“We highly appreciate the support of the Dutch government for our innovative work in brain- drug delivery,” says Willem van Weperen, CEO of to-BBB. “Our brain cancer lead program will address the high medical need of patients with brain cancer, while also establishing our brain delivery platform in humans.”

Brain cancer affects up to 400,000 patients annually in Europe and the United States together . Treatment options for this devastating disease are limited and overall prognoses are poor. The neuroprotective blood-brain barrier (BBB) is limiting the delivery of many anti-cancer drugs to tumors in the brain, especially to micrometastases and invasively growing tumor sprouts.

Based on its proprietary G-Technology®, to-BBB is developing its lead compound 2B3-101, brain- targeted doxorubicin liposomes. These liposomes are coated with the tripeptide glutathione at the tips of polyethylene glycol (PEG) to safely enhance the delivery of free drug to the brain. 2B3-101 has shown reduction of brain tumor growth in proof-of-concept studies at the Netherlands Cancer Institute. Clinical scale batches of 2B3-101 have been produced by to-BBB’s manufacturing partner TTY Biopharm and pivotal preclinical safety studies were finished in 2010. The Phase I/II clinical trial will start in a few months at 3 academic hospitals in the Netherlands led by neuro-oncology experts of the Antoni van Leeuwenhoek hospital (AVL-NKI). The study will establish a safe therapeutic dosage and collect the preliminary evidence of activity in a specific group of women with brain metastases of breast cancer. The clinical development plan for this product was fine-tuned in scientific advice meetings with European regulatory authorities by to-BBB’s clinical development team.

The “Innovation Credit” of Agentschap NL consists of an initial investment of €1.2 million to support the planned Phase I/II study. The company has the option to apply for an additional credit for a pivotal second clinical study.

About to-BBB

to-BBB is a private biotechnology company focusing on enhanced drug delivery across the blood- brain barrier. The Company is developing novel treatments for devastating brain disorders, such as brain cancer, neurodegenerative diseases and lysosomal storage diseases, by combining existing drugs with the G-Technology®, to-BBB’s proprietary brain delivery platform. This technology combines the widely used drug delivery approach of pegylated liposomes with the endogenous tripeptide glutathione as targeting ligand in a novel and safe way. Together with several top tier pharma and biotech companies, to-BBB is investigating the versatility of the G-Technology® for drugs that are unable to reach the brain within a tolerable therapeutic window. to-BBB is applying the G-Technology® for the delivery of doxorubicin for the treatment of brain cancer as its internal lead product 2B3-101.

to-BBB is headquartered in The Netherlands at the Leiden Bio Science Park and established a fully owned subsidiary, to-BBB Taiwan Ltd., in Taipei, Taiwan. Investors in to-BBB include Aescap Venture, Antea Participaties, Jonghoud International and the Industrial Bank of Taiwan Management Corporation (IBTM).

About Agentschap NL and the Innovation Credit Scheme

Agenstchap.nl (www.agentschapnl.nl) is an agency of the Dutch Ministry of Economic Affairs, Agriculture and Innovation that promotes sustainable development and innovation with various financial instruments. The Innovation Credit (Innovatiekrediet) scheme is aimed at supporting high risk, and commercially attractive development projects with an interest-bearing loan of which repayment is waived if the project fails.