Ophthalmic Innovation 2016:

View from the National Eye Institute

Mala Dutta, Ph.D.Lead, Office of Translational Research

National Eye Institute, NIH

NEI Operating Budget in FY2016: $707 million1/

• NEI Research Project Grants: The biggest part of NEI budget.• Non-dilutive funding:

Grantee keeps the IP (Bayh-Dole Act).1/ Post HHS Secretary’s Transfer

The NEI Audacious Goal Initiative“Regenerate neurons and neural connections in

the eye and visual system”

Three Focus areas of AGI• photoreceptor loss• ganglion cell injury• optic nerve regeneration

• Addresses pathogenesis of many vision diseases and conditions. AMD, Glaucoma, LHON, Retinal Degenerations, etc.

• Model for regenerative therapy beyond vision: CNS & spinal cord.

• Translate basic science of plasticity into effective treatments for strabismus, amblyopia, and central visual processing.

The NEI Audacious Goal InitiativeWorkshops to date:•4 Experts Workshops (SfN & ARVO) / 2 Town Halls at ARVO•2 white papers, next one in J. of Neuroscience

For more information please visit: nei.nih.gov/audacious

2 FOAs•“Functional Imaging of the Visual System”

o 5 awards, May 2015, ~$4M total/yr. for 5 yrs.

•“Identifying Neural Regeneration Factors in the Visual System”

o 6 awards, Sept 2016, ~$4M total/yr. for 3 yrs.

Convergence of initiatives

• The NEI Audacious Goals Initiative Catalyzing neuroregenerative medicine for vision

• The BRAIN Initiative at NIH-2014 Providing new tools and technologies to understand and

modulate brain circuitry

• NIH Precision Medicine Initiative – 2015: Medical treatments of the future based on personal

genetic information

• NCATS Tissue Chip at NIH Developing 3-D platforms engineered to support living

human tissues and cells to improve drug screening

NEI Translational Research Program(R24 Grants)

• Multidisciplinary and collaborative research projects• $10M budget: 6-7 ongoing projects; $1.5M/year/ 5 years. Non

renewable grants • Proof of concept Preclinical development IND/IDE

submission NEI U10/UG1 Clinical Vision Research Grant /R34 Clinical Study Development Grant.

• Current portfolio: small molecule photo switches for outer-retinal blindness; gene therapy for a number of ocular disorders (ABCA4-associated disorders, autosomal RP, and achromotopsia); and microRNAs for potent anti-angiogenesis.

Program Director: Neeraj Agarwal, PhD. agarwalnee@nei.nih.gov

Success stories:

• Emory University: Nanoparticle preparation of chemotherapeutic agents microneedles to inject drugs into suprachoroidal space Start-up Clearside Biomedical

• Univ of Miami: Leber Hereditary Optic Neuropathy (LHON) gene therapy product, AAV-ND4 Phase 1 Clinical trial - follow-up U10 grant.

Small Business Grants (SBIR & STTR)

Program Director: Jerry Wujek, PhD, wujekjer@nei.nih.gov

Support small companies to transform innovative ideas into ophthalmic drugs, medical instruments, or assistive devices that help people.

• $20 M/year, 70 small companies• Regulatory Assistance Program

Success Stories:• VisionQuest Biomedical, LLC: Telemedicine system for real-time, large scale eye

screening at sustainable cost.• Photoswitch Biosciences: Small molecule therapeutic photo-switch channel to restore ‐

vision in retinal degenerative disease.• Parion Sciences, Inc: Epithelial sodium channel antagonist to regulate salt & water

transport as a therapeutic for dry eye.

Cell and Gene Therapy in Intramural Program

iPSC Stem Cell Therapy • Use iPS cells to create RPE patch to treat AMD•A major NEI intramural basic to clinical initiative•IND for human trial in 2017/2018•The leading NIH program for neural transplantation

Human Ocular Gene Therapy X-Linked Retinoschisis (XLRS): Phase I / IIa.•One of first NIH in vivo gene therapy programs• Clinical trials with XLRS patients ongoing

X-Linked Retinitis Pigmentosa RPGR Gene Therapy•Pre-Clinical Phase, murine animal model•AAV-based therapeutic rescue

NEI commits nearly $50M in annual clinical trial support

NEI supported DRCR.net : rapid implementation of protocols for large-scale clinical trials•Prompt versus Deferred Panretinal Photocoagulation (PRP) with Intravitreal Ranibizumab (Lucentis) with for Proliferative Diabetic Retinopathy (PDR)

• Phase III, prospective, multicenter randomized • Results: Over 2 years, deferred w/Lucentis beneficial• This trial marks the first major advance in PDR in 40 years

• A Comparative Effectiveness Study of Intravitreal Aflibercept, Bevacizumab and Ranibizumab for Diabetic Macular Edema (DME)

• Safety and efficacy• Results: Over 2 years, all 3 improved vision in DME when starting vision loss milder.

More advanced vision loss, Eylea clear advantage • This study is critical for doctors and patients to make informed decisions in choosing

treatment for diabetic macular edema.

Extramural Clinical Trial Support

Nurturing Vision Research Talent

NEI trains students, fellows and clinicians in vision research.

• Fellowship training in basic science and clinical research engages graduate students, baccalaureate fellows, postdoc fellows and clinicians in vision research.

• Diversity in Vision Research and Ophthalmology (DIVRO) recruits students from underrepresented groups for summer internship program.

End of Slides

Ophthalmic Innovation 2015:View from the National Eye Institute.

Paul A. Sieving, MD, PhD.