Publication date: 08/09/2017
ThromboGenics NV (Euronext Brussels: THR), a biotechnology company developing novel medicines for diabetic eye disease, today issues a business update for the six month period ending 30 June, 2017.
ThromboGenics is developing an industry-leading pipeline of disease modifying drug candidates for diabetic eye disease, particularly diabetic retinopathy (DR) and diabetic macular edema (DME).
The clinical pipeline consists of THR-409 and THR-317, both from the Company's in-house research. The Company's pre-clinical candidates are THR-687, which was in-licensed from Galapagos NV in March 2016 and THR-149, which resulted from a research collaboration with Bicycle Therapeutics.
These products all have different modes of action and will allow the Company to address the four key segments of the rapidly growing diabetic eye disease market:
Dr. Patrik De Haes, ThromboGenics CEO, said:
"ThromboGenics' pipeline, both clinical and pre-clinical, which is targeting the key segments of the diabetic eye disease market, is progressing well. With first results from our Phase II clinical study for THR-317 in the treatment of Diabetic Macular Edema expected in Q1 2018, and our pre-clinical products candidates poised to enter the clinic, we are well positioned to deliver multiple milestones over the next 12 months that could create significant value for our shareholders."
Progressing Preclinical and Clinical Development of Treatments for Diabetic Eye Disease
Diabetic retinopathy (DR) is the leading cause of visual disability and blindness among professionally active adults. More than one in three living with diabetes (35.4%) will develop some form of DR in their lifetime. One in five patients with DR presents with sight threatening diabetic macular edema (DME).
ThromboGenics pipeline comprises of:
THR-317 - anti-PlGF antibody to treat DME
ThromboGenics enrolled the first patients in a Phase II, single-masked, multicenter exploratory study evaluating the safety and efficacy of two dose levels of THR-317 for the treatment of diabetic macular edema (DME) in January 2017.
THR-317 (anti-PlGF) is a recombinant human monoclonal antibody directed against the receptor-binding site of human placental growth factor (PlGF).
The Phase II study will evaluate the safety of three intravitreal injections of two dose levels of THR-317 (4 mg or 8 mg). The trial will also assess THR-317's ability to improve best-corrected visual acuity (BCVA) and to reduce central retinal thickness in subjects with DME.
The study plans to enroll a total of 50 patients (including 10 anti-VEGF treatment resistant patients) over a period of about 12 months. The first results from the study are expected in Q1 2018.
ThromboGenics believes that THR-317 holds potential as a therapy for treatment of DME or DR, as a stand-alone therapy for patients who are not responding well to anti-VEGF, or as an add-on treatment with anti-VEGF medicines.
At the ARVO meeting's Diabetic Retinopathy session in May a presentation on THR-317, entitled "Neutralization of placental growth factor as a novel treatment option in diabetic retinopathy", took place. The study presented looked at the effects of PlGF inhibition on the hallmarks of DR and concluded that PlGF neutralization was equally efficacious compared to VEGF inhibition in terms of vascular leakage, but unlike VEGF inhibition, it also reduces inflammation and fibrosis, without triggering a neurodegenerative response.
In July 2017, ThromboGenics and BioInvent agreed to amend their long-standing agreement, which covers co-development of the novel anti-PlGF monoclonal antibody products, including THR-317 which ThromboGenics is developing for the treatment of DME. Under the amended arrangement, ThromboGenics gains full and exclusive ownership of THR-317 for development and commercialization in all non-oncology indications. ThromboGenics will continue to carry all costs for development of THR-317 in non-oncology indications, and BioInvent is entitled to five percent of the project's economic value. The definitive amended agreement will be put into place by Q3 2017.
THR-409 for Non Proliferative Diabetic Retinopathy - CIRCLE Study
The CIRCLE study is evaluating the ability of multiple doses of THR-409 (ocriplasmin) to induce a total PVD in patients with NPDR. The study is also assessing the safety of multiple doses of THR-409.
ThromboGenics aims to reduce the risk of disease progression to PDR by inducing a total PVD using THR-409. Research has suggested that total PVD, a complete separation of vitreous and retina, could prevent the progression of NPDR to PDR.
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 0.0625mg of THR-409 in subjects with moderate to severe NPDR, to induce total PVD in order to reduce the risk of the patient developing sight-threatening PDR.
In December the protocol of the CIRCLE study was amended to allow the trial to recruit from a broader pool of patients. Patient recruitment has picked up following this protocol amendment.
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.
Furthermore, 2 year follow up of patients may provide insights into THR-409's potential to reduce the risk of progressing from NPDR to PDR.
Further Supportive Ocriplasmin Clinical and Health Economics Data reported
ThromboGenics pioneered the pharmacological vitreolysis drug class through the development of JETREA® (ocriplasmin), the only pharmacological vitreolysis drug approved for the treatment of symptomatic vitreomacular adhesion and vitreomacular traction in over 54 countries globally. Since its first introduction in early 2013, over 27,000 patients have been treated with JETREA®.
ARVO 2017 Baltimore: Ocriplasmin data presentations underwrite continued interest
11 ocriplasmin-related presentations, abstracts and posters were delivered at ARVO (Association for Research in Vision and Ophthalmology) 2017 Annual Vision Research Meeting in Baltimore. These covered preclinical research findings, real-world clinical data, and further characterization of results from different studies, including OASIS and ORBIT and the cost effectiveness of ocriplasmin.
New Ocriplasmin clinical and health economic data were presented at ASRS 2017 meeting in Boston
At the 35th Annual Scientific Meeting of the American Society of Retina Specialists (ASRS) held in Boston, ThromboGenics delivered two poster presentations.
The first poster presentation was entitled "'Comparison of Visual Results in Patients Receiving Vitrectomy for Macular Hole in One Eye and Ocriplasmin for Vitreomacular Traction in the Fellow Eye' (by Arshad M. Khanani et al).
In his conclusion, Arshad M. Khanani MD, MA, Managing Partner and Director of Clinical Research, Sierra Eye Associates and Clinical Associate Professor, University of Nevada, Reno, commented: "Patients who underwent PPV for FTMH benefited from early ocriplasmin treatment in their other eye with VMT that had not progressed to a FTMH. By administering ocriplasmin to these patients we could potentially avoid development of FTMH in the VMT eye with ocriplasmin administration, thus avoiding a second PPV."
In the second poster presentation, entitled 'Budget Impact Analysis of Ocriplasmin for the Treatment of Vitreomacular Traction in the United States', Peter K. Kaiser, MD, Department of Ophthalmology, Cole Eye Institute, Cleveland Clinic, Cleveland, OH presented data from the OASIS randomized trial, a 2-year follow-up study evaluating ocriplasmin for the treatment of symptomatic VMA (VMT) including macular hole. He also presented a new budget impact model that was developed in accordance with the principles of good practice published by the International Society for Pharmacoeconomics and Outcomes Research.
Dr. Kaiser concluded that "The use of ocriplasmin injections for VMT may be affordable to US health plans, as its costs could be offset by an expected reduction in the number of PPVs and a reduction in overall complications. Future research on the cost-effectiveness of ocriplasmin in patients with VMT will be forthcoming to further determine the economic impact of ocriplasmin injections."
Growing pipeline with 5 unique next generation immuno-oncology assets
In August 2017, Oncurious reached principle agreement with VIB to acquire exclusive licences to a portfolio of five unique next generation immuno-oncology assets, based on seminal work originating from the VIB-KU Leuven labs of Massimiliano Mazzone and Gabriele Bergers, and from the VIB-VUB lab of Jo Van Ginderachter. With this acquisition, Oncurious broadens its ongoing clinical development activities in orphan pediatric oncology indications with preclinical research and drug development programs, resulting in an exciting pipeline of next-generation immuno-oncology drugs targeting a broad spectrum of cancers.
VIB Discovery Sciences will take the lead in the pre-clinical development of these new projects. As part of this agreement, VIB will increase its stake in Oncurious, with ThromboGenics remaining the majority shareholder. VIB will also receive a royalty on future sales of any of these assets. ThromboGenics invests an additional €2.1 million in Oncurious.
Clinical Update: TB-403 for Pediatric Brain Cancers
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.
In May 2016, a Phase I/IIa study was initiated with TB-403. The study, which is being conducted by Beat Childhood Cancer (formerly known as NMTRC), aims to recruit 27 patients with Relapsed or Refractory Medulloblastoma. Patient recruitment is on-going.
In January 2017, the European Commission confirmed orphan drug designation for TB-403 for medulloblastoma. The orphan designation allows a pharmaceutical company to benefit from incentives from the European Union to develop a medicine for a rare disease, such as reduced fees and protection from competition once the medicine is on the market.
TB-403 is being developed by Oncurious in conjunction with BioInvent International.
In July, ThromboGenics and BioInvent amended their long-standing monoclonal antibody development agreement. In the amended agreement, BioInvent assumes the project lead for the development of TB-403 in all oncology indications and will increase its share in the economic value of TB-403 from 40% to 50%. Both parties will continue to share equally the costs of developing TB-403 for oncology indications. The definitive amended agreement will be put into place by Q3 2017.
Financial & Corporate Update
In the first half of 2017, ThromboGenics generated total revenues of €2.7 million, including €1.9 million of product sales in the US and €0.8 million in royalty income based on ex-US sales of JETREA®. In the corresponding period in 2016, ThromboGenics reported a total income of €4 million.
During the first six months of 2017, the group reported a gross profit of €0.8 million.
ThromboGenics' R&D expenses for the first half of 2017 amounted to €10.5 million, compared to €12.0 million for the same period in 2016. The first half of 2017 figure included €1.6 million for amortization of intangible assets relating to the ocriplasmin Phase III program in the VMA/VMT indication, compared with €3.4 million in the same period in 2016.
In the first half of 2017, selling and marketing expenses amounted to €2.1 million compared with €2.2 million in H1 2016.
For the first half of 2017, ThromboGenics reported a net loss of €15.2 million, or €0.42 per share. This is on a par with the corresponding period in 2016 when the Company reported a net loss of €15.0 million or €0.42 per share.
As of June 30 2017, ThromboGenics had €65.1 million in cash and investments. This compares to €80.1 million as of December 31, 2016.
Corporate Update: Chairman and Board of Directors
Effective 15 June 2017, ThromboGenics' long-time non-executive director Mr. Thomas Clay was appointed Chairman of the Board of Directors. The appointment coincided with the retirement of Staf Van Reet, PhD (former Chairman of the Board) from ThromboGenics.
Thomas Clay is Vice-President of East Hill Management, a US-based investment company. He also serves as the Chairman and CEO of Golden Queen Mining Co., Ltd., and is a Director of the Clay Mathematics Institute.
Thomas Clay has been a non-executive Director of ThromboGenics NV since 2011. In that year, he replaced his father, Landon T. Clay, who led the first external investment in ThromboGenics back in 2001 when the Company was private.
Effective 8 September 2017, Luc Philips (Lugo BVBA) and Patricia Ceysens (Innov'Activ BVBA) retire from the Board of ThromboGenics nv.
ThromboGenics is a biopharmaceutical company focused on developing innovative treatments for diabetic eye disease. The company's pipeline of disease modifying drug candidates is targeting the key segments of the diabetic eye disease market.
ThromboGenics is currently enrolling patients in a Phase II clinical study evaluating THR- 317, a PlGF inhibitor that is being developed for the treatment of diabetic macular edema, as a stand-alone or as a combination therapy with anti-VEGF treatments.
ThromboGenics is also conducting a Phase IIa clinical trial evaluating multiple doses of THR-409 (ocriplasmin) to induce a total Posterior Vitreous Detachment in patients with Non-Proliferative Diabetic Retinopathy (NPDR).
In addition, 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, are in late stage pre-clinical development.
ThromboGenics pioneered a new drug category of pharmacological vitreolysis with JETREA® (ocriplasmin) which is now approved for the treatment of vitreomacular traction in 54 countries worldwide. ThromboGenics is commercializing JETREA® via its subsidiary ThromboGenics, Inc. in the US. 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 www.thrombogenics.com