Danish Curasight recently announced the expansion of its clinical portfolio, pursuing the diagnostics and treatment of neuroendocrine tumours (NETs), a rare form of cancer with limited treatment options for late-stage patients. BioStock has taken a closer look at the current NET treatment landscape to shed some light on the possibilities this areas holds.
Danish biotech Curasight’s technology revolves around the uPAR receptor, a known biomarker for cancer aggressiveness. Binding to the uPAR protein, the targeting peptide AE105 is “armed” with either Gallium to create the tracer substance uTRACE or with Lutetium to create the short-range radiation therapy uTREAT. The company has presented positive phase II results in several cancer indications regarding uTRACE, most recently in neuroendocrine tumours (NET). The results led to the inclusion of NET as a focus indication in Curasight’s strategy going forward.
Affects the release of hormones
So, let’s take a look at what the current NET treatment landscape looks like. NETs are tumours originating from the neuroendocrine system, which plays an important part in the releasing of hormones into the body. In the US and the EU, more than 400 000 patients are living with neuroendocrine cancer and each year approximately 35 000 new cases are diagnosed. The tumours are formed in the gastrointestinal tract or in the lungs and are most commonly found in the small intestine. Some NETs show rapid growth and causes an overproduction of hormones, whereas others grow slowly, barely causing any symptoms at all.
Poor prognosis for metastasised NET
Treatment of NETs depends on a range of factors, such as where the tumour originates, if the tumour is functional or not, what stage it is in, and the pace of growth. For some patients, active surveillance is enough, where you simply follow the progress using for example blood tests or MRI scans. If the cancer has not spread the tumour can often be removed by surgery. So far, the outlook for a NET patient is fairly good, but when the disease progresses and spreads it becomes dangerous. NET patients with distant metastases have a five-year survival probability of around 35 per cent.
The global market for NET treatments is expected to reach approximately 3.3 billion USD by 2025. There are currently a number of different treatment options for inoperable NET, where the aim is to reduce symptoms and to inhibit the cancer cells from growing. The most commonly used form of treatment are somatostatin analogues. Somatostatin is a hormone that the body produces to control the production of a number of other hormones, like insulin and glucagon. It also controls the emptying of the stomach and bowel. Making up more than 50 per cent of the total NET treatment market, somatostatin analogues helps the body to stop the hormone overproduction associated with NET, thus limiting disease symptoms.
Radionuclide therapy recently entered the scene
Like in so many other cancer indications, chemotherapy, immunotherapy, and radiotherapy is also part of the current treatment regime. One recent entry into the NET treatment market, which is highly relevant for Curasight, was the introduction of Novartis‘ Lutathera in 2018. Novartis had then recently added the drug to its pipeline via its 3.9 billion USD acquisition of Advanced Accelerator Application. Lutathera has a mode of action similar to that of Curasight’s uTREAT candidate, where Lutetium is combined with a binding peptide that targets the somatostatin receptor in gastroenteropancreatic neuroendocrine tumours (GEP-NETs).
Adding Lutathera to standard-of-care has been shown to reduce the risk of disease progression or death of 79 per cent compared to using only standard treatment. Last year the drug was used in a total of 450 medical centres, mainly in the US and EU, and sold for approximately 475 MUSD.
Novartis portfolio also consists of a series of Gallium based tracing ligands for a number of indications in oncology, neurology, cardiology and infectious and inflammatory diseases.
New treatment innovation paves way for Curasight
Novartis’ success with Lutathera and its radiopharmaceutical diagnostics products paves the way for Curasight’s entry into NET with uTRACE and uTREAT. Targeting the uPAR protein, the company aims to provide a more generally applicable treatment option and so far, the results have been promising. In a recently concluded phase II trial with uTRACE in patients of all different tumour grades, 68 per cent of the patients, and 75 per cent of the high-grade (G3/NEC) patients, showed uPAR expressing lesions.
According to the company, the results not only demonstrated that uTRACE may be valuable for planning of therapy and follow-up, but since uPAR was demonstrated in the majority of patients it also constitutes clinical support for Curasight to pursue uPAR-targeted radionuclide therapy in these patients.
Comparing Lutathera to uTREAT, it should be noted that although some of neuroendocrine tumors patients today are treated with somatostatin-receptor targeted radionuclide therapy, not all of these patients are eligible for this treatment due to low or no expression of somatostatin receptors. These, in particular tumours of high grade, could potentially be served by uPAR-targeted radionuclide therapy in the future.
Backed by the above results, Curasight has chosen to advance uTRACE further through the clinical pipeline for NET. The next step will be a phase III study on NET patients with the aim of getting an FDA approval by 2026.
Curasight will also pursue the development of uTREAT for NET and plans initiation of a preclinical study in Q3 2022. However, the priority indication for uTREAT has been and continues to be brain cancer with the completion of the preclinical study expected in Q3 2022.The content of BioStock’s news and analyses is independent but the work of BioStock is to a certain degree financed by life science companies. The above article concerns a company from which BioStock has received financing.