Based on results of a planned interim analysis using data from the first 103 subjects enrolled in the trial (32 subjects in the CF101 1 mg BID dose group, 33 in the CF101 2 mg BID dose group, and 38 in the BID placebo group), the CF101 1 mg dose group was eliminated for futility, and the sample size of the remaining groups was increased. The safety profile and therapeutic index were favorable in this population and warranted continuing the 2 mg CF101 dose group, along with the placebo control. Therefore, only 2 treatment groups remained in the study. Objectives • Eliminated 1 mg dose • Eliminated ’optimal dose’ objective • Eliminated PK objective • Changed order of efficacy assessments. PASI is now the primary efficacy endpoint (PGA was the former primary endpoint) so this is listed first. Design, Duration of Treatment • Changed from 3-arm to 2-arm study by eliminating 1 mg dose • Randomization changed from 2:2:1:1 to 1:1 to reflect removal of the CF101 1 mg followed by CF101 1 mg group and the Placebo followed by CF101 1 mg group • Changed the blinded period from 12 to 16 weeks • After cross-over at 16 weeks, changed from blinded to open-label because now all subjects will be on CF101 2 mg • Changed continued dosing period from 24 to 32 weeks • Added 2 visits (Visits 10 and 11), as needed for additional 8 weeks of study • Made Visit 3, Week 2, a telephone call only, eliminating all assessments except AEs and concomitant medications • Eliminated PK testing • Eliminated interim analysis Number of Subjects • Number of enrolled will be approximately 94 subjects in each group (CF101 2 mg and placebo), for a total of 188. • This will result in an overall total of 291 subjects when added to the 103 subjects included in the interim analysis.

The rationale for this amendment was to incorporate modifications recommended by FDA. • Inclusion criterion: lower age range changed from 14 to 18 years of age. • Exclusion criterion: liver transaminase levels now greater than upper limit of normal, from 2 times upper limit of normal. • Discontinuation from dosing if a Grade 3 or 4 TEAE occurs in vital signs, systemic, or laboratory abnormalities in the Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (U.S. Department of Health and Human Services, Food and Drug Administration, Center for Biologics Evaluation and Research, September 2007), or other unacceptable toxicity develops.

This amendment revised the statistical sections to incorporate • Recommendations from FDA • An interim analysis for dose selection and sample size re-estimation

The original protocol inadvertently omitted an exclusion for topical Vitamin D analogs, which are utilized to treat psoriasis and whose uncontrolled use could confound the study results. This amendment added topical Vitamin D analogs to the list of medications excluded at screening and concomitantly throughout the trial.

At Selected Sites An ex vivo analysis of peripheral blood mononuclear cell (PBMC) from patients with active psoriasis was performed. In PBMC from psoriasis patients, A3AR protein was highly over-expressed in comparison to the PBMC of healthy subjects. An increase of A3AR expression of approximately 16-fold was found in the psoriasis patients over normal control samples, which represents the highest level of A3AR over-expression documented to date in any population with immune-mediated inflammatory disease. Furthermore, analysis of mRNA in a biopsy of psoriatic skin revealed up-regulation of A3AR mRNA expression relative to normal skin, suggesting that CF101, a highly selective A3AR agonist, may demonstrate a very favorable therapeutic index in this disease. Finally, A3AR agonism by CF101 has been shown to de-regulate the PI3K-NF-kappaB signaling pathway, a pathway which is up-regulated in psoriatic epidermis and suppressed in response to clinically effective therapy. The objective of this amendment was to assess PBMC A3AR expression levels at Baseline and during treatment with CF101.

At Selected Sites In the interests of gaining as much information as possible about A3AR behavior and relationship to response, this amendment removed the limit on the number of subjects who may be tested through PBMC sampling. The objective of this amendment is to clarify planned number of patients for PBMC A3AR expression levels assessment introduced to Protocol CF101-202PS with Amendment 5.

Recent analyses from other trials of CF101, as well as of interim data from the current trial, indicated that the therapeutic response to CF101 may be strongly influenced by subject weight and/or BMI. The relationship between this clinical finding and systemic exposure to CF101 is unknown. By obtaining PK data in the treated population, this amendment will enable population PK analysis in this patient population and much more detailed analyses of the relationships between body weight/BMI, exposure, and efficacy of CF101, allowing dosing regimens to be optimized in future clinical use. Therefore, this Amendment added a secondary objective: Evaluate the PK of CF101 in this population.