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):  July 8, 2018

 

Axovant Sciences Ltd.

(Exact name of registrant as specified in its charter)

 

Bermuda

 

001-37418

 

98-1333697

(State or other jurisdiction of incorporation)

 

(Commission File No.)

 

(I.R.S. Employer Identification No.)

 

Suite 1, 3rd Floor

11-12 St. James’s Square

London SW1Y 4LB, United Kingdom

(Address of principal executive office)

 

Registrant’s telephone number, including area code:  +44 203 318 9708

 

 

(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 1.01                                           Entry into a Material Definitive Agreement.

 

Benitec Biopharma License and Collaboration Agreement

 

On July 8, 2018, Axovant Sciences Ltd., through its wholly owned subsidiary, Axovant Sciences GmbH, entered into a license and collaboration agreement (the “License Agreement”) with Benitec Biopharma Limited (“Benitec”). Pursuant to the License Agreement, we received a worldwide, exclusive, royalty-bearing, sub-licensable license under certain patents and other intellectual property controlled by Benitec to develop and commercialize investigational gene therapy BB-301 and related gene therapy products (collectively, the “AXO-AAV-OPMD Program”) for all diseases and conditions.  The AXO-AAV-OPMD Program employs a single vector gene therapy construct which uses DNA directed RNA interference (“ddRNAi”) that is designed to silence expression of the mutant gene associated with oculopharyngeal muscular dystrophy (“OPMD”), while simultaneously adding back a copy of the functional version of the same gene to restore normal gene function.

 

Benitec will perform certain development and manufacturing activities for the AXO-AAV-OPMD Program, and we will reimburse Benitec for its costs incurred, in accordance with an agreed-upon development plan and budget.  We are solely responsible, at our expense, for all other activities related to the development and commercialization of products from the AXO-AAV-OPMD Program.

 

Under the License Agreement, we will also collaborate with Benitec on five additional research plans as part of the “Collaboration Programs” for other genetic neurological disorders using Benitec technologies.  Benitec will perform certain research activities for each Collaboration Program, and we will reimburse Benitec for its costs incurred, in accordance with an agreed-upon research plan and budget.  We will receive a worldwide, exclusive, royalty-bearing, sub-licensable license under certain patents and other intellectual property controlled by Benitec to develop and commercialize products arising from each Collaboration Program.  We are solely responsible, at our expense, for all other activities related to the research, development and commercialization of products arising from the Collaboration Programs.

 

We have agreed to use commercially reasonable efforts to develop and commercialize products from the AXO-AAV-OPMD Program and Collaboration Programs in certain agreed-upon markets.  Benitec has agreed to customary non-compete restrictions limiting its ability to develop or commercialize certain directly-competing gene therapy products.

 

We will make an upfront payment to Benitec of $10.0 million. In addition, we will be obligated to make payments to Benitec totaling up to (i) for the AXO-AAV-OPMD Program, $67.5 million upon the achievement of specified development and regulatory milestones and $120.0 million upon the achievement of specified sales milestones, and (ii) for each Collaboration Program, $33.5 million upon the achievement of specified development and regulatory milestones and $60.0 million upon the achievement of specified sales milestones.

 

Benitec will receive 30% of net profits of world-wide sales of products arising from the AXO-AAV-OPMD Program, subject to an agreed minimum amount for such payments.  This profit sharing payment will be made for so long as we or our affiliates or sublicensees commercialize such products.  We will also pay Benitec a tiered royalty based on yearly aggregate net sales of products arising from each Collaboration Program, subject to specified reductions upon the occurrence of certain events as set forth in the License Agreement. These royalties are required to be paid, on a product-by-product and country-by-country basis, until the latest to occur of the expiration of the last to expire valid claim of a licensed patent covering such product in such country, the expiration of regulatory exclusivity for such product in such country, or ten years after the first commercial sale of such product in such country.

 

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The License Agreement will expire, (i) with respect to the AXO-AAV-OPMD Program, upon the expiration of our obligation to make profit-sharing payments to Benitec as described above, and (ii) with respect to each product from a Collaboration Program, upon the expiration of the royalty payment term described above for such product throughout the world. We may terminate the License Agreement on a program-by-program basis at any time for any reason with prior written notice to Benitec upon 90 days’ prior notice before the first regulatory approval for a product from the applicable program, or upon 180 days’ prior notice thereafter. Either party may terminate the License Agreement for the other party’s uncured material breach of the Agreement or insolvency. If the License Agreement is terminated with respect to a program, all rights and licenses granted to us with respect to such program cease.

 

The foregoing description of the License Agreement does not purport to be complete and is qualified in its entirety by reference to the License Agreement, a copy of which we expect to file as an exhibit to our Quarterly Report on Form 10-Q for the quarter ending September 30, 2018.

 

Silence-and-Replace Technology

 

The Silence-and-Replace technology platform is designed to produce a long-term restoration of normal gene function and is achieved by combining RNA interference (silence) with gene therapy (replace) in a single administration of a single viral vector construct. This approach is applicable to various genetic diseases, particularly autosomal dominant genetic disorders caused by nucleotide repeat expansion.

 

Many neurological and muscular diseases are known to result from the erroneous expression of a mutated gene. RNA interference (“RNAi”) has shown significant potential to silence the expression of these disease-associated genes. Commonly-used RNAi approaches, in which small interfering RNA (“siRNA”) is introduced directly into the cell, achieve only transient gene silencing and are limited by the requirement for repeated administration and variable concentrations of siRNA over time. To provide lasting gene silencing, the Silence-and-Replace technology employs ddRNAi, in which viral vectors deliver a DNA construct that produces short hairpin RNAs (“shRNAs”), which are processed by the cell into siRNAs, which then silence the mutated genes.

 

In an autosomal dominant genetic disorder, particularly one caused by nucleotide repeat expansion, silencing of the mutant gene can also lead to silencing of the wild type gene which may be required for normal function.  The Silence-and-Replace strategy is designed to address this potential issue by delivering a functional copy of the gene that is re-engineered to be resistant to knockdown. The gene that encodes the functional protein is contained within the same viral vector as the ddRNAi construct.

 

AXO-AAV-OPMD Program

 

The AXO-AAV-OPMD Program is an investigational gene therapy being developed as a one-time treatment for OPMD. The Program utilizes an AAV vector to silence the mutant poly-A binding protein N1 (“PABPN1”) gene that causes OPMD and replace with a functional copy of the PABPN1 gene. The Silence-and-Replace approach aims to knock down the expression of the mutant PABPN1 gene through ddRNAi, while at the same time express a re-engineered copy of the PABPN1 gene coding for the functional PABPN1 protein. The gene therapy will be delivered in a single administration directly into target muscle tissue to provide long-term correction of muscle pathology and restoration of function. Depending on the type of AAV vector that we decide to commercialize, it may be necessary for us to use the patented or proprietary technology of one or more third parties to commercialize AXO-AAV-OPMD.  If we are unable to use these technologies or obtain licenses from these third parties when needed or on commercially reasonable terms, our ability to commercialize AXO-AAV-OPMD, if approved, would likely be delayed.

 

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Data from mouse models of OPMD showed gene therapy from the AXO-AAV-OPMD Program provided up to 86% inhibition of PABPN1 expression, while restoring functional PABPN1 up to 63% of normal levels. The A17 mouse model is a well validated in vivo model that is designed to exhibit many of the key pathological features of OPMD patients. The levels of gene silencing and expression achieved in this model coincided with decreased muscle pathology and a restoration of muscle force and muscle weight to near wild-type levels.

 

We expect to initiate a placebo-controlled clinical study for the investigational AXO-AAV-OPMD Program in 2019. The U.S. Food & Drug Administration and European Commission have granted Orphan Drug Designation to the AXO-AAV-OPMD Program for the treatment of OPMD.

 

Oculopharyngeal Muscular Dystrophy

 

OPMD is a muscular disease that is inherited through a primarily autosomal dominant pattern. OPMD is estimated to affect approximately 15,000 people in North America and Europe. The disease generally presents between the ages of 40-70 years old and is characterized primarily by progressive swallowing difficulty (dysphagia), eyelid drooping (ptosis), and weakness of the proximal extremities. Swallowing difficulties can have life-threating consequences, including malnutrition and aspiration pneumonia. As the disease progresses, the dysphagia becomes more severe and other muscles may become involved. There are no products approved for the treatment of OPMD and therefore, treatment options available to patients are limited.

 

OPMD is caused by mutations in the gene coding for PABPN1, a ubiquitously expressed protein that regulates the processing of messenger RNAs. The normal PABPN1 protein contains ten copies of the amino acid alanine, which forms a polyalanine tract.  In OPMD, the mutated PABPN1 gene has an expansion of alanine-encoding trinucleotide repeats, resulting in an abnormally long polyalanine tract. The protein that forms from the mutated gene is prone to aggregating into insoluble nuclear inclusion bodies which leads to muscle cell pathology and disease progression.

 

Additional Research Programs

 

Under our research and development collaboration with Benitec, we will pursue five additional investigational gene therapy research plans as part of Collaboration Programs focused on genetic neurological disorders utilizing Benitec’s technologies. We plan to initiate a research plan to develop gene therapy products targeting the C9orf72 gene which is associated with amyotrophic lateral sclerosis (“ALS”) and frontotemporal dementia (“FTD”). In addition, we plan to initiate four other research plans focused on undisclosed genetic neurological disorders.

 

ALS and FTD are neurological disorders that have been linked to hexanucleotide repeats in the C9orf72 gene.  Thirty to forty percent of familial ALS cases are associated with C9orf72 mutations and these patients have a progressive muscle weakness resulting from the death of motor neurons in the spinal cord and brain.  Patients with FTD associated with C9orf72 mutations have a progressive brain disorder that affects personality, behavior, language and movement.  While the exact role of C9orf72 mutation is unknown, both expression of the mutated C9orf72 and lack of functional C9orf72 are believed to be implicated. We believe Silence-and-Replace gene therapy is a promising approach for the restoration of normal C9orf72 function and has the potential to deliver lasting benefits for ALS and FTD patients.

 

Item 7.01                                           Regulation FD Disclosure.

 

On July 9, 2018, we issued a press release announcing, among other things, the entry into the License Agreement and our conference call to be held at 8:30 a.m., Eastern time, on July 9, 2018.

 

A copy of the press release and the presentation to be discussed on the conference call are furnished as Exhibit 99.1 and Exhibit 99.2, respectively, to this Current Report on Form 8-K and are incorporated by reference into this Item 7.01.  The information furnished under this Item 7.01, including Exhibit 99.1 and Exhibit

 

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99.2, shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or subject to the liabilities of that section. The information shall not be deemed incorporated by reference into any other filing with the Securities and Exchange Commission made by us, regardless of any general incorporation language in such filing.

 

Item 9.01                                           Financial Statements and Exhibits.

 

(d) Exhibits.

 

Exhibit No.

 

 

 

 

 

99.1

 

Press release dated July 9, 2018.

 

 

 

99.2

 

Presentation dated July 9, 2018.

 

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SIGNATURES

 

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

 

 

 

Axovant Sciences Ltd.

 

 

 

 

 

 

Date:  July 9, 2018

By:

/s/ Gregory Weinhoff

 

 

Name:

Gregory Weinhoff

 

 

Title:

Principal Financial Officer

 

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Exhibit 99.1

 

Axovant Announces Global Licensing Agreement for AXO-AAV-OPMD Program for Treatment of Oculopharyngeal Muscular Dystrophy and Broader Platform Collaboration with Benitec Biopharma

 

·                  License grants Axovant worldwide rights to AXO-AAV-OPMD utilizing proprietary Silence-and-Replace technology, which suppresses mutant protein production while restoring expression of functional protein

·                  Plan to initiate placebo-controlled study of AXO-AAV-OPMD in patients with oculopharyngeal muscular dystrophy (OPMD) in 2019

·                  License also grants rights to five additional investigational gene therapy products for neurological conditions

·                  New agreement further demonstrates Axovant’s commitment to the development and commercialization of transformational therapies for neurological diseases

·                  Conference call / webcast to be held July 9, 2018 at 8:30am EDT

 

BASEL, Switzerland, July 9, 2018 (GLOBE NEWSWIRE) — Axovant Sciences (NASDAQ:AXON) today announced that it has licensed exclusive global rights to an investigational Silence-and-Replace gene therapy program from Benitec Biopharma for the treatment of oculopharyngeal muscular dystrophy (OPMD), and has also entered into a research collaboration for the development of five additional gene therapy products in neurological disorders. The Silence-and-Replace gene therapy technology is designed to deliver a combination of DNA-directed RNA interference (silence) along with a functional copy of the gene (replace) in a single vector construct. This approach is applicable to various genetic diseases, including autosomal dominant disorders caused by nucleotide repeat expansion.

 

The lead program, AXO-AAV-OPMD, is in preclinical development, and Axovant plans to initiate a placebo-controlled clinical study in 2019. OPMD is a neuromuscular disease that is caused by mutations in the gene coding for polyA-binding protein nuclear 1 (PABPN1), which can lead to formation of intranuclear inclusion bodies causing muscle cell pathology. Patients with OPMD may have swallowing difficulties with potentially life-threating consequences, including malnutrition and aspiration pneumonia.  OPMD is estimated to affect at least 15,000 patients in North America and Europe, and there are no products approved for treatment of the disease. AXO-AAV-OPMD is an adeno-associated viral (AAV) vector gene therapy delivered via a one-time intramuscular administration, which both silences the mutant PABPN1 gene and replaces it with a functional copy. The U.S. Food & Drug Administration and European Commission have granted Orphan Drug Designation to AXO-AAV-OPMD for the treatment of OPMD.

 

Under the terms of the agreement, Axovant will pay Benitec an upfront payment of $10 million for rights to the AXO-AAV-OPMD program and five additional investigational gene therapy products, as well as payments tied to development, regulatory and commercial sales milestones. In addition, Benitec will receive 30% of the net profits on worldwide sales of AXO-AAV-OPMD and tiered royalties on the other gene therapy products that result from this collaboration. The first additional investigational gene therapy product will target the C9orf72 gene, which is associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).

 

“This expansion of Axovant’s pipeline further demonstrates our commitment to advancing innovative gene therapies for serious neurological diseases,” said Pavan Cheruvu, MD, Chief Executive Officer of Axovant. “OPMD is a debilitating, potentially fatal disease that affects adults in the prime of their careers, and no approved treatment options are currently available.

 



 

AXO-AAV-OPMD directly targets the underlying genetic defect that causes this disease using Silence-and-Replace technology, and I am excited about the potential of our gene therapy program for patients suffering from OPMD.”

 

“The Silence-and-Replace technology is a unique approach in gene therapy, using a single vector to suppress mutant protein production while also restoring expression of the functional protein, and could be an elegant solution to tackling autosomal dominant genetic disorders,” stated Fraser Wright, PhD, Chief Technology Officer of Axovant. “I look forward to collaborating with the research and manufacturing teams at Benitec to advance the progress of the platform and bring additional therapies into the clinic.”

 

Commenting on the agreement, Jerel Banks, MD PhD, Executive Chairman of Benitec Biopharma said: “This agreement with Axovant further demonstrates the importance of Benitec’s core technology and our strategic focus on rapidly progressing these programs into the clinic. We believe Axovant is the ideal partner to take these programs forward, and look forward to working closely with them to develop AXO-AAV-OPMD and other neurological gene therapies.”

 

Teleconference/Webcast Details

 

To participate in the live conference call on July 9, 2018 at 8:30 am EDT, please dial 1-833-652-5918 from the U.S. and Canada or +1 409-767-9227 internationally, and use the passcode 8819919.

 

The live call is being webcast and can be accessed on the “Events and Presentations” page of the “Investors” section of the Company’s website at http://investors.axovant.com. A replay of the webcast will be available for 30 days following the live event.

 

AXO-AAV-OPMD Program

 

The AXO-AAV-OPMD Program is an investigational gene therapy being developed as a one-time treatment for oculopharyngeal muscular dystrophy (OPMD). The Program utilizes an AAV vector to silence the mutant poly-A binding protein N1 (PABPN1) gene that causes OPMD and replace with a functional copy of the PABPN1 gene.  The Silence-and-Replace approach aims to knock down the expression of the mutant PABPN1 gene through ddRNAi, while at the same time express a re-engineered copy of the PABPN1 gene coding for the functional PABPN1 protein. The gene therapy will be delivered in a single administration directly into target muscle tissue to provide long-term correction of muscle pathology and restoration of function.

 

Data from mouse models of OPMD showed gene therapy from the AXO-AAV-OPMD Program provided up to 86% inhibition of PABPN1 expression, while restoring functional PABPN1 up to 63% of normal levels. The A17 mouse model is a well validated in vivo model that is designed to exhibit many of the key pathological features of OPMD patients. The levels of gene silencing and expression achieved in this model coincided with decreased muscle pathology and a restoration of muscle force and muscle weight to near wild-type levels.

 

Axovant expects to initiate a placebo-controlled clinical study for the investigational AXO-AAV-OPMD Program in 2019. The U.S. Food & Drug Administration and European Commission have granted Orphan Drug Designation to the AXO-AAV-OPMD Program for the treatment of OPMD.

 



 

Oculopharyngeal Muscular Dystrophy (OPMD)

 

Oculopharyngeal muscular dystrophy (OPMD) is a muscular disease that is inherited through a primarily autosomal dominant pattern. OPMD is estimated to affect approximately 15,000 people in North America and Europe. The disease generally presents between the ages of 40-70 years old and is characterized primarily by progressive swallowing difficulty (dysphagia), eyelid drooping (ptosis), and weakness of the proximal extremities. Swallowing difficulties can have life-threating consequences, including malnutrition and aspiration pneumonia. As the disease progresses, the dysphagia becomes more severe and other muscles may become involved. There are no products approved for the treatment of OPMD and therefore, treatment options available to patients are limited.

 

OPMD is caused by mutations in the gene coding for polyA-binding protein nuclear 1 (PABPN1), a ubiquitously expressed protein that regulates the processing of messenger RNAs. The normal PABPN1 protein contains ten copies of the amino acid alanine, which forms a polyalanine tract.  In OPMD, the mutated PABPN1 gene has an expansion of alanine-encoding trinucleotide repeats, resulting in an abnormally long polyalanine tract. The protein that forms from the mutated gene is prone to aggregating into insoluble nuclear inclusion bodies which leads to muscle cell pathology and disease progression.

 

About Axovant Sciences

 

Axovant is a clinical-stage biopharmaceutical company dedicated to advancing innovative treatments for patients with serious neurologic and neuropsychiatric conditions, and turning promising therapies into lasting solutions for patients. Axovant is committed to developing and commercializing a pipeline of product candidates by identifying and developing novel treatments for unmet needs in neurology and psychiatry.

 

Forward-Looking Statements and Information

 

This press release contains forward-looking statements, including statements regarding Axovant’s plans to advance the development of AXO-AAV-OPMD and expand its pipeline with additional gene therapy products. Forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially and reported results should not be considered as an indication of future performance. These risks and uncertainties include, but are not limited to: risks associated with our intellectual property position including the ability to obtain issued patents, identify and in-license or acquire third-party patents and licenses, and associated costs; the success, cost, and timing of Axovant’s product development activities, including the timing of the initiation and completion of preclinical and clinical trials, the timing of patient enrollment and dosing in clinical trials, and the timing of expected regulatory filings; and the clinical utility and potential attributes and benefits of AXO-AAV-OPMD Program and collaboration product candidates, including future out-and-in-license opportunities and reliance on collaboration partners, and the ability to procure additional sources of financing. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to Axovant’s business in general, see the “Risk Factors” section of Axovant’s Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC) on June 11, 2018, and other filings that Axovant makes with the SEC from time to time. These forward-looking statements are based on information available to Axovant as of the date of this press release and speak only as of the date of this release. Axovant disclaims any obligation to update these forward-looking statements, except as may be required by law.

 

Contacts:

 

Investors

 

Tricia Truehart

(631) 892-7014

investors@axovant.com

 


Exhibit 99.2

Building a leader in innovative neurological therapies Conference Call to Discuss Global Licensing Agreement for AXO-AAV-OPMD and Broader Platform Collaboration with Benitec Biopharma June 9, 2018

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FORWARD LOOKING STATEMENTS Statements made in this presentation contain forward-looking statements, including statements regarding Axovant’s plans to advance the development of its AXO-AAV-OPMD program and expand its pipeline with additional gene therapy products, Axovant’s expectations about timing of the results for its Phase 1/2 clinical study for AXO-Lenti-PD in Parkinson’s disease and Phase 2 clinical study of REM Sleep Behavior Disorder in LBD, Axovant’s license arrangements with Benitec and Oxford BioMedica, and other elements of Axovant’s clinical development and regulatory strategy. Forward-looking statements can be identified by the words “believe,” “anticipate,” “continue,” “estimate,” “project,” “expect,” “plan,” “potential,” “intend,” “will,” “would,” “could,” “should” or the negative or plural of these words or other similar expressions that are predictions or indicate future events, trends or prospects. Forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially and reported results should not be considered as an indication of future performance. These risks and uncertainties include, but are not limited to: risks associated with the success, cost and timing of our product development activities and clinical trials; the approval and commercialization of Axovant’s product candidates, including AXO-AAV-OPMD and AXO-Lenti-PD; the ability to obtain issued patents; identify and in-license or acquire third party patents; and increased regulatory requirements. These statements are also subject to the risk that clinical trial data are subject to differing interpretations, and regulatory agencies, medical and scientific experts and others may not share Axovant’s views of the clinical study data. In addition, promising interim results or other preliminary analyses do not in any way ensure that later or final results in a clinical trial or in related or similar clinical trials will replicate those interim results. The product candidates discussed are investigational and not approved and there can be no assurance that Axovant’s clinical programs including AXO-AAV-OPMD and AXO-Lenti-PD programs will be successful in demonstrating safety and/or efficacy, that Axovant will not encounter problems or delays in clinical development, or that any of Axovant’s product candidates will ever receive regulatory approval or be successfully commercialized. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to Axovant’s business in general, see the “Risk Factors” section of Axovant’s annual report on Form 10-K filed with the Securities and Exchange Commission on June 11, 2018, and other filings that Axovant makes with the SEC from time to time. These forward-looking statements are based on information available to Axovant as of the date of this presentation and speak only as of the date of this presentation. Axovant disclaims any obligation to update these forward-looking statements, except as may be required by law.

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Building a leader in innovative neurological therapies Targeted approaches addressing the underlying biology of neurological conditions: Silence-and-Replace gene therapy platform across neurological indications Restoration of endogenous dopamine synthesis in Parkinson’s disease AXO-Lenti-PD: potential best-in-class gene therapy for Parkinson’s disease Delivery of three genes that encode critical enzymes necessary for endogenous dopamine synthesis in the brain Partnered with Oxford BioMedica, world leader in lentiviral vector manufacturing Plans for continued pipeline expansion AXO-AAV-OPMD Program: designed to restore function of PABPN1 for treatment of oculopharyngeal muscular dystrophy Orphan drug designation obtained in US and EU Research collaboration for 5 additional gene therapy programs in neurologic indications What we are focused on: Clinical-stage or clinic-ready in 12-18 months Genetically-identifiable targets in indications with well-characterized neurobiology Transformative patient impact

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Global license for AXO-AAV-OPMD Program and broader platform collaboration Axovant granted worldwide rights to AXO-AAV-OPMD program and 5 investigational gene therapy products in neurological conditions Plan to initiate a placebo-controlled clinical study of AXO-AAV-OPMD gene therapy in oculopharyngeal muscular dystrophy (OPMD) patients in 2019 First additional gene therapy product will focus on C9orf72 gene associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) Unique Silence-and-Replace approach is designed to correct the underlying genetic defect causing OPMD Delivers a combination of DNA-directed RNA interference (Silence) along with a functional copy of gene (Replace) to produce a long-term restoration of normal gene function One-time administration using single adeno-associated virus (AAV) vector Axovant to pay $10M upfront; additional payments tied to development, regulatory, and commercial sales milestones on all programs Benitec to receive 30% of net profits on worldwide sales of AXO-AAV-OPMD Program and tiered royalties on any additional products from research collaboration

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Overview of oculopharyngeal muscular dystrophy (OPMD) Neuromuscular disorder caused by mutation in polyA-binding protein nuclear 1 (PABPN1) gene Primarily autosomal dominant inheritance Expansion of alanine-encoding trinucleotide repeats results in abnormally long polyalanine tract Mutated protein misfolds and forms insoluble nuclear inclusion bodies OPMD leads to progressive muscle weakness in the throat, face, and proximal limbs The most severe symptom is dysphagia which can lead to complications such as malnutrition and aspiration pneumonia Estimated to affect at least 15,000 individuals in North America and Europe More common in certain populations including French-Canadian population (1 per 1,000) and Bukharan Jewish population in Israel (1 per 700) No approved products, therefore limited treatment options

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Silence-and-Replace: a novel gene therapy strategy for genetic disorders Delivered in a single vector construct Silencing cannot discriminate between the mutant gene and the wild-type gene, therefore replacing a functional copy of the gene is essential in these conditions SILENCE mutant genes by using RNA interference to knock down expression of pathologic protein REPLACE with a functional copy of the gene, restoring expression of the normal protein & Several autosomal dominant genetic disorders can be treated by silencing the target mutant gene AND expressing a functional gene copy

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Silence-and-Replace: one-time dose allows sustained silencing and gene expression Enzymatic cleavage of hairpin (DICER) siRNA Separates siRNA into single strands Cleavage of mutant mRNA Mutant gene silenced Protein Mutant gene X shRNA continually expressed siRNA-resistant functional mRNA AXO-AAV-OPMD Functional protein

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AXO-AAV-OPMD: Silence-and-Replace PABPN1 GOALS OF THERAPY: Less troublesome dyskinesia Less OFF time More ON time Lower requirement for exogenous L-dopa Silences mutant PABPN1 gene and replaces with a functional copy Delivers sequences for shRNA-mediated knockdown of mutant PABPN1 Functional copy of the PABPN1 gene that is re-engineered to be resistant to knockdown One-time administration of single AAV vector construct into the cricopharyngeal and pharyngeal muscles Orphan Drug Designation granted in US (2018) and EU (2017) AAV Vector Configuration Re-engineered functional PABPN1 PABPN1 shRNA-1 PABPN1 shRNA-2 Muscle Specific Promoter ITR ITR “Replace” with functional copy of PABPN1 “Silence” PABPN1, including mutant form

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86% inhibition of PABPN1 in OPMD mouse model AXO-AAV-OPMD gene therapy reduces mutant PABPN1 and expresses functional copy PABPN1 knockdown 63% expression of PABPN1 transgene at highest dose in OPMD mouse model Functional PABPN1 expression

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AXO-AAV-OPMD gene therapy reverses intranuclear inclusions in mouse model Intranuclear inclusions measured 13 weeks after AXO-AAV-OPMD gene therapy ***P<0.001

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AXO-AAV-OPMD gene therapy restores muscle function and weight in a dose-dependent manner AXO-AAV-OPMD gene therapy normalized tibialis anterior muscle force and weight to wild-type levels at highest dose in mouse model Normal Dose AXO-AAV-OPMD Muscle Force *P<0.05, **P<0.01, ***P<0.001 Dose AXO-AAV-OPMD Muscle Weight *p<0.05, **p<0.001, compared to A17

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AXO-AAV-OPMD: anticipated clinical study design First patient expected to be dosed 2019 All dose cohorts will include matched placebo arm Delivery method: Direct injection into cricopharyngeal and pharyngeal muscles, and injection into the tongue for purposes of biopsy Key assessments: Safety and tolerability, swallowing function, dysphagia severity, and muscle biopsy Placebo-controlled dose escalation study OPMD patients with swallowing difficulty Low dose Placebo Mid dose Placebo High dose Maximum Effective Dose Placebo Cohort 1 Cohort 2 Cohort 3 Endpoints through 52 weeks

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AXO-AAV-OPMD: scalable, high-quality manufacturing process already in place AXO-AAV-OPMD will be produced with scalable, high-yield baculovirus based methodologies and purification processes to control COGS GMP-grade clinical material produced at a top-three, US-based gene therapy contract manufacturing organization Product-specific process developed to produce high upstream productivity and industry-standard purification yield Uses a modified AAV capsid for the generation of highly active viral vector particles Currently manufacturing at 50L scale, with plans for clinical product to be generated at 250L scale

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Financial terms of Benitec transaction Upfront $10.0M in cash AXO-AAV-OPMD Program $67.5M development and regulatory milestones; $120.0M specified sales milestones; Benitec to receive 30% of net profits Each Additional Research Collaboration Program Development, regulatory, and sales milestones; Tiered royalties on net sales

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By YE:18 H2:18 2019 Key upcoming catalysts 2019 Initiate Phase 1/2 Study for AXO-Lenti-PD in advanced Parkinson’s disease Results from Nelotanserin Phase 2 Study of REM Sleep Behavior Disorder in LBD Initial data from AXO-Lenti-PD Phase 1/2 study Initiate clinical study for AXO-AAV-OPMD in oculopharyngeal muscular dystrophy

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