BioNTech unveils Phase 2 lung cancer data amid VEGF bispecifics focus

Last week, the pharmaceutical industry was buzzing with excitement as Summit and Akeso’s bispecific antibody surpassed Merck’s Keytruda in a Phase 3 lung cancer trial. Now, BioNTech is making headlines with promising mid-stage data for its own similar lung cancer treatment.

The German pharmaceutical company presented data at Europe's major cancer conference in Barcelona, showcasing the performance of their PD-L1xVEGF bispecific antibody, BNT327, which they licensed from Biotheus. In a single-arm Phase 2 trial conducted in China, BNT327 achieved a confirmed objective response rate (ORR) of 57.8% among 64 patients with EGFR-mutant non-small cell lung cancer (NSCLC) who had previously received standard treatments. For 13 patients with high PD-L1 expression, the confirmed ORR was even higher at 92.3%.

BioNTech's success with BNT327 brings dual benefits: a notable 37% rise in the company’s stock price following Summit’s announcement of its own PD-1/VEGF bispecific ivonescimab, and encouraging data from the Biotheus-sponsored trial that merit further investigation into BNT327. However, the company has not yet disclosed subsequent steps for this asset.

The promising results from both BNT327 and ivonescimab have heightened expectations for this treatment approach, which did not receive much attention until recently. Larger pharmaceutical companies are cautiously observing from the sidelines, while smaller biotech firms are seizing the opportunity to highlight their developmental plans amid increased stock interest.

According to analysts from TD Cowen, BNT327 demonstrated "solid efficacy" comparable to Summit’s ivonescimab, with fewer anti-VEGF-related toxicities than bevacizumab, an established anti-VEGF antibody.

At the conference, Adrianus Johannes de Langen from Amsterdam University Medical Center, who was not part of the study, described the ORR as “impressive.” However, he noted that it remains uncertain how these results will affect key survival outcomes and which patients might benefit from adding a PD-L1xVEGF bispecific antibody to chemotherapy in the second line, especially given a recent first-line approval for lung cancer.

Last month, the FDA approved Johnson & Johnson’s EGFRxMET bispecific Rybrevant in combination with EGFR tyrosine kinase inhibitor Lazcluze for specific patients with first-line EGFR-mutated NSCLC. However, this combination has significant toxicities, leaving room for bispecific methods, as noted by Dana Farber Cancer Institute oncologist Pasi Jänne.

Instil Bio, another bispecific antibody developer, saw its stock price soar by 493% following Summit’s data announcement. Instil Bio revealed its plans for a PD-L1xVEGF bispecific antibody licensed from ImmuneOnco, expecting to begin mid-stage studies of IMM2510 as a monotherapy for second-line NSCLC in the US later this year. Should these studies prove successful, they may initiate global Phase 3 studies for first-line NSCLC and potentially triple-negative breast cancer.

The surge in promising data comes shortly after Summit reported that ivonescimab reduced the risk of progression or death by up to 49% in certain lung cancer patients in China compared to Keytruda. If these results are replicated in US studies and subsequently approved, ivonescimab could replace Keytruda in first-line NSCLC treatment, a significant achievement given Keytruda’s status as the top-selling cancer drug globally.

Summit's strategic move to challenge Keytruda has clearly paid off, doubling the company's market value to $23.5 billion in just a week. Meanwhile, Merck, the maker of Keytruda, expressed safety concerns regarding Summit’s drug, citing the inherent safety issues associated with VEGF inhibitors. Despite this, the side effects observed in the ivonescimab trial were manageable, suggesting potential for this drug class.

The pharmaceutical industry is closely watching these developments, recognizing the potential of bispecific antibodies in cancer treatment. Large companies like Regeneron and AstraZeneca are weighing the viability of such approaches, with ongoing research into various bispecific candidates. Combining separate VEGF and PD-L1 agents has yielded mixed results in the past, but there is optimism that a dual-targeting "all-in-one molecule" might offer superior efficacy.

Overall, the recent advancements in bispecific antibodies targeting both VEGF and PD-1 or PD-L1 signal a promising frontier in cancer therapy, warranting further exploration and data validation.