Rick,
(for those who follow this thread but have no biology bkgd., mtx can also lead to neutropenia.... it's likely that mtx and R788 have overlying toxicities.)
are you speaking about the RA dose of mtx? i was poking around, but couldn't seem to find the % of incidence of neutropenia with either the RA or cancer doses.
here's birchenough's most recent writeup (4/7).
sales
April 07, 2008
Rigel Pharmaceuticals (RIGL - US$ 19.25) 1-Overweight
Company Update
Management Update
Investment Conclusion
We are maintaining our 1-Overweight rating on
shares of RIGL following a meeting with
management late last week. While partnership
timelines for R788 will likely extend to 1H09,
phase II open label extension data for R788 in
rheumatoid arthritis appear to be improving and
upcoming data in NHL is expected to demonstrate
substantial activity.
Summary
À‰ Please see our comments below
Stock Rating Target Price
New: 1-Overweight New: US$ 31.00
Old: 1-Overweight Old: US$ 31.00
Sector View: 2-Neutral
Overview
RIGL management met late last week with the Lehman Biotech team to update current status of key programs. With focus on next steps for
syk kinase inhibitor R788 RIGL suggested significant partnership interest with >10 interested parties but with timelines likely to extend to
YE08/1H09. Following positive phase II data reported in December open label extension data suggests high retention rates with no new
AEs and progressive improvement in ACR scores.
With additional focus on R788 data in NHL expected at the June 4-7 International Conference on Malignant Lymphoma RIGL suggested
significant activity and we expect response rates in the range of 20-30%. Further data flow should come in 2H08 with publication of R788 RA data by September, presentation of updates RA data at ACR in October and more mature R788 data with biomarker analysis expected
at ASH in December.
Meeting Details
RIGL management met with the Lehman Biotechnology team late last week to review status of ongoing programs. With recent share price
weakness along with other small cap names focus was on potential near term catalysts to reverse the recent trend. While prospects for a
near term partnership appear unlikely phase II data for syk kinase inhibitor RA continue to improve over longer term follow and management
appears optimistic regarding upcoming data in NHL.
Update on R788 in Rheumatoid Arthritis
RIGL indicated that retention rates remain high in the open label extension of its phase II study of R788 in patients with rheumatoid arthritis.
With focus on incremental toxicity RIGL indicated that neutropenia and diarrhea observed within the first 6 weeks of treatment have not
been an issue with longer term dosing. Specifically, patients that were dosed reduced during the randomized study have remained on
therapy with no recurrent neutropenia or worsening GI symptoms and the larger group of patients not requiring dose reduction during the
randomized portion of the phase II study have remained on full dose without incremental toxicity. Importantly, no new off target adverse
events (AEs) have been observed in longer term follow up.
With regards to efficacy RIGL highlighted the fact that during randomized treatment patients with dose reductions continued to experience
progressive improvement in ACR scores and actually had greater improvements in ACR 20, 50 and 70 scores than patients not requiring
dose reduction. Progressive improvement in ACR scores during the randomized study has apparently continued in the open label extension
and RIGL expects detailed data publication targeted for September and ACR presentation targeted for ACR in late October to look better
than prior topline results.
Update on R788 in Non-Hodgkins Lymphoma (NHL)
The phase I/II proof-of-concept study of R788 in patients with various forms of NHL is expected to report initial data at the upcoming
International Conference on Malignant Lymphoma. The study has been increased in size several times and has now enrolled roughly 95
patients with an average 4 months of follow up. Access to lymph node biopsies allows for characterization of syk kinase activation and down
stream phosphorylation and early biomarker data will likely be available at the June Lymphoma meeting in Lugano, although it is likely too
early to make correlation with anti-tumor activity.
Clinician feedback has been positive regarding prospects for R788 activity in NHL and overall we expect initial response rates in the range
of 20-30%. RIGL management expressed confidence in R788 activity and agreed that a 20-30% response rate range would be a
reasonable expectation for an active drug in NHL. The study has been optimized for patients with syk kinase activation, in particular those
failing prior Rituxan + CHOP therapy, and mature subset data should be available at ASH in December to assess more fully the potential for
higher response rates.
Additional Clinical Programs for R788
In addition to the ongoing phase II extension study RIGL is also initiating 2 additional studies to better delineate the safety and efficacy
profile of the drug. The first study is expected to initiate enrollment of 200 patients in May and will evaluate R788 + methotrexate in anti-TNF
failures with data expected in 2Q09. The second study is designed to enroll treatment naïve patients and to assess efficacy of R788 +
methotrexate over a longer 6-month period with MRI assessment of joint destruction and with data expected by mid-09.
An additional phase IIa study is expected to begin in 3Q08 with R788 evaluated in 400 patients with systemic lupus erythmatosis (SLE).
Preclinical efficacy has been most striking in models of lupus nephritis where normalization of BUN and renal histology have been observed.
While difficult to predict at present RIGL is targeting ACR 2009 as a forum for release of phase IIa Lupus data.
Status Update on R788 Partnership Prospects
RIGL described partnership interest in R788 as high with >10 companies expressing initial interest. The process of partnership discussion is
expected to take some time, however, with business development groups just beginning initial diligence. No specific timelines have been
put on a partnership although it appears unlikely before YE08 and more likely 1H09.
Update on other development stage programs
Beyond focus on syk kinase inhibition with R788, RIGL remains committed to introducing 1-2 new development stage candidates each year.
For 2008 increasing attention will be devoted to Jak 3 kinase inhibitor R348 for psoriasis, GvHD and transplant rejection. Upcoming
transplant meetings in the US and EU are expected to show case pre-clinical data for R348 in animal models of heart and kidney transplant
suggesting potential better efficacy than calcineurin inhibitors. While pre-clinical data in most striking in models of chronic transplant
rejection, initial development of R348 will be focused on psoriasis followed by GvHD. Currently a phase I dose ranging study has failed to
identify a maximally tolerated dose (MTD) at doses >1gm/day, with no evidence of anemia, seen with Jak 2 and pan-Jak inhibitors. A phase
II proof-of-concept study is expected to be initiated in 3Q08, with GvHD proof-of-concept trial expected to initiate in 1Q09 and a transplant
rejection phase II study tentatively targeted for 2H09.
Finally, RIGL does expect to see phase Ib data as the American Society of Clinical Oncology (ASCO) annual meeting in June for Merck-
Serono partnered aurora kinase inhibitor R343. RIGL has been surprised by the wider than expected therapeutic window and described a
dosing regimen of q daily x 3 with 25 days off as the most likely schedule to move into phase II. Phase II studies are expected to initiate in
2Q08 with potential data at ASCO 2009. |
