yes and in less than 2 weeks will be annual shareholders meeting and another investors meeting... the rocket fuel for this stock is ready to take off if cudc 907 update on cohort 2 is positive. then in a few months operable data for bcc should be released.
the chatter for iap cudc 427 is that it looked safe and it as a single agent had some complete responses and stable disease. remember that iap really shows its potential when combined with chemo which will be phase 2. they have indicated that they might investigate the iap as single agent for possible mutation if they find it. dont forget the investor conferences at the end of the month too. we should get more updates on cudc 907 on cohort 1 and 2. that to me is even bigger than asco data....
Check out their IAP presentation (actually i think genentech is giving it but its our drug now) cudc 427. The real value of the company will be unlocked with CUDC 907 and potentially CUDC 427. Erivedge is for newbies : )
go look at a one year chart of INFI... they have no approved products and their rise was on their pi3k delta molecule... we have very similar product with a built in hdac molecule... curis is not a revenue story... erivedge helps pay the bills for cudc-907 and soon to be oral iap inhibitor that was created by genentech for phase 2 trials.
the dude abides
key in my opinion to curis is the update on cudc-907 trial data from ph1. pi3k + hdac inhibitor. third cycle of cohort 1 will be completed by tomorrow and we should have more insight. also iap inhibitor which was created by genentech will be another near term driver with asco oral abstract and start of phase 2 soon. good luck!
CUDC-907 will unlock value for cris in the next few months. look for more data on tues and wed earnings/investor conf call this week!!!!!!
ABSTRACT Clinical outcomes for patients with multiple myeloma (MM) have improved substantially since the introduction of novel agents, including the proteasome inhibitor bortezomib and the immunomodulatory drugs thalidomide and lenalidomide. However, most patients with MM eventually relapse and prognosis remains poor among patients with relapsed and/or refractory disease. Combination therapy using agents with different mechanisms of action is emerging as an attractive treatment approach in oncology to increase efficacy and/or overcome resistance to standard treatment regimens. This review discusses unmet needs in the treatment of MM and the development of histone deacetylase inhibitors as a treatment modality for MM
Cabozantinib/XL184 (Exelexis, Inc.) has demonstrated remarkable responses in kidney cancer.
Preclinical results revealed VEGF, KIT and MET inhibition in a variety of solid tumors such as thyroid, ovarian, renal, lung, liver and prostate cancers. A phase II trial demonstrated efficacy in renal cancer with a 28 % objective response rate, stable disease rate of 62 % and median progression free survival of 14.7 months. Predominant toxicities of fatigue and diarrhea were noted. Dramatic responses in bone metastases (three of four patients) make the agent especially valuable for palliation in a disease, where presence of bone metastases is a predictor of worse survival. Cabozantinib is an emerging novel agent with promising activity in advanced kidney cancer. Randomized trials are planned in comparison with standard VEGF inhibitor therapy. Defining the role of MET overexpression would help patient selection and enrich and enhance the future evaluation of this targeted novel agent.
Wayne State University, Detroit, Michigan, MI 48201, USA. firstname.lastname@example.org
Reference: Curr Oncol Rep. 2013 Apr;15(2):76-82.
Activity of cabozantinib in metastatic uveal melanoma: Updated results from a phase II randomized discontinuation trial (RDT).
Adil Daud, MD
CUDC 907 HDAC+PI3k in my opinion could be a gem. Currently in Ph1 trial... Compare against INFI drug that made it go from 6 to 50... IAP inhibitor to start ph2 testing mid year molecule was created by genentech and licensed to Curis... abstract on ph1 to be released at asco. hsp90 outlicensed to debiopharm who is taking forever to enroll patients.... Erivedge slow start to sales... Waiting for operable bcc data in the near future to expand use....
My biggest holding is CRIS.... They have an IAP inhibitor that was licensed from Genentech and my personal favorite CUDC 907 which is HDAC+pan PI3K inhibitor now in Phase 1. Compare against INFI PI3K and look what that did for that stock. My latest buy is TKMR. Very small market cap with decent cash position. iRNA company.
I know Diane Simeone is very involed in cancer stem cells and pancreatic cancer. There is a video of which she talks about xl 184. Go to youtube and type simeone+pancreas. You will see a video called targeting pancreatic cancer stem cells. I have not looked around lately regarding xl 184 and pancreatic but maybe this weekend i will look around to see if i see fresh conversations.
isn't the real news that most are missing is the fact that their technology is working by hitting the target? seems like that is where the $$ is to be made here by proving their technology works for licensing? i am new investor but that is how i am taking the data.
yeh i have been the local digger of info for curis and moved our board to google board which allows links but now am spreading my wings to twitter. some very good sources on there and you can post links and get away from a lot of the #$%$ chat. i have posted several links on there for exel. im learning my way on twitter.
it was from AACR 2013 abstract released today... ill let you dig who funded : )
Approximately 70% of patients with late stage cancers metastasize to the bone. RECIST identifies these tumors as “unmeasureable” for therapeutic response assessment. Cabozantinib (CABO), a tyrosine kinase inhibitor of MET and VEGFR2, has shown promise as an effective therapy for metastatic prostate cancer to the bone. Patients treated with CABO showed a reduction in [Tc99m]-bone scan signal suggesting tumor response to treatment. Nevertheless, a return in signal to pre-treatment levels was observed in these patients following therapy completion. It has yet to be determined if the response observed in bone scans results from tumor death, changes in bone metabolism or vascular alterations in the tumor-stromal microenvironment resulting in reduced transport of the imaging tracer. The study objective was to assess tumor and bone response to CABO in an animal model of bone metastasis using a quantitative multi-modal imaging approach.
Twenty-seven male SCID mice were implanted with PC3 cell line in the right tibia. PC3 cells were transfected with a plasmid expressing a bioluminescence imaging (BLI) reporter for measuring apoptosis. When tumor volumes reached 10mm3 by MRI, mice were distributed into 2 groups: CABO at 30 mg/kg (N=13) and vehicle (N=14). Treatments were delivered by oral gavage once a day for three weeks. Starting pre-treatment, MRI and BLI were acquired every third day and CT every week. Tumor and bone volumes were monitored by manually contouring volumes of interest (VOI) on anatomical MRI and CT images, respectively. The apparent diffusion coefficient (ADC), an indirect measure of tumor cellularity, was calculated from diffusion MRI.
Mice treated with CABO were found to have significantly higher ADC values and slower growth profile than controls (p
i might start charging : )
Prostate cancer (PCa) growth is incurable once it has metastasized to the bone microenvironment (BM). The altered BM provides a permissive niche to support tumour growth, and therapeutic strategies that target tumour-bone interactions and/or restore bone homeostasis are being pursued. This demands preclinical models that faithfully replicate tumour-bone interactions, and non-invasive imaging methods to interrogate such orthotopic models in vivo, improving the accuracy of, and accelerating pre-clinical drug development. We have used a multi-modality imaging approach to assess the radiology and response of an orthotopic VCaP PCa bone metastasis model to the c-Met/VEGFR2 inhibitor cabozantinib.
Direct intratibial injection of 2x106 luc-VCaP cells into male castrate SCID mice resulted in tumour formation within 20 days. The resulting tumours deregulated normal bone function, exhibited a predominantly sclerotic phenotype and, importantly, retained a rearrangement of the ERG oncogene, the most common chromosomal abnormality found in human PCa (40-80% of cases). Mice bearing established intratibial VCaP prostate tumours were treated daily with 30mg/kg p.o. cabozantinib (n=7) or vehicle alone (n=7) for 15 days.
Semi-quantitative photon flux measures from BLI showed a 52% regression after 14 days of treatment (p=0.016). Tumour volume was quantified from T2-weighted MR images acquired from contiguous transverse 500μm slices across the leg, with an in-plane resolution of 156μm2, in which tumour hyperintensity was clearly identifiable. Mean tumour volume was significantly (p=0.038) smaller in the cabozantinib treated group after 15 days treatment (21.9 ± 5.1 mm3) compared to the vehicle cohort (104 ± 43 mm3). These data show that cabozantinib exhibits powerful anti-tumour activity in this clinically relevant model of PCa.
Diffusion weighted MR images were acquired using a 10 b-value EPI sequence, from which the apparent diffusion coefficient (ADC),
Anti-angiogenic treatment of glioblastoma with Vascular Endothelial Growth Factor (VEGF)- or VEGF Receptor 2 (VEGFR2) inhibitors normalizes tumor vessels, resulting in a profound radiologic response and improved quality of life. This approach however does not halt tumor progression by diffuse infiltration, as this phenotype is less angiogenesis dependent. Combined inhibition of angiogenesis and diffuse infiltrative growth would therefore be a more effective treatment approach in these tumors. The HGF/c-MET axis is important in both angiogenesis and cell migration in several tumor types including glioma. We therefore analyzed the effects of the c-MET- and VEGFR2 tyrosine kinase inhibitor cabozantinib (XL184, Exelixis) on c-MET positive orthotopic E98 glioblastoma xenografts, which routinely present with angiogenesis-dependent areas of tumor growth, as well as diffuse infiltrative growth. In in vitro cultures of E98 cells, cabozantinib effectively inhibited c-MET phosphorylation, concomitant with inhibitory effects on AKT and ERK1/2 phosphorylation, and cell proliferation and migration. VEGFR2 activation in endothelial cells was also effectively inhibited in vitro. Treatment of BALB/c nu/nu mice carrying orthotopic E98 xenografts resulted in a significant increase in overall survival. Cabozantinib effectively inhibited angiogenesis, resulting in increased hypoxia in angiogenesis-dependent tumor areas, and induced vessel normalization. Yet, tumors ultimately escaped cabozantinib therapy by diffuse infiltrative outgrowth via vessel co-option. Of importance, in contrast to the results from in vitro experiments, in vivo blockade of c-MET activation was incomplete, possibly due to multiple factors including restoration of the blood-brain barrier resulting from cabozantinib-induced VEGFR2 inhibition. In conclusion, cabozantinib is a promising therapy for c-MET positive glioma, but improving delivery of the drug to the tumor and/or the surrounding tissue may be nee
there are multiple discussions about mek in the list that were discussed this week in europe at a conference. here is another headline MEK Inhibitor Active in NRAS-Mutated Melanoma.
forgot to mention... this board is thin and most of the regulars are on the google groups board for curis... you can find on google finance cris under disussion group