Strike Pharma has developed a technology platform for binding targeted antibodies to nanoparticles, enabling selective delivery to specific cells. The technology can be used for a variety of combinations and treatment options across multiple disease areas. The company has chosen to focus on delivering RNA encapsulated in lipid nanoparticles (LNPs) to T cells, with the goal of reprogramming T cells into CAR-T inside the body for the treatment of autoimmune diseases or cancer.
Today's CAR-T: Complex and costly
CAR-T therapy is an advanced form of cell-based immunotherapy that has revolutionized cancer care by reprogramming the patient's T cells to identify and attack tumor cells. CAR-T has shown good efficacy in treating lymphoma, leukemia and multiple myeloma, among others, where a total of 7 treatments are approved as drugs, and it has recently been shown that it can also have dramatic effects in certain types of autoimmune disease. Despite this, its use is limited by a complex, expensive and time-consuming manufacturing process. The patient's T cells are extracted from the body, genetically modified in a laboratory to express tumor recognition receptors (CARs), cultured to increase in number, and then reintroduced into the patient.
The process also weakens the T cells, which means that patients must be pretreated with chemotherapy to knock out the existing immune system in order to get a good effect from the CAR-T treatment. This is an individual and advanced cell therapy that costs several million per patient, which limits its use.
Strike Pharma's binding technology paves the way for a new generation of CAR-T therapies – so-called in vivo CAR-T – where T cells are reprogrammed directly in the body. By delivering RNA via lipid nanoparticles to the T cells, the need for ex vivo modification is eliminated. This approach has the potential to provide a more cost-effective, scalable and accessible treatment.
Strike Pharma aims for in vivo CAR-T – the holy grail of pharmaceutical companies
In vivo CAR-T is considered the holy grail of cancer immunotherapy and is attracting even the largest pharmaceutical companies. A recent example is AstraZeneca's multi-billion-dollar acquisition of EsoBiotec, which gives them access to the Belgian company's virus-based in vivo cell therapy platform.
Strike Pharmas aims to develop an off-the-shelf product that is both easier to commercialize than current CAR-T therapies and is also not virus-based – unlike the majority of other in vivo CAR-T therapies under development. The company's product candidate STR3/19 consists of a T-cell-targeting antibody that binds to the CD3 receptor on T cells, as well as lipid nanoparticles containing RNA that directs T cells to CD19 on B cells.
According to Strike Pharma, they are the only company to have a binding technology, called affinity conjugation, that allows them to produce the nanoparticle and the antibody separately and then combine them when it is time to give the treatment to the patient. The company is now working on developing both in vitro and in vivo Proof-of-Concept to validate the platform technology. The next step is to establish research collaborations or licensing agreements to enable continued development.
Move to SmiLe incubator
Strike Pharma was founded in 2020 based on research by Professor Sara Mangsbo vid Uppsala UniversityNow the moving load is going to Lund as the company has been accepted to Smiles incubator program, which means several advantages for continued development. Among other things, the company gets access to a newly established lab, expertise and support functions in areas such as business development and financing, as well as a large network of knowledgeable key people and investors.
Per Norlén takes over the helm
The company's organization has also recently been strengthened by Per Norlen took office as CEO on February 1, followed by Magnus Persson as the new chairman of the board in May. Magnus, from Eir Ventures, brings broad knowledge in company development, exit strategy and investments in the life science sector, and Per brings solid experience and expertise in drug development, clinical studies and business development.
Per is a specialist in clinical pharmacology with an associate degree in experimental clinical pharmacology, and has 20 years of experience in clinical drug development – a background that makes him well-equipped for the CEO role at Strike Pharma. Over the past 15 years, Norlén has held leading positions in a number of biotechnology companies, including as CMO and later CEO of Alligator Bioscience, and CEO of companies that Targinta, Evaxion Biotech and WntResearch.
– Strike is in an early development phase, which allows me to benefit from my research background, while my experience in company management, business development and clinical development can create value both by clarifying the deal and by creating an effective development path, says Per.
Before taking up the position of CEO, Per acted as a medical consultant to Strike Pharma for their previous development projects in cancer immunotherapy. His representative Marten Winge only have positive things to say:
– I cannot think of a better successor. Strike Pharma is in very capable hands. It will be a real pleasure to follow the company's progress from the sidelines, says Marten.
BioStock contacted Per to learn more about his new role and the possibilities with the company's technology.
Per, what motivated you to accept the role of CEO of Strike Pharma?
– I see enormous potential in Strike Pharma's technology and its differentiation. The company is in an exciting phase where new research data shows that the platform can also be used to target nanoparticles. Previous development has focused on binding antigens, nucleotides and small molecule products to antibodies. With nanoparticles it becomes possible to change the payload without affecting the external structure, which of course increases scalability enormously. And in particular, it opens up new avenues in perhaps the hottest area in drug development today, so-called in vivo CAR-Ts.
Could you give an overall description of Strike Pharma's technology platform and what you are currently focusing on?
– Our technology makes it possible to bind nanoparticles to antibodies, which in turn allows us to control where the nanoparticles end up in the body. This makes it possible to target basically any treatment to basically any cell, by packaging the substance in a nanoparticle. Specifically, we focus on delivering RNA enclosed in lipid nanoparticles, LNPs, to T cells, with the goal of reprogramming them into CAR-T inside the body. This is called in vivo CAR-T and has been a dream for the pharmaceutical industry for the past decade. The RNA delivered to the T cells encodes a chimeric antigen receptor, CAR, which determines what the T cell attacks. It provides a tool to direct the immune system towards specific targets. CAR-T treatment is already established in blood cancer, but has recently also been shown to have striking effects in certain autoimmune diseases, which we believe is a huge market for in vivo CAR-T.
“We have a conjugation technology based on affinity binding, which allows us to produce LNPs and antibodies as separate entities and combine them at the time of treatment. This has the potential to solve many of the pharmaceutical challenges facing the field.”
You mention that the field is currently grappling with certain challenges. Develop!
– LNPs are spherical lipid structures that are difficult to achieve long-term stability if they are conjugated with antibodies, which is partly due to the fact that the thermodynamic properties change. It is questionable whether it is possible at all to create an LNP with pharmaceutically acceptable quality when conjugated with antibodies. Our technology makes it possible to attach the antibody afterwards, and thus we get around the stability problems by manufacturing and storing LNPs and antibodies separately.
What are the biggest potential advantages of in vivo CAR-T therapy compared to today's CAR-T?
– How about cheaper, faster, safer and better? Today's CAR-T treatment is an advanced individual cell therapy that costs several million per treatment and takes several weeks to manufacture for each individual patient, and where the patient must be pretreated with aggressive chemotherapy to knock out large parts of the existing immune system, with the risks that this entails. In vivo CAR-T is an off-the-shelf treatment that is ready when the patient needs it, which does not need to be personalized, which is many times cheaper to manufacture, which can be titrated in dose and given as repeated treatment and does not require pretreatment with chemotherapy.
We have already seen major deals from AstraZeneca, Abbvie and Sanofi regarding in vivo CAR-T. What is your view of the interest in the area, and how does Strike Pharma's technology differ from other similar projects?
– The interest is enormous and the number of companies jumping into the field is increasing every day. However, the vast majority focus on virus-based platforms, which means that patients are exposed to potentially lifelong virus-mediated gene modification. This is hardly ideal or risk-free, and especially not if the treatment is to be broadened to patients with chronic autoimmune disease.
– We aim to develop a non-viral in vivo CAR-T treatment based on LNPs that, with the help of targeted antibodies, carry RNA to T cells, which leads to a relatively short-term reprogramming of the cells. It is also a treatment that can be repeated as needed, which is attractive in autoimmune diseases that often relapse. Therefore, interest in LNP-based solutions is increasing very quickly, but we are, to our knowledge, the only company that has developed a solution for the need to be able to switch on the antibodies afterwards, in connection with treatment.
Given the transactions in the field we were talking about, and your words about how Strike is holding up, when can we expect potential takers to signal interest?
– We are already seeing great interest and are receiving regular meeting requests from big pharma despite being in such an early development phase. I believe we need to build a larger data package than we have today before we can implement any major out-licensing deal, but I see good opportunities for research collaborations in the near future, perhaps as early as this year.
Could you tell us a little more about what your development plan looks like for an agreement or research collaboration?
– We have already shown that we can target LNP to specific cells, and that the RNA packaged in LNP is expressed and has an effect, but we need to generate more specific data on our development candidate STR3/19. It targets T cells using a CD3 antibody and delivers RNA encoding an anti-CD19 CAR. The goal is to reprogram T cells so that they attack CD19-expressing cells, in principle B cells, which is interesting in B-cell-dependent autoimmunity such as systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA), and in B-cell cancers such as lymphoma. Specifically, we need to show that our drug candidate provides effective reprogramming of T cells and effective elimination of B cells, which we expect to do in the coming year.
Strike Pharma has chosen to move its operations from Uppsala to Lund. What is behind this decision?
– The establishment of Strike Pharma at Smile Venture Hub in Lund gives us access to well-equipped laboratories and infrastructure and experts that are not normally available to smaller companies. In addition, we gain access to investor networks and, above all, proximity to a large number of other biotechnology companies with opportunities for synergies.
You have so far received financial backing from Flerie and Eir Ventures, but are now looking for more investors. Why do you want to broaden your investor base?
– We have a favorable situation with Eir and Flerie as the largest owners, and also great support from, among others, Monesi and AB Ility. Eir Ventures has also chosen to join the board as chairman with managing partner Magnus Persson, which shows their long-term commitment. However, the goal is to bring in another large specialist investor in order to be able to shift towards clinical development and commercialization over time. Our current ownership base is a huge strength. With the explosive development that is taking place around in vivo CAR-T today, the stakes will be raised and you could say that we are preparing for that.
Finally, what milestones do you want to achieve within the next two years?
– We aim to demonstrate preclinical proof of concept towards the end of 2025. Since a successful licensing deal normally requires a solid data package, we will invest heavily in expanding this and also in documenting advantages over, for example, competing technologies. In short, answering the questions an in-licensing partner may have, where our overall goal is to develop such a package and to enter into a larger partnership within 2 years.
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.