Axelar AB

The Challenge

Non-small cell lung cancer (NSCLC) is the most common form of lung cancer and it is among the most deadly of all cancers. Surgery, and to some extent radiotherapy, is used as a therapy for the very few patients with localized tumors. However, most NSCLC patients present with advanced metastatic disease already at the time of diagnosis, and the median survival time with first-line therapy is only around 10 months in spite of recent advances in treatment methods and introduction of new pharmaceuticals¹. The need for new effective targeted treatments is huge.

Axelar's Solution

Axelar has discovered a group of compounds that target the Insulin-like Growth Factor 1-receptor (IGF-1R). IGF-1R is overexpressed on cancer cells and its signaling pathway is believed to be of great importance for cancer cell growth, tumor cell survival and resistance to therapy². IGF-1R is therefore an excellent target for cancer drug development and a range of major tumors including NSCLC may be addressed through inhibition of this receptor. Axelar’s lead product AXL1717 is a small molecule that has been tested in patients with various solid tumors in a Phase I/II clinical study where all major end points were met. A randomized Phase II study in patients with NSCLC is ongoing.

Competitive Advantages

Because IGF-1R is structurally closely related to the insulin receptor, most of the small molecule IGF-1R inhibitors in clinical development also inhibit the insulin receptor with ensuing adverse effects. AXL1717 is the first small molecule inhibitor of IGF-1R in clinical development that clearly does not simultaneously inhibit the insulin receptor. AXL1717 has shown pronounced anti-tumor activity in a range of animal studies, demonstrating not only inhibited tumor growth, but also reduction of tumor size to the point of non-detectable size.

In a recently completed Phase I/II-study, AXL1717 was given as single agent to 49 patients with advanced, progressive, refractory solid tumors with no remaining treatment alternatives available. The data indicated good tolerability and oral bioavailability. The study was performed in a Phase I setting with safety assessments and recommended Phase II dose as the main endpoints. In spite of the trial design, the data also suggested that, particularly in some patients with NSCLC, AXL1717 showed signs of possible clinical benefit.

The 15 NSCLC patients with treatment durations of more than two weeks with AXL1717 showed a median time to progression of 31 weeks and a median survival of 60 weeks. In one NSCLC patient, a partial response was confirmed with RECIST criteria. The Phase I/II data clearly warranted continuing clinical development, and in December 2011 a randomized, open-label Phase II study with AXL1717 versus standard regimen cytotoxic chemotherapy (docetaxel) was initiated in squamous cell and adenocarcinoma NSCLC patients that has progressed from first line treatment. The main objective is to compare progression-free survival after 12 weeks in the two trial arms.  

The Market

Each year 1.1 million patients are diagnosed with lung cancer in the world and the disease accounts for 950,000 deaths annually³. Around 85 % of those patients have NSCLC⁴. Axelar’s lead product is focusing on the two most common types of NSCLC, squamous cell carcinoma and adenocarcinoma, which each year affect approximately 30 % each of the of the NSCLC patients⁵. In the United States