Ardea Biosciences (RDEA) 8-K Regulation FD Disclosure

Exhibit 99.1

Poster #109

A Multi-Center Phase 1, Dose —Escalation Trial to Determine the Safety and Pharmacokinetics/Pharmacodynamics
of BAY 86-9766 (RDEA119), a MEK Inhibitor, in Advanced Cancer Patients
C. D. Weekes¹, D. D. Von Hoff², A. A. Adjei³, L. Yeh⁴, D. Leffingwell⁴, B. Sheedy⁴, C. Iverson⁴, P. Rajagopalan⁵, R. Dubowy⁵, N. Clendeninn^4
1University of Colorado Cancer Center, Aurora, CO;²TGen, Scottsdale, AZ,³Roswell Park Cancer Institute, Buffalo, NY,⁴Ardea Biosciences, Inc. San Diego, CA,⁵Bayer

HealthCare Pharmaceuticals, Montville, NJ
	Thank you to all the patients who participated in this study.

Introduction

The RAS-RAF-MEK-ERK pathway has emerged as a significant focus for molecularly targeted oncology therapeutics. MEK inhibitors may have broad utility in the treatment of human cancers driven by activation of this pathway as a result of phosphorylation of ERK by MEK. BAY 86-9766 is an oral, potent, non-ATP competitive, highly selective inhibitor of MEK1/2 with favorable pharmacokinetics (PK). It is highly protein bound, 98.0%. BAY 86-9766 is active as monotherapy and in combination with other anti-cancer agents in xenograft models of colon, pancreatic, and hepatocellular cancer and other tumor types. Following multiple once daily (qd) dosing of BAY 86-9766 in healthy adult male volunteers at 10 mg qd or 20 mg qd, BAY 86-9766 was readily absorbed with mean Tmax ranging between 1.75 to 2.25 hours and half lives between 13-15 hours. It is currently in Phase 1/2 development as a single agent and in combination targeting solid tumors. The results of the monotherapy dose escalation study RDEA119-101 in advanced cancer patients are presented here.

Methods

Ø Primary Objective:

– Determine the safety and the maximum tolerated dose (MTD) of BAY 86-9766.

Ø Secondary Objectives:

– Evaluate the plasma PK profile of BAY 86-9766.

– Assess pharmacodynamic (PD) markers.

– Evaluate the safety and tolerability of the recommended phase 2 dose.

Ø Key Eligibility Criteria:

– Advanced metastatic or locally recurrent solid tumor:

• No proven effective therapy exists.

• No central nervous system (CNS) metastases requiring treatment.

– Males and females, age > 18 years.

– ECOG Performance Status of 0-1.

– Adequate hematologic, renal, and hepatic function without significant cardiovascular risk.

Ø Methods:

– Patients were given a single dose on Day 1 to determine PK, were off drug for 7 days, and then began a 28-day course of treatment with steady-state PK obtained on Days 15 and 28.

– Safety was assessed by adverse events (AEs), clinical laboratory tests, vital signs, ECGs, ECHO/MUGA scans and physical exams.

– Patients were evaluated every 2 courses for tumor response by RECIST criteria.

– PD assessments included phosphorylated ERK (pERK) and cytokine levels from peripheral blood mononuclear cells (PBMCs) and pERK from hair follicles.

– Dose escalation scheme followed a modified Fibonacci series as shown in Figure 1.

Figure 1: Study Design Scheme

Results

Patient Demographics and Baseline Characteristics

Ø	Of the 69 patients enrolled in the study, the mean age was 61 years (range: 19 — 82 years) across all dose levels.
Ø	A majority of patients were male (39 [57%]) and of white, non-Hispanic ethnic origin (63 [91%]).
Ø	The ECOG Performance Status score at screening was 1 in a majority of patients (49 [71%]).
Ø	Mean time since first cancer diagnosis was 5 years (range: 0.2 — 18.6 years).
Ø	Most frequently reported tumor type was colorectal; data for all tumor types are summarized in Table 1.
Ø	Most common prior cancer therapies were surgery in 66 (97%) patients, chemotherapy in 65 (96%) patients, and radiation in 39 (57%) patients.

Results (cont’d)

Table 1: Primary Tumor Type by Total Daily Dose

	Lower Dose Levels	Higher Dose Levels			Overall
	2 mg - 40 mg	60 mg	100 mg**	160 mg	All dose levels
Primary Tumor Type	N = 27	N = 6	N = 31	N = 5	N = 69
Colorectal	4	3	11	4	22
Melanoma	4	0	4	0	8
NSCLC	2	0	2	1	5
Prostate	3	0	2	0	5
Pancreatic	1	0	4	0	5
Other*	13	3	8	0	24
Totals	27	6	31	5	69

*	Other: 2 mg - 40 mg:Adrenal (3), breast (2), GIST, Ewing’s sarcoma, ovarian, mesothelioma, vaginal, papillary thyroid, perivascular epithelioid sarcoma, chondrosarcoma;60 mg:GE junction adenocarcinoma, biliary, retroperitoneal sarcoma;100 mg: Cholangiocarcinoma (3), hepatocellular, basal cell, chondrosarcoma, liposarcoma, appendiceal,
**	Includes all patients treated at the MTD dose level of 100 mg daily in the dose escalation and MTD cohorts.

Patient Disposition

Ø	Of the 69 patients enrolled, 57 (83%) patients completed the study (28 days of continuous dosing in Course 1).
Ø	A majority of patients (53 [77%]) discontinued from the study due to disease progression categorized as either objective evidence of disease progression (48 [70%]) or symptomatic deterioration (5 [7%]).
Ø	The remaining patients discontinued from the study due to adverse events (12 [17%]) and withdrawn consent (1 [1%]).

Figure 2: Exposure to RDEA119 In Months By Treatment Group

Safety

Ø	RDEA119 was generally well tolerated with AEs reported that are commonly associated with MEK inhibitors.
Ø	A total of 56 SAEs were reported at any dose level of which 12 (21%) were considered possibly related to treatment.
Ø	The DLT dose level was determined to be 160 mg per day (Table 3).
Ø	At the MTD dose level (100 mg per day), 6 (19%) patients discontinued from the study due to an adverse event of which 4 (13%) were considered to be possibly related to treatment with study drug. AE data are presented in Table 2.
Ø	Of the 31 patients treated at the MTD dose level (100 mg per day), 17 (55%) patients had a total of 22 dose interruptions; 4 (13%) of these patients required their dose of study drug to be reduced due to an adverse event of rash (2 patients), peripheral edema (1 patient), or gait imbalance (1 patient).

Table 2: Overall, Most Frequently Reported (≤ 15% of patients) Treatment Related AEs, all Grades, by Total Daily Dose

	Lower Dose Levels	Higher Dose Levels			Overall
	2 mg - 40 mg	60 mg	100 mg*	160 mg	All dose levels
Preferred Term	N (%)	N (%)	N (%)	N (%)	N (%)
Rash**	13 (48)	6 (100)	26 (84)	4 (80)	49 (71)
Diarrhoea	6 (22)	1 (17)	13 (42)	2 (33)	22 (32)
Nausea	5 (19)	1 (17)	12 (39)	0	18 (26)
Vomiting	7 (26)	0	9 (29)	1 (17)	17 (25)
Fatigue	4 (15)	2 (33)	9 (29)	2 (33)	17 (25)
Oedema peripheral	0	0	9 (29)	1 (17)	10 (15)

*	Includes all patients treated at the MTD dose level of 100 mg daily in the dose escalation and MTD cohorts.
**	The term rash includes the Preferred Terms rash, rash macular, rash maculo papular, rash papular, and dermatitis acneiform.

Results (cont’d)

Safety (cont’d)

Ø Rash was the most common AE . A total of 90 events of rash were reported by 49 (71%) patients; 97% (87) were grade 1/2 in severity and 4% (3) were grade 3.

• Treatment guidelines were provided to the sites to minimize rash as follows: Patients were instructed to moisturize the skin twice daily with a thick alcohol-free emollient and minimize exposure to sunlight. Treatment with a topical hydrocortisone 2.5% and/or clindamycin 1% gel for grade 1; same as for mild rash plus doxycycline 100 mg bid or Minocycline 100 mg bid for grade 2 rash; treatment for moderate rash plus Medrol dose pack for a grade 3 rash.

Table 3 : Summary of DLT Events (possibly related CTCAE* grade 3 or higher)

Dose (mg)	Dose Limiting Toxicity	Action Taken with BAY 86-9766
2 mg qd	Lipase increased	Treatment held for 1 week, dosing resumed, at same dose.
60 mg qd	Hypophosphataemia	No action, continued on study.
100 mg qd	Pain of skin and rash	Treatment held ~ 2 weeks, dosing resumed at a reduced dose of 60 mg qd.
160 mg qd	Diarrhoea	Patient withdrew consent.
	Presyncope	Treatment held for 1 week, dosing resumed at 100 mg qd.
80 mg bid	Somnolence and rash	Patient discontinued study due to DLTs.

* CTCAE (Common Terminology Criteria for Adverse Events) V 3.0

CNS and ocular toxicities have been reported with the use of other MEK inhibitors. Those seen in this study and considered possibly related to study drug include:

ØAt the DLT dose (total daily dose of 160 mg), 1 case each of the CNS toxicities of presyncope and somnolence, grade 3, were reported and considered DLTs.

ØAt the MTD dose level (100 mg per day), a total of 10 (32%) patients reported CNS toxicities that were considered possibly related to study drug.

• Grade 3/4 AEs of hallucinations, somnolence, confusion, and neurotoxicity were reported in 3 (10%) patients.

• Grade 1/2 AEs reported in both dose groups were similar and included confusion, dizziness, and abnormal dreams.

Ø At the MTD dose level (100 mg per day), 1 patient reported grade 1 chorioretinopathy during course 1 that recovered following dose reduction, and 1 patient with ocular melanoma developed grade 2 hemi-retinal vein occlusion after 5 courses of treatment, that resolved with intravitreal bevacizumab.

Pharmacokinetics

Ø	Cmax and AUC0-24 values increased with dose in a dose linear manner following single or multiple doses up to 100 mg.
Ø	Accumulation of BAY 86-9766 was modest (median accumulation ratio of Cmax: 1.4, (range 0.4-3.8); AUC0-24: 1.6 (range 0.9-2.5) in all patients) following multiple doses.
Ø	Half life of BAY 86-9766 was approximately 10 to 20 hours following single dose on Day 1.

Figure 3: Mean Plasma Concentration Profiles of BAY 86-9766 at Steady State

Results (cont’d)

Pharmacodynamics

Ø	BAY 86-9766 shows a concentration-dependent increase in inhibition of pERK (Figure 4).
Ø	Emax of 100% pERK inhibition was achieved at multiple doses.
Ø	Estimated leukocyte pERK ED50 corresponds to mean 24 hour steady state plasma levels achieved by the 30 mg to 40 mg qd dose range.
Ø	pERK was also decreased in tumor biopsies (data not shown).
Ø	Stable disease was confirmed in 10 patients across multiple dose groups and is summarized in Table 4.

Figure 4: Isolated Patient Leukocytes Show a Concentration-Dependent pERK Inhibition with resulting ED₅₀ of 227 ng/mL

Methods:Leukocytes were isolated from whole blood after dosing with BAY 86-9766 and stimulating phosphorylation of ERKex vivowith TPA. Data graphed above are from PD and PK samples taken at 2 hours, 3 hours, and 24 hours post dosing. Curve fitting was done using normalized response parameters, n = 169.

Table 4: Confirmed Stable Disease Achieved in Ten Patients Across Multiple Tumor Types and Dose Groups

Dose	Tumor Type	Number of Courses
4 mg qd	Ovarian	10
6 mg qd	Adrenal	6
	Colorectal	12
20 mg qd	Breast	5
30 mg qd	Colorectal	8
60 mg qd	Liposarcoma	15
50 mg bid	Colorectal*	14 (ongoing)
	Ocular melanoma	5
	Ocular melanoma	5 (ongoing)
160 mg qd	Colorectal**	5

*	Began dosing at 50 mg bid. Drug held from C4D28-C5D21 due to CNS AEs. Re-started drug at 30 mg bid.
**	Began dosing at 160 mg qd. Drug held from C1D15-C1D28 due to CNS AEs. Re-started drug at 100 mg qd. Note: One additional patient in the 50 mg bid group is ongoing in Course 4 with stable disease yet to be confirmed.

Conclusions

Ø	BAY 86-9766 was generally well tolerated at doses£ 100 mg daily with rash being the most common treatment-related adverse event.
Ø	Exposure of BAY 86-9766 increased linearly with increasing doses.
Ø	At the MTD, significant inhibition of leukocyte pERK and associated cytokines was observed.
Ø	Stable disease was achieved in 10 patients for an average duration of 8 months.
Ø	Based on the results of this study, Phase 2 development is indicated and being pursued.

22^ndEORTC-NCI-AACR Symposium on “Molecular Targets and Cancer Therapeutics”, Berlin, November 16-19, 2010