NEW YORK – Vertex Pharmaceuticals and Orum Therapeutics this week said they've inked a multi-target option and licensing agreement focused on developing new targeted conditioning agents that can be used with gene-editing therapies.
Vertex paid Daejeon, South Korea-headquartered Orum $15 million upfront for the rights to conduct research using Orum's Dual-Precision Targeted Protein Degradation (TPD²) technology. After the research period for each discovered target, Boston-based Vertex has the option to obtain a worldwide, exclusive license to further research, develop, manufacture, and commercialize degrader-antibody conjugates developed with Orum's technology. Vertex may also make additional option and milestone payments totaling up to $310 million per target for up to three targets as well as tiered royalties on future global annual net sales of any commercialized products.
The latest deal comes as Vertex is working on developing better conditioning agents for its gene therapies. Vertex and CRISPR Therapeutics sell the CRISPR-based gene-editing drug Casgevy (exagamglogene autotemcel) for treating sickle cell disease and transfusion-dependent thalassemia. Casgevy is designed to promote production of functional hemoglobin through a one-time infusion of patients' own cells that are modified outside of the body to increase production of fetal hemoglobin through editing of the BCL11A gene. Before patients can receive the genetically modified stem cells, they must undergo an intensive conditioning process involving chemotherapy, which can cause infertility.
In addition to efforts to develop better conditioning agents, Vertex also has a program that provides fertility preservation services to patients whose insurance doesn't cover it, and this week, the company sued the US Department of Health and Human Services and Office of Inspector General over the OIG's view that anti-kickback and inducement laws prevent Vertex from offering these services to patients with federal healthcare plans.
In its complaint filed in the US District Court for the District of Columbia, Vertex argued that its fertility preservation program would not amount to an illegal kickback and inducement designed to bolster sales of its gene therapy. "If Vertex were able to develop a means of administering gene therapy utilizing a gentler conditioning agent that eliminated the risk of infertility (and Vertex is working diligently on such a program), there would be no need for the fertility preservation program," the company said in the complaint. "Of course, if Vertex were to implement such a change, there would be no conceivable argument that doing so violated the [Anti-Kickback Statute], even if it increased the cost of Casgevy, and even if doing so influenced some patients to take Casgevy who otherwise would not have. It does not matter, for purposes of criminal liability under the AKS, that Vertex is addressing the side effect of infertility via the fertility preservation program or an improved method of administering Casgevy."
To date, Orum's TPD² approach, which combines targeted protein degraders conjugated to immune cell or tumor cell-targeting antibodies, has been largely studied in the cancer setting. Orum's lead therapeutic candidate, ORM-5029, is under development in HER2-expressing solid tumors.
"Vertex is a leader in discovering and developing innovative medicines, including being the first to receive FDA approval of a CRISPR-Cas9 gene-edited therapy, and we are pleased they've selected Orum's TPD² technology to discover novel targeted conditioning agents," Orum CEO and Founder Sung Joo Lee said in a statement. "This agreement with Vertex creates the potential to treat patients in a novel indication space with our leading targeted protein degradation approach for an exciting new therapeutic class of degrader-antibody conjugates."