Cullinan Therapeutics, Inc. Common Stock Study result

Hello, everyone, and thank you for joining us on today's call to discuss the results of zipalertinib plus chemotherapy from the phase III REZILIENT3 trial in first-line EGFR exon 20 insertion mutation non-small cell lung cancer. My name is Nick Smith, and I'm the Head of Investor Relations at Cullinan Therapeutics. Before we begin, I would like to remind you of the safe harbor provisions outlined on slide number 2. During today's presentation, management will be making certain forward-looking statements which are based on current information, assumptions, and expectations that are subject to change and involve risks and uncertainties, which may cause actual results to differ materially from those contained in such forward-looking statements. These risks are fully described in the company's filings made with the Securities and Exchange Commission, including our annual report on Form 10-K. You are cautioned to not place any undue reliance on these forward-looking statements.

In addition, this call contains time-sensitive information accurate only as of the date of the live broadcast, September 14th, 2026. Cullinan undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this call. As shown on slide 3, joining me on the call today are Nadeem Ahmed, Cullinan's Chief Executive Officer, and Dr. Jeff Jones, Chief Medical Officer. It is my pleasure to now turn the call over to Cullinan CEO, Nadeem Ahmed.

Nadeem? Thank you, Nick, and welcome everyone to our call today to discuss the remarkable and potentially practice-changing results for zipalertinib in combination with chemotherapy from the phase III REZILIENT3 trial in first-line EGFR exon 20 insertion mutation non-small cell lung cancer.

Today, we're very much looking forward to providing you with an overview of the results and also our perspective of the exon 20 commercial opportunity, where we firmly believe zipalertinib combination therapy will become a first-line standard of care treatment. These results were showcased last night as a late-breaking oral presentation during the Presidential Symposium at the World Conference on Lung Cancer in Seoul, South Korea. The fact that the study was selected for this plenary session is a clear testament to the significance of these results.

I will also point out that the Presidential Symposium is focused on featuring notable advances in lung cancer research and treatments with the potential to change clinical practice. Before I ask Dr. Jeff Jones, our Chief Medical Officer, to dive into the REZILIENT-3 results, I would like to take a moment to emphasize key elements of the compelling profile of zipalertinib for patients with exon 20 non-small cell lung cancer. Zipalertinib, which we are co-developing with Taiho Oncology, is an oral EGFR inhibitor with unique design characteristics that enable a potentially best-in-class efficacy and safety profile. It was just a few weeks ago when we first announced that the REZILIENT-3 trial met its primary endpoint of median progression-free survival early at a planned interim analysis. This is the first and only study in first-line exon 20 non-small cell lung cancer to achieve its primary endpoint at the interim analysis.

The six-month improvement in median PFS demonstrated by zipalertinib combination therapy is the best PFS result observed to date in the front-line setting. In fact, the first treatment that has shown a median PFS longer than 12 months in this patient population. In addition, Phase II studies have already demonstrated the differentiated and broad clinical profile of zipalertinib across multiple patient subsets. Zipalertinib monotherapy has demonstrated clinically meaningful results in relapsed patients, in patients with brain metastases, and patients harboring uncommon mutations. With our comprehensive clinical development program, we have the opportunity to establish zipalertinib as a future standard of care across multiple EGFR non-small cell lung cancer indications. Firstly, in the second-line setting, our NDA for treatment of relapsed exon 20 non-small cell lung cancer based on the results of the Phase II REZILIENT-1 trial is under active review by the U.S. FDA. The results of the Phase III REZILIENT-3 trial, the subject of today's presentation, enable potential indication expansion into the front-line setting.

Our parallel REZILIENT-2 Phase II study is enrolling a cohort of patients with uncommon mutations in the metastatic disease setting, where we showed promising response rates already. Finally, Taiho has the Phase III REZILIENT-4 trial, an ongoing adjuvant study in patients with exon 20 and uncommon mutations. We look forward to sharing these data in the future. With that, let me turn it over to Jeff to dig into the zipalertinib REZILIENT-3 pivotal results.

Jeff? Thank you, Nadeem. As Nadeem said, we are excited to share results from the randomized Phase III portion of the REZILIENT-3 study.

To begin, let's review the study design. REZILIENT-3 is a Phase III clinical trial to evaluate the efficacy and safety of zipalertinib in combination with chemotherapy in adult patients with previously untreated, locally advanced or metastatic non-small cell lung cancer harboring EGFR exon 20 insertion mutations. Patients were randomized one-to-one to one of two treatment arms. In the investigational arm, patients were treated with oral zipalertinib 100 milligrams twice daily in combination with platinum-based chemotherapy. In the control arm, patients received only platinum-based chemotherapy. As of the May 2026 data cutoff, the study enrolled 279 patients, of which 140 were treated with zipalertinib plus chemotherapy and 139 were treated with chemotherapy alone.

The primary endpoint for the study was progression-free survival, as assessed by blinded independent central review per RECIST criteria. While the primary analysis was expected after 162 progression-free survival events, a pre-planned interim analysis was to be conducted after 122 progression-free survival events. Of the 140 patients randomized to zipalertinib plus chemotherapy, an impressive 62% of patients were still receiving treatment as of the data cutoff. Slide seven summarizes key attributes of the enrolled patient population. While EGFR exon 20 insertion mutations occur with higher frequency in Asian populations, nearly 60% of patients were enrolled in centers outside of Asia, primarily in the U.S. and Europe. More than half, nearly 60% of all enrolled patients had an ECOG performance status of one.

Most notably, approximately 31% of patients enrolled had a history of brain metastases, a rate far higher than the previous PAPILLON and WU-KONG28 studies and a rate more representative of real-world patient populations. As noted previously, the primary endpoint of this phase III trial was progression-free survival, depicted by treatment group on slide number eight. Zipalertinib plus chemotherapy delivered a remarkable, statistically significant 50% reduction in the risk of disease progression or death. Zipalertinib plus chemotherapy demonstrated an unprecedented median progression-free survival of 14.5 months, compared to a median of 8.5 months for chemotherapy alone, a statistically significant and, more importantly, clinically meaningful difference of six months. Extending beyond the previous ceiling of less than 12 months, the progression-free survival of 14.5 months and an absolute benefit of six months over chemotherapy alone is truly without precedent and underscores the potentially practice-changing strength of these data.

Other efficacy variables are summarized on slide number nine. Zipalertinib plus chemotherapy demonstrated a 65% overall response rate, comparable to the results previously reported for the PAPILLON and WU-KONG28 regimens employing amivantamab and sunvozertinib, respectively. What stands out, however, is the durability of response and clinical benefit. Zipalertinib plus chemotherapy demonstrated a median duration of response of 14.2 months. Again, unprecedented in this patient population. Turning now to slide number 10. While the results were still maturing at the May 2026 data cutoff, initial overall survival outcomes are promising. While not yet statistically significant, the hazard ratio of 0.72 favoring zipalertinib plus chemotherapy is very encouraging. The management of CNS metastases in patients with non-small cell lung cancer remains a critical unmet need. The subgroup analysis of patients with CNS metastases depicted on slide number 11 is very important.

Survival outcomes in this patient group were favorably impacted by treatment with zipalertinib plus chemotherapy. Patients with CNS metastases experienced a notable improvement in progression-free survival when treated with the combination regimen, a PFS hazard ratio of 0.38. Moving on to slide number 12. While patients who received zipalertinib plus chemotherapy did experience a higher incidence of adverse events and treatment discontinuations, dose reductions and supportive care may favorably impact patient management. Importantly, higher-grade adverse events were most frequent during the first four cycles of platinum combination chemotherapy, particularly hematologic adverse events. Higher-grade hematologic adverse events were notably less frequent and less severe thereafter. Adverse events occurring in more than 25% of patients are detailed on slide number 13. In general, the safety profile of zipalertinib plus chemotherapy was consistent with the safety profile of the individual agents and consistent with the previously reported zipalertinib monotherapy data.