, (ii) 403,953 shares of any rightscommon stock issued to redeemAcorn Bioventures 2, L.P., or callAcorn 2 LP, in the warrants;Private Placement. Such amount does not include (i) 1,017,105 shares of common stock issuable upon exercise of Pre-Funded Warrants purchased by Acorn LP in the Private Placement and (ii) 1,404,572 shares of common stock issuable upon exercise of Pre-Funded Warrants purchased by Acorn 2 LP in the Private Placement because they are subject to limitations on exercisability if such exercise would result in entities affiliated with the holder beneficially owning more than 4.99% of our common stock then issued and outstanding after giving effect to such exercise. Acorn Capital Advisors, GP, LLC, or Acorn GP, and Acorn Capital Advisors GP2, LLC, or Acorn 2 GP, are the sole General Partners of Acorn LP and Acorn 2 LP, respectively. Anders Hove is the manager of Acorn GP and Acorn 2 GP. By virtue of the foregoing, Anders Hove may be deemed to have voting and investment power over the Shares held by Acorn LP or Acorn 2 LP. The business address of each of Acorn LP, Acorn 2 LP, Acorn GP, Acorn 2 GP and Anders Hove is 420 Lexington Avenue, Suite 2626, New York, NY 10170.
​
•(10)
“Beneficial Ownership Prior to this Offering” consists of (i) 581,470 shares of common stock issued to Delaware Street Capital Master Fund, L.P., or Delaware Fund, in the datePrivate Placement and (ii) 115,000 shares of common stock held by Delaware Fund prior to the Private Placement. Such amount does not include 1,645,774 shares of common stock issuable upon exercise of Pre-Funded Warrants purchased by Delaware Fund in the Private Placement because they are subject to limitations on whichexercisability if such exercise would result in entities affiliated with Delaware Fund beneficially owning more than 4.99% of our common stock then issued and outstanding after giving effect to such exercise. DSC Advisors, L.P., or DSCA, is investment manager of Delaware Fund and DSC Managers, L.L.C., or DSCM, is General Partner of Delaware Fund. DSC Advisors, L.L.C., or DSCA LLC, is General Partner of DSCA. Andrew G. Bluhm is the rightprincipal of DSCA LLC. By virtue of the foregoing, each of DSCA, DSCM, DSCA LLC and Mr. Bluhm may be deemed to exercisehave voting and investment power over the warrants will commenceShares held by Delaware Fund. The business address of each of Delaware Fund, DSCA, DSCM, DSCA LLC and the date on which the right will expire;Mr. Bluhm is 900 North Michigan, Suite 1600, Chicago, IL 60611.
​
•(11)
United States Federal income tax consequences applicable“Beneficial Ownership Prior to this Offering” consists of 696,470 shares of common stock issued to entities affiliated with Parkman Healthcare Partners LLC, or Parkman, in the warrants;Private Placement. Such amount does not include 1,085,315 shares of common stock issuable upon exercise of Pre-Funded Warrants purchased by entities affiliated with Parkman in the Private Placement because they are subject to limitations on exercisability if such exercise would result in entities affiliated with the holder beneficially owning more than 4.99% of our common stock then issued and outstanding after giving effect to such exercise. Gregory Martinez has voting and investment power over the Shares held by entities affiliated with Parkman. The business address of each of Mr. Martinez and the entities affiliate with Parkman is 700 Canal Street, 2nd Floor, Stamford, CT 06902.
​
•(12)
any additional terms“Beneficial Ownership Prior to this Offering” consists of (i) 232,156 shares of common stock issued to LifeSci Venture Partners II, LP, or LifeSci II, in the warrants, including terms, procedures,Private Placement, and (ii) 464,311 shares of common stock issued to LifeSci Venture Partners III, LP, or LifeSci III, in the Private Placement. Such amount does not include (i) 213,285 shares of common stock issuable upon exercise of Pre-Funded Warrants purchased by LifeSci II in the Private Placement and (ii) 426,569 shares of common stock issuable upon the exercise of Pre-Funded Warrants purchased by LifeSci III in the Private Placement because they are subject to limitations relating toon exercisability if such exercise would result in entities affiliated with the exchange, exercise and settlement of the warrants.
​
Holders of equity warrants will not be entitled:
•
to vote, consent or receive dividends;
​
•
receive notice as stockholders with respect to any meeting of stockholders for the electionholder beneficially owning more than 4.99% of our directors or any other matter; or
​
•
exercise any rights as stockholders of VYNE Therapeutics.
​
Each warrant will entitle its holder to purchase the number of shares of preferred stock or common stock at the exercise price set forth in, or calculable as set forth in, the applicable prospectus supplement. Unless we otherwise specify in the applicable prospectus supplement, holders of the warrants may exercise the warrants at any time up to the specified time on the expiration date that we set forth in the applicable prospectus supplement. After the close of business on the expiration date, unexercised warrants will become void.then issued and outstanding
A holder of warrant certificates may exchange them for new warrant certificates of different denominations, present them for registration of transfer and exercise them at the corporate trust office of the warrant agent or any other office indicated in the applicable prospectus supplement. Until any warrants to purchase common stock or preferred stock are exercised, the holders of the warrants will not have any rights of holders of the underlying common stock or preferred stock, including any rights to receive dividends or payments upon any liquidation, dissolution or winding up on the common stock or preferred stock, if any.​
 
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after giving effect to such exercise. Paul Yook as Managing Member of LifeSci II and LifeSci III has voting and investment power over the Shares held by each of LifeSci II and LifeSci III. The business address of each of LifeSci II, LifeSci III and Mr. Yook is 250 West 55th Street, 34th Floor, New York, NY 10019.
(13)
“Beneficial Ownership Prior to this Offering” consists of 668,151 shares of common stock issued to AlphaCentric LifeSci Healthcare Fund, or AlphaCentric, in the Private Placement. Dr. Mark Charest is the Portfolio Manager of AlphaCentric and has voting and investment power over the Shares held by AlphaCentric. The business address of AlphaCentric and Dr. Charest is 36 N. New York Avenue Fl 3, Huntington, NY 11743.
​
(14)
“Beneficial Ownership Prior to this Offering” consists of (i) 445,434 shares of common stock issued to Lytton-Kambara Foundation, or LKF, in the Private Placement and (ii) 9,940 shares of common stock purchased by LKF immediately following the Private Placement. Laurence Lytton, President of LKF, has voting and investment power over the Shares held by LKF. The business address of LKF and Mr. Lytton is 467 Central Park West 17-A, New York, NY 10025.
​
(15)
“Beneficial Ownership Prior to this Offering” consists of 445,434 shares of common stock issued to Micro Cap Partners, L.P., or Micro Cap, in the Private Placement. PAI LLC is the General Partner of Micro Cap, Palo Alto Investors LP, or PAI LP, is the Investment Adviser to Micro Cap, and Dr. Anthony Joonkyoo Yun, MD and Dr. Patrick Lee, MD are co-managers of PAI LLC. By virtue of the foregoing, each of PAI LLC, PAI LP, Dr. Yun and Dr. Lee may be deemed to have voting and investment power over the Shares held by Micro Cap. The business address of Micro Cap, PAI LLC, PAI LP, Dr. Yun and Dr. Lee is 470 University Avenue, Palo Alto, CA 94301.
​
(16)
“Beneficial Ownership Prior to this Offering” consists of 445,434 shares of common stock issued to Worldwide Healthcare Partners LLC, or WHP, in the Private Placement. Samuel D. Isaly, Managing Member of WHP, has voting and investment power over the Shares held by WHP. The business address of each of WHP and Mr. Isaly is 330 Madison Avenue, Suite 3010, New York, NY 10017.
​
Relationships with Selling Stockholders
Each of the selling stockholders has not had any material relationship with the registrant or any of its predecessors or affiliates, within the past three years, except as hereinafter described. As discussed in greater detail above under the section titled “Prospectus Summary — Private Placement,” in October 2023, we entered into the Purchase Agreement with the selling stockholders, pursuant to which we sold and issued shares of our common stock and Pre-Funded Warrants to purchase our common stock. We also entered into the Registration Rights Agreement with the selling stockholders, pursuant to which we agreed to prepare and file, by the Filing Deadline, one or more registration statements with the SEC to register for resale the common stock issued under the Purchase Agreement and the shares of common stock issuable upon exercise of the Pre-Funded Warrants issued pursuant to the Purchase Agreement, and to cause the applicable registration statements to become effective by the Effectiveness Deadline.

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PLAN OF DISTRIBUTION
Each selling stockholder of the securities and any of their pledgees, assignees, donees, transferees or other successors-in-interest, each, a Selling Stockholder, and collectively, the Selling Stockholders, may, from time to time, sell, transfer or otherwise dispose of any or all of their securities covered hereby on the principal Trading Market or any other stock exchange, market or trading facility on which the securities are traded or in private transactions. These sales may be at fixed or negotiated prices. A Selling Stockholder may use any one or more of the following methods when selling securities:
•
ordinary brokerage transactions and transactions in which the broker-dealer solicits purchasers;
​
•
block trades in which the broker-dealer will attempt to sell the securities as agent but may position and resell a portion of the block as principal to facilitate the transaction;
​
•
purchases by a broker-dealer as principal and resale by the broker-dealer for its account;
​
•
to or through underwriters;
​
•
an exchange distribution in accordance with the rules of the applicable exchange;
​
•
privately negotiated transactions;
​
•
settlement of short sales entered into after the effective date of the registration statement of which this prospectus is a part;
​
•
in transactions through broker-dealers that agree with the Selling Stockholders to sell a specified number of such securities at a stipulated price per security;
​
•
through the writing or settlement of options or other hedging transactions, whether through an options exchange or otherwise;
​
•
through the distribution of the securities by any Selling Stockholder to its partners, members or stockholders;
​
•
directly to one or more purchasers;
​
•
through delayed delivery requirements;
​
•
by pledge to secured debts and other obligations or any transfer upon the foreclosure under such pledges; a combination of any such methods of sale; or
​
•
any other method permitted pursuant to applicable law.
​
The Selling Stockholders may also sell securities under Rule 144 or any other exemption from registration under the Securities Act, if available, rather than under this prospectus.
Broker-dealers engaged by the Selling Stockholders may arrange for other brokers-dealers to participate in sales. Broker-dealers may receive commissions or discounts from the Selling Stockholders (or, if any broker-dealer acts as agent for the purchaser of securities, from the purchaser) in amounts to be negotiated, but, except as set forth in a supplement to this Prospectus, in the case of an agency transaction not in excess of a customary brokerage commission in compliance with FINRA Rule 2121; and in the case of a principal transaction a markup or markdown in compliance with FINRA Rule 2121.
In connection with the sale of the securities or interests therein, the Selling Stockholders may enter into hedging transactions with broker-dealers or other financial institutions, which may in turn engage in short sales of the securities in the course of hedging the positions they assume. The Selling Stockholders may also sell securities short and deliver these securities to close out their short positions, or loan or pledge the securities to broker-dealers that in turn may sell these securities. The Selling Stockholders may also enter into option or other transactions with broker-dealers or other financial institutions or create one or more derivative securities which require the delivery to such broker-dealer or other financial institution of securities offered by this prospectus, which securities such broker-dealer or other financial institution may resell pursuant to this prospectus (as supplemented or amended to reflect such transaction). The Selling Stockholders also may transfer the securities in other circumstances in which the transferees, pledgees, donees or other successors-in-interest will be the selling beneficial owners for purposes of this prospectus.

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The Selling Stockholders and any broker-dealers or agents that are involved in selling the securities may be deemed to be “underwriters” within the meaning of the Securities Act in connection with such sales (it being understood that the Selling Stockholders shall not be deemed to be underwriters solely as a result of their participation in this offering). In such event, any commissions received by such broker-dealers or agents and any profit on the resale of the securities purchased by them may be deemed to be underwriting commissions or discounts under the Securities Act. Each Selling Stockholder has informed the Company that it does not have any written or oral agreement or understanding, directly or indirectly, with any person to distribute the securities.
The Company is required to pay certain fees and expenses incurred by the Company incident to the registration of the securities. The Company has agreed to indemnify the Selling Stockholders against certain losses, claims, damages and liabilities, including liabilities under the Securities Act.
We have agreed to keep this prospectus effective until the earlier of (i) the date on which the securities may be resold by the Selling Stockholders without registration and without regard to any volume or manner-of-sale limitations by reason of Rule 144, or (ii) all of the securities have been sold pursuant to this prospectus or Rule 144 under the Securities Act or any other rule of similar effect. The resale securities will be sold only through registered or licensed brokers or dealers if required under applicable state securities laws. In addition, in certain states, the resale securities covered hereby may not be sold unless they have been registered or qualified for sale in the applicable state or an exemption from the registration or qualification requirement is available and is complied with.
Under applicable rules and regulations under the Exchange Act, any person engaged in the distribution of the resale securities may not simultaneously engage in market making activities with respect to the common stock for the applicable restricted period, as defined in Regulation M, prior to the commencement of the distribution. In addition, the Selling Stockholders will be subject to applicable provisions of the Exchange Act and the rules and regulations thereunder, including Regulation M, which may limit the timing of purchases and sales of the common stock by the Selling Stockholders or any other person. We will make copies of this prospectus available to the Selling Stockholders and have informed them of the need to deliver a copy of this prospectus to each purchaser at or prior to the time of the sale (including by compliance with Rule 172 under the Securities Act).

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LEGAL MATTERS
Skadden, Arps, Slate, Meagher & FlomCooley LLP, New York, New York,Reston, Virginia, will pass upon certain legal matters relating to the issuance and salevalidity of the securitiesshares of common stock offered hereby on behalfhereby.
EXPERTS
The consolidated financial statements of VYNE Therapeutics Inc. Additional legal matters may be passedas of and for the year ended December 31, 2022 incorporated in this prospectus by reference from the Annual Report on Form 10-K for the year ended December 31, 2022 have been audited by Baker Tilly US, LLP, an independent registered public accounting firm, as stated in their report. Such financial statements have been so incorporated in reliance upon for us or any underwriters, dealers or agents, by counsel that we will namethe report of such firm given upon their authority as experts in accounting and auditing. The report on the applicable prospectus supplement.
EXPERTSconsolidated financial statements contains an explanatory paragraph regarding the Company’s ability to continue as a going concern.
The financial statements as of December 31, 20202021 and for the year ended December 31, 20202021 incorporated in this Prospectusprospectus by reference to the Annual Report on Form 10-K for the year ended December 31, 20202022 have been so incorporated in reliance on the report (which contains an explanatory paragraph relating to the Company’s ability to continue as a going concern as described in Note 1 to the financial statements) of PricewaterhouseCoopers LLP, an independent registered public accounting firm, given on the authority of said firm as experts in auditing and accounting.
The financial statementsWHERE YOU CAN FIND ADDITIONAL INFORMATION
This prospectus is part of a registration statement we filed with the SEC. This prospectus does not contain all of the information set forth in the registration statement and the exhibits to the registration statement. For further information with respect to us and the securities we are offering under this prospectus, we refer you to the registration statement and the exhibits and schedules filed as a part of the registration statement. You should rely only on the information contained in this prospectus or incorporated by reference in this prospectus. We have not authorized anyone else to provide you with different information. We are not making an offer of these securities in any state where the offer is not permitted. You should not assume that the information in this prospectus is accurate as of December 31, 2019 and for eachany date other than the date on the front page of this prospectus, regardless of the two yearstime of delivery of this prospectus or any sale of the securities offered by this prospectus.
We file annual, quarterly and current reports, proxy statements and other information with the SEC. The SEC maintains a website at www.sec.gov that contains reports, proxy and information statements, and other information regarding issuers, such as us, that file electronically with the SEC.
Copies of certain information filed by us with the SEC are also available on our website at www.vynetherapeutics.com. Information contained in the period ended December 31, 2019or accessible through our website does not constitute a part of this prospectus and is not incorporated by reference in this Prospectusprospectus. We have included our website address as an inactive textual reference only.

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INCORPORATION OF CERTAIN INFORMATION BY REFERENCE
The SEC allows us to “incorporate by reference” information into this prospectus, which means that we can disclose important information to you by referring you to another document filed separately with the SEC. The SEC file number for the documents incorporated by reference to the in this prospectus is 001-38356. The documents incorporated by reference into this prospectus contain important information that you should read about us.
The following documents are incorporated by reference into this document:
•
our Annual Report on Form 10-K for the year ended December 31, 20202022, filed with the SEC on March 14, 2023;
​
•
our Quarterly Reports on Form 10-Q for the quarters ended March 31, 2023, June 30, 2023 and September 30, 2023, filed with the SEC on May 11, 2023, August 14, 2023 have been soand November 13, 2023, respectively;
​
•
our Current Reports on Form 8-K filed with the SEC on January 12, 2023, January 17, 2023, February 10, 2023, February 28, 2023, May 1, 2023 and October 30, 2023 (each to the extent the information in such reports is filed and not furnished); and
​
•
the description of our common stock contained in our Registration Statement on Form 8-A filed with the SEC on January 19, 2018, including any amendments or reports filed for the purposes of updating this description, including Exhibit 4.1 to our Annual Report on Form 10-K for the fiscal year ended December 31, 2022, filed with the SEC on March 14, 2023.
​
We also incorporate by reference into this prospectus all documents (other than current reports furnished under Item 2.02 or Item 7.01 of Form 8-K and exhibits filed on such form that are related to such items) that are filed by us with the SEC pursuant to Sections 13(a), 13(c), 14 or 15(d) of the Exchange Act (i) after the date of the initial filing of the registration statement of which this prospectus forms a part and prior to effectiveness of the registration statement, or (ii) after the date of this prospectus but prior to the termination of the offering. These documents include periodic reports, such as Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q and Current Reports on Form 8-K, as well as proxy statements.
We will provide to each person, including any beneficial owner, to whom a prospectus is delivered, without charge upon written or oral request, a copy of any or all of the documents that are incorporated by reference into this prospectus but not delivered with the prospectus, including exhibits that are specifically incorporated by reference into such documents. You should direct any requests for documents to:
VYNE Therapeutics Inc.
Attn: Corporate Secretary
685 Route 202/206 N., Suite 301
Bridgewater, New Jersey 08807
(800) 775-7936
Any statement contained in reliance onthis prospectus or contained in a document incorporated or deemed to be incorporated by reference into this prospectus will be deemed to be modified or superseded to the report of Kesselman & Kesselman, Certified Public Accountants (Isr.),extent that a member firm of PricewaterhouseCoopers International Limited, an independent registered public accounting firm, given on the authority of said firm as expertsstatement contained in auditing and accounting.this prospectus or any subsequently filed supplement to this prospectus, or document deemed to be incorporated by reference into this prospectus, modifies or supersedes such statement.
 
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​
​
39,266,980 Shares
[MISSING IMAGE: lg_vynetherapeu-4c.jpg]
Common Stock
​
PROSPECTUS
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​
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PART II

INFORMATION NOT REQUIRED IN THE PROSPECTUS
Item 14.   Other Expenses of Issuance and Distribution.Distribution
The following table sets forth the various expenses to be incurred in connection with the sale and distribution of the securities being registered.
​​​Amount​
SEC registration fee​​​$21,570​​
Printing and engraving​​​​*​​
Accounting services​​​​*​​
Legal fees of registrant’s counsel​​​​*​​
FINRA filing fee​​​​*​​
Transfer agent and trustee fees​​​​*​​
Miscellaneous​​​​*​​
Total​​​​*​​
​
*
These feesregistered hereby, all of which will be borne by the Registrant (except any underwriting discounts and commissions and expenses incurred by the selling stockholders for brokerage, accounting, tax or legal services or any other expenses incurred by the selling stockholders in disposing of its shares). All amounts shown are calculated based onestimates except the number of issuances and the amount of securities offered and accordingly cannot be estimated at this time.SEC registration fee.
​
​​​Amount​
SEC registration fees​​​$18,547​​
Accounting fees and expenses​​​​40,000​​
Legal fees and expenses​​​​250,000​​
Miscellaneous fees and expenses​​​​6,453​​
Total​​​$315,000​​
Item 15.   Indemnification of Directors and Officers.Officers
As permitted by Section 102 of the Delaware General Corporation Law, our amended and restated certificate of incorporation and bylaws limit or eliminate the personal liability of each of our directors for a breach of his or her fiduciary duty of care as a director. The duty of care generally requires that, when acting on behalf of the corporation, directors exercise an informed business judgment based on all material information reasonably available to them. Consequently, a director will not be personally liable to us or our stockholders for monetary damages for breach of fiduciary duty as a director, except for liability for:
•
any breach of the director’s duty of loyalty to us or our stockholders;
​
•
any act or omission not in good faith or that involves intentional misconduct or a knowing violation of law;
​
•
any act related to unlawful stock repurchases, redemptions or other distributions or payment of dividends; or
​
•
any transaction from which the director derived an improper personal benefit.
​
These limitations of liability do not affect the availability of equitable remedies such as injunctive relief or rescission. Our amended and restated certificate of incorporation also authorizes us to indemnify our officers, directors and other agents to the fullest extent permitted under Delaware law.
As permitted by Section 145 of the Delaware General Corporation Law, our amended and restated bylaws provide that:
•
we shall indemnify our directors and officers, and may indemnify our employees or agents to the fullest extent permitted by the Delaware General Corporation Law, subject to limited exceptions;
​
•
we shall advance expenses to our directors and officers, and may advance expenses to our employees and agents in connection with a legal proceeding to the fullest extent permitted by the Delaware General Corporation Law, subject to limited exceptions; and
​
•
the rights provided in our amended and restated bylaws are not exclusive.
​
Our amended and restated certificate of incorporation, attached as Exhibit 3.1 hereto and our amended and restated bylaws, attached as Exhibit 3.2 hereto, provide for the indemnification provisions

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described above and elsewhere herein. We have entered into separate indemnification agreements with our directors and officers which may be broader than the specific indemnification provisions contained in the Delaware General Corporation Law. These indemnification agreements generally require us, among other things, to indemnify our officers and directors against liabilities that may arise by reason of their status or service as directors or officers, other than liabilities arising from unlawful conduct. These indemnification

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agreements also generally require us to advance any expenses incurred by the directors or officers as a result of any proceeding against them as to which they could be indemnified. In addition, we have purchased a policy of directors’ and officers’ liability insurance that insures our directors and officers against the cost of defense, settlement or payment of a judgment in some circumstances. These indemnification provisions and the indemnification agreements may be sufficiently broad to permit indemnification of our officers and directors for liabilities, including reimbursement of expenses incurred, arising under the Securities Act of 1933, as amended, or the Securities Act.
Item 16.   Exhibits.Exhibits
​​​​​​Incorporated by Reference​​​​
Exhibit No.​​Description​​Form​​Date​​Number​​Filed Herewith​
 1.1*​​Form of Underwriting Agreement.​​​​​​​​​​​​​
 4.1​​
Form of Common Stock Certificate.
​​S-1/A​​January 12, 2018​​4.2​​​​
 4.2*​​Form of Preferred Stock Certificate.​​​​​​​​​​​​​
 4.3*​​Form of Warrant Certificate.​​​​​​​​​​​​​
 5.1​​
Opinion of Skadden, Arps, Slate, Meagher & Flom LLP.
​​​​​​​​​​​X​
23.1​​
Consent of PricewaterhouseCoopers LLP, independent registered public accounting firm of VYNE Therapeutics Inc.
​​​​​​​​​​​X​
23.2​​Consent of Kesselman & Kesselman, independent registered public accounting firm of VYNE Therapeutics Inc.​​​​​​​​​​​X​
23.3​​Consent of Skadden, Arps, Slate, Meagher & Flom LLP (included in Exhibit 5.1).​​​​​​​​​​​X​
24.1​​
Power of Attorney (included on signature page).
​​​​​​​​​​​X​
​​​​​​​Incorporated by Reference​
​
Exhibit
Number
​​Description​​Form​​
File
Number
​​Exhibit​​Filing Date​
​4.1​​
Amended and Restated Certificate of Incorporation
​​10-K​​001-38356​​3.1​​March 17, 2022​
​4.2​​
Certificate of Designation of Preferences, Rights, and Limitations of Series A Convertible Preferred Stock
​​10-Q​​001-38356​​3.1(b)​​November 14, 2022​
​4.3​​
Certificate of Elimination
​​8-K​​001-38356​​3.1​​January 17, 2023​
​4.4​​
Certificate of Amendment to the Amended and Restated Certificate of Incorporation
​​8-K​​001-38356​​3.1​​February 10, 2023​
​4.5​​
Amended and Restated Bylaws
​​10-Q​​001-38356​​3.2​​November 14, 2022​
​4.6​​
Form of Pre-Funded Warrant
​​8-K​​001-38356​​4.1​​October 30, 2023​
​5.1*​​
Opinion of Cooley LLP
​​​​​​​​​​​​​
​10.1​​
Form of Securities Purchase Agreement, by and among the Registrant and the Purchasers, dated October 27, 2023
​​8-K​​001-38356​​10.1​​October 30, 2023​
​10.2​​
Form of Registration Rights Agreement, by and among the Registrant and the Purchasers, dated October 27, 2023
​​8-K​​001-38356​​10.2​​October 30, 2023​
​23.1*​​
Consent of Cooley LLP (included in Exhibit 5.1)
​​​​​​​​​​​​​
​23.2*​​
Consent of Baker Tilly US, LLP, independent registered public accounting firm
​​​​​​​​​​​​​
​23.3*​​Consent of PricewaterhouseCoopers LLP, independent registered public accounting firm​​​​​​​​​​​​​
​24.1*​​
Power of Attorney (included on the signature page of this registration statement)
​​​​​​​​​​​​​
​107*​​
Filing Fee Table
​​​​​​​​​​​​​
​
*
To be filed by amendment or as an exhibit to a Current Report on Form 8-K and incorporated herein by reference, if applicable.Filed herewith.
​
Item 17.   Undertakings.Undertakings
The undersigned Registrantregistrant hereby undertakes:
(1)
To file, during any period in which offers or sales are being made, a post-effective amendment to this registration statement:
​
(i)
To   to include any prospectus required by Section 10(a)(3) of the Securities Act.Act of 1933;
​
(ii)
To   to reflect in the prospectus any facts or events arising after the effective date of the registration statement (or the most recent post-effective amendment thereof) which, individually or in the aggregate, represent a fundamental change in the information set forth in thisthe registration

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statement. Notwithstanding the foregoing, any increase or decrease in volume of securities offered (if the total dollar value of securities offered would not exceed that which was registered) and any deviation from the low or high end of the estimated maximum offering range may be reflected in the form of prospectus filed with the Commission pursuant to Rule 424(b) if,
​

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in the aggregate, the changes in volume and price represent no more than a 20 percent20% change in the maximum aggregate offering price set forth in the “Calculation of Registration Fee” table in the effective registration statementstatement; and
(iii)
To   to include any material information with respect to the plan of distribution not previously disclosed in the registration statement or any material change to such information in thisthe registration statement,statement.
​
provided,Provided, however, that subparagraphs paragraphs (1)(i), (1)(ii) and (1)(iii) above shalldo not apply if the registration statement is on Form S-3 and the information required to be included in a post-effective amendment by those paragraphs is contained in the reports filed with or furnished to the Commission by the registrant pursuant to Section 13 or Section 15(d) of the Securities Exchange Act of 1934 that are incorporated by reference in thisthe registration statement, or as to a registration statement on Form S-3, is contained in a form of prospectus filed pursuant to Rule 424(b) that is part of the registration statement.
(2)
That, for the purpose of determining any liability under the Securities Act of 1933, each such post-effective amendment shall be deemed to be a new registration statement relating to the securities offered therein, and the offering of such securities at that time shall be deemed to be the initial bona fide offering thereof.
​
(3)
To remove from registration by means of a post-effective amendment any of the securities being registered which remain unsold at the termination of the offering.
​
(4)
That, for the purpose of determining liability under the Securities Act of 1933 to any purchaser:
​
(i)
Each prospectus filed by the registrant pursuant to Rule 424(b)(3) shall be deemed to be part of the registration statement as of the date the filed prospectus was deemed part of and included in the registration statement; and
​
(ii)
Each prospectus required to be filed pursuant to Rule 424(b)(2), (b)(5), or (b)(7) as part of a registration statement in reliance on Rule 430B relating to an offering made pursuant to Rule 415(a)(1)(i), (vii), or (x) for the purpose of providing the information required by Section 10(a) of the Securities Act of 1933 shall be deemed to be part of and included in the registration statement as of the earlier of the date such form of prospectus is first used after effectiveness or the date of the first contract of sale of securities in the offering described in the prospectus. As provided in Rule 430B, for liability purposes of the issuer and any person that is at that date an underwriter, such date shall be deemed to be a new effective date of the registration statement relating to the securities in the registration statement to which thethat prospectus relates, and the offering of such securities at that time shall be deemed to be the initial bona fide offering thereof. Provided, however, that no statement made in a registration statement or prospectus that is part of the registration statement or made in a document incorporated or deemed incorporated by reference into the registration statement or prospectus that is part of the registration statement will, as to a purchaser with a time of contract of sale prior to such effective date, supersede or modify any statement that was made in the registration statement or prospectus that was part of the registration statement or made in any such document immediately prior to such effective date.
​
(5)
That, for the purpose of determining liability of the registrant under the Securities Act to any purchaser in the initial distribution of the securities, the undersigned registrant undertakes that in a primary offering of securities of the undersigned registrant pursuant to this registration statement, regardless of the underwriting method used to sell the securities to the purchaser, if the securities are offered or sold to such purchaser by means of any of the following communications, the undersigned registrant will be a seller to the purchaser and will be considered to offer or sell such securities to such purchaser:
​
(i)
Any preliminary prospectus or prospectus of the undersigned registrant relating to the offering required to be filed pursuant to Rule 424;
​

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(ii)
Any free writing prospectus relating to the offering prepared by or on behalf of the undersigned registrant or used or referred to by the undersigned registrant;
​
(iii)
The portion of any other free writing prospectus relating to the offering containing material information about the undersigned registrant or its securities provided by or on behalf of the undersigned registrant; and
​
(iv)
Any other communication that is an offer in the offering made by the undersigned registrant to the purchaser.
​
(6)
That, for the purpose of determining liability of the registrant under the Securities Act of 1933, each filing of the registrant’s annual report pursuant to Section 13(a) or Section 15(d) of the Securities Exchange Act of 1934 (and, where applicable, each filing of an employee benefit plan’s annual report pursuant to Sectionsection 15(d) of the Securities Exchange Act of 1934) that is incorporated by reference in the registration statement shall be deemed to be a new registration statement relating to the securities offered therein, and the offering of such securities at that time shall be deemed to be the initial bona fide offering thereof.
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(6)   Insofar as indemnification for liabilities arising under the Securities Act of 1933 may be permitted to directors, officers and controlling persons of the registrant pursuant to the foregoing provisions, or otherwise, the registrant has been advised that in the opinion of the Securities and Exchange Commission such indemnification is against public policy as expressed in the Securities Act and is, therefore, unenforceable. In the event that a claim for indemnification against such liabilities (other than the payment by the registrant of expenses incurred or paid by a director, officer or controlling person of the registrant in the successful defense of any action, suit or proceeding) is asserted by such director, officer or controlling person in connection with the securities being registered, the registrant will, unless in the opinion of its counsel the matter has been settled by controlling precedent, submit to a court of appropriate jurisdiction the question whether such indemnification by it is against public policy as expressed in the Securities Act of 1933 and will be governed by the final adjudication of such issue.
 
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SIGNATURES
Pursuant to the requirements of the Securities Act of 1933, as amended, the Registrantregistrant certifies that it has reasonable grounds to believe that it meets all of the requirements for filing on Form S-3 and has duly caused this registration statement to be signed on its behalf by the undersigned, thereunto duly authorized, in the City of Bridgewater, State of New Jersey, U.S.A., on May 6, 2021.November 13, 2023.
​​​​VYNE THERAPEUTICS INC.​
​​​​
By:
/s/ David Domzalski
​
​
David Domzalski
Chief Executive Officer
​​
VYNE THERAPEUTICS INC.
By:
/s/ David Domzalski
​
​
David Domzalski
Chief Executive Officer

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SIGNATURES AND POWER OF ATTORNEY
KNOW ALL MEN AND WOMENPERSONS BY THESE PRESENTS, that each personof the persons whose signature appearsnames appear below constitutes and appoints David Domzalski, Tyler Zeronda and Andrew Saik,Mutya Harsch, and each of them, such person’s true and lawful attorney in fact and agent, with full power of substitution and re-substitution, for such person and in his or her attorney-in-factname, place and agent, each with the power of substitution, for him or herstead, in any and all capacities, to signexecute any and all amendments (including post-effective amendments) to this filing on Form S-3, and supplements to thisRegistration Statement (or any other registration statement andfor the same offering that is to any and all instruments, documents or exhibits filed as partbe effective upon filing pursuant to Rule 462(b) under the U.S. Securities Act of or in conjunction with this registration statement or amendments or supplements thereof,1933), and to file the same, together with all exhibits thereto, and other documents in connection therewith, with the U.S. Securities and Exchange Commission, and such other agencies, offices and persons as may be required by applicable law, granting unto said attorney in fact and agent, full power and authority to do and perform each and every act and thing requisite or necessary to be done in and about the premises, as fully to all intents and purposes as such person might or could do in person, hereby ratifying and confirming all that each said attorneys-in-fact, or his or her or their substitute or substitutes,attorney-in-fact and agent may lawfully do or cause to be done by virtue thereof.hereof.
Pursuant to the requirements of the Securities Act of 1933, the Registrantthis registration statement has duly caused this report to bebeen signed on its behalf by the undersigned thereunto duly authorized.following persons in the capacities and on the dates indicated.
​NameSignature​​CapacityTitle​​Date​
​
/s/ David Domzalski
​
David Domzalski
​​President,
Director and Chief Executive Officer and Director (Principal(Principal Executive Officer)Officer)
​​May 6, 2021November 13, 2023​
​
/s/ Andrew SaikTyler Zeronda
​
Andrew SaikTyler Zeronda
​​
Chief Financial Officer (Principal Financial Officerand Treasurer (Principal Financial andPrincipal Accounting Officer)Officer)
​​May 6, 2021November 13, 2023​
​
/s/ Sharon Barbari
​
Sharon Barbari
​​Director​​November 13, 2023​
​
/s/ Steven Basta
​
Steven Basta
​​Director​​May 6, 2021​
​
/s/ Sharon Barbari
​
Sharon Barbari
​​Director​​May 6, 2021​
​
/s/ Rex Bright
​
Rex Bright
​​Director​​May 6, 2021November 13, 2023​
​
/s/ Anthony Bruno
​
Anthony Bruno
​​Director​​May 6, 2021November 13, 2023​
​
/s/ Patrick LePore
​
Patrick LePore
​​Director​​May 6, 2021November 13, 2023​
​
/s/ Elisabeth Sandoval Little
​
Elisabeth Sandoval Little
​​Director​​May 6, 2021November 13, 2023​
 
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