For the Treatment of Uterine Fibroids and Endometriosis Proellex® For the Treatment of Uterine Fibroids and Endometriosis

Proellex – CBD 4124 Overview of Pharmacology Progesterone receptor modulator (PRM) with specific potential advantages High affinity and selectivity; pure PR antagonist PR Antagonist @ 10-10 M Low affinity for corticosteroid receptors GR Antagonist @ 10-6 M RU-486>CDB-2914>CDB-4059>Proellex Anti-progestin effect oral (in vitro): Proellex>CDB4059>CDB-2914>RU-486 Androgenic: No activity Antiandrogenic: Weak activity Glucocorticoid: No activity

Efficacy Findings ZPE-002 Endometriosis safety study ZPU-003 Phase II Uterine Fibroid Study T8A

Phase 1/2 Endometriosis Trial Proof of Concept Safety Study Patient Population and Treatment N=39 Laparoscopic diagnosis of endometriosis Pain symptom severity mild to moderate Age 20-41 yrs Conducted in Europe 6 mo treatment Dosing; 12.5mg (n = 9), 25mg (n = 10) and 50mg (n = 10) Proellex, QD Active control: open label GnRHa (n = 10) (Lucrin 3.75 mg IM monthly) Endpoints: Pain – Daily Diary Questionnaire Bone loss – Biochemical markers and Dexascans Endometrial stripe measurement by TVUS Endometrial biopsies

Phase 1/2 Endometriosis Trial Reduction in Pain % Pain Free Days – 6 Months of Treatment * Fewer mean days of pain with 50mg Proellex (higher percentage of pain free days than with Lupron) p< 0.05* Lupron not statistically different from 12.5mg and 25mg Proellex dose = Range of pain free days

ZPU-003 Phase II Uterine Fibroid Study Study completed Q1 07 Design: Women with symptomatic bleeding uterine fibroids (menorrhagia) Treatments: Placebo, 12.5mg, 25mg Proellex QD orally Treated for 3 months with 15 month open label extension Status: 127 patients enrolled, 96 completed, 114 intent-to treat Dropouts: Pbo-15, 12.5 mg-8, 25 mg-8 Endpoints: Efficacy: Primary: bleeding (Pictogram Bleeding Assessment Chart) Secondary: pain, Uterine Fibroid QOL, fibroid size (ultrasound) Safety: Endometrial stripe by ultrasound Endometrial biopsies Biochemical bone markers Endocrine tests, serum chemistry, ECG

ZPU-003 Phase II Uterine Fibroid Study Pictoral Blood Loss - MITT Population* 12.5 and 25 mg p < 0.0001 vs Pl Mean PBAC Score mL Menorrhagia MITT* - All subjects who received study medication and have one post-dose primary efficacy measurement

ZPU-003 Phase II Uterine Fibroid Study UFSQOL – Symptom Severity Questions 1-8 High score > severity Month 3 significance values v.s. placebo; 12,5and 25 mg p <0.0001 Spies et al, Obstetrics & Gynecology, vol. 99, No. 2, February 2002

ZPU-003 Phase II Uterine Fibroid Study UFSQOL – Total Score High HRQL scores indicate better HRQL Month 3 significance values v.s. placebo; 12,5 mg p = 0.024; 25 mg p = 0.0016 Spies et al, Obstetrics & Gynecology, vol. 99, No. 2, February 2002

ZPU-003 Phase II Uterine Fibroid Study Hemoglobin <11 ZPU-003 Phase II Uterine Fibroid Study Hemoglobin <11.5 g/DL MITT Population* Mean Hemoglobin g/dL 0.0008 0.0009 1.0 25mg 0.016 0.0002 0.51 12.5mg Mo 3 Mo 2 Mo 1 p values vs placebo MITT* - All subjects who received study medication and have one post-dose primary efficacy measurement

ZPU-003 Phase II Uterine Fibroid Study Shift of Pain to No Pain – BL to 3 Months Comparison: pain present at baseline to no pain at 3 months Placebo p NS, Proellex 12.5 mg p 0.034, Proellex25 mg p 0.008

ZPU-003 Phase II Uterine Fibroid Study Fibroid Volume Reduction at Month 3- Ultrasound * % Volume reduction p = 0.6* p = 0.017*

Proellex® Efficacy Conclusions Endometriosis Pain is reduced significantly and the 50 mg dose overall statistically is significantly better than other Proellex® doses and Lucrin® from week 2 – 26 More pain-free days over 26 weeks with the Proellex® 50 mg dose than Lucrin® (p = 0.05) Uterine Fibroids – compared with placebo Severe bleeding significantly reduced in the first month of treatment (p < 0.0001) Severity of symptoms UFSQOL (p < 0.0001) and HRQOL improve over 3 months (p < 0.025 [12.5 mg] – p < 0.002 [25 mg]) Associated reduction in pain (statistically significant)

Safety Findings ZPE-002 Endometriosis safety study ZPU-003 Phase II Uterine Fibroid Study T8A

ZPU-003 Phase II Uterine Fibroid Study Number (%) of Subjects with Treatment Emergent Adverse Events for Reproductive System and Breast Disorders (>5% Prevalence – Safety Subjects) AE Profile Proellex 12.5 mg N=44 n (%) Proellex 25 mg N=40 Placebo N=43 Subjects with at least one adverse event 37 (84.1) 34 (85.0) 13 (30.2) Amenorrhea 31 (70.5) 30 (75.0) 4 (9.3) Hot flush 9 (20.5) 6 (15.0) 1 (2.3) All other adverse events in other body systems similar to placebo

ZPU-003 Phase II Uterine Fibroid Study Proellex Effects on Estradiol and Progesterone Mean Estrogen pg/mL Progesterone ng/mL P NS vs Pl P NS vs Pl

Phase 1/2 Endometriosis Trial ACTH

Phase 1/2 Endometriosis Trial Bone Resorption Marker (β-Cross Laps) Lupron 3 mo v.s. BL p = 0.023 Proellex all doses mo 3 & 6 v.s. BL p NS n=8 n=7 n=10 Β-cross laps (ng/mL)

Combined Safety Summary ZPU-003 and ZPE-002 Liver function Endometriosis study – no abnormals Fibroid study – No abnormals except 1 - gall stones – treated with cholecystectomy 2 with elevated enzymes and viral hepatitis 1 - asymptomatic autoimmune hepatitis +ve ANA Bone metabolism – no significant effects in either study Hormones LH and FSH unchanged Estrogen maintained within physiological levels Chemistry and ECGs – no change Most common drug related side effects (>%% incidence) Amenorrhea: 78.6% - expected drug effect Hot Flashes: 16.7%

Endometrial Safety Overview Commonly Asked Questions Uterine Bleeding Endometrial thickening and histology

Proellex Safety – Uterine Bleeding Study/Pt Treatment/ Duration Age Findings Event and Outcome ZPE-002 02-201 Proellex 12.5 mg 5 months 37/C Mo. 3 ET 19 mm Mo. 5 ET 25 mm Spotting 21 days after treatment stopped and severe uterine bleeding at 42 days. D&C. Full recovery 02-202 Proellex 25 mg 29/C Mo. 4 ET 37 mm Mo. 5 ET 62 mm Severe uterine bleeding 19 days after treatment stopped. D&C. Full recovery 03-216 Proellex 50 mg 5 1/2 months 35/C Mo. 0 ET 11 mm Mo. 3 ET 11 mm Mo. 6 ET 21 mm Moderate bleeding at 5.5 mo on Rx – severe bleeding at 1 mo later. D&C. Full recovery. 03-209 6 months 32/C Mo. 0 ET 8 mm Mo. 6 ET 20 mm Bleeding at 6 mo on treatment. Increased in severity over 2 days. D&C. Full recovery

Phase 1/2 Endometriosis Trial ZPE-002: Endometrial Thickness and Bleeding

Endometrial Thickening Post-menopausal women ET ≤ 5-7 mm (literature) ET 9-20mm+ in placebo treated premenopausal women Normal cyclical shedding and regeneration of the endometrium every 28 days Prevention of normal endometrial shedding in pre-menopausal women treated with Proellex® results in histological changes which may result in unscheduled bleeding.

Phase 1/2 Endometriosis Trial ZPE-002 Endometrial Thickness

Phase 2 Uterine Fibroid Trial ZPU-003 Endometrial Thickness

Management of Endometrial Thickening and Uterine Bleeding Endometrial thickening occurs with Prolonged treatment exposure Lower dose after 3 months treatment exposure Uterine bleeding Severe and unscheduled occurred only when the ET exceeded 20mm When treatment duration exceeded 5 months Therefore both endometrial thickening and the risk of severe bleeding can be managed by Treatment cycles of 4 months duration Allow an “off-drug interval” until menstruation resumes (4-6 weeks after drug stopped) Resume treatment on day 3-10 of the new menstrual cycle 29 women have gone through 3 treatment cycles successfully in the UF Extension study

Overall Conclusions Proellex is an effective medical treatment for Endometriosis rapid cessation and reduction of pain Uterine fibroids Rapid and maintained reduction in bleeding Significant restoration of QOL Rapid recovery of anemia Proellex safety profile very encouraging No consistent involvement of any organ system Issues of ET and unscheduled bleeding – prospective management paradigm has been developed which makes medical management of endometriosis and uterine fibroids safe and effective Endometrial histology Benign endometrium with class related secondary findings