Alteogen CEO expresses confidence in ALT-B4’s competitiveness

(MK database)

Developing subcutaneous (SC) versions of antibody-drug conjugates (ADCs) will be a game-changing trigger in the highly competitive global landscape of ADC development, according to Alteogen Inc. Chief Executive Officer Park Soon jae.

“In the ADC field, only the first-in-class and best-in-class can ultimately survive,” Park said in a recent interview with Maeil Business Newspaper.

The South Korean biotechnology company signed a major technology transfer deal with Japanese pharmaceutical company Daiichi Sankyo on Friday.

Park is also confident about expanding the company’s ALT-B4, a human recombinant hyaluronidase enzyme technology. As many latecomers enter the ADC market, developing SC formulations is expected to be crucial for competing with established products such as Roche’s Kadcyla and Daiichi Sankyo’s Enhertu.

Park noted that the paradigm for ADCs could shift from intravenous (IV) to SC formulations.

“For companies developing ADCs that target the same indications as Enhertu, if a new drug is significantly superior to existing ones, it could succeed as an IV formulation,” Park said. “Otherwise, strategic positioning, such as using an SC formulation, may be necessary.”

ADCs comprise an antibody to target cancer cells, a toxic payload to kill the cells, and a linker that connects the two.

Since anticancer agents are inherently toxic, ADC technology has gained attention by enabling the precise targeting of cancer cells, similar to a guided missile. However, the high toxicity of payloads had limited dosages to date, as higher doses might harm the body.

Park noted that switching to an SC formulation could potentially allow higher doses while mitigating toxicity concerns.

Due to these benefits of SC formulations, Hybrozyme’s application could expand to targeted protein degradation (TPD) therapies moving forward.

“By partnering with companies with a range of payloads, we can start with SC formulations from the beginning, which maximizes the concentration of drugs administered to patients and enhances therapeutic effects,” he said.

Park is also positive about the feasibility of developing SC formulations for ADCs.

“ADCs are complex, and simply using hyaluronidase as with other drugs is insufficient,” Park said. “We have patented a unique technique for this purpose. The success of an SC formulation is essentially determined in Phase 1 trials – if these are successful, Phase 3 is highly likely to succeed.”

Currently, only two companies globally possess human hyaluronidase-based formulation change technology – Halozyme in the United States and Alteogen. In Korea, companies like Huons Lab and Celltrion are developing SC formulation conversion technologies independently.

Halozyme’s PH20 patent will expire in 2030, and industry expectations are that efforts to replicate it will increase. However, the development challenge for Hybrozyme technology and existing patent barriers make replication difficult.

Given that preclinical trials can take several years to over a decade, restarting from scratch with toxicity tests is costly and time-intensive.

Park noted that Alteogen’s ALT-B4 offers a technological advantage over Halozyme’s Ph20 in terms of drug stability, efficacy, heat stability, and immunogenicity, or the ability to trigger an immune response.

Alteogen also has a favorable patent position.

Halozyme has exclusive agreements with Bristol-Myers Squibb (BMS) for the SC formulation of the immunotherapy drug Opdivo, and with Roche for the SC formulation of the immune-oncology drug Herceptin targeting Enhertu’s biomarker HER2.

Both agreements limit the use of technology exclusively to specified targets, preventing Halozyme from licensing technology for drugs targeting the same molecules and BMS and Roche.

Most of Alteogen’s technology export contracts for ALT-B4, on the other hand, are exclusive by product, not by target, allowing the company to form multiple contracts with various companies. This flexibility could mean that Alteogen’s technology is more scalable than Halozyme’s.