Disclaimer
I am very invested in CVM, for a multitude of reasons, first as a scientist, second as an investor, third as my ego. I believe their recent clinical trial results are phenomenal, and illustrate it's potential as the pre-treatment for cancer in immuno-competent patients with appropriate genotypical and phenotypical screening. The clinical trial poster results as follows…
Safety results were not significantly different between treatment groups.
Leukocyte Interleukin, LI (MK) neoadjuvant immunotherapy did not add excess safety issues or TEAEs.
In the Randomized ITT population, early LI (MK) response decreases mortality and is prognostic/predictive of OS.
ITT Lower Risk LI (MK)+CIZ+SOC absolute OS advantage over SOC alone (Control) increased over time to 14.1% at 5-years; the 0.68 HR corresponds to a 47% prolongation of median survival, having a 46-month median OS advantage over SOC alone. The SCCHN population studied has been without any new therapy options in decades.
Much of this is a mix of science and legal speak, but my translations are as follows:
MK does not add safety issues
MK does not cause safety issues
MK response increases survival, and those that respond are more likely to survive longer
14.1% increased Survival at 5 years, this effect ramping up from 5% at 3 years, 9.5% at 4 years.
The big question that comes to mind after reading the poster is for an experiment: Identify the key oncogenic mutations and biomarkers for the individuals cancer, purify their antibodies before and after at various time points, prove that Multikine is specifically causing the increased survival long-term via immunological induction. This is a doable Phase 1b, proves Mechanism of action, and offers so much therapeutic profiling potential. Single-cell transcriptomics on the immune system profile before and after multikine at various time points would be the dream for future development, but it can only be done in humans because it is specifically confined to the limitations of species-homogenicity. Immune systems are so vast between person to person based on genetic SNPs, let alone species to species. The results wouldn't take years, ideally you'll see the specific changes early on and long-term survival is increased because of an immunological-booster versus greater initial tumour ablation - which the paper from the Phase 2 trial clearly shows a preference towards the former.
Still, there is data missing that I'd rather have to do more comparisons, and my general disdain for biostatisticians remains. There were a lot of ways to illustrate the study that would have made a better story, but I am guessing their FDA consultant favoured a narrow approach. As a Scientist, I have many questions at the molecular, genetic, and clinical level, but the results fit the initial hypothesis: Multikine is an immunotherapy that requires a working immune system, no surprises. Head and Neck cancer has been a therapeutic-resistant cancer, and a dive into some of the pathological and genetic traits of these tumours suggests why. If Multikine is enhancing the immune response, that would resound with the benefits in survival in lower-risk. I maintain that Cisplatin ruined half the study - i.e. the high-risk population, Cisplatin tears through everything, and immune cells are among the first to go as higher populating cells start suffering the most from poor DNA damage and checkpoint control pathways.
If I were an FDA investigator, I would be curious as to the patient drop-out rate, but I don't really know how much depth they would even get. I have spent countless hours going through the TCGA database as a researcher, I know how brutal Kaplan-Meier plots can be. Still, I want to know the full list of reasons for censoring data points. The key paragraph to read from the poster follows, with emphasis on key findings from the early response. As an FDA investigator, I would specifically look into this claim, and if it's true, I would get very excited.
In the as randomized ITT study population (n=923), the overall early response rate was 8.5% (45/529) for the combined LI (MK) treated groups; the early response rates were 8.1% (32/395) for LI (MK)+CIZ+SOC and 9.7% (13/134) for LI (MK)+SOC. The early response rate was 0% (0/394) for SOC; the difference between LI (MK) treated and SOC early response rate, for all patients as randomized, was highly significant (two-sided Fisher Exact test p=0.00000000001 ). The combined LI (MK) treated lower risk population had a 16% (34/212) early response rate and the LI (MK) treated higher risk population had an early response rate of 3.7% (10/269), while a 2.1% (1/48) response rate was noted in the LI (MK) treated subjects who had not been categorized to a risk group in the study. No early responses were observed in the SOC population irrespective of risk group.
At this point, it is safe to assume everyone has read the amazing news from the Rectal cancer trial, with an astounding 100% remission rate in a small-scale trial. The benefits of a trial like this, are the clinicians can really cherry-pick their patients on the front-end, which illustrates their Mechanism of Action in action. These therapies will have a long road ahead of them, but they do not exist in a vacuum. IL-6 and IL-12 are the same class of cytokine, I am just unsure which specific member of the family Cel-Sci has in the Multikine mix vs the recent. Again, I maintain that Multikine is likely the in the first generation of true immunotherapies, but with a ton of space to build out and upon. Cancer is not a single target or pathway disease, and therapies that are able to safely interact and cooperate are going to be key to increasing cure rates.
The next big catalysts are the full paper publication and the FDA clinical trial meeting. I expect other biotech/pharma analysts are pouring over the clinical trial results from ASCO, communicating with their team and investors. The abstract publication definitely caused an increase in price movement and action. My general hypothesis has been that the company has to fight an uphill battle versus the initial reaction of that phase 3 result, but the strong backup from ASCO result's will get digested favourably. The biggest catalyst will be FDA approval or rejection, but base case has and maintains approval based on clear clinical need and effect. The longer term bull case remains to be a path similar to Keytruda, as the drug is able to be tested in other reasonable cancer pathologies. Reasonably speaking, I could see numerous combinatorial studies with other immune therapies and initial tumour ablation therapies, especially as personalized cancer treatment becomes a larger model.
Trend Analysis suggests a multitude of possibilities in the short to medium term, with severe Macroeconomic constraints. This analyst does predict a recession, with very sticky inflation still to come. Biotech's will continue to hurt as interest rates increase simply because they are capital vacuums, and runways will continue to be tested across the board. However, CVM isn't stuck in that position for long, and Forward Cash Flows go from $0 to $$$$$ very quickly after clinical approvals. The market will decide on how much that ultimately ends up as, but CVM remains overweight and undervalued on profit models by large amounts. There are still warrants for purchase of shares at a few price levels, these price levels will likely continue to serve as areas of resistance, and support. How exactly the rest of this turbulent period plays out has dramatic effects on future price movement. FDA approval will remain key to massive price increases, but as the FDA meeting comes closer and closer, volume will increase as investors levy their bets. I continue to contend that this data is superior to anything Keytruda, or any of the other PD-L1 and PD-1 therapies have put out, especially in the face of Bristol-Meyer Squibb's recent failure, and the recent issues of TIGIT, and several other key immunotherapy drugs. Multikine is a multi-component formulation, stimulating multiple pathways in the immune response, and fine tuning and complementation will be key towards increasing efficacy. Furthermore, finer genotypic and phenotypic tumour profiling will greatly predict drug efficacy. However, the FDA remains fluid in position and ideology, offering favouritism towards illogical paths at times. Recent behaviours suggest an organization improving, especially as more clinicians come to see the benefits of therapeutic strategies coming out of Dana Farber and Memorial Sloan Kettering.
Final DISCLAIMER
This is in no way, shape or form, fluid and function, an analytical, qualitative or intelligent compte rendu. The function of this essay is the maddening diatribe of a curious mind, and how this one manages micro- and macro-economic data for a critical investigation into the micro- and macro-economic world. This text is not suitable for direct consumption, and should never be used as a primary or secondary source. The contents of this text are often illogical and offensive, and great care should be given to the reader's personal qualifications and senses. This text is delivered on TradingView, where the userbase is expected to have a level of financial and investigative understanding that would enable them to query appropriate thoughts and abdicate nonsense to the void. May whatever sovereign and omnipotent being you believe in, guide you through this.
www.businesswir...er-Data-at-ASCO?utm_campai...
aacrjournals.org/cli...ostic-Index-for-Head
www.ncbi.nlm.nih.gov...articles/PMC7000688/
www.ncbi.nlm.nih.gov...articles/PMC6591357/
pubmed.ncbi.nlm.nih.gov/32161122/
www.nature.com/artic...s/s41598-017-15173-3
www.frontiersin.org/...immu.2016.00479/full
I am very invested in CVM, for a multitude of reasons, first as a scientist, second as an investor, third as my ego. I believe their recent clinical trial results are phenomenal, and illustrate it's potential as the pre-treatment for cancer in immuno-competent patients with appropriate genotypical and phenotypical screening. The clinical trial poster results as follows…
Safety results were not significantly different between treatment groups.
Leukocyte Interleukin, LI (MK) neoadjuvant immunotherapy did not add excess safety issues or TEAEs.
In the Randomized ITT population, early LI (MK) response decreases mortality and is prognostic/predictive of OS.
ITT Lower Risk LI (MK)+CIZ+SOC absolute OS advantage over SOC alone (Control) increased over time to 14.1% at 5-years; the 0.68 HR corresponds to a 47% prolongation of median survival, having a 46-month median OS advantage over SOC alone. The SCCHN population studied has been without any new therapy options in decades.
Much of this is a mix of science and legal speak, but my translations are as follows:
MK does not add safety issues
MK does not cause safety issues
MK response increases survival, and those that respond are more likely to survive longer
14.1% increased Survival at 5 years, this effect ramping up from 5% at 3 years, 9.5% at 4 years.
The big question that comes to mind after reading the poster is for an experiment: Identify the key oncogenic mutations and biomarkers for the individuals cancer, purify their antibodies before and after at various time points, prove that Multikine is specifically causing the increased survival long-term via immunological induction. This is a doable Phase 1b, proves Mechanism of action, and offers so much therapeutic profiling potential. Single-cell transcriptomics on the immune system profile before and after multikine at various time points would be the dream for future development, but it can only be done in humans because it is specifically confined to the limitations of species-homogenicity. Immune systems are so vast between person to person based on genetic SNPs, let alone species to species. The results wouldn't take years, ideally you'll see the specific changes early on and long-term survival is increased because of an immunological-booster versus greater initial tumour ablation - which the paper from the Phase 2 trial clearly shows a preference towards the former.
Still, there is data missing that I'd rather have to do more comparisons, and my general disdain for biostatisticians remains. There were a lot of ways to illustrate the study that would have made a better story, but I am guessing their FDA consultant favoured a narrow approach. As a Scientist, I have many questions at the molecular, genetic, and clinical level, but the results fit the initial hypothesis: Multikine is an immunotherapy that requires a working immune system, no surprises. Head and Neck cancer has been a therapeutic-resistant cancer, and a dive into some of the pathological and genetic traits of these tumours suggests why. If Multikine is enhancing the immune response, that would resound with the benefits in survival in lower-risk. I maintain that Cisplatin ruined half the study - i.e. the high-risk population, Cisplatin tears through everything, and immune cells are among the first to go as higher populating cells start suffering the most from poor DNA damage and checkpoint control pathways.
If I were an FDA investigator, I would be curious as to the patient drop-out rate, but I don't really know how much depth they would even get. I have spent countless hours going through the TCGA database as a researcher, I know how brutal Kaplan-Meier plots can be. Still, I want to know the full list of reasons for censoring data points. The key paragraph to read from the poster follows, with emphasis on key findings from the early response. As an FDA investigator, I would specifically look into this claim, and if it's true, I would get very excited.
In the as randomized ITT study population (n=923), the overall early response rate was 8.5% (45/529) for the combined LI (MK) treated groups; the early response rates were 8.1% (32/395) for LI (MK)+CIZ+SOC and 9.7% (13/134) for LI (MK)+SOC. The early response rate was 0% (0/394) for SOC; the difference between LI (MK) treated and SOC early response rate, for all patients as randomized, was highly significant (two-sided Fisher Exact test p=0.00000000001 ). The combined LI (MK) treated lower risk population had a 16% (34/212) early response rate and the LI (MK) treated higher risk population had an early response rate of 3.7% (10/269), while a 2.1% (1/48) response rate was noted in the LI (MK) treated subjects who had not been categorized to a risk group in the study. No early responses were observed in the SOC population irrespective of risk group.
At this point, it is safe to assume everyone has read the amazing news from the Rectal cancer trial, with an astounding 100% remission rate in a small-scale trial. The benefits of a trial like this, are the clinicians can really cherry-pick their patients on the front-end, which illustrates their Mechanism of Action in action. These therapies will have a long road ahead of them, but they do not exist in a vacuum. IL-6 and IL-12 are the same class of cytokine, I am just unsure which specific member of the family Cel-Sci has in the Multikine mix vs the recent. Again, I maintain that Multikine is likely the in the first generation of true immunotherapies, but with a ton of space to build out and upon. Cancer is not a single target or pathway disease, and therapies that are able to safely interact and cooperate are going to be key to increasing cure rates.
The next big catalysts are the full paper publication and the FDA clinical trial meeting. I expect other biotech/pharma analysts are pouring over the clinical trial results from ASCO, communicating with their team and investors. The abstract publication definitely caused an increase in price movement and action. My general hypothesis has been that the company has to fight an uphill battle versus the initial reaction of that phase 3 result, but the strong backup from ASCO result's will get digested favourably. The biggest catalyst will be FDA approval or rejection, but base case has and maintains approval based on clear clinical need and effect. The longer term bull case remains to be a path similar to Keytruda, as the drug is able to be tested in other reasonable cancer pathologies. Reasonably speaking, I could see numerous combinatorial studies with other immune therapies and initial tumour ablation therapies, especially as personalized cancer treatment becomes a larger model.
Trend Analysis suggests a multitude of possibilities in the short to medium term, with severe Macroeconomic constraints. This analyst does predict a recession, with very sticky inflation still to come. Biotech's will continue to hurt as interest rates increase simply because they are capital vacuums, and runways will continue to be tested across the board. However, CVM isn't stuck in that position for long, and Forward Cash Flows go from $0 to $$$$$ very quickly after clinical approvals. The market will decide on how much that ultimately ends up as, but CVM remains overweight and undervalued on profit models by large amounts. There are still warrants for purchase of shares at a few price levels, these price levels will likely continue to serve as areas of resistance, and support. How exactly the rest of this turbulent period plays out has dramatic effects on future price movement. FDA approval will remain key to massive price increases, but as the FDA meeting comes closer and closer, volume will increase as investors levy their bets. I continue to contend that this data is superior to anything Keytruda, or any of the other PD-L1 and PD-1 therapies have put out, especially in the face of Bristol-Meyer Squibb's recent failure, and the recent issues of TIGIT, and several other key immunotherapy drugs. Multikine is a multi-component formulation, stimulating multiple pathways in the immune response, and fine tuning and complementation will be key towards increasing efficacy. Furthermore, finer genotypic and phenotypic tumour profiling will greatly predict drug efficacy. However, the FDA remains fluid in position and ideology, offering favouritism towards illogical paths at times. Recent behaviours suggest an organization improving, especially as more clinicians come to see the benefits of therapeutic strategies coming out of Dana Farber and Memorial Sloan Kettering.
Final DISCLAIMER
This is in no way, shape or form, fluid and function, an analytical, qualitative or intelligent compte rendu. The function of this essay is the maddening diatribe of a curious mind, and how this one manages micro- and macro-economic data for a critical investigation into the micro- and macro-economic world. This text is not suitable for direct consumption, and should never be used as a primary or secondary source. The contents of this text are often illogical and offensive, and great care should be given to the reader's personal qualifications and senses. This text is delivered on TradingView, where the userbase is expected to have a level of financial and investigative understanding that would enable them to query appropriate thoughts and abdicate nonsense to the void. May whatever sovereign and omnipotent being you believe in, guide you through this.
www.businesswir...er-Data-at-ASCO?utm_campai...
aacrjournals.org/cli...ostic-Index-for-Head
www.ncbi.nlm.nih.gov...articles/PMC7000688/
www.ncbi.nlm.nih.gov...articles/PMC6591357/
pubmed.ncbi.nlm.nih.gov/32161122/
www.nature.com/artic...s/s41598-017-15173-3
www.frontiersin.org/...immu.2016.00479/full
