On November 9, 2015 Ignyta, Inc. (Nasdaq: RXDX), a precision oncology biotechnology company, reported company highlights and financial results for the third quarter ended September 30, 2015 (Press release, Ignyta, NOV 9, 2015, View Source [SID:1234508136]).
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"Since the beginning of the third quarter of 2015, we have continued to make significant progress toward our objective of becoming a leading precision oncology biotechnology company that can provide patients with a variety of compelling cancer treatment options," said Jonathan Lim, M.D., Chairman and CEO of Ignyta. "We continued to make strategic additions to our clinical pipeline that can help us eradicate residual disease in precisely defined patient populations through our acquisition from Lilly of exclusive worldwide rights to taladegib, a potent, orally bioavailable small molecule hedgehog/smoothened antagonist that has achieved compelling clinical proof of concept and a recommended Phase 2 dose in a Phase 1 dose escalation clinical trial. We also are grateful to Lilly for concurrently investing $30 million by acquiring 1.5 million shares of our common stock at $20 per share."
"In addition, we made strong progress executing development of our existing clinical-stage product candidates, including presenting promising Phase 1 data at leading conferences for entrectinib and RXDX-105, initiating our potentially registration-enabling STARTRK-2 Phase 2 clinical trial of entrectinib, and initiating our Phase 1/1b clinical trial of RXDX-107," continued Dr. Lim. "We expanded our team with incredibly talented people who, along with our existing team members, will help advance our multiple, complementary development programs for the benefit of cancer patients."
Company Highlights
Taladegib Exclusive License and Concurrent Stock Purchase by Lilly
In November 2015, Ignyta announced it had exclusively licensed from Eli Lilly and Company worldwide rights relating to Lilly’s taladegib oncology development program in exchange for an upfront payment of $2.0 million in cash and the issuance to Lilly of approximately 1.2 million shares of Ignyta’s common stock. Taladegib is a potent, orally bioavailable small molecule hedgehog/smoothened antagonist that has achieved compelling clinical proof of concept and a recommended Phase 2 dose in a Phase 1 dose escalation clinical trial. Ignyta also licensed exclusive worldwide rights to the topical formulation of taladegib, which is a late preclinical stage program being developed for the potential treatment of patients with superficial and nodular basal cell carcinoma.
Concurrently with the license, Ignyta entered into a stock purchase agreement with Lilly under which Lilly purchased a further 1.5 million shares of Ignyta common stock at a price of $20 per share in a private placement.
Presentation of RXDX-105 Clinical Data at ENA Conference
In November 2015, Ignyta announced interim results from the company’s ongoing Phase 1 clinical trial of RXDX-105, the company’s orally-available, small molecule multikinase inhibitor with potent activity against such key targets as RET and BRAF, which were presented at the 27th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics in Boston, Massachusetts.
The dose escalation clinical trial was designed to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D), as well as preliminary anti-cancer activity, of single agent RXDX-105 in patients with advanced or metastatic solid tumors that were not selected based on any molecular alteration.
As of the October 26, 2015, data cut-off for the presentation, the findings showed:
A total of 41 patients with a range of solid tumors were dosed in the clinical trial;
RXDX-105 was well tolerated to date:
The most frequent treatment-emergent adverse events were fatigue, vomiting, nausea, decreased appetite, constipation, diarrhea, hypertension and muscle spasms;
Three Grade 3 dose-limiting toxicities were observed: maculopapular rash, fatigue and diarrhea, each of which resolved upon study drug interruption;
There were no treatment-related serious adverse events. Two Grade 4 adverse events had occurred, consisting of intestinal obstruction and anemia, neither of which was considered to be treatment-related. No Grade 5 treatment-related adverse events or cumulative adverse events were observed;
The MTD and RP2D had not yet been determined;
Pharmacokinetic measurements showed increased exposure with increasing dose, with a half-life compatible with once-daily dosing. Dosing in the fed state appears to further increase exposure;
Exposure was reaching levels expected to be efficacious based on tumor growth inhibition in animal models of RET- and BRAF-driven tumors; and
Tumor regression was observed in six patients treated with 275 mg, including one confirmed partial response (40% reduction) in a patient with non-small cell lung cancer (NSCLC) with a KRAS G12C mutation. Two additional patients with thyroid cancer and squamous cell lung cancer exhibited reductions of 20% and 27%, respectively. In patients with tumor regression, there appears to be an exposure/response correlation.
Initiation of STARTRK-2 Phase 2 Clinical Trial of Entrectinib
In September 2015, Ignyta announced the initiation of its Phase 2 clinical trial of entrectinib, the company’s proprietary oral tyrosine kinase inhibitor targeting solid tumors that harbor activating alterations to NTRK1, NTRK2, NTRK3, ROS1 or ALK. This clinical trial is called STARTRK-2, the second of the "Studies of Tumor Alterations Responsive to Targeting Receptor Kinases." The trial is a global, multicenter, open label, potentially registration-enabling Phase 2 clinical trial of entrectinib that utilizes a basket design with screening of patient tumor samples for gene rearrangements of the relevant targets. Such a basket design takes full advantage of entrectinib’s demonstrated preliminary clinical activity across a range of different tumor types that harbor a rearrangement of one of the genes encoding any one of entrectinib’s five protein targets.
Presentation of Updated Interim Entrectinib Clinical Trial Results at European Cancer Conference
In September 2015, the company announced updated interim results of its Phase 1 clinical trials of entrectinib, which were presented in an oral presentation session at the 2015 European Cancer Congress (ECC 2015) in Vienna, Austria.
The clinical trials included the ALKA-372-001 study and the STARTRK-1 study. Both trials were designed to determine the MTD and/or RP2D, as well as preliminary anti-cancer activity, of single agent entrectinib in patients with solid tumors with the relevant molecular alterations: NTRK1 (encoding TrkA), ROS1 or ALK for ALKA-372-001 and NTRK1/2/3 (encoding TrkA/B/C), ROS1 or ALK for STARTRK-1.
As of the August 15, 2015, data cut-off for the presentation, the findings showed:
A total of 92 patients with a range of solid tumors were dosed across both clinical trials, with nine patients treated at or above the RP2D beyond six months and one patient beyond one year.
Entrectinib was well tolerated:
Across both studies, the most frequent (>10% incidence) treatment-related adverse events were fatigue, dysgeusia, paresthesia, nausea, and myalgia. Seven of these were Grade 3 in severity, consisting of fatigue (4 patients), cognitive impairment (2 patients), and diarrhea (1 patient). No Grade 4 treatment-related adverse events were observed;
Across both studies, there were only three treatment-related serious adverse events: Grade 3 cognitive impairment and Grade 3 myocarditis, both of which occurred above the RP2D, and Grade 2 fatigue. All events were reversible and resolved upon dose modification;
The fixed daily dose RP2D was determined to be 600 mg, taken orally once per day (QD);
18 patients across both clinical trials met the company’s expected Phase 2 eligibility criteria, which include:
Presence of an NTRK1/2/3, ROS1 or ALK gene rearrangement, as opposed to other types of molecular alterations (e.g., SNPs, amplifications, deletions);
ALK-inhibitor and/or ROS1-inhibitor naïve; and
Treatment at or above the RP2D;
The response rate in the 18 patients who met these criteria across both studies was 72% (13 responses out of 18 treated patients, as assessed by the clinical sites). Nine of these responders remained on study treatment with durable responses of up to 21 treatment cycles. An additional 3 patients remained on study with stable disease. The responses included:
3 responses out of 4 patients with an NTRK1, NTRK2 or NTRK3 gene rearrangement, including patients with NSCLC, colorectal cancer and salivary gland cancer, with one of the responding patients remaining on treatment at 6 months; a fourth patient with an astrocytoma remained on treatment after two months with stable disease;
6 responses, including one complete response, out of 8 patients with a ROS1 gene rearrangement, all of which were in NSCLC. All of the patients who responded remained on treatment, the longest at 21 months; and
4 responses out of 6 patients with an ALK gene rearrangement, including two NSCLC patients and two patients with other solid tumors; two of the 4 responders had subsequently progressed.
Entrectinib had demonstrated objective tumor response in the central nervous system (CNS), a frequent site of metastases and progression of advanced solid tumors.
Issuance of Patent Covering Composition of Matter of RXDX-107
In October 2015, Ignyta announced that the U.S. Patent and Trademark Office issued U.S. Patent No. 9,150,517, entitled "Bendamustine Derivatives and Methods of Using Same." This patent contains claims that cover the composition of matter of Ignyta’s product candidate RXDX-107, and pharmaceutical compositions comprising RXDX-107. RXDX-107 is the company’s new chemical entity, next generation chemotherapeutic comprising an alkyl ester of bendamustine encapsulated in human serum albumin (HSA) to form nanoparticles. The patent has an expiration date of 2033, which does not include any potential patent term extension.
Initiation of Phase 1/1b Clinical Trial of RXDX-107
In September 2015, the company announced the initiation of its Phase 1/1b clinical trial of RXDX-107. This multicenter, open-label, dose-escalation clinical trial is designed to determine the MTD, RP2D, tolerability, pharmacokinetics and preliminary clinical activity of RXDX-107 in adult patients with locally advanced or metastatic solid tumors.
Enhancement of Leadership Capacity
In September 2015, Ignyta announced that Igor Bilinsky, Ph.D., was appointed to the newly-created role of General Manager, Immuno-Oncology and Senior Vice President, Special Operations, and that Valerie Harding, Ph.D., was appointed to the newly-created role of Senior Vice President, Chemistry, Manufacturing, and Controls.
Third Quarter 2015 Financial Results
For the third quarter of 2015, net loss was $14.6 million, or $0.49 per share, compared with $10.7 million, or $0.55 per share, for the third quarter of 2014.
Ignyta did not record any revenue for the three months ended September 30, 2015 or September 30, 2014.
Research and development expenses for the third quarter of 2015 were $10.4 million, compared with $8.6 million for the third quarter of 2014. The increase was primarily due to an increase in activities relating to development of entrectinib and the company’s other product candidates, including the assets acquired from Teva Pharmaceutical Industries Ltd. in March 2015. The increase between periods was also due to personnel expenses related to hiring and engaging additional employees and consultants to help advance the company’s product candidates and facilities-related expenses as a result of the expansion of the company’s leased facilities space.
General and administrative expenses were $3.9 million for the third quarter of 2015, compared with $2.2 million for third quarter of 2014. The increase was primarily caused by increases in personnel costs and investor relations, audit, legal and intellectual property costs.
At September 30, 2015, the company had cash, cash equivalents and available-for-sale securities totaling $163.1 million and current and long-term debt of approximately $31.0 million. At December 31, 2014, the company had cash, cash equivalents and available-for-sale securities totaling $76.6 million and current and long-term debt of approximately $21.0 million.