ASHG 2018 show preview: Covering the breadth of human genetics in San Diego

Covering the breadth of human genetics in San Diego

ASHG 2018 meeting to showcase the latest on the human genome

Billed as the largest human genetics meeting and exposition in the world, the 68th Annual Meeting of the American Society of Human Genetics (ASHG) will be held at the San Diego Convention Center Oct. 16 through Oct. 20, and is expected to attract more than 6,500 scientific attendees, plus almost 250 exhibiting companies, with ASHG 2018 providing a forum for the presentation and discussion of cutting-edge science in all areas of human genetics.

As ASHG notes, its members and also non-member leading scientists from around the world have been selected to present their research findings at invited, platform and poster sessions during ASHG 2018. Abstracts presented at the event will be published online and are citable. Add to that an exhibit hall—offering attendees the opportunity to view state-of-the-art medical and laboratory equipment, products, services and computer software—and you get both the educational and practical tools designed to enhance human genetics research, teaching and consultation.

Looking back at ASHG 2017 (which was held in Orlando, Fla.), nearly 7,500 people attended, nearly 6,000 of them members of the scientific community, so expect to be in good—and varied—company if you attend. And speaking of attendance, we thought it was worthwhile to look at why you should consider late registration and attend if you weren’t planning to do so this year, or why you might want to put ASHG 2019 on your calendar for next year (and also to give those of you planning to attend a sneak-peek). To that end, we posed a few questions to ASHG 2018 Program Committee Chair Dr. Heather C. Mefford.

DDNews: What is new or significantly altered this year compared to last year/past years, and why was it changed or added; what is the significance?

Dr. Heather C. Mefford: There are a few new things we are trying this year at the meeting. For example, we’ve had feedback from past attendees that the sessions are not very interactive, so for several invited sessions this year, we’re going to try more of a panel discussion approach. Instead of four didactic talks, we’re going to try shorter talks by experts, followed by a significant chunk of the time dedicated to panel discussion that will hopefully involve Q&A from the audience and generate interesting conversations.

We will also be setting up networking inspiration lounges, which are informal spaces for attendees to connect with each other and build on the excitement of the day. In these lounges, attendees will be able to discuss the latest science around specific daily themes and with designated thought leaders.

DDNews: What might you highlight in terms of programming or events for our readers (researchers/administrators involved in drug discovery/R&D/clinical trials and people in diagnostics R&D) and why?

Mefford: The meeting schedule offers a clinical track that includes many such sessions. For example:

• “Clinical Spotlight” invited sessions on topics such as polygenic risk scores and prenatal genetic testing

• “Diagnostic Challenges” event featuring the review and discussion of unique cases

• Workshops and sessions on aspects of clinical life, such as patient communication, translational genetics, medical decision-making and variants of uncertain significance

• CoLabs—three theaters in the Exhibit & Poster Hall featuring programming on clinical, laboratory and data topics

If you’ve never attended the ASHG Annual Meeting before, my first advice would be to spend a little time doing your homework—look at the schedule before you get there and figure out a few sessions you might want to attend. The other piece of advice I have is don’t be shy—we are all friendly, and we’re all eager to have first-time attendees feel comfortable and help them figure out their place at the meeting and in the society. I would also suggest looking at the networking sessions and the parties, and to find a buddy who can help you navigate the schedule, get you to those places and introduce you to people.

DDNews: What other events/programming would you highlight or are particularly proud of and why?

Mefford: ASHG and the European Society of Human Genetics (ESHG) partner each year to produce a joint session at each organization’s meeting called the “Building Bridges” session. This year’s session, on prenatal genetic testing, will involve two speakers from Europe and two speakers from America in order to get perspectives from both continents. Prenatal genetic testing is an area that is evolving quickly, with new, non-invasive technologies available and the opportunity to diagnose earlier and earlier. We also chose this topic because we think there are differences between the American and European healthcare systems that might generate some interesting discussion.

DDNews: Is there anything you can tell us about plans for next year, either in general or in terms of upcoming additions/changes?

Mefford: The ASHG 2019 Annual Meeting will take place in Houston, Texas, Oct. 15-19, and the 2019 Program Committee will be chaired by Dr. Kiran Musunuru. We will begin soliciting proposals for invited sessions and interactive invited workshops after ASHG 2018, with a deadline of Dec. 13, 2018. Abstracts for ASHG 2019 will be due June 6, 2019. Additional planning for the 2019 meeting, including specific events and initiatives, will take place after the 2018 meeting concludes, and will incorporate feedback from attendees.

DDNews: Just in general, why would you recommend attending the event?

Mefford: I’m excited for ASHG 2018, first and foremost for the science. We had a fantastic response to our call for abstracts this year, with nearly 3,700 abstracts submitted. We’ve put together a really nice program with a diverse set of topics that will be of interest to the full range of our attendees—ranging from trainees to senior faculty, from clinicians to basic researchers to computational biologists. I think there’ll be something for everyone.

Mentoring and networking

The Conference to Career offering, run jointly by ASHG and The Jackson Laboratory, aims to help trainees make the most of their time at a national meeting by learning how to navigate, network, and effectively communicate with other members. The in-person component of the program takes place before the meeting begins, on Tuesday, Oct. 16 at 10 a.m.

Once on site, trainees can network with peers and find a buddy to navigate the meeting with at ASHG Peer Networking Trivia the afternoon of Tuesday, Oct. 16. In addition, the Trainee-Mentor Luncheons, scheduled on Wednesday, Oct. 17, and Thursday, Oct. 18, provide an opportunity to network and get advice from potential mentors at different career stages.

ASHG annual awards

The following awards will be presented at the 2018 ASHG Annual Meeting.

William Allan Award

This is the top prize given by ASHG. It was established in 1961 in memory of William Allan (1881-1943), who was one of the first American physicians to conduct extensive research in human genetics. The Allan Award is presented annually to recognize substantial and far-reaching scientific contributions to human genetics, carried out over a sustained period of scientific inquiry and productivity.

Curt Stern Award

This honors the memory of Curt Stern (1902-1981) as an outstanding pioneering human geneticist. This award is presented yearly for outstanding scientific achievements in human genetics that have occurred during the last 10 years.

Arno Motulsky-Barton Childs Award for Excellence in Human Genetics Education

Formerly known as the Excellence in Human Genetics Education Award before it was renamed in 2015, this recognizes outstanding contributions to human genetics education. Nominees must have made contributions that are recognized nationally or internationally as being of exceptional quality and great importance to human genetics education.

Victor A. McKusick Leadership Award

Established by ASHG in honor of the late Dr. Victor A. McKusick, this award is presented on behalf of the society to an individual whose professional achievements have fostered and enriched the development of various human genetics disciplines.

Advocacy Award

This honors individuals or groups of individuals who have exhibited excellence and achievement in promoting the science of human genetics and its application for the common good.

Mentorship Award

This honors ASHG members who have significant records of accomplishment as mentors. The award is open to individuals at all academic ranks, but eligible candidates must have demonstrated a sustained pattern of exemplary mentorship at the graduate student, postdoctoral, residency or fellowship level.

Early-Career Award

Recognizes scientists who are in the early stages of their careers as independent investigators. The candidate must not have been an independent investigator for more than 10 years and the work submitted for consideration must have been primarily the product of the candidate’s independent lab.

C.W. Cotterman Awards

Each September, the editorial board of The American Journal of Human Genetics selects two articles published in the journal in the previous year that best represent outstanding scientific contributions to the field of human genetics.

ASHG/Charles J. Epstein Trainee Awards for Excellence in Human Genetics Research

Honors excellence in research conducted by predoctoral and postdoctoral trainees (including genetic counseling trainees) through merit-based awards that recognize highly competitive abstracts submitted and presented at the ASHG Annual Meeting.

Social events and networking opportunities

Opening Reception

Wednesday, Oct. 17, 7 p.m. to 9 p.m.

San Diego Convention Center

An evening of mingling, relaxing and a little rock and roll. Share your experiences from the first day of the meeting, discuss innovations you discovered and share ideas you’ve generated, as well as wind down and socialize.

#ASHG18 Tweetup

Thursday, Oct. 18, 7:30 p.m. to 9 p.m.

Garage Kitchen + Bar, 655 Fourth Ave., San Diego

Ever wonder what all of those people on Twitter or other social media look like in person? Here’s your chance to find out.

Exhibit & Poster Hall hours

Wednesday, Oct. 17

10 a.m. to 4:30 p.m.

Thursday, Oct. 18

10 a.m. to 4:30 p.m.

Friday, Oct. 19

10 a.m. to 4:30 p.m.

Where it’s mostly happening

Meeting venue

San Diego Convention Center

111 West Harbor Drive, San Diego

(619) 525-5000

Headquarter hotels

The San Diego Marriott Marquis & Marina

333 West Harbor Drive, San Diego

(619) 234-1500

Hilton San Diego Bayfront

1 Park Blvd., San Diego

(619) 564-3333

RECENT GENETIC AND GENOMIC RESEARCH AND DEVELOPMENT NEWS IN HONOR OF ASHG 2018

First-in-class for cystic fibrosis?

Boehringer Ingelheim partners with several U.K.-based entities to develop gene therapy for the disease

INGELHEIM, Germany—Boehringer Ingelheim recently announced that it is joining in global collaboration with Imperial Innovations, Oxford BioMedica (OXB) and the UK Cystic Fibrosis Gene Therapy Consortium (GTC), which consists of Imperial College London and the Universities of Oxford and Edinburgh. The goal of said collaboration: to develop a first-in-class, long-term therapy for patients with cystic fibrosis (CF). The new partnership brings together the academic partners’ leading expertise in developing gene therapy for CF and OXB’s leading expertise in manufacturing lentiviral vector-based therapies with Boehringer Ingelheim’s capabilities in drug discovery and the clinical development of novel breakthrough therapeutic agents.

Cystic fibrosis is a genetic disease that causes persistent lung infections and usually limits a person’s ability to breathe over time. There are more than 2,000 known mutations in the gene for the cystic fibrosis transmembrane conductance regulator (CFTR), many of which result in a person developing CF. Existing treatments and those under development can only slow the progression of disease and thus CF continues to be associated with considerable morbidity, mortality and a high burden of therapy.

“Through this collaboration, we are joining forces with some of the top talents in this disease space to propel treatment advances forward,” said Dr. Clive R. Wood, senior corporate vice president of discovery research at Boehringer Ingelheim. “Bringing together our existing expertise as a leader for nearly a century in the discovery and development of therapies that have advanced patient care in respiratory diseases with the gene therapy knowledge of our partners, we aim to unlock unprecedented opportunities for patients with this devastating disease, who are desperately waiting for better treatment options.”

In addition, existing treatments will have varying effects depending on a patient’s mutation status, as determined by the particular gene variation that causes their disease. Thus, there is a critical unmet need for therapies that address all CFTR mutations; gene therapy has the potential to provide such a solution.

The collaboration will focus on a novel approach using a replication-deficient lentiviral vector in an inhaled formulation, to introduce a healthy copy of the CFTR gene into the cells of the lung. This method has demonstrated high gene transfer efficiency and offers the possibility of repeated administration to maintain the therapeutic effect. Gene therapy is the only therapeutic approach to date that can address all CFTR gene mutations, thus potentially offering a universal treatment option.

“The UK CF Gene Therapy Consortium has, for the last 17 years, vigorously sought to establish whether gene therapy can become a clinically viable option for patients with CF,” said Prof. Eric Alton, coordinator of the UK Cystic Fibrosis Gene Therapy Consortium. “From the beginning the GTC identified that this goal would require incremental increases in knowledge. We have, therefore, built on our nonviral gene therapy experience to develop a new viral vector-based product, which is currently funded by the Health Innovation Challenge Fund (a partnership between the Wellcome Trust and the Department of Health and Social Care) and the Cystic Fibrosis Trust. It is with great pleasure that we now join forces with two world-class organisations.

“Boehringer Ingelheim will provide its multinational industry expertise, including a rich heritage in the respiratory field, to drive the product towards the clinic, whilst Oxford BioMedica is the acknowledged leader in the field of lentiviral vector manufacturing. The GTC believes that this partnership provides CF patients with the optimal chance to establish gene therapy as routine clinical practice, relevant to all patients, irrespective of their mutation status, and in due course to both prevent lung disease as well as treat established problems. We would like to take this opportunity to warmly thank all of our fundraisers who have supported us over many years.”

“This novel three-way partnership brings together an unparalleled combination of clinical, scientific, manufacturing and commercial skills in an effort to develop new treatments and make a major contribution to the lives of patients affected by cystic fibrosis,” added John Dawson, CEO of Oxford BioMedica. “The GTC has been working determinedly for over 15 years to get to this exciting point of forming a partnership with Boehringer Ingelheim, a global pharmaceutical company with respiratory expertise. Our contribution to this partnership reaffirms our leading position in the development and manufacturing of lentiviral vector gene therapy products at large scale. We look forward to working with our new academic and industry partners.”

Boehringer Ingelheim has received an option to license the exclusive global rights to develop, manufacture, register, and commercialize this lentiviral vector-based gene therapy for the treatment of cystic fibrosis. Financial terms were not disclosed. During the option period the partners will work closely together to pursue the development of this innovative approach financed by Boehringer Ingelheim.

Andrew Tingey, director of healthcare licensing at Imperial Innovations said, “The UK Cystic Fibrosis Gene Therapy Consortium shows the power of world-class academic groups collaborating to develop advanced potential therapies. We were delighted to have been chosen as the technology transfer partner for the GTC and have worked closely with them during the development of this potential new gene therapy, securing the intellectual property necessary to drive forward its commercial development and to support the collaboration with Boehringer Ingelheim and Oxford BioMedica. The combination of expertise and resources realized by this deal will give the project a unique opportunity to develop an advanced therapy that could significantly impact the lives of thousands of people living with cystic fibrosis, and we are delighted to have played the lead role in securing this partnership.”

Mount Sinai researchers restore vision using retinal stem cells

NEW YORK—Researchers at Mount Sinai have successfully restored vision in mice through activating retinal stem cells, something that reportedly has never been done before. Their study, published in the August 15 online issue of Nature, could transform treatment for patients with retinal degenerative diseases, which currently have no cure.

“This study opens a new pathway for potentially treating blinding diseases by manipulating our own regenerative capability to self-repair,” explained lead investigator Dr. Bo Chen, an associate professor of ophthalmology and director of the Ocular Stem Cell Program at the Icahn School of Medicine at Mount Sinai. “This is the first step to finding promising cures for patients that involve self-repair as opposed to medicine or invasive procedures.”

In zebrafish, Müller glial cells (MGs) are a source of retinal stem cells that can replenish damaged retinal neurons and restore vision. In mammals, MGs do not have regenerative capability after photoreceptors are lost, and therefore retina damage cannot fix itself. As a result, in patients with diseases like macular degeneration or retinitis pigmentosa that kill retinal cells, the disease progression is often irreversible. Researchers hypothesized if they could somehow reactivate MGs and bring back vision.

A team of scientists did a two-step gene transfer to reprogram MGs into blind mice. First, they activated dormant stem cells to become active stem cells. The second step involved another gene transfer to help stem cells develop into rod photoreceptor cells. After this two-step reprogramming, investigators found that new rod photoreceptors were generated and integrated into the existing retinal structure, instead of floating around and being ineffective. They saw no difference between these new cells and real rod photoreceptor cells. These cells sensed light, which then triggered information to be sent to the visual cortex (brain) and restored function of the visual pathway. Between four and six weeks after the reprogramming, the blind mice were able to sense light and regained their vision.

While vision was restored to some degree, researchers could not measure the degree of improvement, and must do further testing to find this out.

Sarepta gains rights to multiple CNS-targeted gene therapy programs

CAMBRIDGE, Mass.—Sarepta Therapeutics Inc., a commercial-stage biopharmaceutical company focused on the discovery and development of precision genetic medicine to treat rare neuromuscular diseases, announced this summer that it has made a strategic investment and entered into a license and option agreement with Lacerta Therapeutics, a gene therapy company using a constellation of proprietary adeno-associated virus (AAV) vector technologies to develop central nervous system (CNS)-targeted treatments and lysosomal storage diseases.

Sarepta expects to benefit from Lacerta’s expertise in AAV-based CNS-targeted gene therapies, will gain access to Lacerta’s capsid screening and proprietary OneBac manufacturing platform and process for the licensed products, and bolsters its pipeline to 11 gene therapy programs, with three CNS-focused programs from Lacerta.

“Today’s investment with Lacerta bolsters Sarepta’s position as a leader in precision genetic medicine and moves us forward on our mission is to deliver life-enhancing therapies to those living with underserved diseases and in so doing to become one of the most meaningful global genetic medicine companies in the coming few years,” said Doug Ingram, Sarepta’s president and CEO.

Specifically, the Lacerta relationship provides Sarepta with the following:

• With this transaction, Sarepta has added up to three CNS gene therapy targets to its already significant pipeline of 20 programs in various stages of development, expanding the company’s presence in gene therapy and broadening its therapeutic focus into CNS-targeted therapies.

• Lacerta’s founders, nine in all, who are widely published (over 500 papers among them) in leading peer-reviewed journals, are highly regarded in gene therapy clinical research and have worked at leading centers across the United States, including University of Florida, Nationwide Children’s Hospital, CHOP/University of Pennsylvania and Weill Medical College of Cornell.

• Regarding Sarepta’s license and option to three CNS gene therapy assets, Lacerta will manage the majority of preclinical development while Sarepta will lead clinical development and commercialization. Sarepta will owe development and sales-based milestones to Lacerta and pay single-digit royalties on net sales.

“Our co-founders have dedicated their careers to the development of AAV gene therapy platforms for the treatment of multiple diseases. Lacerta’s mission is to advance these technologies to develop novel treatments for patients with CNS disorders,” said Dr. Joseph Reddy, president and CEO of Lacerta Therapeutics. “We are pleased to begin our collaboration with Sarepta Therapeutics, a gene therapy leader, as it represents a significant step in advancing Lacerta’s treatments to the clinic.”

Looking at the landscape of cell and gene therapies

WASHINGTON, D.C.—In early August, the ARM Foundation for Cell and Gene Medicine released its first-of-its-kind “Health Economic Impact Landscape Analysis” of regenerative medicine advanced therapy.

The analysis includes a comprehensive review of published academic literature, health technology assessments and value frameworks related to the global health economic impact of cell and gene therapies. The analysis is the initial step in the foundation’s broader Economic Impact Project, which will ultimately provide a framework to measure and forecast the effect that breakthrough and potentially curative therapies will have on national and global healthcare economies.

“We are in a new era of value-based medicine. A macroeconomic analytical framework is necessary to objectively assess the clinical, economic, and social impact that regenerative therapies will have on the healthcare economy,” said Morrie Ruffin, executive director of the ARM Foundation.

“It is critical to have better tools for assessing economic value,” said David Smith of Pepper, Hamilton LLP and a co-chair of the Economic Impact Steering Committee. “The increasing availability of safe and effective cell and gene therapies will offer potential benefits and outcomes that in aggregate could profoundly impact the overall cost of care for a given disease or family of diseases. Therefore, more comprehensive macroeconomic models that include additional value inputs, such as indirect patient and caregiver costs, and that look at cost-effectiveness over lifetime horizons should be built to better quantify that impact to support development and application of these therapies.”

The next step for the Economic Impact Project will be to convene a national and international Stakeholder Value Input Consensus Panel to examine macroeconomic value inputs that can be measured and optimized for maximum utility in model development.

Sangamo announces data from trial of gene therapy for hemophilia A

RICHMOND, Calif.—Early August saw Sangamo Therapeutics Inc. announce positive preliminary data from a Phase 1/2 clinical trial evaluating SB-525, a cDNA gene therapy candidate for hemophilia A (the Alta study). SB-525 is being developed as part of a global collaboration between Sangamo and Pfizer Inc. for the development and commercialization of potential gene therapy programs for Hemophilia A.

The Alta study is an open-label, dose-ranging clinical trial designed to assess the safety and tolerability of SB-525 in up to 20 adult subjects with severe Hemophilia A. To date, five patients have been treated at three dose levels. A sixth patient is scheduled for treatment later this month. During the initial dose escalation phase, this study enrolls two patients per dose cohort.

Preliminary observations:

• In the Alta study, SB-525 has been generally well tolerated to date with no treatment-related serious adverse events and no use of tapering courses of oral steroids.

• The fifth patient in the study, the first at the third dose level, was treated in June and has achieved therapeutic factor VIII activity levels.

• A dose dependent effect has been observed in the study, with patients in the second dose cohort reporting reduced use of factor replacement.

Sangamo and Pfizer expect to present detailed data from the Alta study at a hematology conference in the fourth quarter.

“We have made good progress with dose escalation in this study and are encouraged by the safety and tolerability profile to date and by the attainment of therapeutic factor VIII activity levels in the first patient in the third dose cohort,” said Dr. Edward Conner, chief medical officer of Sangamo. “We look forward to generating additional data to assess the consistency and sustainability of the Factor VIII expression observed.”

Krystal’s gene therapy candidate gains orphan status

PITTSBURGH—Krystal Biotech Inc., a gene therapy company dedicated to developing and commercializing novel treatments for patients suffering from dermatological diseases, announced in August that the U.S. Food & Drug Administration had granted Orphan Drug Designation to the company’s second product candidate, KB105, currently in preclinical development for treatment of patients with transglutaminase 1 (TGM-1) deficient autosomal recessive congenital ichthyosis (ARCI). There are currently no treatments for this disease that affects approximately 20,000 patients worldwide.

“We are pleased to receive Orphan Drug Designation for KB105 to treat ARCI as this is an important step forward in our efforts to bring hope to ARCI patients and their families,” said Suma M. Krishnan, founder and chief operating officer of Krystal Biotech. “We are excited by the results of the pharmacology data in animal models to date for ARCI that we submitted to the Office of Orphan Product Development. We are on track to file an IND for KB105 in the fourth quarter of 2018.”