8-K

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): August 5, 2019

Proteostasis Therapeutics, Inc.

(Exact name of registrant as specified in its charter)

Delaware	001-37695	20-8436652
(State or other jurisdiction of incorporation)	(Commission File Number)	(I.R.S. Employer Identification No.)
80 Guest Street, Suite 500 Boston, MA		02135
(Address of principal executive offices)		(Zip Code)

Registrant’s telephone number, including area code (617) 225-0096

(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:

☐ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

☐ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

☐ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

☐ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

Title of each class	Trading Symbol(s)	Name of each exchange on which registered
Common stock, par value $0.001 per share	PTI	The Nasdaq Global Market

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.  ☒

Item 7.01 Regulation FD Disclosure.

Exhibit 99.1 attached hereto is the slide presentation used by Jane Davies, M.D., when presenting data from our double and triple cystic fibrosis transmembrane conductance regulator (CFTR) modulator combination studies on Tuesday August 6, 2019, at the 13^th Australasian Cystic Fibrosis Conference in Perth, Australia. Dr. Davies is an investigator for the CFTR modulator combination clinical trials in cystic fibrosis patients conducted by Proteostasis Therapeutics, Inc. (the “Company”). The presentation will be available through the Company’s website.

The furnishing of the attached presentation slides is not an admission as to the materiality of any information therein. The information contained in the presentation slides is summary information that is intended to be considered in the context of more complete information included in the Company’s filings with the U.S. Securities and Exchange Commission, or the SEC, and other public announcements that the Company has made and may make from time to time by press release or otherwise. The Company undertakes no duty or obligation to update or revise the information contained in this report, although it may do so from time to time as its management believes is appropriate. Any such updating may be made through the filing of other reports or documents with the SEC, through press releases or through other public disclosures.

The information in this Item 7.01 of this Current Report on Form 8-K and Exhibit 99.1 attached hereto is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section or Sections 11 and 12(a)(2) of the Securities Act of 1933, as amended. The information contained in this Item 7.01 and in the presentation slides attached as Exhibit 99.1 to this Current Report shall not be incorporated by reference into any filing with the SEC made by the Company, whether made before or after the date hereof, regardless of any general incorporation language in such filing, except as expressly set forth by specific reference in such filing.

Item 9.01. Financial Statements and Exhibits.

(d) Exhibits.

Exhibit    No.	Exhibit Name
99.1	Australasian CF Conference Presentation, furnished herewith

EXHIBIT INDEX

Exhibit    No.	Exhibit Name
99.1	Australasian CF Conference Presentation, furnished herewith.

SIGNATURES

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

Date: August 5, 2019	PROTEOSTASIS THERAPEUTICS, INC.
	By:	/s/ Meenu Chhabra
		Meenu Chhabra
		President and Chief Executive Officer

EX-99.1

Jane Davies, MD, on behalf of the study team Imperial College London Royal Brompton Hospital, London, UK NOVEL CFTR MODULATOR COMBINATIONS: EVALUATION OF THE CORRECTOR PTI-801, POTENTIATOR PTI-808, AND AMPLIFIER PTI-428 IN CF SUBJECTS 13° AUSTRALASIAN CYSTIC FIBROSIS CONFERENCE 3 – 6 August 2019 Perth, Australia Exhibit 99.1

Relationships Fees received by Imperial College London for participation in Advisory Boards and Clinical trial leadership: Proteostasis Therapeutics, Vertex Pharmaceuticals, AbbVie, Galapagos and Flatley

Proteostasis Therapeutics’ Approach to Restoration of CFTR Activity Novel CFTR modulators have been tested in multiple clinical paridigms Regulatory Designation Add-on to approved modulators Double combination Triple combination Potentiator PTI-808 Fast Track (FDA) Corrector PTI-801 Fast Track (FDA) Amplifier PTI-428 Breakthrough Therapy (FDA) Orphan Drug (FDA, EMA) Conductance Activity Stability Folding Translation Splicing Transcription PTI-808 Potentiator PTI-801 Corrector PTI-428 Amplifier

Exploring the Capacity for More in Homo- and Heterozygous HBE Cells Mature CFTR Immature CFTR Na-ATPase F508del/F508del HBE F508del/nonsense HBE PTI-801 PTI-808 PTI-428 TEZ IVA VX-659 + + + + + + + + + + + + - - - - - - - - - - - - - - - - - - - - - - - - + + + + + + + + + + + + - - - - - - - - - - - - - - - - - - - - - - - - Immunoblot Electrophysiology

Double and Triple Combination Study Design CF Subjects ≥ 18 years of age Lung function 40-90% (ppFEV1). Not taking CFTR modulator therapies Not excluding subjects with lung colonization with organisms associated with a more rapid decline in pulmonary status Primary Objectives Safety and tolerability of dose combinations of PTI-801, PTI-808 and PTI-428 Secondary Objectives PK profile of multiple dose combinations Treatment effect on FEV1 over time Exploratory Objectives Treatment effect on sweat chloride PTI-801: 600 mg PTI-808: 150 mg PTI-428: 30 mg Placebo PTI-801: 400 mg PTI-808: 300 mg (ongoing) Placebo -7 Day 1 14 7 Screening period PTI-801: 200 mg PTI-808: 300 mg PTI-428: 30 mg PTI-808: 300 mg PTI-808: 150 mg PTI-801: 300 mg PTI-808: 300 mg PTI-801: 200 mg PTI-808: 100 mg F508del homozygous not taking CFTR modulator therapies

Over 50 Subjects Completed Combination Studies in North America and in Europe

Triple combination Double combination Cohort 1 n=12 Cohort 2 n=13 Placebo n=6 Low dose double n=9 Mid dose double n=5 Placebo n=4 PTI-801 dose 200 mg 600 mg - 200 mg 300 mg - PTI-808 dose 300 mg 150 mg - 100 mg 300 mg - PTI-428 dose 30 mg 30 mg - - - - Age, year (mean SD) 29.7 (9.6) 35.3 (10.6) 27.8 (7.0) 36.1 (12.4) 26.0 (8.8) 26.3 (4.5) Baseline ppFEV1 (mean, SD) 54.1 (10.3) 66.6 (13.4) 65.0 (12.6) 57.0 (16.6) 50.7 (12.7) 69.6 (7.1) Baseline sweat chloride mmol/L (mean, SD) 104.5 (9.2) 100.3 (8.1) 93.8 (8.1) 99.9 (10.6) 98.7 (13.4) 109.5 (1.4) Height, cm (mean, SD) 168.0 (9.2) 168.0 (7.6) 171.4 (7.2) 167.8 (10.4) 172.8 (4.9) 161.3 (9.4) BMI, kg/m2 (mean, SD) 20.1 (2.0) 22.9 (4.2) 19.9 (2.2) 22.2 (2.1) 22.3 (0.9) 22.7 (2.3) Subjects with lung colonization status* 1 2 2 0 0 1 Double and Triple Combination Study Demographics *Lung Colonization status associated with a more rapid decline in pulmonary status (e.g., Burkholderia cenocepacia and Mycobacterium abscessus) excluded in the ad hoc subset analysis

Triple combination Double combination Cohort 1 n=12 Cohort 2 n=13 Placebo n=6 Low dose double n=9 Mid dose double n=5 Placebo n=4 PTI-801 dose 200 mg 600 mg - 200 mg 300 mg - PTI-808 dose 300 mg 150 mg - 100 mg 300 mg - PTI-428 dose 30 mg 30 mg - - - - Subjects completed study (n) 11 13 6 8 5 4 Safety summary and key respiratory adverse events (n) At least one AE 11 9 5 8 3 4 Pulmonary exacerbation* 1 0+ 1 0 0 0 Cough 0 0 1 1 0 0 Chest discomfort 0 0 0 1 1 0 Dyspnoea 0 1 0 0 0 0 Other adverse events (n) Nausea (most frequent AE in triple study) 1 1 2 0 0 0 Headache (most frequent AE in double study) 1 0 1 2 0 1 Double and Triple Combinations Generally Well Tolerated *Excluded in the ad hoc subset analysis +1 PE post treatment period

Double combination resulted in a +6.6 ppFEV1 improvement compared to placebo* Triple combination resulted in a +8 ppFEV1 improvement compared to placebo* Statistical Significance in Improvement in Lung Function Achieved with both Double and Triple Combinations No plateau in ppFEV1 response was observed at the end of 14 day treatment period with the PTI triple PTI Triple Combination PTI-801: 600 mg, PTI-808: 150 mg, PTI-428: 30 mg PTI Double Combination PTI-801: 300 mg, PTI-808: 300 mg *Previously disclosed data on October 17, 2018 and March 25, 2019 placebo placebo n=5 n=8 n=3 n=3

Double combination resulted in -12 mM improvement in sweat chloride compared to placebo* Triple combination resulted in -24 mM improvement in sweat chloride compared to placebo* Statistical Significance in Sweat Chloride Improvement Achieved in both Double and Triple Combinations PTI Triple Combination PTI-801: 600 mg, PTI-808: 150 mg, PTI-428: 30 mg PTI Double Combination PTI-801: 300 mg, PTI-808: 300 mg *Previously disclosed data on October 17, 2018 and March 25, 2019 placebo placebo n=5 n=10 n=3 n=6

PTI-808 exposure PTI-801 exposure low high Double Triple Drug Exposure Driven Sweat Chloride Improvement in Subjects Treated with PTI-801 and PTI-808

Potential Best-in-Class Double Backbone Serves as a Next Step in a Global Phase 2 Leading into Phase 3 Study Program

Double and Triple Combination Phase 2 Study Design for Patients with at least one F508del Mutation CF Subjects ≥ 18 years of age Homo- or heterozygous for the F508del mutation Lung function 40-90% (ppFEV1) BMI ≥ 16 and ≤ 30 Respiratory stability at least 28 days prior to dosing Targeted enrollment of 30 homozygous subjects and 30 heterozygous subjects Double (PTI-801: 600 mg PTI-808: 300 mg) Triple (PTI-801: 600 mg PTI-808: 300 mg PTI-428: 10 mg) Placebo Day 1 14 28 Primary Objectives Safety and tolerability Secondary Objectives PK profile of double and triple drug combinations Treatment effect on FEV1 Treatment effect on sweat chloride Exploratory Objectives CFQ-R Global Phase 3 study Screening period

THANK YOU Lead investigators Damian Downey, MD, Patrick Flume, MD, and Manu Jain, MD, global study teams and all participating people with Cystic Fibrosis and their families 13° AUSTRALASIAN CYSTIC FIBROSIS CONFERENCE 3 – 6 August 2019 Perth, Australia