PCOMMUNIQUE DE PRESSE- Draft August 15 RELEASE9

NNicDes résultats précliniques prometteurs pour de Ox renforce son équipe de directionicOx’s Nitric Oxide-Releasing Steroid, HCT 1026 shows positive clinical results in the treatment of skin inflammationHCTNCX 10262, Sshows positive clinical results PromisingFavorable Clinical Results in Skin Blanchingnouveaux composés nitrés

in a second phase I/II study of the contact urticaria model PNicOx announces pPositive preliminary phase I/II results

in contact urticaria

- Commeneces second dermatology study ew data reclinical results announced for Alzheimer’s drug,on NSAID

- Data presented at the 7^th International Conference on

Alzheimer’s Disease and Related Disorders in Washington DC -in neuroinflammation presented at Washington Alzheimer’s conference-

Sophia-Antipolis, France. June xxx, 2000 - NicOx S.A. (Nouveau Marché: NICOX) announced today at the 7th International Conference on Alzheimer’s Disease and Related Disorders, in Washington from 6th to 13th July, that -Alzheimer’sneuroinflammationwithfor itsa were presented at the 7th International Conference on Alzheimer’s Disease and Related DisordersNCX 2216 is onethe first of a series of new compounds that NicOx is developing in the field of neuroinflammation, which further broadens the company’s product development pipeline. .

For the first time positive clinical results with HCT 1026 from its first clinical dermatology study in 16 healthy subjects with methyl nicotinate-induced contact urticaria (press release March 15 2000). Preliminary results from the study showed a significant anti-inflammatory activity.

The phase I/II study, which began in March this year, compared HCT 1026 1% ointment against , placebo, NSAID flurbiprofen 1% ointment and a reference compound, niflumic acid 3% ointment. The ointments were applied under occlusion [what does this mean??] for 3 1/2 hours, after which the irritant [methyl nicotinate? So, if I understand correctly, the compound was given as a preventative not a therapeutic?] was applied at each test site. Skin blood flow was monitored during the following 25 minutes. In this clinical model, which is sensitive tofor the detection of anti-inflammatory activity, HCT 1026 1% ointment showed a potent and significantly higher anti-inflammatory activity compared to the reference compound and placebo placebo, assessed by laser doppler as changes in skin blood flow. No adverse effects or topical intolerance were reported.

NicOx has also announced initiation of a new second [also phase I/II?] dermatology clinical dermatology study with two concentrations of HCT 1026, 0.3% and 1% ointment. This is the second next study in a series of different clinical models for the evaluation of the activity of HCT 1026 in dermatology. The new study is is trial is being performed in C. P. C. A. D. (Prof. Ortonne),at Hôpital l’Archet 2, Nice (France) under the supervision of Dr. Queille-Roussel. It is a randomised, masked [double blind?] investigator study, involving 24 healthy subjects with UV-induced erythema (sunburn-like reaction) and an intra-individual comparison of the anti-inflammatory properties of HCT 1026 [, 0.3% and 1% ointment], placebo and a 0.1% reference steroid cream 0.1%. Each tproductreatment will beis given administered as six applications on four test zones exposed to three different UV doses.

Mr Michele Garufi, Chairman and CEO of NicOx, commented “After the positive preliminary results in urinary incontinence, these results confirm the anti-inflammatory potency of HCT 1026 and the high therapeutic ptherapeutic interestotential of HCT 1026 also in topical dermatological applications. Dermatology is one of the key areas of interest for NicOx where we are also developing novel compounds beyond the NO-NSAID class. As a result, our full pipeline of dermatology compounds creates a sound basis for collaboration with partners in this field.”

HCT-1026, a nitro-flurbiprofen derivative, represents a new approach for the prevention and treatment of dermatological inflammatory disorders. A topical formulation has been developed and showed excellent local tolerability in pre-clinical studies.

by Professor Gary Wenk from the University of Tucson (Arizona) and characterised for the first time an NOa nitric oxide-releasing- brain inflammation was characterised. neuroinflammation. The paper was written by Professor Gary Wenk from the University of Tucson, Arizona, who conducted the trials and with whom NicOx has a collaboration for the development of the drug [is he to conduct further studies?]. neuroinflammation brain inflammation resultingitsithe drug’stsreduce [what are these behavioural impairments?]. . peroxinitrite the of powerful oxidants (such as peroxinitrite) to [can we be more specific on administration?]..

Comment by McGeer on the importance of anti-inflammatory drugs in this pathology [mention that he is a world-renowned for his expertise in neurobiology]

seon NCX 2216 ithets of NCX 2216 forinexpandingthe expansion of., including a broad range of animal models. antioxidentantioxidantforofother eworkchemochemicallyAOMb Preliminary animal studies have shown that NO-releasing aspirin NCX-4016 is more potent in preventing the formation of aberrent crypt foci (Life Sciences , 1998, 62,P4367) and is safer in terms of gastric safety than aspirin (Gastroenterology, 1999, 116,689) )NSAIDs as the prevention of -,-NovemberMarchMay14XX2810..eécliniques dpour ’ clinique , –that a topical formulation ofpositive human clinical results with HCT 1026 NCX 1022 showed promisingfavorable results in a Phase I clinical dermatology study evaluating local skin vasoconstriction, (a human skin blanching assay approved by the FDA). NCX 1022 is a nitric oxide-releasing derivative of the steroid, hydrocortisone, in development for the treatment of psoriasis in a dermatological study of skin inflammationmethyl nicotinate-induced contact urticaria induced by UV ligh whicht. is a chronic skin conditiondisease in which itchy scaly pink patches form on the elbows, knees, scalp, and other parts of the body.

Sophia Antipolis, le 127 septembre^er octobre 2001 - NicOx SA (Nouveau Marché: NICOX), la société pharmaceutique émergente spécialiste de l’oxyde nitrique (NO), annonce la nomination du Dr. Marco Sardina au poste de Directeur Médical Senior et du Dr. Romano Rivolta au poste de Directeur Chimie et Formulation. Les deux postes seront rattachés au Dr. Giancarlo Santus, Vice-Président en charge du Développement.