PRTC: resTORbio Announces Positive Topline Results

RNS Number : 6889V

PureTech Health PLC

25 July 2018

 

25 July 2018

PureTech Health plc

PureTech Health Affiliate resTORbio Announces Positive Topline Results in Phase 2b Trial of RTB101

PureTech Health plc (LSE: PRTC) ("PureTech Health"), a clinical-stage biopharmaceutical company developing novel medicines for dysfunctions of the Brain-Immune-Gut (BIG), today announced that its independent affiliate, resTORbio (NASDAQ: TORC), reported positive topline results from its Phase 2b clinical study. Details are provided below in the resTORbio press release, and a conference call to discuss the results will be hosted today at 8.30 EDT / 13.30 BST. To participate in the conference call, please dial [phone] and refer to conference ID 3181638. A live webcast of the call can be accessed in the "Investors" section of the resTORbio website at www.restorbio.com. An archived webcast recording will be available on the resTORbio website beginning approximately two hours after the call.

Joe Bolen, PhD, Chief Scientific Officer of PureTech Health commented: "resTORbio's proprietary TORC1 inhibitor, RTB101, has significantly reduced the percentage of elderly individuals with respiratory tract infections (RTIs) across two Phase 2 clinical studies at the 10 mg once daily dose.  We are very pleased with these positive results and believe RTB101 may be a promising new treatment for elderly individuals who are at high risk of RTI-associated morbidity and mortality."

The full text announcement from resTORbio is as follows:

resTORbio Announces Positive Topline Results in Phase 2b Trial of RTB101

-- Statistically significant and clinically meaningful 30.6% reduction in the percentage of patients with one or more laboratory-confirmed respiratory tract infections (RTIs), the primary endpoint of the trial, in the RTB101 10 mg once daily cohort compared to the placebo cohort --

-- Statistically significant 68.4% reduction in the incidence of laboratory-confirmed RTIs in the pre-specified analysis of asthma patients 65 years and older treated with RTB101 10 mg once daily --

-- Statistically significant 66.7% reduction in the incidence of laboratory-confirmed RTIs in the pre-specified analysis of patients 85 years and older treated with RTB101 10 mg once daily --

--All doses were well-tolerated; RTB101 10 mg once daily had a comparable safety profile to placebo--

 --The Phase 2b trial successfully identified a dose and patient populations with high unmet need for upcoming pivotal trials --

-- Conference call 8:30 AM Eastern Time today --

BOSTON, July 25, 2018 -- resTORbio, Inc. (Nasdaq: TORC) today announced positive topline results from its dose-ranging Phase 2b clinical trial that enrolled 652 elderly patients at increased risk of morbidity and mortality associated with respiratory tract infections (RTIs). In this trial, RTB101, an oral, selective, and potent inhibitor of target of rapamycin complex 1 (TORC1), demonstrated a statistically significant and clinically meaningful reduction in the percentage of patients with one or more laboratory-confirmed RTIs during the 16-week treatment period compared to placebo, the primary endpoint of the study, with the 10 mg once daily dose. Greater TORC1 inhibition with RTB101 10 mg in combination with everolimus 0.1 mg did not meet the primary endpoint, suggesting that that less TORC1 inhibition with RTB101 10 mg once daily may have greater benefit in high-risk elderly patients.

"This Phase 2b has successfully defined a dose, RTB101 10 mg once daily, to be evaluated in future pivotal studies. That dose led to a statistically significant decrease in the incidence of laboratory-confirmed RTIs and was well-tolerated in the high-risk elderly patients enrolled in the Phase 2b study. We have also identified patient populations that were particularly high responders," said Joan Mannick, M.D., Co-Founder and Chief Medical Officer of resTORbio. "We believe the findings of this trial provide us with a clear path forward for pursuing a pivotal program for RTB101 to reduce the incidence of RTIs in high-risk elderly patients. We look forward to working closely with the U.S. Food and Drug Administration (FDA) and other regulatory agencies on this program."

"The majority of RTIs requiring hospitalizations in the very elderly and the majority of asthma exacerbations are caused by viruses for which there are currently no approved therapies," said Professor Sebastian Johnston, Professor of Respiratory Medicine and Allergy at the National Heart and Lung Institute, Imperial College London. "The magnitude of reduction in the incidence of laboratory-confirmed RTIs observed with RTB101 suggests that, if successfully developed and approved, RTB101 may be a new promising treatment for the very elderly and elderly patients with asthma who are at high risk of morbidity and mortality associated with RTIs."

"The primary endpoint of this Phase 2b study, the percentage of patients with laboratory-confirmed RTIs, was chosen based on feedback from the FDA, and we look forward to discussing these results at our end of Phase 2 meeting with the agency," said Chen Schor, Co-Founder, President and CEO of resTORbio. "RTIs are the fourth leading cause of hospitalization in patients 65 years and older, and the second leading cause of hospitalization in patients 85 years and older in the U.S. We are committed to helping the millions of elderly patients at high risk of morbidity and mortality due to RTIs."

The Phase 2b trial was a two-part, randomized, double-blind, placebo-controlled clinical trial conducted during the winter cold and flu season in the southern hemisphere (Part 1) and northern hemisphere (Part 2). Patients enrolled were those at increased risk of morbidity and mortality from RTIs including patients who were: (i) 85 years of age or older, or (ii) 65 years of age or older with asthma, type 2 diabetes mellitus (T2DM), chronic obstructive pulmonary disease (COPD), or current smokers. The doses investigated in Part 1 were RTB101 5 mg and RTB101 10 mg once daily. The doses investigated in Part 2 were RTB101 10 mg once daily, RTB101 10 mg twice daily and RTB101 10 mg in combination with everolimus 0.1 mg once daily.

The following was observed in an analysis of the primary endpoint:

·     A 30.6% decrease relative to placebo in the percentage of all patients treated with RTB101 10 mg once daily who developed one or more laboratory-confirmed RTIs (p=0.026)

·     A 20.6% decrease relative to placebo in the percentage of all patients treated with RTB101 5 mg once daily who developed one or more laboratory-confirmed RTIs (p=0.108)

·     No decrease relative to placebo in the percentage of patients treated with either RTB101 10 mg twice daily or the combination of RTB101 10 mg + everolimus 0.1 mg once daily who developed one or more laboratory-confirmed RTIs, suggesting that less TORC1 inhibition with RTB101 10 mg once daily may have greater benefit in high-risk elderly patients

To better understand the activity observed in the RTB101 10 mg once daily cohort, a pre-specified analysis of each patient subgroup enrolled in the study was conducted. The following decreases in the percentage of patients with laboratory-confirmed RTIs were observed in the RTB101 10 mg once daily cohort as compared to the placebo cohort:

·     A 68.4% decrease in all asthma patients (p=0.0002)

·     A 66.7% decrease in all patients 85 years of age and older (p=0.007)

·     A 26.9% decrease in all T2DM patients (p=0.020)

·     No decrease was observed in either COPD patients or current smokers; a 42.0% decrease in all patients was observed when excluding patients with COPD (p=0.002) and a 43.9% decrease in all patients was observed when excluding current smokers (p=0.001)

All doses were observed to be well-tolerated. Data from the RTB101 10 mg once daily cohort are as  follows: Adverse events (AEs) were balanced between the RTB101 10 mg once daily and placebo treatment groups. 4.5% of subjects in the RTB101 10 mg once daily cohort and 7.2% of subjects in the placebo cohort had a serious adverse event, none of which were considered related to study drug. 4.5% of subjects in the RTB101 10 mg once daily cohort and 6.1% of subjects in the placebo cohort discontinued study drug due to an AE. All AEs were mild or moderate except for 11 severe AEs in the RTB101 10 mg once daily cohort and 22 severe AEs in the placebo cohort.

This Phase 2b is the second study in which RTB101 10 mg once daily was observed to be well-tolerated and reduce the incidence of RTIs in the elderly. Together, these studies enrolled more than 900 elderly people.

Conference Call and Webcast Information

resTORbio management will host a conference call today at 8:30 a.m. ET to discuss the results of the Phase 2b trial. To participate in the conference call, please dial [phone] (domestic) or [phone] (international) and refer to conference ID 3181638. A live webcast of the call can be accessed in the "Investors" section of the Company's website at www.restorbio.com. An archived webcast recording will be available on the resTORbio website beginning approximately two hours after the call.

Phase 2b Trial Design

The purpose of the exploratory dose-finding, randomized, double-blind, placebo-controlled, multi-center Phase 2b clinical trial was to determine if RTB101 alone or in combination with everolimus decreased the incidence of RTIs in high-risk elderly patients, as well as to evaluate safety and tolerability alone or in combination with everolimus, to support dose selection for pivotal trials.

The study enrolled 652 patients at increased risk of morbidity and mortality from RTIs including patients who were: (i) 85 years of age or older, or (ii) 65 years of age or older with asthma, T2DM, COPD, or current smokers. The study consisted of two parts. Part 1 was conducted during the winter cold and flu season in the southern hemisphere and 179 elderly patients were randomized to receive either placebo, RTB101 5 mg or RTB101 10 mg once daily. At the end of Part 1, an interim analysis was conducted by an unblinded data monitoring committee who selected the RTB101 10 mg dose to move forward into Part 2 of the study. Part 2 was conducted during the winter cold and flu season in the northern hemisphere and 473 elderly patients were randomized to receive either placebo, RTB101 10 mg once daily, RTB101 10 mg twice daily, or RTB101 10 mg in combination with everolimus 0.1 mg once daily. All patients were treated with study drug for 16 weeks, and then were followed for an additional eight weeks off study drug.

The primary endpoint of the trial was a reduction, as compared to placebo, in the percentage of patients with one or more laboratory-confirmed RTIs during the 16 weeks of study drug treatment. A pre-specified exploratory endpoint was a reduction, as compared to placebo, in the percentage of patients with one or more laboratory-confirmed RTIs in each of the patient subgroups (≥ 85 years of age, ≥ 65 years of age with asthma, COPD, T2DM, or current smokers).

Additional information about the study [NCT03373903] can be obtained at www.ClinicalTrials.gov.

About Respiratory Tract Infections

The reduced ability of the aging immune system to effectively detect and fight infections results in increased susceptibility of the elderly to RTIs. In the U.S., RTIs are the fourth leading cause of hospitalizations and seventh leading cause of death in people age 65 years and older. Additionally, the majority of asthma exacerbations are caused by RTIs, and the majority of RTIs are caused by viruses for which there are no currently approved therapies.  

A survey was conducted by resTORbio of 100 physicians in the U.S. that treat approximately 25,000 patients aged 65 years or older monthly. Depending on their specialty, the physcians surveyed estimated that they would prescribe a therapeutic that reduced the incidence of laboratory-confirmed RTIs by 25% to approximately 30-50% of their high-risk elderly patients. Data from market surveys may not predict actual prescribing behavior should RTB101 receive regulatory approval.

About RTB101

RTB101 is an oral, selective, and potent inhibitor of TORC1. RTB101 inhibits the phosphorylation of multiple targets downstream of TORC1. Inhibition of TORC1 has been observed to extend lifespan and healthspan in aging preclinical species and to enhance immune, cardiac and neurologic functions, suggesting potential benefits in several aging-related diseases.

About resTORbio

resTORbio, Inc. is a clinical stage biopharmaceutical company targeting TORC1 and other biological pathways that regulate aging to develop innovative medicines with the potential to extend healthy lifespan. resTORbio's lead program is selectively targeting TORC1, an evolutionarily conserved pathway that contributes to the decline in function of multiple organ systems, including the immune, cardiovascular and central nervous systems.

Forward Looking Statements

This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the federal securities laws. Investors are cautioned that statements in this press release which are not strictly historical statements, including, without limitation, express or implied statements or guidance regarding our plans to develop and commercialize RTB101 alone or in combination with everolimus, including the therapeutic potential and clinical benefits thereof, and the potential patient populations that may be addressed by our product candidates, our ongoing and future clinical trials for RTB101 alone or in combination with everolimus, including the timing of the initiation and anticipated results of these trials, as well as the intended regulatory path for our product candidates and interactions with regulatory authorities, constitute forward-looking statements identified by words like "believe," "expect," "may," "will," "should," "seek," "anticipate," or "could" and similar expressions. Such forward-looking statements are subject to a number of risks and uncertainties that could cause actual results to differ materially from those anticipated, including, without limitation, risks associated with: the delay of any planned clinical trials and/or development of RTB101, either alone or in combination with everolimus; our ability to successfully demonstrate the efficacy and safety of our lead product candidate; the clinical results for our lead product candidate which may not support further development of additional indications; and obtaining, maintaining and protecting our intellectual property; as well as those risks more fully discussed in the section entitled "Risk Factors" in the Annual Report on Form 10-K filed by resTORbio, Inc. with the Securities and Exchange Commission, as well as discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the Securities and Exchange Commission. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing its views as of any subsequent date. resTORbio explicitly disclaims any obligation to update any forward-looking statements.

About PureTech Health

PureTech Health (LSE: PRTC) is an advanced, clinical-stage biopharmaceutical company developing novel medicines for dysfunctions of the Brain-Immune-Gut (BIG). The Company has developed deep insight into the connection between these systems and the resulting role in many chronic diseases, which represent the majority of healthcare spend and have proven resistant to established therapeutic approaches. By harnessing this emerging field of human biology, PureTech Health has developed new categories of medicines with the potential to have great impact on people with serious diseases.

PureTech Health is advancing a rich pipeline of innovative therapies across two divisions. Its Affiliates division includes two product candidates that are preparing for potential regulatory approval in the United States and Europe and a number of clinical and pre-clinical programmes. These affiliates have developed ground-breaking platforms and therapeutic candidates in collaboration with some of the world's leading scientific experts.

PureTech's Internal division (Ariya) is advancing a pipeline fuelled by recent discoveries in lymphatics and immune cell trafficking to modulate disease in a tissue-specific manner. These programmes build on a new understanding of the transport and biodistribution of various immune system components in order to develop targeted therapies for diseases with major unmet needs including cancer and autoimmune and neuroimmune disorders. One of these programs, which is focused on the oral administration of nucleic acids and other biologics using milk exosomes, is being advanced in collaboration with Roche for the potential application across their antisense oligonucleotides platform.

For more information, visit www.puretechhealth.com or connect with us on Twitter @puretechh.

Ownership Information

PureTech Health owns 9,800,396 shares of resTORbio, which is equal to approximately 34.9% of the outstanding shares of resTORbio.

Forward Looking Statement

This press release contains statements that are or may be forward-looking statements, including statements that relate to the company's future prospects, developments and strategies. The forward-looking statements are based on current expectations and are subject to known and unknown risks and uncertainties that could cause actual results, performance and achievements to differ materially from current expectations, including, but not limited to, those risks and uncertainties described in the risk factors included in the regulatory filings for PureTech Health plc. These forward-looking statements are based on assumptions regarding the present and future business strategies of the company and the environment in which it will operate in the future. Each forward-looking statement speaks only as at the date of this press release. Except as required by law and regulatory requirements, neither the company nor any other party intends to update or revise these forward-looking statements, whether as a result of new information, future events or otherwise.

This announcement contains inside information for the purposes of Article 7 of Regulation (EU) 596/2014.

Contact:

Investors	EU media
Allison Mead Talbot [phone] [e-mail]	Ben Atwell, Rob Winder [phone] [e-mail]

 

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