Rigel and Novartis initiated four programs, but the T and B cell programs seem to have ended at the research phase. From looking at the agreement, it would appear that rights to the targets it identified -- apparently only the T Cell program bore such fruit -- are now non-exclusive. Unclear to me if there is any financial obligation to Novartis if anything comes of further development outside of Novartis, but my read is that there is not.
Relevant snips from the S-1 and 10-Ks allow us to follow this:
>>2000 S-1 The goal of our T cell program is to identify early steps in the process of T cell activation. We have commenced screening using our post-genomics combinatorial biology technology and have identified novel drug targets. This program has been partnered with Novartis since May 1999.
2002 10-k We have identified novel drug targets in this program that have been partnered with Novartis since May 1999.
2003 10-k The first research project, a joint research project, was focused on identifying small molecule drug targets that regulate T cells in the area of transplant rejection. The second research project, also a joint research project, related to the identification and validation of small molecule drug targets that mediate specific functions of B cells in the area of autoimmunity. During 2002, Novartis notified us that it was terminating the research phases of the initial T Cell and B Cell joint projects in November 2002 and February 2003, respectively. The third research project, a project currently being carried out at Novartis, is focused on identifying small molecule drug targets that regulate chronic bronchitis. Novartis may terminate this chronic bronchitis research at any time. In July 2001, we amended the agreement to add a three-year joint project at Rigel in the area of angiogenesis in lieu of a project at Novartis.
Once a drug target from any of the four ongoing research projects has been identified and validated, Novartis has the right to conduct compound screening on such drug target on an exclusive basis for two years thereafter. Novartis will have the option to extend this exclusive right for up to five additional one-year periods so long as Novartis pays us an annual fee for such right and satisfies certain diligence conditions. Upon the expiration or termination of this right, both we and Novartis shall have the non-exclusive right to use, and allow others to use, such drug target for compound screening.
2004 10-k Currently, only the Novartis oncology and chronic bronchitis programs and the Daiichi program are in the research phase of the agreements.<<
The 2000 10-K says they were identified, but there has been no announcement that Novartis took them into screening for over two years now. Research is still being published, however (note that G Aversa is from Novartis; perhaps that would have been mentioned after the "Rigel Pharmaceuticals; and." part in the new paper below, but for some editorial glitch)). I would guess this is to enhance the reputation of the scientists involved, but that that program is dead.
>>J Immunol. 2004 Jun 15;172(12):7324-34.
A Novel Role for p21-Activated Protein Kinase 2 in T Cell Activation.
Chu PC, Wu J, Liao XC, Pardo J, Zhao H, Li C, Mendenhall MK, Pali E, Shen M, Yu S, Taylor VC, Aversa G, Molineaux S, Payan DG, Masuda ES.
Rigel, Inc., South San Francisco, CA 94080; and.
To identify novel components of the TCR signaling pathway, a large-scale retroviral-based functional screen was performed using CD69 expression as a marker for T cell activation. In addition to known regulators, two truncated forms of p21-activated kinase 2 (PAK2), PAK2DeltaL(1-224) and PAK2DeltaS(1-113), both lacking the kinase domain, were isolated in the T cell screen. The PAK2 truncation, PAK2DeltaL, blocked Ag receptor-induced NFAT activation and TCR-mediated calcium flux in Jurkat T cells. However, it had minimal effect on PMA/ionomycin-induced CD69 up-regulation in Jurkat cells, on anti-IgM-mediated CD69 up-regulation in B cells, or on the migratory responses of resting T cells to chemoattractants. We show that PAK2 kinase activity is increased in response to TCR stimulation. Furthermore, a full-length kinase-inactive form of PAK2 blocked both TCR-induced CD69 up-regulation and NFAT activity in Jurkat cells, demonstrating that kinase activity is required for PAK2 function downstream of the TCR. We also generated a GFP-fused PAK2 truncation lacking the Cdc42/Rac interactive binding region domain, GFP-PAK2(83-149). We show that this construct binds directly to the kinase domain of PAK2 and inhibits anti-TCR-stimulated T cell activation. Finally, we demonstrate that, in primary T cells, dominant-negative PAK2 prevented anti-CD3/CD28-induced IL-2 production, and TCR-induced CD40 ligand expression, both key functions of activated T cells. Taken together, these results suggest a novel role for PAK2 as a positive regulator of T cell activation.<<
Though perhaps it could be resurrected if the publications generate sufficient interest. Anybody got a read on interesting they are (ahem, Rick?)? So the oncology and bronchitis programs are still going, and there are still potential funding, milestone, and royalty revenues from those. These programs are scheduled to end this July.
Meanwhile, the internal programs continue as the VC finish their second bailout . . . from the most recent 10-K:
>>For some programs, we may also seek to enter into collaborations for the development of compounds that we have discovered. For example, we have received preliminary human efficacy data for our lead compound R112 for the treatment of allergic rhinitis. We expect that this program could be the basis of our next corporate collaboration, which we anticipate entering into in 2004.
R112—Product Candidate for Allergic Rhinitis. We completed a Phase I clinical trial of R112 in 18 patients in December 2002, a single-dose Phase I/II clinical trial of 20 patients in June 2003 and a multi-dose safety trial of 24 patients in December 2003. We are planning to initiate in the second quarter of 2004 a Phase II clinical trial that will measure allergic symptom improvement and treatment. We expect to receive the results of this trial in the second half of 2004.
R803—Anti-Hepatitis C Virus Product Candidate. We completed our initial Phase I clinical trial of R803 in January 2004 in the United Kingdom and the results will be part of the U.S. IND package that we expect to file with the FDA in the first quarter of 2004. We plan to commence a Phase I/II clinical trial of R803 in the U.S. during the second quarter of 2004 with initial results measuring viral titer reduction available in the second half of 2004.
R406—Product Candidate for Rheumatoid arthritis. In January 2004, we selected R406 as our lead product candidate for initial clinical trials in rheumatoid arthritis. We expect to file an IND application with the FDA for the indication of rheumatoid arthritis in the second half of 2004. <<
Haven't looked at the Pfizer angle yet. Anyone know if there would be news on that front any time soon?
So Rigel is going to have a lot of important news flow in the second half. If it gets weak this summer, I may be looking to buy.
Cheers, Tuck |
