ImClone's Late-Stage Pipeline Includes a Potential Erbitux Competitor
The Pink Sheet Daily. 2008 Aug 5, S Haley
ImClone's pipeline, with five clinical-stage monoclonal antibodies, one a late-stage Erbitux look-alike, and another half-dozen nearing IND readiness, makes the biotech a logical acquisition for any pharma looking to bolt on not only biotech capabilities but an oncology portfolio.
Indeed, the maturity of ImClone's pipeline of cancer biologics is one reason Bristol-Myers Squibb is trying to buy out the remaining shares it doesn't already own in the company. That and gaining control of the blockbuster oncologic Erbitux (cetuximab), which the companies currently commercialize together ("The Pink Sheet" DAILY, July 31, 2008).
Altogether, New York-based ImClone has five monoclonal antibodies in the clinic and another six are IND ready, ImClone Chief Medical Officer Eric Rowinsky told investors during the firm's half-year earnings call July 24.
ImClone's lead candidate is IMC-1121B, an unpartnered angiogenesis inhibitor that targets vascular endothelial growth factor-2. It is the biotech's first molecule to enter Phase III since Erbitux. ImClone is accelerating 1121B's development based on "clinical signals exhibited by other VEGF inhibitors that would not be expected to inhibit the VEGF-2 receptor as strongly as" it does, Rowinsky said.
A Phase III study of 1121B in metastatic breast cancer is set to launch this quarter under a special protocol assessment with FDA that stipulates a progression-free survival endpoint.
The study aims to enroll 1,100 women with unresectable locally recurrent or metastatic breast cancer who have not received prior chemo ("The Pink Sheet" DAILY, April 22, 2008). It is being conducted by the Cancer International Research Group.
A second Phase III trial is planned to launch within the year testing 1121B as a second-line therapy against gastric cancer, "an indication with a much more abbreviated time line," Rowinsky noted.
ImClone also has Phase II studies going to test 1121B in metastatic melanoma, unresectable liver cancer and refractory kidney cancer, Rowinsky said, adding that all of the trials are "briskly accruing patients."
A Phase II trial is also recruiting patients for an open-label study of 1121B against platinum-refractory persistent or recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer. Over the next few months, Phase II studies are set to open in breast, lung, colorectal and prostate cancers, as well.
IMC-11F8 has Erbitux-like characteristics
IMC-11F8, an anti-epidermal growth factor inhibitor, has EGFR-binding characteristics similar to cetuximab, according to an abstract presented in June at the annual meeting of the American Society of Clinical Oncology. Interim data from the 44-patient Phase II open-label study in metastatic colorectal cancer described in the abstract show an acceptable safety profile, as well as a 65.2 percent objective response rate, Rowinsky said during the call.
KRAS genetic status of the tumor was not part of patient selection for the trial, but a retrospective analysis is being performed, Rowinsky said. EGFR inhibitors, including Erbitux, have demonstrated efficacy in patients with wild-type KRAS tumors, but not in those with tumor KRAS mutations.
ImClone is in final planning for global Phase III studies of 11F8 in CRC and in non-small cell lung cancer, which will prospectively screen patients "based on molecular profiling data" identified from trials of other EGFR inhibitors, Rowinsky said. The trials are set to launch in 2009.
Commenting on the BMS takeover bid, Rodman & Renshaw analyst Michael King observed that the increased focus on personalized medicine led by the KRAS biomarker in CRC and the potential role of EGFR inhibitors in NSCLC "may have hastened [BMS'] decision to step in."
There has been speculation that BMS, also based in New York, may have timed its offer to gain control of IMC-11F8, which, according to ImClone, could "have significant competitive effect" on Erbitux and which ImClone says it owns exclusively ("The Pink Sheet" DAILY, Aug. 4, 2008).
IMC-A12 targets the insulin-like growth factor-1 receptor
ImClone is planning to begin pivotal studies of IMC-A12 in the second half of 2009.
During the second quarter of 2008, Phase II studies opened in head and neck cancer and in advanced liver cancer. In addition, a series of Phase I/II trials of IMC-A12 in advanced pancreatic cancer opened enrollment in May, a Phase I trial testing it in combination with the mTOR inhibitor temsirolimus (Wyeth's Torisel) in patients with advanced solid malignancies and lymphoma launched in June, and a Phase II trial in patients with several types of soft tissue sarcoma launched in July.
During the second half of the year, other Phase II studies are set to test A12 in second line treatment of prostate, neuroendocrine and NSCLC and in early stage CRC.
Many of those studies are being conducted by U.S. cooperative groups through the National Cancer Institute, Rowinsky said, adding that they do not duplicate ImClone-sponsored trials.
Finally, Phase I programs for IMC-18F1, a VEGFR-1 inhibitor, and IMC-3G3, which targets platelet-driven growth factor alpha, will be completed in the second half of 2008, and Phase II studies of both are planned for 2009.
ImClone plans to submit INDs in the second half of 2008 for six other candidates, including an IGg-1 mAb that targets FMS-like tyrosine kinase3, the most commonly mutated protein in acute myelogenous leukemia.
