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Chinese biotech Pregene Biopharma has entered into a licensing pact with Gilead’s Kite Pharma that could be worth as much as $1.52 billion, under a deal that looks to accelerate the development of next-generation in vivo cell therapies. Pregene will receive $120 million upfront and could earn as much as $1.52 billion in milestone payments, according to a Chinese regulatory filing and a person familiar with the matter. Pregene will also be eligible for royalties on future product sales. The Kite partnership marks yet another large cross-border deal with a Chinese biotech , and underscores growing demand for in vivo therapeutic technologies . The deal combines Kite’s cell therapy expertise with Pregene’s platform for developing CAR-T, CAR-NK and TCR-T treatments, aiming to streamline the path from discovery to clinical development for in vivo therapies that treat diseases directly inside the body. “By combining Kite’s cell therapy expertise with our respective strengths at Pregene, we aim to overcome technical barriers, accelerate proof-of-concept studies, and bring transformative medicines to patients faster, especially in oncology, autoimmune diseases and other areas where innovation is urgently needed,” Pregene chief scientific officer Zhang Jishuai said in a news release. Based in Shenzhen, Pregene has built a pipeline of autologous and allogeneic cell and gene therapies, with multiple programs in clinical development. Pregene has also worked with Belgian biotech EsoBiotec, which was acquired by AstraZeneca and had reported promising CAR-T cell therapy results earlier this year.

The first shards of human data on in vivo CAR-T cell therapy look promising, based on recent separate reports from two biotech companies’ academic-led studies in China. Last week, a Chinese startup called Genocury became the second company to share initial clinical data on a CAR-T treatment that doesn’t require a patient’s cells to be extracted from their body. Genocury said that an advanced large B cell lymphoma patient went into complete remission after one month of in vivo CAR-T therapy, and has remained in remission for over three months. Notably, the in vivo CAR-T therapy does not require lymphodepletion, a course of chemotherapy that conventional CAR-T therapies require before treatment and that comes with toxicities. “This is good news for the field and demonstrates the increasing momentum around in vivo CAR-T approaches,” said University of Pennsylvania CAR-T pioneer Bruce Levine, who isn’t involved in Genocury’s studies but is a scientific founder of another in vivo CAR-T company called Capstan. Last week’s results follow Belgian startup EsoBiotec’s announcement in January that a multiple myeloma patient who received the lowest dose of its in vivo CAR-T therapy had no detectable cancer cells in their bone marrow at one month, without any significant adverse events during treatment. That patient also did not receive prior lymphodepletion. The data from both companies come from investigator-initiated studies in China, which biotech startups have been leveraging more frequently to quickly generate early clinical data on their experimental treatments. EsoBiotec is working with Pregene Biopharma which, like Genocury, is based in Shenzhen. In March, AstraZeneca announced plans to acquire EsoBiotec for $425 million, plus additional payments. At least five groups have begun clinical trials for in vivo CAR cell therapies. Aside from EsoBiotec and Genocury, Myeloid Therapeutics, Interius BioTherapeutics and Umoja Biopharma are all studying experimental in vivo cell therapies in patients. In conventional CAR-T therapy, a patient’s cells are extracted, engineered, and then reinfused — a complex, expensive process that can take weeks to months. The therapy, while transformative for certain blood cancers, comes with safety risks from the lymphodepletion before treatment and immune overreaction (cytokine release syndrome and ICANS) afterwards. And so far, comparatively less complex “off-the-shelf” treatments using donor cells have yet to take off. Makers of in vivo cell therapy hope that their treatments can become a different kind of “off-the-shelf” option. Their therapies deliver genetic material to turn the patient’s immune cells into cancer-fighting ones directly in the body. The companies are using different technologies to deliver their treatments and are also going after a range of diseases. The delivery technologies fall into two camps: viral and non-viral. Researchers have more concerns around the potential risks of a virus-based therapy, including of secondary cancer, but it’s an older and more proven approach. Non-viral delivery is newer and more challenging, and fewer companies have reached clinical studies. It is unclear based on Genocury’s disclosures whether it is using a viral or non-viral approach. A photo on its website mentions both viral and non-viral methods, and the company could not be reached for comment. EsoBiotec is developing a lentiviral-based cell therapy that goes after BCMA, a well-known target for multiple myeloma. Interius, which expects to report clinical data later this year, and Umoja are likewise studying lentiviral-based therapies. Umoja, like Genocury, is developing a CD19-targeted CAR-T therapy for blood cancer, and it plans to study the treatment in autoimmune disease as well. AbbVie has an option to license that therapy, and in January the startup raised $100 million to jumpstart its clinical studies. Interius’ therapy targets another immune cell protein called CD20, and it’s studying its B cell cancer therapy in both Australia and Germany. The Philadelphia biotech’s therapy is meant to make both ​​CAR-T and NK cells directly in the body. On the other hand, Sid Mukherjee’s startup Myeloid is using mRNA delivered non-virally. It uses fatty acid envelopes called lipid nanoparticles — similar to what’s used in the Covid vaccines. However, as its name suggests, it’s targeting a type of immune cell called myeloid cells. It has two programs in the clinic going after solid tumors — an area of cancer that conventional CAR-T therapies have yet to crack.