Notoriously difficult to treat cancer
Glioblastoma is the most common form of primary intracranial brain tumor, where the effect of current treatments has been limited, among other things, by the fact that glioblastoma tumor cells can differ greatly, not only between different patients but also within the same tumor. This is because the tumor can arise from different types of brain cells, either immature neural stem cells or more developed so-called glial cells. Not only is the disease basically resistant to today's standard treatments, the tumor cells are also difficult to remove through surgery without damaging the brain. At the same time, the protective blood-brain barrier, which is supposed to prevent toxic substances from entering the brain, also prevents drugs from passing through and attacking the tumor.
Lunda Company Xintela has discovered that cells in tumor tissue express the company's marker on the cell surface, and studies are now underway both in vitro and in vivo, to evaluate these targeting antibodies with the aim of slowing tumor growth. In January of this year, Xintela announced that it had been able to establish that the company's antibody binds to tumor cells and has a killing effect on both glioblastoma cells from patients' tumors and in an animal model of glioblastoma. Xintela plans to apply for orphan drug status for its ADC therapy, which could provide market exclusivity for ten years from market approval. If granted, the project will also become even more attractive to a partner or project beneficiary with greater financial muscle - something that is often a prerequisite for a smaller company to succeed in going all the way to market, especially in such a recognized difficult-to-treat disease indication. Xintela has communicated that it is working to identify a suitable industrial partner, preferably a larger pharmaceutical company.
Antibody-based treatments on the rise
Antibodies have the advantage of being able to very specifically find and bind to cancer cells and have a targeted effect there. In short, they attack only the tumor and spare the surrounding, healthy cells. This also explains why antibody-based treatments are showing such a strong development curve in the pharmaceutical industry today.
Currently, there are only a few approved drugs for the treatment of glioblastoma. These are usually used in various combinations with each other, but unfortunately, at best, they achieve a median survival of only 15 months. There is therefore a great need to find new and even more effective drugs that can improve the conditions for glioblastoma patients, and great hope is placed in antibody-based drugs – either in the form of immunotherapy or in the form of ADCs, i.e. antibodies that attack the cancer with precision, which is the concept that Xintela is working with.
The concept is based on XINMARK technology
Xintela's treatment concept is based on the company's proprietary XINMARK Technology, which makes it possible to detect certain tumor cells and target the treatment to those cells to slow the growth of the tumor. In its previous preclinical studies, Xintela has seen promising study results showing that the targeting antibodies have a cell-killing effect on glioblastoma cells. It has also identified a suitable antibody and produced a so-called Antibody-Drug Conjugate (ADC), where a cytotoxic agent is linked to the antibody which then binds to the tumor cells and delivers the cytotoxic agent directly to the tumor.
The concept is based on Xintela's cell surface markers, specific proteins that sit as recognition flags on the surface of certain cells, and which make it possible to detect certain specific tumor cells so that treatment can be directed to those cells to slow down the growth of the tumor.
By developing therapeutic antibodies that bind to cancer cells, Xintela's goal is to treat cancer in a more direct and effective way than current treatments, thereby prolonging patient survival. The company's treatment method could be used as a standalone treatment, but could also potentially complement available treatment.
Great growth potential in the most important markets
Sales of drugs for the treatment of glioblastoma are expected to grow significantly over the next eight years, according to a report from Global Data. According to the analysis company, a fivefold increase in the value of the seven largest markets by 2024 is entirely possible, which would correspond to almost SEK 30 billion. A new and more effective treatment that extends the average survival of glioblastoma patients, if only by a few months, would have very large market potential. According to Xintela, there is also the possibility that the company's technology could be used for new cancer indications in addition to glioblastoma in the future.
Xintela's marker plays a central role in ovarian cancer
Some time ago, an American research group published a scientific article on cancer research related to ovarian cancer. The article has identified Xintela's marker, integrin α10β1, as a central player in the growth of tumors in the ovaries. Although glioblastoma is Xintela's focus area, it is of course very interesting that a study has been able to confirm the importance of Xintela's marker also in another cancer indication, which indicates that the possibility exists to use the target molecule against several types of cancer.
– Our focus area is glioblastoma, but it is of course interesting that another research group identifies our marker integrin α10β1 as a central player in another cancer indication. We see these results as supporting Xintela's focus on using integrin α10β1 as a target molecule in the treatment of cancer, said Evy Lundgren-Åkerlund in a comment on the American research findings, when they were presented in July last year.
Competitors back to square one
Despite some progress, current treatment for glioblastoma remains palliative, i.e. only relieving symptoms, and unfortunately not curative. Only modest improvements in survival have been achieved in newly diagnosed patients when treated with the latest chemotherapy agents. bevacizumab, nimotuzumab and temozolomide, and treatment options for recurrent, or so-called relapsing, disease are still very limited.
At the beginning of April this year, the pharmaceutical giant was able to Bristol-Myers Squibb disappointed found that the primary endpoint of improved overall survival compared to RocheAvastin (bevacizumab) with its drug candidate Wonderful (nivolumab) against glioblastoma in the phase III study CheckMate-143. With Opdivo now also not being shown to prolong survival in glioblastoma patients, these patients are still without effective treatment options. Bristol-Myers Squibb does have two remaining studies evaluating Opdivo in glioblastoma, but it is becoming increasingly clear that new mechanisms are required to treat the disease – a need that Xintela has the potential to satisfy with its integrin-targeted ADC product.
Earlier this year, another disappointment came when the Lexington-based pharmaceutical company Agenus was forced to pull the handbrake on its phase II combination study with the cancer vaccine Prophage and Avastin. The decision was made after there was no encouraging evidence that the combination performed better than Avastin alone in prolonging survival in glioblastoma patients. Prophage is a cancer vaccine, and the study results were an example of something that is not entirely unusual for cancer vaccines, namely, on the one hand, proven safety but on the other hand, too weak an effect to have any significant impact on the disease. The tumor cells' natural defenses simply make it too difficult for the immune system to eliminate them.
Agenus' negative news came just a few weeks after Incyte decided to invest in Agenus' discovery platform for antibody drugs by signing an agreement with $60 million upfront and up to $350 million in milestone payments. With the conclusion of the clinical trial with Prophage, another door was opened for the vulnerable patient group suffering from glioblastoma.
This failure also clearly demonstrates the dire need for innovative thinking and new mechanisms of action to treat glioblastoma. The great need is of course another incentive for Xintela, which has communicated that it is now focusing on identifying a suitable development partner for its cancer project with a unique ADC candidate.
Professor of Neurosurgery places Xintela's glioblastoma concept "at the absolute forefront"
The American neurosurgeon professor Marcus Keep who has both collaborated with and invested in Xintela believes that the company has a good chance of obtaining orphan drug status for the drug candidate, which he describes as “a precision-guided missile that only hits the intended target, the tumor cells.” Earlier this spring, BioStock did a Skype interview with Professor Keep, which can be seen below, where he describes the development as now moving towards a completely new horizon for the treatment of glioblastoma, a development in which Xintela is far ahead.
Click below to watch the interview with Professor Marcus Keep.
The content of Biostock's news and analysis is independent, but Biostock's operations are to some extent financed by companies in the industry. This post refers to a company from which BioStock has received funding.
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