Vertex Pharmaceuticals is exploring new ways to prepare patients for intensive therapies like its sickle cell treatment Casgevy, announcing Tuesday a deal with Orum Therapeutics to develop a different kind of conditioning regimen than the chemotherapies that are currently used.
Under the terms of the partnership, Vertex will pay Orum $15 million for rights to study the biotechnology company’s so-called degrader-antibody conjugates, or DACs, as a preconditioning agent for gene editing medicines. After a set period of research, Vertex will have an option to license a DAC for each target covered by the collaboration. Orum can receive as much as $310 million in development and commercial milestone payments for each of up to three targets.
Vertex, with partner CRISPR Therapeutics, last December won Food and Drug Administration approval for Casgevy, the first CRISPR gene editing-based treatment to reach market. Cleared for sickle cell disease and severe beta thalassemia, Casgevy costs $2.2 million per patient.
Casgevy comes with significant, and potentially life-long, benefits. But patients undergoing treatment must first receive a course of chemotherapy that can cause painful mouth sources, low blood cell counts and organ damage — side effects that some older people, or those whose organs are already weakened by their disease, may not be able tolerate. Notably, it also carries a high risk of infertility, forcing a difficult choice on prospective patients who still hope to start a family.
These risks are seen as major hurdles to adoption of Casgevy, which Vertex expects will have a gradual launch. The company offers fertility preservation services for people insured commercially, but is currently barred from doing so for those covered by Medicaid. (On Monday, the company sued the U.S. government to change that.)
Vertex, and other companies in the same field, have therefore been interested in identifying and developing novel conditioning agents that are better tolerated than the current chemotherapy regimen.
Orum saw Vertex’s interest as an opportunity to expand into a new area. “We knew we could meet this unmet need, but our internal focus as a biotech is on oncology and immuno-oncology, so we thought it made sense to partner with a more established leader in this space,” said Sung Joo Lee, Orum’s CEO.
In a statement, a Vertex spokesperson said improving conditioning regimens could help more patients access treatments like Casgevy. “A safer and gentler conditioning regimen would reduce both the short-term side effects and long-term risks associated with the current process, improving the experience for patients,” the spokesperson said.
Orum’s research is part of a wider fascination in biotech with the potential of antibody-drug conjugates, a type of treatment that pairs a targeting antibody with a toxic payload to precisely reach and kill tumor cells. However, Orum is taking a slightly different approach, focusing on combining ADCs with a field known as targeted protein degradation. Rather than use a toxin, the startup pairs antibodies with a protein-degrading compound.
"We hope what we’re doing really improves upon the targeted therapy space, whereas traditional ADCs are improving the chemotherapy space,” Lee said.
This is the second deal for Orum in the past year. In November, the biotech announced a collaboration with Bristol Myers Squibb, gaining $100 million upfront to advance its work in cancer research.
Orum is developing a drug dubbed ORM-5029, which is in a Phase 1 clinical trial and targets HER2-expressing solid tumors in patients with breast cancer. The company expects to complete the study in 2025.