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With the impending announcement of the Phase IIb data for Rigel's (NASDAQ:RIGL) lead compound R-788, I thought I would share my analysis.

Rheumatoid Arthritis is a chronic debilitating disease that requires life-long treatment, which makes it a lucrative market but also at the same time very competitive. For a product that is somewhat late in entering the market, it needs a competitive edge to successfully penetrate an already established market. That edge is a product that can be administered orally. R-788 will revolutionize the treatment of RA as it is a small molecule that can be given orally, as opposed to the competitors which are given as intravenous or subcutaneous injection and are often associated with injection-type reactions or frequent visits to the doctor’s office for IV administration.

In June 2008, the company announced completion of patient enrollment on Taski-2 and that the results from both studies should be available in late summer 2009. (TASKi2 Aug’09)

The company was seeking partnership in 1Qtr of ’09 but backed out due to lack of suitable partner and awaiting release of Taski-2 results to seek a partnership, which would result in a better deal for Rigel since the compound in further into development.

From a scientific standpoint, I am fairly impressed with the results from the Phase IIa study and expect the results from Taski-2 and Taski-3 to be positive. Here is the breakdown of the scientific data and Taski-1 data compared to marketed agents:

Phase IIa study

Taski-1

Inclusion Criteria

  • met ACR criteria for RA
  • active RA > 12 months, receiving MTX for at least 6 months, receiving stable dose of MTX for at least 4 weeks
  • Active disease, defined as: >6 swollen joints and >6 tender joints, high C-reactive protein level, or morning stiffness lasting > 45 minutes

Primary Endpoint

  • Response rate according to ACR 20% improvement criteria (ACR20) at 3 months

Secondary Endpoint

  • ACR50
  • ACR70
  • Disease Activity Score 28

Response @ week 12 (3 months)

50mg bid+MTX(n=46)

100 mg (n=49)

150 mg (n=47)

Placebo + MTX (n=47)

ACR20

32%

65% (p=.008)

72% (p<.001)

38%

ACR50

17%

49%

57%

19%

ACR70

2%

33%

40%

4%

DAS-28

16%

26%

49%

8%

SAFETY

Neutropenia (ANC <1500)

2%

10%

30%

0%

This is your gold standard Phase IIa, dose-finding study. I’m especially impressed with the nice dose response you see in this study; with no difference between 50 bid vs placebo with significant incremental response at 100bid and 150bid dose. With 100 bid being the most optimal dose.

41% of pts on 100 bid achieved ACR20 response in week 1 of tx vs 13% placebo.

There were no alarming safety risks associated with this compound other than neutropenia, which is expected with this drug class.

Neutropenia, rapidly resolved with drug discontinuation and with dose reduction

*Patients from Mexico for some reason achieved a higher clinical response. This just could be random due to limited sample size and geography and similar trends were also observed in other RA studies.

Patient Characteristics

(phase IIa)

R788

Placebo

Age

52.1

54.3

Disease Dur

17.2 yrs

16.5 yrs

# Tender Joints

16..4 (only 28 assessed)

17.2

Swollen Joints

13.2

13.0

DAS28

5.41

5.46

No Prior DMARD

2.1

2.1

% taking Pred

42

51

% Rheu Fac +

66

72

Results of Phase IIa vs Competitors

R788 (n=49)

Enbrel

Remicade

Administration

100 mg BID PO

25 mg BIW SQ

10mg/kg q4weeks

n=30

n=59

n=88

n=81

MTX/P

MTX/R

MTX/P

MTX/E

MTX/P

MTX/R

ACR20 (3 month)

38%

65%

33%

66%

ACR20 (6 months)

TASKI-2

27%

71%

20%

58%

ACR20 (1year)

17%

59%

ACR50 (3 mo)

19%

49%

0%

42%

ACR50 (6 mo)

TASKI-2

3%

39%

5%

26%

ACR50 (1year)

9%

38%

ACR70 (3 mo)

8%

33%

0%

15%

ACR70 (6 mo)

TASKI-2

0

15%

0%

11%

ACR70 (1year)

2%

19%

When you compare the efficacy results from this phase IIa study to the competitors', the results are very similar. Although this was only a phase II study, which tends to inflate the results, I think the results are robust and compelling.

Based on the results from this study, Rigel decided to move forward with development and initiated 2 additional studies.

Taski-2

The purpose of this Phase IIb study is to determine if addition of R-788 100 mg two times a day or 150 mg once daily is effective in the treatment of Rheumatoid Arthritis in patients with inadequate response to MTX.

Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study

Estimated Enrollment n=420 patients

Randomized to receive:

R-788 100 mg two times a day or R-788 150 mg once daily or placebo

Primary Endpoint

ACR20 response rate [RR] at 6 months

Secondary Endpoint

Compare response rates of 100 mg BID vs 150 mg QD as determined by ACR20, 50, 70 etc… at 6 months

Taski-3

The purpose of this study is to determine if R-788 100 mg two times a day is effective in RA patients who have previously failed ‘biologic’ therapy. (Enbrel, Remicade, Rituxan, etc)

Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study

Estimated Enrollment n=195

Randomized to receive:

R-788 100 mg two times a day OR placebo

Primary Endpoint

ACR20 RR at 3 months

Secondary Endpoint

ACR50, 70, ACRn, DAS28-CRP, DAS28-ESR at 3 months

Update 2/3/09

Taski-2 enrollment completed Dec08 w/ 457 pts

Taski-3 enrollment expected to be completed Apr09 w/ expected 195 pts

Results expected July and August ‘09

Announced that it will delay its intention to seek partnership until results from Taski-2 -3 are known

  • Get more potential partners involved
  • Can’t start Phase III w/out partnership. This may limit the type of deal worked out

CASH POSITION – they have enough cash to operate until end of ’09 well after Phase IIb result annoucements

Source: Rigel Pharmaceuticals: A Game Changer in the Works?