Glioblastoma (GBM) is a rare disease with a devastating impact, affecting approximately 3-4 per 100,000 adults yearly. It stands as the deadliest brain tumour among adults, with a median overall survival of around 15 months and a mere 5-year survival rate of 6.8%. The poor response to the Standard of Care (SoC) for GBM contributes to this outcome. SoC typically involves maximal safe surgical resection, followed by concurrent radio- and chemotherapy (temozolomide [TMZ]), along with adjuvant TMZ cycles every six months. Unfortunately, due to the delicate position and invasiveness nature of this tumour, complete resection is not possible for most patients forcing the neurosurgeon to leave a safety margin that is not fully removed. Also, there is an overlooked time window between surgery and radio- and chemotherapy that leads to exceptionally high recurrence rates, especially local recurrences that occur within 1-2 cm from primary tumour.
To tackle such an unforgiving disease, TargTex has developed NANO-PL, a new therapeutic approach that leverages piperlongumine (PL) submitted to a nanosizing process and loaded into a hydrogel matrix. This technology allows for enhanced bioavailability and a superior diffusion profile. NANO-PL (1) bypasses the BBB as it is applied locally (during resection surgery); (2) acts on an underexplored time window between surgery and initial radiation and chemotherapy; (3) has a broad biomarker coverage capable of tackling the heterogeneity of GBM, and (4) has an outstanding diffusion profile, attacking infiltrating tumour cells, which is one of the key differentiating points from other local application solutions. Gliadel, for instance, in addition to severe and frequent adverse events, has limited diffusion and therefore offer little protection against recurrence. NANO-PL’s preclinical in vivo tests showed tumor eradication with one single administration and it was also found to be equipotent to GBM stem cells and tumours previously reported to be TMZ resistant. NANO-PL has reached a unique position where the technology demonstrated maturity level to start a global clinical trial study. The next steps require substantial financial support to ultimately bring to the market a transformative solution with the potential to finally give GBM patients a chance at living longer.
Nonetheless, bringing a new drug to the market to treat such a merciless disease, is a high-risk endeavour. Many have tried at an extremely high cost, and, while some offer incremental improvements over the SoC, none of them is an actual cure. This scarce success track is the result of many obstacles that must be overcome. First, as with any new drug, NANO-PL must demonstrate in a clinical trial that the robust pre-clinical results showing safety and efficacy translate to humans. Second, regulatory bodies (such as EMA and FDA) impose stringent criteria for clinical trial authorization. Third, despite the dire need for novel therapies, the medical community sometimes shows inertia in trying and adopting new solutions which could delay the acceptance of NANO-PL, even ones that potentially can be added to the SoC without any additional step to the current procedures.
TargTex has implemented a set of targeted actions to address each of these barriers, including maintaining ongoing dialogue with regulatory authorities to ensure that final preclinical studies are aligned with both EMA and FDA expectations. In parallel, the company has strengthened its advisory board with leading experts in the GBM field, who are highly engaged and supportive of advancing a potentially breakthrough therapy. Several leading clinical sites have already been secured to participate in the NANO-PL Phase 1/2a trial. With trial initiation, TargTex will further strengthen its market positioning while activating a broad and well-established network of partners, including manufacturing collaborators, CROs, clinical sites, KOLs and the GBM patient advocacy organizations. The implementation of the clinical trial is, nonetheless, a demanding enterprise and financial support will play a key role in securing the required resources for a young biotech company such as TargTex.
The conclusion of nPL4GBM project will grant clinical information of the product and, hopefully, bring hope to these patients that suffer from this dreadful brain tumour around the world.
