UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): September 5, 2018

Aileron Therapeutics, Inc.

(Exact Name of Company as Specified in Charter)

Registrant’s telephone number, including area code: (617) 995-0900

Not applicable

(Former Name or Former Address, if Changed Since Last Report)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

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 13(a) of the Exchange Act.  ☒

On September 5, 2018, Aileron Therapeutics, Inc. (the “Company”) appointed Manuel C. Alves Aivado, M.D., Ph.D., the Company’s Senior Vice President, Chief Medical Officer, as President and Chief Executive Officer of the Company, effective as of September 6, 2018. In connection with his appointment as President and Chief Executive Officer, on September 5, 2018, the Board of Directors of the Company (the “Board”) elected Dr. Aivado to the Board as a Class III director with a term expiring at the 2020 annual meeting of stockholders, effective as of September 6, 2018.

Dr. Aivado will succeed John Longenecker, Ph.D. whose resignation as President and Interim Chief Executive Officer of the Company was effective as of September 6, 2018. Dr. Longenecker is expected to continue his employment with the Company through September 30, 2018.

Dr. Aivado, age 48, has served as our Senior Vice President, Chief Medical Officer since September 2014. From March 2012 until September 2014, Dr. Aivado served as vice president of clinical development and pharmacovigilance at Taiho Oncology, Inc., a pharmaceutical company. From October 2006 until March 2012, Dr. Aivado served as senior medical director in the clinical development group at GlaxoSmithKline, Inc., a global pharmaceutical company. In addition, Dr. Aivado was an instructor in medicine at Beth Israel Deaconess Medical Center/Harvard Medical School. Prior to his industry experience, Dr. Aivado practiced clinical medicine in Germany for nearly ten years, during which time he was awarded the Dr. Mildred Scheel cancer research scholarship award in 2002. Dr. Aivado is a German board-certified physician for internal medicine, hematology and medical oncology, and he received an M.D. and Ph.D. from the Medical School of the University of Dusseldorf, in Germany. The Company believes that Dr. Aivado is qualified to serve on its Board due to his extensive knowledge of the Company and his significant background in pharmaceutical research and development.

A copy of the Company’s press release announcing Dr. Aivado’s appointment as President and Chief Executive Officer and election to the Board, and Dr. Longenecker’s resignation as President and Interim Chief Executive Officer is furnished, but not filed, as Exhibit 99.1 to this Current Report on Form 8-K.

In connection with his appointment, on September 6, 2018, Dr. Aivado entered into a new employment agreement with the Company (the “New Employment Agreement”) superseding his current employment agreement, dated as of July 23, 2014. Under the New Employment Agreement, Dr. Aivado has agreed to serve as, and assume the duties of, the Company’s President and Chief Executive Officer. Pursuant to the New Employment Agreement, Dr. Aivado will be paid a base salary at a rate of $41,666.67 per month, which is based on an annualized base salary of $500,000. Beginning in 2019, following the end of each calendar year that Dr. Aivado is employed by the Company, he will be eligible to receive a discretionary performance target bonus of up to 50% of his then annual base salary based on the achievement of performance milestones set by the Board or the Compensation Committee of the Board. Following the end of the 2018 calendar year, Dr. Aivado will be eligible to receive a discretionary performance target bonus calculated on the basis of 35% of his base salary as of August 31, 2018 pro-rated for the first eight months of the fiscal year and 50% of his current base salary under the New Employment Agreement pro-rated for the remaining four months of the fiscal year. The amount of such bonus and the achievement of such milestones will be determined by the Board in its sole discretion. Dr. Aivado will also be entitled to receive reimbursement of up to $4,000 per month for travel and living accommodations pursuant to the New Employment Agreement.

Pursuant to the New Employment Agreement, the Company has also granted Dr. Aivado options to purchase 232,914 shares of common stock of the Company under the Company’s 2017 Stock Incentive Plan. The options will have an exercise price equal to the closing price of the Company’s common stock on September 6, 2018. The options vest in equal monthly installments over four years from September 6, 2018.

On September 6, 2018, Dr. Aivado also entered into a Severance Agreement (the “Severance Agreement”) with the Company. Under the Severance Agreement, if the Company terminates Dr. Aivado’s employment other than for “Cause” or by reason of death or “Disability,” or Dr. Aivado terminates his employment for “Good Reason” and, in each case, not upon or within twelve months of a “Change in Control Event” (each as defined in the Severance Agreement), Dr. Aivado will be entitled to receive (A) his then current base salary for twelve months following the date of his termination and (B) payments on Dr. Aivado’s behalf of the monthly premiums for medical insurance coverage under COBRA until the earlier of the date that is twelve months following the date of his

termination or the date on which Dr. Aivado becomes eligible to receive group health insurance coverage through another employer (collectively, the “Standard Severance Benefits”). If the Company terminates Dr. Aivado’s employment other than for “Cause” or by reason of death or “Disability,” or Dr. Aivado terminates his employment for “Good Reason,” in each case upon or within twelve months of a “Change in Control Event,” Dr. Aivado will be entitled to receive the Standard Severance Benefits for a period of eighteen months following the date of his termination and a lump sum payment equal to one and one-half times his target bonus for the year in which he is terminated, and the vesting of any unvested equity awards will accelerate in full on the date of his termination. Dr. Aivado’s receipt of any post-separation benefits under the Severance Agreement are conditioned upon his execution of a severance and release of claims agreement in a form satisfactory to the Company.

In addition, pursuant to the Company’s standard form of indemnification agreement Dr. Aivado entered into in connection with his employment as Senior Vice President, Chief Medical Officer, the form of which was filed with the Securities and Exchange Commission as Exhibit 10.12 to Amendment No. 1 to the Company’s Registration Statement on Form S-1 (File No. 333-218474) on June 19, 2017, the Company may be required to, among other things, indemnify Dr. Aivado for some expenses, including attorneys’ fees, judgments, fines and settlement amounts incurred by him in any action or proceeding arising out of his service as an officer or director of the Company.

Dr. Aivado was not selected as President and Chief Executive Officer or elected as director pursuant to any arrangement or understanding between him and any other person. There are no family relationships between Dr. Aivado and any director, executive officer or any person nominated or chosen by the Company to become a director or executive officer of the Company.

The foregoing descriptions of Dr. Aivado’s New Employment Agreement and Severance Agreement do not purport to be complete and are qualified in their entirety by reference to the complete text of each such agreement, copies of which will be attached as an exhibit to the Company’s Quarterly Report on Form 10-Q for the three months ending September 30, 2018.

The following exhibit relating to Item 5.02 shall be deemed to be furnished, and not filed:

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

Exhibit 99.1

Aileron Therapeutics Announces the Appointment of Dr. Manuel Aivado as Chief Executive Officer

WATERTOWN, Mass., September 6, 2018 — Aileron Therapeutics (NASDAQ: ALRN), the clinical-stage leader in the field of stapled peptide therapeutics for cancers and other diseases, today announced that Manuel Aivado, MD, PhD, has been named President and Chief Executive Officer and elected to its Board of Directors. Since 2012, Dr. Aivado has served as Aileron’s Senior Vice President and Chief Medical and Scientific Officer. He succeeds John P. Longenecker, PhD, who was appointed interim CEO on May 15, 2018.

“We are very pleased to announce this well-deserved promotion for Dr. Aivado” said Aileron Chairman Jeff Bailey. “Manuel clearly best exemplifies the skill set and talent needed to lead the company through its next stage of development.”

“I am very excited to take on this new responsibility at Aileron as we further expand the clinical development of our lead product candidate, ALRN-6924, into combination therapies. ALRN-6924 represents the proof-of-concept for Aileron’s stapled peptide technology, which I believe to be capable of producing additional novel drug candidates that address previously undruggable targets”, said Dr. Aivado. “In the future, we plan to broaden the applicability of our technology and expand our external collaborations. I am pleased with the external recognition that ALRN-6924 and our stapled peptide technology have earned in the scientific community, and I look forward to additional collaborations translating this recognition into therapeutic and commercial success.”

Dr. Aivado brings more than 20 years of scientific, medical, and executive leadership to this position. Most recently, Dr. Aivado led Aileron’s clinical testing of stapled peptides against intracellular targets and designed and implemented the ALRN-6924 first-in-human trial. ALRN-6924 was selected for the “Best of ASCO Meetings”, which highlights the most cutting-edge science and education from the world’s premier oncology event. Prior to joining Aileron, Dr. Aivado served as Vice President of Clinical Development and Pharmacovigilance at Taiho Oncology, Inc. He previously served as a Senior Medical Director in clinical development at GlaxoSmithKline. In addition, Dr. Aivado was an Instructor in Medicine at Beth Israel Deaconess Medical Center/Harvard Medical School. Prior to his industry experience, Dr. Aivado practiced clinical medicine in Germany for nearly ten years, during which he was awarded the Dr. Mildred Scheel cancer research scholarship award in 2002. Dr. Aivado is a German board-certified physician in internal medicine, hematology and medical oncology. He received his MD and PhD degrees from the Medical School of the University of Dusseldorf, Germany.

About ALRN-6924

ALRN-6924 is a first-in-class product candidate designed to reactivate wild-type p53 tumor suppression by disrupting the interactions between p53 and its two primary suppressor proteins, MDMX and MDM2. Aileron believes ALRN-6924 is the first and only product candidate in clinical development that can equipotently bind to and disrupt the interaction of MDMX and MDM2 with p53. Based on preclinical data and preliminary evidence of safety and anti-tumor activity in its ongoing clinical trials, the Company believes there may be a significant opportunity to develop ALRN-6924 as a monotherapy or combination therapy for a wide variety of solid and liquid tumors. ALRN-6924 is currently being evaluated in multiple clinical trials for the treatment of acute myeloid leukemia (AML), advanced myelodysplastic syndrome (MDS) and peripheral T-cell lymphoma (PTCL). For information about its clinical trials, please visit www.clinicaltrials.gov.

About Aileron

Aileron is a clinical-stage biopharmaceutical company advancing stapled peptides, a novel class of therapeutics for cancers and other diseases. Stapled peptides are chemically stabilized alpha-helical peptides that are modified to improve their stability and cell penetrability while maintaining high affinity for large protein surfaces. Our goal is to use our proprietary stapled peptide drug platform to create first-in-class therapeutics, like ALRN-6924, that may be able to address historically undruggable targets that underlie many diseases with high unmet medical need. Our platform enables us to chemically stabilize and improve the performance and activity of a broad range of alpha-helical peptides that we believe can potentially activate and inhibit key cellular functions that are otherwise difficult to target with existing drug technologies, including small molecules and monoclonal antibodies. For more information, visit www.aileronrx.com.

Forward-Looking Statements

Statements in this press release about Aileron’s future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements about the Company’s strategy and clinical development plans. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words.

Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including whether Aileron’s cash resources will be sufficient to fund its continuing operations for the periods and/or trials anticipated; whether results obtained in preclinical studies and clinical trials will be indicative of results obtained in future clinical trials; whether Aileron’s product candidates will advance through the clinical trial process on a timely basis, or at all; whether the results of such trials will warrant submission for approval from the United States Food and Drug Administration or equivalent foreign regulatory agencies; whether Aileron’s product candidates will receive approval from regulatory agencies on a timely basis or at all; whether, if product candidates obtain approval, they will be successfully distributed and marketed; whether the Company will be able to enter into additional collaborations; and other factors discussed in the “Risk Factors” section of Aileron’s quarterly report on Form 10-Q for the period ended June 30, 2018, filed on August 7, 2018, and risks described in other filings that Aileron may make with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Aileron specifically disclaims any obligation to update any forward-looking statement, whether because of new information, future events or otherwise.

Investors:

Aileron Therapeutics

Don Dougherty, CFO

617-995-0900

ddougherty@aileronrx.com

Hans C. Vitzthum

LifeSci Advisors, LLC.

617-535-7743