Dear all Good evening (including Mason)
When I ready Masons post I really did double check my logic and went through his post. If nothing else it reconfirmed my faith in IMU science.
Its good to double check thing. IT appeared to be an ill informed post at best.
I have copied parts of Masons post back here with my responses in blue. I have debunked his post by simply referring to IMU announcements readily available and its quite easy.
Hervaxx is a very good drug in development. Hence why IMU wish to do 3 further trails and are looking to partner with someone.
I am a long term holder and am always going to do my own research as everyone else should.
I appreciate the post but.....I dont know the motivation of a random poster who just appears . MY radar is up.
I am happy with IMU performance both in science and as an investment. It all stacks up to me.
This is a risky business but as the years roll on I am just feeling more assured that IMU have an abundance of talented scientists who have also got a whole platform of drugs to develop. They are all as happy and excited to work on this ground breaking drug development. I am a holder but with any additional funds I shall buy more.
See my response and I have NOT picked on all aspects of his post. Its too long. Buy key items I have debunked to my satisfaction.
My Post is in blue below and underlined.Goodness me. You have not answered myquestions at all.
For anyone invested in IMU, the following lines ofinformation need to be read very carefully. Many here have tried to underminewhat I say by insulting me or saying I do not know more than the IDMC, however,what I am about to share with you is data that I have extracted fromcredentialed researchers around the world, and the Food and Drug Administration(FDA) and the European Medicines Agency (EMA) guidance papers. I will providereferences for everything I say and encourage anyone to debunk my work usingreferences and interpretations of their own.
Null hypothesis? That’srubbish! Unless you are simply referring to safety data, where there was noadded toxicity over SOC which was chemo in this instance. So that is actually apositive statement.
Incorrect. A null hypothesis is not rubbish.Rothman et al. states "Null hypothesis testing is a foundational stone ofstatistical analysis" (1). Hypothesis testing uses statistical analyses todetermine if there is an effect within the data (2). In research, there are twohypotheses:
H0 (the null hypothesis): there is no differencebetween the study arms
H1 (the alternative hypothesis): there is adifference between the study arms
The null and alternative hypotheses are mutuallyexclusive, which means that only one can be true. To determine which is truerequires the use of statistical analyses. There are two common statisticalanalyses metrics used to accept or reject the null hypothesis include the pvalue and confidence intervals.
The p value is quite simple to interpret, where ifthe p value is below the level of significance set at the beginning of thestudy (either 0.01, 0.05, or 0.10), then you may reject the null hypothesis andtherefore accept the alternative hypothesis (3). In other words, a p value lowerthan 0.05, for example, indicates that a relationship is significant and thereis indeed a difference between study arms. However, if the p value is above thelevel of confidence (or not significant), then you accept the null hypothesis(that there is no difference between the study arms). If anyone on this forumwould like to dispute the importance or relevance of the p value (particularly the significance level of 0.05), then you can first debunk why it has been used for almosta century in research and why the 0.05 significance level has been acornerstone in FDA decision making for 50-years (3; below).
Now, the questions I have asked you, @Owl vs Fox, are whether you accept of reject the null hypothesis, andwhat statistical analyses metric you used to determine this. The correct answeris as follows:
For progression free survival (PFS), we accept the null hypothesis (that there is nodifference between the study arms), as the p value of 0.266 is not significant(>0.10) (statistical analysis metric). Also, given that the interim PFS data reflected a HR of0.532 with an 80% confidence interval of 0.267 and 1.060 (intervals which cross '1'; accept nullhypothesis), we can be more confident of accepting the nullhypothesis (there is no difference between the study arms). This is because thePFS HR has decreased from 0.532 to 0.719 over the space of 5-months and the 80%confidence interval would have further included '1'. Also, I believe that thisincrease in PFS HR is due to patients developing therapy acquired resistance toHER-Vaxx, which I had discussed as something I noticed in the HER-Vaxx phase 1trial about 4 months ago (here). In short, HER-Vaxx has failed toshow a significant benefit over standard of care chemotherapies for progressionfree survival in this patient population.
I disagree and this is why
Response: From IMU announcement 5 July2021.
The IMU announcement statesHer-vaxx showed a reduced risk of death of 58.2% in the Her-vaxx plus chemo groupcompared with chemotherapy alone.
For patients receiving Her-vaxxplus chemotherapy median overall survival was 14.2 months compared with 8.8months on chemotherapy alone. This will improve with final results..
Patients receiving Her-vaxx andchemotherapy the reduction in tumour size is substantially higher in patients thatreceive Hervaxx plus chemotherapy
Overall the Her-vaxx datademonstrates Her-vaxx may provide treatment benefits consistent with monoclonalantibodies with corrresponding immune response without toxicity
Based on this data it is safe to assume that inthis patient population, HER-Vaxx is no different from standard of carechemotherapy.
HER-VAXX recruitment wasstopped early on IDMC recommendation for safety & efficacy in a Ph2. Thatis not done lightly, nor a common occurrence. So I’m accepting of the publishedP value.
I disagree
Based on what Istated earlier based on announcements by IMU
Mason statements do not correlate with facts announced by IMugene
In IMU announcementdated 1 September 2021 its stated
Imugenes PFS wascomparable to the landmark Genentech/Roche registrational ToGA study PFS HR .71(compared to Hervaxx .719) withouttoxicity. Thats a great result
Yes, the IDMC recommended that the HER-Vaxx trialbe discontinued early. The IDMC rely on the statistical analyses underpinningthe trial to make their conclusions about stopping a clinical trial early. As Ihave discussed above, the statistical analyses used in the HER-Vaxx trial arewell below the FDA and EMA standards and as such, are non-comparable to theHerceptin TOGA study data. Thus, efficacy being the primary driver of earlycessation is highly questionable. Of course the drug is not going to addtoxicity if it failing to show a significant benefit over the standard of caretreatments.
If you accept the published HER-Vaxx PFS HR pvalue (p = 0.226), you therefore also accept the null hypothesis - that thereis no difference between the study arms. I'm glad that we agree on this.
I disagree
The results speak for themselves and are groundbreaking and good. Scientists within IMU are in fact continuing with theirtrials and will continue to advance her- vaxx as their stated aim ofcombination therapies and additionl trials. They have announced 3 more.
If the IDMC results were as bad as Mason say whyis Hervaxx continuing to be developed, increased trials results and such positiveannouncements backed up by scientific data reviewed by an IDMC.IMU is in factspending more research funds to continue their development of Her-vaxx. Its fantasticin my view
Very simply, when reviewing published data onclinical trials, you really need to look at each trial individually & thestage of the trial & number of participants & the primary &secondary endpoints, of which there can be many parameters in Immuno-oncology.
Absolutely incorrect. There are fundamentals thatare industry standard accross multiple different areas of research to ensurequality of reporting. Here are some examples of FDA and EMA guidance documentshighlighting 95% confidence intervals and significance set to 0.05 in clinicalresearch, as well as a good many other things.
(FDA) Non-Inferiority Clinical Trials to EstablishEffectiveness (4)
(FDA) Providing Clinical Evidence of Effectivenessfor Human Drug and Biological Products (12)
(EMA) GUIDELINE ON THE CHOICE OF THENON-INFERIORITY MARGIN (5)
So for example a trial on 15 participants on anOrphan status trial that has shown efficacy, you cannot expect to havestatistical significance, nor are such trials powered for that. You need tolook at results.
HER-Vaxx are not functioning within an orphan statusspace. IMU are competing against a drug (Herceptin) that has been establishedin the market for decades. HER-Vaxx needs to be better than Herceptin to makeit into the multi-billion dollar US markets, or it will be a failure.
ResponseI disagree with your logic as IMU is already proven better
Hervaxxis better. Similar PFS without the toxicity.-see announcement 1 sep 2021. Lookup the toxicity of Herceptin and you will see Her-vaxx is just massively betterfor patients . This is when its given so late to patients. Wait till its allowedto be given to less ill patients with less compromised immune systems.
At this point in time, HER-Vaxx cannotdemonstrate significant benefit over standard of care chemotherapy, let aloneHerceptin. This also highlights why strong statistical analysis methods arerequired - to unequivocally prove that HER-Vaxx is better than Herceptin.
Response: Why would methods acceptable to the IDMC and have had peer reviewed results and published papers at ESMO that have now resulted in new trials and developments taking place be now questioned by Mason and be believed by us?
I have looked at the results in depth and sharedmy research publicly. I have extensively compared the findings of HER-Vaxxphase 2b trial to industry standards and the Herceptin TOGA study, and foundmajor holes that no one is addressing. Maybe it is you that needs to look atthe results.
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HER-Vaxx failed to show a significant benefit overstandard of care chemotherapy for PFS in this patient population.
Just not accepted based on above as supported by IMU announcements. I could go further but I think I have said enough
I encourage anyone on this forum to take the timeto prove where that has not happened.
The rest of your comments are not why I am here.If you have a problem with a contrarian view, that's not my problem. I have 0'ill wishes' towards IMU holders and instead want to discuss the fundamentalsof a stock that thousands of people have invested their hard earned money into.
1 https://www.tandfonline.com/doi/full/10.1080/19466315.2021.1886164
2 https://www.investopedia.com/terms/h/hypothesistesting.asp
3 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6169785/pdf/nihms-987338.pdf
4 https://www.fda.gov/media/78504/download
5 https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-choice-non-inferiority-margin_en.pdf
6 https://chicagounbound.uchicago.edu/cgi/viewcontent.cgi?referer=&httpsredir=1&article=1148&context=public_law_and_legal_theory
7 https://newswire.iguana2.com/af5f4d73c1a54a33/imu.asx/3A574809/IMU_Imugene_HER-Vaxx_Phase_2_PFS_Data_and_Flags_Three_New_Trials
8 https://ascopubs.org/doi/abs/10.1200/JCO.2021.39.15_suppl.e16065
9 https://measuringu.com/confidence-levels/
10https://sci-hub.se/https://www.thelancet.com/journals/lancet/article/PIIS014067361061121X/fulltext
11 https://stats.idre.ucla.edu/other/mult-pkg/faq/general/faq-what-are-the-differences-between-one-tailed-and-two-tailed-tests/
(20min delay)