NEW YORK – At the JP Morgan Healthcare Conference in San Francisco on Wednesday, EQRx outlined a path forward for its pipeline of precision oncology drugs after receiving disappointing feedback from the US Food and Drug Administration last year on sugemalimab, a PD-L1 monoclonal antibody it was developing in non-small cell lung cancer.
The agency had asked EQRx to conduct a second Phase III trial with a patient cohort that is more representative of the diverse US population and demonstrate that patients' overall survival on sugemalimab is noninferior to the comparator. The agency had also said it will not accept interim readouts from such a trial. EQRx and partner CStone Pharmaceuticals tested the immunotherapy in the GEMSTONE-301 trial, which was carried out in Guangzhou, China.
"The FDA direction that has been given around use of single-country data and data in particular from China is a direction that's here to stay, so we just need to move on," said EQRx CEO Melanie Nallicheri. Based on the FDA's feedback, EQRx discontinued development of sugemalimab in NSCLC and is focusing on advancing aumolertinib, a third-generation EGFR inhibitor, and lerociclib, a selective CDK4/6 inhibitor.
According to Nallicheri, EQRx has $1.4 billion in cash on hand, providing a cash runway into 2028, which the company plans to use judiciously. "We understand there was revenue that we had hoped would come in earlier," Nallicheri said. "Because of that, we're going to be even more disciplined."
Lerociclib is currently in a Phase II trial as a first- and second-line treatment for hormone receptor-positive, HER2-negative metastatic breast cancer patients. Nallicheri said that EQRx's data shows the drug has a potency and selectivity profile that allows it to be dosed continuously. "We believe that could translate into better and improved efficacy and benefit for patients," said Nallicheri. "Continuous target coverage is ultimately going to be important … in a CDK4/6 [inhibitor]."
Nallicheri noted that some other drugs in that class have good efficacy but leave "room for improvement" due to issues such as gastrointestinal toxicities and neutropenia that don't allow for continuous dosing, as well as drug-drug interactions and overlapping toxicities that prevent development of combination therapies. In comparison, EQRx's early trials have shown a better tolerability profile than competitors' drugs, causing lower rates of adverse events such as neutropenia and gastrointestinal toxicity in patients.
"What we need to do now is show that that data actually holds when we study it in larger patient populations," said Nallicheri. That's the goal of the ongoing Phase II trial, which involves about 100 patients in the US, Europe, and Mexico.
Additionally, G1 Therapeutics, which originally discovered and developed lerociclib before licensing it to EQRx in 2020, has also partnered with Genor Biopharma to develop the drug in the Asia-Pacific region. Genor is running two Phase III trials of lerociclib in first- and second-line metastatic breast cancer.
"While we don't control those studies, that data will be available and will be additive, complementary to the data we are generating, which together would continue to build the body of evidence for lerociclib as a next-generation, best-in-class CDK4/6 inhibitor," Nallicheri said, adding that uses for lerociclib could possibly expand to MRD-positive breast cancer or continuation therapy, combination therapies, and use in other hormone-driven cancers such as metastatic endometrial cancer.
EQRx is expecting that data readouts in Q2 or Q3 2023 will confirm lerociclib's potential, and, if all goes well, the company will seek market approval in the metastatic breast cancer setting in the US in 2025.
Alongside lerociclib, EQRx will continue developing its third-generation EGFR inhibitor, aumolertinib. The company is comparing the activity of aumolertinib plus chemotherapy against aumolertinib alone or against AstraZeneca's Tagrisso (osimertinib) in a Phase III trial in EGFR-mutated NSCLC. EQRx expects to submit a regulatory application in 2027.
In May, EQRx reported that aumolertinib beat AstraZeneca's first-generation EGFR inhibitor Iressa (gefitinib) in a head-to-head trial in that same setting. It has filed a marketing authorization application for aumolertinib in the UK and plans to submit another to the European Medicines Agency in 2023.
Additionally, EQRx is now collecting real-world reports on the use of aumolertinib in China, where it is approved under the name Ameile as first- and second-line therapy for EGFR-mutated NSCLC. Nallicheri said that oncologists in China are seeing good efficacy and tolerability from patients on the drug. For example, physicians in China have found that when they switch patients to aumolertinib after they experience liver toxicities or interstitial lung disease on another EGFR inhibitor, those patients do well and have better quality of life. "That's anecdotal, but it gives us really great confidence," Nallicheri said.