Cartherics Pty Ltd, a pioneering biotechnology firm headquartered in Melbourne, is making significant strides in cancer treatment under the expert leadership of Prof. Alan Trounson, a world-renowned stem cell biologist and IVF pioneer. The company is at the forefront of developing innovative cell-based immunotherapies, concentrating its efforts on a robust portfolio of CAR-T (Chimeric Antigen Receptor T-cell) and CAR-NK (Natural Killer) cell products. Utilizing a groundbreaking allogeneic (off-the-shelf) cell platform, Cartherics employs induced pluripotent stem cells (iPSCs) derived from donated umbilical cord blood. This unique approach allows for the differentiation of these iPSCs into various immune system cells, including NK cells and T cells. The flagship product, CTH-401, represents an investigational allogeneic iPSC-derived CAR NK cell therapy specifically designed to target solid tumors. Following a fruitful pre-investigational new drug (pre-IND) meeting with the U.S. Food and Drug Administration (FDA), CTH-401 is poised to enter clinical trials for ovarian cancer in 2025. If the preliminary clinical data proves promising, CTH-401 will progress to a basket trial aimed at other carcinoma types expressing TAG-72. Prof. Alan Trounson, the CEO of Cartherics, shares insights into the transformative potential of iPSCs for CAR-T therapies, the evolving landscape of immunotherapies, and the future of cell and gene therapy (CGT) within the Asia-Pacific (APAC) region.
Could you explain more about the advantages of using iPSCs from cord blood for creating your ‘off-the-shelf’ CAR-NK and CAR-T therapies?
Umbilical cord blood is a rich source of pristine blood cells that exhibit minimal spontaneous or induced mutations, thus enhancing genetic reliability. These cells can be carefully selected for homozygosity at the HLA locus, key for ensuring transplant compatibility and immunological efficacy. iPSCs derived from such cord blood can be cultivated indefinitely and have the potential to differentiate into any cell type within the human body. The gene-editing capability of these iPSCs allows for precise modifications, ensuring therapeutic products are devoid of potential oncogenic inducers. Importantly, they are generated as exact clones, akin to a pharmaceutical product’s consistency. This level of precision is uniquely attainable through pluripotent stem cells. The process of directing gene-edited iPSCs into functional CAR-T and CAR-NK products employs a proprietary methodology and a sophisticated manufacturing process. As a result, CAR-NK cells can be utilized as a ready-to-use allogeneic therapy, while CAR-T cells necessitate further modifications for allogeneic application.
Your lead product, CTH-401, targets TAG-72, a well-validated tumour marker. What makes TAG-72 a particularly compelling target for CAR-NK therapy, and how does CTH-401 differentiate itself from other therapies targeting similar markers?
TAG-72 is a highly recognized pan-adenocarcinoma marker prominently expressed on the surfaces of cancers originating from internal organs. Its expression is restricted in adult tissues, primarily localized to the secretory uterine endometrium, with transient presence during embryonic development. Significantly, TAG-72 is found in upwards of 90 percent of ovarian cancer cases and is prevalent in many adenocarcinomas including those affecting the pancreas, stomach, liver, and kidney. The uniqueness of CTH-401 lies in its classification as the only natural killer (NK) cell product currently under development that integrates a CAR targeting TAG-72. It is clonally derived and subjected to DNA deep sequencing to assure safety, specifically mitigating risks associated with secondary cancers and undesirable genetic mutations. Notably, we have also knocked out two genes that inhibit immune cell cytotoxicity, particularly in solid tumors. This distinctive feature set of CTH-401 augments its therapeutic potential, offering a highly targeted and efficacious treatment avenue for patients grappling with solid tumors.
Are there any strategic partnerships or collaborations that have been crucial to Cartherics’ advancements? How do you see these partnerships evolving as the company grows?
Cartherics actively collaborates with leading universities and medical research institutions to harness federal and state grants aimed at product development. Additionally, strategic collaborations with companies like ToolGen Inc. in Korea grant access to cutting-edge gene editing and gene knockout technologies that are pivotal to our research. Cartherics has also extended rights to certain products to Shunxi Holdings in Greater China, where both Shunxi and ToolGen maintain stakes in Cartherics. These partnerships not only facilitate technological advancements but also lay a solid foundation for the company’s growth and research expansions.
Beyond CTH-401, what other products or therapies are in your pipeline that you are most excited about, and what therapeutic areas are they focused on?
The Cartherics platform presents a multitude of opportunities for further development, targeting critical cancer indications such as triple-negative breast cancer, glioblastoma (brain cancer), and various adenocarcinomas like pancreatic, prostate, and gastric cancers. Beyond oncology, we are investigating therapeutic avenues for conditions such as endometriosis. Opportunities also exist in addressing other medical concerns such as autoimmune disorders, fibrosis, and neurological conditions. While our primary focus remains on cancer indications, we recognize and are actively exploring viable pathways into these additional areas through collaborations with various reputable institutions.
With the growing global demand for immunotherapies, do you have plans to expand beyond Australia, particularly into markets like the US, Europe, or Asia?
Cartherics is strategically open to extending its reach beyond Australia, evidenced by our ongoing partnership in Greater China. As we evolve, establishing collaborations and partnerships within the US and Europe is a logical progression. Nevertheless, our primary focus will remain on the development and testing of our initial products within Australia, adhering to FDA licensing protocols to ensure compliance and safety standards.
In five years, where do you see Cartherics and the field of cell-based cancer immunotherapies? What breakthroughs do you hope to achieve?
In five years, I envision immunotherapies solidifying their role as a cornerstone in cancer management, potentially integrating antibodies and molecular techniques to regulate immune function more effectively. There’s a strong possibility that cancer might be transformed from a life-threatening disease into a more manageable condition, characterized by robust control mechanisms. While the full realization of this vision may span a decade or longer, preliminary recognitions could emerge within five years. Additionally, I anticipate that Cartherics will be leading innovations and establishing a dominant position in pharmaceutical advancements within the medical field.
How do you see the current trends in CGT shaping the future of cancer immunotherapies, and where exactly does Cartherics fit?
The evolution of cell and gene therapies facilitated by pluripotent stem cells and advanced gene editing techniques, like CRISPR Cas9, has dramatically altered the landscape of therapeutic intervention in oncology. The incredible potential of these technologies hinges on ongoing adaptation and innovation within the research community. Cartherics stands in a strong position, bolstered by a comprehensive research foundation and deep-rooted collaborations within the biomedical and academic sectors. Our forward-looking strategy involves continuously bringing innovative therapies through the pipeline into clinical development and their eventual therapeutic application. By leveraging the robust research ecosystem within Australia, alongside government support, Cartherics is poised to remain at the forefront of biotechnology dedicated to outcome-driven solutions.
Ayesha Siddiqui
**Interview with Prof. Alan Trounson, CEO of Cartherics Pty Ltd**
**Interviewer:** Thank you for joining us today, Prof. Trounson. Cartherics is making significant strides in cancer treatment through your innovative approach to cell-based immunotherapies. Could you explain more about the advantages of using induced pluripotent stem cells (iPSCs) from cord blood for creating your ‘off-the-shelf’ CAR-NK and CAR-T therapies?
**Prof. Trounson:** Certainly! Umbilical cord blood provides a unique source of pristine blood cells with minimal mutations, enhancing genetic reliability. We can select these cells for compatibility at the HLA locus, crucial for ensuring successful transplants. The iPSCs derived from cord blood can differentiate into various immune cells, which we can cultivate indefinitely. Additionally, the gene-editing capabilities allow us to create products that are free from potential oncogenic risks. Our proprietary processes ensure these CAR-NK cells are ready-to-use, while CAR-T cells require further modifications. This consistency is vital in the realm of biotherapeutics.
**Interviewer:** Your flagship product, CTH-401, targets the TAG-72 tumor marker. What makes TAG-72 a compelling target for CAR-NK therapy, and how does CTH-401 stand out from similar therapies?
**Prof. Trounson:** TAG-72 is present in over 90% of ovarian cancer cases and is found in many adenocarcinomas, which makes it a strategic target. CTH-401 is unique as it’s the only NK cell product in development specifically targeting TAG-72. We ensure safety through rigorous genetic screening and have knocked out genes that can inhibit cytotoxicity against solid tumors. This specificity not only enhances the therapeutic effectiveness but also reduces the risk of secondary cancers, which is crucial for patient safety.
**Interviewer:** Partnerships often play a vital role in biotechnology advancements. Can you discuss any key collaborations that have contributed to Cartherics’ growth and how you see these evolving?
**Prof. Trounson:** Absolutely! Our collaborations with leading universities and medical institutions have been instrumental in supporting our research and product development through grants. We also work with companies like ToolGen Inc. in Korea, which provides us with advanced gene editing technologies. Furthermore, our partnership with Shunxi Holdings in Greater China expands our reach and resources. As we grow, I anticipate deepening these collaborations and potentially exploring new partners in markets such as the US and Europe.
**Interviewer:** Beyond CTH-401, what other therapies or products are you particularly excited about in your pipeline?
**Prof. Trounson:** We have several promising candidates targeting major cancer types like triple-negative breast cancer and glioblastoma, as well as various adenocarcinomas. We’re also exploring treatments for conditions like endometriosis and other medical challenges, including autoimmune disorders and neurological conditions. While oncology is our primary focus, we’re actively seeking to expand our therapeutic reach in collaboration with established institutions.
**Interviewer:** As the demand for immunotherapies grows globally, are there plans for Cartherics to expand beyond Australia?
**Prof. Trounson:** Yes, we are actively exploring expansion, particularly in regions like Greater China through our existing partnerships. We understand the importance of breaking into markets such as the US and Europe as we develop our products. However, our initial focus will remain on ensuring the successful development and testing of our therapies within Australia before achieving FDA licensing.
**Interviewer:** Looking ahead, where do you see Cartherics and the field of cell-based cancer immunotherapies in five years?
**Prof. Trounson:** In five years, I envision that immunotherapies will solidify their role as cornerstone treatments in oncology. I am optimistic about breakthroughs in robust, targeted therapies that enhance patient outcomes. At Cartherics, we aim to be at the forefront, expanding our portfolio and delivering innovative solutions to improve the lives of cancer patients. We are driven by the potential of iPSCs and committed to transforming cancer treatment paradigms.
**Interviewer:** Thank you for sharing your insights, Prof. Trounson. It’s truly exciting to see the future of cancer treatment unfold, and we wish Cartherics continued success in its innovative endeavors!
**Prof. Trounson:** Thank you! It was a pleasure discussing our work and vision.