Frequently asked questions regarding the GeneTx KIK-AS Clinical Trial

GeneTx Biotherapeutics has announced it has received IRB approval from Rush University Medical Center in Chicago, IL to begin the «KIK-AS» (Knockdown of UBE3A-antisense in Kids with Angelman Syndrome) Phase 1/2 clinical study of GTX-102.

What does this mean?

• The United States Food and Drug Administration’s Investigational New Drug (IND) program is the means by which a Sponsor obtains permission to start human clinical trials and to ship an experimental drug across state lines (usually to clinical investigators) before a marketing application for the drug has been approved.

What is a clinical trial?

• Although there are many definitions of clinical trials, they are generally considered to be research studies in human beings that follow a pre-defined protocol to assess the safety and effects of an “intervention.” In the KIK-AS study, the clinical trial is evaluating the safety and assessing the effects of an investigational drug called “GTX-102” in patients with Angelman syndrome (AS).

What type of drug is GeneTx bringing to clinical trial?

• GeneTx will be evaluating GTX-102, an investigational antisense oligonucleotide (ASO).
• Antisense oligonucleotides or “ASOs” are short pieces of RNA and/or DNA that are often intended to bind to RNA in the body to increase or decrease the production of protein that is associated with a disease.
• Investigational GTX-102 is intended to target the father’s normally silent copy of the UBE3A gene in an attempt to produce the UBE3A protein that is missing or deficient in the neurons of the brain in people with AS.

Is GTX-102 considered a gene therapy?

• No, GTX-102 is not a gene therapy and does not alter the gene thought to be responsible for AS. Investigational GTX-102 is intended to target the father’s normally silent copy of the UBE3A gene in an attempt to produce the UBE3A protein that is missing or deficient in the neurons of the brain in people with AS.

GeneTx announced that they will be initiating a Phase 1/2 study called KIK AS in early 2020. What is a Phase 1/2 study and why is GeneTx’s study named KIK AS?

• A Phase 1 study evaluates the safety , side effects, and various doses of an investigational new drug. A Phase 2 study assesses whether the investigational new drug is potentially effective.
• KIK AS stands for Knockdown of UBE3A-antisense in kids with Angelman Syndrome.

Who can participate in this clinical trial and where are the study sites located?

• The major criteria for entry or participation are listed on clinicaltrials.gov (https://clinicaltrials.gov/ct2/show/NCT04259281).
• The planned sites will be located in: Boston, Chicago, Cincinnati, Denver, Los Angeles, New York City and Ottawa, Canada.

When will GeneTx start the KIK-AS study of GTX-102?

• The KIK-AS study will be open for enrollment at Rush University Medical Center in Chicago, IL at the end of February 2020. GeneTx anticipates additional sites opening in Boston, Cincinnati, Denver, Los Angeles, New York and Ottawa, Canada and will update the Angelman community accordingly and list these sites on clinicaltrials.gov once they are open for enrollment.

Why can only deletion positive individuals participate?

• This is the first study in humans. It is designed to evaluate safety, and also to understand if there is any potential benefit, so a population of patients as similar to each other as possible is being enrolled.
• Patients with a deletion were selected because they do not make protein or have any functional protein. With other genotypes, patients may have some protein already and having the body make more might theoretically lead to too much UBE3A protein.
• Ongoing pre-clinical work is underway to evaluate GTX-102 in other genotypes.

What if my child doesn’t have laboratory documentation of UBE3A deletion?

• Contact the doctor who confirmed your child’s diagnosis and ask for a copy of the laboratory report.

Why are the ages limited from 4-17? When will you include older or younger patients?

• We hope to include patients of other ages in future studies based on the results of this first study.

How is GTX-102 administered?

• GTX-102 is administered by a lumbar puncture (LP) or spinal tap.
• An LP, also called a spinal tap, is a procedure where a small needle is placed into the lower back between the bones of the back. Some of the fluid surrounding the spinal cord and brain called the cerebral spinal fluid (CSF) is removed and GTX-102 is injected. Your study doctor will explain this to you in more detail.

What are the risks of GTX-102 and lumbar puncture?

• You will need to speak to a study doctor for that information.

Will there be travel reimbursement offered to study participants?

• Yes, the study Sponsor (GeneTx) will reimburse for travel. The study site can provide more details if your child is selected to be screened.

Have ASOs been used in patients with other diseases?

• ASOs have been used in other diseases, some of which are neurological disorders. In 2016 an ASO was approved by FDA for the treatment of a neurological disease called Spinal Muscular Atrophy which is administered by lumbar puncture like the investigational drug in the KIK AS study. Currently there are several clinical trials evaluating investigational ASOs administered by lumbar puncture such as for Huntington’s disease, Batten Disease, ALS, and others.

What is GeneTx Biotherapeutics’ role in the KIK AS study?

• GeneTx Biotherapeutics is the Sponsor of the KIK-AS study. As the Sponsor, GeneTx’s responsibilities include a number of important elements such as selecting the study investigators; monitoring the progress of the study; ensuring all required regulatory approvals are obtained; and ensuring the study is conducted in accordance with the research plan, etc.

What is the Foundation for Angelman Syndrome Therapeutics’ (FAST) role in the KIK AS study?

• FAST has no role in the KIK-AS study. FAST funded the preclinical studies of an antisense oligonucleotide for the treatment of Angelman syndrome at the laboratory of Dr. Scott Dindot at Texas A&M University. In December 2017, FAST formed GeneTx Biotherapeutics, LLC as a subsidiary and licensed the technology, invented by Dr. Dindot, from Texas A&M University Systems.

Who is Ultragenyx Pharmaceutical and what is their role for this study?

• Ultragenyx (UGX) is a biopharmaceutical company specializing in rare diseases. They have secured an option to acquire GeneTx and are currently partnered with GeneTx for the development program of GTX-102 and are providing staff support, including strategic guidance and clinical expertise.