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Gregory Pepin is a co-partner of a Wealth Management company in switzerland. He has a Master of Science degree in Finance and Actuary Science from HEC Lausanne (Switzerland). He also teaches Finance at the University of St. Joseph (Lebanon). Gregory is a strong believer of the Graham Theory that... More
  • AB Science : The French Exception ? 29 comments
    Oct 31, 2012 1:05 PM | about stocks: ABSCF

    On October 30th 2012, AB Science announced a breakthrough news for Pancreatic Cancer.

    Let's go in detail with the press release, just to make sure people really understand the true meaning of that news :

    "AB Science SA (NYSE Euronext - FR0010557264 - AB), a pharmaceutical company specializing in the research, development and commercialization of protein kinase inhibitors, announced today the results from a phase 3 study evaluating the effect of masitinib in combination with Gemzar® (gemcitabine, Eli Lilly and Company) on overall survival (OS) in patients with pancreatic cancer. Briefly, masitinib in combination with Gemzar® significantly extended median OS by 6 and 2.7 months in two independent patient populations, representing 65% and 45% of the overall population; namely, patients with a genetic biomarker - collected from simple blood sample - indicative of aggressive disease progression, and patients with cancer pain. Pain intensity and the discovered genetic biomarker were shown to be of prognostic value for survival under Gemzar® alone and at the same time predictive of increased survival with masitinib in combination with Gemzar® for those patients identified as having a poor prognosis with Gemzar® alone."

    Nobody succeed in Pancreatic Cancer in the past, the only viable treatment is Gemzar (Gemcitabine), as we see in that portion of the release. It seems that AB Science has been statistically significant in term of efficacy for two independent group (that could overlap each other) of 65% and 45%. That is an impressive samples and more important a first in that Cancer. Now, more important we see the notion of BioMarker and Genetics. It is the first formal case that I know off, where result are clearly linked to genetic for Cancer. That is the future of medicine concerning Treatment of Cancer.... and AB Science seems to be at the top of it.

    AB Science also announced that the European Medicines Agency (EMA) has accepted to review a Marketing Authorization Application (MAA) for conditional approval of masitinib in combination with Gemzar® in the treatment of pancreatic cancer, following filing of this dossier.

    Needless to say that it speaks by itself. The EMA already accepts to study the conditional approval that is, with GIST 2nd Line of treatment, the second AMM under study. Pretty impressive.

    Full data has been submitted for presentation at the American Society of Clinical Oncology (OTC:ASCO) Gastrointestinal Cancers Symposium (24-26 January 2013, in San Francisco, California).

    I guess many Fund that never heard of AB Science will have their awareness raise concerning AB Science during that conference as I assume, if the EMA accepted the AMM for study and that AB science deposits some patents and based on the little info that this release provide, the full data will probably be pretty impressive to say the least and could be one of the attraction at ASCO.

    Filing for the conditional approval of masitinib in combination with Gemzar® in the treatment of non resectable, advanced adenocarcinoma pancreatic cancer was accepted by EMA on the basis of results from a phase 3 study that showed masitinib in combination with Gemzar® significantly extends overall survival in two independent patient populations having the worst prognosis. These populations consisted of patients with a gene expression profile (or genetic biomarker) indicative of aggressive disease progression (65% of pancreatic cancer patients), and patients with cancer pain (45% of pancreatic cancer patients). In this prospective, international, randomized, double-blinded clinical trial, 348 patients received either masitinib in combination with Gemzar®, or placebo in combination with Gemzar®. A planned ancillary pharmacogenomic study, based on RNA extracted from whole blood samples before treatment start, was also conducted to identify genetic expression patterns predictive for overall survival and/or treatment benefit.

    AB Science seems to have found a clear genetic pattern that they can diagnose to identify the profile of patient and therefore the right treatment to take (Gemcitabine alone or along with Masinitib). I assume the diagnostic by itself already have a lot of value as it is a first clearly. It also explain a little more why the EMA accepted to review the MMA

    AB Science made two important discoveries based on data from these studies.

    • First, pancreatic cancer patients characterized by the discovered genetic biomarker (approximately 65% of all patients) reported very poor survival when receiving placebo plus Gemzar®, with a median OS of 5 months. However, this same genetic biomarker was highly predictive of significantly extended survival in patients receiving masitinib in combination with Gemzar®, with a median OS increased by 6.0 months to 11.0 months, corresponding to a hazard ratio of 0.29 (p=0.000038). OS rates at 12 and 18 months were respectively, 41.4% and 18.5% in the masitinib plus Gemzar® treatment arm versus 11.1% and 4.2% in the placebo plus Gemzar® arm.

    So now we come down to the clear data....so 65% of the patient are reacting positively to the combinaison of Masintinib and Gemzar. That is an impressive level. Aside of being able to identify exactly the profile concern, the data itself are impressive : Hazard Ratio of 0,29, that is exceptionnal. Usually when you have an HR of 0,66 it is already a hit so the lower the HR is the best it is.... The survival rate at 12 and 18month compare to placebo + Gemzar is just incredible. But now, the biggest news is the P-Value.... We are talking about a P-Value of 0,000038. To give you an order of idea it is the same P-value for the Bozon of Higgs.... that is the most impressive portion of those data (along with the HR i would say)

    • Second, patients presenting with a certain threshold of pain intensity at the time of study entry (approximately 45% of all patients) were revealed to have a very poor prognosis when receiving placebo plus Gemzar®, with a median OS of 5.4 months. In these patients, the combination therapy of masitinib plus Gemzar® showed a statistically significant extended survival, with median OS increased by 2.7 months to 8.1 months, corresponding to a hazard ratio of 0.61 (p=0.010). OS rates at 12 and 18 months were respectively, 32.2% and 18.2% in the masitinib plus Gemzar® treatment arm versus 17.8% and 7.8% in the placebo plus Gemzar® arm.

    Those data are less impressive then the previous one, but stays very strong and are still unique in the pancreatic cancer. The Hazard ratio is strong and the p value is good too. Again here the impressive part is the 12month and 18month survial along with the Median OS.

    Besides being predictive for masitinib plus Gemzar® treatment efficacy, these two factors were also of prognostic value for overall survival in patients treated with Gemzar® as a single agent. Regarding the genetic biomarker, patients harboring this 'aggressive genetic fingerprint' had a median OS of 5.0 months whilst patients without this fingerprint had a median OS of 14.3 months. Regarding the prognostic factor of 'pain intensity', patients exceeding a certain threshold of pain at baseline had a median OS of 5.4 months versus 15.4 months in patients without pain.

    Now, according to me, that portion of the release is also very impressive because it talks about the diagnostic aspect of their discovery. It seems that AB Science have been able to demonstrate (and probably be able to diagnose) the profile of each patient and therefore they can define which treatment is the best. Aside of that, it also show a huge difference between a third of those patient that has a OS median of 14,3month and the two third that has a OS median of 5.0. The diagnostic tools AB science probably develop is more then valuable and should not be ignore in the middle of that amazing release.

    Results in the overall study population did not show a significant advantage for masitinib in combination with Gemzar® as compared with Gemzar® treatment alone. Median OS was 7.7 months in the masitinib plus Gemzar® treatment arm versus 7.0 months in the placebo plus Gemzar® treatment arm (p=0.74; hazard ratio=0.90). This finding of a non significant survival improvement in the overall population is explained by the fact that masitinib is not indicated when Gemzar® is highly efficient; namely, the situation defined by an absence of both pain and genetic biomarker detecting "aggressiveness".

    No surprise here, and it in fact increase the value of the previous data disclose.

    In fact, I will give you some personal though overall and the end of that post to make you realize how big of a revolution that is...

    Olivier Hermine, MD, PhD, President of the Scientific Committee of AB Science commented: "The prognostic factors of 'pain intensity' and 'aggressive genetic fingerprint' revealed by AB Science are two major discoveries in this devastating disease that has a high unmet medical need. We previously knew that pain was correlated with poor prognosis in pancreatic cancer. Our current working hypothesis is that pain flags the presence of mast cells in the tumor microenvironment and mast cell activation may help transform the tumors into a more aggressive form. On the other hand, the genetic biomarker is really revolutionary since it would be the first time that RNA expression from whole blood samples is capable of predicting overall survival in patients depending upon the treatment received. In addition, this genetic biomarker could be used as a prognostic tool: patients with the 'aggressive genetic fingerprint' and receiving the standard treatment of Gemzar® monotherapy had a median OS of only 5 months, whilst patients without this genetic biomarker survived on average for 14.3 months. It is encouraging that masitinib seems to improve significantly survival in patients with the worst prognosis and who represent the highest unmet medical need".

    Alain Moussy, CEO of AB Science declared: "We knew that masitinib had an antimetastatic potential thanks to our recent GIST study as 2nd line treatment in Gleevec-resistant patients. That study revealed masitinib did not outperform sunitinib, the current 2nd line treatment for GIST, in terms of PFS (progression-free survival) but did significantly improve median OS with a hazard ratio of 0.29. The pancreatic cancer phase 3 study delivers a second clinical proof of masitinib's antimetastatic effect in cancer, again showing comparable PFS between treatment arms whilst overall survival was significantly increased in two independent subpopulations. In patients with 'pain' median OS was increased by 2.7 months with a corresponding hazard ratio of 0.61, and in patients with the 'aggressive genetic fingerprint' median OS was improved by an impressive 6.0 months with a hazard ratio of 0.29, when treated with the masitinib plus Gemzar® combination. It seems that the inhibition of mast cell activity in cancer is one of the key drivers of masitinib. However, masitinib evidently does more since other tyrosine kinase inhibitors of mast cells have failed in the pancreatic cancer or GIST indications. Masitinib seems to touch key pathways that are involved with metastatic progression in cancer, the very mechanism which eventually leads to death".

    Masitinib received orphan drug designation in the treatment of pancreatic cancer from both FDA and EMA.

    Both quote are very instructive and explain even more the power of Masinitib and its potential. The antimetastatic effect can clearly be consider for many others cancers. One could say, sky is the limit and he might not be wrong.

    Some personal thoughts :

    I would like to say a couple of things that draw my interest and share it with you :

    - the P-value of the study is just amazing, especially on Pancreatic cancer that is ..Unique

    - the true increase of survival on Pancreatic is even more impressive. If you look in details you will see that the combination of their diagnostic discovery + their efficacy on 65% of patient leads to a much higher OS Median. Here is why :

    With their diagnostic, they identify 35% of the population with gemcitabine alone has a median OS of 14,3month, 65% other had a median OS of 5.0 but now their true Median OS will be 11month thanks to the treatment using Masintinib + Gemcitabine.

    So the real Median OS now for pancreatic cancer, if we use the combination of their diagnostic tools + Masintinib + Gemzar or Gemzar alone (pending the diagnostic) is : 35% * 14,3 + 11*65% = approx 12,3month... that is impressive... and that is the true meaning of that press release.... for people that take times to read.

    - Value of the market : 220K case per year, let's assume 80K in accessible market for AB Science, 65% of 80K = 52K. Assumption of treatment price : 25K euros? So revenue per year = 52K * 25K = 1,3 billions euro per year.

    - Gaining market share won't be hard because the treatment would be in addition to Gemcitabine and therefore carries a great interest for Gemcitabine producer as it increase revenue on their product too.

    - It was the hardest Phase 3. Analyst had pretty no expectation on it. So just imagine the integration of that in the true value of the company over the long term?

    Anyway, to summarize, AB Science is just getting one step closer to their goal of being a Pharma. The P-value and data just has that one (along with GIST 2nd Line) are just another "solid" (if not guarantee) element that they will succeed. It is now just a matter of TIME.

    What is the true value of AB Science? I won't go into describing what I believe is the long term true value except if I'm ask because I think any people trying to calculate it will realize it is in billionS if not tens of billions....

    However, here is the joke...... (there is always a joke).

    You would assume that a company with :

    - 8 phase 3 on-going

    - 1 Phase 3 data on pancreatic cancer (where everyone failed) with an unbelievable HR and P-value on a pretty big population size (and therefore market)

    - 2 Phase 2 data with statistical significantly in term of p-value on efficacy (GIST 2nd Line but also - let's not forget - Alzheimer)

    - 2 AMM under study by the EMA.

    - A probable product to be approve in the next 2 years top

    - FULLY OWN their product and therefore the profit that it could generate

    - APPROVAL already in Veterinary (with some small double digit growth revenue)

    - Enough cash without revenue until first potential approval

    would be value how much ? by Nasdaq standard you would assume somewhere around 2-3 billions right ?

    Well here is the French Exception, AB Science is value as i'm writing today less then 600 millions euros (780Musd). Amazing right ? Why ?

    There is many reason according to me :

    - Euronext isn't a biotech index

    - Awareness on the company is still low

    - Company is control by the founders which kills the "speculation effect"

    - Most Fund in Europe (that are the mainly expose to the story) are not clever and long term enough to realize the true undervalue of the company

    - French Quality : We always have hard trouble in believing in true success and therefore we always miss it (the gain of it) so we are often late in the party....

    - Retail base shareholder that also don't think long term. Small profit is enough.... they would say :)

    Another French exception : Doing -4% on such a news... They did -10% on Alzheimer Phase 2.... so i guess they still had room to drop further on such a great news day.

    Anyway, I will keep the same position I always kept all along : IT IS A SCREAMING BUY FOR ANY MID-LONG TERM investor that just know HOW TO COUNT.

    IT WILL EVENTUALLY RISE TO THEIR TRUE VALUE IN THE LONG TERM. PATIENT and WISE long term INVESTOR will understand that days like today and value like now are gift from god for people that missed the train many times already.

    So I hope you guys will take full advantage of it. AB Science just did a breakthrough in Science... and nobody realized it in France so far... It is the Famous French Exception (if not the European Exception) so take advantage of it... because amazing story like that could spread out quickly at any moment...

    DISCLOSURE : LONG through equity, through ALL the convertible debt and buying regularly to take advantage of the stupid market

    DISCLOSURE 2 : Thank you stupid market :) keep doing that, I LOVE IT

    DISCLOSURE 3 : Hopefully I won't be the only one taking advantage of the stupid market :)

    Disclosure: I am long OTC:ABSCF.

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Comments (29)
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  • stock_khoj
    , contributor
    Comments (19) | Send Message
     
    Hi Greg,

     

    Thanks for sharing your thoughts and interpretation of the results. As you mentioned many times earlier, it's a great opportunity for a long term investor. I don't understand why can't they do whatever needed to get the ADRs listed in US exchanges. It could boost the stock price up 100%+ instantly.

     

    By the way, I was wondering, wouldn't masitinib qualify for MAA / CHMP accelerated assessment/ approval or AB Science didn’t ask for it. The Orphan designation (already granted) should make is eligible for accelerated assessment for both the indications GIST & Pancreatic Cancer. Accelerated assessment can be completed in 150 days.

     

    Also can they file for US FDA approval for Pancreatic Cancer treatment with the bio-marker or pain as the criteria or do they need another P3 before they can file for FDA? If they need another P3 trial, can they request approval for compassionate use?

     

    Look forward for your thoughts on these.

     

    Thanks
    2 Nov 2012, 02:26 AM Reply Like
  • Gregory Pepin
    , contributor
    Comments (121) | Send Message
     
    Author’s reply » Going for an ADRs listed US Exchange now would be expensive and a waste of short term money. You should see the low valuation compare to the true long term value as an opportunity to take advantage off. Eventually the price will rise to the real value of the company that is much much higher.

     

    AB Science could qualify for it i guess BUT :
    Remember, the overall population went negatif (or should I say not stastitical significant) so due to that, you can only go for the conditional approval (for the sub group) since the full approval request that the overall population is positive.
    On the positive side, we know, thanks to the amazing p-value that if - and they will probably do it - they do a confirmation study focus only on the sub group that succeed, the overall population will be positive on that study and therefor they would be entitle to request full approval with fast track process.
    Now the other good news, due to the very tough death rate of that disease, the phase 3 focused on the sub group would be very fast (and they could still get along with the phase 3 underway the conditional approval).

     

    Concerning the US FDA, I assume they are in discussion now for either compassionate usage or conditionnal approval like with the EMA. But again, as soon as they get a phase 3 result (that would be fast again due to the nature of the disease) positive on the overall group because of the biomarket and pain criteria as the focus of enrollment. They will be able to go all-in in term of approval with both EMA and FDA.

     

    THE MAIN THING TO UNDERSTAND :
    The sub group is pretty big (we are talking about 65% and 35% patient that are "independant" even if they do overlap also). That is a very big market
    The P-value (especially for the 65% subgroup) makes the success of a potential confirmatory study on the subgroup pretty much certain...
    They will eventually succeed in getting approve on that subgroup because both efficacy and p-value is huge, just a matter of time...
    For long term investor time is your friend ;) take advantage of it.

     

    Also, I'm pretty sure, they have the diagnostic tools or mechanism and i'm pretty sure it is a easy and fast process or they would have specify it since it is more then important in their success and on top of that, they cannot have a long diagnostic process due to the very low median OS.

     

    I think more surprise will come on that study.

     

    People should ask themself, what did they patent ?
    My gut feeling : The biomarker they found and the diagnostic tools link with it.... :) would make sense..... no ? :)
    2 Nov 2012, 06:16 AM Reply Like
  • stock_khoj
    , contributor
    Comments (19) | Send Message
     
    Thanks Greg,

     

    Very insightful. I understand now. I can't think of anybody else who knows the company well over you and you are prompt in responding as well. Appreciate it

     

    Thanks again for your efforts to educate the investor community.
    2 Nov 2012, 11:46 AM Reply Like
  • Emeric Blond
    , contributor
    Comments (3) | Send Message
     
    Great explanation !! Thanks !
    2 Nov 2012, 04:06 PM Reply Like
  • su
    , contributor
    Comments (9) | Send Message
     
    Think you may be overegging the pudding;
    The primary end point was not met in this study although as you say sub group analysis was very impressive regarding the fantastic p value; don't believe the americans are very keen on subgroup analyses in cancer trials though.
    Further, we haven't been told of the side effects of the treatment and how many dropped out through side effects.
    That said, I was sufficiently encouraged to buy a few more last Thursday in view of the potential and the many trials underway not least the mastocytosis trial which should hopefully succeed.
    4 Nov 2012, 02:52 PM Reply Like
  • Gregory Pepin
    , contributor
    Comments (121) | Send Message
     
    Author’s reply » Just to answer your remark :
    - We are talking about Pancreatic Cancer, and not Prostate Cancer or anykind of cancer that has already tons of treatment available.
    - The real data people should look is the combinaison of Masinitib and their diagnostic system. Both together allow to know which group you are in and therefor expend your OS Median.
    - Concerning side effect, well we know toxicity of AB Science Molecule is good because it has been approved to be tested in non oncology and also on top of that, the GIST phase 2 (2nd Line) trial showed safety data better then Sutent with a statistical significancy.
    - I agree with you that "the common" investor will not look beyong the "overall population" whereas the clever one will look deep and see that 100% of the population is concern by AB Science :
    35% using only their diagnostic system
    65% using the diagnostic then the treatment....
    And by the way 65% for a sub group, that is pretty impressive....
    Finally, they always said they would add a genetic study at the end of pancreatic phase 3 study, that is a clear message that from the beginning they knew they would go for sub-group and not overall population but they probably had to go for the overall population to figure out the sub-group. I wouldn't be surprise (I would even expect) a follow up Phase 3 study on subgroup only that will show this time "Efficacy" for the entire population so that the "common" investor will be happy... too bad he will miss the buying opportunity the "clever" investor will have already see by reading in details the data.

     

    I think long term is looking pretty good here... :)
    5 Nov 2012, 07:56 AM Reply Like
  • su
    , contributor
    Comments (9) | Send Message
     
    Just a little worried by the other drugs under development in phase 3 for pancreatic cancer including abraxane, and the Clavis drug not to mention the Threshold pharma drug in phase 2; the two phase 3 trials are about to read out in the fourth quarter
    6 Nov 2012, 09:32 AM Reply Like
  • FOURMI
    , contributor
    Comments (9) | Send Message
     
    I agree that the Pancreatic cancer environment might change within the next couple of years, this will likely become a stratified market. Other players my come in: like Abraxane with their SPARC biomarker, Clavis with their hENT-1 biomarker, trametinib, etc.
    However, I do not recall I have ever seen results that were so striking (HR=0.26 for overall survivall !) in a subpopulation that represents 65% of patients, and that is detected only with blood sampling (as far as I know, SPARC and hENT-1 require tumor biopsies, so invasive stuff...).
    7 Nov 2012, 05:51 AM Reply Like
  • FOURMI
    , contributor
    Comments (9) | Send Message
     
    I agree, that the Pancreatic cancer environment might change within the next couple of years, this will likely become a stratified market. Other players my come in: like Abraxane with their SPARC biomarker, Clavis with their hENT-1 biomarker, trametinib, etc.
    However, I do not recall I have ever seen results that were so striking (HR=0.26 for overall survivall !) in a subpopulation that represents 65% of patients, and that is detected only with blood sampling (as far as I know, SPARC and hENT-1 require tumor biopsies, so invasive stuff...).
    7 Nov 2012, 05:52 AM Reply Like
  • su
    , contributor
    Comments (9) | Send Message
     
    Fourmi
    Thank you for that comment;
    as a hstopathologist, I should be aware of how difficult pancreatic tumour biopsies can be to interpret though their number seems to have gone right down over the years perhaps as a result of centralisation of hepatobiliary surgery in this country, the UK...
    7 Nov 2012, 03:11 PM Reply Like
  • FOURMI
    , contributor
    Comments (9) | Send Message
     
    Hi Su,
    I have no experience with it but I have always heard that those pancreatic tumor biopsies were difficult to perform (it is obviously easier to biopsy skin Melanoma), you seem to agree with that. Hence, there is a big advantage if a stratification biomarker is based on blood sampling.
    I have no idea either on how difficult it is to interpret those pancreatic biopsies, but what do you mean by that? In the case of SPARC and hENT-1 markers, I believe the tests are done by IHC, and that a score is defined in both cases. I guess the evaluation of those IHC scores is not always black or white, so the conclusion may be difficult to draw in some cases; is that what you mean by "difficult to interpret"?
    8 Nov 2012, 02:49 PM Reply Like
  • FOURMI
    , contributor
    Comments (9) | Send Message
     
    Gregory, I believe the whole question to determine the risks of investing in AB Science now is: "what could prevent masitinib to be approved for pancreatic cancer by EMA?".
    I guess we can list the following risks:
    - EMA might not like the retrospective analysis of their stratified population.
    - EMA might find the number of patients tested in this population a little to low (320*0.65 in phase III = 208 patients, only half of them treated with the experimental drug... only 100 patients at the end of the day).
    However, given the relatively good safety profile, + the great benefit that seems to be brought, I guess they could receive a conditional approval for the subpopulation identified.
    Now, the next question is: "what could prevent AB Science to not maximize this approval and make the best of masitinib approval in pancreatic cancer?". The risks are:
    - No marketing / sales force... so it might be difficult to maximize the profits if they want to keep control of marketing and sales.
    - What about pricing & reimbursement? Even if masitinib gets approval in EU, there is no guarantee that it will get reimbursed by public healthcare systems, given the small number of patients in phase III.
    - Finally, what about the US market? When do they want to submit, how are they compliant with the companion diagnostics regulations, what is their sales force there?
    8 Nov 2012, 02:52 PM Reply Like
  • Gregory Pepin
    , contributor
    Comments (121) | Send Message
     
    Author’s reply » Those are very good question. I'm going to answer them below : (copy paste your comment)

     

    - EMA might not like the retrospective analysis of their stratified population.

     

    That is a real short term risk to consider. AB Science took the approach to define the stratified population from an overall general population. They couldn't do different anyway and had no choice. Now the EMA (and FDA) could simply reject that approach in the short term by asking a confirmatory study and provide no conditional approval until the study is done.
    However, that is a pure short term risk and AB science should be look at as a great long term buying.
    The confirmatory Study that will anyway probably done (since it would also be mandatory with a conditional approval) will most likely be very fast and won't need full enrollment due to the significant difference in survival that will lead to probably a quick closing of the study).
    Remember two elements: HR and the p-value. Those two elements just confirm that it is just a matter of time to get it approve.
    will it be :
    - Conditional Approval + Confirm study + Full approval following
    - No conditional Approval + Confirm Study + Full approval following ?

     

    Won't change much as it will end up with full approval within the next 24-36month top i would say. Odds of success : 1-p-value = 99,9996% so we are pretty good here)

     

    - EMA might find the number of patients tested in this population a little to low (320*0.65 in phase III = 208 patients, only half of them treated with the experimental drug... only 100 patients at the end of the day)

     

    Well, Pancreatic cancer being a very aggressive disease that has no real treatment and considering the solid benefit and the good safety profile. I think you won't need to enroll thousands and thousands of patient because you have a very solid p-value and a great HR. I would expect the confirmatory study to be around the same size as the primary pancreatic study however i would think it would be done within 12-18month due to quick differentiation that would force the study to be done earlier for ethical reason. (Big difference in death rate for example between placebo and non placebo).

     

    - No marketing / sales force... so it might be difficult to maximize the profits if they want to keep control of marketing and sales.

     

    Agree on the risk of marketing. Now two elements to keep in mind :
    - Pancreatic cancer treatment provided by AB Science comes in complement to the one in place so they won't be any "negative competition" from Gemcitabine but in fact probably help from it as it would also increase revenue for Gemcitabine.
    Also, Pancreatic Cancer being so aggressive it is most likely easier to get to the patient then other disease because the clock is ticking and i would assume patient are more aware (or become more aware) about clinical options.
    Finally, we shouldn't exclude licensing either however, licensing AFTER approval provide a great share of revenue that is much more favorable to AB science (50/50? even better since they control the supply chain).

     

    - What about pricing & reimbursement? Even if masitinib gets approval in EU, there is no guarantee that it will get reimbursed by public healthcare systems, given the small number of patients in phase III.

     

    Cancer being a priority and Cancer pricing is pretty much set by healthcare systems. I wouldn't worry about that. Keep in mind that the cost of development AB Science occured to develop their product until approval is pretty low compare to the industry standard (we won't reach the 200Meuros spent for all the application to be approvable) therefor they are much more flexible in term of pricing then we could think. Cost of production being most likely very low, return will stay pretty high.
    Now I would expect the product to be a grade A drug so you could expect cost around 30 to 50Keuros fully reimburse due to the high benefit it provides and the high priority cancer has and the orphan drug status it carries;)

     

    - Finally, what about the US market? When do they want to submit, how are they compliant with the companion diagnostics regulations, what is their sales force there?

     

    I assume they probably are in discussion with the FDA. Now being a Euro company probably makes advancement less easier then being a US company. It is the same for US company toward EMA (Check ONYXX for example, they have conditional approval in FDA for one of their drug but need to do phase 3 with no conditional approval in europe).
    Now the nature of the disease we are talking about could make things easier for AB Science but I think the FDA and the EMA will follow at the end if you have a vision of 24-36month. Now in the short term, hopefully they are talking with them and hopefully it will end up positive and similar to EMA position.
    Now for sales force etc. I would duplicate my answers for EMA. Markets are similar etc. Now for reimbursement, the process is longer but considering that Meds such as Dendreon product has opportunity to be reimburse, I don't see any reason why a drug with an HR so great wouldn't be reimburse too. Orphan Drug status helping its case a lot ;)

     

    Overall i would say that the HR and the p-value (same for GIST) just indicate that now it is only a matter of time before success (meaning approval) so any investor willing to hold onto their shares will be greatly reward. Now in the short term there is a lot of potential news catalyst that could accelerate the run up such as FDA situation, other data, ASCO presentation, EMA position, New studys underway, Vets collaboration or development etc. etc.
    9 Nov 2012, 05:48 AM Reply Like
  • FOURMI
    , contributor
    Comments (9) | Send Message
     
    Thanks, for your very thoughtful comments and answers.
    I agree with you general conclusion that even if (conditional) approval is not granted this time, it will come at some point anyway (although the market environment may change dramatically until then).
    9 Nov 2012, 08:46 AM Reply Like
  • su
    , contributor
    Comments (9) | Send Message
     
    Fourmi
    Pancreatic biopsies are difficult to obtain and dangerous to obtain as there are a lot of arterial vessels around the head of the pancreas, the commonest site for tumours, which can be punctured...
    Interpretation is also difficult as chronic pancreatitis can look quite similar to adenocarcinoma, particularly well differentiated carcinoma, and a lot of pancreatic cancers appear well differentiated which is quite surprising for such a lethal tumour.
    No direct experience of hent or Sparc immunostains but doubt whether they will tell you whether a given biopsy of pancreas is benign or malignant.. most immunostains at other sites don't.
    8 Nov 2012, 05:40 PM Reply Like
  • Gregory Pepin
    , contributor
    Comments (121) | Send Message
     
    Author’s reply » So we could say that the approach of AB science with a simple blood sample gives them an amazing advantage to find out the right treatment for pancreatic patient ?
    9 Nov 2012, 05:48 AM Reply Like
  • su
    , contributor
    Comments (9) | Send Message
     
    Have to agree that this is a much less invasive approach though a biopsy might still be required to confirm carcinoma rather than a mimic such as chronic pancreatitis or autoimmune IgG4 related pancreatitis; immunostains can be difficult and there may be grey areas due to limited tumour cells, equivocal staining, edge artefact.
    Don't know whether hent and sparc are membrane or cytoplasmic stains.
    9 Nov 2012, 08:18 AM Reply Like
  • FOURMI
    , contributor
    Comments (9) | Send Message
     
    Both are membrane/surface markers as far as I know.
    9 Nov 2012, 08:47 AM Reply Like
  • Gregory Pepin
    , contributor
    Comments (121) | Send Message
     
    Author’s reply » Celgene just announced statistical significant data on pancreatic cancer. That is a good news for patient but I think overall survival improvement is probably very limited (lower then AB science).
    I believe that because :
    - they raised the amount of patient enroll (and finished with over 800patients) the more patient they had the less the difference of survival has to be
    - if they were a big difference in survival (in the tune of 6 month for example Masinitib concerning that 65% population) the study would have been stop very early for ethical consideration
    - they would have issue an even more aggressive release if the efficacy was really impressive

     

    Also on top of that the toxicity is infortunatly pretty important on celgene product. I assume when AB will do their confirmatory study on their subgroup the study will end very quickly and won require 800+ patient to show statistical signicancy.

     

    So celgene news is a good news for pancreatic patient but I think they will be inferior to AB science both in safety and efficacy (at least on the subgroup they identify.) I think the number of patient they enroll was clearly a good math calculation to get statistical result despite a small increase in median OS (heck it is still an improvement and it is great even if safety isn t great )
    10 Nov 2012, 02:19 PM Reply Like
  • FOURMI
    , contributor
    Comments (9) | Send Message
     
    Hi Greg,
    The OS improvement with Abraxane might not be so great in the overall population, but it may well be thanks to their SPARC biomarker. Who knows, they might have achieved greater results in this SPARC positive sub-population?
    During their phase I-II, the high-SPARC score patients achieved a median OS that was close to 18 months (no comparison arm and only based on 20-ish patients, still pretty striking).
    Also, there was another very important news release today: unfortunately, the LEAP trial failed for Clovis...
    http://aol.it/SHIaMn
    12 Nov 2012, 01:34 PM Reply Like
  • Gregory Pepin
    , contributor
    Comments (121) | Send Message
     
    Author’s reply » the SPARC score patients is i believe the 33% subgroup in which AB science isn't targeting with their product.
    13 Nov 2012, 10:52 AM Reply Like
  • FOURMI
    , contributor
    Comments (9) | Send Message
     
    No, this is unlikely that the signature identified for masitinib has anything to do with SPARC (the masitinib signature seems to be based on RNA, while SPARC is on tumor/stroma cell surface; in addition, there was nothing more communicated on the masitinib signature). Therefore, they may be some overlap between high-SPARC patients and those who can benefit from masitinib (maybe leaving an opportunity for combination Abraxane+Gem+masitinib?).
    Anyway, Pancreas cancer is big so there is certainly room for the 2 compounds, leaving more treatment options and hope for patients.
    13 Nov 2012, 11:47 AM Reply Like
  • Gregory Pepin
    , contributor
    Comments (121) | Send Message
     
    Author’s reply » Ok thanks sorry for my wrong interpretation
    however I expect that the safety will be better (much better in fact) with masinitib.

     

    anyway due to the tough cancer we are talking about, more then 2 treatment would be great
    13 Nov 2012, 02:17 PM Reply Like
  • wubblepumpe
    , contributor
    Comment (1) | Send Message
     
    HI Gregory,

     

    thank you very much for all your input.

     

    Waht comments do you have for the latest Celgene pancreatic cancer P3 results? http://bit.ly/W0SDDL

     

    Without much data in the PR can you speculate about the impact on AB Science?
    11 Nov 2012, 01:24 AM Reply Like
  • Gregory Pepin
    , contributor
    Comments (121) | Send Message
     
    Author’s reply » My answer on celgene data is just above your comment ;);)
    11 Nov 2012, 06:10 AM Reply Like
  • su
    , contributor
    Comments (9) | Send Message
     
    Agree that the Celgene paclitaxel product is cytotoxic as is gemcitabine so combinations with the less toxic masitinib might be the likely outcome but will require further trials; have to wait til January to assess the measure of improvement in survival offered by celgene's study when they do a late breaking presentation at the American cancer conference.
    11 Nov 2012, 01:55 PM Reply Like
  • stock_khoj
    , contributor
    Comments (19) | Send Message
     
    Hi Greg,

     

    When can we expect to hear from AB Science on the EMA Acceptance of Marketing Authorization Application for Masitinib for the treatment of Pancreatic Cancer? It is almost 2 months / 58 days and wondering what's a reasonable time for acceptance under EMA review process timelines.

     

    Thanks in advance
    13 Dec 2012, 02:34 AM Reply Like
  • Gregory Pepin
    , contributor
    Comments (121) | Send Message
     
    Author’s reply » It takes up to a year i think.
    13 Dec 2012, 05:02 AM Reply Like
  • stock_khoj
    , contributor
    Comments (19) | Send Message
     
    The total time for approval indeed is close to one year. I was hoping AB Science could announce the acceptance of the application like they did for the GIST. It seems like they already did per one of your statement above "AB Science also announced that the European Medicines Agency (EMA) has accepted to review a Marketing Authorization Application (MAA) for conditional approval of masitinib in combination with Gemzar® in the treatment of pancreatic cancer, following filing of this dossier." Can't wait to see the biomarker & the subset detail at the upcoming ASCO conference.

     

    Celgene market cap gone up $3 bil overnight on successful Abraxane trail announcement with limited details, which is expected to be a marginally beneficial (~2 month improvement) with AEs/ toxic and limited patient pool. At that rate "what should be AB Science worth" which could benefit 65% or more patient pool and can increase OS by >100% at minimal AEs.

     

    Thanks
    13 Dec 2012, 08:57 AM Reply Like
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