Gene Therapy in Ophthalmology Update 14 Early Positive Results in Ongoing Gene Therapy Wet AMD and Stargardt’s Disease Studies

Last week, Oxford BioMedica and its partner Sanofi announced positive results in their ongoing gene therapy clinical trials for wet AMD and Stargardt’s disease. In an interim review of their Phase I (RetinoStat) and Phase I/IIa (StarGen) trials, the Data Safetly Monitoring Board (DSMB), an independent panel of specialists in the fields of ophthalmology, virology and vectorology, gave the go ahead to proceed to a final patient cohort in the Phase I study in the case of the RetinoStat trial, and to a third patient cohort in the Phase I/IIa study of the StarGen trial.

The companies announced the following:

DSMB highlights of ongoing RetinoStat Phase I study:

● Nine patients treated to date (n=3 at each of dose levels 1, 2 and 3)

● No serious adverse events related to RetinoStat or its method of administration

● Long-term safety profile now up to 18 months post-treatment (dose level 1)

● Successful retinal transduction, as shown by substantial increase in expression and secretion of endostatin and angiostatin proteins measured in the anterior chamber of the eye following a single administration of RetinoStat. So far, expression is sustained for up to 12 months post-treatment at dose level 1 (n=3) and up to six months post-treatment at dose level 2 (n=3) (The extent of the followup to date on dose level 2. Longer term results are expected to be achieved.)

● DSMB support received to proceed to final patient cohort (n=9, confirmatory dose level)

The RetinoStat open label, dose escalation Phase I study will enrol 18 patients total with"wet" AMD and will evaluate three dose levels to assess safety and aspects of ocular physiology.

The study is led by Professor Peter Campochiaro at the Wilmer Eye Institute at Johns Hopkins, Baltimore and Oxford BioMedica has now opened a second clinical site at the Oregon Health and Science University, Portland with Dr Andy Lauer as principal investigator.

Further results from this study are expected in Q4 2012.

On the basis of pre-clinical data, it is anticipated that RetinoStat may require only a single administration which would give the product a significant advantage in the market over currently available treatments that often require frequent, repeated administration.

DSMB highlights of ongoing StarGen Phase I/IIa study:

● Eight patients treated at dose level 1 to date (n=4 severe level of disease, n=4 less severe)

● No serious adverse events related to StarGen or its method of administration

● Long-term safety profile now up to 12 months post-treatment (dose level 1)

● DSMB support received to proceed to third patient cohort (n=4, dose level 2)

The StarGen open label, dose escalation Phase I/IIa study will enrol up to 28 patients and will

evaluate three dose levels for safety, tolerability and aspects of biological activity.

In the US, the study is led by Professor David Wilson at the Oregon Health and Science University, Portland, Oregon. In France, Professor Jose-Alain Sahel leads the study at Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Paris.

StarGen has received European and US Orphan Drug Designation which brings development, regulatory and commercial benefits.

Further results from this study are expected in Q4 2012.

As noted above for the RetinoStat treatment, on the basis of pre-clinical data, it is anticipated that a single application of StarGen to the retina could potentially either provide long-term or permanent correction. There are currently no approved treatments available for Stargardt disease.

John Dawson, Chief Executive Officer of Oxford BioMedica, said:"The continued progress of our ophthalmology portfolio, supported by another positive DSMB review, is encouraging - particularly given that early RetinoStat data demonstrate sustained therapeutic protein expression in the eye following a single administration. The favourable safety profile of our novel ocular gene therapies further supports the wider LentiVector platform safety package with over 33 patients treated to date across the ocular and Parkinson's disease programmes."

PRIVATE CLIENT STUDIES – Arthur D Little 1972 1994 and Spectrum Consulting 1994 2001

In addition to the hundreds of articles and columns written over my 30-plus years of consulting, I led over 100 client-sponsored studies, covering a variety of topics. Here are the titles of most of the reports I either wrote or led the effort in producing. Some of the titles have been partly redacted to prevent identification of the client.

Note that nearly all of the studies until 1985 involved contact lenses, at which time I began consulting in medical lasers.

(Bolded studies can be found online.)

1972
● Worldwide Review of Soft Contact Lenses Made of Hydron (B&L Soflens), August 1972

1974
● Technological Developments in Ophthalmic Lens Materials and Processes, February 1974

1976
● The Contact Lens Business--An Emerging Opportunity, June 1976
● Investigation of the Coating Buildup Problem on Soft Contact Lenses, November 1976
● The Soft Contact Lens Business--Profile of an Opportunity, December 1976

1978
● Technical Assessment of a Soft Contact Lens Automated Machining Center, April 1978

1979
● The Contact Lens Solutions Business: An Opportunity for -- --, January 1979
● An Evaluation of Wesley-Jessen's Contact Lens Technology, August 1979
● Identification of a Soft Contact Lens Licensing Partner for -- --, November 1979
● Current and Future Developments in the Contact Lens Industry, December 1979
● An Evaluation of Titmus Eurocon's Contact Lens Technology, December 1979

1980
● A Technology Forecast: Vision Devices 1980-2000, January 1980
● The Development of an Improved Eyeglass Frame Material and Manufacturing Process, March 1980

1981
● Projections of the Markets for Hard Gas Permeable Contact Lenses, January 1981
● The Technical Evaluation of Frontier Contact Lenses Inc., January 1981
● An Overview of the U.S. Contact Lens Business, January 1981
● The Development of Novel Low Cost Disinfection Systems for Soft Contact Lenses, February 1981
● A Worldwide Review of Hard Gas Permeable Contact Lenses, February 1981
● Technical Evaluation of a New Contact Lens Manufacturing Process, February 1981
● An Analysis of the Contact Lens Business of -- --, March 1981
● A Worldwide Overview of the Ophthalmic Industry for the Scottish Development Authority, June 1981
● A Comparison of Low, Medium, and High Water Content Contact Lens Systems, July 1981

1982
● Technical Evaluation of an IOL Research and Manufacturing Operation, January 1982
● The Offering of a Contact Lens Company to Prospective Buyers, Winter 1982
● The Offering of a Retail Optical Business (Inventory, Lab Equipment and Fully-Equipped Dispensing Offices) to Prospective Buyers, Spring 1982
● The Development of a Low Cost Chemical Disinfection System for Soft Contact Lenses, February 1982
● An Overview of Diagnostic and Surgical Ophthalmic Equipment, July 1982
● Current Developments in Hard Gas Permeable Contact Lenses, December 1982

1983
● Assessment of a New Contact Lens Manufacturing Technology, January 1983
● Evaluation of a Soft Lens Cleaning Device, February 1983
● Technological Developments in the U.S. Contact Lens Industry, April 1983
● Near Term Trends in the U.S. Contact Lens Industry, June 1983
● Technological Assessment of -- --, October 1983
● Packaging of a Peroxide Neutralization System, November 1983
● Analysis of R&D and Regulatory Capabilities of Major U.S. Contact Lens Companies, December 1983

1984
● Background Papers on Soft Contact Lenses and Care Products, January 1984
● A Background Report on the Contact Lens Industry in the U.S., January 1984
● The Establishment of a Transfer Price for Contact Lens Blanks, January 1984
● Development of a Tensile Testing Method for Contact Lens Materials, January 1984
● An Overview of Trends and Developments in Eyeglasses and Contact Lenses, March 1984
● The Offering of a Contact Lens Laboratory and Fitting Clinic, April 1984
● The Establishment of a Transfer Price for Intraocular Lenses, April 1984
● The Outlook for the Ophthalmic Products Industry, May 1984
● An Assessment of Competitive Soft Lens Tinting Technologies, June 1984
● Current Trends in the U.S. Contact Lens Industry, September 1984
● Survey of Practitioner Attitudes Toward Cosmetic Extended Wear, November 1984

1985
● Comparison of Estimated Soft Lens Manufacturing Costs, February 1985
● An Update of Near Term Trends in the U.S. Contact Lens Industry, May 1985
● Contact Lens Manufacturing Techniques, August 1985
● The Offering of a New Soft Bifocal Contact Lens for Licensing, September 1985
● Entry Strategy to the U.S. Contact Lens Market, October 1985
● Update of the U.S. Ophthalmic Industry, November 1985
● Technology Assessment of the Green YAG Laser, November 1985

1986
● The Outlook for Refractive Surgery: The Impact of the LRK Technique, March 1986
● The Valuation of an IOL and a Surgical Instrument Companies, June 1986
● The Valuation of an Ophthalmic Products Company, November 1986
● A Brief Study of the CL Market in Japan, November 1986
● The Valuation of an Ophthalmic Instrument Company, December 1986

1987
● Ophthalmology Technical Alert Service, 1987
● An Overview of the Presbyopic Market Place: The Prospects for a New Viable Bifocal Contact Lens Design, February 1987
● A Detailed Survey of the CL Market in Japan, February 1987
● The Outlook for Viscoelastic Substances in Ophthalmology, May 1987
● An International Overview of Contact Lenses, June 1987
● The Nature and Evolution of the Soft Contact Lens Industry in the United States, August 1987 (B&L vs. the IRS)

1988
● The Current and Theoretical Production Capacity of the U.S. Contact Lens Industry, April 1988
● Evaluation of CooperVision, June 1988
● Medical Laser Overview, August, 1988
● Technical and Market Analysis of -- --, July 1988
● Ophthalmic Market Overview, September 1988
● Technology Overview: Ultrasound Catheter Market, December 1988

1989
● Ophthalmic Surgical Equipment Overview, March 1989
● U.S. Market for Soft Contact Lens Lubricant/Rewetting Drops, March 1989
● Contact Lens and Care Product Market Overview, May 1989
● Update: The Outlook for Laser Refractive Surgery, August 1989

1990
● Development of a Manufacturing Plan for Medical Lasers: Product Selection, January 1990
● Technology Overview: Phoenix Laser Systems, March 1990
● Current Developments in Laser Refractive Surgery, July 1990
● Opportunities for Collaboration, September, 1990
● An Evaluation of a New Eyeglass Lens Molding Process, Phase I: Technology Overview, September 1990
● Overview of High-Index Plastic Eyeglass Lens Materials, November 1990
● Background Information on the Contact Lens Industry, December, 1990
● Profitability in the Ophthalmic Industry, December, 1990

1991
● Contact Lens and Care Product Overview, January, 1991
● Current Developments in Laser Refractive Surgery, March 1991
● An Overview of the U.S. IOL Industry, April 1991
● Ophthalmic Industry Overview, August 1991
● Overview of Current Developments in Refractive Surgery, August 1991
● Technology Overview: Phoenix Laser Systems, October 1991
● Overview of the IOL Industry, September 1991

1992
● Excimer Lasers in Surgery, February 1992
● Current Developments in Laser Refractive Surgery, March 1992, updated July 1992
● New Ophthalmic Laser Technologies, June 1992
● Historical Overview of Ophthalmic Lasers in the Mid-1980s (legal case), July 1992
● Medical Laser Technology Alert Reports, monthly, July 1992 - April 1993

1993
● Technology Overview and Strategic Partnering for Unique Medical Laser Product Company, September 1993
● The Outlook for Refractive Surgery Centers, September 1993
● A Cost Comparison of Refractive Surgery vs. Eyeglasses and Contact Lenses, October 1993
● An Overview of Current Developments in Refractive Surgery, December 1993

1994
● An Assessment of a Laser-based Method to Alleviate Heart Attacks, February 1994
● The Outlook for a Laser-based Technique to Cure Psoriasis, March 1994
● Current Developments in Laser Refractive Surgery, August 1994, updated April 1995
● An Assessment of an Unique Laser-based Technique to Diagnose Severe Burns, August 1994

1995
● Estimated Market for a New Mid-IR Laser Delivery Fiber, February 1995
● The Outlook for Refractive Surgery, March 1995
● An Analysis of the Hawaii PRK Market, May 1995

1996
● Potential Laser (and non-laser) Sources for Activating Photofrin, March 1996
● Search for a Diode Laser Source for Activating Photofrin, April 1996
● A White Paper -- Laser Hair Removal: An Application Whose Time has Come, October 1996
● Worldwide Market Overview of Ophthalmic and Dermatologic Lasers, December 1996

1997
● U.S. Market Opportunities for ICON Centers for Cosmetic Surgery, March 1997
● Refractive & Cosmetic Surgery -- Any Synergies?, November 1997
● An Overview of the Medical Laser Industry, December 1997

1998
● Worldwide Medical Laser Marketplace, May 1998
● An Investigation into the Use of "Bermuda Cards", July 1998
● Review of Photodynamic Therapy for Treating ARMD, December 1998

1999
● Update: Trends in Refractive and Cosmetic Laser Surgery, November 1999
● An Evaluation of ThermoLase's Technologies, December 1999

2000
● A Look at the Future of Refractive Surgery, February 2000

2001
● A Brief Overview of the Opportunities for a 3 micron Medical Laser System, July 2001
● Adoption Rates of Soft Contact Lenses, IOLs, and Refractive Surgery, September 2001