Ariad Pharmaceuticals, Inc. (NASDAQ:ARIA) announced initiation of the Phase 1/2 clinical trial of AP32788, an investigational tyrosine kinase inhibitor (TKI) designed as a targeted therapy for patients with non-small cell lung cancer (NSCLC) with specific mutations in EGFR or HER2. AP32788 targets tumors driven by EGFR or HER2 kinases and was designed to achieve selective inhibition of these kinases with exon 20 mutations. There are currently no approved targeted treatment options available for the approximately four to nine percent of EGFR-mutated lung tumors with exon 20 insertion mutations in NSCLC patients.1Additionally, approximately two percent of NSCLC patients2 have HER2 mutations, with the majority having exon 20 insertion mutations.
“In the preclinical data presented at the AACR meeting last month, AP32788 demonstrated the ability to inhibit all tested EGFR and HER2 mutants, including exon 20 insertion mutants,” stated Tim Clackson, Ph.D., president of research and development and chief scientific officer of ARIAD. “We are pleased to be advancing AP32788, the next promising cancer medicine in the ARIAD pipeline, into clinical study for patients who currently have no targeted treatment options in these orphan oncology disease subsets.”
Clinical Trial Design
The trial will be conducted in two parts: a dose escalation phase, followed by an expansion phase. The initial Phase 1 dose-escalation trial segment will include patients with advanced NSCLC. Patients enrolled in this multicenter study will be refractory to standard available therapies. The primary objective of the Phase 1 segment of the trial is to determine the safety, tolerability, pharmacokinetic profile, and recommended Phase 2 dose (RP2D) of orally administered AP32788. ARIAD expects to enroll approximately 20 to 30 patients in this portion of the trial.
The Phase 2 expansion phase of the trial will include four histologically and molecularly defined patient cohorts, including:
- NSCLC patients with EGFR exon 20 activating insertions with no active, measurable central nervous system (CNS) metastases;
- NSCLC patients with HER2 exon 20 activating insertions or point mutations with no active, measurable CNS metastases;
- NSCLC patients with EGFR exon 20 activating insertions or HER2 exon 20 activating insertions or point mutations and active, measurable CNS metastases; and,
- NSCLC with other targets against which AP32788 has shown preclinical activity (examples include EGFR exon 19 deletions or exon 21 substitutions [with or without T790M mutations] and other uncommon EGFR activating mutations) with or without active, measurable CNS metastases.
The Phase 2 segment of the trial is planned to enroll approximately 80 patients and will evaluate anti-tumor activity of AP32788 in these molecularly defined patient populations.
“While there are approved TKIs for use in NSCLC patients with common EGFR activating mutations, there is a need for targeted treatment options to address the subset of patients with EGFR exon 20, HER2, and other uncommon EGFR mutations,” said Robert C. Doebele, M.D., Ph.D., associate professor, division of medical oncology, University of Colorado. “This trial will evaluate the safety, tolerability and optimal dose of AP32788, and the potential activity in NSCLC patients who currently have no targeted treatment options.”
ARIAD’s Phase 1/2 clinical trial of AP32788 is expected to enroll patients at up to seven centers during the dose-escalation phase. Additional centers will be activated for enrollment of the expansion cohorts.
EGFR mutations represent the largest known, targetable subset of NSCLC. While the most common types of EGFR mutation are addressed by approved TKI therapies, there are no targeted treatment options available for the approximately 4 to 9 percent of EGFR-mutated lung tumors with exon 20 insertion mutations. In addition, patients with HER2 mutations, mostly exon 20 insertion mutations, comprise approximately 2 percent of NSCLC patients and also have no currently approved targeted treatment options. ARIAD estimates that there are approximately 6,000 patients in the United Statesliving with EGFR exon 20 or HER2 point mutations, based on a broader data set of 175,000 patients with stage IIIb or IV NSCLC living in the U.S. in 2015, according to Kantar Health. (Original Source)
Shares of Ariad Pharmaceuticals closed last Friday at $8.21, up $0.18 or 2.24%. ARIA has a 1-year high of $10.07 and a 1-year low of $4.37. The stock’s 50-day moving average is $7.34 and its 200-day moving average is $6.27.
On the ratings front, Ariad has been the subject of a number of recent research reports. In a report issued on May 24, Jefferies Co. analyst Eun Yang reiterated a Buy rating on ARIA, with a price target of $13, which represents a potential upside of 58.3% from where the stock is currently trading. Separately, on May 23, William Blair’s Y Katherine Xu reiterated a Buy rating on the stock and has a price target of $10.
According to TipRanks.com, which ranks over 7,500 financial analysts and bloggers to gauge the performance of their past recommendations, Eun Yang and Y Katherine Xu have a total average return of -3.7% and 3.3% respectively. Yang has a success rate of 56.8% and is ranked #3471 out of 3891 analysts, while Xu has a success rate of 45.3% and is ranked #1229.
Overall, one research analyst has rated the stock with a Sell rating, 4 research analysts have given a Buy rating to the stock. When considering if perhaps the stock is under or overvalued, the average price target is $10.00 which is 21.8% above where the stock closed last Friday.
ARIAD Pharmaceuticals, Inc. operates as an oncology company which engages in the discovery, development, and commercialization of small-molecule drugs for the treatment of cancer. Its products include Iclusig and Caregivers. The company was founded by Harvey J. Berger in April 1991 and is headquartered in Cambridge, MA.