Tango Therapeutics (NASDAQ:TNGX) is preparing to move further into late-stage development for its PRMT5 inhibitor vopimetostat, newly appointed CEO Malte Peters said during a Guggenheim fireside chat. Peters, who has served on Tango’s board since 2018, told attendees the company should not expect a “drastic strategic change” following his transition into the CEO role.
Peters said the company has now achieved clinical proof of concept for vopimetostat and that his primary mandate is to help evolve Tango into a “full-blown, late-phase drug development company,” with the goal of achieving regulatory approval for vopimetostat either as monotherapy or potentially in combination with a RAS inhibitor.
Vopimetostat pivotal plans in second-line pancreatic cancer
On study design, Peters confirmed a previously discussed 300-patient randomized trial with a hierarchical endpoint structure that evaluates progression-free survival first and then overall survival. He said the company believes it can enroll the study rapidly given the number of patients affected by pancreatic cancer. While acknowledging that treatment paradigms may change, Peters said Tango is confident the design—randomized against chemotherapy in the second-line setting—is “executable.” He also emphasized the study’s global footprint, spanning the U.S., Europe, and Asia-Pacific, as a factor supporting enrollment.
Peters also said Tango plans to provide an updated monotherapy data set later this year, though the exact timing has not been decided. He cited FDA preferences against very frequent data cuts and suggested an update could potentially coincide with presentation of combination data.
Early combination efforts with Revolution Medicines RAS inhibitors
Tango has also begun evaluating vopimetostat in combination with Revolution Medicines’ RAS inhibitors, including the pan-RAS inhibitor daraxonrasib and the KRAS G12D-selective inhibitor zoldonrasib. Peters said the program was driven by “very encouraging and exciting” preclinical findings, where the two companies observed synergy when combining the agents.
The first patient in the combination study was enrolled in June of last year, Peters said. Since then, he reported strong interest and rapid enrollment momentum, including more patient requests than the company can currently accommodate. As of the discussion, Peters said the study had enrolled 14 patients in the daraxonrasib arm and 16 patients in the zoldonrasib arm.
Asked whether preclinical synergy will translate clinically, Peters said it is too early to know given immature data, but he said he would not rule out “significant upside potential” for the combination relative to each component alone.
How Tango is thinking about dose selection and future development paths
When discussing criteria for selecting a recommended Phase 2 dose, Peters said the company is oriented around a benchmark for RAS inhibitor monotherapy in second-line pancreatic cancer—around 29% to 30% depending on the compound—and expects or hopes to perform “significantly better” in combination. However, he emphasized that the current data set is not yet sufficient to make conclusions.
Peters also highlighted the importance of duration measures such as duration of response and progression-free survival, noting that these therapies do not produce “chemotherapy-like” rapid responses. He said both RAS inhibition and PRMT5 inhibition may require time on treatment for patients to benefit, and he stressed Tango’s intent to wait for a mature data set before drawing conclusions.
Looking ahead, Peters said the company’s objective is to present combination data along with a connected clinical development plan, though he said it is too early to outline specific next steps such as expansion cohorts or potential regulatory discussions.
On the choice between daraxonrasib and zoldonrasib combinations, Peters said Tango currently has no reason to assume a significant efficacy difference between the two agents based on publicly available information. He said any differentiation in development strategy would depend on seeing the full data set.
Broader pipeline updates: lung cancer, TNG456, and additional opportunities
Peters said the combination study is also open to non-small cell lung cancer, but enrollment progress has been greater in pancreatic cancer. He attributed this to patient availability and to lung cancer’s more “fractionated” genetic landscape. He said Tango is beginning to make progress in lung cancer enrollment and expects the data to guide future direction.
Peters also discussed Tango’s CNS-active molecule TNG456, stating that the clinical trial has recently started dose escalation and has reached exposure levels he described as clinically meaningful. He said the company has enrolled the first few patients with glioblastoma and non-small cell lung cancer and reiterated guidance to release data for TNG456 later this year. While the company has not specified exactly how large the data set will be, he described it as a normal dose-escalation study with two arms (GBM and NSCLC) and said investors should expect a “fairly robust” data set later this year. Peters also confirmed that a combination with abemaciclib remains part of the clinical plan, supported by preclinical data.
Beyond pancreatic and lung cancer, Peters said Tango is continuing to explore vopimetostat in a tumor-agnostic cohort enrolling MTAP-deleted cancers regardless of histology. He highlighted what he called interesting signals, including three of three head and neck cancer patients responding, and said the company plans to enroll more patients to better understand potential opportunities, including the possibility of either tumor-agnostic development or targeted pursuit of specific indications.
Finally, Peters referenced TNG961, a program tied to FOCAD deletion biology, and said there are co-deletions of FOCAD and MTAP in an estimated 10% to 12% of pancreatic cancer patients and about 6% to 8% of lung cancer patients. He said Tango is considering whether combining compounds could be attractive for patients with both alterations.
In closing, Peters said Tango expects an active year of updates, including more mature pancreatic cancer monotherapy data, combination results with Revolution Medicines’ RAS inhibitors, lung cancer monotherapy updates, and TNG456 dose-escalation data.
About Tango Therapeutics (NASDAQ:TNGX)
Tango Therapeutics is a clinical-stage biotechnology company dedicated to developing precision medicines that exploit genetic vulnerabilities in cancer cells. Leveraging a proprietary synthetic lethality platform, the company identifies and targets tumor-specific dependencies in DNA damage response and related pathways. By focusing on tumor cell collateral sensitivities, Tango aims to bring differentiated small-molecule therapies to patients with genetic alterations that confer increased susceptibility to targeted inhibition.
The company’s lead pipeline comprises several early-stage programs, including inhibitors designed to selectively disable DNA repair proteins in tumor cells while sparing normal tissues.
