Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Another story from BigL on Yahoo worth reading
New therapy prevents lung cancer growth in mice
By smspaz3 · Yesterday at 10:20 am · 2 replies
In Non-small cell lung cancer - Stage IV
Recommend Follow replies Problem More options
Shared with the public
http://feedproxy.google.com/~r/sciencedaily/health_medicine/lung_cancer/~3/ TRwv8OosVsE/120813130625.htm?utm_source=feedburner&utm_medium=email
Explore topics in this post
2 replies Reply
Oldest firstNewest first
By gpawelski
Reply 3290276
Yesterday at 12:59 pm
Report post
Thanks for this!
Cancer stem cells (CSCs), are aggressive cells thought to be resistant to current anti-cancer therapies and which promote metastasis, are stimulated via a pathway that mirrors normal stem cell development. Disrupting the pathway, researchers are able to halt expansion of CSCs.
One approach is to force the CSCs into a differentiated state, thereby impairing stem characteristics, such as self-renewal. Interference with the Notch, Wnt, or Hedgehog pathways that are thought to regulate differentiation, are strategies that have been proposed.
Erivedge (vismodegib) is one such drug that inhibits Hedgehog signaling by targeting the serpentine receptor Smoothened (SMO), and has produced promising anti-tumor responses in clinical studies of cancers driven by mutations in this pathway.
Breast cancer represents a benchmark for studying the influence of Notch pathways on CSCs. A significant reduction of mammosphere-forming effeciency has been achieved with gamma-secretase inhibitor (GSI). Since a similar effect was seen with the EGFR tyrosine kinase inhibitor gefitinib, it is conceivable that the dual inhibition of Notch and EGFR may exert a synergistic effect on lung cancer.
And a number of Wnt modulators or inhibitors have been identified like COX-2 inhibitors (celecoxib and rofecoxib). The Wnt activity identifies the colon CSC population.
The capacity to study human tumor microenvironments enables the functional profiling platform to conduct discovery work on the most sophisticated classes of compounds that influence cell signaling at the level of Notch, Hedgehog and Wnt, among others (Gonsalves, F, et al. 2011).
http://www.inspire.com/groups/lung-cancer-survivors/discussion/new-therapy-prevents-lung-cancer-growth-in-mice/
The Pancreas Cancer Microenvironment
Christine Feig1, Aarthi Gopinathan1, Albrecht Neesse1, Derek S. Chan1, Natalie Cook1,2, and David A. Tuveson1,2,3
+ Author Affiliations
Authors' Affiliations: 1Li Ka Shing Centre, Cambridge Research Institute, Cancer Research UK; 2Department of Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom; and 3The Lustgarten Foundation Pancreatic Cancer Laboratory at Cold Spring Harbor, Cold Spring Harbor, New York
Corresponding Author:
David Tuveson, Li Ka Shing Centre, Cambridge Research Institute, Cancer Research UK, Robinson Way, Cambridge CB2 0RE, United Kingdom. Phone: 44-1223-404190; Fax: 44-1223-404199; E-mail: david.tuveson@cancer.org.uk
Abstract
Pancreatic ductal adenocarcinoma (PDA) is a common and lethal malignancy resulting in more than 250,000 deaths per year worldwide. Despite extensive efforts, cytotoxic and targeted therapies have provided only limited efficacy for patients with PDA to date. One contributing factor to the failure of systemic therapies may be the abundant tumor stromal content that is the characteristic of PDA. The PDA stroma, aptly termed the tumor microenvironment, occupies the majority of the tumor mass, and consists of a dynamic assortment of extracellular matrix components and nonneoplastic cells including fibroblastic, vascular, and immune cells. Recent work has revealed that the PDA stroma supports tumor growth and promotes metastasis and simultaneously serves as a physical barrier to drug delivery. Accordingly, methods that alter stromal composition or function, for instance interference with the vasculature via Notch/Hedgehog pathway inhibition or relief of vascular compression by hyaluronidase, are under active investigation. Here, we will review our current understanding of the PDA tumor microenvironment, and highlight opportunities for further exploration that may benefit patients. Clin Cancer Res; 18(16); 4266–76. ©2012 AACR.
http://clincancerres.aacrjournals.org/content/18/16/4266.abstract
Courtesy of BigL on Yahoo.
rbf welcome aboard. I hope all the normal yahoo members come over and join us. This site has so much more to offer as far as posting ability is concerned.
I can't for the life of me explain the price drop other than to believe it will just be temporary and offers a great opportunity for those who want to increase or start a position. I commented several times over on Yahoo how to me it is similar to what happened with SGEN after they received approval last August. Take a look at their chart and how it popped on approval to over $22 then traded in a range between $17 and $22 until May when it started a run to $28 then falling back some after their recent qtr but still higher than its old range.
I think we are in a similar pattern; then all of a sudden the sentiment will change without notice and we will start a nice uptrend taking out multi year highs in a short period. Obviously this is all just my opinion but I can't believe we could be held down for much longer, there is just way too much potential here.
I have been buying what were supposed to be trading shares from $5.11 down to $4.34 up through last week. Each time I thought we would have a nice 5-10% pop and I was going to trade them out. That hasn't worked out too well yet, but I am confident it will.
Good luck and let's keep reminding the regulars over in the cesspool to come join us, the air is better over here.
One of the good things about Ihub is you can post nearly unlimited length messages. I hope we start to get others to move on over from fhat cesspool. Thanks for the info
Me too. Now lets get everyone else over her
Just testing to see if I can reply from my phone. I just dowloaded the app. Without the app it wouldnt allow me to post from my phone in the past.
Meg, I tried to post this on Yahoo but it wouldn't let me, that site stinks.
Meg do you think any of these posts really impact the stock price? If so, then by all means go ahead with your quest. Personally I can't imagine too many shares being sold or purchased based on a person's opinion in a message board. I do think that message board postings which include links to detail support do have an impact but the drivel posted by the many aliases here, I don't believe have any meaningful impact other than to tick us off if you let them. Since Yahoo doesn't appear to have a limit on the number of ignores in your list just utilize it for all these idiots who are just trying to piss in your cheerios.
You do have to give the shorts their credit. I can't imagine having shorted a stock like Curis. The past month anyone who is short has made some money. The big question is when do they wake up and find out the 20% gain they made this past month is wiped out with a 50%, 100% or more loss due to some as yet unpublished report on the efficacy of one of the clinical trials.
While I am waaaayyyy too overextended to the long side, my personal belief (at worst) is that this stock even without any additional indications and poor performance with the current indication Curis will be worth a minimum of $5-8 in the next couple of years. So IMO I believe I don't have any downside in the long term and I firmly believe I have tremendous upside. There are way too many millions being spent by people smarter than me on testing this compound in other indications and more indications will come over time. I do believe some of them will bear fruit and that is not counting anything from 101, 0932, 907 or the other compounds in the lab that we don't know about.
Good luck with your quest although I can't imagine anyone who has a decent amount of $$ to invest actually believes any of the nonsense the supposed shorts post. Maybe I am wrong and unsupported message board rants actually impact stock prices but I doubt it.
I wish it were that easy
Bangtime, sorry but I don't have the time nor the expertise to do as you ask in the detail you are looking for. Just to let you know my background is in accounting as I am a CPA and about 8 years ago I stumbled across Curis and bought my first 1,000 share on a whim without knowing a thing about the company on the news they signed a deal with Wyeth. At the time I thought that deal would give a very good short term trade and stupidly I thought it would go from $6 and change to $9 based on the reported value of the deal over its life. That deal didn't move the stock and the deal ultimately fell apart.
Over the years I went from being a short term trader to a long term investor reading as much about the company as I could find and buying and selling (mostly buying) shares along the way, luckily buying a lot under $2 and some even under a buck. I have traded along the way but own more shares today than I ever before. Luckily the trades overall have been positive for me with the exception of some recent purchases.
As far as your question about timing of news from trials and expected due dates, I don't know. Some of the trials according to the clinical trials website are way overdue. Why we haven't heard anything about the results yet, I don't know. It could be that the NCI is not obligated to update it in a timely basis or it could be something else. For example the lung cancer trial was originally scheduled to be completed in 12/10 and stayed that way on the site until June where they changed the completion date to 08/2022. My belief is that is a typo and should read 08/2012 but that was unchanged for years after the original estimated primary completion date. I can't tell you why that is. IMO we are overdue for news on several trials that are underway.
Bottom line to me is that IMO Roche, the NCI and others wouldn't be spending tens of millions on these studies unless there was evidence to support the trials. While I am not qualified to know why they decided to do these studies, the scientists are and they decided to move forward with all 36 of the studies for a drug that until this year wasn't even approved for sale. To me this is evidence that it will work on some other indications. Will many of them fail, I am sure they will BUT it will only take one or two to show they work for the stock to skyrocket IMO. Good luck with your investment and education. Follow the links that BigL posts over on Yahoo as well as the other stories that come out. You don't have to be an expert in the field to make a decision as to whether or not you think the stock has good upside potential. The short term trading will be meaningless in the long term. Now time to get ready to leave for work.
Jeffries presentation, worth a listen
I am surprised there wasn't been more discussion about the Jeffries presentation over on Yahoo. I felt Dan did a great job of explaining the potential Curis has for current and new investors. Some snipets
He said at around the 1:00 minute mark that just for Erivedge, "it represents substantial growth upside for Curis investors"
At the 3:20 mark he summarizes the investment thesis as "We have a deep pipeline, with multiple milestones and value inflection points lined up for the next 6, 12 and 18 months. Erivedge in and of itself represents a very attractive growth potential for our shareholders...."
At 4:20 "Roche has publicly stated that for the label we currently have they expect that 1.5% of all bcc cases, approximately 30,000 cases in the US alone annually, and in the operable, the suboptimal setting where surgery isn't appropriate, another 2% of the total to be used in combination with surgery, will comprise another 40,000 patients...."
At 6:30 he discusses the Gorlin's syndrome patients which would add another 4-5,000 patients.
At 10:00 he discusses again the market opportunity where it is "clearly over a Billion dollar opportunity for Roche where Curis will receive a 5% starting royalty up to a high single digit royalty and that ramping up is very rational and it hits the highest royalty well before we hit a Billion in sales annually.. Later this year expect EU approval which will trigger another milestone plus expanded market opportunity as well as Australia, Canada and Switzerland."
At 13:00 he summarizes the operable trial and reiterates that with the data released recently "42% of patients had complete histological clearance and a full 96% had either complete clearance or a partial response which bodes extremely well for it to be used in the neo adjuvant setting going forward"
At 14:15 he discusses the trials that were presented at ASCO where there "was nothing overwhelming and the good news is there was nothing negative and we did see some signals as there was an enhancement of stable disease in Chondrosarcoma by a couple of months and then the pancreatic trial in combination with Gemcitabine there was an increase in PFS by 2 months, a little over 2 months. I will caution that while this fits with what we expect mechanistically but these are still intermittant data it is not complete and the numbers are not robust enough to draw any conclusions but we still remain optimistic that a signal will emerge with a number of trials pending in the ligand driven mechanism trials..."
At 16:45 "...as an overview, just the mutation driven cancer presents an very significant growth and value proposition for our shareholders. Just the advanced bcc population in the US alone represents approximately 30,000 patients and even if we penetrate just 50% of that market represents a significant market potential plus the possiblility of other markets...."
At 17:45 he begins discussing 101. Oral formulation is anticipated for filing IND in Q3 of 2012.
At 23:39 he discusses the head and neck trial "where the first 3 patients treated with a sub optimal dose 2 had complete response and 1 had a partial response. He said it is too early to make any judgements because you could get burned but anectodally they are encouraged and look forward to giving updates as they become available. They expect to complete the phase 1 dose escalation by end of year."
At the end he summarizes that the IV formulation represents a viable commercial opportunity for 101 in head and neck cancer as evidenced by the early results even if they are not successful with the oral formulation. He also reiterated "just from Erivedge, milestones and royalties ramping up the business model has been substantially de-risked .. with tremendous upside over the next 6, 12, and 18 months for our shareholders."
While I attempted to be 100% accurate in the above, I would recommend all take the 1/2 hour to listen to the conference. As everyone who knows my posts, I am unbelievably bullish on the potential of Curis in the near and long term.
My additional thoughts and comments:
Just for grins and giggles, my calculation based on the $7,500 monthly price for Erivedge, for every 10,000 patients on drug annually it will translate into over $60 million in royalties annually to Curis at a 7% average royalty rate. This for a company that has a cash burn rate of $20-25 million per Dan during the presentation. Just in the approved setting, we will be extremely profitable if they can capture 1/3 of the market in the US alone under the current approval. Add in Gorlin's patients and the potential for operable, and the market grows significanlty. Best of all that is the US market alone. I would guess the rest of the world could double almost the size of the market potential. Throw in other cancer indications and the question becomes:
How high is too high for the stock price of Curis to get to? GLTA.
Debio ASCO poster link
http://www.debiopharm.com/media/publications/72-debio-0932/3188-a-phase-i-study-of-debio-0932-an-oral-hsp90-inhibitor-in-patients-with-solid-tumors-.html
From the poster:
ANTI TUMOR ACTIVITY
• Anti-tumor activity could be assessed in 45/50 patients enrolled (5 patients had no evaluable
on-treatment disease assessment).
• Partial response was observed in 2 patients, one with NSCLC (see case history) and one
with breast cancer.
• Out of 8 patients with lung cancer, 1 had partial response, 4 had stable disease, and 3 had
progressive disease.
CASE HISTORY
• 63-year old Caucasian male.
• Diagnosis of Stage IV Kras-mutated adenocarcinoma of the lung in Nov 2007.
• Progressive disease after four regimens of systemic anti-cancer therapy, ending Aug 2009.
• Started Debio 0932 100 mg Q2D in July 2010.
• 40% reduction in target lesion diameter after 16 weeks of treatment (partial response).
• Response duration: 16 weeks.
• Treatment was well tolerated, with facial acneiform skin rash.
CONCLUSION
Debio 0932 was generally well tolerated at doses up to 1600 mg Q2D and 1000 mg QD
• Debio 0932 showed promising signs of anti-tumor activity in patients with advanced
solid tumors, especially in lung cancer
• The recommended Phase 2 dose (1000 mg QD) will be tested in an additional 30
patients in an ongoing expansion study
• A Phase I-II study of Debio 0932 in combination with standard of care in the first- and
second-line treatment of NSCLC is planned
Nature article
You will need to create an account to view the article
http://www.nature.com/nrd/journal/v11/n6/full/nrd3753.html
News and Analysis
Nature Reviews Drug Discovery 11, 437-438 (June 2012) | doi:10.1038/nrd3753
PIPELINE PIONEERS:
Vismodegib
Andrzej Dlugosz1, Sid Agrawal2 & Peter Kirkpatrick3
In January 2012, vismodegib (Erivedge; Curis/Genentech), a small-molecule inhibitor of the Hedgehog signalling pathway, was approved by the US Food and Drug Administration (FDA) for the treatment of basal cell carcinoma (BCC).
BCC is a common form of skin cancer, largely caused by exposure to ultraviolet radiation1. Although most cases are curable by surgery, if the disease progresses to unresectable locally advanced or metastatic forms it can be life-threatening1.
BCC is associated with inappropriate activation of the Hedgehog signalling pathway (Fig. 1a), which has a key role in cell growth and differentiation during embryogenesis and early development but appears to be inactive in most adult tissues2. Most patients with BCC tumours (such as those with Gorlin syndrome) have loss-of-function mutations affecting the protein Patched homologue 1 (PTCH1), which normally inhibits signalling by the protein Smoothened homologue (SMO)1, 2. Activating mutations in SMO are present in ~10% of BCCs2. Hedgehog pathway activation caused by overexpression of Hedgehog ligands has also been observed in several other tumour types including pancreas, colon, prostate and ovarian carcinomas2.
Basis of discovery
Evidence that the Hedgehog signalling pathway could be a tractable pharmacological target came from the characterization of the teratogenic natural product cyclopamine as an antagonist of SMO3. Vismodegib (Fig. 1b), a selective SMO antagonist with greater potency and more favourable pharmaceutical properties than cyclopamine, was identified through high-throughput screening and subsequent medicinal chemistry optimization3.
Drug properties
Vismodegib inhibits Hedgehog pathway signalling by binding to and inhibiting SMO3, 4. It showed promising antitumour activity in preclinical studies3 (for example, producing tumour regression in a medulloblastoma allograft mouse model that is dependent on the Hedgehog pathway for growth) as well as in its first Phase I trial in patients with advanced BCC5.
Clinical data
The efficacy and safety of vismodegib (150 mg per day orally) was investigated in a single-arm, open-label, two-cohort trial involving 104 patients with either metastatic BCC (n = 33) or locally advanced BCC (n = 71)4. Patients with locally advanced BCC were required to have lesions that were considered to be inoperable and that had recurred after radiotherapy, unless radiotherapy was contraindicated or inappropriate (for example, in patients with Gorlin syndrome, which was diagnosed in 21% of the trial population)4. In the metastatic BCC cohort 97% of patients had received prior therapy, and in the locally advanced BCC cohort 94% of patients had received prior therapy4.
The main efficacy outcome measure of the trial was objective response rate (ORR) as assessed by an independent review facility4. In the metastatic BCC cohort, tumour response was assessed according to the RECIST (Response Evaluation Criteria in Solid Tumors) criteria, whereas in the locally advanced BCC cohort the tumour response evaluation included measurement of the externally assessable tumour, photographic assessment of ulceration, radiographic assessment of target lesions (if appropriate) and tumour biopsy4. An objective response for patients in the locally advanced BCC cohort required at least one of the following criteria and the absence of any criterion for disease progression: =30% reduction in lesion size (sum of the longest diameter (SLD)) from the baseline in target lesions by radiographic assessment; =30% reduction in SLD from the baseline in the externally visible dimension of target lesions; and complete resolution of ulceration in all target lesions4. Complete response was defined as an objective response with no residual BCC on sampling tumour biopsy4.
Of the 104 patients enrolled, 96 patients were evaluable for ORR4. In the efficacy-evaluable metastatic BCC cohort (33 patients) the ORR was 30.3% with no complete responses, and in the efficacy-evaluable locally advanced BCC cohort (63 patients) the ORR was 42.9%, which included 13 patients (20.6%) with a complete response4. The median response duration was 7.6 months in both the metastatic BCC cohort and the locally advanced BCC cohort4.
Indications
Vismodegib is approved by the FDA for the treatment of adults with metastatic BCC, or with locally advanced BCC that has recurred following surgery or who are not candidates for surgery, and who are not candidates for radiation4.
Analysis | basal cell carcinoma
Analysing issues in the treatment of BCC is Andrzej Dlugosz, M.D., Poth Professor of Cutaneous Oncology, Department of Dermatology and the University of Michigan Comprehensive Cancer Center, Michigan, USA.
Although the fraction of BCC patients with either metastatic or advanced disease is far less than 1%, the lack of effective treatments makes vismodegib (and other Hedgehog pathway antagonists in development) an important therapeutic advancement.
Side effects associated with the use of vismodegib are generally considered to be minor to moderate, and include muscle spasms, altered taste perception, weight loss, fatigue, nausea and hair loss. The development of hair loss is not surprising given the important role of Hedgehog signalling in hair growth, and additional class-specific side effects may help to uncover previously unappreciated roles for Hedgehog signalling in other adult organs or tissues. It will be important to see whether modified dosing regimens, combination therapies or other approaches can maintain efficacy while minimizing side effects.
The relatively benign side-effect profile of vismodegib could help in expanding its use as a systemic therapy for additional groups of patients with BCC. For example, given the ability of vismodegib to cause impressive tumour shrinkage, it may be highly useful in a neoadjuvant setting for 'medical debulking' prior to surgery: a smaller tumour would mean a smaller surgical scar. This would be applicable to BCCs arising sporadically or in patients with Gorlin syndrome. Prior to adopting this approach, however, it will be important to rigorously assess whether any potential tumour cells remain in clinically regressed regions, as there could be an increased risk of recurrence if surgical excision leaves some of these cells behind.
As with other drugs targeting key oncogenic drivers, resistance to vismodegib has been reported in patients with advanced or metastatic BCC and medulloblastoma, including mutations leading to a drug-resistant form of SMO or amplification of the Hedgehog pathway transcriptional effector GLI2. However, in these patients, previous treatments with DNA-damaging agents may have contributed to the development of resistance, and a recently completed prevention trial in patients with Gorlin syndrome (ClinicalTrials.gov identifier: NCT00957229) could clarify whether resistance develops in patients with treatment-naive BCC. Given the initial report of a >90% reduction in new BCC development in these patients with Gorlin syndrome (Tang , J. Y.et al. J. Invest. Dermatol. 131, S92; 2011), studies are also needed to investigate whether systemic Hedgehog pathway blockade could prevent sporadic BCC development in other high-risk patients.
Another area in which future study seems to be warranted is the use of topical formulations of SMO antagonists in patients with BCC, for which discordant results have been reported in clinical trials so far. One agent, CUR61414, had no clinical activity despite showing encouraging preclinical data, whereas another agent, LDE225, produced complete or partial responses in 12 out of 13 treated BCCs6, although residual nests of apparent tumour cells were detected at the end of the 4-week treatment interval.
Overall, the promising efficacy of vismodegib as a single agent in BCC underscores the pivotal role of mutation-driven Hedgehog pathway activation in the development and maintenance of these cancers. It is not yet clear whether vismodegib or related drugs in development will be efficacious in Hedgehog-activated internal cancers with other driver mutations. However, based on the data currently available and emerging, it seems likely that these agents will be useful for preventing and treating at least some BCCs.
Targeted Therapy for the Treatment of Basal Cell Carcinoma and Melanoma: Implications for Patients and Healthcare Practitioners
Jean Y. Tang, MD, PhD, Chairperson; Keith T. Flaherty, MD; Vernon K. Sondak, MD Faculty and Disclosures
CME Released: 05/03/2012; Valid for credit through 05/03/2013
Slides/Video CME Information Earn CME Credit »
This CME activity was developed to be distributed on Medscape.
Hello, and welcome to this CME-accredited video titled Targeted Therapy for the Treatment of Basal Cell Carcinoma and Melanoma: Implications for Patients and Healthcare Practitioners. I am Dr. Jean Tang from the Stanford School of Medicine, and I am joined by Dr. Keith Flaherty of the Massachusetts General Hospital Cancer Center at Harvard Medical School and Dr. Vernon Sondak from H. Lee Moffitt Cancer Center and Research Institute. Welcome to you both, and thank you for joining me.
Our learning objectives today are to identify the patient symptoms and disease characteristics that influence the diagnosis and treatment strategy for basal cell carcinoma (BCC); to describe the mechanism of action and emerging evidence supporting the clinical utility of hedgehog inhibitors in treating BCCs; to demonstrate the management of treatment-related side effects in patients with BCC taking hedgehog inhibitors; to evaluate novel agents in ongoing clinical trials for the treatment of BCC and melanoma; to describe molecular tests and patient characteristics that facilitate individual treatment planning for melanoma; and lastly, to evaluate newly approved treatment options for advanced metastatic melanoma.
First, for an overview of BCC and other types of skin cancer, I wanted to emphasize that skin cancer is the most common cancer in the United States.
Approximately 3.6 million Americans will be diagnosed with a new skin cancer this year. The 3 most common types are the BCC abbreviated as BCC, squamous cell carcinoma, or SCC, and melanoma. The topic of this program will focus on BCCs and melanomas.
BCCs have at least an estimated 1 million new cases per year in the United States. And according to the American Cancer Society (ACC), 75% of all skin cancers are of the BCC type. They rarely metastasize, but because of the surgery and the destructive modalities required to treat BCCs, they are the fifth most costly cancer in the Medicare population.
Because they're quite common, the age-adjusted incidence rates per 100,000 Caucasians are shown here: 475 cases in men, 250 cases in women. This attributes to an estimated lifetime risk of BCCs in the Caucasian population as more than 30% in men and a little less than 30% in women. The risk of developing a second BCC once you've already had one is quite high: within the first 3 years of having a first BCC, an individual will have a 44% chance of developing a second BCC.
KEY TAKEAWAYS
So the key takeaway points are that BCCs are the most common cancer in the United States, and their incidence is actually increasing likely due to increased sun exposure in the US population.
Now I'd like to review the current treatment approaches in BCC.
Common treatment options for low-risk BCCs are listed here, and this is according to the National Comprehensive Cancer Network () Guidelines. For low-risk BCCs, curettage and electrodesiccation is an option as well as surgical excision, Mohs micrographic surgery, cryosurgery, or treatment with liquid nitrogen and topical cream applications with imiquimod—also known as Aldara™—or 5-fluorouracil (5-FU). Radiation therapy is an option and also for superficial types of BCC, photodynamic therapy also is approved.
However, for those BCCs that are locally advanced or metastatic, treatment options are quite limited. What do we mean by locally advanced BCCs? These are BCCs that are not amenable to surgery and may not be amenable to radiation therapy. And this picture illustrates a gentleman with basal cell nevus syndrome (BCNS) with large, locally advanced BCCs that would be difficult to operate on.
So, for these cases of advanced BCCs, what are the common treatment options? Radiation therapy is possible. However, in a patient with a genetic disease such as BCNS, this radiation therapy is actually contraindicated. How about other chemotherapies? Cisplatin and doxorubicin have also been reported in the literature, but the overall response rate is not great. Case reports have also illustrated the use of epidermal growth factor receptor inhibitors but again, the overall responses to these therapies are not spectacular. What we're most excited about today is the targeted new therapies with hedgehog pathway antagonists.
HEDGEHOG PATHWAY ANTAGONISTS
What's unique about BCC tumors is they have mutations in genes involved in the hedgehog signaling pathway. The hedgehog signaling pathway is illustrated in this cartoon diagram here.
Because vismodegib inhibits the hedgehog signaling pathway, we wanted to investigate the effect of vismodegib on patients with multiple BCCs, patients with BCNS. And as you recall, BCNS patients inherit a gene mutation that causes them to have abnormally high hedgehog signaling pathway.
In this randomized clinical trial, we gave 41 patients vismodegib at 150 mg daily vs placebo. These patients were randomized 2:1. Forty-one patients were enrolled from 3 clinical centers from September 2009 to December 2010, and our primary end point was what did vismodegib do for prevention of new BCC tumors? Our secondary end points included what did this drug do for reduction in size of existing BCCs? And also was vismodegib safe and tolerable in this relatively healthy patient population?
These 2 pictures or sets of pictures illustrate before and after effects of vismodegib. At baseline, one of our BCNS patients has multiple superficial BCCs shown on her back. And after 5 months of treatment, we see approximately 90% clearance of all the superficial tumors on her back.
On the other panel, showing the baseline photograph of a gentleman's face the blue arrow highlights the multiple nodular BCCs located on his forehead, on his cheek, and on his nose. While each of these tumors individually may be treatable with surgery, the total burden of his BCC disease is quite high, and these treatments of the particular BCCs can lead to significant scarring and morbidity. And as you can see from the bottom photo after 5 months, these nodular BCCs disappear.
The overall results of our trial are summarized in this graph. On the Y-axis, the number of new BCC tumors are shown over time. BCNS subjects randomized to vismodegib developed very few new BCC tumors, while those patients randomized to placebo developed multiple new BCC tumors. And this difference was statistically significant.
KEY TAKEAWAYS
The key takeaway points from this presentation are listed here. The cure rate is excellent for most BCCs with current surgical or topical therapies. And by cure rate, I mean greater than 85% cure. However, for those BCCs that are locally advanced or metastatic, there are limited therapeutic options. We are extremely excited about the recent FDA approval of vismodegib, which is the first in class small molecule inhibitor of the hedgehog signaling pathway, and we have clinical trial results showing that vismodegib works for BCC prevention in BCNS patients. Thank you very much for allowing me to speak about my research and about the current clinical trials.
Hello, my name is Keith Flaherty. I'm a medical oncologist from the Massachusetts General Hospital Cancer Center in Boston Massachusetts. I'd like to review for you the clinical data generated with selective antagonists of smoothened, a new small molecule targeted therapy approach for BCC.
The biology of BCC became elucidated in the mid to late 90s when mutations that affect 2 key proteins that are related to one another were identified in nearly all cases of sporadic and familial BCC. Familial BCC, referred to as Gorlin's syndrome or BCNS, is characterized by numerous BCCs emerging over the course of one's lifetime and typically an adult patient having many lesions present at any 1 moment in time.
Sporadic BCC of course is typically single lesion occurring and can become very advanced if not attended to and sometimes occur in very cosmetically sensitive parts of the body. 90% of sporadic BCCs have so-called patched mutations. Patched is a surface membrane protein as I'll review in a cartoon in just a moment, and it's related and connected in fact to another protein referred to as smoothened, which is mutated in approximately 10% of BCCs. Putting those two together again, about all cases have a mutation in either of these 2 proteins.
As this cartoon depicts, patched and smoothened are surface membrane receptors, and they in fact communicate to one another. Under normal physiologic conditions, these 2 proteins are associated, and when patched is bound to smoothened, smoothened is retained in the membrane and does not activate downstream signaling. However, when the ligand for patched engages it, it releases smoothened, and smoothened translocates to the nucleus and drives the transcription of a large number of genes including ones that are critical for growth factor receptor expression and activation.
Mutations that occur in either patched or smoothened essentially release smoothened from the control otherwise exerted by patched. So these mutations break the connection between these 2 proteins, and therefore mutations on either side of this balance can release smoothened and allow it to generate signaling downstream. The inhibitors that have been explored in this setting to try to counter these mutations are inhibitors that block the activity of smoothened, so the molecule that otherwise would be released into the cell.
The pivotal data that established this approach in advanced BCC are summarized here. A phase 2 clinical trial was conducted in 2 cohorts, a cohort of patients who had metastatic BCC, some of whom had BCNS as a precursor, and patients with locally advanced BCC, typically patients with sporadic cases.
You can see that response was the primary end point of this trial. And the standard dose was administered to all patients, 150 mg once a day in a capsule. With responses primary end point the duration of response and overall duration of disease control were key secondary end points. And again, the focus of this study was to document early efficacy as had been observed in a phase 1 clinical trial with this same agent in a similar patient population.
The patient demographics are shown here for the 2 cohorts. The patients with metastatic BCC had a median age of approximately 60, a male:female distribution in about a 3:1 ratio in favor of males. Patients with locally advanced tumors had a similar age, the male:female distribution slightly less skewed. And you can see the characteristics shown here in terms of the either inoperable or advanced nature of their disease.
The degree of regression that was observed was highly variable but still quite consistent. And approximately 80% of the patients demonstrated some degree of tumor regression in the locally advanced cohort, which was the larger of the 2 cohorts. A small subset of patients had no apparent biologic effect, with tumors in fact worsening at least to a slight degree early in the course of therapy.
Several patients had complete regression at least on clinical grounds of BCCs that at baseline had been large and locally advanced, so truly quite a remarkable spectrum of clinical activity.
When one looks at objective responses here categorized by patients who had sufficient degree of response, generally 30% regression or greater that was confirmed on subsequent evaluation as well, you see the response rate in the locally advanced cohort as assessed by the investigators was approximately 60%. And on central review of both radiographic images as well as cutaneous photography, it was closer to 40% by an independent review panel.
In the metastatic cohort, the response rate documented by investigators approached 50%, and on independent review in this case of radiographic evaluations of metastatic disease, it was approximately 30%. Again, this denotes the patients who had sufficient regression to constitute an objective response and categorizes patients with more minor degrees of regression as having so-called stable disease.
Here's a nice illustration of a patient with multifocal disease affecting the face and where surgery to eradicate this disease would certainly have been a difficult undertaking and would have had severe cosmetic consequences. One sees after just a relatively short course of therapy, several weeks, clear improvement of these lesions, and with more time and more follow-up, complete eradication.
The common adverse events are shown here. Typically, vismodegib, the first available inhibitor of smoothened to have achieved FDA approval, is usually associated with mild or moderate toxicities when administered at the standard dose of 150 mg a day. Muscle spasms and altered taste or dysgeusia are the most symptomatic toxicities. Alopecia and in some cases weight loss can also be observed, but again, these are usually mild or moderate in severity.
When severe or even if moderate and intolerable, toxicity can easily be managed with a dose interruption, and sometimes patients could require more than 1e dose interruption to be able to maintain treatment in the long term.
Again, this is a medication that is started at a standard dose of 150 mg orally and is supplied in 150-mg capsules only. So, interruption and again potentially repeated interruption is a recommended strategy. Rarely, patients had to discontinue therapy altogether because of toxicity in clinical trials, and so it's anticipated that interruption of varying degrees of duration will usually be sufficient to allow patients to maintain treatment.
KEY TAKEAWAYS
The key takeaways are that in the long history of management of advanced BCC, chemotherapy drugs have been notoriously ineffective. Other targeted therapy approaches have not taken hold. It was the elucidation of mutations that activate the smoothened signaling access that really shed light on the unique biology of this tumor and led to the development of selective smoothen antagonists, which now have been established as a treatment standard for these patients with either locally advanced or metastatic disease. Vismodegib specifically is the first of the FDA-approved drugs. There are a large number of other agents in this class that are currently still in clinical trials.
My Comment: The above was copied from a presentation on Medscape which requires a free account to gain access. I bolded the portions above. Go to the link below if you want to see the charts and pictures which are quite striking.
http://www.medscape.org/viewarticle/762573
Full news release::
Curis Announces Collaborator Roche's Submission of Marketing Authorization Application for Vismodegib in Advanced Basal Cell Carcinoma
LEXINGTON, Mass., Dec 22, 2011 (BUSINESS WIRE) -- Curis, Inc. CRIS -2.58% , a drug development company seeking to develop next generation targeted small molecule drug candidates for cancer treatment, today announced that its collaborator Roche has submitted a Marketing Authorization Application (MAA) for vismodegib (GDC-0449, RG3616) to the European Medicines Agency (EMA). The MAA is currently under review for the treatment of adults with advanced basal cell carcinoma (BCC) for whom surgery is considered inappropriate. Vismodegib is a first-in-class, investigational, oral medicine designed to selectively inhibit signaling in the Hedgehog pathway and is being developed by Roche and Genentech, under a collaboration agreement between Curis and Genentech, a member of the Roche Group.
Curis earned a $6 million milestone payment from Genentech as a result of the MAA submission to the EMA. If vismodegib receives Marketing Authorization by the EMA , Curis will also be entitled to receive an additional milestone payment as well as royalties on any future sales.
"We continue to be extremely pleased with Roche and Genentech's efforts in progressing vismodegib towards commercialization. Vismodegib is now under review for approval in both the United States and Europe, with an FDA PDUFA action date of March 8, 2012, in the U.S.," said Dan Passeri, Curis President and Chief Executive Officer. "Vismodegib represents a potential advance for patients suffering from this serious and debilitating form of BCC, for whom no current therapeutic alternatives are available. We continue to remain hopeful that this important treatment for advanced BCC will be approved in these territories."
The application is based on clinical data from ERIVANCE BCC/SHH4476g, a pivotal Phase II study of vismodegib in patients with advanced BCC. The results were presented at the Seventh European Association of Dermato-Oncology (EADO) Congress in July 2011 as well as at the European Multidisciplinary Cancer Congress (EMCC) in September 2011.
About Basal Cell Carcinoma
BCC is the most common cancer in Europe and the United States. The disease is generally considered curable when the cancer is restricted to a small area of the skin. However, in a small group of people, if the disease is left untreated or does not respond to treatment, the cancer may advance further into the skin, bones or other tissues, or spread to other parts of the body. In such rare cases, the disease can become difficult to treat and life-threatening. There are no approved therapies to treat advanced basal cell carcinoma.
About Vismodegib and the Hedgehog Pathway
Vismodegib is designed to selectively inhibit signaling in the Hedgehog pathway by targeting a protein called Smoothened. The Hedgehog signaling pathway plays an important role in regulating proper growth and development in the early stages of life and becomes less active in adults. However, mutations in the pathway that reactivate Hedgehog signaling are seen in several different types of cancer. Abnormal signaling in the Hedgehog pathway is implicated in the more than 90 percent of BCC cases.
Genentech is also evaluating vismodegib in a Phase II trial in patients with operable forms of BCC, which opened for patient enrollment in October 2010. Furthermore, vismodegib is being evaluated by third-party investigators in a number of other cancers and in people with BCC who have Gorlin syndrome, a condition that affects many areas of the body and increases the risk of developing BCC. For more information, visit http://www.clinicaltrials.gov .
About the Curis-Genentech Collaboration
Under the ongoing collaboration agreement between Genentech, a wholly owned member of the Roche Group, and Curis, vismodegib (GDC-0449, RG3616) was discovered by Genentech and was jointly validated by the parties through a series of preclinical studies. Pursuant to this collaboration, Genentech and Roche are responsible for global clinical development, and Genentech (U.S.), Roche (Ex-U.S. excluding Japan and Korea) and Chugai Pharmaceuticals (Japan and Korea) are responsible for commercialization of vismodegib. Curis is eligible to receive cash payments upon the successful achievement of specified clinical development and regulatory approval milestones, as well as royalties assuming successful commercialization of vismodegib by Genentech and its sublicensees, which include Roche and Chugai.
About Curis, Inc.
Curis is a drug development company that is committed to leveraging its innovative signaling pathway drug technologies to seek to create new targeted small molecule drug candidates for cancer. Curis is building upon its previous experiences in targeting signaling pathways, including the Hedgehog pathway, in its effort to develop proprietary targeted cancer programs. For more information, visit Curis' website at www.curis.com .
Curis Cautionary Statement: This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including without limitation statements regarding: the expected timing for FDA's review of the NDA for vismodegib; and the potential for vismodegib to have a clinical benefit in treating advanced BCC patients. Forward-looking statements used in this press release may contain the words "believes", "expects", "anticipates", "plans", "seeks", "estimates", "assumes", "will", "may," "could" or similar expressions. These forward-looking statements are not guarantees of future performance and involve risks, uncertainties, assumptions and other important factors that may cause actual results to be materially different from those indicated by such forward-looking statements including, among other things:
-- Although the FDA has indicated that it expects to complete its review of the NDA on or before March 8, 2012, the FDA may not complete its activities within this time frame.
-- The EMA and/or FDA could impose additional unanticipated requirements, including additional clinical trials, to gain approval of vismodegib in advanced BCC, and any failure to satisfy the FDA's additional requirements could significantly delay, or preclude outright, approval of vismodegib.
-- The EMA and/or FDA may not be satisfied with the results of anticipated pre-approval inspections of Genentech's and Roche's manufacturing facilities and the facilities of third party laboratories and manufacturers of active pharmaceutical ingredients (APIs) and other materials used in the manufacture of vismodegib, and, as a result, Genentech and Roche may be unable to gain approval of vismodegib, if at all, within the time frame indicated above.
-- Genentech and Roche may not ultimately demonstrate to the satisfaction of the EMA and/or FDA the safety and efficacy profile of vismodegib in the treatment of advanced BCC, in which case vismodegib will not be approved for sales and marketing for the treatment of such indication.
-- Even if vismodegib receives marketing authorization, the EMA and/or FDA may impose limitations on the approved indications for use or the conditions to approval, or impose requirements for post-marketing testing and surveillance to monitor the safety and efficacy of the product. Moreover, vismodegib's benefit/risk profile may not be widely accepted by the medical community or third party payors for the treatment of advanced BCC.
-- Curis also faces other important risks relating to the successful development and commercialization of vismodegib, and with respect to its business, operations, financial condition and future prospects generally, that are discussed in its Quarterly Report on Form 10-Q for the quarter ended September 30, 2011 and other filings that it periodically makes with the Securities and Exchange Commission.
In addition, any forward-looking statements represent the views of Curis only as of today and should not be relied upon as representing Curis' views as of any subsequent date. Curis disclaims any intention or obligation to update any of the forward-looking statements after the date of this press release whether as a result of new information, future events or otherwise.
Comments on the video, with these results could there be any way the FDA would not approve 0449? I can't imagine this not being approved earlier than the PDUFA date of 03/08/12. My guess is that we get word of approval by 01/15/12. The recent run-up is later than what I expected as I would have expected it to be over $4 upon the news of the FDA acceptance but better late than never. The big question is how high do we go leading up to approval and how high afterwards? Will there be irrational exuberance to the upside or will it sell on the news? I can't imagine it selling on news of approval but I have felt that way many times with this and other stocks I have owned over the years, and I guess it will depend on how high we get leading up to FDA approval.
As I posted recently, I think when you count milestone payments plus royalties in 2012, we have a very reasonable chance of making $.50/share for 2012. Granted, milestone payments are not recurring but royalties are sure to ramp up in future years which should more than make up for the milestones after 2012. If the analysts start to project EPS of $.50 or more, even at an average historical multiple of 15 times earnings for the overall market it still means a $7.50 stock price. Now we know a small growing biotech will have a much higher multiple than 15 times earnings associated with it. If the studies for pancreatic and lung cancer is positive coupled with FDA and EU approval, how high will we get in 2012? What would be considered irrational based on our prospects?
I know I am getting ahead of myself but things will get very exciting in the coming weeks and months. In the coming weeks we know the company is projecting 2 big news items, EU news and operable bcc data. Throw in the possibility of the FDA approving Vismodegib early and within the next month we could easily get 3 company changing news releases. GLTA and let's hope the news comes our way. For 2011 our stock price is up over 100% and we could easily be up by a higher percentage in 2012 with the right pieces of news that don't seem that far fetched.
Great video worth watching courtesy of BigL over on Yahoo. The entire video is worth watching but the pictures at the 13 minute mark are unbelievable. The pictures are graphic so be careful.
boo ya watch video 16-Dec-11 10:29 pm
perhaps this vid helped the recent run up..
von hoff is da man!
Patient testimonials for Vismodegib:
Every so often I would read posts on the Gorlin Syndrome board to see what patients had to say about 0449 and it has been a while since I read the board. IMO after reading posts from a couple of patients, I don't think there is ANY DOUBT that the drug will work on operable bcc and that Roche will continue on with a phase 3. The results for those poor people who are affilicted with Gorlin's syndrome sound truly amazing and while we are invested in the stock for a financial gain it is great news that these patients finally have a drug that will enhance their quality of life, that is assuming the FDA approves the drug. Here is what actual patients that were on the trial had to say:
"Just to give you some follow-up on my situation, I completed the 18 months of the trial on Vismodegib in the beginning of August. In about 12 days, all the muscle cramps that I had were gone. Now, almost 6 weeks off of the drug, I have had no return of Basal Cell Carcinomas, no return of palmar pits. I have a bit of fuzzy hair growing back on my head and legs, and no return of the palmar pits. My final weight loss total on the drug was 50 pounds and two more have come off since then:))))) This part makes me extra happy!
My personal advice / thoughts, if you have lots of BCC's, the side affects are worth it! It is AMAZING to me that I have not had ANY skn cancer surgery since June of 2009. "
"Even the cramps are becoming manageable. I usually take almost 25 gulps of water before bed with the pill each night. Hydration is important throughout the day as I notice when I occasionally visit my gym.
I attempted to run a half mile the other day. I think I ran a quarter mile and the cramps hit hard as they did once before during a similar attempt. With the weight loss of 20 pounds, I felt more than able, but the cramps made me feel like an idiot (lol).
I've had one hair cut to since starting on the drug almost a year ago. Aside from some acne here and there and these two side effects, there is really nothing else for me of significance. I have to struggle to see any semblance of eye brows though. Fortunately, I believe glasses make it less noticeable."
This was in response to a question who also posted the above:
"The vast majority of my BCCs were gone after 9 months. I had 67 or so on my face. Some bruises from them still remain even if the cancer might technically be gone."
Here is another post from the same patient in response to a question about before and after pictures:
"For nearly the past 10 years, I avoid pictures at almost all costs. I think I can count the number I've agreed to on my hands. The contrast is stunning at times still. One of the study doctors say it was as if I was a new person. I believe she said the difference was greater than anyone else at Columbia.
I walked into a bathroom at a Barnes & Noble months ago and almost didn't recognize the person in the mirror. I remember staring at the mirror in the brightly lit room for several seconds. I've also noticed the difference in my face in mirrors at the gym from a distance. Given that I wear a lot of sunscreen, my face is like a white sheet. I'm laughing as I type this.
I might ask for a few "before" pics the next time I visit Columbia if I feel brave."
From a different thread on the same board:
"I am finishing month 18, the last month of the trial and I have been bcc free for over a year, there are some typical side effects and there extent varies with each person. "
The above were copied from the Gorlin's syndrome board link below. When you enter the site you have to just click "enter as guest" and you don't have to register. The above posts were copied from the thread on the left side of the screen after you enter titled "Gennetech submits new drug application".
http://forums.delphiforums.com/n/main.asp?webtag=Gorlinsyndrome&nav=messages&msg=2581.1&prettyurl=%2FGorlinsyndrome%2Fmessages%2F%3Fmsg%3D2581%2E1
This sounds like a truly wonderful drug and I hope for their sake (as well as our financial sake) that the FDA doesn't stall the approval process. There are other threads on the site as well that you might want to read through to get a feeling for what these people live with.
From Curis' website I would think they have treated about 80 patients or will shortly:
Debio 0932
Licensed to Debiopharm SA
Debio 0932 is a small molecule inhibitor of Heat Shock Protein 90 (Hsp90). Curis licensee Debiopharm is finalizing the Phase I dose escalation study of this molecule and expects to initiate a Phase Ib trial in early 2012 and a Phase II study during the second half of 2012.
Debiopharm has indicated that it expects to present data from the Phase I dose escalation study at a medical conference in 2012.
About the Debio 0932 Phase I Clinical Trial
The first part of the study (Phase Ia) is an open-label, multi-center, dose escalation trial evaluating the safety and tolerability of escalating multiple dose levels of Debio 0932 as a single agent given orally in patients suffering from advanced solid tumors or lymphoma.
The dose-limiting toxicities, maximum tolerated dose, and pharmacokinetic parameters will be determined by using both every other day and daily administration regimens. Resulting data will guide the recommended Phase Ib dose and schedule. The secondary objective will be to assess whether changes in pharmacodynamic biomarkers indicative of Hsp90 inhibition by Debio 0932 can be reliably measured in patient samples.
The objective of the Phase Ib study, an expansion cohort of certain solid tumor and/or lymphoma patients, will be to further assess the safety profile, pharmacokinetics and pharmacodynamics of Debio 0932 at a potential Phase II dose level, and to make a preliminary assessment of anti-tumor activity in patients with advanced solid tumors.
Debiopharm has indicated that it expects to treat up to 80 patients in the Phase Ia portion of the trial. Once the recommended dose for each schedule is reached, Debiopharm may treat up to 40 additional patients at the chosen dose and schedule as part of the Phase Ib expansion phase.
Debio 0932 demonstrated high potency in vitro and in vivo across a wide range of cancers. Most notably, Curis scientists observed complete tumor regression following oral administration of Debio 0932 in a mouse xenograft model of acute myelogenous leukemia (AML). Tumor regression has also been observed after treatment of Debio 0932 in mouse xenograft models of breast, non-small cell lung, gastric cancer and glioblastoma brain cancers. In this preclinical testing, the compound also demonstrated an ability to effectively cross the blood brain barrier, and demonstrated an ability to extend survival in an intracranial glioblastoma model. GLP toxicity studies suggest that Debio 0932 appears to be well tolerated at potentially efficacious doses.
About the Debiopharm License Agreement
On August 6, 2009, Curis entered into a license agreement with Debiopharm S.A., a Swiss corporation. Pursuant to the license agreement, Curis granted to Debiopharm a worldwide, exclusive royalty-bearing license with the right to grant sublicenses to develop, manufacture, market and sell any product containing the Company’s Hsp90 inhibitor technology, including Curis’ lead Hsp90 compound under development, CUDC-305 (since renamed Debio 0932). Debiopharm will assume all future development responsibility and incur all future costs related to the development, registration and commercialization of products under the agreement. Curis is eligible to receive up to an aggregate of $90 million in payments, as well as royalties on sales by Debiopharm or its sublicensees.
About Hsp90
Hsp90 is a member of a class of proteins called molecular chaperones that play a fundamental role in the folding, stabilization and degradation of their client proteins under normal or stressful conditions. Hsp90, in particular, has become an attractive therapeutic target for the treatment of cancer because a majority of its client proteins are involved in cellular signaling transduction and have been identified as potential contributors to various aspects of cancer cell growth and survival. Inhibitors of Hsp90 activity may be of therapeutic value if they can prevent Hsp90 chaperones from protecting proteins involved in cancer and allow them to be degraded.
I guess Debio wouldn't have been my first choice but from what Dan was saying it sounds as if things are moving along. He said during the conference that he expects something from Debio at ASCO and beginning of the phase 2 in the second half of next year. I wish it were quicker but at least it is moving in the right direction. Our milestone payments alone next year should be more than enough to cover our burn rate.
We could easily have $30-40 million in milestone payments next year counting the grant money. I would think we will get at least $10 million each for FDA and EU approvals from Roche, add in another $4 million of grant money for the recent agreement, then another $5-10 million from Debio during the second half of '12. In addition we will get another $8 million this year or early next year for EU acceptance. Throw in royalties for 9 months in the US and probably 6-9 months from the EU and next year should be very profitable on a EPS basis. My expectation for total revenue (including milestones) next year are in the neighborhood of $60-75 million. If that happens we could easily have another doubling (and more) of our stock price in 2012 IMO. GLTA.
As MarketAce pointed out over on Yahoo, Curis is up 100% year to date and my guess (hope) is that we are not done yet for this year. 100% return in a year for any stock is good when you have owned it all year but let's be realistic, 100% from $1.98 isn't a big dollar rise. Next year if things fall into place and we have a similar (or higher) % increase, then it will start to become a more meaningful rise in dollar terms which is very possible IMO. I am very happy where we are at considering where we were but I am looking forward to what next year will bring.
Today's conference didn't provide anything new but Dan did reiterate the fact that "the FDA in its acceptance of the filing did not require a panel which underscores the quality of the data that was submitted supporting the prospects of approval". My hope is that without the need for a panel, hopefully it will speed up the process for approval and we could hear by the middle of next month. That would put approval on pace with the time frame of what Zelboraf was approved in earlier this year.
During the conference he also again said that EU news could come by the end of this month which would be great. It may not come until early next year but it would be nice if it came sooner.
As far as revenue potential he stated that we are waiting on Gennentech to provide guidance on pricing and market potential but said "royalties could cover their cash burn and then some." Right now they don't know how much but it is nice that they are stating what has been projected by other investors.
As far as operable bcc the presentation on page 6 states "data and development decision expected in late 2011 or early 2012". When asked during the q&a session about prospects he stated that surgery will still be used for most of the indications in operable bcc but depending on size, location and other factors it could be used to enhance patients lives due to lower scaring.
Debio should commence their phase 2 in second half 2012 which will trigger another milestone.
Continued to discuss prospects for 101 optimistically. Hope to launch a phase 2 in late 2012 or early 2013.
Also discussed recent grant for 907 which first milestones to be received during 2012. Filing of IND in mid 2012 is their current expectation.
The will end the year with about $30 million and possibly more if they receive the EU milestone this month.
If we were able to go up over 3% on such a terrible market day on relatively little volume, what happens if any of the catalysts gets released and create a surge in volume with trading in the millions of shares? It looks to me like the longs are finally holding on to their shares and for some reason someone new is now accumulating. Even though we exceeded our normal volume, 404,000 volume today is still very low. Today's close was the highest since 7/26/11.
Here's to hoping we get some great news soon with an explosion in volume. There are more than enough potential catalysts that appear ready to pop in the near term. GLTA.
Now if we can only get everyone else to come on by.
BTH, if your assumptions are correct, I would be thrilled. Those assumptions for US sales alone would produce $2.25 billion in revenue/year assuming 30,000 patients at $75,000 each. That in turn would produce revenue to Curis of over $150 million/year for US sales alone for one indication.
Granted the above assume everyone gets the drug and it is priced at full rate to everyone. Even if that is not true, when you add in sales to the rest of the world, the above assumptions don't seem too far off to me. Add in other potential indications and the revenue potential to Roche and in turn Curis could be huge and is the reason I am so optimistic about its prospects. The next 6 months will be transformative for Curis which in turn would have a big impact for its investors.
How long have you been following it?
Have you followed the Stand Up 2 Cancer videos? Connecting the dots from the interviews with Von Hoff, it appears that Vismodegib could really help the current standard of care. Von Hoff stated that it is his hope that within the next 2-3 years he hopes that the 1 year survival rate for pancreatic cancer goes from less than 20% to greater than 80%. IMO since he has access to the results, the combo therapy that includes 0449 must be working. Maybe it is just wishful thinking since I am way overweighted in Curis, but I am really optimistic this could fly in the coming months. I have been invested in Curis since 1/04 and really loaded up on it over the past couple of years.
Considering the company only has 30 employees and is currently spending in the neighborhood of $20-25 million/year, it won't take much success for 0449 for Curis to become very profitable. IMO sales of it will ramp up very quickly since there isn't any other standard of care for advanced bcc. Estimates range from 20-40,000 patients annually just in the US for this indication. Since we currently will not have any other competition, we should get a very large percentage of patients prescribed the drug from the outset. Since patients will then probably need to be on it for multiple years, as time goes on there will be even more patients on it as the survival rate increases, and that is just for advanced bcc.
Assuming annual costs of around $50,000 for the drug (which I think is conservative) with a 5-9% royalty rate and Curis will be profitable next year. Assuming approval, they will get 3 more milestone payments for 0449 alone then ongoing royalties beginning upon drug approval. I wouldn't be surprised to see at least $50 million in revenue (including milestones) in 2012 which translates into net income of at least $.25/share. Granted not much but what type of multiple gets assigned to a profitable early stage biotech with tremendous upside potential depending on the outcome of the other trials? The following year add in full year royalties for not just the US but the rest of the world and royalties and net income are even higher. We should be profitable this quarter based solely on the 1 $8 million milestone payment and there is a chance we get another before year end if the EU accepts our application. Throw in the debio milestone next year and possible upfront licensing deal for 101 and there can be a big upside surprise in revenue. Personally I hope they don't partner up 101 but management knows better than I as to whether or not it is in our best interest.
I agree with you about Yahoo, it does suck, I just hope the regulars over there come here so I am not talking to myself LOL. What is your alias on Yahoo?
The following clinical trials had primary completion dates during 2010 and 2011 where we haven't yet heard the results. Personally I am hoping we hear what happened with the Pancreatic (9/11) and Lung (12/10) Cancer studies the most.
Combination Chemotherapy With or Without GDC-0449 in Treating Patients With Advanced Stomach Cancer or Gastroesophageal Junction Cancer Primary completion date 4/11
Cisplatin and Etoposide Phosphate With or Without GDC-0449 or Cixutumumab in Treating Patients With Extensive-Stage Small Cell Lung Cancer Primary completion date 12/10
GDC-0449 in Treating Young Patients With Medulloblastoma That is Recurrent or Did Not Respond to Previous Treatment Primary completion date 7/11
Gemcitabine Hydrochloride With or Without GDC-0449 in Treating Patients With Recurrent or Metastatic Pancreatic Cancer Primary completion date 9/11
Evaluation of Food Effect on Pharmacokinetics of GDC-0449 Primary completion date 12/11
GDC-0449 in Treating Patients With Recurrent Glioblastoma Multiforme That Can Be Removed by Surgery Primary completion date 12/11
From Curis' 10Q filed for the 3rd qtr 2011 we now know that data from operable bcc will be available by the end of this month or early 2012. For some reason I didn't know that was coming up since the primary completion date according to the clinical trials website shows a date of 11/2012. The big question for this study is how well it works and whether or not the side effects are tolerable. Even if this is prescribed for 10% (or more) of the operable bcc cases estimated at 2 million/year in the US alone, it will increase the market potential dramatically. Royalties for a company with only 30 employees will translate into a very profitable company in a relatively short period of time IMO.
Genentech is also conducting a separate phase II clinical trial of vismodegib in patients with operable nodular basal cell carcinoma, which is a less severe form of the disease and accounts for a significant percentage of the approximately two million BCCs diagnosed annually in the United States. This study was initiated by Genentech in October 2010 to test vismodegib as a single-agent therapy in approximately 50 patients with operable nodular BCC in a US-based, open label, two-cohort clinical trial. All patients will receive a 150 mg daily oral dose of vismodegib for 12 weeks. The primary outcome measure for the first cohort is the rate of complete histological clearance of target nodular BCC lesions at the time of tumor excision (which may occur up to 12 weeks following initiation of treatment) while the primary outcome measure for the second cohort is the rate of durable complete clearance of target nodular BCC lesions at the time of excision (which may occur up to 36 weeks following initiation of treatment). We expect that data will be available from this trial later this year or early in 2012. We also anticipate that Genentech will provide us with its plans for future development in operable BCC within this timeframe and we look forward to providing further updates on this in the future.
Lots of things on the horizon that could make the stock explode and that doesn't even include the Debio agreement plus the potential of CDUC 101. If that continues to impress, Curis will be a very good short AND long term play. Once we get FDA approval (assuming it happens by 3/12) it will remove the risk to investors at current prices IMO.
Why do you say expect the operable bcc results to come in Jan and not this month? We know the drug works on it based on the results of gorlins syndrome but will the side effects prove too much for it being prescribe in a lot of cases of operable bcc? If we get good news out of this study coupled with EU approval any day now and the stock could start a nice rise. I like the 80% rise in 2011 and look forward to a bigger increase in 2012 with the right news.
How long have you been following Curis? Do you post over on Yahoo at all for Curis?
Thanks, I hope this board becomes more active. I post over on the Yahoo board but that is acting up way too much and I will begin posting here and hope others follow. Investorshub is a much better place to post than Yahoo anyway.
There are many upcoming catalysts that might come any day now. Here is a short list of things we know for certain will be coming very shortly:
Operable bcc data - Due by end of year or early 2012
EU filing - Again acceptance is due by end of year or early 2012
FDA approval - Due no later than 3/8/12 but could come in about a month based on what happened earlier with other skin cancer drug from Roche which came in 2 1/2 months.
EU acceptance - Due a few months after acceptance
In addition to the above which we know will happen shortly we know the NCI is conducting many trials some of which the results are way overdue such as lung cancer, pancreatic cancer (several trials) as well as other trials. The next 6 months will be very interesting to see, hopefully it is interesting in a very good and rewarding way. GLTA.
Operable BCC results due any day now. From the 3rd qtr 10q
Tried posting over on Yahoo but that site isn't working and I think from now on I will begin posting here instead. Hopefully the regulars on Yahoo come over here. I have always liked this site better anyway but there haven't been enough people posting related to Curis here but hopefully that will change.
Here is a potential catalyst that could come out any day now. According to the 3rd qtr 10q, data from the operable bcc study could come out by end of year or early 2012.
Genentech is also conducting a separate phase II clinical trial of vismodegib in patients with operable nodular basal cell carcinoma, which is a less severe form of the disease and accounts for a significant percentage of the approximately two million BCCs diagnosed annually in the United States. This study was initiated by Genentech in October 2010 to test vismodegib as a single-agent therapy in approximately 50 patients with operable nodular BCC in a US-based, open label, two-cohort clinical trial. All patients will receive a 150 mg daily oral dose of vismodegib for 12 weeks. The primary outcome measure for the first cohort is the rate of complete histological clearance of target nodular BCC lesions at the time of tumor excision (which may occur up to 12 weeks following initiation of treatment) while the primary outcome measure for the second cohort is the rate of durable complete clearance of target nodular BCC lesions at the time of excision (which may occur up to 36 weeks following initiation of treatment). We expect that data will be available from this trial later this year or early in 2012. We also anticipate that Genentech will provide us with its plans for future development in operable BCC within this timeframe and we look forward to providing further updates on this in the future.
Curis upgrade:
The analyst is even more bullish than I am for projected sales. This is from my Schwab account otherwise I would post a link. If he sees potential peak sales of over a billion dollars, yes BILLION, how can he only give it a price target of $7? GLTA and let's hope he is in the ballpark of future revenue because even if his revenue estimates for only advanced bcc is close, his target is substantially below what the price will be in the future. Royalties of those amounts end up in the bottom line since there are no costs for royalty revenue. Here is the story:
RESEARCH ALERT-Roth Capital raises Curis to buy
10:58 am ET 07/08/2011 - Reuters
* Raises price target to $7 from $4.60
* Sees higher chance of positive study results in two cancer types for main drug
* Shares up 9 pct
July 8 (Reuters) - Roth Capital Partners upgraded Curis Inc to "buy" from "neutral," following a full presentation of mid-stage studies of its cancer drug, vismodegib, sending its shares up 9 percent.
In March, vismodegib, which is being co-developed with Roche Holding's unit Genentech, shrank tumors in patients with advanced basal cell carcinoma (BCC) -- a type of potentially fatal skin cancer.
Analyst Joseph Pantginis now saw higher chances of the drug showing positive results in treating advanced BCC, an indication for which he believes the drug will earn the company $275-$475 million in peak sales. He also sees a 60 percent chance that the drug shows positive results from the current mid-stage study in treating patients with operable BCC. Pantginis estimates peak sales potential of $650-$675 million in operable BCC.
"The combination of potential milestones and royalty flow could have a significant impact in offsetting the burn rate at Curis," Pantginis said.
He also raised his price target on the company's stock to $7 from $4.60.
The analyst saw long-term partnering opportunities from Curis' early-stage cancer compound CUDC-101.
Shares of the Lexington, Massachusetts-based company, which have gained 14 percent since the mid-stage results were reported, were up 5 percent at $3.89 on Friday morning on Nasdaq after climbing as high as $4.03 earlier. (Reporting by Vidya L Nathan in Bangalore; Editing by Sriraj Kalluvila)
.
It is years down the road for 101 approval and there really isn't any way of knowing what it will trade at since there are way too many unknown questions such as: Will they have to partner it out?; what will be the split?; what will it be approved for?; when will it be approved?; how many shares will be outstanding at that point?; and on and on.
What we do know is that if it is approved even with the above unknown's, it will be trading at many times its current level. The more immediate question will be what will the stock trade at once 0449 gets approved in 2012? Approval and milestone payments for that alone will create a nice little run up that could help fund continued developement of 101 so we won't have to parter it out unless it is very favorable to us which will increase our share price even more. Things look very promising for Curis at the current time and I am looking forward to the announcement of fda submission and approval for 0449 first and then we can look forward to the possiblilities of 101 in the future. GLTA and hopefully the second half shows as big a percentage gain in the pps as the 1st half did.
This story is from the street.com and I wonder why they only mentioned the 1 abstract? I would think positive data on the lung cancer abstract or the pancreatic abstract could provide as much or more of a pop to Curis than the one mentioned. Although Wednesday could provide good news, as the article below states, we may have to wait until the actual presentations to find out the juicy details.
http://www.thestreet.com/story/11114682/1/cancer-stocks-on-tap-asco-abstract-preview.html
BOSTON (TheStreet) -- Biotech investors take note: On Weds. May 18, the American Society of Clinical Oncology (ASCO) will be posting online the full content of cancer drug research abstracts to be presented next month at its closely watched annual meeting in Chicago.
The ASCO research abstracts will be posted on the medical society's web site starting at 6 p.m. EDT -- free for everyone to browse and download. The ASCO annual meeting -- the most important cancer drug research meeting every year -- runs June 3-7.
Biotech traders start focusing on "ASCO stocks" early in the year, well before the release of research abstracts.
A research abstract is simply a summary of clinical data to be presented at a medical conference. The abstract typically includes a brief description of the clinical study, the types of patients enrolled and sometimes, a brief summary of the study results, including efficacy and safety data.
Research abstracts can be flinty on the important details investors want to know. Think of a research abstract as a placeholder a company uses to reserve a spot at a medical meeting. A cancer research meeting like ASCO is a very hot ticket, so companies vie for presentation slots well in advance. Often, that means the cancer drug data companies want to present isn't ready or fully analyzed yet. ASCO abstracts, therefore, often summarize the study but put off disclosing the important details (like if the drug being studied works and is safe) until the actual data presentation at the meeting.
To make it easier for investors to search ASCO's annual meeting web site next Wednesday, I put together a list of abstracts most interesting to Wall Street, arranged alphabetically by drug sponsor.
Roche and Curis(CRIS_)
Abstract No. TPS173
Abstract title: A randomized, double-blind placebo-controlled phase II study of FOLFOX with or without GDC-0449 (vismodegib) in patients with advanced gastric and gastroesophageal junction carcinoma (NCI 8376).
Copied from Yahoo board for ASCO presentations that I posted on 4/19/11. Sure hope what we hear is promissing news regarding the studies. We need promissing results on other cancer types for us to get to a much higher level as far as stock price is concerned and information from ASCO could provide that, at least that is my hope. GLTA
ASCO 2011 abstracts
Here is an early look at what we will hear about at the upcoming ASCO meeting in June. I did a search on the early planner and found the following presentations. I could not find anything so far related to the bcc results being presented but this was just the advanced planner section and I believe the release date for abstracts will be May 18th. We will hear info on Pancreatic, Gastric and NSCLC based on the abstracts found so far.
Abstract #TPS173
A randomized, double-blind placebo-controlled phase II study of FOLFOX with or without GDC-0449 (vismodegib) in patients with advanced gastric and gastroesophageal junction carcinoma (NCI 8376).
Deirdre J. Cohen, MD
Poster: 45C
----------------------------------------------------- ---------------------------
Abstract #10537
The role of GDC-0449, a hedgehog (Hh) pathway inhibitor, on epithelial–mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC) cells lines and its effect on erlotinib and cisplatin.
Main Maitah
Poster: 20D
----------------------------------------------------- ---------------------------
Abstract #3092
Phase I trial erlotinib, gemcitabine, and the hedgehog inhibitor, GDC-0449.
Shanique R. Palmer, MBBS
Poster: 18A
________________________________________
This is a Hedgehog result not necessarily 0449
Abstract #7065
Hedgehog inhibition and radiation therapy in non-small cell lung cancer.
Jing Zeng, MD
Poster: 24E
----------------------------------------------------- ---------------------------
de Sauvage presentation now available.
http://webcast.aacr.org/console/player/15176?mediaType=audio
From what I can tell it is well worth listening to although not a whole lot of new info. He did say that one of the 33 patients in the phase 1 study was probably mis diagnosed when admitted to the study and the tumor type he had, if they had diagnosed him properly at the beginning, they would have realized that he wouldn't have responded and would not have let him in the study. He was one of the 4 that were shown to have had disease progression out of the 33 enrolled. What that means to me is that the phase 1 study is even more impressive since instead of an 88% positive response rate it would have been over 92% when taking into account stable disease as well as partial and complete responses.
He discussed the Medulloblastoma patient who developed resistance and felt that the resistance could have been developed prior to the treatment and they isolated the resistance. He feels that possibly the resistance can be overcome with a cocktail approach and have identified a compound in which to test it. He said there could be other resistance types built up and they might be able to overcome them as well once the resistance type is determined.
Overall it was educational but nothing really new as far as I could tell but I don't understand the science behind it since I am a CPA and not a scientist and those with the correct background may have a different take. Onward and upward for Curis.
Additional link courtesy of Hedgehog_info over on Yahoo, well worth the time to go through all the links at the site.
http://www.biooncology.com/research/hedgehog/index.html
AACR meeting 4/2-4/6
This is from a post I made over on Yahoo. I also copied a related post from another that is worth the read.
Here are the links that I found when I did a search on hedgehog. The first link is to the 45 results that come up at the upcoming conference. Whether it is directly linked to 0449 by specific mention of it or indirectly linked through the totally new way of treating cancer that could arise with hedgehog, it is still good for 0449 and Curis IMO.
45 results for hedgehog at upcoming conference:
http://www.abstractsonline.com/Plan/SSResults.aspx
Targeting the hedgehog pathway in meduloblastoma and basal cell carcinoma (presented by Frederick De Sauvage)Wednesday, Apr 06, 2011, 9:30 AM -10:00 AM
http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=9780ea8d-00b7-4f3b-b11d-914c36acd260&cKey=0dd60c9e-af60-4603-88af-ef7926a7c6ab&mKey=%7b507D311A-B6EC-436A-BD67-6D14ED39622C%7d
Translation of Basic Science into Successful Clinical Outcomes
http://www.abstractsonline.com/Plan/ViewSession.aspx?sKey=9780ea8d-00b7-4f3b-b11d-914c36acd260&mKey=%7b507D311A-B6EC-436A-BD67-6D14ED39622C%7d
An investigator-initiated, phase II randomized, double-blind, placebo-controlled trial of GDC-0449 for prevention of BCCs in basal cell nevus syndrome (BCNS) patients (my comment, this is 0449)
http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=289dc36e-8df8-4ad3-9887-2b7f4b071e8c&cKey=d602b85a-0834-4720-8bac-b37b85a25068&mKey=%7b507D311A-B6EC-436A-BD67-6D14ED39622C%7d
Opening Plenary Session: The Future of Cancer Research: Challenges and Opportunities (my comment, notice Von Hoff and Jean Yang's presentations)
http://www.abstractsonline.com/Plan/ViewSession.aspx?sKey=289dc36e-8df8-4ad3-9887-2b7f4b071e8c&mKey=%7b507D311A-B6EC-436A-BD67-6D14ED39622C%7d
The Hedgehog Signaling Pathway: Biology and Therapeutics (my comment, this is a major symposium which includes presentations by Jean Yang)
http://www.abstractsonline.com/Plan/ViewSession.aspx?sKey=9be61e9e-e01d-4b76-b2cd-777910741fff&mKey=%7b507D311A-B6EC-436A-BD67-6D14ED39622C%7d
Stromal desmoplasia is induced by a hypoxia and HIF-1a mediated increase in sonic hedgehog formation in pancreatic cancer (my comment, this includes presentations by Von Hoff who has done other 0449 testing for bcc, could we find out how it is doing in pancreatic setting?)
http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=47bc7326-261b-4a47-bce4-058d0936a256&cKey=6d457c6a-ed81-4a87-b524-85af3ccd2cbe&mKey=%7b507D311A-B6EC-436A-BD67-6D14ED39622C%7d
Evaluation of optimal dosing schedule on steady-state pharmacokinetics of orally administered hedgehog pathway inhibitor GDC-0449 in cancer patients
http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=271ac6e9-4b12-4e9d-afa4-854888e7c268&cKey=88c2958c-222b-42d8-8eab-e834bf9bcfd4&mKey=%7b507D311A-B6EC-436A-BD67-6D14ED39622C%7d
Here is the search result for Von Hoff who may provide updates for 0449 in pancreatic cancer. Not all of these relate to hedgehog. I don't know for certain if his involvement in hedgehog with pancreatic cancer is 0449 related but I do know he was one of the lead investigators in Scottsdale for the phase 1 bcc testing.
http://www.abstractsonline.com/Plan/SSResults.aspx
Based on the above results, I am very optimistic we could find out a decent amount of information out of the conference. Hedgehog is clearly is viewed as a potentially game changing treatment option which could mean additional cancer types for 0449 to treat. GLTA, the next couple of weeks will be interesting to say the least.
Courtesy of Hedgehog_info over on Yahoo
Re: aacr meeting 4/2-4/6
Here are few of the more important ones....
http://www.pathway2curis.com/hedgehog-aacr-2011-t55.html
The more information you can get from the company the better for all of us. Good luck with your questions, I hope you can get something out of him.
Re BCNS, here is how the study was to be designed. The fact that the placebo group is now being offered 0449 is not surprising. It is great news because of what it means but I am not too sure if this is something that Curis would be allowed to disclose since it is part of the ongoing study that they are not conducting. They are at the mercy of Roche and NCI as to what they are allowed to disclose IMO.
Detailed Description:
This is a Phase II, 18 month, double blind, randomized placebo-controlled, two arm multicenter clinical study design. During the 18-month treatment period, the safety and chemopreventive efficacy of 150 mg/day GDC-0449 versus placebo will be assessed, and include evaluations of the skin at monthly intervals for the first three months and then every 3 months for the next 15 months. Removal of new surgically eligible BCCs (SEBs) will be done by primary skin care physicians (PSCPs) or at Study Centers. A Data Safety Monitoring Board (DSMB) will review unblinded results for an interim analysis when 20 subjects have completed 12 months of drug. This review will focus on adverse events and efficacy results. Subjects will be monitored for the development of new SEBs after they discontinue study treatment. At the end of the 18 months, given that the observed adverse events are minimal, patients on placebo will be offered the opportunity to take GDC-0449 for 18 months in an open label continuation, followed by six months observation, and patients on GDC449 will be monitored for the next 24 months for assessment of the duration of benefit after stopping the drug.
http://clinicaltrials.gov/ct2/show/NCT00957229?term=gdc-0449&rank=1
The company has stated that they expect results in the first half of 2011 and the data if positive, will serve as a basis for NDA filing. In 2009 they had projected late 2010 as to the expected results so that estimate got delayed somewhat. Hopefully the results are announced early 2011 but I am guessing it will be during the second qtr at the earliest since they said 1st half and not first qtr.
I wish more investors would use the IHUB board for Cris, I like the way this board is set up so much more than the Yahoo board but nobody seems to post over here. I guess if we get good results it will attract more investors to the stock and in turn to this board.
Good luck with your investment and I believe the drug works, it is just a matter of timing and whether or not current investors like us will benefit or not. I hope the approval comes quickly so we don't see too much future dilution going forward. Seeing a 10% dilution in the near term removes a lot of risk IMO and I really hope they are able to time it so they raise the funds at $2.50 or higher net price to the company. The way the stock is moving they may be able to raise the funds over $3 which would be great news to me.