Elicera on AstraZeneca’s acquisition of Neogene Therapeutics
Interest in cell therapies is on the rise, which is noticeable both in research and the huge deals that have been made in the field in recent years. One of the latest proofs of this is AstraZeneca’s acquisition of Neogene Therapeutics, which develops T-cell receptor therapies. BioStock contacted the Swedish cell and gene therapy company Elicera Therapeutics, who commented on the importance of the acquisition for the cell and gene therapy field.
Cell therapy is an emerging field in the treatment of cancer. With this therapy, the patient’s immune system is modulated to attack the tumour more specifically by using cells – either the patient’s own or donated ones. Unlike conventional drugs, cell therapies are mostly individualised. They are considered to have the potential to fill a great need that today’s cancer drugs fail to achieve.
Increasing interest in cell therapy
Lately, it has become clear that the area is attracting interest. Research in cell therapy has increased in recent years, as has the focus of the global pharmaceutical giants. Several have chosen to acquire smaller biotech companies active in cell therapy, which signals the companies’ belief in this treatment form. Some examples of this are Gilead’s acquisition of Kite Pharma for USD 11.9 billion in 2017 and Celgene’s choice to acquire Juno Therapeutics for USD 9 billion in 2018. Sanofi’s acquisition of Kymab in 2021 involved an upfront payment of approximately USD 1.1 billion with up to an additional 350 MUSD upon achievement of milestones.
Perhaps the most recent example is the transaction between AstraZeneca and the cell therapy company Neogene Therapeutics, which meant that the pharmaceutical giant recently acquired all shares in Neogene in a deal worth up to a total of 320 million USD. Neogenes’ focus is on T-cell receptor (TCR-T) therapies for the treatment of cancer.
TCR and CAR-T in cancer treatment
But what is this kind of cell therapy really? First, a brief explanation of our bodies’ defence against cancer is required. Our immune system plays a fundamental role in eliminating tumour cells. This includes the T-cells, a type of white blood cell, which are particularly important attackers.
However – as is widely known – too often, the immune system is not sufficient to successfully fight the tumour or tumours, which is reflected in the high mortality rate in many cancer forms. That is why great resources have been put into researching the modification of the important T-cells, with the aim of strengthening their attack on the cancer cells. The technique involves extracting T-cells from the patient, then genetically modifying them in a laboratory so that they express receptors that can recognise and bind to specific cancer cells. Finally, the enhanced T-cells are returned to the patient by infusion in the hospital. This can provide a tumour specificity that the T-cells are otherwise lacking. The two most common receptor types used are the T-cell receptor and chimeric antigen receptors (CARs).
TCR therapies and CAR T-cell therapy are considered to have great potential to revolutionise cancer care. CAR T cell therapy alone is estimated to reach a global market value of USD 25 billion by 2028. Read more about CAR T-based therapy here.
Elicera at the forefront with technology to weaponize CAR/TCR therapies
If we take a closer look at CAR T-cell therapy in Sweden, we see that the only R&D company in the country that develops and evaluates this type of cell therapy is Elicera Therapeutics. The biotech has a total of four drug candidates in the pipeline, two of which are CAR T-cell therapies: ELC-301 for the treatment of Non-Hodgkin’s B-cell lymphoma, and ELC-401 for the treatment of solid tumours, initially against glioblastoma (brain tumour).
An important asset for the company is the proprietary and commercially available platform technology – iTANK (immunotherapies Activated with NAP for efficient Killing) – which arms the CAR T-cells with immune-activating properties to optimise their effect. iTANK, which is applied to both CAR-T candidates, was developed to address two of the biggest challenges facing CAR T-cell therapies in the treatment of solid tumours: tumour antigen heterogeneity and a hostile tumour microenvironment.
At the end of January, Elicera announced that it had submitted a clinical trial application (CTA) to relevant Swedish authorities to start a phase I/II study for the evaluation of ELC-301 in difficult-to-treat and/or metastatic B-cell lymphoma. The study is intended to investigate tolerance, toxicity, biological effects and anti-tumour response, and constitutes a major milestone for the company’s CAR T programme. It will be the first time for one of the company’s CAR T-cell therapies, as well as its iTANK platform technology, to be tested in the clinic. The study is fully financed from the previously received grant from the European Innovation Council (EIC) and Vinnova in combination with existing cash. Read more about this here.
Elicera’s CEO comments
BioStock reached out to Jamal El-Mosleh, CEO of Elicera Therapeutics, to get his comments on the rising interest in cell-based therapies.
Jamal, in recent years we have seen a number of acquisitions of smaller biotech companies active in cell therapies, the latest made by AstraZeneca. What would you say is the reason for the great interest?
– The reason for the great interest is that there are still major challenges for TCR and CAR T-cells in the treatment of solid tumours, and that in a sense it is easier for the large pharmaceutical companies to acquire technologies/therapies than developing them themselves from scratch. The two main challenges that TCR and CAR T-cell therapies are facing in the treatment of solid tumours are the heterogeneous expression of TCR/CAR target antigens, and local immunosuppression that makes it difficult for these therapies to reach and kill cancer cells. This acquisition is another example of the increasing number of deals we are seeing between Big Pharma and smaller specialised companies.
If you look outside Sweden’s borders, there are a number of biotech companies developing CAR T-cell treatments. What would you say separates Elicera’s candidates from the others?
– Elicera’s candidates are armed with the company’s commercially available iTANK platform that is universally compatible with CAR/TCR T-cell therapies for a broad targeted and parallel attack on solid cancer. Many CAR/TCR T-cell therapies in development lack this type of arming and thus cannot trigger a parallel immune response against cancer.
– More specifically, the iTANK platform is used to incorporate a transgene into TCR and CAR T-cells that encodes a neutrophil-activating protein (NAP) from the bacterium Helicobacter pylori. Upon activation, NAP, which is secreted from the CAR (NAP) T-cells, has been shown to enhance CAR T-cell function and, above all, activate a parallel immune response against cancer via CD8+ killer T-cells. This is expected to lead to a broad attack against most antigen targets on the cancer cells. The iTANK platform is also independent of tumour types and target antigens, so it can be applied to Elicera’s own CAR T-cell therapies, as well as other TCR and CAR T-cell therapies under development.
What are the biggest challenges in the development of CAR T cells?
– CAR/TCR T-cell therapies have curative potential but also face several challenges that can be categorised into three groups: 1) effect challenges, 2) logistical/production challenges, and 3) safety challenges. At Elicera, you can say that through the iTANK technology, we focus on solving the challenges in category 1. As I mentioned above, within this category, there are two main challenges that TCR and CAR T-cell therapies face in the treatment of solid tumours.
– The first is the heterogeneous expression of CAR/TCR target antigens, which increases the risk that some tumour cells are not attacked and instead form CAR/TCR T-cell-resistant tumours. The other is an immunosuppressive microenvironment in the tumour which both exhausts the CAR/TCR T-cells and makes it more difficult for them to infiltrate the tumour (thereby inhibiting their potential to kill cancer cells). At Elicera, we believe that improvement of CAR/TCR T-cell therapy can be achieved using the iTANK platform, which solves the problem of antigenic heterogeneity and reduces immunosuppression within solid tumours.
At the end of January, you announced submitting a CTA for the start of a phase I/II clinical study with ELC-301 in difficult-to-treat and/or metastatic B-cell lymphoma. In what way does the candidate have the potential to improve the treatment of this disease?
– Today, B-cell lymphoma is mainly treated with chemotherapy in combination with an anti-CD20 antibody called Rituximab. Over 50 per cent get rid of their tumours completely, but between 20-50 percent of these patients stop responding to standard-of-care, or relapse after a complete response. In addition, only about 40 per cent of patients with B-cell lymphoma treated with CD19 CAR T-cell therapies achieve a sustained complete response. 30 per cent of patients are resistant to CD19 CAR T-cell therapies, and 20 per cent relapse after CAR T-cell therapy. Thus, Elicera’s iTANK-enhanced CD20-based CAR T-cell therapy, ELC-301, has the potential to more than double the number of B-cell lymphoma patients who achieve complete sustained tumour responses.
Finally, given AstraZeneca’s recent acquisition in the field, does Elicera see opportunities for out-licensing its own candidates or what does the strategy look like for further development?
– Elicera’s strategy is based on entering into collaboration and license agreements for the iTANK platform. The platform, which can be applied to – and whose patents in addition to CAR T-cells – also cover TCR therapy, means a broad market for potential collaboration and licensing partners because we can target both CAR T and TCR companies. We at Elicera, therefore, see opportunities to collaborate with TCR companies that experience the same development challenges as CAR T companies.
– As part of the continued work, Elicera has hired LifeSci Partners, who will assist us in gearing up our business development efforts and intensifying discussions with potential partners. LifeSci Partners is a leading life science strategy and transaction advisor with global reach and very broad experience from oncology transactions, and we look forward to our collaboration.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.