Business Wire

Genkyotex Meets Both Primary and Secondary Interim Efficacy Endpoints in Phase 2 Trial of GKT831 in Primary Biliary Cholangitis

Jaa

Regulatory News:

Genkyotex (Paris:GKTX) (Brussels:GKTX) (Euronext Paris & Brussels: FR00011790542 – GKTX) announced today that its lead product candidate GKT831, a NOX1/4 inhibitor, met both the primary and secondary interim efficacy endpoints with high statistical significance after only 6 weeks of treatment. The data establish GKT831 as an attractive therapeutic option in a broad PBC population and support its development in multiple fibrotic diseases including NASH and IPF.

GKT831 achieved even greater GGT reductions (29%, p<0.01 vs placebo) in patients with higher baseline GGT (≥ 2.5 XULN, n=68), suggesting that it may also benefit patients with more advanced disease, the patient population with the highest medical need and limited therapeutic options.

In addition, the progressive reductions from baseline to week 2 and to week 6 suggest that further improvements can be achieved with continued treatment. Specifically, the 400mg twice daily dose (BID) achieved a 15% reduction in GGT at week 2 and a 23% reduction at week 6. ALP reductions were 12% at week 2 and 17% at week 6.

The interim analysis was conducted in 92 patients after 6 weeks of treatment. Final study results after 24 weeks of treatment in 111 PBC patients are expected in Spring 2019. The final results will also include additional endpoints assessing quality of life (fatigue and pruritus), fibrosis and cholestasis.

Elias Papatheodorou, Chief Executive Officer of Genkyotex, commented: “The clinical data further establish GKT831 as a novel anti-fibrotic candidate and confirm the therapeutic value of NOX inhibition for patients. NOX inhibitors are an emerging therapeutic class able to address many human diseases with unmet medical need. Following these interim results we are investigating options in non-alcoholic steatohepatitis (NASH) and primary sclerosing cholangitis (PSC).

Philippe Wiesel, Chief Medical Officer of Genkyotex, commented: “The significant effect on the primary endpoint GGT, a marker of inflammatory and cholestatic liver injury, provides clinical confirmation of GKT831’s mechanism of action. We are very impressed by the highly significant effect on ALP, which indicates cholangiocyte protection. Importantly, ALP is a key endpoint used globally for regulatory approval. We are looking forward to the launch of the NIH funded IPF Phase 2 trial scheduled in H1 2019, the continuation of the JDRF funded DKD Phase 2 trial, and of course, seeing the final data of the PBC Phase 2 trial at week 24 in Spring 2019.”

About the PBC phase 2 trial of GKT831

The 24-week placebo-controlled study is being conducted in 62 centers (US, Canada, Belgium, Germany, Greece, Italy, Spain, UK and Israel). The trial enrolled PBC patients with inadequate response to ursodeoxycholic acid (UDCA). This is a difficult to treat patient population likely to progress to cirrhosis and eventually liver transplant or death. To be eligible for the trial, patients were required to have elevated alkaline phosphatase (ALP; >1.5XULN) and elevated gamma glutamyl transpeptidase (GGT; >1.5 XULN).

The primary efficacy endpoint is change in GGT at week 24. Key secondary endpoints include additional markers of liver and bile duct injury, markers of inflammation, non-invasive markers of liver fibrosis including liver stiffness assessed by transient elastography, the Enhanced Liver Fibrosis (ELF) score, and circulating collagen fragments including proC3. In addition, indicators of quality of life including pruritus and fatigue will be assessed. Markers of bile acid metabolism and immune activation will be also investigated.

A total of 111 patients have been allocated according to a 1:1:1 randomization ratio to three groups: UDCA plus placebo, UDCA plus GKT831 400mg once a day (OD) and UDCA plus 400mg twice a day (BID). This trial is one of the largest phase 2 PBC trials conducted to date.

For additional information about the trial design and eligibility criteria, please refer to the ClinicalTrial.gov website: NCT03226067.

About the interim analysis and baseline patient characteristics

The interim efficacy analysis was conducted when 92 patients completed 6 weeks of treatment. At baseline, mean ALP levels were respectively 304, 282, and 350 IU/L in the placebo, 400mg GKT831 OD, and 400mg GKT831 BID groups. Mean baseline GGT levels were respectively 224, 215, and 237 IU/L in the placebo, 400mg GKT831 OD, and 400mg GKT831 BID groups.

Changes in the primary efficacy endpoint GGT, a marker of liver and bile duct injury, were: -7% in the placebo, -12% in the 400mg OD, and -23%, in the 400mg BID groups (p<0.01 for the 400mg BID group vs placebo).

Changes in the key secondary efficacy endpoint ALP, a marker of bile duct injury, were: -2%, in the placebo, -8%, 400mg OD and -17% 400mg BID groups (p<0.001 for the 400mg BID group vs placebo). In PBC, a reduction in ALP of at least 15% is considered a meaningful biochemical response. Reduction of 15% in ALP was achieved in 53% of patients in the 400mg BID group compared to 16% in the placebo and 26% GKT831 400mg OD groups.

Markers of liver injury and inflammation were assessed. Although enrolled patients had relatively low levels of liver transaminases and high sensitivity C-reactive protein, dose dependent reductions were observed.

 
Baseline Patient characteristics and absolute changes in GGT & ALP
Baseline patient characteristics       Placebo   GKT831
400mg OD
  GKT831
400mg BID
N       31   31   30
Age (years)       56 (10)   56 (10)   55 (9)
Females (%)       97   84   93
GGT (IU/L)       224 (212)   215 (154)   237 (193)
ALP (IU/L)       304 (151)   282 (89)   350 (177)
ALT (IU/L)       44 (18)   44 (22)   55 (34)
AST (IU/L)       44 (19)   43 (20)   50 (33)
Total bilirubin (µmol/L)       10.2 (4.1)   11.0 (4.6)   10.8 (4.7)
hsCRP (mg/L)       5.0 (4.9)   5.8 (5.7)   4.7 (5.1)
Absolute and percent changes in GGT & ALP at week 6
GGT percent changes (%)       -7 (18)   -12 (23)   -23 (23)
GGT absolute changes (IU/L)       -16 (63)   -19 (81)   -57 (69)
ALP percent changes (%)       -2 (16)   -8 (13)   -17 (13)
ALP absolute changes (IU/L)       -17 (64)   -25 (43)   -62 (64)
Values expressed as mean (SD). Baseline: Day 1.

About clinical safety and pharmacokinetic (PK) analysis

To date, GKT831 has been well tolerated in PBC patients. On October 25 2018, the 3rd Safety Monitoring Board assessed safety data collected in 110 patients allocated to GKT831 400mg OD, GKT831mg BID, or placebo. From the patients reviewed, 87 patients had completed 6 weeks of treatment, 69 subjects had reached week 12 and of these 41 had completed the full 24-week treatment. The SMB provided a positive recommendation. A single serious adverse event (SAE), a case of grade 1 urinary tract infection, has been reported to date. Study drug was not interrupted and the SAE was deemed unrelated to study drug. Importantly, to date there has been no patient drop out due to pruritus.

An initial PK analysis was conducted. Plasma levels of GKT831 and its main active metabolite GKT138184 were measured after 2, 12, and 18 weeks of dosing. Available drug levels at the time of the interim analysis were analyzed. As anticipated, patients receiving 400mg BID had higher through (pre-dose) levels compared to patients receiving 400mg OD. Overall, these results indicate that drug exposure levels were consistent with expectations and with the two dosing levels included in the trial. These results will inform dose selection for future clinical trials of GKT831 in multiple fibrotic disorders.

Conference call details

Genkyotex will host a conference call today, Monday, November 5 2018 at 03:00 pm CET / 09:00 am EDT to discuss these results.

To access the conference call, please dial the following numbers:

France: +33 (0)1 72 72 74 03
Belgium: +32 24 03 58 16
Switzerland: +41 445 831 805
United Kingdom: +44 207 194 37 59
United States: +1 (646) 722 49 16

Pin: 79 25 79 31#

The presentation commented by the management team will be available on the link below:

Genkyotex conference call

A replay of the conference call will be available for 90 days after the session with the following logins:

France: +33 (0)1 70 71 01 60
Belgium: +32 24 03 72 61
Switzerland: +41 225 804 208
UK: +44 203 364 51 47
US: +1 (646) 722 49 69
Access code: 41 88 03 324 #

About Primary Biliary Cholangitis

PBC is an orphan chronic autoimmune disease resulting in the progressive destruction of bile ducts. Decreased bile flow and build up of toxic bile acids results in further bile duct damage and liver injury. Over time, patients develop progressive liver fibrosis, cirrhosis, liver failure and are at higher risk of developing liver cancer. PBC affects primarily women and has a major impact of quality of life by causing fatigue and itching.

About Genkyotex

Genkyotex is the leading biopharmaceutical company in NOX therapies, listed on the Euronext Paris and Euronext Brussels markets. A leader in NOX therapies, its unique therapeutic approach is based on a selective inhibition of NOX enzymes that amplify multiple disease processes such as fibrosis, inflammation, pain processing, cancer development, and neurodegeneration.

Genkyotex’s platform enables the identification of orally available small-molecules that selectively inhibit specific NOX enzymes. Genkyotex is developing a pipeline of first-in-class product candidates targeting one or multiple NOX enzymes. The lead product candidate, GKT831, a NOX1 and NOX4 inhibitor is evaluated in a phase II clinical trial in primary biliary cholangitis (PBC, a fibrotic orphan disease) and in an investigator-initiated Phase II clinical trial in Type 1 Diabetes and Kidney Disease (DKD). A grant from the United States National Institutes of Health (NIH) of $8.9 million was awarded to Professor Victor Thannickal at the University of Alabama at Birmingham (UAB) to fund a multi-year research program evaluating the role of NOX enzymes in idiopathic pulmonary fibrosis (IPF), a chronic lung disease that results in fibrosis of the lungs, the core component of the program will be to conduct a Phase 2 trial with the GKT831 in patients with IPF. This product candidate may also be active in other fibrotic indications. Its second product candidate, GKT771, is a NOX1 inhibitor targeting multiple pathways in angiogenesis, pain processing, and inflammation, currently undergoing preclinical testing.

Genkyotex also has a versatile platform well-suited to the development of various immunotherapies (Vaxiclase). A partnership covering the use of Vaxiclase as an antigen per se (GTL003) has been established with Serum Institute of India Private Ltd (Serum Institute), the world’s largest producer of vaccine doses, for the development by Serum Institute of cellular multivalent combination vaccines against a variety of infectious diseases. This partnership could generate approximately €150 million in future revenues for Genkyotex, before royalties on sales.

For further information, please go to www.genkyotex.com .

Disclaimer

This press release may contain forward-looking statements by the company with respect to its objectives. Such statements are based upon the current beliefs, estimates and expectations of Genkyotex’s management and are subject to risks and uncertainties such as the company's ability to implement its chosen strategy, customer market trends, changes in technologies and in the company's competitive environment, changes in regulations, clinical or industrial risks and all risks linked to the company's growth. These factors as well as other risks and uncertainties may prevent the company from achieving the objectives outlined in the press release and actual results may differ from those set forth in the forward-looking statements, due to various factors. Without being exhaustive, such factors include uncertainties involved in the development of Genkyotex’s products, which may not succeed, or in the delivery of Genkyotex’s products marketing authorizations by the relevant regulatory authorities and, in general, any factor that could affects Genkyotex’s capacity to commercialize the products it develops. No guarantee is given on forward-looking statements which are subject to a number of risks, notably those described in the registration document (document de reference) registered by the French Markets Authority (the AMF) on 27 April 2018 under number R.18-037, and those linked to changes in economic conditions, the financial markets, or the markets on which Genkyotex is present. Genkyotex products are currently used for clinical trials only and are not otherwise available for distribution or sale.

Contact information

INVESTORS
NewCap
Dušan Orešanský, Tristan Roquet Montégon and Emmanuel Huynh
+33 1 44 71 94 92
genkyotex@newcap.eu
or
MEDIA
NewCap
Nicolas Merigeau, Arthur Rouillé
+33 1 44 71 00 15
genkyotex@newcap.eu
or
US
LifeSci Advisors, LLC
Brian Ritchie
+1-212-915-2578
britchie@lifesciadvisors.com

Tietoja julkaisijasta

For more than 50 years, Business Wire has been the global leader in press release distribution and regulatory disclosure.

Tilaa tiedotteet sähköpostiisi

Haluatko tietää asioista ensimmäisten joukossa? Kun tilaat mediatiedotteemme, saat ne sähköpostiisi välittömästi julkaisuhetkellä. Tilauksen voit halutessasi perua milloin tahansa.

Lue lisää julkaisijalta Business Wire

Smithers Viscient announces the appointment of Ian Siragher to the position of Managing Director24.1.2019 13:30Tiedote

Smithers Viscient, a global contract research organization (CRO), today announced the appointment of Ian Siragher to the position of Managing Director. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20190124005031/en/ Ian Siragher, Managing Director, Smithers Viscient Europe (Photo: Business Wire) Siragher will assume operational responsibility for the Smithers Viscient European site in Harrogate, UK. His experience includes high technology start-ups, running SME business, sales, marketing and regulated industry programs within the analytical, pharmaceutical and drug delivery industries. He brings a wealth of entrepreneurial experience with proven strengths in scientific knowledge, operational and strategic planning, coupled with a strong client focus. “We are delighted to welcome Ian to our business,” said Susan Shepherd, President, Smithers Viscient. “Ian is an excellent appointment for us; he is a proven operational leader

HCL Technologies Honors Humanitarian Leaders at the 2019 World Economic Forum in Davos24.1.2019 13:22Tiedote

HCL Technologies, a global technology company, today announced its Goodwill Champions Awards Night to honor humanitarian leaders from around the world. The event will take place on January 24th, 2019, at the HCL Pavilion in Davos and will celebrate these heroic organizations committed to pursuing distinct noble causes, primarily focused on global education, youth development, and women empowerment. This is the first year the awards have been presented, and HCL Technologies plans to issue them each year in a global forum. The award recipients are Katja Iversen, CEO of Women Deliver, which advocates for global investments in gender equality and health; Olajumoke Adekege, Founder of Young Business Agency, which provides employability skills training and recruitment services to young job seekers globally; Chiara Tiles, Founder of We Do it Together – which produces films, documentaries, TV, and other forms of media, uniquely dedicated to the empowerment of women; Baillie Aaron, Founder and

P&G Joins TerraCycle’s Loop – an Environmentally Friendly and Convenient E-Shopping Platform – With 11 Household Brands24.1.2019 13:00Tiedote

The Procter & Gamble Company (NYSE:PG) today announced the introduction of reusable, refillable packaging on some of its most popular products as part of a new effort that aims to change the world’s reliance on single use packaging and disposable waste. Additionally, new “collect and recycle” circular solutions that help eliminate waste were also introduced as part of a partnership with LoopTM, a circular e-commerce platform developed by international recycling leader TerraCycle. Many of P&G’s largest global brands, including PanteneTM, TideTM, CascadeTM and Oral-BTM will participate in this innovative platform later this year. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20190124005087/en/ Pantene is introducing a unique bottle made with lightweight, durable aluminum for its shampoo and conditioner. (Photo: Business Wire) Loop is a first of its kind global packaging and shopping circular solution which aims to improve the e

RSM and DSI Agree to Cross-Border Insolvency Strategic Alliance24.1.2019 13:00Tiedote

Two well-known and respected firms in the global restructuring industry have formed a strategic alliance and international collaboration to further support their respective clients amid a growing wave of cross-border insolvency and international restructuring projects. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20190123005735/en/ U.K.-based restructuring practice RSM Restructuring Advisory LLP ("RSM"), part of audit, tax and consulting firm RSM UK, and U.S.-based restructuring firm Development Specialists, Inc. (DSI), have announced an agreement to collaborate and augment each respective firm's services in dealing with transnational cases. "We're delighted to announce that we'll be collaborating with DSI on cross-border projects,” said Graham Bushby, a Partner and Head of Restructuring Advisory at RSM. “DSI is working on some significant transnational cases and brings a wealth of experience to the arena, which RSM can capa

Total Eren and NBT Secure the Financing for the First Phase of The 250 MW Syvash Wind Project in Ukraine from a Consortium Led by EBRD24.1.2019 11:00Tiedote

NBT AS (“NBT”), a utility-scale wind power developer based in Oslo, and Total Eren SA (“Total Eren”), a leading renewable energy Independent Power Producer (“IPP”) based in Paris, have signed definitive financing agreements for the first phase of a 250 MW wind project located in the Kherson region of Ukraine. The €155M financing agreement was signed at a special meeting of Ukraine’s National Investment Council in Davos. The project’s start of construction is imminent. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20190124005105/en/ The onshore wind project, called Syvash wind farm (“Syvash”) has been developed by Norway-based NBT together with France-based Total Eren. At its full capacity, Syvash represents a €380 million total investment. Syvash will consist of 64 wind turbines and will be located on 1,300 hectares of land in the southern Kherson region of Ukraine. Once completed, it is expected to become the country’s large

STARMUS V, Host of The Stephen Hawking Medal, Hosts a Special Evening in Davos at WEF with Jean-Michel Jarre, Brian May and Luminary Scientific Panel24.1.2019 11:00Tiedote

This year, WEF was treated to a rare panel discussion bridging the fields of astronomy and music. Global CEOs and international media had the opportunity to hear from Dr. Brian May, Jean-Michel Jarre and Dr. Garik Israelian discuss STARMUS and the special connection between science and music. Flanked by a panel of renowned scientists, astronauts, and Nobel laureates, Jean-Michel Jarre introduced his groundbreaking tribute to the Apollo Missions for their 50th Anniversary. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20190124005171/en/ WEF panel for STARMUS, Michel Mayor, Jean-Michel Jarre, Garik Israelian, and moderator Marco Larsen engage with the Davos audience. Photo by: Andres Eggenberger The esteemed panel included Swiss Astronaut Claude Nicollier, Garik Israelian, Brian May, and Michel Mayor. (Special thanks to the support from Kaspersky Labs and to the Stephen Hawking Medal for Science Communication sponsor, Omega.) T

Uutishuoneessa voit lukea tiedotteitamme ja muuta julkaisemaamme materiaalia. Löydät sieltä niin yhteyshenkilöidemme tiedot kuin vapaasti julkaistavissa olevia kuvia ja videoita. Uutishuoneessa voit nähdä myös sosiaalisen median sisältöjä. Kaikki STT Infossa julkaistu materiaali on vapaasti median käytettävissä.

Tutustu uutishuoneeseemme