Biotech Values

[DewDiligence]

OXGN’s interim results in AMD are about as expected:

[If you’ve been reading this board for a while, you’ll know my often-expressed view that OXGN’s phase-1/2 AMD trial at Johns Hopkins is hard to take seriously due to the slower-than-molasses rate of patient enrollment. Today’s OXGN press release is consistent with such a viewpoint. I continue to believe that OXGN’s CA4P has a chance to be effective as a local formulation in AMD, but it is probably too toxic to work as a *systemic* treatment in an elderly population that is frequently heart-impaired. CA4P may be better-suited to *myopic* degeneration, where patients are much younger.

I am disappointed that there are no visual-acuity data in today's PR. It's nice that one patient showed an improvement on the OCT scan, but the FDA's primary efficacy criterion in AMD is the change in visual acuity relative to baseline.

Annotations in italics below by Dew.]

http://biz.yahoo.com/bw/040518/185978_1.html

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OXiGENE Announces Interim Results of Wet Age-Related Macular Degeneration Trial of Combretastatin A4 Prodrug

Tuesday May 18, 3:47 pm ET

Data Presented to 2nd International Conference on Vascular Targeting

WALTHAM, Mass.--(BUSINESS WIRE)--May 18, 2004-- OXiGENE, Inc. (NASDAQ: OXGN, XSSE: OXGN) today announced that interim results from the Phase I/II clinical trial of Combretastatin A4 Prodrug (CA4P) in patients with wet age-related macular degeneration (wet AMD) were presented at the 2nd International Conference on Vascular Targeting. The study's co-investigator, Peter Campochiaro, M.D., professor of ophthalmology at Johns Hopkins University School of Medicine's Wilmer Eye Institute, presented the data Tuesday at the 2nd International Conference on Vascular Targeting in Miami Beach, Florida.

[Only 7 patients have been enrolled in 10 months]: Seven patients have received treatment with CA4P in this dose escalation pilot study, including one patient on the first dose level who experienced objective biological response to the investigational drug as measured by optical coherence tomography (OCT). The area of choroidal neovasculariztion (CNV) in the patient's study eye decreased by approximately 100 microns, a reduction that Dr. Campochiaro said was "not within the realm of spontaneous changes." CNV occurs when abnormal blood vessels sprout behind the retina, leaking blood and other fluid into the retina and triggering the sudden and severe central vision loss known as wet AMD.

[That QTc bugaboo simply won’t go away. QTc-prolongation appears to be manageable in the patients actually treated, but it’s reasonable to infer that QTc-prolongation is limiting patient enrollment.]: Dr. Campochiaro reported that CA4P has been well tolerated up to doses of 36 mg/m2 and the side effects observed were increased blood pressure and pulse and an increase in QTc interval below clinical significance. No serious or dose-limiting adverse events were reported.

[The following result in *myopic degeneration (not AMD) is impressive but is old news from last year]: In addition, a 35-year-old patient with myopic macular degeneration experienced a significant improvement in visual acuity after he received CA4P treatment at The Wilmer Eye Institute under a special exemption from the U.S. Food and Drug Administration. Prior to beginning a regimen of CA4P treatments, the patient had visual acuity of 20/50 in the study eye with active leakage in both eyes that had persisted following other treatment approaches. After the patient was treated with the systemically administered CA4P, his vision was restored to 20/20 with significantly reduced leakage in each eye.

"While significant data must still be collected in this study, the interim results regarding biological activity and safety are quite promising," said Dai Chaplin, Ph.D., OXiGENE's chief scientific officer and head of research and development. "This is particularly true given that the study is a Phase I/II trial principally designed to demonstrate proof of concept. Dr. Campochiaro's presentation complements the numerous pre-clinical tests that illustrate the ability of CA4P to inhibit development and promote regression of CNV."

Dosing is underway in the second of three patient cohorts that have been established to evaluate CA4P at 27, 36 and 45 mg/m2. The compound is being assessed for safety, tolerability, dose-limiting toxicities and potential efficacy. A total of 15 patients are expected to be enrolled in the trial. Wet AMD is the leading cause of severe vision loss among Americans over age 60. The disease affects approximately 2 million to 3 million in the U.S.

This year, OXiGENE plans to expand its clinical program in ophthalmology by initiating a clinical study in patients with myopic macular degeneration. As part of the expansion of its ophthalmology program, the Company is pursuing local, non-systemic methods of administering its vascular targeting agents to the posterior segments of the eye. While instances of hypertension were noted in the Phase I/II study by Dr. Campochiaro, he indicated that a local method of delivery could substantially reduce systemic exposure to CA4P and further improve its safety profile in this clinical setting. [Translation: CA4P is probably too toxic for *systemic* treatment in AMD.]

Also during Tuesday's presentation, Dr. Campochiaro discussed his pre-clinical work with CA4P, published last year in the peer-reviewed journal Investigative Ophthalmology and Visual Science. Dr. Campochiaro and his colleagues at Johns Hopkins conducted experiments on transgenic mice with CNV caused by an over expression of vascular endothelial growth factor in the retina and mice with laser-induced rupture of Bruch's membrane. In both groups of animals, daily intraperitoneal injections of CA4P resulted in a "significant reduction" in established CNV, putting the compound "in select company," he reported.
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