GB-5121

A Gossamer Bio drug designed to penetrate into the central nervous system (CNS) to treat a rare cancer affecting the brain and spinal cord is discontinuing clinical development after reports of serious complications, including a fatal case of severe brain bleeding. In a regulatory filing, Gossamer said the FDA placed a partial clinical hold on all tests of the drug, GB5121, due to the adverse events observed. In addition to the fatal intracranial hemorrhage, the filing noted atrial fibrillation and a sudden death event whose cause was not specified. A partial hold stops a study from enrolling new patients, though patients currently enrolled may continue to receive an experimental drug. However, San Diego-based Gossamer said it has decided to discontinue development of GB5121 altogether. GB5121 was in development as a potential treatment for primary central nervous system lymphoma, in which cancer cells from lymph tissue form in the brain and spinal cord. The small molecule was designed to block Bruton’s tyrosine kinase, or BTK, an enzyme associated with the proliferation of cancers. While BTK inhibitors are approved for certain blood cancers, GB5121 offers a particular ability to penetrate the CNS to hit the BTK target there. Gossamer was studying GB5121 in an open-label Phase 1b/2 study enrolling patients with advanced cases of CNS lymphoma. The company signaled problems with the trial last month. In its report of 2022 financial results, Gossamer said it had decided to pause enrollment due to the drug’s observed risk/benefit profile. The company also cited its decision to prioritize development of seralutinib, a potential treatment for pulmonary arterial hypertension (PAH). When Gossamer disclosed the clinical trial pause on GB5121, no details about the risks observed in the study were disclosed. In its 2022 annual report, Gossamer said it would discuss the data with the study’s data review committee to determine the next steps, adding that it expected to report data from the study at relevant medical conferences. Gossamer’s focus now turns to seralutinib, previously known as GB002, a small molecule administered by inhalation. Last December, Gossamer reported that this drug met the main goal of a Phase 2 study in PAH. Since then, the company said the FDA has provided feedback on the plans for the Phase 3 clinical trial, which is expected to start in the second half of this year. As of the end of 2022, Gossamer said its cash position was $256 million.

In a short Securities and Exchange Commission filing Monday, Gossamer Bio revealed that the safety issues included atrial fibrillation, a sudden death and a fatal brain bleed. Gossamer Bio is ending development of a lymphoma med after reports of two deaths and other serious adverse events in a phase 2 trial that was paused in March citing the “benefit/risk profile observed to date.” In a short Securities and Exchange Commission filing Monday, Gossamer revealed that the safety issues included atrial fibrillation, a sudden death and a fatal brain bleed. The FDA has now placed a clinical hold on all trials of GB5121, which was being tested for primary central nervous system lymphoma. March 17, Gossamer paused enrollment in the phase 1 portion of the trial, partly because of the benefit/risk profile and also to conserve cash for lead asset seralutinib. Now, all work related to GB5121 has been discontinued and the ongoing studies shelved. Gossamer revealed GB5121, a central nervous system-penetrant Bruton’s tyrosine kinase (BTK) inhibitor, in October 2021, hoping to patch up a hole left in its pipeline by a two-time failed lead asset. At the time, CEO Faheem Hasnain called BTK a “validated target” but one that has yet to prove its abilities in the CNS. GB5121, as well as another candidate GB7208, were “specifically optimized and designed” to overcome the limitations of other BTK inhibitors, with potential applications in oncology and autoimmune disorders, according to the chief executive. The goal was for GB5121 to address disease without causing side effects elsewhere. Fellow BTK inhibitor GB7208 has been directed toward multiple sclerosis and remains in the discovery phase, according to Gossamer’s pipeline. Seralutinib, meanwhile, is in phase 2 testing for pulmonary arterial hypertension. Gossamer's shares had dropped almost 10% to $1.01 in premarket trading Tuesday morning from a closing price of $1.12 on Monday—a day that also saw the stock sink over 10%.