Tango Therapeutics, Inc. Study result

Good morning, everyone, and thank you for joining us on today's call. This morning we issued a press release describing the data we will present at ESMO, which can be found on the Investors and Media section of our website, www.tangotx.com. Before we begin, let me review our safe harbor statement. We will make forward-looking statements on this call that are subject to important risks and uncertainties discussed in detail in today's press release and in our filings with the Securities and Exchange Commission. This call is being recorded, and a replay will be available on our website. The agenda for this morning's call is as follows. Malte Peters, Tango's President and CEO, will share some introductory remarks. We're pleased to be joined today by Dr. Brian Wolpin, Director of the Hale Family Center for Pancreatic Cancer Research, Dana-Farber Cancer Institute, who will present the clinical data.

Adam Crystal, our President of R&D, will discuss our registration and expansion strategy for vopimetostat and PDAC. Matt Gall, CFO, will share some financial highlights and provide an overview of important upcoming events. Malte will then conclude the call, and we will open it up to Q&A. I will now turn the call over to Malte.

Thank you, Liz, and good morning, everyone. Since I joined Tango as CEO in January 2026, we have developed a clear mission to deliver vopimetostat to patients with pancreatic cancer as quickly as possible. In order to achieve that goal, we need to accomplish three things. First, build on the body of clinical data. The updated clinical data that we are sharing today, and that will be presented at ESMO this weekend, confirms what we believe to be an unprecedented and potentially best-in-class safety and efficacy profile. This strong clinical profile may be attributable to some of vopimetostat's unique properties that have created a favorable drug-drug interaction with daraxonrasib that has yielded impressive clinical activity and a safety profile that to date appears to be superior compared to that of single-agent daraxonrasib.

We believe we are seeing a 1 plus 1 equals 3 type synergy with this combination, exceeding our expectations across all metrics. Second, establish an innovative and efficient registrational strategy. Based on recent FDA feedback, we are preparing to start a phase III study for this combination in first-line pancreatic cancer. Our discussions with the agency were productive and collaborative, and we now have a study design that is ready to go. We are committed to starting the study in the first half of 2027. In addition, we plan to seek FDA's guidance regarding a possible accelerated approval for the combination in second-line pancreatic cancer patients. Lastly, to support these efforts, we need to grow and evolve our organization to execute against these goals. We have evolved the organization significantly since I became CEO.

We have an experienced leadership team in place, and we are laser-focused on operational excellence and execution as we enter late-stage clinical development and become a pre-commercial organization. That is not enough. While executing against our pivotal study in frontline pancreatic cancer is our primary goal, the data and evolving landscape, along with a strong biological rationale, position us to further advance novel scientific approaches into the clinic. We aim to begin these efforts studying the combination in MTAP-type pancreatic cancer, supporting our ambition for vopimetostat to be a PRMT5 combination partner of choice for any RAS inhibitor. Over time, this may create the potential to evaluate combinations beyond RAS and to extend the impact of the PRMT5 program into additional tumor types and treatment settings.

Tango is well positioned to move into the next stage of vopimetostat development and to continue on the path to creating meaningful benefit for patients and value for shareholders. On today's call, we are primarily focused on pancreatic cancer, and so I wanted to set the stage and outline the opportunity here. In the U.S. alone, each year, approximately 60,000 people are diagnosed with metastatic pancreatic cancer, and approximately 40% of those patients harbor an MTAP deletion. As standard of care evolves, we believe the percentage of patients receiving treatment at each line of therapy will increase, with treatment options that have the potential for greater patient benefit without toxic chemotherapy. On the call today, we are very pleased to have Dr. Brian Wolpin of Dana-Farber Cancer Institute join us to present the updated clinical data for this combination.

Dr. Wolpin is the Director of the Gastrointestinal Cancer Center at Dana-Farber and will be the lead investigator in our planned phase III trial.

Dr. Wolpin? Excellent. Thank you, Malte, very much.

I appreciate the opportunity to present the data on behalf of all of the investigators and the patients and the team at Tango. To start out with, to think about how the standard of care in pancreatic cancer is evolving. Really historically, this has been a disease treated with chemotherapy. In metastatic disease, the vast majority of patients really had limited options, and these options generally were multi-agent chemotherapy.

However, in recent months, with the approval of now the first RAS inhibitor for patients with pancreatic cancer, in particular metastatic pancreatic cancer, we see that the landscape starts to shift toward a more targeted approach toward treatment of patients with this disease. Now I think really as the next step comes additional options to add drugs to RAS inhibitors to create even greater durability, higher response rates, and ultimately more benefit for patients facing this difficult disease. This slide provides some of the mechanism as background to vopimetostat, which is an MTA-cooperative PRMT5 inhibitor. 30%-40% of pancreatic cancers have a biallelic deletion in MTAP. This deletion leads to an accumulation of the substrate for this enzyme, MTA. MTA then binds to PRMT5 and causes a partial inhibition of PRMT5 function.

Vopimetostat as an MTA-cooperative PRMT5 inhibitor then has a selectivity toward further reduction in PRMT5 function in tumor cells, therefore providing a therapeutic window for treatment in cancer cells compared to normal cells. There is now substantial preclinical data looking at the combination of PRMT5 inhibition and RAS inhibition across a host of different models and different scenarios. You can see on the left our data in a PDX model of a cell line that is MTAP null and KRAS G12D mutant, and you can see the benefit in this model to vopimetostat and to daraxonrasib, but then really the appearance of a synergistic benefit with the two of them together. On the right, you see a similar type experiment, again, another cell line-derived xenograft model.

Again, MTAP null, in this case, KRAS G12D mutant, and you see data for vopimetostat and zoldonrasib, in this case, a G12D specific RAS inhibitor, again, showing similar results with an apparent synergistic effect between a RAS inhibitor and PRMT5 inhibitor in these cell line xenograft models. Today we'll show data for vopimetostat plus daraxonrasib. We're going to focus on that aspect of the phase I dose escalation trial. Additional data with zoldonrasib will be presented in the poster at ESMO. As you can see, these are patients with second or third-line treatment of metastatic pancreatic cancer. They must all have MTAP biallelic deletion and a RAS mutation. You can see from the key inclusion criteria that MTAP loss was defined either by next-generation sequencing or by immunohistochemistry, ECOG performance status of 0 or 1, and no prior therapy with similar agents.

On the right of the slide, you can see the dose escalation range with vopimetostat given at either 200 milligrams once daily or 250 milligrams once daily and daraxonrasib administered at 100 milligrams once daily. We will talk about 34 patients in the safety analysis, 27 in the efficacy analysis, with those patients defined as patients who had at least 14 weeks since the initial administration of the combination. You can see in the bottom right that MTAP status was defined largely by next-generation sequencing and also with a smaller proportion by immunohistochemistry, with very high concordance between these two methods for defining MTAP loss. If we now look at the baseline patient characteristics for those enrolled to the study, you will see in the first column is vopimetostat and daraxonrasib in patients with pancreatic cancer.