- Here are my notes from the presentation last night. New updates are in bold.
- Libigel FDA filing will be same division that approved elestrin
- submit libigel NDA in 2012
- male testosterone gel market in 2010: 2 products combined for $1.1b sales
- Abbott Labs $ABT quickly filed patent infringement suit, Teva asserted non infringement in NDA (this confirms that the ABT lawsuit was regarding BioTGel rather than some other Teva generic testosterone product filed via ANDA pathway)
- 3400 women randomized to date in Libigel safety study. >3600 women yrs exposure (this is a new update. reach 4000 no later than july or august. hopeful that could stop early and be sure of statistics for endpt. >1300 pts on tx over 1 yr. >700 over 2 yr, 10-12 >3yrs
- coprimary endpoints in efficacy trials are SSE and change in "mean desire" score
- Sought SPA to make sure FDA was on board with concept and what BPAX was doing for FSD
- p2 2.5 SSE during baseline 4 wks, at month 3 was 7.5 sse. placebo only increased to 4.1 (3.4 difference with Libigel)
- On safety study, 65% of pts have high BP and cholesterol. 4-5% have prior CV event
- both efficacy trials covered by SPA
- next safety update by end of May 2011
- 2009- 4m offlabel rx written for testosterone (includes both male products or compounding). no 2010 #s yet
- two papers published (JAMA and NEJM) showed 43% rate of FSD/low desire in female population (higher rate than males)
- 30% of women that complain about low desire/sevual dysfunction to their OB/GYN are currently treated with off label products
- cancer vaccines- 15 p1 and 2 trials ongoing at no cost
- melanoma and prostate clinical trials will start this year
- think that the later they partner libigel, the better the transaction will be for stockholders
- effiacy data early 4th qtr in October -November timeframe (this is another slight slip)
- topline saefty data 3q12
- Additional pill plus data 2011 (oral use)
- cash well into 2nd or 3rd qtr 2012
- q&a session:
- Will they get any efficacy data from safety trial? Safety trial has broader population (surgically and naturally menopausal women) But will collect/obtain minimal efficacy information
- ovaries produce 50% of woman's testosterone (hence efficacy trials are in surgically menopausal women)
- how does teva plan to position biotgel upon approval? we dont know yet- Teva hasn't told us. Reiterated that BioTGel was filed as NDA not ANDA
- Warner Chilcott not doing safety study for Intrinssa despite supposedly huge market-- do they know something bpax doesn't? W-C doesn't really fund much r&d. They made the acquisition to get PG's currently marketed products. Not want to fund $100-150m safety study. BPAX believes "other people should be in this mkt" but no one else is.
- male testosterone market was only $25m in 1995.
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May 26, 2011 London, UK #THU0254
MPI-0485520, A SMALL MOLECULE INHIBITOR OF IKKE/TBK1 IS ACTIVE IN A MOUSE COLLAGEN-INDUCED ARTHRITIS MODEL B. Richards 1, V. Baichwal 1, M. Cronin 1, L. Reeves 1, D. Papac 1, A. Yungai 1, P. Sebahar 1, R. Holcomb 1, D. Wettstein 1, P. Bartel 1,*, R. Carlson 1 1MYREXIS, Salt Lake City, United States Background: Activation of the innate immune system has been proposed as a potential trigger for chronic inflammation associated with rheumatoid arthritis (RA). The innate immune system is activated within fibroblast-like synoviocytes via Toll-like receptors (TLRs) leading to secretion of proinflammatory chemokines that promote recruitment of inflammatory cells to the joint. The IKK-related kinases IKKε and TBK1 are essential in propagating TLR activation to IRF3 and IRF7 transcription factors. Phosphorylation of IRF3/7 leads to increased production of proinflammatory factors (IFN-β, RANTES, IP-10, MIP-1α, and IL-6) and proteinases (MMP-3 and MMP-9) and several of these proteins have been previously shown to be overexpressed in synoviocytes from RA patients. Objectives: To determine if the potent and selective IKKε/TBK1 inhibitor MPI-0485520 reduces collagen-induced arthritis (CIA) in mice. Methods: MPI-0485520 in vitro activity was assayed using recombinant IKKε and TBK1 enzymes. Production of the TLR3-induced cytokines, RANTES, IFN-β, IP-10, and MIP-1α, by fibroblast-like synoviocyte cells was measured by ELISA. In vivo efficacy of MPI-0485520 was determined in a mouse model of collagen-induced arthritis. Clinical arthritis score, weight, anti-collagen IgG titers and joint histology were evaluated in diseased mice. Results: MPI-0485520 potently inhibits IKKε and TBK1 activities in vitro with IC50 values < 1 nM and reduces TLR3-induced RANTES, IFN-β, IP-10, and MIP-1α production in cultured fibroblast-like synoviocytes with IC50 values of 61, 12, 48 and 35 nM, respectively. MPI-0485520 also demonstrated efficacy in a collagen-induced arthritis model. Mice dosed for 16 days with either 100 or 150 mg/kg MPI-0485520 showed significant, dose-dependent reduction (p < 0.05) of 29% and 45%, respectively, in cumulative clinical arthritis score (number of joints affected, degree of erythema, and amount of swelling). The 100 and 150 mg/kg doses were well tolerated and resulted in 23% and 42% lower weight loss (p < 0.05), respectively, than vehicle-treated, collagen-immunized mice. Measurement of paw and joint histology showed a significant reduction (p < 0.05) of 37% in inflammation, pannus formation, cartilage loss, and bone destruction at the 150 mg/kg dose. The titer of arthritis-inducing anti-collagen antibodies was not modulated by MPI-0485520. Conclusions: To our knowledge, this is the first example of an IKKε/TBK1 small molecule inhibitor demonstrating activity in a mouse model of arthritis. These results are consistent with IKKε-knockout mouse studies which demonstrated a role for IKKε in the progression of induced arthritis. Based on these observations, we anticipate that an orally available drug targeting the IKKε/TBK1 kinases may benefit patients suffering from rheumatoid arthritis.
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