Proellex® For the Treatment of Uterine Fibroids and Endometriosis

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

2. 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

3. ZPE-002Endometriosis safety studyZPU-003Phase IIUterine Fibroid Study Efficacy Findings T8A

4. Phase 1/2 Endometriosis TrialProof 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

5. Phase 1/2 Endometriosis TrialReduction 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

6. ZPU-003Phase IIUterine Fibroid StudyStudy 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

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

8. ZPU-003Phase IIUterine Fibroid StudyUFSQOL – 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

9. ZPU-003Phase IIUterine Fibroid StudyUFSQOL – Total Score High HRQL scores indicate better HRQLMonth 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

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

11. ZPU-003Phase IIUterine Fibroid StudyShift 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

12. 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)

13. ZPE-002Endometriosis safety studyZPU-003Phase IIUterine Fibroid Study Safety Findings T8A

14. ZPU-003Phase IIUterine Fibroid StudyNumber (%) of Subjects with Treatment Emergent Adverse Events for Reproductive System and Breast Disorders (>5% Prevalence – Safety Subjects)

15. Progesterone ng/mL Mean Estrogen pg/mL P NS vs Pl ZPU-003Phase IIUterine Fibroid StudyProellex Effects on Estradiol and Progesterone P NS vs Pl

16. Phase 1/2 Endometriosis TrialACTH

17. Phase 1/2 Endometriosis TrialBone 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=7 n=8 n=10 Β-cross laps (ng/mL)

18. Combined Safety SummaryZPU-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%

19. EndometrialSafety Overview Commonly Asked Questions Uterine Bleeding Endometrial thickening and histology

20. ProellexSafety – Uterine Bleeding

21. Phase 1/2 Endometriosis TrialZPE-002: Endometrial Thickness and Bleeding

22. 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.

23. Phase 1/2 Endometriosis TrialZPE-002 Endometrial Thickness

24. Phase 2 Uterine Fibroid TrialZPU-003 Endometrial Thickness

25. 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

26. 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