Astellas and Kelonia Therapeutics Forge $575M Collaboration to Advance In Vivo CAR-T Therapies

On February 15, Astellas Pharma, Inc. (Tokyo Stock Exchange ticker symbol: 4503) and Kelonia Therapeutics announced that Xyphos Biosciences, Inc., a wholly-owned subsidiary of Astellas, and Kelonia Therapeutics have entered into a research collaboration and licensing agreement to develop novel immuno-oncology therapies. Under the terms of the agreement, the two companies plan to combine Kelonia’s iGPS with Xyphos’ ACCEL technology to develop innovative in vivo CAR-T cell therapies for up to two programs.

The terms of the agreement show that Xyphos will be responsible for the development and commercialization of the collaborative research products. Kelonia will receive a $40 million upfront payment from the first project.If Xyphos exercises its option for the second project, Kelonia Therapeutics will receive an additional $35 million, along with potential milestone and contingent payments totaling nearly $800 million (approximately 5.75 billion RMB).In addition, Kelonia will receive R&D funding from Astellas for collaboration-related work and is eligible to receive tiered royalties of up to double-digit percentages of net sales.

This is Kelonia Therapeutics' first major collaboration since its establishment.The company officially launched after successfully securing $50 million in Series A financing in April 2022, with support from investors such as Alta Ventures, Horizons Ventures, and Venrock.

Regarding this collaboration, Adam Pearson, Chief Strategy Officer of Astellas, stated: "Astellas has positioned immuno-oncology as a primary focus of its R&D strategy. By leveraging Kelonia's iGPS technology and combining it with ACCEL technology, this will create synergies for breakthrough research from both companies, ultimately expanding Astellas' portfolio to provide innovative in vivo CAR-T cell therapies for cancer patients."

Kevin Friedman, CEO and founder of Kelonia Therapeutics, stated, "The combination of Kelonia's in vivo gene delivery capabilities with ACCEL technology represents an ideal technological pairing for universal CAR-T cell therapy."

In addition to its collaboration with Astellas, Kelonia Therapeutics is also developing a cell therapy for multiple myeloma and leveraging it.The preclinical study results of its iGPS technology were announced at the 26th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT) last year., indicating that this technology can effectively deliver CAR molecules specifically to target cells in mice and non-human primates.

Kelonia's iGPS technology is built on the foundation of lentiviral vectors (LVV) and incorporates uniquely defined targeting molecules specific to iGPS particles and optimized fusion protein designs on the viral envelope. After the target immune cells recognize and bind to specific antigens on the LVV surface, the fusogenic molecule proceeds to transduce the immune cells for gene delivery. This achieves dual selection of both the targeting molecule and the fusogenic molecule, enhancing the precision and efficiency of gene delivery.

This design helps reduce the single-dose amount, supports systemic administration without requiring additional chemotherapy before treatment. It directly expresses the target CAR in patients to achieve precise cell therapy, offering an "off-the-shelf" treatment that avoids issues caused by the ex vivo modification process in traditional CAR-T therapies, effectively shortening the treatment cycle and reducing costs.

Preclinical studies have shown that intravenous infusion of iGPS particles expressing anti-CD20 CAR into non-human primates, without preparative chemotherapy, can produce potent CAR-T cells across a 10-fold dose range. Even at the highest dose level, no clinical toxicity or related biomarker evidence, including cytokine release syndrome or neurotoxicity, was observed.

Apart from the name Kelonia Therapeutics, which is less familiar to many, Astellas also seems less "well-known" compared to Japanese pharmaceutical companies like Takeda and Eisai.In fact, Astellas is the second-largest pharmaceutical enterprise in Japan, only after Takeda, and was established on April 1, 2005, through the merger of two century-old companies: Yamanouchi Pharmaceutical and Fujisawa Pharmaceutical. In the 2020 global pharmaceutical sales ranking, Astellas' revenue ranked just behind Takeda Pharmaceutical Co., Ltd. and Otsuka Holdings.

Currently, Astellas' franchise areas include oncology, urology, immunology (transplantation), cardiology, and infectious diseases. The priority areas for research and development include infectious diseases, diabetes, gastrointestinal diseases, oncology, and central nervous system disorders. Astellas entered China in 1994, and its products marketed in the Chinese market cover various specialized therapeutic fields such as oncology, transplantation immunology, and urology.

This "venerable" pharmaceutical company, newly merged and transformed, has frequently laid out its CGT track in recent years, prioritizing gene medicine as a strategic plan launched in 2018 to help offset the patent expiration of some of its best-selling drugs.

Among them, the most notable was Astellas' acquisition of gene therapy startup Audentes Therapeutics in December 2019 at a 110% premium for $3 billion, thereby obtaining gene therapy pipelines such as AT132, AT702, AT751, and AT753.

However, starting from May 2020, AT132 began to experience a series of patient deaths in clinical trials, which subsequently led to two regulatory suspensions. After evaluation, Astellas plans to abandon the development of AT132, and the losses incurred from this pipeline will be included in the impairment losses of the last quarter of 2021, amounting to $390 million. In addition to AT132, Astellas has also terminated the clinical development of the AT702, AT751, and AT753 pipelines. The losses resulting from the termination of these products were recorded as $170 million in impairment losses in Astellas' Q1 2022 financial report.

In November 2023, Astellas announced the safety and efficacy of the AAV gene therapy AT132 for X-linked myotubular myopathy (XLMTM), as well as the causes of death for four patients in the trial.Data show that AT132 has therapeutic significance for XLMTM, and Astellas will actively communicate with the FDA to lift the clinical hold on AT132 as soon as possible.

Despite the bumpy road into emerging tracks, Astellas has never given up.According to incomplete statistics, in recent years, Astellas has successively acquired Ocata Therapeutics, Universal Cells, Inc., Quethera, Xyphos Biosciences, Inc., Audentes Therapeutics, Inc., and other companies, rapidly expanding and advancing its layout in the CGT field.

In a recent interview, Yoshitsugu Shitaka, Chief Scientific Officer of Astellas, stated that Astellas encountered some setbacks while developing such therapies. However, he said that Astellas believes these issues have now been resolved and expects to initiate multiple human trial projects within a few years.

Let us look forward to more established pharmaceutical companies partnering with Biotech, leveraging their respective strengths in the emerging field of CGT to accelerate the rapid development of this track.

References:
1. Yima Guest "10-fold Dose Potent In-situ CAR-T Preparation in the Body, Without Additional Chemotherapy"

2. Pharma Representative Home "The Development History of Astellas in the 2023 Global Top 50 Pharma Companies"