Despite their promise, antibody-drug conjugates (ADCs) have been tricky to bring to market, but the U.K. biotech formerly known as Glythera wants to change that.
The Newcastle-based company has just renamed itself Iksuda Therapeutics—from a Sumerian word meaning "all-conquering"—and says it intends to overcome “the issue of ADC instability” which has seen so many candidates fail in development.
It’s also announced a big change in direction, shifting from licensing its technology to partners to in-house drug development, with a focus on hard-to-treat solid tumors.
According to Iksuda’s CEO Dave Simpson, Ph.D., the company will “create a new generation of stable, effective ADCs for treating the most severe cancers and improving patient lives,” with two candidates due to be selected for clinical trials later this year. He anticipates the first programs to get underway will be for ovarian and lung cancers.
ADCs take the form of an antibody, linker and drug—generally a toxin—and are designed to deliver a cell-killing payload to malignant tissues while limiting exposure to healthy tissues. Despite hundreds of trials, only a handful of ADC products have made it through to market, including Pfizer’s Mylotarg for leukemia, Seattle Genetics/Takeda’s lymphoma therapy Adcetris and Roche’s Kadcyla for breast cancer.
Stability is a perennial issue for ADCs, and it is often the linker part of the molecule that leads to problems—if it’s not stable enough, for example, it can release the toxic compound before the drug has bound to the cancer cell, causing off-target side effects and reducing its efficacy. A meta-analysis of 870 clinical trials published last year suggested that the main cause of severe ADC toxicities was related to off-target delivery.
Iksuda has developed a new linker technology dubbed PermaLink it claims makes ADCs more effective and with fewer side effects, along with new toxins and antibody components.
Recent ADC failures include AbbVie’s Stemcentrx-sourced cancer therapy SC-007, ADC Therapeutics’ HER2-targeting drug ADCT-502 for breast cancer and Sanofi’s SAR428926, licensed from Immunogen.
In July, the FDA placed a partial hold on Mersana’s lead candidate XMT-1522 after a patient death in a phase 1 trial that it said was potentially drug-related. The company has since issued a response to the regulator seeking to have the hold lifted.