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): June 6, 2018

 

 

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, 5 th Floor

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))

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.

On June 6, 2018, the Company issued the press release attached hereto as Exhibit 99.1.

The furnishing of the attached press release is not an admission as to the materiality of any information therein. The information contained in the press release 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. For important information about forward looking statements, see the “Safe Harbor” section of the press release in Exhibit 99.1 attached hereto.

The information in this Item 7.01 of this Current Report on Form 8-K and Exhibit 99.1 attached hereto shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, 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 press release 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 8.01 Other Events.

Spokespersons of the Company plan to present the information in the presentation slides attached hereto as Exhibit 99.2.

On June 6, 2018 the Company announced the following information:

Proteostasis Therapeutics, Inc. today announced positive results from the Company’s ongoing 14-day dosing study of PTI-801 in CF patients on background Orkambi ®  (lumacaftor/ivacaftor) therapy. The Company believes these results support the goal of studying PTI-801 as part of the Company’s proprietary double and triple combination therapy regimens.

The randomized, double-blind, placebo-controlled Phase 1 study is being conducted at 30 sites in the U.S. and Europe. At the time of data cut, 49 subjects on background Orkambi were randomized, and 48 had completed 14-days of dosing with PTI-801 at three escalating dose levels, or placebo. At the request of participating study sites, up to an additional 10 subjects will be enrolled in the highest dose cohort. The study was designed to evaluate the safety, tolerability and pharmacokinetics (PK) of PTI-801, a third generation cystic fibrosis transmembrane conductance regulator (CFTR) corrector. Sweat chloride (SC) and body mass index (BMI) were evaluated as exploratory endpoints; change in ppFEV 1  was evaluated as part of the safety analysis. Blood glucose levels were evaluated as part of an ad hoc analysis in subjects with cystic fibrosis-related diabetes (CFRD), a subgroup that made up nearly half of the enrolled subjects.

Safety and PK results were as expected. At higher doses, PTI-801 demonstrated a statistically significant improvement in SC and BMI in the 14-day treatment period. Overcoming the typical acute drop in FEV 1 associated with lumacaftor exposure, an improvement in ppFEV 1 was observed across all dose cohorts, although the change was not statistically significant. Two thirds of subjects in all PTI-801 cohorts were above ppFEV 1 baseline by the end of the treatment period and approached baseline by the end of the 7-day follow up period. In hyperglycemic CFRD subjects, PTI-801 led to a statistically significant normalization of glucose levels at the three dose levels analyzed.

By the end of the second quarter of 2018, the Company plans to initiate the Phase 2 study of its once-a-day triplet regimen, which includes PTI-428, PTI-808, and PTI-801. The Company anticipates reporting initial data from its ongoing doublet study of PTI-801 and PTI-808, followed by triplet study results, all later this year.

About the PTI-801 Phase 1 Study

This randomized, double-blind Phase 1 study is evaluating PTI-801 as a once-a-day oral capsule in combination with Orkambi in people with CF ages 18 and older who have two copies of the  F508del mutation. The primary objectives for the study are safety, tolerability and pharmacokinetics. The study randomized 49 subjects to three dose levels of PTI-801 or placebo for two weeks (10 in placebo, 14 in PTI-801 100 mg, 13 in PTI-801 200 mg, and 12 in PTI-801 400 mg). The study continues to recruit subjects in the PTI-801 400 mg dose cohort and final analysis will be performed upon its completion, which is expected in the third quarter of 2018.

PTI-801 was generally well tolerated. The majority of adverse events were mild or moderate. The most common adverse events were pulmonary exacerbations (10%), regardless of treatment group. There was one discontinuation due to an adverse event in the PTI-801 100 mg treatment group (constipation) prior to the first dose of the study drug.

In active treated subjects, improvements in SC levels and FEV 1 showed a trend to return to pre-treatment levels during the post-treatment 7-day follow up period. A summary of the within-group lung function and sweat chloride data is provided below:

 

PTI-801 in CF subjects on background Orkambi

    Day 14 Sweat Chloride
(mmol/L) 		  Mean Observed Within-
Group
Change in Sweat Chloride
(mmol/L) 		  Mean Observed
Absolute Within-
Group Change in FEV 1
(percentage points)

Placebo + Orkambi

  82.8   1.2

n.s.

  1.7

n.s.

PTI-801 100 mg + Orkambi

  81.4   -4.7

n.s.

  1.9

n.s.

PTI-801 200 mg + Orkambi

  71.0   -10.6

(p<0.005*)

  2.5

n.s.

PTI-801 400 mg + Orkambi

  55.8   -15.6

(p<0.0005*)

  0.6 #

n.s.

 

* all p-values are within group p-values

 

#   one subject experienced a pulmonary exacerbation and a change of -18.0 pp FEV 1

In subjects who received PTI-801 treatment, there were statistically significant changes in BMI and weight compared to baseline. Detailed data on these endpoints are noted below:

 

PTI-801 in CF subjects on background Orkambi

Within-Group Change From

Baseline to Day 14

  Mean Observed Within-Group
Change in BMI at Day 14 (kg/m2) 		  Mean Observed Within-Group
Change in Weight at Day 14 (Kg)

Placebo + Orkambi

  0.066

n.s.

  0.16

n.s.

PTI-801 100 mg + Orkambi

  0.235

n.s.

  0.66

(p<0.05)

PTI-801 200 mg + Orkambi

  0.052

n.s.

  0.13

n.s.

PTI-801 400 mg + Orkambi

  0.311

(p<0.01)

  0.93

(p<0.005)

P<0.05, ANCOVA, within-group changes

A subgroup of 21 subjects enrolled in PTI-801 across all cohorts were diabetic, a proportional representation of the prevalence of cystic fibrosis-related diabetes (CFRD) in the U.S. adult CF population. CFRD is an important and highly prevalent complication associated with reduced quality of life, weight loss, lung function decline, and increased mortality. Fasting blood glucose levels were assessed as part of the study’s safety measurements. In hyperglycemic, diabetic subjects, an ad hoc analysis showed the 200 mg dose of PTI-801 led to the normalization of glucose levels (p<0.05). Statistical analysis for 400 mg dose of PTI-801 will be performed upon completion of that cohort’s enrollment. Importantly, no changes in blood glucose were observed in placebo treated and non-diabetic subjects who received either placebo or PTI-801.

Safe Harbor

To the extent that statements in this report are not historical facts, they are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Words such as “aim,” “may,” “will,” “expect,” “anticipate,” “estimate,” “intend,” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. Examples of forward-looking statements made in this report include, without limitation, statements regarding expected presentations and expected timing of the initiation of, patient enrollment in, data from, and the completion of, our clinical studies and cohorts for our clinical programs. Forward-looking statements made in this release involve substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by the forward-looking statements, and we, therefore cannot assure you that our plans, intentions, expectations or strategies will be attained or achieved. Such risks and uncertainties include, without limitation, the possibility final or future results from our drug candidate trials (including, without limitation, longer duration studies) do not achieve positive results or are materially and negatively different from or not indicative of the preliminary results reported by the Company (noting that these results are based on a small number of patients and small data set), uncertainties inherent in the execution and completion of clinical trials (including, without limitation, the possibility that FDA comments delay, change or do not permit trial commencement, or intended label, or the FDA requires us to run cohorts sequentially or conduct additional cohorts or pre-clinical or clinical studies), in the enrollment of CF patients in our clinical trials in a competitive clinical environment, in the timing of availability of trial data, in the results of the clinical trials, in possible adverse events from our trials, in the actions of regulatory agencies, in the endorsement, if any, by therapeutic development arms of CF patient advocacy groups (and the maintenance thereof), and those set forth in our Quarterly Report on Form 10-Q for the quarter ended March 31, 2018 and our other SEC filings. We assume no obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.

Orkambi ® , Kalydeco ® and Symdeko™ are trademarks of Vertex Pharmaceuticals Incorporated.

The above information is not an admission as to the materiality of any information therein. 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.

Item 9.01 Financial Statements and Exhibits.

(d) Exhibits.

 

Exhibit No.

  

Description

99.1    Press release, furnished herewith.
99.2    Presentation slides, filed 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: June 6, 2018     PROTEOSTASIS THERAPEUTICS, INC.
    By:  

/s/ Meenu Chhabra

      Meenu Chhabra
      President and Chief Executive Officer

Exhibit 99.1

 

LOGO

Proteostasis Announces Positive Data from Ongoing Phase 1 Study of PTI-801 in Cystic Fibrosis Patients on Background Orkambi ® Therapy

Results Show Statistically Significant Improvement in Sweat Chloride, Body Mass Index, Weight and Blood Glucose

Treatment Led to a Statistically Significant Improvement in Blood Glucose Levels and the Reversal of Hyperglycemia in a Diabetic CF Subpopulation

Improvement in FEV 1 Observed Across All Dose Cohorts

Company to Host Conference Call and Webcast Today at 5:00 p.m. ET

BOSTON, Mass. – June 6, 2018 – Proteostasis Therapeutics, Inc. (NASDAQ:PTI), a clinical stage biopharmaceutical company dedicated to the discovery and development of groundbreaking therapies to treat cystic fibrosis (CF) and other diseases caused by dysfunctional protein processing, today announced positive results from the Company’s ongoing 14-day dosing study of PTI-801 in CF patients on background Orkambi ®  (lumacaftor/ivacaftor) therapy. The Company believes these results support the goal of studying PTI-801 as part of the Company’s proprietary double and triple combination therapy regimens.

The randomized, double-blind, placebo-controlled Phase 1 study is being conducted at 30 sites in the U.S. and Europe. At the time of data cut, 49 subjects on background Orkambi were randomized, and 48 had completed 14-days of dosing with PTI-801 at three escalating dose levels, or placebo. At the request of participating study sites, up to an additional 10 subjects will be enrolled in the highest dose cohort. The study was designed to evaluate the safety, tolerability and pharmacokinetics (PK) of PTI-801, a third generation cystic fibrosis transmembrane conductance regulator (CFTR) corrector. Sweat chloride (SC) and body mass index (BMI) were evaluated as exploratory endpoints; change in ppFEV 1  was evaluated as part of the safety analysis. Blood glucose levels were evaluated as part of an ad hoc analysis in subjects with cystic fibrosis-related diabetes (CFRD), a subgroup that made up nearly half of the enrolled subjects.

Safety and PK results were as expected. At higher doses, PTI-801 demonstrated a statistically significant improvement in SC and BMI in the 14-day treatment period. Overcoming the typical acute drop in FEV 1 associated with lumacaftor exposure, an improvement in ppFEV 1 was observed across all dose cohorts, although the change was not statistically significant. Two thirds of subjects in all PTI-801 cohorts were above ppFEV 1 baseline by the end of the treatment period and approached baseline by the end of the 7-day follow up period. In hyperglycemic CFRD subjects, PTI-801 led to a statistically significant normalization of glucose levels at the three dose levels analyzed.

“Sweat chloride is the first diagnostic test to identify CF patients and the reduction of mean SC concentration levels to 55 mmol, levels below the CF disease diagnostic criteria, after only two weeks of treatment, is very encouraging and I believe a clear sign of a pharmacological effect of PTI-801. This is the first time the addition of a novel CFTR corrector in Orkambi treated CF subjects has improved sweat chloride values to Kalydeco ® -like levels,” said Manu Jain, M.D., lead investigator of the study and Professor of Medicine, Pulmonary and Critical Care, at Northwestern Medicine.

LOGO

 

Jennifer Taylor-Cousar, M.D., M.S.C.S., a lead investigator for the PTI-428 study in CF subjects on Symdeko™ therapy and Associate Professor of Medicine and Pediatrics at National Jewish Health, commented: “It is widely accepted that Orkambi may not represent the optimal background on which to add and deliver a Kalydeco-like benefit in lung function in a short term study. PTI-801’s emerging drug profile supports studying it as an add-on with Symdeko background therapy, the emerging standard of care CFTR modulator treatment.”

“With the addition of PTI-801 to Orkambi, we saw improvements in sweat chloride and weight that, at certain dose levels, reached Kalydeco-like levels and the numerical improvement in FEV 1 suggests PTI-801 could potentially double what Orkambi achieves alone. We believe these results demonstrate our ability to deliver a second potential add-on CFTR therapy to enhance current and future CFTR modulator treatments,” said Meenu Chhabra, President and Chief Executive Officer of Proteostasis. “We believe these results support our development plans for PTI-801 as part of our proprietary doublet and triple combinations. By the end of this quarter, we plan to initiate the Phase 2 study of our once-a-day triplet regimen, which includes PTI-428, our novel CFTR amplifier, PTI-808, our potentiator, and PTI-801. We anticipate reporting initial data from our ongoing doublet study of PTI-801 and PTI-808, followed by our triplet study results, all later this year.”

About the PTI-801 Phase 1 Study

This randomized, double-blind Phase 1 study is evaluating PTI-801 as a once-a-day oral capsule in combination with Orkambi in people with CF ages 18 and older who have two copies of the  F508del mutation. The primary objectives for the study are safety, tolerability and pharmacokinetics. The study randomized 49 subjects to three dose levels of PTI-801 or placebo for two weeks (10 in placebo, 14 in PTI-801 100 mg, 13 in PTI-801 200 mg, and 12 in PTI-801 400 mg). The study continues to recruit subjects in the PTI-801 400 mg dose cohort and final analysis will be performed upon its completion, which is expected in the third quarter of 2018.

PTI-801 was generally well tolerated. The majority of adverse events were mild or moderate. The most common adverse events were pulmonary exacerbations (10%), regardless of treatment group. There was one discontinuation due to an adverse event in the PTI-801 100 mg treatment group (constipation) prior to the first dose of the study drug.

In active treated subjects, improvements in SC levels and FEV 1 showed a trend to return to pre-treatment levels during the post-treatment 7-day follow up period. A summary of the within-group lung function and sweat chloride data is provided below:

 

PTI-801 in CF subjects on background Orkambi

 
     Day 14 Sweat Chloride
(mmol/L) 		     Mean Observed Within-
Group
Change in Sweat Chloride
(mmol/L) 		     Mean Observed
Absolute Within-
Group Change in  FEV 1
(percentage points) 		 

Placebo + Orkambi

     82.8       

1.2

n.s.

 

 

    

1.7

n.s.

 

 

PTI-801 100 mg + Orkambi

     81.4       

-4.7

n.s.

 

 

    

1.9

n.s.

 

 

LOGO

 

PTI-801 200 mg + Orkambi

     71.0       

-10.6

(p<0.005

 

*) 

   

2.5

n.s.

 

 

PTI-801 400 mg + Orkambi

     55.8       

-15.6

(p<0.0005

 

*) 

   

0.6

n.s.

#  

 

 

* all p-values are within group p-values
#   one subject experienced a pulmonary exacerbation and a change of -18.0 pp FEV 1

In subjects who received PTI-801 treatment, there were statistically significant changes in BMI and weight compared to baseline. Detailed data on these endpoints are noted below:

 

PTI-801 in CF subjects on background Orkambi

 

Within-Group Change From

Baseline to Day 14

   Mean Observed Within-Group
Change in BMI at Day 14 (kg/m2) 		     Mean Observed Within-
Group Change in Weight
at Day 14 (Kg) 		 

Placebo + Orkambi

    

0.066

n.s.

 

 

    

0.16

n.s.

 

 

PTI-801 100 mg + Orkambi

    

0.235

n.s.

 

 

    

0.66

(p<0.05

 

) 

PTI-801 200 mg + Orkambi

    

0.052

n.s.

 

 

    

0.13

n.s.

 

 

PTI-801 400 mg + Orkambi

    

0.311

(p<0.01

 

) 

    

0.93

(p<0.005

 

) 

P<0.05, ANCOVA, within-group changes

 

A subgroup of 21 subjects enrolled in PTI-801 across all cohorts were diabetic, a proportional representation of the prevalence of cystic fibrosis-related diabetes (CFRD) in the U.S. adult CF population. CFRD is an important and highly prevalent complication associated with reduced quality of life, weight loss, lung function decline, and increased mortality. Fasting blood glucose levels were assessed as part of the study’s safety measurements. In hyperglycemic, diabetic subjects, an ad hoc analysis showed the 200 mg dose of PTI-801 led to the normalization of glucose levels (p<0.05). Statistical analysis for 400 mg dose of PTI-801 will be performed upon completion of that cohort’s enrollment. Importantly, no changes in blood glucose were observed in placebo treated and non-diabetic subjects who received either placebo or PTI-801.

Conference Call and Webcast

Proteostasis will hold a conference call and accompanying webcast today, June 6, 2018, at 5:00 p.m. ET to discuss the data announced today. The conference call can be accessed by dialing 844-534-7315 from the United States or 574-990-3007 from outside the United States and referring to conference ID 2798270. A live webcast and accompanying slide presentation will be available on the Investor Events page in the Investors & Media section of the company’s website,  www.proteostasis.com . A replay of the webcast will be available on the company’s website shortly after the conclusion of the conference call.

LOGO

 

About Proteostasis Therapeutics, Inc.

Proteostasis Therapeutics, Inc. is a clinical stage biopharmaceutical company developing small molecule therapeutics to treat cystic fibrosis and other diseases caused by dysfunctional protein processing. Headquartered in Boston, MA, the Proteostasis Therapeutics team focuses on identifying therapies that restore protein function. In addition to its multiple programs in cystic fibrosis, Proteostasis Therapeutics has formed a collaboration with Astellas Pharma, Inc. to research and identify therapies targeting the Unfolded Protein Response (UPR) pathway. For more information, visit www.proteostasis.com .

Safe Harbor

To the extent that statements in this release are not historical facts, they are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Words such as “aim,” “may,” “will,” “expect,” “anticipate,” “estimate,” “intend,” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. Examples of forward-looking statements made in this release include, without limitation, statements regarding expected presentations and expected timing of the initiation of, patient enrollment in, data from, and the completion of, our clinical studies and cohorts for our clinical programs. Forward-looking statements made in this release involve substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by the forward-looking statements, and we, therefore cannot assure you that our plans, intentions, expectations or strategies will be attained or achieved. Such risks and uncertainties include, without limitation, the possibility final or future results from our drug candidate trials (including, without limitation, longer duration studies) do not achieve positive results or are materially and negatively different from or not indicative of the preliminary results reported by the Company (noting that these results are based on a small number of patients and small data set), uncertainties inherent in the execution and completion of clinical trials (including, without limitation, the possibility that FDA comments delay, change or do not permit trial commencement, or intended label, or the FDA requires us to run cohorts sequentially or conduct additional cohorts or pre-clinical or clinical studies), in the enrollment of CF patients in our clinical trials in a competitive clinical environment, in the timing of availability of trial data, in the results of the clinical trials, in possible adverse events from our trials, in the actions of regulatory agencies, in the endorsement, if any, by therapeutic development arms of CF patient advocacy groups (and the maintenance thereof), and those set forth in our Quarterly Report on Form 10-Q for the quarter ended March 31, 2018 and our other SEC filings. We assume no obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.

Orkambi ® , Kalydeco ® and Symdeko™ are trademarks of Vertex Pharmaceuticals Incorporated.

LOGO

 

CONTACTS:

Investors:

David Pitts

Argot Partners

212.600.1902

david@argotpartners.com

Media:

David Rosen

Argot Partners

212.600.1902

david.rosen@argotpartners.com

SLIDE 1

Proteostasis Therapeutics, Inc. (PTI) June 2018 Investor Deck Exhibit 99.2

SLIDE 2

Safe Harbor and Disclaimer To the extent that statements in this presentation are not historical facts, they are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Words such as “aim,” “may,” “will,” “expect,” “anticipate,” “estimate,” “intend,” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. Examples of forward-looking statements made in this presentation include, without limitation, statements regarding the expected timing of the initiation of, patient enrollment in, data from, and our completion of, our clinical studies and cohorts for PTI-428, PTI-801, PTI-808 and our combination therapy candidates as well as cash guidance. Forward-looking statements made in this presentation involve substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by the forward-looking statements, and we therefore cannot assure you that our plans, intentions, expectations or strategies will be attained or achieved. Such risks and uncertainties include, without limitation, the possibility final or future results from our drug candidate trials (including, without limitation, longer duration studies) do not achieve positive results or are materially and negatively different from or not indicative of the preliminary results reported in this presentation (noting that these results are on a small number of patients and small data set), uncertainties inherent in the execution and completion of clinical trials (including, without limitation, the possibility FDA requires us to run cohorts sequentially or conduct additional cohorts or pre-clinical or clinical studies), in the enrollment of CF patients in our clinical trials, in the timing of availability of trial data, in the results of the clinical trials, in possible adverse events from our trials, in the actions of regulatory agencies, in endorsement, if any, by therapeutic development arms of CF patient advocacy groups, and those set forth in our Quarterly Report on Form 10-Q for the quarter ended March 31, 2018, and our other SEC filings. We assume no obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise. This presentation also contains estimates and other statistical data made by independent parties and by us relating to, among other items, disease incidence, market size and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. Projections, assumptions and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of risk and uncertainty. New risks emerge from time to time, and neither we nor any other person makes any representation as to the accuracy or completeness of such data or undertakes any obligation to update such date after the date of this presentation. By attending or receiving this presentation you acknowledge you are solely responsible for your own assessment of the market and our market position and that you will conduct your own analysis and are solely responsible for forming your own view of the potential future performance of our business. The trademarks included in this presentation are the property of the owners thereof and are used for reference purposes only. Such use should not be construed as an endorsement of the Company or its securities.

SLIDE 3

PTI Overview Clinical stage biopharma developing novel therapeutics for cystic fibrosis (CF) and other diseases caused by dysfunctional protein processing Developing novel small molecules for CF combination therapy PTI-808: Novel Potentiator PTI-801: Third Generation Corrector that is additive in vitro to first and second generation correctors PTI-428: Novel Class of CFTR Modulator: Amplifiers Leveraging potential therapeutic benefit of multiple stand-alone combination options including PTI-801 and PTI-808 as a doublet and PTI-808, PTI-801, and PTI-428 as a triplet PTI-801 and PTI-428 can potentially be developed as add-on therapies to current and future standard of care CFTR modulator therapies $63.3 million as of March 31, 2018 in cash, cash equivalents and short-term investments As of May 3, 2018, net proceeds from ATM were $7.8 million in addition to cash balance above Cash position estimated to be sufficient to fund operations into early 2019

SLIDE 4

CORRECTOR PTI-801 PTI Approach to Restoration of CFTR Activity is Uniquely Orthogonal to Approved Modulators Amplifiers, such as PTI-428, selectively increase the amount of immature CFTR protein in the cell, providing additional substrate for correctors and potentiators to act upon Potentiators, such as PTI-808 and KALYDECO® (ivacaftor), act by increasing the opening time of the CFTR channel, resulting in higher ion flow Correctors, such as PTI-801, ORKAMBI® (lumacaftor/ ivacaftor) or SYMDEKOä (tezacaftor/ivacaftor), are thought to facilitate the processing of mutated CFTR protein substrate, leading to improved delivery to the cell membrane POTENTIATOR PTI-808 AMPLIFIER PTI-428 ORKAMBI®, KALYDECO®, and SYMDEKOä are trademarks of Vertex Pharmaceuticals Inc.

SLIDE 5

PTI Cystic Fibrosis Clinical Pipeline Discovery Preclinical Development Clinical Development HV CF PTI-428 + First Generation Amplifier*& PTI-801+ Third Generation Corrector* PTI-808 First Generation Potentiator & Received Breakthrough Therapy Designation and * Fast Track designation from FDA + Additive in vitro to first and second generation correctors Combination therapy PTI-428/PTI-801/PTI-808* PTI-801/PTI-808

SLIDE 6

PTI-428 and PTI-801 are Differentiated in Doublet, Triplet and Quadruplet Combination Formats in vitro TEZA-tezacaftor, IVA-ivacaftor, OLA-olacaftor or VX-440, DMSO-vehicle control PTI-801 and PTI-428 are additive to approved or late stage modulators in vitro Doublet and triplet combinations of PTI investigational drugs restored CFTR activity to at least healthy carrier levels in vitro F508del Homozygous HBE cells

SLIDE 7

12 Month Key Milestones PTI-808/PTI-801/PTI-428 combination study protocol endorsed with high strategic fit score by CF patient advocacy groups in the U.S. and Europe PTI-801/PTI-808 combination study initiated in CF patients Breakthrough Therapy Designation for PTI-428 granted by the FDA PTI-801 14 day dosing, additional data in CF subjects on Orkambi® PTI-808/PTI-801/PTI-428 combination study initiates in CF subjects PTI-428 starts dosing in CF Subjects on Symdekoä clinical study PTI-808/PTI-801 initial data from combination study in CF subjects PTI-808/PTI-801/PTI-428 combination study preliminary data in CF subjects Early 2019 initial data from PTI-428 in CF Subjects on Symdekoä Orkambi® and Symdekoä are trademarks of Vertex Pharmaceuticals, Inc. 2018 2018

SLIDE 8

PTI-801-01 CF Study Summary and Updates

SLIDE 9

PTI-801 Doubled CFTR Activity in vitro of Symdeko Based Triple Combinations Teza-tezacaftor, Iva - ivacaftor, Ola-olacaftor or VX-440, Isc-short circuit current F508del/F08del HBE cells PTI-801 belongs to a novel chemical series that showed additive efficacy in vitro with first (tezacaftor and lumacaftor) and second generation (olacaftor or VX-440) correctors Second generation correctors (VX-440,445,659,152) require exclusion of subjects in the clinic with G6PD deficiency Unlike lumacaftor and tezacaftor, when combined with ivacaftor under chronic conditions, PTI-801 in vitro efficacy showed sustained increase in CFTR current that appeared less sensitive to the ivacaftor-mediated decrease

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PTI-801-01 Study Design CF Subjects ≥ 18 years of age Lung function 40-90% (FEV1) Background treatment with ORKAMBI® for a minimum of 3 months according to label Randomization 4:1 (active:placebo) Follow-up Placebo F508del Homozygous on ORKAMBI® -28 Day 1 7 14 21 Follow-up Follow-up Follow-up PTI-801 (400 mg, enrolling) PTI-801 (200 mg) PTI-801 (100 mg) n=14 n=13 n=12 n=10 Primary Objectives Evaluate the safety and tolerability of PTI-801 in combination with ORKAMBI® Exploratory Objectives Evaluate the treatment effect on sweat chloride and weight over time Secondary Objectives Evaluate the PK profile of multiple oral doses of PTI-801 Evaluate the PK profiles of ivacaftor and lumacaftor Evaluate the treatment effect on FEV1 over time

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PTI-801 + Orkambi® CF Study Has 30 Active Clinical Sites in Europe and North America Subjects have been on Orkambi® for an average of 2.3 years ranging from 4 months to 4.6 years As a group, screened subjects experienced a lung function decline of approximately 3 ppFEV1 per year compared to the first 6 months of Orkambi® treatment

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PTI-801 14 Day Study with Orkambi® Disposition Summary Placebo Randomized (n=10) Completed Study (n=8) CF Subjects on ORKAMBI® (n=49) 100 mg Randomized (n=14) Completed Study (n=12) 200 mg Randomized (n=13) Completed Study (n=13) 400 mg Randomized (n=12) Completed Study (n=9) In the 400 mg cohort, 2 subjects on placebo and 2 subjects on active were in the follow-up period at the time of data cut 1 subject each in the 100 mg and 400 mg cohorts discontinued due to subject decision 1 subject in the 100 mg cohort discontinued due to an adverse event (constipation) prior to dosing

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PTI-801 14 Day Study with Orkambi® Demographics Summary Variable Placebo (n=10) 100 mg (n=14) 200 mg (n=13) 400 mg (n=12) Total (n=49) Female (n, %) 3 (30.0) 8 (57.1) 7 (53.8) 5 (41.7) 23 (46.9) Male (n, %) 7 (70.0) 6 (42.9) 6 (46.2) 7 (58.3) 26 (53.1)  Height, cm (Mean, SD) 169.3 (7.41) 166.3 (7.28) 168.6 (9.39) 170.9 (8.29) 168.6 (8.09)  Weight, kg (Mean, SD) 64.8 (12.01) 60.7 (9.90) 65.6 (9.15) 66.3 (11.37) 64.2 (10.46)  BMI, kg/m² (Mean, SD) 22.5 (3.29) 22.0 (3.80) 23.1 (2.80) 22.5 (2.41) 22.5 (3.07)  Age, Year (Mean, SD) 27.5 (9.86) 31.0 (9.62) 32.8 (11.30) 30.5 (11.29) 30.7 (10.38)  Baseline ppFEV1 Percentage point (Mean, SD) 62.0 (13.38) 56.8 (11.90) 62.9 (11.06) 60.3 (12.45) 60.4 (11.99) Baseline Sweat Chloride mmol/L (Mean, SD) 79.1 (13.01) 78.0 (18.72) 81.6 (14.52) 71.3 (20.61) 77.5 (17.04)

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Ivacaftor Exposures Lumacaftor Exposures Clinical data supports lack of drug-drug interactions of PTI-801 on Orkambi® as expected from preclinical data PTI-801 Did Not Impact Ivacaftor and Lumacaftor Exposure Levels AUC – area under the curve

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PTI-801 Achieved Dose-Dependent Increase in Exposure in CF Subjects on Background Orkambi® Average PTI-801 exposure at steady state was approximately EC50 at 100 mg and in excess of EC75 at 400 mg

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PTI-801 14 Day Study with Orkambi® Safety Summary PTI-801 was generally well tolerated No SAE, no AE leading to discontinuation and mostly mild-moderate AE Only severe AEs were neck pain and poor sleep quality (unlikely related to study drug) No clinically significant safety signals in chemistry, hematology lab, ECG Category Placebo (n=10) 100 mg (n=13) 200 mg (n=13) 400 mg (n=12) Total (n=48) At Least One AE (n, %) 5 (50.0) 9 (69.2) 8 (61.5) 11 (91.7) 33 (68.8) Respiratory-related adverse events n (%) Infective pulmonary exacerbation of cystic fibrosis n (%) 1 (10.0) 2 (15.4) 1 ( 7.7) 1 ( 8.3) 5 (10.4) Cough n (%) 0 ( 0.0) 1 ( 7.7) 2 (15.4) 1 ( 8.3) 4 ( 8.3) Chest discomfort n (%) 0 (0.0) 1 (7.7) 0 (0.0) 1 (8.3) 2 (4.2) Dyspnoea exertional n (%) 0 (0.0) 0 (0.0) 1 (7.7) 0 (0.0) 1 (2.1) Other adverse events n (%) Headache n (%) 0 ( 0.0) 2 (15.4) 1 ( 7.7) 1 ( 8.3) 4 ( 8.3)

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PTI-801 Treatment Led to a Significant Reduction in Sweat Chloride Which Continued to Decline to Day 14 P<0.005, ANCOVA, within-group change Within-Group Change From Baseline to Day 14 Mean Observed Within-Group Change in Sweat Chloride Baseline to Day 14 (mmol/L) Placebo + Orkambi® 1.2 n.s. PTI-801 100 mg + Orkambi® -4.7 n.s. PTI-801 200 mg + Orkambi® -10.6 (p<0.005*) PTI-801 400 mg + Orkambi® -15.6 (p<0.0005*)

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400 mg of PTI-801 Reduced Sweat Chloride Levels Below CF Disease Diagnostic Threshold Orkambi data adapted from Ratjen et al., Lancet Respiratory Medicine, June 9, 2017 Kalydeco data adapted from Ramsey et al. New England Journal of Medicine, November 3, 2011

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Changes in ppFEV1 in PTI-801 Treated Subjects Were Consistent With Pharmacologically Active CFTR Correctors Mean Observed Within-Group Absolute Change in ppFEV1 from Baseline to Day 14 (percentage points) Placebo + Orkambi® 1.7 n.s. PTI-801 100 mg + Orkambi® 1.9 n.s. PTI-801 200 mg + Orkambi® 2.5 n.s. PTI-801 400 mg + Orkambi® 0.6# n.s. n.s. - not statistically significant by ANCOVA # cohort still enrolling, one subject experienced a PE and a -18 ppFEV1 percentage points change from baseline at day 14 By the end of the 7-day follow up period, FEV1 values approached baseline across all dose cohorts absolute change in ppFEV1

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Decrease in ppFEV1 Observed at 4h Post First Dose Correlated with Increasing Lumacaftor Exposure Levels Placebo (n=10) 100mg (n=13) 200mg (n=13) 400mg (n=12) PTI-801 exposure n.a. ~EC50 ~EC50-EC75 >EC75 Average Lumacaftor Exposure Cmax at Day 1 (ug/mL) 26.9 28.5 38.1 28.1 Subgroup of CF subjects on background Orkambi who experienced a drop in FEV1 4hr post dose % of Subjects Below Baseline ppFEV1 at Day 1 40% 67% 85% 67% Average absolute ppFEV1 change at Day1 -2.0 -2.7 -3.4 -2.1 Average absolute ppFVC decrease at Day1 -1.7 -0.3 -3.1 -0.1

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Ad Hoc Analysis Showed Response to PTI-801 Emerged in Subjects Who Did Not Experience Acute First Day Drop in FEV1 Mean Observed Absolute Within-Subgroup Change in ppFEV1 from Baseline to Day 14 for Subgroup of Subjects At or Above Baseline in ppFEV1 at Day 1 (percentage points) Placebo + Orkambi 3.8 n.s. PTI-801 100 mg + Orkambi 4.9 (p< 0.005) PTI-801 200 mg + Orkambi 8.7 n.s. PTI-801 400 mg + Orkambi -0.1# n.s. ANOVA within subgroup p value n.s. - not statistically significant # one subject experienced a PE and a -18 ppFEV1 absolute change from baseline at day 14 P<0.05, ANOVA, within-group changes

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Mean Observed Absolute Within-Subgroup Change in ppFEV1 from Baseline to Day 14 for Subgroup of Subjects Below Baseline in ppFEV1 at Day 1 (percentage points) Placebo + Orkambi -1.9 n.s. PTI-801 100 mg + Orkambi 0.4 n.s. PTI-801 200 mg + Orkambi 1.4 n.s. PTI-801 400 mg + Orkambi 1.1 n.s. ANOVA within subgroup analysis n.s. - not statistically significant Ad Hoc Analysis Showed Response to PTI-801 Was Attenuated in Subjects Who Experience Acute First Day Drop in FEV1

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PTI-801 400 mg Led to Improved BMI and Weight in CF Subjects During Treatment Period (p<0.05) P<0.05, ANCOVA, within-group changes Mean Observed Within-Group Change in BMI at day 14 (kg/m2) Mean Observed Within-Group Change in Weight at day 14 (Kg) Placebo + Orkambi® 0.066 n.s. 0.16 n.s. PTI-801 100 mg + Orkambi® 0.235 n.s. 0.66 (p<0.05) PTI-801 200 mg + Orkambi® 0.052 n.s. 0.13 n.s. PTI-801 400 mg + Orkambi® 0.311 (p<0.01) 0.93 (p<0.005)

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PTI-801 Treatment Led to Improved Glucose Levels In Diabetic CF Subjects (p<0.05) and Reversal of Hyperglycemia P<0.05, ANCOVA, within-group changes Statistics not done for 400 mg subgroup due to small sample size Prevalence of diabetic subjects in the recruited sample is expected based on the overall proportion of the cystic fibrosis-related diabetes (CFRD) in the US adult CF population No decreases in blood glucose were observed in placebo treated and non-diabetic subjects who received either placebo or PTI-801

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PTI-428-01 CF Study Summary

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Data in CF Subjects on Background Orkambi® Suggested that PTI-428 is Generally Well Tolerated and Provided Statistically Significant Improvement in Lung Function *Michael W et al. The Lancet Respiratory Medicine, 2017, Volume 5 , Issue 2 , 107 – 118 Orkambi® is a trademark of Vertex Pharmaceuticals, Inc. POC – proof-of-concept 2-year, PROGRESS study of long term Orkambi® efficacy showed CF patients continue to experience lung function decline despite treatment Information on historical Orkambi® usage was available for 79% of the subjects enrolled in the 28-day study and of those, 95% were on Orkambi® therapy for an average of 1.8 years Average lung function prior to dosing was 59% ppFEV1 Follow-up Follow-up PTI-428 50 mg Placebo F508del Homozygous on ORKAMBI® -28 Day 1 14 28 35 n= 4 n= 20

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During Treatment, PTI-428 at 50 mg Led to Increased CFTR Protein Expression in Nasal Mucosa Samples at Steady State Average maximum increase in CFTR protein levels was 1.4x (+90.2 ng/mg) higher than baseline in nasal mucosa samples

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PTI-428 Led to Mean Absolute Improvements in ppFEV1 of 5.2 percentage points from Baseline Compared to Placebo (p<0.05) Treatment effect of PTI-428 was achieved by day 14 and sustained through 28 days of dosing Based on amplifier's mechanism of action, improvements in sweat chloride were not expected No meaningful changes in sweat chloride levels in PTI-428 treated patients were observed PTI-428 50 mg Treatment Effect (PTI-428 n=20, Placebo n=4) Day 7 Day 14 Day 28 Mean absolute change in ppFEV1 percentage points (95% CI) +4.9 (-0.2, 10.1) +5.2 (0.4, 10.0) +5.2 (0.3, 10.1) p value n.s. p<0.05 p<0.05 Mean relative change in ppFEV1 (95% CI) +8.3% (-0.9, 17.6) +9.0% (1.2, 16.9) +9.2% (1.2, 17.2) p Value n.s. p<0.05 p<0.05 ppFEV1 changes expressed as least-square mean vs placebo

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Individual Responses Showed Majority of PTI-428 Treated Patients Experienced Lung Function Improvement at Day 14, Sustained Through Day 28 Individual subject absolute change in ppFEV1 from baseline at day 14 and at day 28 of treatment period* Average absolute change from baseline in observed ppFEV1 was 2.1 (SD 4.9) at day 14 and 1.3 (SD 3.2) at day 28 * Observed data as available in per protocol set, SD – standard deviation Change at Day 14 Change at Day 28

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PTI-428 Granted Breakthrough Designation from the FDA PTI-428 received Breakthrough Therapy Designation by FDA in March 2018 for treatment of CF patients homozygous for F508del on background Orkambi® therapy Grant was given based on clinical evidence of increased lung function during the 28-day, once-a-day treatment with PTI-428 in CF subjects on Orkambi® background The study provides first evidence that genotype agnostic CFTR amplifiers have the potential to provide additional benefit to CF patients on existing CFTR modulator therapy Since the inception of the program, less than half of the drugs submitted for Breakthrough Therapy under the FDA Safety and Innovation Act have been granted the designation. In the CFTR modulator category, BTD has been granted to Kalydeco® Orkambi®, and Symdekoä PTI has started a clinical study in CF subjects on background Symdekoä therapy with initial data expected in early 2019, to support a development path towards NDA

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12 Month Key Milestones PTI-808/PTI-801/PTI-428 combination study protocol endorsed with high strategic fit score by CF patient advocacy groups in the U.S. and Europe PTI-801/PTI-808 combination study initiated in CF patients Breakthrough Therapy Designation for PTI-428 granted by the FDA PTI-801 14 day dosing, additional data in CF subjects on Orkambi® PTI-808/PTI-801/PTI-428 combination study initiates in CF subjects PTI-428 starts dosing in CF Subjects on Symdekoä clinical study PTI-808/PTI-801 initial data from combination study in CF subjects PTI-808/PTI-801/PTI-428 combination study preliminary data in CF subjects Early 2019 initial data from PTI-428 in CF Subjects on Symdekoä Orkambi® and Symdekoä are trademarks of Vertex Pharmaceuticals, Inc. 2018 2018

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Thank You