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As a follow up to our earlier post back in January, here's more info. We are working diligently to move gene therapy toward a clinical trial, yet we also have some significant obstacles to overcome which we want to share with you.

Delays: Two Sources


As we said in our February 2017 Update, manufacturing of gene therapy vector is a common bottleneck. Unfortunately, that has been our experience, with repeated manufacturing difficulties resulting in delays, pushing back timelines for preclinical studies and further manufacturing activities. We've been actively working to resolve these issues – we have multiple strategies in place, plus some hopeful results to bolster our efforts – and we continue to push for a Phase I clinical trial as soon as possible.

Route of Administration

We expected our gene therapy to be administered via a lower back (intrathecal) injection into the central nervous system. While that might still prove to be the case, the route of administration is not set in stone and we will follow where the preclinical data leads us. We're evaluating two alternative routes of administration: intrathecal and intravenous.

IND Timeline: Three Alternatives

As a result of these delays and because we learned some processes take longer than previously estimated, we need to push back our timeline, again. We face some pretty significant unknowns, and therefore we can't give a more hard-and-fast date (sorry), but we still want the NPC community to know the facts.

Depending on how things go in 2018 with our manufacturing and evaluating the route of administration, here are three estimates for timeline to file an IND.

Best-case scenario. File IND in early 2020.

Moderate-case scenario. File IND in early 2021.

Worst case scenario. It's possible that Galyatech won't be able to resolve the manufacturing issues we've encountered. (We hope this is not the case, but it is possible.)

(For reference: In February 2017, we anticipated filing an IND in 2018.)

NPC Community: One Commitment

While these delays are disappointing and the unknowns are daunting, we remain committed to developing a safe and effective gene therapy for NPC1 disease – including initiation of a Phase I clinical trial – as quickly as possible.

We hope to have more encouraging news to share with the NPC community this year. However, even if results are not good, we will do our best to keep you informed.

2017 was a productive year at Galyatech! And we're hoping to make much more progress in 2018! Read more below!

A Look Back on 2017

In 2017, we:


  • performed 3 in vitro preclinical tests in cells

  • designed 3 in vivo preclinical animal model studies (plus 2 additional supplementary studies)

  • initiated 1 in vivo preclinical study in mice (and another study coming soon)

Animal Model Colonies

  • established 1 Npc1 mouse colony (with an existing mouse model)

  • worked closely with 1 existing NPC1 cat colony


  • manufactured more than 10 preparations of non-pathogenic AAV9 virus

  • experimented with more than 3 different variations of the virus components


  • entered more than 10 new legal agreements, including:

    • 1 new research collaboration agreement with a major scientific research institution and

    • 6 agreements with organizations and consultants in areas of manufacturing, animal models, and process development

Project Management

  • participated in 100's of phone and/or teleconference calls

  • sent and received around 4,000 emails

  • received great advice from our 3 scientific advisory board (SAB) members: Brittney Gurda, Cristin Davidson and Steven Gray


  • were in-person at 5 conferences/symposiums focused on gene therapy and/or rare disease:

    • WORLD Symposium (Feb 2017)

    • NYAS: Gene Therapy for Rare Diseases Conference (Apr 2017)

    • Hanson Wade: Gene Therapy for Rare Disorders (Apr 2017)

    • Michael, Marcia, and Christa Parseghian Scientific Conference for Niemann-Pick Type C Research (June 2017)

    • Global Genes 2017 RARE Patient Advocacy Summit (Sep 2017)

Next Update

We hope to share more details with you soon in the next update!

We are excited to share with you results from a recent experiment that demonstrate the efficacy of GALYA-1 DNA in human cells. Read more below!

Gene Therapy-Treated Cells Make Functional NPC1 Protein and Reduce Cholesterol Storage

Researchers at the University of Pennsylvania (UPenn), in collaboration with Galyatech, used human NPC1 fibroblasts (skin cells) to test the efficacy of GALYA-1 DNA.

Why and how did we do this? Before we manufacture GALYA-1 on a large scale, it is important to show that GALYA-1 DNA 'works' – ie. that when we insert it into a human NPC1 affected cell, the cell starts to produce functional NPC1 protein, which it didn't do before the DNA was added.

In the UPenn experiment, some cells were given both GALYA-1 DNA, which contains a copy of the human NPC1 gene, to treat the disease, and green fluorescent protein (GFP) DNA, which makes the cells bright green, to identify which cells got GALYA-1 DNA. After treatment, many cells showed NPC1 protein and GFP expression that coincided with low levels of stored cholesterol, which indicates that the NPC1 protein was functional. This is a good therapeutic result.

In contrast, cells that were not treated didn't make enough functional NPC1 protein to prevent cholesterol storage. This is a well-known negative consequence of NPC1 disease.

These results clearly demonstrate the efficacy of GALYA-1 DNA in human fibroblasts in vitro: treated cells made functional NPC1 protein and cleared out stored cholesterol. You can see the proof for yourself, below.

Microscope Images

To help visualize these results, the following images show the same three human NPC1 cells: one treated (top-left) and two untreated (bottom and right). In the cells,

green is GFP,

red is NPC1 protein, and

blue is stored cholesterol (filipin staining).

Image G1: Green, Red, & Blue

In image G1, you can see that cell #1 is bright green and red; this cell was treated with GFP DNA and GALYA-1 DNA. Cells #2 and #3 were not treated with any DNA and are blue. These two untreated cells lack green or red color, which indicates there is no GFP or NPC1 protein in them. In contrast, the treated cell (#1) is brightly green and red indicating strong expression of GFP and NPC1 protein.
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Image G2: Red & Blue

In Image G2, the green color has been removed to show the extent of NPC1 protein expression (red) in the treated cell (#1). Again, the two untreated cells (#2 and #3) lack red color indicating no NPC1 protein, while the treated cell is bright red indicating expression of NPC1 protein. This is a good result, therapeutically.
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Image G3: Blue

Image G3 is the most exciting of the three because here we have visual confirmation that not only do cells treated with GALYA-1 DNA produce NPC1 protein (red color inside cell #1 in the previous images), but more importantly this NPC1 protein is functional! By removing both the red and green colors, we see only the cholesterol (blue, filipin staining). The two untreated cells (#2 and #3) have bright blue color indicating lots of cholesterol storage, while the treated cell (#1) shows very little blue color, which indicates that the NPC1 protein performed its function of transporting cholesterol out of the lysosomes! This cell shows very little stored cholesterol and therefore we can be confident that the cell made functional NPC1 protein when treated with GALYA-1 DNA.
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Developing GALYA-1

We continue to push forward with GALYA-1 development, including the preclinical mouse and cat studies and manufacturing. Galyatech remains committed to developing GALYA-1 as a safe and effective drug – including initiation of a Phase I clinical trial – as quickly as possible.

Since our last update we've made a lot of progress toward developing GALYA-1. Read more below!

Dr. Steven Gray Joins SAB

We are very happy to announce that Dr. Steven Gray, PhD (UNC Gene Therapy Center) joined Galyatech's Scientific Advisory Board (SAB) in November 2016. Steven's gene therapy expertise and preclinical development experience are an invaluable contribution to our goal of initiating a Phase I clinical trial as quickly as possible. Dr. Gray successfully directed the development and testing of an AAV9 gene therapy for the rare neurological disorder, Giant Axonal Neuropathy (GAN), which began a Phase I clinical trial in 2015.

Pre-PreIND with FDA

Toward the end of 2016, Galyatech had discussions with the FDA and received valuable advice about GALYA-1 development which we've since put into action, described below.

Preclinical Study Designs

Building on the FDA's advice, we came up with robust preclinical study designs to evaluate GALYA-1 in NPC1 mouse and cat models. These studies will generate the necessary preclinical data to support an FDA investigational new drug (IND) filing for GALYA-1.


The FDA also gave us advice about manufacturing the gene therapy vector – a critical step, and a common bottleneck, in the process of preparing for a Phase I clinical trial. It takes time to evaluate different manufacturing facilities and to lay the groundwork for vector production for a clinical trial. We are committed to doing the process right and work is underway to produce GALYA-1.

Updated Timeline

When we launched Galyatech in June 2016, we aimed for starting a Phase I clinical trial in the second half of 2017. Though Galyatech continues to work diligently on moving gene therapy toward a clinical trial, the manufacturing and preclinical study processes indicate this timeline needs to be modified.

We now anticipate filing an IND with the FDA by the end of 2018. Galyatech is blazing a new trail into the unknown with an optimistic timeline, though unexpected delays may occur. We remain dedicated to developing GALYA-1 as a safe and effective drug – including initiation of a Phase I clinical trial – as quickly as possible.

CNPDA Family Conference

We wanted to share with you one more piece of exciting news. Last November, Andrew Wilkinson and his wife Jennifer attended the CNPDA family conference in Beijing! It was a pleasure to meet many NPC families, doctors and researchers in person. :) While there, Andrew presented results from the NPC gene therapy mouse study published by NIH (see October 2016 update).
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A lot has happened since our last update!

Today, an NPC gene therapy mouse study by the National Institutes of Health (NIH) was published in the journal Human Molecular Genetics.

Galyatech has a non-exclusive license with the NIH for the NPC gene therapy vectors used in this study, including the vector AAV9-EF1a-NPC1, which provides the proof-of-concept foundation for the ongoing development of GALYA-1.

Here are links to the Abstract and Full PDF (Free) and NIH's press release.

Here are videos from the published paper and a brief visual summary of efficacy data, along with other announcements.

Video G1: Three Mice – Treated, Untreated, Normal

Video G2: Untreated, Treated (Shown at Multiple Weeks)

Gene Therapy-Treated Mice Lived Longer with Improved Weight and Motor Activity

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Mean Survival ± SD: 69 days ± 3.1 vs. 166 days ± 89.2
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Week of Peak Weight: 6 weeks vs. 12 weeks
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Pct Weight Change (6-9 weeks): -17% vs. approx. +9%

Developing GALYA-1

The NIH mouse study publication is very exciting news! With this key proof of concept research now complete, our commitment remains to develop GALYA-1 as a safe and effective drug – including initiating a Phase I clinical trial – as quickly as possible. We are making progress toward this goal by preparing for efficacy studies in cats and GLP toxicology studies, as well as pushing forward with manufacturing of GALYA-1. Learn more below!

Testing in NPC1 Cats

We have a strong existing partnership with Dr. Charles Vite at the University of Pennsylvania –home of the only large animal model for NPC – and we are prepared to begin gene therapy efficacy studies in the NPC1 cat model soon. Demonstrating efficacy in cats will provide a stronger foundation for a Phase I clinical trial.

Pre-PreIND Scheduled

The FDA has agreed to our request for a pre-preIND interaction to give us advice about our remaining preclinical studies, especially toxicology. This communication with the FDA is a key step in the process of developing GALYA-1 as a safe and effective drug.

Manufacturing Moving Forward

The manufacturing of some components of the non-pathogenic virus is complete! We continue to move forward with manufacturing in parallel with remaining preclinical studies so that we can start toxicology studies for GALYA-1 as soon as possible.

NPUK Family Conference

Andrew Wilkinson and his wife Jennifer attended the NPUK Family Conference last month! It was great to meet many NPC families, as well as doctors and researchers, in person. :) It was a pleasure to be there.
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Where We're Going Next (China)

Andrew and Jennifer are going to China next week to attend the Chinese Niemann-Pick Disease Association (CNPDA) family conference! We will meet families, researchers and doctors in Beijing November 4-6 and will give a presentation on Saturday evening. For all the families in China and Asia, come join us in person! We really want to meet you face to face. :)