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They have reportedly been able to express over fifty proteins successfully in mouse models without a single failure of expression using GENESIS with TRACE. In my opinion, this is about the accelerated development of their preclinical pipeline more than anything else.
In the case of advanced metastatic melanoma with visceral lesions, you won't need to electroporate the visceral lesions directly if there is an accessible cutaneous lesion. The point of Oncosec's electoroporation platform is to drive a systemic immune response. Once you drive that immune response, the activated T-cells will target for destruction those tumor cells that carry matching antigens; this is how the abscopal effect works. Because the visceral tumors carry the same "fingerprints" as the electroporated tumor, they too will be targeted once the T cells become activated with the tumor matching neoantigens.
For cancers that don't have cutaneous lesions, Oncosec has developed technology that supposedly works with any tissue condition and optimizes protein expression. Oncosec has reportedly been able to successfully express over fifty different proteins intratumorally in preclinical models using this new technology.
Staccani, I appreciate your input and I am acutely aware of the differences between the trials' inclusion/exclusion criteria. While there are proportionally more advanced metastatic patients in the DVAX and IDRA trials, I don't think EP pIL-12 with pembrolizumab is any less effective in stage IV versus stage III. The most important requirements for anti-PD-1 response appears to be an adequate number of exhausted TIL that contain PD-1 expression as well as PD-L1 on tumor cells. If you can't produce an adequate immune response that targets specific tumor antigens, then you'll see progression at any stage.
Oncosec had targeted patients with very low percentages of exhausted phenotypes on CD8 TIL. The UCSF discovery and validation studies are very compelling, but indeed this needs to be validated with even larger numbers. The fact that the enrolled patients in the p2b trial had very low numbers of exhausted TIL only suggests one thing - T cell activation was lacking. In other words, all patients had "cold" tumors. In my opinion, this makes their patient population more challenging to convert to responders. They could have included anti-PD-1 nonresponders who had higher percentages of the exhausted phenotype, but they did not - they chose the worst of the worst (those who had virtually no immune responses).
TLR9 agonists function in part through their ability to promote the release of IL-12 through mature dendritic cells. Immunopulse IL-12 achieves the same thing, but in a more direct and prolonged manner.
To clarify, I think at least some of the responders in the TLR9/Ipi arm will progress because the exhausted TIL phenotypes containing expressed PD-1 will eventually inhibit further tumor cell destruction. Also, as a side note, Ipi's safety profile is not too good when it is administered systemically.
The DVAX subset responses are certainly outstanding, but these are treatment naive patients and their anti-PD-1 refractory population didn't respond very well.
The verdict is still out on the aerosol delivery system for a TLR9 agonist. Maybe it makes sense with NSCLC, but what about other cancers?
Das, yes, that's a good summary - the partially exhausted T cells need to exist in the first place for anti-PD-1 agents to work their magic. In patients who are responding to anti-PD-1 therapies, they have adequate CD8-positive TIL with upregulated PD-1. The discovery and validation cohorts studied by UCSF staff identified 30% as the magic threshold. This still has to be validated by much larger studies, but the dataset published last year is quite compelling - all patients with the exhausted phenotype greater than 30% had responses to anti-PD-1 therapy.
Now the question is, if that premise is true, how would intratumoral IL-12 increase the percentages of intratumoral exhausted TIL phenotypes?
Here's the gist: Interleukin 12, which by the way is naturally produced by professional antigen presenting cells (for example dendritic cells), stimulates the production of interferon gamma in Th1 cells, and it helps in the reactivation and survival of memory CD4-positive T cells. The production of interferon gamma draws in more antigen presenting cells (which help to release more IL-12) to drive adaptive immunity, promotes natural killer cell activity (innate immunity), and induces PD-L1 expression on tumor cells. In order for tumor infiltrating lymphocytes to exist in the first place, the tumors' antigens must be identified by professional antigen presenting cells (dendritic cells). Those dendritic cells then must traffic the antigens to T cells for activation. Activation requires interaction between CD28 and its ligands (CD80 and CD86) on dendritic cells. Once those T cells become activated, they can then recognize tumor cells' expressed antigens and target them for destruction. Chronic T cell activation upregulates a host of checkpoints on activated T cells; these, collectively, are the partially exhausted TIL phenotypes. PD-1 is just one checkpoint present in the partially exhausted TIL, but it is a powerful one due to the upregulation of PD-L1 on tumor cells in the presence of interferon gamma. Again, PD-1 expression on TIL first requires a strong immune response - that is a key prerequisite along with the PD-L1 on tumor cells.
So what is preventing some of these patients from observing adequate immune responses (significant numbers of TIL) and the significant upregulation of PD-1 on T cells? It could be a number of things including inadequate presentation of tumor antigens (i.e. insufficient numbers of dendritic cells); the lack of tumor antigens that are recognized as being foreign; insufficient interleukin 12 production; or perhaps CTLA-4 outcompeting CD28 ligands (CD80 and CD86) on dendritic cells. In my opinion, in the Immunopulse IL-12 w/ pembro p2b trial, CTLA-4 expressed on T regs are the main culprit for preventing T cell activation and survival in nonresponders. In the data just presented last week by Dr. Algazi, you see a significant increase in FOXP3 T regs in proximity to CD8-positive T cells among nonresponding patients. If you block the CTLA-4 checkpoint on the T regs you essentially allow the T cells to become activated by inhibiting the CTLA-4s' ability to outcompete CD28 for the same ligands on dendritic cells.
TCR clonality in this case is a measure of the proliferation of lymphocytes containing antigen specific T cell receptors. I think Dr. Algazi is saying that nonresponders aren't seeing a proliferation of these antigen specific TCRs intratumorally. The more tumor infiltrating lymphocytes you have, the greater the TCR clonality. It's another way to look at how robust the response is to specific tumor antigens.
Titan, other than the response and safety data presented in the tavo/pembro combination p2b poster, there is something else that really caught my eye. The nonresponders to the combination are seeing significant increases in FOXP3-positive Treg cells.
Why is this important? FOXP3-positive Tregs promote CTLA-4 expression. This expression inhibits immune responses, because CTLA-4 outcompetes CD28 for ligands on antigen presenting cells.
Adding an encoded anti-CTLA-4 agent in a PIIM construct will more than likely lead to complete responses across the board. I would value a multigene construct with encoded anti-CTLA-4 well into the billions of dollars.
Das, here are data that were presented earlier in the year - take a look at figure 3...
http://oncosec.com/wp-content/uploads/2017/02/ASCO-SITC-ONCS-Presentation-Handout.pdf
And you are precisely correct about the percentage of partially exhausted TIL requirement for responses to anti-PD-1 therapies. Getting over 30% for the phenotype leads to responses with anti-PD-1 drugs. Between 20%-30% is probably a matter of ratios between Tregs and exhausted TIL; some get responses and others do not to anti-PD-1 drugs. Below 20% will not get you a response with anti-PD-1 drugs.
New data being presented at SITC by Dr. Algazi should have more individual patient stats.
Das, good questions, and thanks especially for bringing up the one about the Idera data. I looked at their most recent trial presentation on their website and there was indeed one complete responder out of the ten patients. That one CR has not progressed after a year. This makes it 40%PR and 10%CR. I also noticed that SAEs was 44% for grade 3; this is typical for systemic anti-CTLA-4 treatment.
The 33% BORR in the subset versus 50% BORR in the full set discrepancy is likely due in part to skewing in the % of partially exhausted CD8 TIL present at baseline for the patients who were previously treated with checkpoint inhibitors. Looking at individual patient data (previously reported), 7 out of the 9 actual checkpoint inhibitor nonresponder patients enrolled in the trial had an exhausted phenotype less than 4% - these were not only 'cold' tumors, but they were 'frozen' (my word) tumors. In the real world clinic, nonresponders to anti-PD-1 therapies can have a partially exhausted phenotype up to 30% (based on discovery and validation cohorts treated at UCSF). As you might imagine, converting a nonresponding patient to a responding one with say 25% partially exhausted CD8 TIL at baseline will be easier than converting one with say 4% partially exhausted TIL at baseline.
The Idera and Dynavax trials recruited actual nonresponders to anti-PD-1 therapy, but there were no exclusion criteria that would have refused patients with relatively high percentages of partially exhausted CD8 TIL.
Idera has developed an intratumorally-delivered TLR9 agonist that they are currently testing in a clinical trial. They are enrolling anti-PD-1 refractory metastatic melanoma patients into two arms in a phase 1/2 trial - one is an Ipi/IMO-2125 combo and the other is a Nivo/IMO-2125 combo. No results have been posted yet for the Nivo/IMO-2125 arm.
Updated results for the Ipi/IMO-2125 arm show 50% overall response rate and 0% complete responses. No data have been posted yet for duration of responses.
I think the Ipi/IMO-2125 arm will end up with responders mostly progressing due to the PD-1 upregulation over time. The Ipi/IMO-2125 arm will be a dead end in my opinion. And systemic anti-CTLA-4 leads to many SAEs. Yet, Baker Bros own over 10 million shares of Idera.
Even though there are no data yet on the Nivo/IMO-2125 trial arm, I think we can predict how well it will do by looking at Dynavax's KEYNOTE-184 trial. There was a 12-patient subset with metastatic melanoma that failed anti-PD-1 therapy and were subsequently treated with SD-101 (intratumoral TLR9) and Keytruda. Tumors shrunk in 42% of patients, but only 17% actually had a partial response. There were no complete responders among these patients either.
Also, don't forget, UCSF/Oncosec had intentionally selected patients who were the worst of the worst immunologically for the Immunopulse IL-12 with pembro predicted nonresponder trial. Many of these patients had no detectable exhausted T cells present at baseline. Again, this is the reason I think the PISCES trial will do so well - they won't be so restrictive with their enrollment criteria.
Also, just a side note... intratumoral expression of an anti-CTLA-4 checkpoint inhibitor encoded on a polycistronic plasmid vector will be much more effective and safer than the systemic route. If Oncosec includes this in any of their new PIIM constructs, we will likely see most if not all patients becoming complete responders in my opinion. This would easily drive the company's valuation well into the tens of billions of dollars, because the platform could be applied to any solid tumor type. I've said this before and I will say it again, these PIIM constructs are going to be completely disruptive.
Interesting how Dan mentioned checkpoint modulators being included in the PIIM platform - this ought to scare the living daylights out of several major companies.
DNA-encoded checkpoint inhibitors with immune stimulation in one product= major disruption.
I would have to check the actual numbers again, but I think nearly half turned out to be actual anti-PD-1 nonresponders.
The other patients enrolled had failed a host of other therapies, including CTLA-4 checkpoint inhibitor therapy.
Adam missed the biggest distinction of them all...
The Epacadostat plus pembro combination ECHO 202 trial had enrolled (almost entirely) treatment naive patients, i.e. no prior therapies, whereas the Immunopulse IL-12 combo trial had enrolled patients who had failed prior therapies AND had very low percentages of the partially exhausted T cell phenotype. Some even had no detectable partially exhausted cells at all at baseline.
Moreover, the complete response numbers from the Immunopulse IL-12 and pembro combo is over 40%, and the Epac combo was around 14%. Nearly every single responder in the Immunopulse IL-12 and pembro trial is seeing a complete response.
Also, duration of response and the safety profile are shaping up to be better than Epac plus pembro.
I also concur with the value of licensing, and after seeing the abstract for the first reported multigene construct, I am inclined to think that the platform could be used for personalized cancer vaccines. This approach could be licensed for many solid tumor types and at various stages of disease progression. Systemic anti-PD-1 will still need to be coupled with the intratumoral therapy, therefore companies with approved checkpoint inhibitors would benefit greatly. And Merck may just be the tip of the iceberg.
No, they are saying that out of the responders, none of them have progressed.
Progressed=tumor size increases or cancer spreads
DOR=Duration of Response
Every single patient in the study who has responded to treatment hasn't progressed - that by itself is a big deal! Duration of response cannot be determined if they continue to be responders and show no sign of progressing.
Yes! They are suggesting that the multigene construct can be used for personalized tumor vaccines.
And they are encoding an element that improves antigen presentation intratumorally - this ought to speed up and drive strong immune responses that are unique to the neoantigen(s) being targeted. You don't necessarily need to encode all of the most promising neoantigens identified on tumors, just the ones necessary to get the immune response ball rolling. In situ vaccination then takes over.
By the way, there is a lot of research money being poured into personalized vaccines right now. Oncosec is very well positioned in this respect because their approach can be off-the-shelf ready to administer, and the response would be robust owing to the encoded IL-12 and new encoded gene for professional antigen presenting cells. The customization is in the antigen(s) selected from a patient's tumor mutation profile.
Not one single responder has progressed!
This first functional characterization of a multigene construct is a plug-and-play - antigens can be customized to individual patients.
One significant, yet overlooked point regarding the phase 2 combination trial for predicted nonresponders...
The selected patients had VERY low partially exhausted T cell percentages. In other words, they were selecting the worst of the worst immunologically speaking. None of the patients had more than 22% PD-1-positive CD8 T cells. The PISCES trial will enroll actual progressing patients to anti-PD-1 therapy who have higher percentages of the partially exhausted phenotype; this bodes very well for Oncosec and Merck. Not all anti-PD-1 nonresponders have such low levels of inflamed tumors. Again, the trial selected the worst of the worst. In fact, some of these patients didn't have any detectable CD8 T cells with the exhausted phenotype.
The PISCES trial will do well in my opinion, based on the simple fact that there will be more patients with relatively higher partially exhausted phenotype at baseline.
I still cannot get over those CR numbers! Nearly every single responder to the combo became a complete response over time, and none of those patients are progressing.
Thanks for sharing that article, Guti. It seems abundantly clear that local interferon gamma production is essential to get responses. There is a very strong correlation between interferon gamma fold change and response/nonresponse. It is interesting to see them use a p40 MAB in their study.
In terms of nonresponders to Immunopulse IL-12 in combination with Pembro... do these patients have more p40 expression on tumor cells? Or is it CTLA-4 outcompeting CD28? Or is it limited intratumoral IL-12 expression, perhaps owing to tumor heterogeneity? Or, is it just a matter of pseudoprogression? I think some of these questions will be addressed this week and we will have a better sense of why some patients respond (and respond very well) and some don't.
Has anyone noticed how nearly every single partial responder - it might even end up being every responder over a few more months - to the phase 2 combination ends up being a complete responder! Swimmer plots illustrate these conversions. The updated data showed 9 out of 22 patients being complete responders.
None of these treated patients who obtained a response ever actually progressed - that speaks to the robust tumor antigen-specific, i.e. neoantigen, immune response. That probably would not have been possible if IL-12 was not expressed sufficiently intratumorally. IL-12 stimulates the production of interferon gamma by T helper cells. In turn, this increases the activity of antigen presenting cells, which produce even more IL-12, thus driving significant tumor-specific immune responses. This creates a positive feedback loop intratumorally and improves the odds of neoantigen presentation - the reason it is being called an in situ vaccine platform. In theory, every single tumor antigen can be presented, and you radically improve the odds of a response when you have more macrophages present intratumorally.
In addition, the corollary immune cells that result from interferon gamma production are the partially exhausted phenotypes. In the presence of interferon gamma, PD-1 becomes unregulated by T cells and tumor cells respond by upregulating PD-1 ligands. This is where anti-PD-1 checkpoint inhibitors come into play. Without the pre-existing partially exhausted T cells present, you wouldn't get responses from anti-PD-1 drugs.
It looks like Oncosec might even be using a P2A-linked IL-12-encoded construct as a backbone to its upcoming multigene platform. If you aren't familiar with the P2A-linked gene, you should investigate how its expression compares to the current IRES structure.
Reminder: SITC abstracts will be embargoed until 8AM EST on November 7.
A new publication available ahead of print...
https://www.futuremedicine.com/doi/abs/10.2217/imt-2017-0096?journalCode=imt
Pura, first, in terms of their tissue sensing electroporation device, there are no other companies with the technology to my knowledge.
Second, no other companies are transfecting DNA intratumorally using an electroporation device.
Third, no other company is encoding multiple proteins on plasmids and delivering them intratumorally.
Oncosec is approaching cancer with a platform that takes advantage of a tumor's full antigenic repertoire. They don't need to sample tumors to identify the neoantigens, and patients' cells will manufacture the proteins required to drive immunity.
It is not clear yet what their multigene construct(s) will encode, but we will find out next week.
Looking ahead... if Oncosec is in fact improving DNA transfection to maximize protein production with any tissue conditions AND it can transfer DNA encoding multiple proteins simultaneously and intratumorally, then in my opinion it is going to completely disrupt the current market.
THIS HAS TECHNOLOGICAL DISRUPTION WRITTEN ALL OVER IT!
Data will be presented on their multigene platform in less than two weeks. You be the judge.
If I am interpreting the slide correctly, I believe the figure on the right shows patients with disease control (CR+PR+SD). Note how nearly every single one of those plots lands above 20% PD-1-positive T Cells. There may be two that are just below 20% (potentially the stable disease patients?).
Why is this important?
If these are the responders in the combination trial, it demonstrates that the combination can significantly increase partially exhausted T Cell phenotypes; it provides more validation for the use of the biomarker (below 20%=no response, above 30%=response, between 20%-30%=response/no response); and it establishes an intratumoral immune target/threshold for achieving responses in advanced melanoma (and potentially in many other cancers).
There is something HUGE in the slide deck from the World Congress of Melanoma.
http://oncosec.com/oncosec-technologies/publications/
I'm not talking about the missing pages.
There is one slide in there that will potentially provide context to the late breaking SITC abstract acceptance.
Remember this: exhausted phenotypes on CD8 positive t-cells are a double edged sword; they aren't good to have if you got a monotherapy that isn't a checkpoint inhibitor, but great to have if the monotherapy is followed up with an anti-PD-1!
There are many differences in exclusion/inclusion criteria between these trials.
Moreover, patients who have failed prior therapies are much less likely to respond to a given treatment than treatment naive or all-comers. Also, Oncosec/UCSF was selecting patients who had very few exhausted CD8-positive Tcells - even if we question the biomarker assay, the fact remains that the enrolled patients did not have "hot" tumors. These were the worst of the worst immunologically; there was no such requirement in the other trials.
At some point I had a WAG that if shown to be effective and ultimately approved they would price it around $50k. That was based on the company's addressable patient population estimates for anti-PD-1 nonresponders in advanced melanoma (10,000) and the company's projected market potential numbers for the US ($500M). I have seen them throw out a $1B number as well in company slides; this may account for patients in Australia?
I know that price tag has been thrown around, but I agree with Lowe on this point - I just don't think it will be priced that high. That's the price for some of the checkpoint inhibitors on the market, like pembro.
Now that the dust has settled somewhat, here are my personal thoughts on the updated combination data released yesterday.
These patients are not treatment naive - they have failed prior therapies. An unknown percentage of them have failed checkpoint inhibitor therapies including anti-PD-1. The question on some peoples' minds is whether or not the predicted nonresponder trial patients are indeed representative of an anti-PD-1 nonresponder population in advanced melanoma. They used a biomarker assay to select predicted nonresponders. While some, including myself, have questioned the reliability of the assay in accurately predicting nonresponders to anti-PD-1 therapy in advanced melanoma, a couple things come to mind.
The selected patients' exhausted phenotypes are well below the 30% CTLA-4/PD-1hi CD8+ threshold that is highly predictive of response to anti-PD-1 monotherapies. UCSF clinical researchers and others developed the assay thresholds based on observations in discovery and validation cohorts. The assay is based on a total of 40 patients. They "discovered" and "validated" that 100% of patients with greater than 30% of the exhausted phenotypes would respond; and 100% of those with less than 20% of the exhausted phenotypes would not respond. And those patients who fall somewhere in between the thresholds are split between responders and nonresponders. See https://www.jci.org/articles/view/87324.
At baseline, according to previously presented data, the patients enrolled in the combination trial that was just discussed yesterday by Algazi includes patients who are overwhelmingly below that 20% exhausted phenotype threshold. To see any responses out of these patients suggests to me that Immunopulse IL-12 is in fact elevating the exhausted phenotypes to the point where some of the patients land above the 30% threshold. Those who don't achieve responses, therefore, may be in that hit or miss zone or still below the 20% exhausted phenotype threshold. The question that needs to be answered is whether or not real anti-PD-1 nonresponders have something going on intratumorally that prevents them from observing significant elevations in their exhausted CD8-positive phenotype cells. Are their t-regs playing a role? Are CTLA-4 checkpoints on CD8 Tcells putting the breaks on immune responses?
Something to keep in mind for the PISCES trial: there will be enrolled patients who will be close to that 30% threshold for predictive response. The combination trial that was discussed yesterday by Algazi selected patients who were, again, way below 20%. The PISCES trial won't be as restrictive; there will be patients in that 20%-30% zone who would be more likely to achieve responses than patients who have very low percentages.
Another observation... I have never seen so many complete responses in either treatment naive or treatment experienced patients with stage III/IV metastatic melanoma. Those numbers are quite remarkable. You simply never see that level of response! I cannot express enough the significance of those data. Epacadostat plus pembrolizumab hasn't even come close to that percentage IN TREATMENT NAIVE PATIENTS!! I think these data alone will lead to some deal between Oncosec and Merck in a first line setting for metastatic melanoma and perhaps other indications as well. Really, no other combination has demonstrated anything close. This is the second time - the first was the retrospective analysis published last year that showed 50% complete responses in patients who went directly from Immunopulse IL-12 to an anti-PD-1 regimen - that have demonstrated such high levels of response.
Take a close look at Epac plus pembro data for advanced melanoma. Those patients are all treatment naive! All the patients in the immunopulse plus pembro trial had prior treatments. This is a complete no brainier.
While the data don't answer that question specifically, and that has been one of my critiques as well, the complete responders numbers are quite shocking. Also, to have a BORR at 24 weeks of 50% in patients who ALL HAD PRIOR TREATMENT AND ARE THE WORST OF THE WORST in terms of tumor infiltrating lymphocytes, tells me that the combination is certainly working well. I have never seen complete response rates this good in any combination trial thus far for metastatic melanoma, even in trials for treatment naive patients.
The company will be following up with more details on these data through a press release - my guess would be either tonight or tomorrow considering the presentation is tomorrow.
On April 19, 2016 Oncosec delivered unanticipated news about its monotherapy trial follow up at the 2016 AACR in New Orleans. At progressive disease, there were 75% of patients (6/8) who went straight from intatumoral pIL-12 to anti-PD-1/PD-L1 therapy and responded. Out of those 6 who responded, 4 of them were complete responders - that is 50% of the patients who went directly to the anti-PD-1/-PD-L1 therapy! That simply never happens with anti-PD-1 drugs; typically less than 9% turn out to be complete responders following monotherapy pembrolizumab, nivolumab, etc.
Why do I think they observed those responses immediately following progressive disease on Immunopulse IL-12? The intratumoral pIL-12 delivered via electroporation elevates local interferon gamma. In doing so, it drives immunity. However, it is a double edged sword because while driving immunity it is also upregulating PD-1 and CTLA-4 phenotypes on CD8 T-cells and increasing PD-L1 on tumor cells. This creates the 'substrate' that allows the anti-PD-1/-PD-L1 to work effectively. Without those exhausted T-cell phenotypes present to begin with, pembrolizumab, nivolumab, etc wouldn't be all that effective.
So why bring this up?
In two days, we will have another follow up to the monotherapy data, this time with n=51.
To get around Inovio's IP for intramuscular delivery of encoded antibodies on plasmids - this would be important for a systemic anti-PD-1 for example - I think Oncosec has something very special planned. There has been movement on this front in addition to the intratumoral multigene constructs.
I don't share all my DD, but I am dropping this hint.
This is a good illustration of why single or even double agent targets do not cut it in immuno-oncology for the majority of solid tumors. There are several major obstacles that need to be overcome INTRATUMORALLY. Sometimes immunity is driven without the help of immunotherapy, and in these cases checkpoint inhibitors alone get the job done. But for the majority, immune responses are inadequate due to the various obstacles.
For example, you likely can't drive a strong immune response if CTLA-4 on T cells outcompetes CD28 for ligands on antigen presenting cells. Overcoming this obstacle will help T cells recognize the full repertoire of tumor antigens. This is one of the reasons why I hope the new multigene construct includes an encoded CTLA-4 antibody. I cannot think of anything more valuable to immuno-oncology than a sustained release of an intratumoral CTLA-4 antibody. Anti-PD-1 would theoretically be the only necessary systemically administered agent once the exhausted T cell phenotypes reach a certain threshold.
There are definitely paid promotions out there - this appears to be one of them:
Inovio delivers its products in a similar fashion, i.e. electroporation of genes encoded on plasmids, but here are the differences between the two:
1. Inovio administers its products systemically through muscle tissue, whereas Oncosec delivers its products intratumorally.
2. Inovio pre-selects antigens to go on the plasmids to ultimately drive vaccinations. Oncosec takes an in-situ tumor vaccination approach for cancer; this takes advantage of a tumor's full antigenic repertoire.
3. Oncosec appears to be able to deliver a suite of encoded genes on each plasmid - we'll see data on this next month - whereas Inovio is delivering mostly single antigens, sometimes two, in each product. To address all the mechanisms of tumor escape and immunity require multiple therapeutic protein expressions in the tumor microenvironment. Inovio's approach is one that is limited in terms of therapeutic scope. Oncosec is attempting to drive immunity by creating the right conditions in the presence of all potential neoantigens. In addition, Oncosec may likely be attempting to address Tregs and checkpoints as well in their multigene constructs - we will soon see if I'm correct on this.
4. Oncosec has an electroporation device that supposedly maximizes gene delivery through tissue sensing. Inovio doesn't have this technology.