SEC Filings

8-K
AVEXIS, INC. filed this Form 8-K on 12/13/2017
Entire Document
 

 

 

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

 

FORM 8-K

 

CURRENT REPORT

Pursuant to Section 13 or 15(d) of the
Securities Exchange Act of 1934

 

Date of Report (Date of earliest event reported): December 13, 2017

 

AVEXIS, INC.

(Exact name of registrant as specified in its charter)

 

Delaware

(State or other jurisdiction of incorporation)

 

001-37693

 

90-1038273

(Commission File No.)

 

(IRS Employer Identification No.)

 


 

2275 Half Day Rd, Suite 200

Bannockburn, Illinois 60015

(Address of principal executive offices and zip code)

 

Registrant’s telephone number, including area code: (847) 572-8280

 

 

(Former name or former address, if changed since last report.)

 


 

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

 

o            Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

 

o            Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

 

o            Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

 

o            Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

 

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

 

Emerging growth company x

 

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. x

 

 

 



 

Item 7.01                                           Regulation FD Disclosure.

 

On December 13, 2017, AveXis, Inc. (the “Registrant”) will host a live webcast to announce that the U.S. Food and Drug Administration (the “FDA”) has notified the Registrant that it may initiate its planned Phase 1 trial of AVXS-101 in spinal muscular atrophy (“SMA”) Type 2 using the intrathecal formulation produced by the Registrant’s Good Manufacturing Practice commercial manufacturing process. A copy of the slides to be presented during the webcast is being furnished as Exhibit 99.1 to this Current Report on Form 8-K.

 

The information in this Item 7.01 of this Current Report on Form 8-K (including Exhibit 99.1) is being furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that Section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such a filing.

 

Item 8.01.             Other Events.

 

On December 13, 2017, the Registrant issued a press release regarding the initiation of its planned Phase 1 trial of AVXS-101 in SMA Type 2 using the intrathecal formulation produced by the Registrant’s Good Manufacturing Practice commercial manufacturing process. A copy of this press release is furnished herewith as Exhibit 99.2 to this Current Report on Form 8-K and is incorporated herein by reference.

 

Item 9.01.             Financial Statements and Exhibits.

 

(d) Exhibits

 

Exhibit

 

 

Number

 

Exhibit Description

99.1

 

Slide Presentation, dated December 13, 2017, titled “Phase 1 SMA Type 2 Trial Initiation and Study Design.”

99.2

 

Press Release, dated December 13, 2017, titled “AveXis Announces Plan to Initiate Phase 1 Trial in SMA Type 2 Utilizing Intrathecal Delivery of AVXS-101.”

 

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SIGNATURES

 

Pursuant to the requirements of the Securities Exchange Act of 1934, the Registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

 

  Date: December 13, 2017

AVEXIS, INC.

 

 

 

 

 

By:

/s/ Sean P. Nolan

 

 

Sean P. Nolan

 

 

President and Chief Executive Officer

 

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Exhibit 99.1

December 2017 Phase 1 SMA Type 2 Trial Initiation and Study Design

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2 This presentation contains forward-looking statements, including statements about: the timing, progress and results of preclinical studies and clinical trials for AVXS-101, including statements regarding the potential of AVXS-101 to positively impact quality of life and alter the course of disease in patients with SMA Type 1 and SMA Type 2, the timing of initiation of studies or trials, our expectations regarding timing for meetings with regulatory agencies, our ability to meet future commercial demand for AVXS-101 through our manufacturing facility, our manufacturing strategy and developments, key regulatory and development milestones and our research and development programs. These statements involve substantial known and unknown risks, uncertainties and other factors that may cause our actual results, levels of activity, performance or achievements to be materially different from the information expressed or implied by these forward-looking statements. We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements we make. Factors that may cause actual results to differ materially from any future results expressed or implied by any forward-looking statements include the risks described in the “Risk Factors” sections of the Company’s Annual Report on Form 10-K for the year ended December 31, 2016 and the Company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2017, as well as those set forth from time to time in the Company’s other SEC filings, available at http://www.sec.gov. The forward-looking statements in this presentation represent our views as of the date of this presentation. We anticipate that subsequent events and developments will cause our views to change. However, while we may elect to update these forward-looking statements at some point in the future, we have no current intention of doing so except to the extent required by applicable law. You should, therefore, not rely on these forward-looking statements as representing our views as of any date subsequent to the date of this presentation. Disclaimers

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SMA Types: A Devastating Disease 3 TYPE 1 TYPE 2 TYPE 3 TYPE 4 SMN2 Copy Number Two Three** Three or Four Four to Eight Onset Before 6 Months 6-18 Months Early childhood to early adulthood (juvenile) Adulthood (20s-30s) usually after 30 Incidence per Live Birth Approximately 60% Approximately 27% Approximately 13% Uncommon; limited information available Developmental Milestones Will never be able to sit without support Difficulty breathing & swallowing Can’t crawl/will never walk Will never be able to walk without support Most will never stand without support Stand alone and walk independently, but may lose ability to walk over time Stand alone and walk but may lose ability to walk in 30s-40s Survival <10% Event free* by two years of age 68% alive at age 25 Normal Normal *Event = Death or >16-hr/day ventilation continuously for > 2 wks, in the absence of an acute reversible illness **100% have 3 copies (PNCR)

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AVXS-101 Targets the Primary SMN Gene 4 NORMAL INDIVIDUAL SMA-AFFLICTED INDIVIDUAL SMA-AFFLICTED INDIVIDUAL TREATED WITH AVXS-101 SMN Genes SMN Protein SMN1 Primary SMN2 Back up SMN Genes SMN Protein SMN1 SMN2 Back up SMN Genes SMN Protein SMN1 SMN2 Back up AVXS-101 Primary Functional SMN Protein Not-functional SMN Protein

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Our Solution: AVXS-101 An Innovative Treatment Approach for SMA 5 scAAV ITR Continuous Promoter Human SMN Transgene scAAV ITR KEY COMPONENTS PURPOSE Recombinant AAV9 Capsid Shell Ability to deliver across the blood brain barrier (BBB) and into the spinal cord - Avoids the need for intrathecal delivery when treating infants Non-replicating virus does not modify the existing DNA of the patient. scAAV ITR (Self-complementary DNA technology) Enables rapid onset of effect which is key in a quickly deteriorating population Continuous Promoter Activates the transgene to allow for continuous and sustained SMN expression Human SMN Transgene Full copy of a stable, functioning SMN gene that is introduced into the cell’s nucleus Recombinant AAV9 Capsid Shell Rendering adapted from DiMattia et al. Structural Insight into the Unique Properties of Adeno-Associated Virus Serotype 9. J. Virol. June 2012. Gene therapy is the right approach for SMA: Monogenic mutation that drives the pathology

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Phase 1 Trial of AVXS-101 in SMA Type 2 6 Route of Administration One-time intrathecal dose Prednisolone 1 mg/kg 1 day Pre-GT Trial Design 27-patient, Dose-comparison AVXS-101 PHASE 1 TRIAL OVERVIEW – SMA TYPE 2 Study Sites 11 centers in U.S. Safety Safety and Tolerability of intrathecal administration of AVXS-101 Determination of optimal dose SAFETY OBJECTIVE Primary Ability to stand alone for at least 3 seconds Secondary Ability to walk without assistance, defined as taking at least 5 steps independently displaying coordination and balance Exploratory Hammersmith Functional Motor Scale – Expanded Change from baseline in fine and gross motor components EFFICACY OBJECTIVES: PATIENTS LESS THAN 24 MONTHS* Primary Change from baseline in Hammersmith Functional Motor Scale – Expanded Secondary Ability to walk without assistance, defined as taking at least 5 steps independently displaying coordination and balance Exploratory Change from baseline in fine and gross motor components EFFICACY OBJECTIVES: PATIENTS AT LEAST 24 MONTHS* *Additionally, compelling, demonstrable, documented evidence of efficacy as determined by changes in developmental abilities as captured during videotaping sessions during site visits and/or captured/provided by parent/legal guardian will be collected for all patients in all age groups.

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Phase 1 Trial: Key Enrollment Criteria 7 Inclusion 60 months of age and younger at day of vector infusion as defined by the following features: Bi-allelic SMN1 gene deletion 3 copies of SMN2 gene Ability to sit unassisted for 10 or more seconds Negative gene testing for SMN2 gene modifier mutation (c.859G>C) Onset of clinical signs and symptoms consistent with SMA at less than 12 months of age Exclusion Historical or current ability to stand or walk Use of invasive ventilatory support Use or requirement of non-invasive ventilatory support for 12 or more hours daily over the two weeks prior to dosing Key Enrollment Criteria Kaufman et al. Prospective cohort study of spinal muscular atrophy types 2 and 3; Neurology. 2012 Oct 30; 79(18): 1889–1897.

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Phase 1 Trial: Dose Comparison & Methodology 8 Dose Comparison Stratified into two groups based on age at time of dosing: Less than 24 months of age (n=15) At least 24 months and less than 60 months (n=12) Methodology Cohort 1 (n=3) – Lower Dose/Dose A (6.0 X 1013 vg) Patients less than 24 months of age 4 week interval after each patient to review safety data prior to continuation If safety is established by the DSMB, advance to Dose B Cohort 2 (n=3) – Higher Dose/Dose B (1.2 X 1014 vg) All ages up to 60 months 4 week interval after each patient to review safety data prior to continuation If safety is established by the DSMB, Cohort 2 will be expanded to include 21 additional participants Expanded Cohort 2 (n=21) – Higher Dose/Dose B (1.2 X 1014 vg) Enrollment continues until 12 patients less than 24 months, and 12 patients at least 24 months and less than 60 months, receive Dose B Dose comparison & methodology

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Phase 1 Trial: Natural History Comparison 9 Compared to well-characterized natural history 100% of SMA Type 2 children will never walk without support 95% of children will never stand without assistance More than 30% will die by 25 years of age COHORT: PATIENTS LESS THAN 24 MONTHS OF AGE Compared to well-characterized natural history These patients experienced a mean change of =-0.33 points (standard deviation =4.07) over 12 months Suggests minimal change over a 12-month interval in natural history populations COHORT: PATIENTS BETWEEN 24 AND 60 MONTHS OF AGE The study cohorts will be compared to eligibility-matched, patient-level data drawn from the Pediatric Neuromuscular Clinical Research Network (PNCR) that mirrors the well-characterized natural history WELL-CHARACTERIZED NATURAL HISTORY COMPARISON Kaufman et al. Prospective cohort study of spinal muscular atrophy types 2 and 3; Neurology. 2012 Oct 30; 79(18): 1889–1897. Mercuri et al. Patterns of disease progression in type 2 and 3 SMA: Implications for clinical trials; Neuromuscular Disorders. 2016 Feb; 26(2): 126-31.

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Looking Ahead: Upcoming Milestones 10 SMA Type 1 end-of-Phase 1 Meeting with FDA: On December 5, 2017, AveXis had an end-of-Phase 1 meeting with FDA with respect to AVXS-101 for SMA Type 1. The company anticipates providing an update on feedback from FDA following the receipt of the final meeting minutes in early January. SMA Type 1 EU Trial: AveXis incorporated EU specific Scientific Advice from the EMA into the protocol design and expects to initiate a pivotal trial of AVXS-101 in SMA Type 1 in the EU in the first half of 2018. Rett Syndrome and Genetic ALS Programs: AveXis anticipates providing an update on the progress and timelines of its early-stage programs in Rett Syndrome and genetic ALS in the first quarter of 2018. Upcoming milestones

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Q&A

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Exhibit 99.2

 

 

 

Media Inquiries:

 

Lauren Barbiero

 

W2O Group

 

646-564-2156

 

lbarbiero@w2ogroup.com

 

 

 

Investor Inquiries:

 

Jim Goff

 

AveXis, Inc.

 

650-862-4134

 

jgoff@avexis.com

 

AveXis Announces Plan to Initiate Phase 1 Trial in SMA Type 2 Utilizing

Intrathecal Delivery of AVXS-101

 

– The FDA notified AveXis it may initiate the Phase 1 trial in SMA Type 2 based on a review of data provided by the company; trial to commence immediately –

 

– The trial will evaluate safety, dosing and proof of concept for efficacy –

 

– The trial will use product produced from the new GMP process at the AveXis facility –

 

– Conference call and webcast today at 4:30 p.m. EST –

 

Chicago, Ill. (December 13, 2017) — AveXis, Inc. (NASDAQ: AVXS), a clinical-stage gene therapy company developing treatments for patients suffering from rare and life-threatening neurological genetic diseases, today announced the U.S. Food and Drug Administration (FDA) has notified the company that, based on review of data submitted, the company may initiate its planned Phase 1 clinical trial of AVXS-101 for patients with spinal muscular atrophy (SMA) Type 2 via the intrathecal (IT) route of administration, using material produced by the company’s Good Manufacturing Practice (GMP) commercial manufacturing process at the AveXis manufacturing facility. The company plans to initiate this trial immediately.

 

“We are quite pleased to initiate our first trial of AVXS-101 in patients with SMA Type 2,” said Sean Nolan, President and Chief Executive Officer of AveXis. “Our goal has been to expand the study of gene therapy beyond Type 1 infants to address the urgent medical needs of children with SMA Type 2, and we look forward to understanding the potential clinical impact of AVXS-101 in these patients who, left untreated, will never walk on their own and most will never stand without assistance.”

 

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U.S. Phase 1 Trial in SMA Type 2 (STRONG)

 

The open-label, dose-comparison, multi-center Phase 1 trial — known as STRONG — is designed to evaluate the safety, optimal dosing, and proof of concept for efficacy of AVXS-101 in two distinct age groups of patients with SMA Type 2, utilizing a one-time IT route of administration. The trial will enroll 27 infants and children with a genetic diagnosis consistent with SMA, including the bi-allelic deletion of SMN1 and three copies of SMN2 without the SMN2 genetic modifier, who are able to sit but have no historical or current ability to stand or walk.

 

Two dosage strengths will be evaluated and patients will be stratified into two age groups: patients less than 24 months, and patients at least 24 months but less than 60 months. There will be at least a four-week interval between the dosing of the first three patients for each dose being studied and, based on the available safety data, a decision will be made whether to proceed.

 

·                  Cohort 1 (Dose A) will receive a dose of 6.0 x 1013 vg of AVXS-101 and enroll three patients less than 24 months of age.

 

·                  If safety is established according to the Data Safety Monitoring Board (DSMB), the study will proceed to Cohort 2.

 

·                  Cohort 2 (Dose B) will receive a dose of 1.2 X 1014 vg of AVXS-101 and enroll three patients less than 60 months of age.

 

·                  If safety is established according to the DSMB, an additional 21 patients will be enrolled until there are a total of 12 patients less than 24 months, and 12 patients at least 24 months but less than 60 months of age, who have received Dose B.

 

According to the well-characterized natural history of the disease by the Pediatric Neuromuscular Clinical Research Network, 100 percent of children with SMA Type 2 will never walk without support, 95 percent of children will never stand without assistance and more than 30 percent will die by 25 years of age. Additionally, children with SMA Type 2 experienced a mean decrease of - 0.33 points on the Hammersmith Function Motor Scale Expanded over a 12-month period.

 

Outcome Measures for Patients Less than 24 Months of Age

 

·                 The primary outcome measure for patients less than 24 months of age at the time of dosing is the achievement of the ability to stand without support for at least three seconds.

·                 The secondary outcome measure is the proportion of patients who achieve the ability to walk without assistance, defined as taking at least five steps independently while displaying coordination and balance.

·                  Developmental abilities, including motor function, will be evaluated as exploratory objectives.

 

Outcome Measures for Patients Between 24 and 60 Months of Age

 

·                 The primary outcome measure for patients between 24 months and 60 months of age at the time of dosing is the achievement of change in Hammersmith Functional Motor Scale Expanded from baseline.

·                 The secondary outcome measure is the proportion of patients who achieve the ability to walk without assistance, defined as taking at least five steps independently displaying coordination and balance.

·                 Developmental abilities, including motor function, will be evaluated as exploratory objectives

 

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The trial is projected to be conducted at 11 sites in the United States, including: Ann and Robert H. Lurie Children’s Hospital of Chicago, Boston Children’s Hospital, Children’s Hospital of Philadelphia, David Geffen School of Medicine at UCLA, Johns Hopkins Pediatric Neurology, Nationwide Children’s Hospital, Stanford University Medical Center, University of Central Florida College of Medicine, University of Texas Southwestern Medical Center, University of Utah and Washington University School of Medicine.

 

For more information about these clinical trials, please visit clinicaltrials.gov.

 

“This Phase 1 trial in children with SMA Type 2 will allow us to evaluate safety, optimal dosing and proof-of-concept for efficacy of AVXS-101 compared to the well-characterized natural history using the one-time intrathecal route of administration,” said Dr. Sukumar Nagendran, Chief Medical Officer of AveXis. “Because AVXS-101 targets the root cause of SMA, we are optimistic that we will observe a similar preclinical to clinical translation in this Type 2 trial as was seen in the SMA Type 1 study using intravenous administration.”

 

SMA Type 1 Update

 

On December 5, 2017, the company had an end-of-Phase 1 meeting with FDA with respect to AVXS-101 for SMA Type 1.  The company anticipates providing an update on feedback from FDA following the receipt of the final meeting minutes in early January.

 

Today’s Conference Call Information

 

AveXis will host a conference call and webcast at 4:30 p.m. EST today, December 13, 2017. Analysts and investors can participate in the conference call by dialing (844) 889-6863 for domestic callers and (661) 378-9762 for international callers, using the conference ID 2945908. The webcast can be accessed live on the Events and Presentations page in the Investors and Media section of the AveXis website, www.AveXis.com. The webcast will be archived on the company’s website for 90 days and will be available for telephonic replay for 14 days following the call by dialing (855) 859-2056 (Domestic) or (404) 537-3406 (International), conference ID 2945908.

 

About SMA

 

SMA is a severe neuromuscular disease characterized by the loss of motor neurons leading to progressive muscle weakness and paralysis. SMA is caused by a genetic defect in the SMN1 gene that codes SMN, a protein necessary for survival of motor neurons. The incidence of SMA is approximately one in 10,000 live births and is the leading genetic cause of infant mortality.

 

The most severe form of SMA is Type 1, a lethal genetic disorder characterized by motor neuron loss and associated muscle deterioration, which results in mortality or the need for permanent ventilation support before the age of two for greater than 90 percent of patients. SMA Type 2 typically presents between six and 18 months of age, and those affected will never walk without support and most will never stand without support. SMA Type 2 results in mortality in more than 30 percent of patients by the age of 25.

 

About AVXS-101

 

AVXS-101 is a proprietary gene therapy candidate of a one-time treatment for SMA Types 1 and 2, designed to address the monogenic root cause of SMA and prevent further muscle degeneration by addressing the defective and/or loss of the primary SMN gene. AVXS-101 also targets motor neurons, providing rapid onset of effect and crossing the blood brain barrier to allow targeting of both central and systemic features.

 

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About AveXis, Inc.

 

AveXis is a clinical-stage gene therapy company developing treatments for patients suffering from rare and life-threatening neurological genetic diseases. The company’s initial proprietary gene therapy candidate, AVXS-101, is in the pivotal phase of study for the treatment of SMA Type 1, and a Phase 1 trial for SMA Type 2. The company also intends to expand the study of gene therapy into two additional rare neurological monogenic disorders: Rett syndrome (RTT) and a genetic form of amyotrophic lateral sclerosis (ALS) caused by mutations in the superoxide dismutase 1 (SOD1) gene.

 

For additional information, please visit www.avexis.com.

 

Forward-Looking Statements

 

This press release contains “forward-looking statements,” within the meaning of the Private Securities Litigation Reform Act of 1995, regarding, among other things, AveXis’ research, development and regulatory plans for AVXS-101, including the potential of AVXS-101 to positively impact quality of life and alter the course of disease in patients with SMA Type 1 and SMA Type 2, the expected timing of the initiation of AveXis’ planned clinical trial in SMA Type 2, ability to enroll for, and the results of, AveXis’ planned clinical trials in SMA Type 1 and SMA Type 2, the overall clinical development of AVXS-101, if approved, AveXis’ research, development and regulatory plans for AVXS-101, including AveXis’ commercial manufacturing process, timing of feedback from FDA on AVXS-101, AveXis’ ability to meet future commercial demand for AVXS-101 through its manufacturing facility and expectations regarding AveXis’ research, development and regulatory plans for its programs for treatment of RTT and genetic ALS. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual results to differ materially from those projected in its forward-looking statements. Meaningful factors which could cause actual results to differ include, but are not limited to, the scope, progress, expansion, and costs of developing and commercializing AveXis’ product candidates; regulatory developments in the U.S. and EU, as well as other factors discussed in the “Risk Factors” and the “Management’s Discussion and Analysis of Financial Condition and Results of Operations” sections of AveXis’ Annual Report on Form 10-K for the year ended December 31, 2016, filed with the SEC on March 16, 2017, and AveXis’ Quarterly Report on Form 10-Q for the quarter ended September 30, 2017, filed with the SEC on November 9, 2017. In addition to the risks described above and in the Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the SEC, other unknown or unpredictable factors also could affect AveXis’ results. There can be no assurance that the actual results or developments anticipated by AveXis will be realized or, even if substantially realized, that they will have the expected consequences to, or effects on, AveXis. Therefore, no assurance can be given that the outcomes stated in such forward-looking statements and estimates will be achieved.

 

All forward-looking statements contained in this press release are expressly qualified by the cautionary statements contained or referred to herein. AveXis cautions investors not to rely too heavily on the forward-looking statements AveXis makes or that are made on its behalf. These forward-looking statements speak only as of the date of this press release (unless another date is indicated). AveXis undertakes no obligation, and specifically declines any obligation, to publicly update or revise any such forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

 

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