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Geo,
Anyone can come to a conclusion after the fact. Give us something we can use.
Best Regards,
RRdog
Stoneroad,
That is a fair answer to my provocation. I hear you about that.
Best Regards,
RRdog
FTM
Front line testing had a very aberrant number in the measurment of the control arm. I have long contended that in one form or another the front line test would revert to the mean and vindicate the efficacy of bavi. I assume this may come out in the MOS numbers where measurement is difficult to obfuscate. That is all I have to comment as of now.
As far as your very fine comments on second line it sounds like you are finally crossing the Rubicon of 12 months or better and joining me on the other side. I hope this is correct and I do not want to put words in your mouth. It is getting lonely over here but it is also beautiful.
Please let me know if I can expect company with a "clear statement".
Moving on --my advice is to start turning your math and statistical ability to the "burn rate" to be discussed in the coming CC. I predict a sizable drop in the "burn rate" as Avid revenue guide lines will be raised for the 5th consecutive qtr and as the large expensive trials burn off (trials with over 50 sites).
The only new trial is for "imaging" and it is an inexpensive 1 site trial. How cool is that. PPHM gets to approach a 10-15 billion a year market with a short fuse 1 site trial. IMO that's good value for your investor dollar.
The "burn rate" is a key statistic. Focus a bit on this piece of financial data as it affects "dilution".
It is too soon to calculate whether the added Zeibel in house legal expense actually saves dollars. It may. I think mgmt and Zeibel were unfairly tarred and feathered. There are numerous distinct advantages to bringing this guy in house. One "stonehead" contributor to this board actually was close to selling his entire position because he was so off put by this development. Sanity appears to have now returned as I see stony but bullish commentary.
Best Regards,
RRdog
Mojo,
This is an interesting enrollment map guesstimate.
Currently that would put you at 11.6 months toward MOS.
I note that PPHM cryptic MOS for control arm of <6 implies a range of approx 5.1-5.9 months so there is some range in your guess of current 11.6 months.
You are getting pretty close to the Rubicon as well.
Best Regards,
RRdog
JakeD,
I don't focus on the chart. I focus on step functional events.
If you want to focus on a chart look at ARNA.
Regards,
RRdog
FTM,
We are in agreement on Doxy. More important Dr. Thorpe is in agreement.
I don't want to get too far ahead of ourselves but, we are also in agreement re "radiation" and in agreement with Dr. Thorpe. (Always good to agree with the good Dr. because he knows what he is talking about even if we don't).
If you really want to see Dr. Thorpes' eyes light up like an NIR image,--- ask about radiation. As good as doxy is with bavi-- radiation is far better in upregulating PS on the surface of cancer cells.
The implication I draw from all of this is that PPHM needs a big partner to initiate a long laundry list of clinicals using radiation and bavi alone, radiation and bavi and doxy, radiation and bavi and different chemo, all of these in different amounts and dosages.
The latent value in the PPHM IP portfolio is staggering and this is one example. The latent portfolio value is growing.
Best Regards,
RRdog
Geo,
We could beat 12 months even if MOS triggered after May 21 date.
(See FTM analysis of percentage recruitment this a.m.)
Come on across the river and stop worrying so much about every little thing.
Regards
RRdog
Jake D,
The Rubicon is a wide river. Before you come across remember that second line tests "never" (?) outperform 1st line tests historically.
My breakthrough guess here is that doxy is "far" superior as a chemo with bavi. Still just IMO and a guess.
Getting lonely over here but, since you did such good work on site recruitment come on across. The key is always in the "time" factor.
Regards,
RRdog
FTM,
"Crossing the Rubicon" is at about 12 months MOS. After that you get into a place where this 2nd line NSCLC test out performs the MOS for 1st line.
Come on across the river. It's nice over here on the other side.
Best Regards,
RRdog
FTM,
"When the facts change, I change my opinion. What do you do madam?" ---John Maynard Keynes
A doubling of control group MOS puts you at approx 12 mos. We are getting closer.
Regards
RRdog,
JakeD,
I was going to send this message to FTM but, since you are starting to pick up on some of my research techniques I will address it to you. Your post on recruitment dates was excellent.
FTM
I am glad you are aware of long enrollment in pancreatic cancer trials. A similar situation exists in the 2nd line NSCLC trial.
Does the Earth really circle the sun?? Sometimes watching what goes on in the investment community one would wonder. Perhaps:
"The Earth be flat and at the ends thar be dragons".
Anyway, lets return to a simpler analysis of MOS in 2nd line NSCLC. I stand by my prediction and though I may be high end, you and Mojo may be low.
The reasons I fix on this number are the following:
1. It is a hard data number. ORR and PFS are softer numbers involving some human measurement and judgement. There is nothing soft about MOS. Either you are alive or not.
2. The PPHM double blinded and randomized test with independent review is the most well designed test PPHM has yet run and the results are near immediate. It will be difficult to quibble with the MOS number coming out of this test.
3. The MOS number in 2nd line has a "direct affect" on PPHM ability to finance in a less dilutive fashion.
4. Because this number in 2nd line NSCLC is against a deadly, unmet need PPHM has the best chance to advance the drug quickly and to get the whole bavi program broadened to other indications.
Much has been written about various ratios and possible outcome of this trial. I would like to try and simplify:
1. The trial completed enrollment on Oct 6th 2011. If all the patients were enrolled exactly on Oct 6th, we are now nine months into MOS or approximately >50% better than the control arm
which we know to be <6 months. In addition, we would be roughly 25% better than the mean average of MOS in all phase III NSCLC tests. This in itself is not a bad result.
2. However, we know that all patients in this clinical were not enrolled on the last day. Rather, they were enrolled in double blind and randomized fashion along with the control arm over the course of 17 months.
3. If the average enrollee starts from the average date of enrollment that patient would now be 8.5 + 9 = 17.5 months into the clinical without achieving MOS. If the average enrollee starts from a date that is 75% of the enrollment process then that patient would now have run 4.25 + 9 = 13.5 months without achieving MOS.
4. These numbers (preceding paragraphs) lead me to believe that the estimates of MOS for the treatment arm of this trial between 9-11 months are low end.
5. One argument for the low end estimates is that 2nd line results should not exceed 1st line results where patients are "healthier". I recall Dr. Thorpes' remarks that "they are all pretty sick". In addition, I would remind everyone that every clinical test is a separate ecosystem of patients. That is why FTM is so adamant about comparing the result to the control arm of the particular test.
Thirdly, I would make the point that 1st line testing was primarily using c/p while this clinical is using D. Dr. Thorpe will tell you that D (doxy) is the chemo with the most synergistic activity with bavi. Therefore, it is possible to get better results. I am not saying it is definite but it is possible.
6. In a randomized double blind study the control arm and the treatment arm are recruited at the same pace (otherwise it would not be random and blind). We know that as of Oct 6 2011 the control arm had reached an MOS number of <6 but, it is extremely unlikely in a statistical sense that the number was achieved on the same date as the unblinding. Unblinding was set when the test met its primary and secondary goals of ORR and PFS. We know that <6mos fits several times into the perameter of a 17 month recruitment. What we don't know is when exactly that MOS for control was achieved. The delta between the MOS date for control arm and the unblinding date of Oct 6th is similar to my estimate of the average enrollee date on the treatment arm.
In conclusion, I stand by my prediction that MOS numbers in general estimate are low. I may be high end. It will be interesting to see the final result and it should augur well for PPHM shareholders. There are a number of implications from these results which will be discussed later.
Best Regards,
RRdog
Geo,
It be so.
Remember the whole world thought the world was flat until Columbus proved it was round.
Best Regards,
RRdog
Came in late Sunday from golf trip. Read over 100 messages in a very lively and thoughtful debate.
I stand by my estimates on 2nd line MOS. I may be high but I think FTM and Mojo are low.
More later.
Best Regards,
RRdog
FTM,
We are working on 1st line and Pancreatic. Intuitively, we believe as you do that the numbers may be supportive of PPHM effort overall.
Both clinicals are long enrollment periods and non- linear ramp up. If I ever get comfortable with the estimates I will revert back. I have long felt that the "measurement" used in the 1st line NSCLC was flawed and aberrant and that the overall result would revert more to the mean which would be more favorable to PPHM.
Best Regards,
RRdog
Thank you Jake D
I appreciate the comment as I know you are not a starry eyed optimist.
RRdog
FTM
If you use a linear ramp up of patients and clinical sites (even distribution) the number is indeed higher. However, all our experience with PPHM, other biotechs, and life in general would lead us to believe that ramp ups are not linear. Just take a look at the ramp up in Pancreatic cancer for PPHM testing and you can deduce just how uneven things can get. We are much more comfortable with a back loaded approach.
Many times the ramp up is hindered by doctors that would rather see their patients on SOC rather than some new treatment. PPHM clinicals are beautiful in the sense that the placebo arm for NSCLC 2nd line was the SOC and bavi addition has a long history of low side affects. It may have therefore been possible to enroll a little faster.
If you take a rough average of your high, Mojo high estimate and our estimate you would come in somewhere around 14 months and counting. Averaging from your lower estimates with our numbers would be about 12.8 mos and counting.
I think you are correct in thinking that the FDA would notice such an MOS figure in a deadly disease. An AA would be possible.
I am less concerned with the FDA than with potential partners.
"Gin" for the shareholders would be a well crafted partnership in some form or regional partnership. IMO PPHM has several potential partners that are looking at data under a "non disclosure" agreement. Just a guess. The hiring of attorney in house specialist only serves to strengthen this opinion.
Staying focused once again, I am more concerned firstly with a financial event and then an FDA event. All numbers are inter related.
Best Regards,
RRdog
FTM,
As previously suggested-- IMO there is every possibility that your date could be roughly correct and your MOS way low. You conservatively figured from the Oct 6 enrollment completion date.
The average enrollee has been in the study a lot longer than from the study completion date even assuming a very non-linear ramp up of patients and sites in the clinical trial. The study began in early June of 2010.
The possibility where your date is backed up would only enhance the possibility of greater MOS than generally assumed by both you and MOJO. It will be interesting to see where all this falls out.
The entire study seems to have been enrolled over a 17 month period. In our in house calculation, we conservatively assume 25% enrollment in the first 8.5 months and 75% of the enrollment in the last 8.5 mos. Our blended average for current MOS equals 16.25 mos and counting. Even if we are considerably high in estimate we believe your estimates are considerably low.
Please let me know if you disagree with starting enrollment date or ramp up estimates of weighted clinical patients and we would recalculate.
Best Regards,
RRdog
Geo,
No interim announcements on NSCLC MOS.
RRdog
Mojo,
Applaud the brilliance of your graphic analysis of MOS range for Phase II 2nd line NSCLC. It implies a 58-94% improvement over the control arm and we could live with that.
FTR, and without divulging our methodology, our internal estimate for the same MOS figures is well in excess of yours. Looking forward to the final result.
Best Regards,
RRdog
Geo,
Glad you agree with me. I agree with you on the CC questioning. PPHM approach is too fearful. They have an opportunity to take on legitimate questions from shareholder/owners with legitimate answers. If they don't want to answer a question for competitive reasons they can always demur.
As for the FDA, it is IMO. I don't want to discuss how I reach my opinion but, I do some diligence. Let's see what the comments are on Cotara on the next CC and we'll get a better fix.
Best Regards,
RRdog
JR,
You sound more like me. You have stopped focusing on every little moving average and started looking for step function fundamentals. Glad to have you aboard. Agree with you about alternate financing other than ATM--that goes without saying. By the way, if you really want to be technical, I would focus more on the calendar than on candlestick formulations.
Also, would take the opposite of the GNTA argument. The prevailing wisdom is that the FDA would never deal (SPA) with a very small biotech (.01). Reality is the FDA deals with small biotech companies all the time.
Additionally, re Garnick:
IMO Garnick does know how to kill programs he thinks are a waste of his time. IMO he still believes an acceptable resolution with the FDA re Cotara is doable. IMO the FDA is keenly aware of PPHM prerequisites for a deal and the FDA would also still not be working on this if they didn't think an acceptable resolution with PPHM was both "doable and desirable."
Every day without news from PPHM is now a PR whispering "look at the calendar, look at the calendar---you can count can't you??"
Lastly, I have admonished "don't swing at pitches in the dirt". The Russell BS is another pitch in the dirt. Russell managers bot millions of shares of PPHM without ever understanding anything about the company, just to balance their average, and they bot high. Now Russell managers are selling millions of shares of PPHM without ever understanding any change in fundamental position and they are selling low. This should tell you never invest in these index funds they are run robotically.
The dollar amounts involved in the sale of several million Russell shares are insignifigant in the institutional world and though it is annoying short term it is meaningless long term. The Russell has nothing to do with MOS.
Best Regards
RRdog
Geo,
IMO no interim PR on lung cancer.
RRdog
Geo,
The MOS data on lung cancer most important number in PPHM history so far. I would advise no interim data. IMO I believe no interim PR will be forthcoming. Most important to get data complete and correct. Worry about something else.
Best Regards
RRdog
FTM
Why is the Pallis study done in 2010 of Doxy + Carbo vs Doxy alone listed as not stat signifigant since it seems to be better.
Best Regards,
RRdog
FTM
Thank you. Much appreciated.
RRdog
FTM
PPHM may be 8 months out after "final" enrollment but as much as 9.5 months out on "average" enrollment. A 50% increase over control arm (<6 months) in PPHM phase II clinical is not only possible but IMO probably a lock.
Let's say that <6 mo equals 5.8 mo . Then a 50% improvement would equal 8.7 mo . The average enrollee in the PPHM 2nd line phase II clinical may already be well past the 8.7 mo level.
The better and much more important target might be a 50% improvement over the composite mean average of "Phase III" tests of 2nd line NSCLC of 7.2 months. For this we would need approx 10.8 months. This would be achieved if PPHM MOS went out past approx. Sept 7th.
It is interesting to note that the 7.2 mo mean average MOS in second line phase III testing was achieved with an average 2.7 mo PFS number. In the bavi random phase II the PFS for the respective doses was 4.2 mo and 4.5 mo.
Sunstar in post 80813 extrapolated a "low", "medium" , and "high" relationship of PFS to MOS as 7.2-7.7mos, 8.5-9.1 mos, and 10.6-11.3 mos. PPHM is already well past the low range so we can throw that possibility out. Your last enrollee to my average enrollee puts PPHM out somewhere between 8-9.5 mos which is the medium range. If the clinical runs toward the high end of the Sunstar extrapolation that would put PPHM in the 10.6-11.3 mos.
That would make my target of 50% improvement on mean average phase III testing a fair possibility.
Mid range, where we are, would yield approx an 18-26% improvement over mean average phase III mos for 2nd line NSCLC and that is not bad.
I agree with you that a 50% improvement over the control arm would be a good result but PPHM might get something better.
One never knows "do" one. That's why you run these clinicals.
The real question, when you get past all the mumbo jumbo of these numbers is, will they, in conjunction with all the background outstanding data such as the early testing in MBC be enough to motivate a BP partner??? Again I would think that would be a fair possibility and hopefully that possibility will be reflected in the price of PPHM.
The price of PPHM is not a trivial matter as regards dilution and financing.
At the time of the MOS announcement the "Russell selling" should be well out of the way. If the MOS turned out 50% better than phase III composite MOS at 10.8 months + PPHM should press for AA.
If the numbers are good Chris Keenan should be on alert for a massive PR effort to broadcast the achievement in several different modes. Otherwise, why pay him and PPHM could save the expense of his salary. Institutional groundwork should be ongoing as of now. Repeat--institutional groundwork should be ongoing as of now as the data matures.
Best Regards,
IMO only
RRdog
Stone,
Ask Chris Keenan.
RRdog
North America ¦ United States
Pharmaceuticals (GICS) ¦ Drugs (Citi)
Equities
4 June 2012 ¦ 7 pages
Bristol-Myers Squibb (BMY)
Alert: Anti-PD-1–a Revolutionary Immunotherapy for SolidTumors
We hosted a dinner at the ASCO meeting in Chicago with Brian Daniels, Global
Head of Clinical Development & Medical Affairs, Rezo Canetta, Head of Oncology
Clinical Development & Robert LaCaze, Global Head of Oncology Marketing.
Conclusion — BMY’s anti-PD1 program was the center of attention at this year’s
ASCO, providing a new modality for cancer treatment.Its Ph-I data for BMS-936558,
its anti-PD-1 antibody provided a durable clinical benefit across 3 indications
including lung(NSCLC), renal cell carcinoma(RCC) & metastatic melanoma. BMY
confirmed its decision to move all 3 indications into Ph-III for Lung(both squamous &
non-squamous), RCC in 2012 & melanoma in 4Q12/1Q13. We are not carrying any
sales for ‘558 in our BMY model & see multi-billion-dollar potential for its anti-PD-1
antibody, much like Yervoy. We maintain our Buy rating and $40 price target.
Immunotherapy in Advanced Non-Small Cell Lung Cancer — Of the 73 patients,
who averaged >3 prior therapies (40% on prior kinase inhibitor), 13 showed an OR
including 3 unconfirmed, which translates to an RR of 18% (14% ex-unconfirmed).
This is competitive with current later-line NSCLC therapies, like Tarceva, which
accounts for ~$2B in worldwide oncology sales. In particular, the 3mg/kg dose
(n=18) showed an RR of 28%. Treatment was well tolerated, with serious TRAEs
only seen in 8% of pts. (1 death). BMY is in the process of negotiating its clinical
trial design that is likely to include both squamous & non-squamous lung cancer pts.
Renal Cell Carcinoma — Of the 32 patients, who averaged >2 prior therapies, 10
showed an OR (incl. 2 unconfirmed), for an RR of 31%. This RR was seen in both
the 1mg/kg and 10mg/kg arms. The PFS at 24 weeks was 67% in the 10mg/kg arm.
These results continue to compare favorably to current therapy (Inlyta showed an
RR of 11% in Sutent- failure patients). Serious TRAEs were seen in 12% of patients.
Metastatic Melanoma — Of the 90 patients, who had averaged >2 prior therapies
(excluding Yervoy, but including 7 pts. previously on BRAF inhibitors), 23 pts.
showed an objective response (OR), incl. 3 unconfirmed, for a response rate (RR)
of 26% (22% RR ex-unconfirmed). The 1mg/kg and 3mg/kg doses had RR of 29%
and 41%, resp. PFS at 24 wks in the 3mg/kg group was 55%. Efficacy looks at least
as solid as Yervoy, which had RR of 11% in its Ph-III. Serious treatment-related AEs
look slightly higher for ‘558 at 19% (no deaths) vs. 10%-15% for the Yervoy trial. We
see the MM market as >$3B peak&assume ~$1.5B from MM sales for Yervoy in ‘15.
Following is data from Roche re Breast Cancer Results re T-DM1
Investor Update
Basel, 3 June 2012
Roche’s targeted investigational breast cancer medicine, trastuzumab emtansine (T-DM1), reduced the risk of cancer worsening or death by 35 percent in pivotal phase III trial
Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the Phase III EMILIA study of trastuzumab emtansine (T-DM1) met its co-primary endpoint, of a significant improvement in the time patients with HER2-positive metastatic breast cancer (mBC) lived without their disease getting worse (progression-free survival; PFS). The study showed that the risk of disease worsening or death was reduced by 35 percent for people who received trastuzumab emtansine compared to those who received lapatinib plus Xeloda® (capecitabine) chemotherapy (HR=0.65, p-value <.0001). The EMILIA study is the first randomised Phase III trial of trastuzumab emtansine in patients with HER2-positive mBC who had previously received Herceptin® (trastuzumab) and a taxane chemotherapy.
There was also a trend for patients who received trastuzumab emtansine to live longer (overall survival, or OS, the other co-primary endpoint of the study) than those who received lapatinib plus Xeloda, but these data are currently not mature. The safety profile of trastuzumab emtansine was consistent with that seen in previous studies, with fewer patients who received trastuzumab emtansine experiencing Grade 3 or higher (severe) adverse events (AEs) than those who received lapatinib plus Xeloda (40.8 percent compared to 57 percent).
The EMILIA data will be presented in the plenary session at the 48th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago by Kim Blackwell, M.D., Duke University School of Medicine (Abstract #LBA1, Sunday 3 June at 1:45 pm CDT). The EMILIA data were also featured in the official ASCO press programme on Saturday 2 June.
“The encouraging efficacy, safety profile and quality of life results from the EMILIA study support our belief that trastuzumab emtansine may have an important role for patients with HER2-positive metastatic breast cancer,” said Hal Barron, M.D., Chief Medical Officer and Head, Global Product Development. “We are working with global regulatory authorities to submit these data as quickly as possible and hope that trastuzumab emtansine will soon be available to patients with this aggressive type of breast cancer.”
Based on the EMILIA findings, Roche and Genentech plan to submit applications for trastuzumab emtansine in HER2-positive mBC this year to the European Medicines Agency (EMA) and US Food and Drug Administration (FDA).
Trastuzumab emtansine is an investigational medicine known as an antibody-drug conjugate (ADC). It is comprised of the antibody trastuzumab and the chemotherapy DM1 attached together using a stable linker. Trastuzumab emtansine is designed to target and inhibit HER2 signalling and deliver the chemotherapy directly inside HER2-positive cancer cells.
Study results
The results presented at ASCO represent the final analysis of PFS and the first interim analysis of OS.
There was a significant improvement in the time patients receiving trastuzumab emtansine (n=495) lived without their disease getting worse compared to those who received lapatinib plus Xeloda (n=496), as assessed by an independent review committee: median PFS was 9.6 months versus 6.4 months, respectively.
The first interim OS analysis demonstrated a trend towards improved OS in patients receiving trastuzumab emtansine versus those who received lapatinib plus Xeloda: median OS was 23.3 months for patients who received lapatinib plus Xeloda but had not been reached for patients receiving trastuzumab emtansine and requires longer follow-up (HR=0.62; P=0.0005).
As the hazard ratio for OS did not cross the pre-specified stopping boundary for the study, the OS analysis is not considered statistically significant at this time. The final analysis is expected to take place by 2014.
One-year survival in patients who received trastuzumab emtansine was 84.7 percent versus 77.0 percent for patients who received lapatinib plus Xeloda. Two-year survival was 65.4 percent versus 47.5 percent, respectively.
The response rate (the percentage of patients with tumour shrinkage) was 43.6 percent for those who received trastuzumab emtansine versus 30.8 percent of patients who received lapatinib plus Xeloda.
The time-to-symptom progression, a patient-reported measure of quality of life, was also improved in patients who received trastuzumab emtansine: 7.1 months in patients who received trastuzumab emtansine versus 4.6 months in patients who received lapatinib plus Xeloda.
Fewer patients who received trastuzumab emtansine experienced Grade 3 or higher (severe) AEs than those who received lapatinib plus Xeloda, at 40.8 percent versus 57 percent, respectively. For people receiving trastuzumab emtansine, compared to those receiving lapatinib plus Xeloda, the most common (occurring in more than 2 percent of patients) Grade 3 or higher AEs were low platelet count (12.9 percent versus 0.2 percent), increased levels of enzymes released by the liver and other organs (in most patients these levels had returned to normal by the time of the next dose of trastuzumab emtansine; aspartate aminotransferase: 4.3 percent versus 0.8 percent; alanine aminotransferase: 2.9 percent versus 1.4 percent) and anaemia (2.7 percent versus 1.6 percent).
For those patients receiving lapatinib plus Xeloda compared to those receiving trastuzumab emtansine, the most common Grade 3 or higher AEs were diarrhoea (20.7 percent versus 1.6 percent), hand-foot syndrome (16.4 percent versus 0) and vomiting (4.5 percent versus 0.8 percent).
About the EMILIA study
EMILIA (TDM4370g/BO21977) is an international, Phase III, randomised, open-label study comparing trastuzumab emtansine alone to lapatinib in combination with Xeloda in 991 patients with HER2-positive locally advanced or metastatic breast cancer whose disease progressed after initial treatment with Herceptin and a taxane-based chemotherapy.
Participants in the trastuzumab emtansine arm received:
Trastuzumab emtansine 3.6 mg/kg dose every three weeks
Participants in the lapatinib plus Xeloda arm received:
Lapatinib 1250 mg dose daily, every three weeks.
Xeloda 1000 mg/m2 dose, twice daily, days 1 – 14, every three weeks.
The co-primary efficacy endpoints of the study are PFS (as assessed by an independent review committee) and OS. Safety is also a primary endpoint of the study. Other study endpoints include and one-year and two-year survival rates, safety profile, PFS as assessed by investigator, objective response rate, duration of response and quality of life.
About trastuzumab emtansine
Trastuzumab emtansine is an ADC being studied in HER2-positive cancers. It is comprised of the antibody trastuzumab and the chemotherapy agent DM1 attached together using a stable linker. Trastuzumab emtansine is designed to target and inhibit HER2 signalling and deliver the chemotherapy agent DM1 directly inside HER2-positive cancer cells. Trastuzumab emtansine binds to the HER2-positive cancer cells, and is thought to block out-of-control signals that make the cancer grow while also calling on the body's immune system to attack the cancer cells. Once trastuzumab emtansine is absorbed into those cancer cells, it is designed to destroy them by releasing the DM1.
In addition to EMILIA, there are two ongoing Phase III studies of trastuzumab emtansine:
MARIANNE is comparing three different regimens (trastuzumab emtansine alone, trastuzumab emtansine plus pertuzumab, and Herceptin plus a taxane chemotherapy) in patients with HER2-positive mBC who have not been previously treated for their metastatic disease.
TH3RESA is comparing trastuzumab emtansine to physician's choice of treatment in people with HER2-positive mBC who have already received both Herceptin and lapatinib.
Genentech, a member of the Roche Group, licenses technology for trastuzumab emtansine under an agreement with ImmunoGen, Inc.
Building on the results of trastuzumab emtansine studies to date, Roche/Genentech have approximately 25ADCs in the pipeline.
About breast cancer
Breast cancer is the most common cancer among women worldwide. Each year about 1.4 million new cases of breast cancer are diagnosed worldwide, and over 450,000 women will die of the disease annually.1 In HER2-positive breast cancer, increased quantities of the human epidermal growth factor receptor 2 (HER2) are present on the surface of the tumour cells. This is known as “HER2 positivity” and affects approximately 15-20 percent of women with breast cancer.2 HER2-positive cancer is a particularly aggressive form of breast cancer.3
About Roche
Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is the world’s largest biotech company with truly differentiated medicines in oncology, virology, inflammation, metabolism and CNS. Roche is also the world leader in in-vitro diagnostics, tissue-based cancer diagnostics and a pioneer in diabetes management. Roche’s personalised healthcare strategy aims at providing medicines and diagnostic tools that enable tangible improvements in the health, quality of life and survival of patients. In 2011, Roche had over 80,000 employees worldwide and invested over 8 billion Swiss francs in R&D. The Group posted sales of 42.5 billion Swiss francs. Genentech, United States, is a wholly owned member of the Roche Group. Roche has a majority stake in Chugai Pharmaceutical, Japan. For more information: www.roche.com.
All trademarks used or mentioned in this release are protected by law.
References
1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM. GLOBOCAN 2008, Cancer Incidence and Mortality Worldwide: IARC Cancer Base No. 10 [Internet]. Lyon, France: International Agency for Research on Cancer; 2010. Available from: http://globocan.iarc.fr.
2. Wolff A.C et al. American Society of Clinical Oncology/ College of American Pathologists Guideline Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer. Arch Pathol Lab Med - Vol 131, January 2007.
3. Slamon D et al. Adjuvant Trastuzumab in HER2-Positive Breast Cancer. N Engl J Med 2011; 365:1273-83.
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Jake
rrdog,
what's your take on russell and impact on pphm? i appreciate your input.
tia
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You are too smart to even ask this question. What does the Russell have to do with MOS???
If the Russell temporarily caused 10 trillion shares to be sold down to a penny what would that have to do with PPHM selling their platform.
There is much too much worry on this board about irrelevant "red herring" type issues. Concentrate on "value creation divided by share capitalization". The valuation that PPHM will get for their IP platforms is not a function of the public share price driven by buyers and sellers at the margin.
PPHM has many ways to finance other than ATM if they need more time.
Best Regards,
RRdog
FTM
Thanks for that very interesting Avastin comp on NSCLC.
Much appreciated.
Regards,
RRdog
FTM,
Agree with your sentiments completely.
It is very important how PPHM structures the initial commercial
deals.
The potential is enormous.
Mgmt/BOD was(contrary to popular opinion) extremely competent in the way they structured and "timed" the option issuance.
The second leg of the stool was 2nd line data (and continuing data)
The third leg of the stool will be commercial transaction. I expect them to show continued competence on the initial commercial propositions. They have had a long time to think about this issue.
IMO PPHM attitude towards Avid may be changing as well. I expect Avid to move up to a 20mm rate by next conference call. They are at a 30% "accounting profit" rate. Actual "free cash flow" after putting back non cash items, depreciation, costs absorbed for the mother company is IMO closer to 50% rate. PPHM may be shifting from a "total no leverage" position to a "reasonable leverage" position without mortgaging Avid to the hilt. Avid could easily support 40mm in debt at a 10% rate. Such leverage
would be a form of bridge financing and could always be paid down from a later commercial transaction. No IP encumbered as collateral. IMO several lenders would be available for such a transaction.
Best Regards,
RRdog
At some point you just call a spade a spade. DD has to be about the shallowest biotech guru in captivity.
"The last refuge of a scoundrel" --he's down to "P Values".
Just IMO
RRdog
Congrats FTM. Thanks for the good statistical work.
RRdog
You are quite a guy.
Regards,
RRdog
This looks like a pretty good waterfall drop on the data. The placebo dies today. The real question: is the data compelling enough to set up a meaningful commercial transaction????
As a PPHM shareholder I would love to see a bid for the whole company. However, if I were management , I would try to make as narrow a deal as possible that would stem dilution and allow PPHM to move forward in numerous other areas. Drug companies may want to wait for MOS???
Best Regards,
IMO
RRdog
Follow up:
The BMY poster on NSCLC seems to be about 14-18% ORR with no PFS data, no recurrence data, no side effects data.
Regards,
RRdog
I expect Bristol Myers to put out an abstract at ASCO covering a "Phase I trial" in 2nd line NSCLC. They are looking for 2x the SOC ORR. There may be numbers discussing the overall size of this market (billions) and the overall size of sales of existing SOC drugs in this area (more billions).
Were PPHM to have good results in NSCLC, it would not surprise me if other large Pharma would want to compete with BMY in this area and therefore view PPHM aggressively--especially since PPHM represents a different MOA.
Still expect PPHM ORR and PFS in the first half of 2012.
Best Regards,
In my opinion only
RRdog
Jake,
What is also interesting about the options is that they vest in 8 quarterly pieces over two years so it will take a "sustained move' or a deal to really profit from this not just a pop.
IMO future capital raises in the opinion of mgmt will be anti- dilutive (above) relative to the .46 grant price.
Best Regards,
Just an opinion
RRdog
Thoughts on option grants:
I take the opposite position of this message board.
1. There is no justice but there is legality.
2. If PPHM shareholders should have learned anything it is that "Timing takes precedence over fundamentals"
3. Mgmt and board have timed this perfectly. This is a legal evasion of the insider trading rules.
Best Regards,
All IMO only
RRdog