- Interim Phase 1 Data: On October 10, 2016, AveXis reported interim data as of September 15, 2016 from the ongoing Phase 1 trial of AVXS-101 in SMA Type 1, as presented by Jerry Mendell, M.D., director of the Center for Gene Therapy at The Research Institute at Nationwide Children's Hospital, at the 21st International Annual Congress of the World Muscle Society in Granada, Spain.
- AVXS-101 appears to have a favorable safety profile and to be generally well tolerated in patients studied as of September 15, 2016. There had been a cumulative total of 118 adverse events (AEs) reported, 34 of which were determined to be serious adverse events (SAEs) and 84 were determined to be non-serious AEs. As previously reported, a total of 5 AEs in 4 patients were treatment-related. Two were deemed treatment-related SAEs (experienced by 2 patients) and three were deemed non-serious AEs (experienced by 2 patients). All consisted of clinically asymptomatic liver enzyme elevations. All of the elevated liver enzyme AEs and SAEs were clinically asymptomatic and resolved with prednisolone treatment. There were no clinically significant elevations of gamma-glutamyl transferase (GGT), alkaline phosphatase or bilirubin, and as such Hy's Law was not met. Other non-treatment-related AEs were expected and were associated with SMA.
- All patients in Cohort 2 (proposed therapeutic dose) were event-free, defined as death or requiring at least 16 hours per day of ventilation support for breathing for greater than two weeks in the absence of an acute reversible illness, or perioperatively. The median age at last follow-up for Cohort 2 was 17.3 months, with the oldest patient at 27.4 months of age. As previously reported, one patient in Cohort 1 (the low-dose cohort) had a pulmonary event in the third quarter. The patient had increased use of bi-level positive airway pressure (BiPAP) in advance of surgery related to hypersalivation, a condition experienced by some SMA patients; the event was determined by independent review to represent progression of disease and not to be related to the use of AVXS-101.
- Mean increases in CHOP-INTEND scores of 9.0 points in Cohort 1 and 24.8 points in Cohort 2 were observed, reflecting improvement in motor function. The Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) is a test developed to measure motor skills of patients with SMA Type 1.
- 11 out of 12 patients in Cohort 2 achieved CHOP-INTEND scores of at least 40 points.
- 9 out of 12 patients in Cohort 2 achieved CHOP-INTEND scores of at least 50 points.
- 3 out of 12 patients in Cohort 2 achieved CHOP-INTEND scores of at least 60, which is in a range considered to be normal.
- For the first time, interim data from the trial were presented that highlighted patient achievement of key motor development milestones. As of September 15, 2016, two-thirds of patients in Cohort 2 had achieved the ability to sit unassisted, including one patient whose achievement of this milestone was confirmed after September 15. In Cohort 2, 11 of 12 patients achieved head control, 7 of 12 patients could roll over completely and 11 of 12 patients could sit with support. Two patients were walking independently, including one whose achievement of this milestone was confirmed after September 15. These two patients each achieved earlier and important developmental milestones such as crawling, standing with support, standing alone and walking with support.
- On November 1, 2016, AveXis announced the pivotal study of AVXS-101 in SMA Type 1 will reflect a single-arm design, using natural history of the disease as a comparator, and will enroll approximately 20 patients. This update was based on the receipt of the minutes following a Type B meeting with the U.S. Food and Drug Administration (FDA).
- In addition to evaluating safety, the planned program is expected to evaluate achievement of motor milestones, specifically patients' ability to sit unassisted, as well as an efficacy measure defined by the time from birth to an "event," defined as death or requiring at least 16 hours per day of ventilation support for breathing for greater than two weeks in the absence of an acute reversible illness, or perioperatively.
- The FDA also indicated its preference for a design with co-primary endpoints consisting of a measure of developmental milestone achievement (such as sitting unassisted) along with a clinically meaningful measure of survival (such as time to an "event" as described above). Based on FDA's suggestions as well as other expert input, AveXis continues to evaluate a number of the details of the trial design. More specific information will be made available at the time the study is initiated, which is expected in the first half of 2017.
- The Company's strategy with the SMA Type 1 program is to complete the ongoing Phase 1 trial and, in parallel, execute on the single-arm pivotal trial, while continuing collaborative discussions with the FDA regarding the most expeditious pathways for FDA approval of AVXS-101.
- On September 13, 2016, the Company completed an underwritten public offering of 4,887,500 shares of its common stock, 4,597,645 shares of which were issued and sold by the Company, including the exercise in full by the underwriters of their option to purchase 637,500 shares from the Company, and 289,855 shares of which were sold by PBM Capital Investments, LLC (PBM), an existing stockholder of the Company, each at a public offering price of $34.50 per share. After deducting the underwriting discounts and commissions and other offering expenses payable by the Company, the net proceeds to the Company were approximately $149.1 million. The Company did not receive proceeds from the sale of the common stock by PBM.
- Provide quarterly updates on the ongoing Phase 1 trial of AVXS-101 in SMA Type 1.
- Initiate a Phase 1 safety and dosing study of AVXS-101 via intrathecal (IT) delivery in patients with SMA Type 2 in the second half of 2016.
- Report 13.6 months of data for all patients in the ongoing SMA Type 1 Phase 1 trial in the first quarter of 2017.
- Initiate pivotal trials of AVXS-101 in patients with SMA Type 1 in the United States and Europe in the first half of 2017.
- Cash Position: As of September 30, 2016, AveXis had $263.6 million in cash and cash equivalents.
- R&D Expenses: Research and development expenses were $14.1 million for the third quarter of 2016 (which included $2.7 million of non-cash stock-based compensation expense), compared to $6.3 million for the same period in 2015 (which included $5.3 million of non-cash stock-based compensation expense), an increase of $7.8 million. The increase in research and development expenses was primarily attributable to an increase in expenses necessary to support the advancement of the Company's manufacturing product development efforts, clinical and pre-clinical programs, primarily the ongoing trial of AVXS-101 in SMA Type 1, and increases in employee compensation. Partially offsetting the increase in R&D spending was lower stock-based compensation expense of $2.6 million.
- G&A Expenses: General and administrative expenses were $7.1 million for the third quarter of 2016 (which included $2.7 million of non-cash stock-based compensation expense), compared to $3.7 million for the same period in 2015 (which included $1.5 million of stock-based compensation expense), an increase of $3.4 million. The increase in general and administrative expenses was primarily attributable to an increase in employee compensation, legal and professional fees and other infrastructure costs to support the company's overall growth, and higher stock-based compensation expense.
- Net Loss: Net loss was $21.1 million, or $0.87 per share, for the third quarter of 2016, compared to a net loss of $9.9 million, or $1.32 per share, for the third quarter of 2015.
|Three Months Ended September 30,||Nine Months Ended September 30,|
|General and administrative||7,082,683||3,740,077||17,324,863||6,651,233|
|Research and development||14,097,713||6,289,350||40,542,323||18,756,214|
|Total Operating Expenses||21,180,396||10,029,427||57,867,186||25,407,447|
|Net loss and comprehensive loss||$||(21,081,808||)||$||(9,940,658||)||$||(57,636,873||)||$||(25,313,037||)|
|Weighted-average basic and diluted common shares outstanding||24,166,113||7,504,148||20,958,421||7,042,977|
|Basic and diluted net loss per common share||$||(0.87||)||$||(1.32||)||$||(2.75||)||$||(3.59||)|
|September 30,||December 31,|
|Cash and cash equivalents||$||263,642,069||$||62,251,860|