Alteogen(196170) signaled an additional technology export deal in the second half, drawing industry attention to which modality (drug delivery method) will be the protagonist of this "mega-deal." Alteogen, which is currently conducting multiple material transfer agreements (MTAs), is expanding the application scope of its technology that converts intravenous (IV) medicines into subcutaneous (SC) formulations from existing antibodies and proteins to ribonucleic acid (RNA), raising the possibility that a new modality will be included in the deal.
On Aug. 26, according to the investment banking (IB) industry, Alteogen is said to have entered the final stage of an additional technology export deal. While the specific counterparty or technology field has not been disclosed, the industry is giving greater weight to the possibility that new modalities not seen in existing deals—such as RNA and in vivo CAR-T—will be included.
Alteogen's core technology, ALT-B4 based on the Hybrozyme® platform, converts antibody therapeutics administered by intravenous (IV) infusion into subcutaneous (SC) administration.
Based on this, the company has signed successive deals with global pharmaceutical firms including France's Sanofi, Merck (MSD) in the United States, Daiichi Sankyo in Japan, AstraZeneca in the United Kingdom, and GSK plc. On the 5th, it also added an exclusive deal for one product with an undisclosed partner.
At the beginning of the year, Alteogen set a goal to expand its commercialized items to nine or more by 2030. With MSD's "Keytruda SC (product name CUREXO)" commercialized, Sanofi's "Dupixent SC" and Daiichi Sankyo's "Enhertu SC" are also in clinical and development stages.
◇ Beyond antibodies and ADCs to "RNA"… expanding the delivery platform
Alteogen is extending ALT-B4's application from antibodies, antibody-drug conjugates (ADCs), and bispecific antibodies to RNA therapeutics such as small interfering RNA (siRNA).
RNA is a substance that produces proteins or regulates gene activity based on genetic information contained in DNA. RNA therapeutics are broadly divided into messenger RNA (mRNA) and siRNA, and in terms of commercialization and clinical development, siRNA is relatively ahead.
The key challenge for RNA therapeutics is to deliver RNA safely and efficiently to the desired cells. To address this, delivery technologies such as GalNAc, which binds to hepatocyte receptors to help deliver RNA to the liver, and lipid nanoparticles (LNPs), which encapsulate RNA and deliver it into cells, have advanced, accelerating clinical development of RNA therapies.
A representative commercialized case leveraging RNA delivery technology is Novartis of Switzerland's hyperlipidemia siRNA Therapeutic "Leqvio." Recently, development of treatments for metabolic dysfunction–associated steatohepatitis (MASH) and Alzheimer's disease using RNA has also been active.
Alteogen has also been pursuing collaborations to develop SC formulations of RNA therapeutics. In June, at "BIO USA" in San Diego, United States, Alteogen CEO Jeon Tae-yeon said, "We are currently conducting an MTA with a global pharmaceutical company that has RNA therapeutics, and the proof-of-concept (POC) results are coming out positively," and added, "We are seeing positive results even in areas that have not been attempted so far."
In particular, the expansion of RNA delivery technology may not be limited to SC administration of RNA therapeutics. In vivo CAR-T, which delivers RNA to desired immune cells to create CAR-T cells directly in the body, is cited as a representative application of RNA delivery technologies. This is why the industry is focusing on in vivo CAR-T alongside RNA as Alteogen's next-generation modality candidates.
◇ "In vivo CAR-T" also likely… an expanded version of RNA delivery technology
Beyond RNA, another area drawing industry attention is "in vivo CAR-T." In vivo CAR-T is a therapy that creates CAR-T cells by delivering genetic material such as RNA directly to immune (T) cells inside the body.
Conventional CAR-T therapies remove a patient's T cells from the body, genetically modify and culture them, and then reinfuse them into the patient. In contrast, in vivo CAR-T bypasses such cell harvesting and ex vivo culturing by delivering CAR genetic information to T cells within the patient's body.
Ultimately, the crux of in vivo CAR-T lies in both "what genetic information is inserted" and "how that genetic information is delivered to the desired cells." If a technology is secured to selectively deliver RNA to the desired T cells, CAR-T cells can be generated directly in the body.
Conventional CAR-T is considered to have drawbacks such as complex manufacturing, high expense, and long preparation times. If in vivo CAR-T is commercialized, expectations are that it could streamline these steps and greatly improve treatment access.
Research is particularly active on expanding CAR-T's application beyond blood cancers to autoimmune diseases. Because CAR-T cells can proliferate in the body and act continuously after a single administration, it is also drawing attention as a next-generation cell therapy.
◇ Big Pharma also racing to secure "RNA→in vivo CAR-T" technologies
Global Big Pharma has recently been actively pursuing RNA-based in vivo CAR-T technologies for this reason. In particular, technology that uses circular RNA (circRNA) to express CARs in the body is drawing attention as a next-generation platform.
Notably, in February, Eli Lilly and Company acquired Orna Therapeutics, which holds circular RNA–based in vivo CAR-T technology, for up to $2.4 billion (about 3 trillion won). In addition, AstraZeneca, Gilead in the United States, and Bristol Myers Squibb (BMS) have entered the competition by acquiring companies related to in vivo CAR-T.
Competition is now expanding beyond securing CAR-T technologies themselves to obtaining technologies that genetically reprogram immune cells in the body directly using RNA. As RNA delivery technology emerges as a core foundation for implementing in vivo CAR-T, RNA and in vivo CAR-T are becoming intertwined as a single technology race.
If the in vivo CAR-T market for autoimmune diseases grows, the points of connection with SC administration technologies could also increase. Unlike cancer, autoimmune diseases require consideration of long-term treatment and the potential for repeated administration, which could increase the value of convenient in-body administration methods over complex approaches that harvest cells in hospitals, manipulate genes, and then reinfuse them.
Indeed, in August last year, AbbVie acquired Capstan Therapeutics, which owns LNP-based in vivo technology, for $2.1 billion (about 3 trillion won). Capstan is currently conducting a phase 1 clinical trial of the autoimmune disease therapy "CPTX2309."
An IB industry source said, "Alteogen's next technology export is worth watching not merely for SC formulation of RNA therapeutics but for the possibility of expansion to in vivo CAR-T based on RNA delivery technology," and added, "If the technology application scope expands from the existing antibody- and protein-centered SC platform to RNA and in-body immune cell reprogramming, the deal size could become a large-scale transaction that surpasses past technology exports."