Roche Acquires Qilu Regor's Next-Gen CDK Inhibitor Portfolio to Tackle CDK4/6 Resistance in Breast Cancer

The day before the National Day holiday, RocheEntered into an agreement with Regor Therapeutics to acquire its CDK inhibitor portfolio for an upfront payment of $850 million along with other potential milestone payments. This upfront payment surpasses the previous record set by BMS’s $800 million upfront payment for Baili Tianheng's bispecific ADC. On the same day, during Roche's R&D Day event, there was a brief introduction of this project.

The first-generation CKD4/6 inhibitors in the CDK inhibitor field have been approved.For the treatment of HER2-negative breast cancer, such asIbrance, Verzenio, and Kisqali. The idea of creating the next generation is to reduce toxicity first. The most significant toxicity is neutropenia. Industry experts believe that this side effect mainly comes from CDK6 activity. Therefore, it's necessary to develop selective inhibitors targeting CDK4 to reduce toxicity. Pfizer'sAtirmociclib is a selective inhibitor of CKD4.

And the next generation ofThe idea is that introducing activity to CKD2 canOvercome ExistingCDK4/6 inhibitor resistance. Pfizer has already done this, in addition to developing CKD4 inhibitors.Atirmociclib, Pfizer has also developed a CKD2 inhibitor. PF-07104091, and inLaunched this yearatirmociclibUnitedPF-07104091'sPhase 3 clinical trial aims to combat resistance to CDK4/6 drugs. At ESMO, Pfizer released data showing that in 18 patients with ER-positive/HER2-negative breast cancer, the ORR was 28%, all of whom were previously treated with frontline CDK4/6 inhibitors.

The Next-Generation CKD Inhibitor Developed by Regor Therapeutics Recently Introduced by RocheRGT-419B It is directly a CKD2/4 inhibitor.2020SABCSA preclinical poster showed that incorporating low levels of CDK2 activity in the molecule can counteract Cyclin E/CDK2-driven resistance.

The first-in-human trial data of RGT-419B was presented at last year's SABCS. This trial included 12 patients, all of whom also received CDK4/6 inhibitor therapy. Among them, three cases showed confirmed responses (one of which relapsed at 32 days), and there was one unconfirmed response that was still ongoing as of the data cutoff date on September 26, 2023.

On the surface,RGT-419B The ORR data of Regor Therapeutics' rigratinib in the same population was comparable to that of Pfizer’s atirmociclib/PF-07104091 combination therapy. However, an important difference between the two therapies may lie in safety. Regor reported a 25% incidence of neutropenia (all below grade 3), while Pfizer reported a 27% incidence of grade 3 or higher neutropenia, along with dose-limiting toxicity observed at the highest dose.

Crossover Trial Comparison:atirmoCiclib in combination with PF-07104091 vs RGT-419B

Roche pointed out that the market for CDK inhibitors is expected to reach up to 15 billion US dollars by 2030, including the potential expansion into early-stage breast cancer populations. Another CDK inhibitor molecule included in this collaboration, RGT-587, is Ph1 ready and is a CDK4 selective inhibitor with brain penetrability.

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