CHOROIDEREMIA RESEARCH FOUNDATION HOLDS 2019 INTERNATIONAL CHOROIDEREMIA SYMPOSIUM

On June 6-7, the Choroideremia Research Foundation (CRF) hosted its 2019 International Choroideremia Symposium in Philadelphia, Pennsylvania.  With the support of the Center for Advanced Retinal and Ophthalmic Therapeutics at the University of Pennsylvania, CRF developed an agenda geared toward answering key questions raised by ongoing research, and developing consensus opinion on paths forward for the organization and its community.  The Symposium was attended by 20 international experts in CHM from 5 countries in addition to representatives from biotech industry and the patient community to bring multiple perspectives toward the singular goal of developing treatments to end blindness.

The Symposium was held using an open moderated discussion format, engaging all in attendance to help discuss topics and answer questions using the collective expertise of those in attendance.  The first day focused on pre-clinical topics which could provide better understanding of disease mechanisms and, in corollary, additional avenues toward the development of new therapies.  Much discussion revolved around the underlying mechanisms of retinal cell dysfunction and death in CHM, which like many retinal diseases requires additional investigations.  The group discussed a series of potential therapeutic approaches including the use of stem cells, neuroprotective agents, optogenetics, and reversal of the normal aging process in cells, and how research on these approaches could be supported.  Discussions on day 2 of the Symposium reviewed ongoing natural history studies and clinical trials, bringing together leaders in these respective areas to identify lessons learned from these trials and potential next steps.  Lastly, a robust discussion was held to begin developing a classification system to stage the progression of CHM in patients, as well as the ideal outcome measures to be used in future clinical trials.

“The 2019 International Choroideremia Symposium was a tremendous success,” says Christopher Moen, Chief Medical Officer of CRF.  “The topics reviewed at the Symposium identified several opportunities for research projects which could drive CHM toward future therapies that could work alongside gene replacement therapy.  We’re excited at the future of CHM research and fortunate to have such tremendous support from our medical and scientific community.”

About the Choroideremia Research Foundation

CRF was founded in 2000 as a fundraising and patient advocacy organization to stimulate research on CHM. Since its inception, the CRF has provided over $2 million in research awards and is the largest financial supporter of CHM research worldwide. Research funded by the CRF has led to the development of a CHM animal model, the pre-clinical production of gene therapy vectors currently in clinical trials, and the CRF Biobank which stores tissue and stem cell samples donated by CHM patients.

4DMT and ROCHE Expand Ophthalmology Partnership to Develop and Commercialize Multiple AAV Gene Therapy Products

4D Molecular Therapeutics (4DMT), a leader in Therapeutic Vector Evolution for adeno-associated virus (AAV) gene therapy vector discovery and product development, today announced the expansion of its 2016 research agreement with F. Hoffmann-La Roche Ltd and Hoffmann-La Roche Inc. into a broad long-term partnership to develop and commercialize multiple ophthalmology products.

The expanded agreement will allow each company to leverage its primary strengths to bring highly-optimized gene therapeutics to ophthalmology patients as expeditiously as possible. 4DMT will be responsible for vector discovery and optimization, product design and engineering, pre-clinical and early-stage clinical development, including manufacturing activities, while Roche will conduct pivotal clinical trials and commercialize the new therapeutics globally.

4DMT’s intravitreally-delivered choroideremia clinical candidate, 4D-110, is the first collaboration program; IND-enabling studies and activities are underway. Additional clinical candidate development programs are underway to treat retinal diseases with high unmet need.

“Together we elected to expand our partnership after 4DMT completed proprietary intravitreal vector discovery and characterization. We have created clear synergies between 4D’s vector discovery, gene therapy development and manufacturing capabilities and Roche’s expertise in late-stage clinical development and global biologics commercialization. The decision to expand our partnership represents validation of our ophthalmology platform, clinical candidates and team,” said David Kirn MD, CEO and co-founder of 4DMT.

“This expanded partnership could prove a major catalyst to bring new therapies for blinding retinal disorders. 4D’s gene therapy technology and Roche’s expertise in biologics and should be a powerful combination,” says Jeffrey S. Heier, MD, Co-President and Medical Director, Ophthalmic Consultants of Boston.

“The expansion of this partnership holds promise for accelerating treatments for our patients with retinal diseases,” says Dr. Stephen Rose, Chief Scientific Officer of Foundation Fighting Blindness, positioned as the largest non-governmental/non-commercial supporter of R&D for inherited retinal degenerations.

“The prospect of an intravitreally-delivered gene therapy for choroideremia could potentially benefit the whole population of patients with this condition,” explains Ian MacDonald MD, Professor in the Department of Ophthalmology and Visual Sciences, University of Alberta.

Affecting approximately 200,000 patients in the US and similar numbers in Europe, inherited retinal diseases are, collectively, a major cause of adult and childhood blindness. Mutations in more than 200 genes are known to cause these rare, orphan conditions for which there are currently few approved therapies. More common diseases of the retina affect several million patients in the US and EU.

About 4D Molecular Therapeutics (4DMT)

4DMT is focused on the discovery and development of targeted and proprietary AAV gene therapy products for use in patients with severe genetic diseases with high unmet medical need. Our robust discovery platform, termed Therapeutic Vector Evolution, empowers us to create customized gene delivery vehicles to deliver genes specifically to any tissue or organ in the body, by optimal clinical routes of administration, at manageable doses and with resistance to pre-existing antibodies. These proprietary and targeted products may be developed to treat both rare genetic diseases and large market complex diseases. 4DMT is creating a diverse and deep product pipeline through its own internal 4D products, as well as through partnered programs.

4DMT patient advocacy organization partners in ophthalmology include Foundation Fighting Blindness and Choroideremia Research Foundation.

About 4DMT’s Therapeutic Vector Evolution

Gene therapy has shown promise for the treatment of rare diseases, yet current clinical stage gene therapy products are not targeted and are generally based on one of a few AAV vectors that are “naturally-occurring” or “wild-type”, meaning they were found in nature (e.g. as laboratory contaminants or as monkey infections). These first-generation AAV vectors, while generally safe and well-tolerated in patients, do not have targeted or optimized delivery properties and often require aggressive and/or invasive injection at high doses to attempt the desired transduction of target cells in the body. 4DMT is advancing the field of AAV vector technology by deploying principles of evolution and natural selection to create vectors that efficiently and selectively target the desired cells within the diseased human organ via clinically optimal routes of administration, at manageable doses and with resistance to pre-existing antibodies in the population. Our Therapeutic Vector Evolution platform deploys an estimated 100 million unique AAV variants with extensive diversity, from over 35 unique and proprietary 4DMT AAV vector libraries. After defining the Target Product Profile, and the associated Target Vector Profile, 4DMT then applies proprietary methods to identify lead vectors for the specific Target Vector Profile from within our AAV libraries. The result is a customized, novel, and proprietary pharmaceutical-grade product uniquely designed for targeted therapeutic gene delivery and efficacy in humans.

4DMT Now Recruiting for Natural History Studies!

4D Molecular Therapeutics Enrolling Patients in Natural History Study in Lead Clinical Program to Develop Gene Therapy Treatment for Choroideremia
 

Intravitreal delivery to the retina is critical to Choroideremia treatment

4D Molecular Therapeutics (4DMT), a leader in gene therapy product discovery and development, is accepting patients for enrollment in its Choroideremia Natural History Study (NHS). This study is an important step in developing a groundbreaking gene therapy product optimized for intravitreal administration to treat Choroideremia (CHM) patients. 4DMT has deployed its proprietary AAV vector discovery platform, Therapeutic Vector Evolution, to create and optimize a proprietary AAV vector for intravitreal delivery to the retina. This vector is designated to be the basis for the first 4DMT experimental gene therapeutic targeted for the treatment of CHM. 4DMT is working in close collaboration with the Choroideremia Research Foundation on CHM product development and the Natural History Study.

Choroideremia Natural History Study (NHS) Purpose
The NHS is a multi-center US-based study designed to evaluate disease progression in a wide variety of individuals with CHM. Understanding more about clinical endpoints as the disease progresses will aid in identifying both potential participants and the best clinical measures for upcoming 4DMT clinical trials. Participants in the study will be assessed every six months over two years. At each visit, they will undergo a series of photographic, imaging and clinical evaluations.

The study is accepting males with a confirmed CHM diagnosis aged 14 and up. There is no exclusion for good visual acuity. Additional information about the NHS study criteria, locations, and contact information may be found at clinicaltrials.gov

Two clinical sites are actively recruiting for the study:

Retina Foundation of the Southwest
9600 N Central Expressway, Suite 200
Dallas, TX 75231
Contact: Kirsten Locke
Tel: 214-363-3911 ext. 114
Email: kglocke@retinafoundation.org
Principal Investigator: David Birch, PhD

Retina-Vitreous Associates Medical Group
1127 Wilshire Boulevard, #1620
Los Angeles, CA 90017
Contact: Janet Kurokouchi
Tel: 310-289-2478 – Clinical Trial Department
Email: jkurokouchi@laretina.com
Principal Investigator: David Liao, MD

A third site for the NHS, the Moran Eye Center at the University of Utah, is not currently enrolling patients but expects to do so in the near future. They are currently compiling a list of interested CHM patients. If you are interested in enrolling at this study site contact:

John A. Moran Eye Center – University of Utah
65 Mario Capecchi Drive
Salt Lake City, UT 84132
Contact: Katie Rogers
Email: katie.rogers@utah.edu
Tel: 801-581-2352 – Ask for Clinical Study Staff Office
Principal Investigator: Paul Bernstein, MD

“The Choroideremia Research Foundation and its community are thrilled at the initiation of 4DMT’s Natural History Study. This milestone brings us one step closer to a treatment that could end blindness from CHM,” said Christopher Moen, MD, President of the Choroideremia Research Foundation.

“This clinical study is a significant milestone for the company and a critical step forward for our lead program to treat choroideremia. We are convinced the data generated in this study will accelerate the clinical development of our lead product,” said Dr. David Kirn, co-founder and CEO, 4D Molecular Therapeutics.

4DMT Announces Plans for CHM Natural History Study

4dmt-logotype-retina
4DMT is accepting inquires from interested choroideremia (CHM) patients for their upcoming Natural History Study.  In partnership with the Choroideremia Research Foundation, 4DMT seeks to develop a gene therapy product optimized for intravitreal administration to treat Choroideremia.
Natural History Studies track disease progression and are an essential first step in developing efficient clinical stages of testing in rare diseases. The purpose of this study is to evaluate disease progression as well as determine the feasibility of measuring endpoints for subsequent clinical trials in the hopes of providing medical benefit through gene therapy to all choroideremia patients and their families.
Enrollment for 50 patients begins in fall 2016 at 5 study sites throughout the United States. We will be updating you as the study opens and patients are being accepted.
Eligibility requirements include but are not limited to:  participants must be 14 years or older and have a CLIA Certified Genetic Diagnosis with visual acuity ≥ 20/200 or better.
Study participation requirements:
Attend Study Site Visits
  •          One visit every 6 months, for 24 months
Assessments Include
  •          Medical history review
  •          Visual and eye exam
  •          Photography and imaging
Email questions to  CHM@4Dmoleculartherapeutics.com

Gene Therapy Trial Results Released!

Robert E MacLaren In a letter published by the New England Journal of Medicine today, Dr. Robert Maclaren released positive long-term results from the initial 6 Choroideremia patients treated in the clinical trial at the University of Oxford. These results, which show sustained effects of gene therapy, represent another critical step toward the approval of gene therapy for Choroideremia.


The six-month results of this clinical trial were reported in the Lancet in 2014, and demonstrated improvement of vision in 2 patients with no change in vision of the remaining 4 patients. The results published today provided the continued evaluation of these 6 patients up to 3-4 years after treatment. The 2 patients whose visual acuity improved at six months demonstrated sustained effects of the treatment at approximately 3.5 years despite the continued loss of vision in the untreated eye during this period. 3 additional patients have maintained their visual acuity in the treated eye at 3-4 years despite declines in vision of the untreated eye. Patient 6, who received the lowest dose of gene therapy due to surgical issues, had continued decline of visual acuity in both eyes. In summary, 5 of 6 patients who received gene therapy have improved vision in their treated eye compared to the untreated eye after several years of observation.


“The CRF is thrilled to receive the results of Dr. Maclaren’s long-term observation of patients in his Choroideremia clinical trial,” reports Christopher Moen, CRF President. “These results show that gene therapy for Choroideremia is successful and has the potential to end blindness from this disease. These results bring us one step closer to the first approved treatment for Choroideremia, a treatment we have waited our whole lives for. We thank Dr. Maclaren and his team for their ground-breaking work on behalf of the Choroideremia community.”


Regarding these results, Dr. Maclaren states, “This shows that the visual acuity gains that were reported in the Lancet were real and also long-lasting. I think that is the key take-home message. The improved clarity is presumably due to the remaining cells in the central retina being healthier.” Dr. Maclaren will be presenting these results at the Association for Research in Vision and Ophthalmology Annual Meeting in Seattle, WA next week.


The gene therapy vector was developed by a team of researchers, led by Dr. Maclaren and Dr. Miguel Seabra, and is now the property of NighstaRx Ltd. The approach uses a virus known as adeno-associated virus (AAV) to deliver a normal copy of the gene causing Choroideremia into cells of the eye. The CRF provided significant financial support for the pre-clinical research and development of this gene therapy vector. Dr. Maclaren has completed his phase I/II trial involving a total of 12 patients and has announced the intention to proceed with a phase II study enrolling 30 patients later this year.
H Eric Hartman, CRF Executive Director, also noted his thanks to the CRF membership for their generous long-term support. “It is only through the dedication and generosity of our members and friends that enables the CRF to provide the crucial financial backing of for the amazing advancements in CHM research.”


Click here for more information about this treatment and NightstaRx.

CRF Announces Partnership With 4DMT

4dmt-logotype-retina

 

D.Peterson

 

 

 

4D Molecular Therapeutics and the Choroideremia Research Foundation Partner to Develop Gene Therapy Treatment for Choroideremia

 

Emeryville, CA, February 23, 2016 — 4D Molecular Therapeutics (4DMT), a leader in Adeno-Associated Virus (AAV) gene therapy vector discovery and product development, and the Choroideremia Research Foundation (CRF), a non-profit dedicated to finding a cure for choroideremia, today announced a  partnership to develop a gene therapy product optimized for intravitreal administration to treat Choroideremia.

 

Under the terms of the agreement, CRF will provide 4DMT funding to deploy its proprietary AAV vector discovery platform, Therapeutic Vector Evolution, to create and optimize a proprietary AAV vector for intravitreal delivery to the retina. This vector will be the basis of a 4DMT experimental gene therapeutic that will be evaluated and developed by 4DMT in close collaboration with the CRF.

 

“We believe that 4D’s Therapeutic Vector Evolution approach to AAV vector design, which creates a vector with the ability to successfully penetrate the retina via intravitreal delivery, rather than subretinal injection, can potentially change the future of Choroideremia gene therapy,” said Christopher Moen, MD, President of the CRF.  “The outcomes of this collaboration may offer tremendous benefit to our patient community, and our unique partnership can serve as a model for other rare disease groups.”

 

“CRF brings their crucial clinical expertise, network of doctors, trial investigators and patients together to inform the best possible product design, clinical trial design, and trial execution for this important program,” said David Kirn, MD, co-founder and CEO of 4DMT. “Teaming up with CRF allows us to pursue our vision of providing the best gene therapy products to patients who truly need them.”

 

Further terms of the agreement were not disclosed.

 

About Choroideremia

A rare, inherited form of blindness, Choroideremia is an x-linked retinal disease that begins as night blindness in childhood and progresses to complete blindness. It affects an estimated 1 in 50,000 people in the United States, predominantly males, and has no effective treatment.

 

About the Choroideremia Research Foundation

The CRF was founded in 2000 as a fundraising and patient advocacy organization to stimulate research on CHM.  Since its inception, the CRF has provided over $2 million in research awards and is the largest financial supporter of CHM research worldwide.  Research funded by the CRF has led to the development of a CHM animal model, the pre-clinical production of gene therapy vectors currently in clinical trials, and the CRF Biobank which stores tissue and stem cell samples donated by CHM patients.

 

About 4D Molecular Therapeutics

4DMT is focused on the discovery and development of targeted and proprietary AAV gene therapy vectors and therapeutic products. Our robust discovery platform, termed Therapeutic Vector Evolution, empowers us to create customized gene delivery vehicles to deliver genes to any tissue or organ in the body, by optimal clinical routes of administration and with evasion of pre-existing antibodies. These proprietary and targeted products allow us to treat both rare genetic diseases and complex large market diseases. 4D is creating a diverse and deep product pipeline through partnerships, while progressing internal 4D products toward clinical trials in parallel. 4D partners include: Pfizer (PFE), Roche (SIX: ROG; OTCQX: RHHBY), uniQure (QURE), AGTC and Benitec.

 

About 4DMT’s Therapeutic Vector Evolution

Current clinical stage gene therapy products are based on AAV (Adeno-Associated Virus) vectors that are generally “wild-type” or primitive vectors, meaning they were found in nature as laboratory contaminants or as monkey infections. These first-generation AAV vectors, while generally safe and well-tolerated in patients, do not have optimized delivery properties and often require aggressive and/or invasive dosing to attempt the desired transduction of target cells. 4DMT is advancing the field of AAV vector technology by deploying principles of evolution and selection to create vectors that efficiently and selectively target the desired cells within the diseased human organ via clinically optimal routes of administration. Our Therapeutic Vector Evolution platform deploys approximately 100 million unique AAV variants from proprietary 4DMT AAV libraries with unmatched diversity. 4DMT then applies proprietary methods to identify lead vectors that are highly optimized for a specific target cell and organ, route of therapeutic administration, and capacity to evade pre-existing antibodies in patients. The result is a customized, novel, and proprietary pharmaceutical-grade vector uniquely designed for therapeutic gene delivery in humans.

 

Contact:

Investors

Peter Rahmer, 646-378-2973

prahmer@troutgroup.com

 

Media

Sharon Tetlow, 415-515-3902

stetlow@4dmt.com

Gene Therapy Trials Begin in Germany

At Tübingen Department of Ophthalmology in Germany, the first gene therapy trial for Choroideremia patients began on January 13th. This milestone was preceded by many years of preparatory work in Tübingen – sponsored by the nonprofit Tistou and Charlotte Kerstan Foundation. In this case, the team was able to move forward based on results from Oxford, where Professor Robert MacLaren developed this new treatment and tested for the first time on patients in the United Kingdom. At this time, more than 20 patients have been treated at several centers in the context of clinical studies around the world. In addition to the original center at Oxford Eye Hospital, trials are currently underway in Edmonton (Canada), Miami (USA). Tübingen is the latest center to begin trials for Choroideremia patients.

The aim of gene therapy is a therapeutic gene sequence to replace a mutated gene, which is responsible for a disease like Choroideremia. By introducing the therapeutic gene, the disease process can be stopped. This works not only in the laboratory – even in children (in the case of another severe retinal disease, Leber’s Congenital Amaurosis) it works so well that an approval for general treatment is likely.

In the case of Choroideremia, it also seems to work well. Initial results have confirmed the safety of the treatment and shown a positive effect For example, in the microperimetry (a kind of visual field examination), the higher the relative dose, the greater was the increase in sensitivity of the treated retina (MacLaren et al, Lancet, January 2014). However, the goal of treatment can also be seen in the natural disease progression – the steady deterioration of visual function stops, with no further progression towards blindness. Many adult patients with Choroideremia know their sight is getting worse and there is currently no other treatment option, the interest in these studies is very high.

We thank the Tübingen University Eye Clinic team (Director: Prof. Bartz-Schmidt) and the Research Institute of Ophthalmology team (Director: Prof. Ueffing) who together are enabling Choroideremia patients access to these trials in Germany.