ThromboGenics Business Update - Q1 2016

LEUVEN, Belgium, May 13, 2016 /PRNewswire/ --

Developing Novel Medicines Targeting Diabetic Eye Disease 

Highlights 

• ThromboGenics is focused on developing novel medicines for the treatment of diabetic eye disease

• ThromboGenics presented its new drug development pipeline with 4 compounds, targeting novel treatments for diabetic retinopathy (DR) - non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR), in the presence or absence of diabetic macular edema (DME)

• ThromboGenics initiated a Phase IIa clinical study (CIRCLE) evaluating THR-409 (ocriplasmin) to induce a complete posterior vitreous detachment (PVD), to prevent patients with non-proliferative diabetic retinopathy from progressing to proliferative diabetic retinopathy, a serious sight threatening condition

• ThromboGenics signed a global and exclusive license agreement with Galapagos to develop and commercialize integrin antagonists for the treatment of diabetic eye disease. The Company has started to explore the potential of these compounds for the treatment of NPDR and PDR

• Full report of OASIS 2 year follow up study with JETREA^® (ocriplasmin) for the treatment of symptomatic VMA/VMT and Macular Hole (n=220) has been submitted and accepted for publication in a prestigious peer reviewed ophthalmology journal

• 15 ocriplasmin-related posters and presentations, with new research findings, were presented at the Association for Research in Vision and Ophthalmology (ARVO) 2016 annual meeting in Seattle

• Following a collaboration agreement with the US-based NMTRC (Neuroblastoma and Medulloblastoma Translational Research Center), ThromboGenics' subsidiary, Oncurious, has initiated a Phase I/IIa study with TB-403 for the treatment of medulloblastoma, the most common pediatric malignant brain tumor

• Cash and investments were €96.9 million as of the end of March 2016, compared with €101.4 million at the end of December 2015

ThromboGenics NV (Euronext Brussels: THR), a biotechnology company focused on developing novel medicines for diabetic eye disease, today issues a business update for the three month period ending 31 March, 2016.

ThromboGenics is focused on developing novel medicines for diabetic eye disease, particularly diabetic retinopathy (DR) and diabetic macular edema (DME).

Over the last two years, ThromboGenics has developed an attractive pipeline of disease modifying drug candidates. The pipeline consists of THR-409, THR-317, both from its in-house research, as well as THR-149 which resulted from a research collaboration with Bicycle Therapeutics, and THR-687, which was recently in-licensed from Galapagos NV.

These products all have different modes of action and allow the Company to address the four key segments of the evolving diabetic eye disease market:

• Non-proliferative DR
• Proliferative DR
• Non-proliferative DR with DME
• Proliferative DR with DME

ThromboGenics believes its diabetic eye disease pipeline is one of the strongest in the industry.

In addition, ThromboGenics, through its oncology spin-off Oncurious, is conducting a Phase I/IIa clinical trial in children assessing TB-403 for the treatment of medullablastoma, the most common malignant brain tumor in children. This oncological development program is jointly conducted with ThromboGenics' research partner BioInvent International AB.

Dr. Patrik De Haes, ThromboGenics' CEO, said: "ThromboGenics has entered a new era as we progress our exciting drug development pipeline of potential new disease modifying medicines for the treatment of diabetic eye disease. Diabetic Retinopathy and Diabetic Macular Edema (DME) are significant indications where there are clear unmet medical needs and a strong demand for improved or add-on treatment options. With our ambitious pipeline, we believe we are well positioned to address all key segments of the diabetic eye disease market and to generate attractive returns for our shareholders."

Research & Development Activities - Novel Disease Modifying Medicines for Diabetic Eye Disease  

Diabetes, Diabetic Retinopathy and DME 

Diabetes is a major healthcare problem globally with 9% of adults 18 years and older suffering from this disease World Health Organization (WHO). (2015). Diabetes. Fact sheet N°312. http://www.who.int/mediacentre/factsheets/fs312/en/  21 May 2015..

Diabetic retinopathy (DR) is the leading cause of visual disability and blindness among professionally active adults (Cunha-Vaz, 1998; Fong et al., 1999). Worldwide, the prevalence rate of vision-threatening PDR or DME was estimated to be 11.72% of the diabetic population in 2010 (Yau et al., 2012).

DR progresses from mild, non-proliferative to more severe or even proliferative stages. As DR progresses, there is a gradual closure of retinal blood vessels leading to impaired perfusion and retinal ischemia. When this progresses beyond certain thresholds, severe non-proliferative diabetic retinopathy (NPDR) is diagnosed.

The more advanced stage of diabetic retinopathy, PDR, is characterized by the development of new blood vessels at the inner surface of the retina as a result of retinal ischemia. These new vessels are prone to bleed, resulting in vitreous hemorrhage. They may also undergo fibrosis and contraction, which may lead to epiretinal membrane formation, vitreoretinal traction bands, retinal tears and traction or retinal detachments.

PDR is considered high risk when the new vessels are accompanied by vitreous hemorrhage, or when they cover a significant area of the optic disc. Even in the absence of vitreous hemorrhage, patients who progress to PDR are at high risk of severe vision loss.

An Ambitious Pipeline of Novel Medicines Targeting Diabetic Eye Disease such as Diabetic Retinopathy and DME  

Over the last 18 months ThromboGenics has been working to develop a pipeline of next generation medicines that are designed to treat the various forms/symptoms of DR and DME.

ThromboGenics pipeline comprises of:

• THR-409 (ocriplasmin) - is in a Phase IIa (CIRCLE) clinical study evaluating the efficacy and safety of multiple doses and/or half-doses of ocriplasmin in inducing total posterior vitreous detachment (PVD) in patients with non-proliferative diabetic retinopathy (NPDR). The Phase IIa study was initiated in early 2016.

• THR-317 - a PlGF inhibitor being developed for DME and potentially as a combination therapy for current anti-VEGF treatments. THR-317 is expected to enter the clinic around end of 2016.

• THR-149 - a selective plasma kallikrein inhibitor being developed to treat the edema associated with DR. This compound is the result of the Company's research collaboration with Bicycle Therapeutics.

• THR-687 - an integrin antagonist being developed to treat a broad range of patients with DR, with or without DME. THR-687 was in-licensed from Galapagos NV in March.

On March 18, 2016, ThromboGenics hosted an R&D investor meeting in London presenting more detailed information on its new development pipeline in diabetic eye disease.  

The webcast replay of the event is available on the ThromboGenics' website.

THR-409 for Non Proliferative Diabetic Retinopathy  

In January 2016, the Company announced the initiation of its Phase IIa (CIRCLE) study.

The CIRCLE study is evaluating the efficacy and safety of multiple doses of THR-409 (ocriplasmin) in inducing total posterior vitreous detachment (PVD) in patients with non-proliferative diabetic retinopathy (NPDR).

Research has suggested that total PVD, a complete separation of vitreous and retina, prevents the progression of NPDR to PDR. This could be explained by total PVD leading to elimination of the scaffold needed for the development of new blood vessels and/or the improvement of oxygen supply to the retina, thereby reducing retinal ischemia, production of VEGF, vascular outgrowth and neovascularization.

ThromboGenics believes that by using multiple doses of THR-409 it can reduce the risk of patients' disease progressing from NPDR to proliferative diabetic retinopathy (PDR) by inducing a total PVD.  PDR is the major cause of blindness in patients with diabetes. Patients who progress to PDR are at high risk of experiencing severe vision loss or complete blindness.

The CIRCLE study is a Phase II, randomized, double-masked, sham-controlled, multi-center study that will evaluate the efficacy and safety of up to 3 intravitreal injections of either 0.125mg or half of the approved dose (0.0625mg) of THR-409 in subjects with moderately severe to very severe NPDR, to induce total PVD and reduce the risk of the patient progressing to sight-threatening PDR.

A total of 230 subjects will be recruited into the CIRCLE trial, approximately 92 in each THR-409 arm (0.125mg or 0.0625mg) and 46 in the sham arm. Patients will be accrued from sites across the US, Canada and EMEA.

The primary endpoint of the CIRCLE study is the percentage of patients with total PVD by the month 3 visit, confirmed by both B-scan ultrasound and SD-OCT.

The study has a number of secondary endpoints that are designed to provide further insights into ocriplasmin's potential in reducing the risk of progression of NPDR to PDR.

THR-317 - anti PIGF antibody to treat DME  

THR-317 is a disease modifying, anti PlGF antibody that due to its mode of action has the potential to treat a broad range of patients with late stage diabetic eye disease either alone or in combination with anti-VGEF treatments.

ThromboGenics has chosen to start the development of THR-317 for the treatment of diabetic edema and expects to start the clinical development of this novel antibody later in 2016.

The Phase I/II study that is planned expects to recruit 50 patients, either anti-VEGF naïve patients or anti-VEGF poor responders. The trial will have two arms comparing a low dose of THR-317 with a high dose of THR-317. The trial will assess the safety of THR-317 and will look at best corrected visual acuity and retinal thickness to evaluate the product's efficacy. The first results from this clinical trial are expected in late 2017/early 2018.

Oncurious NV - Developing TB-403 for Pediatric Brain Cancers 

Oncurious is developing TB-403 for the treatment of pediatric tumors.

TB-403 is a humanized monoclonal antibody against placental growth factor (PlGF). PlGF is expressed in several types of cancer, including medulloblastoma. High expression of the PlGF receptor neuropilin 1 has been shown to correlate with poor overall survival. Medulloblastoma is the most common pediatric malignant brain tumor, accounting for 20% of all brain tumors in children.

Treatment with TB-403 in relevant animal models for medulloblastoma has demonstrated beneficial effects on tumor growth and survival. The favorable safety profile of TB-403 has already been demonstrated in clinical trials in patients with other diseases.

In March 2016, Oncurious and its development partner BioInvent International signed a partnership agreement with the Neuroblastoma and Medulloblastoma Translational Research Center (NMTRC) to accelerate the clinical development of TB-403 for the treatment of medulloblastoma in the US. The NMRTC is a non-profit organization with the mission to bring forward new effective therapies against neuroblastoma and medulloblastoma. Headquartered at Helen DeVos Children's Hospital in Grand Rapids, MI, NMTRC is a network of 18 leading university hospitals and pediatric clinics in the US.

On May 2, Oncurious and BioInvent initiated a Phase I/IIa study with TB-403. The study, which is being conducted by NMTRC, aims to recruit a total of 27 patients with Relapsed or Refractory Medulloblastoma, with first results expected to be reported in 2017.

JETREA Update 

JETREA^® Regulatory & Markets Access 

ThromboGenics' first commercial drug JETREA^® is now approved globally in 54 countries and reimbursed in over 20 countries. Globally, over 20,000 patients have received a treatment with JETREA^®.

With that, ThromboGenics confirms its pioneering position in pharmacological vitreolysis as a new drug class.

Importantly, following the completion of a regulatory bridging study, Alcon is now also taking final steps before submitting JETREA^® for approval in Japan, the second largest pharmaceutical market in the world.

Further JETREA^® approvals and country launches are anticipated in 2016.

Ocriplasmin Research Findings Presented at ARVO  

New JETREA^® research findings were presented at the Association for Research in Vision and Ophthalmology (ARVO) 2016 annual meeting in Seattle at the beginning of May.

15 ocriplasmin-related presentations, abstracts and posters were delivered at ARVO. These covered preclinical research findings, real-world clinical data, and further characterization of results from different studies, including OASIS, ORBIT, and OVIID conducted in the US and Europe.

The data update confirmed the product's safety profile as described in the approved product label, without new safety signals. Moreover, new clinical studies and real-world data continued to confirm that appropriate patient selection leads to improved treatment outcomes.

Financial Update 

Cash and investments were €96.9 million as of the end of March 2016, compared with €101.4 million at the end of December 2015.

About ThromboGenics 

ThromboGenics is a biopharmaceutical company focused on developing innovative treatments for diabetic eye disease.

ThromboGenics' attractive pipeline of disease modifying drug candidates is targeting the key segments of the diabetic eye disease market.

ThromboGenics is conducting the CIRCLE study, a Phase II clinical trial to assess THR-409 (ocriplasmin) as a potential treatment to prevent the patients with non- proliferative diabetic retinopathy to progress to proliferative diabetic retinopathy.

THR-317, a PIGF inhibitor is being developed to treat diabetic macular edema, or as a combination therapy with anti-VEGF treatments, is expected to enter the clinic in 2016

In addition, the new pipeline includes THR-149, a plasma kallikrein inhibitor, which has resulted from research collaboration with Bicycle Therapeutics, and THR-687, an integrin antagonist, which was in-licensed from Galapagos.

ThromboGenics pioneered the new drug category of pharmacological vitreolysis with JETREA^® (ocriplasmin) which is now approved for the treatment of vitreomacular traction in over 50 countries worldwide. ThromboGenics is commercializing JETREA^® via its subsidiary ThromboGenics, Inc. in the US. Alcon, a division of Novartis, commercializes JETREA^® outside the United States.

ThromboGenics is headquartered in Leuven, Belgium, and is listed on the NYSE Euronext Brussels exchange under the symbol THR.

More information is available at http://www.thrombogenics.com

Important information about forward-looking statements 

Certain statements in this press release may be considered "forward-looking". Such forward-looking statements are based on current expectations, and, accordingly, entail and are influenced by various risks and uncertainties. The Company therefore cannot provide any assurance that such forward-looking statements will materialize and does not assume an obligation to update or revise any forward-looking statement, whether as a result of new information, future events or any other reason. Additional information concerning risks and uncertainties affecting the business and other factors that could cause actual results to differ materially from any forward-looking statement is contained in the Company's Annual Report. 

This press release does not constitute an offer or invitation for the sale or purchase of securities or assets of ThromboGenics in any jurisdiction.  No securities of ThromboGenics may be offered or sold within the United States without registration under the U.S. Securities Act of 1933, as amended, or in compliance with an exemption therefrom, and in accordance with any applicable U.S. state securities laws. 

For further information please contact:

ThromboGenics
Wouter Piepers,
Global Head of Corporate Communications & IR
+32-16-75-13-10 / +32-478-33-56-32
[email protected]

Citigate Dewe Rogerson
David Dible/Sylvie Berrebi
Tel: +44-20-7282-2867 
[email protected]
[email protected]

SOURCE ThromboGenics