On May 10, 2016 Ignyta, Inc. (Nasdaq: RXDX), a precision oncology biotechnology company, reported company highlights and financial results for the first quarter ended March 31, 2016 (Press release, Ignyta, MAY 10, 2016, View Source [SID:1234512213]).
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"During 2016, we have continued to make significant progress towards becoming a leading precision medicine company focused on the development of first-in-class and best-in-class therapies for the benefit of cancer patients, and we have steadily advanced each of our three clinical stage assets," said Jonathan Lim, M.D., Chairman and CEO of Ignyta. "For our lead program, entrectinib, we have continued to successfully execute our potentially registration-enabling Phase 2 clinical trial, STARTRK-2. We also announced at the AACR (Free AACR Whitepaper) Annual Meeting compelling results from our two Phase 1 clinical trials, highlighting entrectinib’s emerging safety and efficacy profile. For the RXDX-105 program, we selected a recommended Phase 2 dose and initiated the Phase 1b portion of our ongoing clinical trial. For the taladegib program, we reported a complete response in a patient with medulloblastoma – providing the first clinical proof of concept for taladegib in a solid tumor type outside of advanced basal cell carcinoma. Finally, we strengthened our balance sheet, enabling us to continue to move rapidly to develop meaningful new therapies for the benefit of cancer patients."
Company Highlights
Updated Entrectinib Data Presented at AACR (Free AACR Whitepaper) Annual Meeting
In April 2016, updated results of the two Phase 1 clinical trials of entrectinib, the company’s proprietary oral tyrosine kinase inhibitor targeting solid tumors harboring activating alterations to NTRK1, NTRK2, NTRK3, ROS1, or ALK, were presented in an oral plenary session at the 2016 Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) in New Orleans, Louisiana.
The data cut-off for the AACR (Free AACR Whitepaper) presentation was March 7, 2016. Highlights of the data included:
Safety
A total of 119 patients with a range of solid tumors had been dosed across the two Phase 1 clinical trials, with 45 patients treated at the recommended Phase 2 dose (RP2D) of 600 mg, taken orally once per day (QD).
Entrectinib was well tolerated:
Across both studies, the most frequent (>10% incidence) treatment-related adverse events were fatigue (44%), dysgeusia (41%), paresthesia (28%), nausea (24%), and myalgia (22%).
The vast majority of treatment-related adverse events were Grade 1 or 2 in severity.
The most frequent (>2% incidence) Grade 3 treatment-related adverse events were fatigue (4%) and anemia (3%).
Adverse events were reversible with dose modification.
There was no evidence of cumulative toxicity, hepatic or renal toxicity, or QTc prolongation.
Efficacy
Across the two Phase 1 clinical studies, there were 25 patients treated who met the company’s Phase 2 clinical trial eligibility criteria, which include:
Presence of NTRK1/2/3, ROS1, or ALK gene rearrangements, as opposed to other types of molecular alterations (e.g., SNPs, amplifications, deletions);
Naïve to inhibitors of the relevant target (Trk, ROS1, or ALK, respectively); and
Treatment at or above the RP2D.
Among the 25 patients treated who met the company’s Phase 2 clinical trial eligibility criteria, tumor regression was seen in 80% (20 out of 25 treated patients):
Twenty-four patients had tumors that were evaluable by RECIST criteria. The overall response rate by RECIST was 79% (19 responses, including two complete responses, out of 24 treated patients, as assessed and confirmed by the clinical sites).
One patient had an astrocytoma. Assessment by RECIST criteria demonstrated stable disease. However, since RECIST criteria are not validated for primary brain tumors, the clinical site performed three-dimensional volumetric analysis of this patient’s tumor to determine changes in tumor size, which resulted in an estimated 45% decrease in tumor size from baseline.
The responses included:
with respect to patients with NTRK1/2/3 gene rearrangements who met the company’s Phase 2 eligibility criteria, three confirmed responses out of three patients evaluable by RECIST criteria, one of whom had metastases to the central nervous system that resulted in a complete response. In addition, a patient with an astrocytoma had a response as determined by volumetric analysis. Two of these Trk patients remained on study, one of whom had been on study for longer than 12 months;
with respect to patients with ROS1 gene rearrangements who met the company’s Phase 2 eligibility criteria, 12 confirmed responses out of 14 patients, including 11 confirmed responses out of 13 patients with non-small cell lung cancer (NSCLC). Eleven of the ROS1 responders remained on study in response, with the longest at 27 months. One ROS1 NSCLC patient has met the criteria for RECIST progression but has remained on study due to clinical benefit; and
with respect to patients with ALK gene rearrangements who met the company’s Phase 2 eligibility criteria, four confirmed responses out of seven patients, with another patient having stable disease. Two of the responders remained on study in response, as did the patient with stable disease.
Many of these responses occurred rapidly, within the first four weeks of entrectinib treatment. Seventeen of the patients remained on study treatment, having received up to 27 months of treatment. Of note, three of four patients with primary or metastatic central nervous system (CNS) disease responded.
In addition, the AACR (Free AACR Whitepaper) presentation included a late-breaking case study of a 20-month-old baby boy with NTRK3-rearranged infantile fibrosarcoma that had metastasized to the brain, who had exhausted all available therapies and was enrolled under a compassionate use protocol and therefore was not included in the Phase 1 cohort. The patient was first dosed in February 2016, and after five weeks of treatment experienced a decrease in his brain lesions of approximately 58%, as estimated from radiology assessment, with accompanying clinical improvement.
Expansion of RXDX-105 Clinical Trial
In March 2016, the company announced the selection of an RP2D and the initiation of the Phase 1b portion of its Phase 1/1b clinical trial of RXDX-105, the company’s orally available, small molecule multikinase inhibitor with potent activity against such targets as RET and BRAF. The Phase 1b portion of the study utilizes a basket design focusing on patients with solid tumors that contain molecular alterations of RET or BRAF. In addition, based on clinical data seen to date, the company intends to build into the Phase 1b portion of the study one or more baskets to evaluate RXDX-105 in both squamous non-small cell lung cancer and non-small cell lung adenocarcinoma.
Taladegib Complete Response Outside of Basal Cell Carcinoma
In April 2016 at the AACR (Free AACR Whitepaper) Annual Meeting, the company reported the first clinical proof of concept for taladegib in a solid tumor type outside of advanced basal cell carcinoma, in a patient with medulloblastoma who had a complete response. The company further announced that it would be exploring medulloblastoma and other solid tumor types driven by hedgehog pathway alterations in a Phase 1b basket study, which is expected to be initiated in the third quarter of 2016.
Financing Transaction
In May 2016, the company issued an aggregate of 9.2 million shares of its common stock in an underwritten public offering at a purchase price of $6.25 per share, which resulted in aggregate gross proceeds of $57.5 million.
First Quarter 2016 Financial Results
For the first quarter of 2016, net loss was $25.5 million, or $0.79 per share, compared with $23.5 million, or $1.15 per share, for the first quarter of 2015.
Ignyta did not record any revenue for the three months ended March 31, 2016, or for the three months ended March 31, 2015.
Research and development expenses for the first quarter of 2016 were $19.8 million, compared with $20.2 million for the first quarter of 2015. During the first quarter of 2015, the company recorded an in-process research and development charge representing the net value of the assets exchanged for the intellectual property assets acquired from Teva, as well as related transaction and drug product costs. Excluding these costs, research and development costs would have increased in 2016 as compared to 2015 by $12.7 million, primarily due to an $8.0 million increase in the development costs associated with the company’s entrectinib, taladegib, and other product candidates. The remaining increase in costs between periods was due to personnel expenses related to hiring and engaging additional employees and consultants to help advance the company’s product candidates.
General and administrative expenses were $5.2 million for first quarter of 2016, compared with $2.8 million for first quarter of 2015. The increase was primarily caused by increases in personnel costs, as well as higher facilities-related expenses resulting from the expansion of the company’s leased facilities space. The increase was also attributable to increases in legal and intellectual property costs, consulting fees, and depreciation expenses.
At March 31, 2016, the company had cash, cash equivalents, and available-for-sale securities totaling $151.2 million and current and long-term debt of approximately $31.0 million. This balance does not include the gross proceeds of $57.5 million from the May 2016 underwritten public offering. At December 31, 2015, the company had cash, cash equivalents, and available-for-sale securities totaling $172.1 million and current and long-term debt of $31.0 million.