Challenge to AstraZeneca's Cancer Drug as Synlogic's TY-9591 Outperforms Osimertinib

On March 9, Synlogic announced that its self-developed drug TY-9591 has successfully outperformed AstraZeneca's renowned lung cancer treatment, Osimertinib, in a pivotal Phase II clinical trial.

Founded in 2017, Synlogic is an innovative pharmaceutical company set to go public on the Hong Kong Stock Exchange in August 2024. TY-9591, a deuterated variant of Osimertinib, is the company's lead pipeline candidate.

Market reaction to this announcement was swift, interpreting it as a significant challenge to Osimertinib, which is widely regarded as a "miracle drug" for lung cancer. On March 10, Synlogic's stock surged by over 40% in early trading, ultimately closing with a 16.18% increase.

In response to this emerging competitor, AstraZeneca stated on March 11 that it could not provide feedback due to the limited information currently available from the study.

Osimertinib, the world's first third-generation EGFR-TKI drug, was approved in the U.S. in 2015 and entered the Chinese market in 2017. It has consistently generated robust sales, reaching nearly $5.8 billion globally in 2023. Even with the arrival of domestic third-generation EGFR-TKI drugs, Osimertinib has maintained a dominant position, controlling around 80% of the small molecule targeted lung cancer drug market in China.

Notably, Osimertinib's compound patent will not expire until 2032.

Synlogic's strategy involves deuterated modifications to Osimertinib. This approach is considered one of the least risky and most straightforward methods to enhance existing drugs. Domestic companies like Zai Lab and HEC Group have also focused on deuterated drugs, with Zai Lab's Donafenib being a notable example that was approved in 2021.

In terms of indications, Synlogic is targeting lung cancer with brain metastases, a critical factor affecting the survival of lung cancer patients. The occurrence of brain metastases is significantly higher in patients with EGFR mutations, with risks ranging from 40% to 60%. Osimertinib is recognized for its effectiveness in managing brain metastases, contributing to its success in head-to-head trials.

While Synlogic has not disclosed specific Phase II data, it reported that the trial enrolled 224 patients, achieving the primary endpoint of intracranial objective response rate (iORR). More detailed results are expected to be shared at upcoming international or domestic clinical conferences.

The announcement has sparked both enthusiasm and skepticism within the industry. Critics have raised questions about Synlogic's choice of objective response rate as the primary endpoint, arguing that it does not align with industry standards and differs from AstraZeneca's original trial design.

In a previous instance in September 2024, another company, Kangfang Biopharma, claimed a decisive victory in a head-to-head trial against Merck's Keytruda based on multiple data points, but lacked overall survival data, prompting a cautious response from Merck.

Osimertinib's rise to first-line treatment status was largely due to its achievement of significant median progression-free survival (PFS) data. For patients with brain metastases, Osimertinib demonstrated a PFS increase from 9.6 months to 15.2 months, solidifying its reputation as a leading treatment.

Although Synlogic has reported an impressive 100% iORR in its single-agent treatment for non-small cell lung cancer with brain metastases, this single data point alone may not be sufficient to sway the medical community, and consensus will depend on comprehensive results.

In the competitive landscape, Osimertinib faces challenges not only from Synlogic but also from several other third-generation EGFR-TKI drugs that have recently entered the market. Companies like Betta Pharmaceuticals and Bayer are already exploring fourth-generation TKIs, and Johnson & Johnson's dual-antibody combination has received FDA approval.

As Osimertinib stands firm against this growing competition, it is clear that strong clinical data is just one aspect of maintaining its market position. This is a critical factor that Synlogic and other competitors must take into account.

On March 11, Synlogic's stock declined nearly 9%, resulting in a market capitalization decrease of over HKD 1 billion.