Magrolimab

“We have a pipeline that can deliver at this point, but we will absolutely further optimize it,” Gilead Sciences\' Dietmar Berger, M.D., Ph.D., told Fierce.\n Dietmar Berger, M.D., Ph.D., joined Gilead Sciences as chief medical officer at the start of this year after the company’s oncology department suffered some prominent setbacks. The run of bad luck included two back-to-back phase 3 flops of Trodelvy in non-small cell lung cancer and bladder cancer as well as the demise of the anti-CD47 drug magrolimab from a $4.9 billion acquisition.But Berger, who boasts a deep background in cancer drug development, still believes the virology giant made the right move to branch out into oncology and immunology.“I am a strong believer that diversification for Gilead is the right decision,” Berger told Fierce in an interview on the sidelines of the 2025 American Society of Clinical Oncology (ASCO) annual meeting.“I also think that oncology and immunology are the right areas for Gilead, because of the emerging science … and because we can apply a lot of the strength that Gilead has—for example in chemistry, in protein design and deep understanding of biology—very strongly to oncology and immunology.”As a new head of development joining a biopharma company, it’s natural to think about ways to improve the portfolio, he said. “We have a pipeline that can deliver at this point, but we will absolutely further optimize it,” Berger added.The CMO said he’s trying to build a “balanced” and “partially derisked portfolio” by combining direct cytotoxic mechanisms with immuno-oncology. Again, diversification is key here. At ASCO, Gilead’s cell therapy unit Kite Pharma reported some early positive data for its anti-CD19/CD20 bicistronic CAR-T therapy in advanced B-cell lymphoma. Another bivalent CAR-T candidate partnered with the University of Pennsylvania targeting EGFR and interleukin-13 receptor alpha 2 recorded notable tumor shrinkage in eight (62%) of 13 patients with recurrent glioblastoma, a notoriously aggressive and hard-to-treat brain cancer.Trodelvy also had a positive story to tell at this year’s ASCO, courtesy of two positive phase 3 readouts in first-line triple-negative breast cancer (TNBC). In a potentially practice-changing data set, Trodelvy and Merck & Co.’s Keytruda significantly reduced the risk of progression or death by 35% versus Keytruda and chemotherapy in first-line PD-L1-positive TNBC.In immuno-oncology, Berger highlighted GS-1811, an anti-CCR8 antibody Gilead obtained from Jounce Therapeutics. The drug, designed to remove immunosuppressive tumor-infiltrating T regulatory cells, is still in early-stage development.All told, Gilead has 58 projects across virology, oncology and immunology in its portfolio, the largest and most diverse pipeline in the biopharma\'s history. Challenges in ADC and immuno-oncologyFor Trodelvy, new TROP2 competition has arrived in the form of AstraZeneca and Daiichi Sankyo’s Datroway and Merck and Kelun-Biotech’s sac-TMT.In Trodelvy’s home base of second-line TNBC, the Gilead drug is the only one that has demonstrated an overall survival benefit. Parallel data that could help experts compare these drugs side by side in a cross-trial fashion have not yet read out, Berger explained.Besides first-line TNBC, Trodelvy is also being tested in earlier-line HR-positive, HER2-negative breast cancer, which could represent a bigger patient population than TNBC. Following the Evoke-01 flop, the Evoke-03 study for Trodelvy and Keytruda in first-line PD-L1-high NSCLC remains ongoing.Since Gilead’s $21 billion acquisition of Immunomedics in 2020, the company still has only one antibody-drug conjugate asset, whereas other players in the space such as AstraZeneca and Pfizer have developed multiple products.The Immunomedics deal was a strategic acquisition designed to give Gilead an anchor in its diversification into solid tumors, and the company then built R&D capabilities around that, Berger noted.“That bit of a time lag is largely based on: How do you build an oncology organization?” Berger said.New oncology molecules are now coming out of Gilead’s internal research capabilities, and the company will also “focus strongly” on external opportunities, he said. Berger wouldn’t name specific ADC projects outside of Gilead that he’s interested in. Toward the end of 2024, before Berger officially moved across from Sanofi, Gilead penned a deal with Tubulis to develop a topoisomerase I inhibitor-based ADC.“There’s usually the question, do you combine different mechanisms, or do you double down on a specific pathway,” Berger said of target selection for ADCs.Choosing the linker is dependent on whether a bystander effect—in which the cytotoxic payload from the ADC kills cells surrounding the target cell—is desired, and the toxin needs to be carefully evaluated because these payloads hit different tumor types differently, Berger noted.Meanwhile, things don’t look too promising for Gilead’s late-stage immuno-oncology program, the Arcus Biosciences-partnered domvanalimab. The drug is one of the few remaining anti-TIGIT antibodies still in development after companies such as Merck, Bristol Myers Squibb, GSK and BeOne (formerly BeiGene) walked away from the field. Roche’s Genentech, where Berger used to lead oncology clinical development, has all but abandoned tiragolumab after several disappointing studies, and the pharma is now only waiting for two fully enrolled phase 3 trials to read out.Berger argued that domvanalimab may still stand a chance. The TIGIT molecules that have failed so far are mostly Fc-competent antibodies, whereas domvanalimab is Fc-silent.Fc-enabled anti-TIGIT antibodies theoretically have enhanced tumor-killing effects because they can bind to FcγRs and activate immune cells. But they could possibly also eliminate certain regulatory T cells and therefore lead to unwanted immune responses. Before nixing its TIGIT candidate vibostolimab, Merck had noted a higher rate of immune-related adverse events in at least two failed phase 3 trials. Only data will tell whether Fc-competence is the key. Gilead and Arcus are running two phase 3 trials that combine domvanalimab with Arcus’ PD-1 drug zimberelimab and chemotherapy in first-line NSCLC and gastric, gastroesophageal junction and esophageal adenocarcinoma.Gilead has a stated goal to have 30% of its revenue from oncology products by 2030. Berger acknowledged that the huge clinical success—and potential imminent approval—of twice-yearly lenacapavir for HIV prevention could make achieving that goal harder but said the company remains committed to a target of 30% of revenue from outside virology.“It does place a stronger focus on oncology,” Berger said. “But don’t get me wrong, I think we are in a good spot now.”