Use these links to rapidly review the document
TABLE OF CONTENTS

Table of Contents

Filed Pursuant to Rule 424(b)(3)
Registration Statement No. 333-221968

Prospectus

Leap Therapeutics, Inc.
3,734,914 Shares
Common Stock

        This prospectus relates to the possible resale by the selling stockholders (the "Selling Stockholders") identified in this prospectus of up to 3,734,914 shares of our common stock, par value $0.001 per share (the "Common Stock"), which includes (i) 1,867,457 shares of our Common Stock issued on November 14, 2017 and (ii) an aggregate of 1,867,457 shares of our Common Stock (the "Warrant Shares") issuable upon exercise of common stock purchase warrants issued on November 14, 2017 (the "Warrants") in a private placement transaction, which closed on November 14, 2017. We are registering these shares on behalf of the Selling Stockholders, to be offered and sold by them from time to time.

        We are not selling any shares of Common Stock under this prospectus and will not receive any of the proceeds from the sale of shares of Common Stock by the Selling Stockholders. However, we may receive proceeds from the cash exercise of the Warrants, which, if exercised in cash at the current applicable exercise price with respect to all of the Warrants to purchase 1,867,457 shares of Common Stock, would result in gross proceeds to the Company of $11.4 million.

        The Selling Stockholders may offer the shares of our Common Stock and Warrant Shares from time to time and at such prices as each Selling Stockholder may determine through public or private transactions or through other means described in the section entitled "Plan of Distribution" or a supplement to this prospectus. Each Selling Stockholder may also sell the shares under Rule 144 under the Securities Act of 1933, as amended, if available, rather than under this prospectus.

        We are registering the offer and sale of the shares of our Common Stock and Warrant Shares pursuant to certain registration rights granted to the Selling Stockholders. The registration of these shares does not necessarily mean that any of the shares will be offered or sold by the Selling Stockholders. The timing and amount of any sale is within the sole discretion of each Selling Stockholder.

        The Selling Stockholders will pay all underwriting discounts and selling commissions, if any, in connection with the sale of the shares of Common Stock and Warrant Shares. We have agreed to pay certain expenses in connection with this registration statement and to indemnify the Selling Stockholders against certain liabilities. To our knowledge, as of the date of this prospectus, no underwriter or other person has been engaged to facilitate the sale of shares of Common Stock and Warrant Shares in this offering.

        We are an emerging growth company as that term is used in the Jumpstart Our Business Startups Act of 2012 and, as such, have elected to comply with certain reduced public company reporting requirements for this prospectus and future filings.

        Our Common Stock is listed on The NASDAQ Global Market under the symbol "LPTX." On December 7, 2017, the closing price of our Common Stock was $6.76 per share.

        Investing in our Common Stock involves a high degree of risk. You should carefully read the risks and uncertainties included herein under the heading "Risk Factors" on page 7 of this prospectus, and under similar headings in our Annual Report on Form 10-K for the fiscal year ended December 31, 2016 and our Quarterly Reports on Form 10-Q for the quarterly periods ended March 31, 2017, June 30, 2017 and September 30, 2017, which have been filed with the Securities and Exchange Commission and are incorporated by reference in this prospectus and in the other documents that are filed after the date hereof and incorporated by reference into 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 of this prospectus. Any representation to the contrary is a criminal offense.

   

The date of this prospectus is December 15, 2017.

---

Table of Contents

TABLE OF CONTENTS

---

Table of Contents

ABOUT THIS PROSPECTUS

        This prospectus is part of a registration statement on Form S-3 that we filed with the U.S. Securities and Exchange Commission (the "SEC"), using a "shelf" registration process. By using such registration statement, the selling stockholders identified herein (the "Selling Stockholders") may, from time to time, offer and sell (in one or more transactions as described under "Plan of Distribution") up to 3,734,914 shares of our common stock, par value $0.001 per share (the "Common Stock"), including 1,867,457 shares of Common Stock issuable upon the exercise of the warrants (the "Warrant Shares") issued in our private placement offering which closed on November 14, 2017. We will not receive any of the proceeds from the sales of the Common Stock by the Selling Stockholders.

        This prospectus provides you with a general description of us and our securities. We may add, update or change in a prospectus supplement any of the information contained in this prospectus or the documents incorporated by reference. For further information about our business and our securities, you should refer to the registration statement and the reports incorporated by reference in this prospectus, as described in "Additional Information" and "Incorporation of Certain Information by Reference". This prospectus contains summaries of certain provisions contained in some of the documents described herein, but reference is made to the actual documents for complete information. All of the summaries are qualified in their entirety by the actual documents. Copies of some of the documents referred to herein have been filed, will be filed or will be incorporated by reference as exhibits to the registration statement of which this prospectus is a part, and you may obtain copies of those documents as described below under the heading "Where You Can Find More Information."

        You must not rely upon any information or representation not contained or incorporated by reference in this prospectus. You should rely only on the information contained in this prospectus and in any prospectus supplement (including in any documents incorporated by reference herein or therein). You should not assume that the information contained in this prospectus is accurate on any date subsequent to the date set forth on the front of the document or that any information we have incorporated by reference is correct on any date subsequent to the date of the document incorporated by reference, even though this prospectus is delivered or securities are sold on a later date. We and the Selling Stockholders have not authorized anyone to provide you with any different information. The Selling Stockholders are offering to sell our securities, and seeking offers to buy, only in jurisdictions where offers and sales are permitted.

        Leap Therapeutics, Inc. and its subsidiaries are collectively referred to herein as "Leap", "the Company", "we", "us", and "our", unless otherwise specified or the context indicates otherwise.

1

---

Table of Contents

 

2

---

Table of Contents

3

---

Table of Contents

4

---

Table of Contents

5

---

Table of Contents

 

6

---

Table of Contents

RISK FACTORS

        An investment in our securities involves a high degree of risk. Before making an investment decision, you should carefully consider the risks described below and under "Risk Factors" in any applicable prospectus supplement and in our most recent Annual Report on Form 10-K, and in our updates to those Risk Factors in our Quarterly Reports on Form 10-Q or Current Reports on Form 8-K following the most recent Form 10-K, and in all other information appearing in this prospectus or incorporated by reference into this prospectus and any applicable prospectus supplement. The material risks and uncertainties that management believes affect us will be described in those documents. In addition to those risk factors, there may be additional risks and uncertainties of which management is not aware or focused on or that management deems immaterial. Our business, financial condition or results of operations could be materially adversely affected by any of these risks. The trading price of our securities could decline due to any of these risks, and you may lose all or part of your investment. This prospectus is qualified in its entirety by these risk factors.

Additional Risks Relating to This Offering and Our Common Stock

         The sale of a substantial amount of our Common Stock, including resale of the shares of Common Stock issuable upon the exercise of Warrants acquired in the Private Placement, in the public market after this offering could adversely affect the prevailing market price of our Common Stock and cause stockholders to experience dilution.

        We have outstanding an aggregate of 12,354,014 shares of our Common Stock as of November 30, 2017. The Warrants are exercisable for an aggregate of 2,958,094 shares of Common Stock, subject to adjustment as provided in the Warrants, including 1,867,457 shares of Common Stock being offered pursuant to this prospectus. The Warrants are exercisable at any time. Pursuant to the registration rights granted in the Private Placement, we agreed to register the resale by the Selling Stockholders named herein of the shares of Common Stock issuable upon exercise of the Warrants. Two Purchasers have opted not to register their Shares or Warrant Shares and therefore, such Shares and Warrant Shares are not included in this offering. Upon such registration, these registered shares will become generally available for immediate resale.

        Sales of substantial amounts of shares of our Common Stock in the public market, or the perception that such sales might occur, could adversely affect the market price of our Common Stock, and the market value of our other securities, and could result in dilution to shareholders who hold our Common Stock. Further, pursuant to the terms of the Purchase Agreements and the Warrants, we have agreed to solicit stockholder approval in connection with Nasdaq Rule 5635(d) pursuant to a proxy statement that we plan to file with the SEC for the inclusion of a full ratchet anti-dilution feature as a term of the Warrants. If stockholder approval of the inclusion of such anti-dilution feature is obtained, and if we issue Common Stock, options or Common Stock equivalents at a price less than the exercise price of the Warrants, subject to certain customary exceptions, the exercise price of the Warrants will be reduced to that lower price. Such a decrease in exercise price may cause holders to exercise the Warrants which could result in dilution to our existing stockholders at an accelerated rate.

        In addition, we may issue additional shares of Common Stock or other equity or debt securities convertible into Common Stock in connection with a future financing, acquisition, employee arrangements or otherwise. Any such issuance could result in substantial dilution to our stockholders and could cause our stock price to decline.

        A substantial number of shares of Common Stock are being offered by this prospectus, and we cannot predict if and when the purchasers may sell such shares in the public markets. In addition, certain holders of shares of our Common Stock have additional rights, subject to some conditions, to require us to file registration statements covering the sale of their shares or to include their shares in registration statements that we may file for ourselves or other stockholders. We have also registered the

7

---

Table of Contents

offer and sale of all shares of Common Stock that we may issue under our equity compensation plans. Furthermore, in the future, we may issue additional shares of Common Stock or other equity or debt securities convertible into Common Stock in connection with a financing, acquisition, litigation settlement, employee arrangements or otherwise. Any such issuance could result in substantial dilution to our existing stockholders and could cause our stock price to decline.

         We may become obligated to pay liquidated damages if we fail to file, obtain effectiveness and maintain effectiveness of a registration statement under the Purchase Agreements we entered into with the Selling Stockholders.

        We have granted to the Selling Stockholders resale registration rights pursuant to the terms of Purchase Agreements. In addition to the registration rights, the Selling Stockholders are entitled to receive liquidated damages upon the occurrence of a number of events relating to filing the Registration Statement, the Registration Statement becoming effective and maintaining an effective registration statement covering the securities being registered. The liquidated damages will be payable upon the occurrence of each of those events and each monthly anniversary thereof until cured. The amount of liquidated damages payable per 30-day period is equal to 1.0% of the purchase price paid by such Purchaser and may increase to 2.0% under certain circumstances, provided, however, the maximum aggregate liquidated damages payable to a Selling Stockholder is 10% of the aggregate purchase price paid by a Purchaser for the Shares and Warrants pursuant to the Purchase Agreement. We may also be responsible for the actual damages suffered by a Selling Stockholder in certain circumstances.

         Our share price may be volatile, which could subject us to securities class action litigation and our stockholders could incur substantial losses.

        The market price of shares of our Common Stock could be subject to wide fluctuations in response to many risk factors listed in this section, and others beyond our control, including:

•

the results of clinical trials or development activities of our programs, or any future programs we may acquire;



•

actual or anticipated fluctuations in our financial condition and operating results;



•

failure to meet or exceed financial estimates and projections of the investment community or that we provide to the public;



•

issuance of new or updated research or reports by securities analysts;



•

fluctuations in the valuation of companies perceived by investors to be comparable to us;



•

additions or departures of key management or other personnel;



•

disputes or other developments related to proprietary rights, including patents, litigation matters, and our ability to obtain patent protection for our technologies;



•

announcement or expectation of additional debt or equity financing efforts;



•

sales of our Common Stock by us, our insiders or our other stockholders; and



•

general economic and market conditions.

        These and other market and industry factors may cause the market price and demand for our Common Stock to fluctuate substantially, regardless of our actual operating performance, which may limit or prevent investors from readily selling their shares of Common Stock and may otherwise negatively affect the liquidity of our Common Stock. In addition, the stock market in general, and NASDAQ and emerging growth companies in particular, have experienced extreme price and volume

8

---

Table of Contents

fluctuations that have often been unrelated or disproportionate to the operating performance of these companies. In the past, when the market price of a stock has been volatile, holders of that stock have instituted securities class action litigation against the company that issued the stock. If in the future any of our stockholders brought a lawsuit against us, we could incur significant legal expenses, settlement costs or damage awards that are not covered by, or exceed the limits of, our available directors' and officers' liability insurance, which could adversely impact our financial condition, results of operations or cash flows. Such a lawsuit could also divert the time and attention of our management.

9

---

Table of Contents

CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS

        This prospectus and each prospectus supplement, including the documents that we incorporate by reference, contains or may contain forward-looking statements as that term is defined in the federal securities laws. The events described in forward-looking statements contained in this prospectus, including the documents that we incorporate by reference, may not occur. Generally, these statements relate to our business plans or strategies, projected or anticipated benefits or other consequences of our plans or strategies, financing plans, projected or anticipated benefits from acquisitions that we may make, or projections involving anticipated revenues, earnings or other aspects of our operating results or financial position, and the outcome of any contingencies. Any such forward-looking statements are based on current expectations, estimates and projections of management. We intend for these forward-looking statements to be covered by the safe-harbor provisions for forward-looking statements. Words such as "may," "expect," "believe," "anticipate," "project," "plan," "intend," "estimate," and "continue," and their opposites and similar expressions are intended to identify forward-looking statements. We caution you that these statements are not guarantees of future performance or events and are subject to a number of uncertainties, risks and other influences.

        Forward looking statements involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward looking statements. We believe that these factors include, but are not limited to, the following:

•

our ability and plan to develop and commercialize DKN-01 and TRX518;



•

the status, timing and results of preclinical studies and clinical trials;



•

the potential benefits of DKN-01 and TRX518;



•

the timing of our product candidate development programs;



•

our ability to obtain and maintain regulatory approval of our product candidates;



•

our estimates of expenses and future revenues and profitability;



•

our estimates regarding our capital requirements and our needs for additional financing;



•

our estimates of the size of the potential markets for DKN-01 and TRX518;



•

our ability to attract collaborators with acceptable development, regulatory and commercial expertise;



•

the benefits to be derived from any collaborations, license agreements, and other acquisition efforts, including those relating to the development and commercialization of DKN-01 and TRX518;



•

sources of revenues and anticipated revenues, including contributions from any collaborations or license agreements for the development and commercialization of products;



•

our ability to create an effective sales and marketing infrastructure if we elect to market and sell DKN-01 and TRX518 directly;



•

the rate and degree of market acceptance of DKN-01 and TRX518;



•

the timing and amount of reimbursement for DKN-01 and TRX518;



•

the success of other competing therapies that may become available;



•

the manufacturing capacity for DKN-01 and TRX518;



•

our intellectual property position;

10

---

Table of Contents

•

our ability to maintain and protect our intellectual property rights;



•

our results of operations, financial condition, liquidity, prospects, growth and strategies; and



•

changes in the industry in which we operate and the trends that effect the industry.

        You should also consider carefully the statements set forth in the section titled "Risk Factors" or elsewhere in this prospectus and the documents incorporated or deemed incorporated herein by reference, including but not limited to the risks described in under "Risk Factors" and elsewhere in our most recent Annual Report on Form 10-K and in our updates to those risk factors in our Quarterly Reports on Form 10-Q and Current Reports on Form 8-K and other factors described elsewhere in this prospectus. Any one or more of these uncertainties, risks and other influences could materially affect our results of operations and whether forward-looking statements made by us ultimately prove to be accurate. Our actual results, performance and achievements could differ materially from those expressed or implied in these forward-looking statements. Except as otherwise required by law, we undertake no obligation to publicly update or revise any forward-looking statements, whether from new information, future events or otherwise.

        DKN-01 and TRX518 are investigational drugs undergoing clinical development and have not been approved by the U.S. Food and Drug Administration (the "FDA"), nor been submitted to the FDA for approval. DKN-01 and TRX518 have not been, and may never be, approved by any regulatory agency or marketed anywhere in the world. Statements contained in this prospectus should not be deemed to be promotional.

11

---

Table of Contents

USE OF PROCEEDS

        We will not receive any proceeds from the sale of our Common Stock by the Selling Stockholders. However, we may receive proceeds from the cash exercise of the Warrants, which, if exercised in cash at the current exercise price with respect to all 2,958,094 Warrant Shares, would result in gross proceeds to us of approximately $18.0 million, and if exercised in cash at the current exercise price with respect to the 1,867,457 Warrant Shares registered in this offering, would result in gross proceeds to us of approximately $11.4 million. The Warrants contain anti-dilution adjustments which, in the event that securities are issued by the Company in certain circumstances at a price lower than the current exercise price of the Warrants, would lower the exercise price of the Warrants and reduce the proceeds to be received by us. The use of proceeds from such Warrant exercises, if any, will not be subject to any restrictions. Under certain conditions set forth in the Warrants, the Warrants are exercisable on a cashless basis. If the Warrants are exercised on a cashless basis, we would not receive any cash payment from the Selling Stockholders upon any exercise of the Warrants. For information about the Selling Stockholders, see "Selling Stockholders."

        The Selling Stockholders will pay any underwriting discounts and brokerage commissions and any similar expenses they incur in disposing of the Common Stock. We will bear all other reasonable costs, fees and expenses incurred in effecting the registration of the Common Stock covered by this prospectus, including all registration and filing fees, fees and expenses of compliance with securities or "blue sky" laws, listing application fees, printing expenses, transfer agent's and registrar's fees, costs of distributing prospectuses in preliminary and final form as well as any supplements thereto, and fees and disbursements of counsel for the Company and the independent registered public accounting firm and other persons retained by the Company.

12

---

Table of Contents

SELLING STOCKHOLDERS

        As described in the prospectus summary, in the Private Placement, the Purchasers acquired shares of our Common Stock and Warrants exercisable for shares of our Common Stock, subject to the limitations described below. In connection with the closing of the Private Placement, we entered into Purchase Agreements containing certain registration rights, pursuant to which we agreed to prepare and file one or more registration statements covering the resale of the shares of Common Stock issued in the Private Placement and issuable upon exercise of the Warrants (without regard to the limitation described below), and to maintain the effectiveness of such registration statement(s) until the earliest of (i) two years after the effective date of the registration statements(s), (ii) such time as all such shares of Common Stock and Warrant Shares have been sold in accordance with the registration statement(s) or in accordance with Rule 144 under the Securities Act, or (iii) such time as such shares of Common Stock and Warrant Shares may be sold by the Purchasers without volume limitations or other restrictions, pursuant to Rule 144 under the Securities Act. We are filing this Registration Statement to comply with our registration requirements under the Purchase Agreements. Two Purchasers have opted not to register their Shares or Warrant Shares and therefore such Shares and Warrant Shares are not included in this offering. For additional information regarding the issuance of Common Stock and the Warrants in the Private Placement, see "Prospectus Summary—Private Placement."

        The following table sets forth for each Selling Stockholder, the name, the number and percentage of shares of Common Stock beneficially owned as of November 30, 2017, the maximum number of shares of Common Stock that may be offered pursuant to this prospectus and the number and percentage of shares of Common Stock that would be beneficially owned after the sale of the maximum number of shares of Common Stock pursuant to this prospectus. The information presented in the table is based on 12,354,014 shares of our Common Stock outstanding on November 30, 2017.

        The Warrants held by the Selling Stockholders are immediately exercisable and therefore, for purposes of the table below, shares of Common Stock and percentage ownership of shares beneficially owned prior to the offering listed in the following table assumes the shares of Common Stock underlying the Warrants are deemed to be outstanding and to be beneficially owned by the Selling Stockholder holding the Warrants, but are not treated as outstanding for the purpose of computing the percentage ownership of any other Selling Stockholder.

        Under the terms of the Warrants, certain Selling Stockholders may not exercise the Warrants to the extent such exercise would cause such Selling Stockholder, together with its affiliates and attribution parties, to beneficially own a number of shares of Common Stock which would exceed 4.99% or 9.99% of our then outstanding Common Stock following such exercise, excluding for purposes of such determination shares of Common Stock issuable upon exercise of the Warrants which have not been exercised. The number of shares in the second column does not reflect this limitation.

        Only those Selling Stockholders listed below may offer and sell the Common Stock pursuant to this prospectus and any accompanying prospectus supplement. The Selling Stockholders may offer all or less than all of the shares listed in the table below for sale pursuant to this prospectus and any accompanying prospectus supplement from time to time. Accordingly, no estimate can be given as to the shares of Common Stock that the Selling Stockholders will hold upon consummation of any such sales, but for purposes of the last two columns below, we have assumed that all of the shares of Common Stock that may be offered pursuant to this prospectus will be sold by the Selling Stockholders.

        Beneficial ownership is determined in accordance with the rules of the SEC, except that the following table does not reflect any applicable beneficial ownership limitation described above, with the effect that beneficial ownership of the Selling Stockholders is calculated and presented (for purposes of disclosure in this prospectus only) on a fully as converted basis. Unless otherwise indicated, this table is based on information supplied to us by the Selling Stockholders and certain of our records and, unless

13

---

Table of Contents

otherwise indicated, to our knowledge, the persons named in the table have sole voting and investment power with respect to all shares beneficially owned, subject to community property laws where applicable.

14

---

Table of Contents

15

---

Table of Contents

        No offer or sale pursuant to this prospectus may occur unless the Registration Statement that includes this prospectus has been declared effective by the SEC and remains effective at the time a Selling Stockholder offers or sells shares of Common Stock. We are required, under certain circumstances, to update, supplement or amend this prospectus to reflect material developments in our business, financial position and results of operations and may do so by an amendment to this prospectus, a prospectus supplement or a future filing with the SEC incorporated by reference in this prospectus.

Relationships with the Selling Stockholders

        Prior to the Closing of the Private Placement, Eli Lilly and Company was a more than 5% direct holder of our outstanding Common Stock. The purchase by Eli Lilly and Company of shares of our Common Stock and Warrant to purchase shares of our Common Stock in the Private Placement was approved by our board of directors in accordance with our amended and restated by-laws and related party transaction policy.

16

---

Table of Contents

PLAN OF DISTRIBUTION

        Each Selling Stockholder of the securities named herein may, from time to time, sell any or all of their securities covered hereby on any stock exchange, market or trading facility on which the securities are traded, in private transactions or otherwise. These sales may be at fixed or negotiated prices or at market prices prevailing at the time of sale. 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;



•

an exchange distribution in accordance with the rules of the applicable exchange;



•

privately negotiated transactions;



•

settlement of short sales;



•

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;



•

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 2440; and in the case of a principal transaction a markup or markdown in compliance with FINRA IM-2440.

        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 may pledge or grant a security interest in some of all of the shares of Common Stock owned by them and, if any of them defaults in the performance of its secured obligations, the pledgees or secured parties may offer and sell the shares of Common Stock from time to time pursuant to this prospectus or any supplement or amendment to this prospectus under Rule 424(b)(3) or other applicable provision of the Securities Act, amending, if necessary, the list of Selling Stockholders to include the pledgee, transferee or other successors in interest as Selling

17

---

Table of Contents

Stockholders under this prospectus. The Selling Stockholders also may transfer and donate the shares of Common Stock in other circumstances in which case the transferees, donees or other successors in interest will be the selling beneficial owners for purposes of this prospectus.

        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. 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. We are not aware that any Selling Stockholder has any written or oral agreement or understanding, directly or indirectly, with any person to distribute the securities.

        We are required to pay certain fees and expenses incurred by us incident to the registration of the securities. We have agreed to indemnify the Selling Stockholders against certain losses, claims, damages and liabilities, including liabilities under the Securities Act.

        We agreed to keep this prospectus effective until the earlier of (i) two years after the effective date of the registration statement(s) covering the resale of the shares of Common Stock issued in the Private Placement and issuable upon exercise of the Warrants, (ii) such time as all such shares of Common Stock and the Warrant Shares have been sold in accordance with the registration statement(s) or in accordance with Rule 144 under the Securities Act, or (iii) such time as such shares of Common Stock and the Warrant Shares may be sold by the Selling Stockholders without volume limitations or other restrictions pursuant to Rule 144 under the Securities Act. The resale securities will be sold only through registered or licensed brokers or dealers if required under applicable state securities laws.

        Under applicable rules and regulations under the Exchange Act, any person engaged in the distribution of the shares of Common Stock 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. Registration of the securities named herein does not mean any of such securities will be offered and sold.

18

---

Table of Contents

LEGAL MATTERS

        The validity of the securities being offered hereby will be passed upon by Morgan, Lewis & Bockius LLP. Julio E. Vega, a partner at Morgan, Lewis & Bockius, purchased 32,868 shares of Common Stock and Warrants to purchase 32,868 shares of Common Stock in the Private Placement, but is not included as a Selling Stockholder in this prospectus and such shares are not being registered in this offering.

EXPERTS

        The consolidated balance sheets of Leap Therapeutics, Inc. and Subsidiaries as of December 31, 2016 and 2015, and the related consolidated statements of operations and comprehensive loss, redeemable preferred stock and stockholders' deficiency, and cash flows for each of the years then ended, have been audited by EisnerAmper LLP, independent registered public accounting firm, as stated in their report, which is incorporated herein by reference. Such financial statements have been incorporated herein by reference in reliance on the report of such firm given upon their authority as experts in accounting and auditing.

DISCLOSURE OF COMMISSION POSITION
ON INDEMNIFICATION FOR SECURITIES ACT LIABILITIES

        Insofar as indemnification for liabilities arising under the Securities Act may be permitted to our directors, officers and controlling persons pursuant to the foregoing provisions, or otherwise, we have been advised that in the opinion of the SEC 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, we will, unless in the opinion of our counsel the matter has been settled by controlling precedent, submit to a court of appropriate jurisdiction the question whether such indemnification by us is against public policy as expressed in the Securities Act and will be governed by the final adjudication of such issue.

ADDITIONAL INFORMATION

        This prospectus is part of a Registration Statement on Form S-3 that we have filed with the SEC relating to the shares of our securities being offered hereby. This prospectus does not contain all of the information in the Registration Statement and its exhibits. The Registration Statement, its exhibits and the documents incorporated by reference in this prospectus and their exhibits, all contain information that is material to the offering of the Securities hereby. Whenever a reference is made in this prospectus to any of our contracts or other documents, the reference may not be complete. You should refer to the exhibits that are a part of the Registration Statement in order to review a copy of the contract or documents. The Registration Statement and the exhibits are available at the SEC's Public Reference Room or through its Website.

        We file annual, quarterly and current reports, proxy statements and other information with the SEC. You can read and copy any materials we file with the SEC at its Public Reference Room at 100 F Street, N.E., Washington, D.C. 20549 and at its regional offices, a list of which is available on the Internet at http://www.sec.gov/contact/addresses.htm. You may obtain information on the operation of the Public Reference Room by calling the SEC at 1-800-SEC-0330. The SEC maintains an Internet site at http://www.sec.gov that contains reports, proxy and information statements, and other information regarding issuers, such as us, that file electronically with the SEC. Additionally, you may access our

19

---

Table of Contents

filings with the SEC through our website at http://www.leaptx.com. The information on our website is not part of this prospectus.

        We will provide you without charge, upon your oral or written request, with a copy of any or all reports, proxy statements and other documents we file with the SEC, as well as any or all of the documents incorporated by reference in this prospectus or the Registration Statement (other than exhibits to such documents unless such exhibits are specifically incorporated by reference into such documents). Requests for such copies should be directed to:

Investor Relations
Leap Therapeutics, Inc.
47 Thorndike Street, Suite B1-1
Cambridge, Massachusetts 02141
Telephone number: (617) 714-0360

        You should rely only on the information in this prospectus and the additional information described above and under the heading "Incorporation of Certain Information by Reference" below. We have not, and the Selling Stockholders have not, authorized any other person to provide you with different information. If anyone provides you with different or inconsistent information, you should not rely upon it. The Selling Stockholders are not making an offer to sell these securities in any jurisdiction where the offer or sale is not permitted. You should assume that the information in this prospectus was accurate on the date of the front cover of this prospectus only, and that any information we have incorporated by reference was accurate on the date of the document incorporated by reference only. Our business, financial condition, results of operations and prospects may have changed since such date.

INCORPORATION OF CERTAIN INFORMATION BY REFERENCE

        The SEC allows us to "incorporate by reference" information that we file with it into this prospectus, which means that we can disclose important information to you by referring you to those documents. The information incorporated by reference is an important part of this prospectus. The information incorporated by reference is considered to be a part of this prospectus, and information that we file later with the SEC will automatically update and supersede information contained in documents filed earlier with the SEC or contained in this prospectus and any accompanying prospectus supplement.

        We incorporate by reference the documents listed below that we have previously filed with the SEC:

•

our Annual Report on Form 10-K for the fiscal year ended December 31, 2016, filed with the SEC on March 31, 2017;



•

our Quarterly Reports on Form 10-Q for the fiscal quarter ended March 31, 2017, filed with the SEC on May 12, 2017, for the fiscal quarter ended June 30, 2017, filed with the SEC on August 11, 2017, and for the fiscal quarter ended September 30, 2017, filed with the SEC on November 13, 2017;



•

our Current Report on Form 8-K filed with the SEC on January 26, 2017, including the exhibits attached thereto and filed therewith;



•

our Current Report on Form 8-K filed with the SEC on June 21, 2017;



•

our Current Report on Form 8-K filed with the SEC on November 17, 2017, including the exhibits attached thereto and filed therewith; and

20

---

Table of Contents

•

the description of our common stock contained in our Registration Statement on Form 8-A, filed on January 20, 2017, including any amendments thereto or reports filed for the purposes of updating this description.

        All reports and other documents that we file with the SEC under Sections 13(a), 13(c), 14 or 15(d) of the Exchange Act after the date of the Registration Statement but before the termination of the offering of the Securities hereunder will also be considered to be incorporated by reference into this prospectus from the date of the filing of these reports and documents, and will supersede the information herein; provided, however, that all reports or portions thereof that we "furnish" to the SEC will not be considered incorporated by reference into this prospectus. We undertake to provide without charge to each person (including any beneficial owner) who receives a copy of this prospectus, upon written or oral request, a copy of all of the preceding documents that are incorporated by reference (other than exhibits, unless the exhibits are specifically incorporated by reference into these documents). You may request a copy of these materials in the manner set forth under the heading "Additional Information," above.

21

---

Table of Contents

 

3,734,914 Shares

Common Stock

PROSPECTUS

December 15, 2017

---