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Man kld2, I've been feeling that here for the past 5 years, and I have the deepest respect for the OncoSec team past and present for their hard work...Bring on the Disruption!
Hschlauch, I love it when you talk dirty...
Nicely Stated Efesdee!
That’s true Hargrove, I recently heard hschlauch say, “I’m not saying I’m Dr. Pierce, but then again no one has ever seen me at Dr. Paris in the same room at the same time!
Keep it coming Hargrove, I love the levity!
See post #41,000 I copied the images and I can see them – – can you?
Lasers, let me know if you can open My last post? I think it will only work from my phone because I’m signed in to the biotech investor
Solid Warrent explanation by RLC on the The Biotech Invester board:
Ok so warrant exercise threw me off a bit today. Emotions have gone from upset, to happy, to upset, and finally back to happy. I've settled on being fairly happy with the news. Let me explain why...
I truly think Dan came into the company because of the data, and the confidence this company would make a splash in the biotech/pharma world. As all know, the company went through a very rough 2 years or so and, as a result, was forced to do some capital raises on terms that were... unfavorable to put it politely. When you look at the capital structure, the ONLY thing wrong with it is the warrant structure in my opinion.
*Forgot to note that the placement agent warrants have all been exercised and aren't included in the total
This is likely a large barrier for astute investors that would otherwise love to put some money here. I actually saw several folks on Twitter mention the "horrendous" or "terrible" warrant structure, BEFORE the news broke today. I really think Dan put the hammer down and said we cannot have this. We're about to move into the limelight and do not want this to be the first impression we make on many new (serious) investors.
The first warrants given to the May 2016 investors (Series A) that the company "induced" to be exercised were the worst warrants on the books. They had a 9 YEAR TERM (expiration was all the way to 5/24/2025). So to get the Series A investor to exercise the warrants and get them off ONCS books, they offered them 1,377,411 new warrants with a $2.26 exercise price and a 2 year expiration date (exp 11/13/2019). Again, this somewhat sucks as it is dilutive to our investment, but 1.) I think it was necessary for this company to "grow up" and 2.) it brought in some nice cash and can likely delay a capital raise by months (which the way the stock is moving, could likely amount to much dilution saved in the long run).
The other (conditional) warrants given to the Oct 2017 investors, are only allowed to be exercised if/when the original Oct 2017 warrants (4,553,200 warrants @ $1.25 exercise price and 2022-2023 expiration dates) are exercised in full (these are the warrants I listed as New 2 & New 3). They offered these investors 1,138,300 warrants at similar terms to the ones above ($2.26 exercise and 2 year expiration), with the following inclusions:
(i) warrants will become exercisable only if and when each October 2017 Investor exercises in full and for cash certain warrants to purchase Common Stock that were sold to such investors in the Company’s equityfinancings completed in October 2017, and
(ii) warrants will contain certain prohibitions against short sales by the October 2017 Investors with respect to the Common Stock issuable upon exercise of the October 2017 Investor Warrants.
If you notice, OncoSec is getting rid of all the long term warrants! If the Oct 2017 warrants (New 2 & New 3) are exercised (likely to happen IMO and will bring in more cash, probably another drop in PPS), the only warrants that go beyond 2020 are at a $4.50 exercise (and there's only 1 million of them). And they'd only have 3.5 million warrants issued! This is a pure clean up.... plain and simple.
So again... to me this just looks like a CEO saying "time to stop the child's play and grow up!". It does suck we have to deal with the consequences of this (dilution!), but in all reality, we knew they had warrants with shit terms. This was 100% necessary for this company to move forward (and be taken serious by investors) IMO and Dan/Punit are choosing to do this at a good time given the volume and price action lately.
How do you know TV?
Staccani, I think you need to read this regarding your concerns about stage IV, subcutaneous tumors otherwise thought of a soft tissue tumors:
The OncoSec GENESIS™ research generator was developed specifically for gene electro-transfer. It features customizable electroporation parameters for construct-specific optimization of expression, and it is the only in vivo electroporation device enabled with TRACE™ Technology (Tissue-Based, Real-Time Adaptive Control Electroporation.) TRACE™ technology incorporates an electrochemical tissue-sensing control system to automatically adjust pulse width and treatment duration in real time during the electroporation procedure. This feature enables tissue- and therapeutic-specific delivery optimization, maximizing uptake of the therapeutic while reducing unnecessary cell ablation or damage. In research models, GENESIS™ with TRACE™ has yielded higher and more consistent in vivo protein expression versus fixed-parameter electroporation, even in heterogeneous tissues.
Potential advantages of using GENESIS™ with TRACE™ for the objectives of animal immunization include cost savings versus recombinant protein administration, a shortened pre-immunization timeline relative to recombinant protein production, and display of the immunizing antigen in its native conformation. The latter benefit may be particularly relevant for certain therapeutic indications, including immuno-oncology, in which many key targets require functional agonism and/or structurally-complex therapeutic modalities such as multimeric forms. To date, OncoSec has generated multiple high-titer antibody libraries against immuno-therapeutic targets.
The OncoSec Technology Access Program makes OncoSec's electroporation technologies available to collaborators for preclinical research. Devices are available for intratumoral, intradermal, and intramuscular delivery
I forgot about that--I think your right on.
Would that be common when partnering for a company to take a stock position
prior to deal? Or would that be insider trading?
Thanks TV, I missed hsch say that. Could you direct me to the Post?
Yes...
What do you think happen to multi-gene mouse trial data that was share at SITC?
You bet Lazers, do you have any thoughts why no multi-gene news this morning?
you bet Kld2, any thoughts on why no multi-gene news today?
Yeah Twiz, Exciting isn't it?
RLC's (The Biotech Investor) "transcript" post of Algazi Conf. Call:
Listened to the call a couple times and typed this up (haha man do I miss Patti! She was amazing at getting super accurate transcripts out quickly). Started as notes but sort of turned into a transcript (haha). There were a few things I couldn't understand and/or interpret on the call (mostly some scientific terms said too quickly or quietly), it's not proofed and I paraphrased a few things.... But for the most part it's VERY accurate (I bolded some things in the Q&A that got me excited):
Punit's Intro
* Company feels IT-TAVO-EP is a viable solution for patients refractory to checkpoint inhibitor treatments
* Ipilimumab ORR following progression on Pembro is 13% and not all of those responses are durable (implying that cold tumors VERY rarely turn hot on their own... and even if they do, they don't have the immune environment needed to have a durable response. A solution is NEEDED)
Alain Algazi (Presentation)
* Combo trial is treating cold tumor population that's VERY unlikely to respond to Pembro mono-therapy
* A little discomfort upfront, but virtually zero side effects... very favorable to other injection approaches where you don't have the discomfort at treatment, but tend to have some severe side effects
* Tumor takes up plasmid expressing IL-12. Beauty is that it does this for a week or so at a time. IL-12 is expressed where the tumor antigens are, right in the tumor micro environment for a long period of time. You get long, focused exposure with very little circulating IL-12. This leads to regression of treated and untreated lesions.
* Of the 23 patients in this data set, 10 had prior anti-Pd1 treatment (Pembrolizumab/Keytruda) and 7 had prior anti-CTLA-4 treatment (Ipilimumab/Yervoy)
* In combo study population, we would’ve expected a ~6% ORR from these patients... but we saw a 50% ORR.
* We had a lot of CR’s. Durable CR’s and still in remission. One new lesion that was retreated and it’s gone now too. So these patients had durable remissions... a lot of deep responses... and a high ORR.
* One patient, a pig farmer & electrician, who was technically a progressor on Tavo+Pembro treatment according to RECISTv1.1 because he had some flare in tumors before eventually getting better... progressed on 2 differenent PD-1 checkpoint treatments (Nivolumab and Pembrolizumab). He couldn’t work or even walk because he had huge tumors on his heel, but he’s completely functional now. Counted as having PR bc of clinically relevant response. He grandfathered out of the trial... they’re trying to get him an extension bc he wants more treatments. "He looks great!"
* Another patient (CR) progressed on TVEC treatment
* Another patient (PR) progressed on Ipilimumab
* Didn’t have anybody falling out of remission after the 12 months, when we stopped treatment. So these are durable remissions and these people are still doing very, very well.
* Toxicity doens’t capture the whole picture. This side effect profile basically looks exactly like Pembro... it doesn’t add a lot of toxicity.
* Data suggest IT-TAVO-EP is an effective therapeutic modality in refractory anti-PD1 patients.
* People might question the biomarker... well the next step is PISCES. The best biomarker for non-response is non-response, so we’re using refractory anti-PD1 patients and we’re going to validate these findings in that study.
* Chris Twitty Has done a lot of translational work on this data so we have a lot of insight into what’s going on biologically.... some correlative data to support what we’re seeing clinically
Mechanistically:
* They see increase in cytokines levels, particularly in responders
* They see increase in natural killer cells (an innate immunity)
* They see an increase in proliferating CD8 positive cells, particularly with the combo therapy... so they think they’re seeing a synergistic effect where they’re seeing more proliferating CD8 positive t-cells in the tumor.
* They also see an increase in adaptive resistance... Regarding the melanoma score.... If you give IT-TAVO-EP monotherapy you see a significant net increase in PD-L1 staining suggesting adaptive resistance, and this is much more pronounced with the combo therapy. Of course in the combo therapy, you’re really addressing that adaptive resistance with the PD-1 antibody.
* You also see an increase in inflammatory gene expression, and this also appears to suggest synergies between IT-TAVO-EP and Pembrolizumab
* Pembro isn’t designed to turn tumors from cold->hot, but they’re getting a super robust increase in cold->hot tumors with Tavo+Pembro (over the IT-TAVO-EP mono), again suggesting a synergistic effect.
* TIL’s increased in treated and untreated lesions, in responders you see an increase in the effect to regulatory t-cell ratios vs the non responders you don’t. See they think the difference between the two is whether you’re increasing those ratios. Dr. Algazi is working on an investigator sponsored trial where they’re adding up a catostat which will help to deplete some of those regulatory cells. So because this is well tolerated, they can do triplet combo and he expects they’ll be well tolerated... and we’ll find that out soon.
* Data demonstrates IT-TAVO-EP promotes innate and adaptive cellular responses triggering adaptive resistance and a partially exhausted immune response that Pembro is able to reinvigorate, suggesting clinical synergy and potentially a really effective comination.
Q&A
* Q( Chris Twitty): In your practice, how do you decide when to give anti-PD1? Do you do testing or just throw everyone on anti-PD1 treatment immediately?
* A (Dr. Algazi): The standard has been everyone goes on anti-PD1 antibody... that’s the most common practice. We’re in an academic center so we feel comfortable using these assays because we feel they’re useful and can identify patients. But the standard has been to use PD-1 monotherapy. The alternative in standard of care is to use Nivolumab-Ipilimumab combo which can be extraordinarily toxic.
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* Q (Chris Twitty): Do you use the biomarker assay when patients come in looking for treatment options?
* A (Dr. Algazi): It’s not a validated assay so technically we can’t use it for clinical decision making. So we have limitations because it’s not an FDA approved assay.
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* Q (Chris Twitty): So in the bigger context then, of all the patients that come in and you put them on a PD-1 inhibitor about a third will be the rapid progressors, about 40% will be subjective, and then the ones that respond. So in the greater context, where does this data fit into the current practice of patients with metastatic melanoma in terms of response rate and ability to respond when you combine Tavo and Pembro?
* A (Dr. Algazi): With the data we have now, if you’re looking at the first line... you could potentially stratify your patients and that’s what we did. Patients who had high partially exhausted t-cell proportions... we just put them on Pembro mono therapy. That was the standard while we were running the trial. And those patients tended to respond. And the patients less likely to respond we put them on TAVO+Pembro and half went into remission. So now just by stratifying patients by selection, we’re increasing the remission rate so that the majority of patients are going into remission without getting any of the severe side effects of the current alternative in standard of care (Nivo-Ipi combo)
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* Q: (Robert Andtbacka?) Of course predicted responders weren’t included in the combo study, so assuming this therapy was used on the total population what would you expect the ORR to be?
* A (Dr. Algazi): I would say 75%. The caveat is we’re looking at patients with accessible lesions. So I think there’s still a technological front where you can actually make devices and I know Punit and the OncoSec team has been working on refining devices and working on ways to access more lesions. I gave a similar talk at a Merck meeting at ASCO and there was a lot of interest in saying “Can I do a pancreas using this techinology?”... and you can’t right now, but why not? You could actually have an endoscopy... there may be ways to adapt this so it can be used in other settings.
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* Q (Robert Andtbacka?): Chris you did a lot of work on the immune signature and we’re looking at the biopsies and so on... Can you comment on the cold profile that you see and how that converts to a hot profile... and how that relates to the clinical response that we subsequently see?
* A (Chris Twitty): The TIL assay does a really good job in that we can look at the patients that were enrolled, add the low PD1, CTLA-4 population and contrast that with the patients that were excluded from the trial that have high PD1, CLTA-4 population and we see a pretty clear division, in terms of not only PD-L1 expression but gene expression. And this gets modulated with the combo therapy, so we see these levels really jump up on the gene sets in the volcano plots. So certainly that classic gene signature is there, but then if you look these other broader immune markers are there as well, so we see clinality that a lot of people are becoming to understand being an important player in terms of how it fits into immune responses... so we see a significant increase in clinality after treatment and we also see peripheral effects as well and all of this seems to cut with the responders suggesting that as you would expect this is an immune based therapy, so phenotypes by flow... memory markers, slack markers and the peripherally proliferating exhausted t-cells as well. So it all supports this concept of a signature up-regulated in the responding population. In terms of prediction, it wasn't really something we were trying to focus on. One of the interesting things that's going to be highlighted in Alain's SITC poster is that the clinality in the blood does seem to really, at screen, seem to separate between the responders and the non-responders so that's a higher clinality in the non-responders and a lower clinality in the blood and we're going to drill into that a little deeper and see what we can understand there, but that's the one thing that's teasing at something that we might be able to predict coming into this.
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* Q (Robert Andtbacka): How soon can you see changes in the blood or tumor biopsies after initiation of therapy?
* A (Chris Twitty): Clinically it happens pretty quick... as early as cycle 4. But immunologically we tend to see changes after cycle 2, so after 1 cycle of therapy we see immunological changes that... I'd be cautious to say we can identify the responders... but certainly they're changes that tend to support the concept that they will become responders.
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* Q (Robert Andtbacka?): And with that then can you also determine the depth of the response, because you had mentioned something about that Alain, saying if you develop a certain signature you're more prone to a CR than a PR or is the data still too early to determine this?
* Follow up Q (Punit): Do you want to put it into the context of the recent publication you guys did? There's now 2 publications that really highlight the predictive capability of this assay and I think that's worth noting.
* A (Dr Algazi): It's pretty robust... I think you can give a pretty good prediction. You don't get the level of granularity you need to determine who will be CR vs PR, but the assay does a good job predicting responders vs non-repsonders.
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* Q (Robert Andtbacka?): So moving onto the PISCES trial we're doing now, which is taking patients that have failed a PD-1 inhibitor and then putting them on this combo therapy to try to change these cold tumors to hot tumors. What about the patient populations in the existing Phase 2b combo study and the upcoming PISCES study... are they different or are they similar?
* A (Dr. Algazi): The prediction would be that they're the same. But personally, if I'm investing in something or thinking about doing something, you always want to maintain a healthy skepticism. I think it's going to be exactly the same. It's really a validating study. Because I think the assay is a good one. But when you see the data, it's kind of a done deal. If you're seeing a great remission percentage in that population, these are demonstrated refractory patients because they didn't respond. Clinically, if you give someone a PD-1 antibody, you don't see people magically responding at week 30. For the most part, you see what's going to go on within the first 12 weeks... 18 max. And we're going to wait long enough to make sure they're truly non-responders, but I predict we're going to see exactly the same thing. From an investment perspective... if you wait for this data, that would be like saying I'm going to invest in Merck because Permbrolizumab is a hot drug... well you should have done that a few years ago. And I don't know anything about the investment side... I have a 401-k and that's it.
* A (Punit): The interesting thing in the existing combo study, is that while we've had a mix of post and pre PD-1 patients, in the PISCES trial we're only enrolling post PD-1 patients. There are 11 patients that will be highlighted on the poster that had prior checkpoint therapy.
* A (Robert Andtbacka?): It's one thing to have an assay that's highly predictive, it's another to have actual non-responding patients and that's why we're doing the PISCES now.
* A (Dr. Algazi): It's really a validation. It's a really robust validation. We talked a lot about how the trial is designed and I think it's going to be a really robust test of the technology and I think this is going to be pretty definitive.... It's almost like the subsequent Phase 3 is almost like an anti-climax because if we see good signal in this... I think this is the proof.
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* Q (Robert Andtbacka?): So you didn't show median PFS... we showed PFS but I didn't see median PFS.
* A (Dr. Algazi): That's because we don't know the median PFS because everybody is still in remission. We haven't had anybody fall out of remission yet and I see these people in clinic on a regular basis. The most common complaint is "Do I have to keep getting scanned and coming in?" But they're all doing really well.
* A (Robert Andtbacka?): One thing I'll say about the treatment itself, is we have a patient who has been on multiple therapies and had progressed on all of those therapies... and that patient has had universally CR to the Tavo+Pemrbo. It's interesting to see that because you're expecting that since he progressed on so many therapies he'd progress here, but he didn't... he had a CR.
* A (Dr. Algazi): One of the lessons I think I've learned in Melanoma is that if you have a focal intervention it's just like (inaudible?)... you don't see responses because.... here with IT-TAVO-EP it's very clean. You're doing one thing... expressing IL-12. As opposed to trying to develop a virus construct or somethign like that, that's doing multiple things. And even some of the things that you'd think would be more focal like a TLR agonist you get a lot of systemic inflamation of the protein based therapy. Here you're really just targeting the therapy where you need it and getting an extended delivery, so it really is doing exactly what you want in a measured way.
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* Q (Dan O'Connor): Can you talk a little more about the patients that had prior checkpoint experience and what occurred with those patients?
* A (Dr. Algazi): The one that's the most striking is the one I showed where he had 50 lesions throughout his lower extremity and groin nodes and he initially had a flare but ultimately his tumors got smaller and smaller over time and you saw this really robust response. He's actually been off for 3 months after sort of graduating and the tumors are smaller than they've ever been. And that's true of other patients that had prior checkpoint inhibitor therapy... some of them had very rapid remissions. So we are seeing some sign of refractory patients responding. But this is a smaller group of people than will be on the 48 patient PISCES Phase 2.
* A (Robert Andtbacka?): And to add to Dr. Algazi,many times we find these patients when we start these therapies, it's not uncommon for them to have progression... whether that's true progression with new lesions forming or just having the existing lesions increasing in size, but then the patients respond. The other thing we often see, especially since we're treating patients with in transit disease, many times you still see the pigmentation... and we've done this so many times that we still see pigmentation and we wonder why there's any residual tumor at all but it's just pigmentation.
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* Q (Dan O'Connor): So when you look at the totality of the safety profile... to me it seems incredibly remarkable... there's really extremely little side effects associated with the therapy. Can you comment from your point of view on that?
* A (Dr. Algazi): The big thing is the injection you have to deal with the electric current. We use local anesthesia and most tolerate it well... it's often transient. We were taking these 5 minute time points... asking what kind of pain do you have every 5 minutes and it was almost always invariably zero. So the only thing is just dealing with the procedure, but between the procedure you just don't see a lot of side effects which makes it really easy for people to do. It also makes it combinable, so one thing I'm exciting about is doing a triplet combo therapy here and there's triplets being done, but you know those are all likely going to be riddled with nasty side effects. I think it's going to be tolerable and possible to do a lot of things with this and there's a lot of potential for growth. And I think we're seeing corroborating data... in Brisbane, Australia I gave a talk about the systemic effects of the priming therapy and we're seeing that you really do get systemic effects so I think this really could be a real wave of the future because it's combinable and well-tolerated.. and the only thing is dealing with the minor discomfort with the procedure itself... and I know OncoSec is working on reducing the discomfort involved with the procedure.
* A (Robert Andtbacka?): We're currently just using TAVO right now, but really this is a platform and it lets us consider other plasmids and so on we can electroporate in as well.
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* Q (Dr. Algazi): An interesting question academically is do you need systemic therapy? Do you need to give drugs through IV to get an immune response?
* A (Robert Andtbacka?): That's a really good point Alain and I think that with some of the things we're seeing right now, I'm not convinced you'll need systemic therapy. I think there's more data needed but depending on how you do the local therapy, you may be able to get enough of a systemic response but the jury is still out. As we've learned more about intratumoral therapies, it used to be we saw minimal systemic effects, but we're seeing more systemic effects now.
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* Question about dosing change/escalation:
* A (Dr. Algazi): Almost everyone is responding so I think we have a good dose. We're seeing really robust clinical effect We're seeing abscopal effects, we see what appears to be synergy and we're going to validate that synergy so it appears to be a an effective dose. Maybe we could go a little higher but I'm not sure what the added benefit would be because we're already seeing pretty robust effects clinically.
* A (Robert Andtbacka?): To add to that, with seeing the robust results we're seeing, it also becomes a matter of practicality... how many times do we want to bring patients in for treatment and so on.
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Intro of New CEO, Dan O'Connor:
Dan: We ran a little bit over time so I'll make this brief. The data that you saw here this morning is the reason why I joined this company... plain and simply. I really appreciate everyone's work on this technology. I think we have a really important data set in front of us. I'm looking forward to amplifying this data set to the public in the months and weeks to come. And I really appreciate your support. I'm looking forward to the PISCES study which is open and now screening for patients.
So where's the news! It is Monday after all
Wow, how benevolant.
Lazers...I don't know if your experience in BP would help with this question, but it is something my wife asked and I thought it was interesting, and that is, "does the time of year have any impact upon when to acquire another company, like fiscal year or tax year?"
That got me laughin' Chick :o)
Oh yeah, it’s refreshing – – I love seeing buys of eight and 10,000 shares at a pop. Really good sign the big boys are coming in, while watching the retailers jump around taking profits.
Well, I got to say lasers – – I haven’t been this excited for This company in years
Well if that happens check, I guess I’ll be visiting you on your yacht parked at your own island down in the Mediterranean
Yes I completely agree with you, that’s why am happy that the timing of the PIIM Platform is showing up at just the right time here!
And if I were Merck lasers, That’s the last thing I would want to see happen after having spent the last three years doling out multi millions of dollars of keytruda That helps a company achieve notable results with a PD-1 drug, Only to see that little company make multimillion dollar deals with other businesses off that data – – it doesn’t make sense to me that they would do that, but I do like the idea of others being interested to leverage a negotiation/bidding war.
That’s a great point chick, I’d be all over that too.
That PIIM platform alone will, I think, generate acquistion intrest...but then, I thought this back in 2012 when il-12 was out-dating their bleomycin chemo platform : /
WOW, does show what a bag holder I am!
Chick, I may have said this before, but the potential of the upcoming pipelines and their broad aplicability to multiple indications in the non-resonder environment with an already predictable amazing safety profile, do to it ability to lower even the toxicity of it's combination drug, make this a multi billion company. $30 a share is "Chick"en-feed :)
If I were Merck, I wouldn't want to risk this platform being available to to other big Pharma to either improve their results of Opdivo/Yervoy or even outdo Keytruda/IL-12 platform.
Yeah, Adam doesn't get too far into the specifics to hedge against conclusions at early phase development, but with regards the comparison of Epacadostat to ImmunoPulse, those distincetions your pointing out are forcasting a greater success rate -- BUT also, ImmunoPulses squeeky clean safety profile of only mild grade one adverse events, comparitively:
Hey Ash, easy on TJ with the "old" stuff OK ;)
Actually it’s not the entire float, it would be considered half the float since there is equal amounts of buying and selling occurring.
We’ll see something pop once there’s a greater increase in the buying which just hasn’t happened throughout the day.
I think an important take away from the article is feursteinPoints out that insight has a $23 billion market value, and that half of that value– – Meaning over $11 billion of that market value – – is attributed to the still unapproved epacadostat. He’s basically saying that ImmunoPulse /OncoSec should be valued similarly if not more so since it is further along in its development.
By ADAM FEUERSTEIN @adamfeuerstein NOVEMBER 8, 2017Will tiny OncoSec break out with promising melanoma immunotherapy study results?
The addition of an experimental immunotherapy from OncoSec Medical (ONCS) to Merck’s (MRK) checkpoint inhibitor Keytruda is shrinking tumors in almost half of the skin cancer patients treated in a small clinical trial, according to updated results announced Wednesday.
That’s an encouraging tumor response rate, on par with what Incyte (INCY) has observed when its IDO inhibitor epacadostat is combined with Keytruda in skin cancer patients.
Similar results, so investors — besotted by all things cancer immunotherapy — must be equally enthusiastic about OncoSec and Incyte, right?
Nope, not even close. Incyte carries a $23 billion market value, with the still-unapproved epacadostat accounting for approximately half of that. OncoSec’s total market value: a microscopic $40 million. Shares of OncoSec closed Tuesday at $1.25.
Investors have largely ignored OncoSec’s approach to boosting patients’ response rates to cancer immunotherapy, but that might start to change with the updated data being presented Wednesday at the Society of Immunotherapy for Cancer (SITC) annual meeting.
Last month, Steve Cohen’s family office Point72 Asset Management disclosed a 5.7 percent stake in the tiny biotech company. An investment of that size is not even a rounding error for an $11 billion hedge fund, but it does show someone on Wall Street is taking notice.
OncoSec, just like Incyte and dozens of other competing drug companies, is trying to find a solution to a biologic roadblock that, to date, has limited the efficacy of checkpoint inhibitors like Keytruda or Bristol-Myers Squibb’s Opdivo to a minority of cancer patients. In melanoma, these drugs are generally effective in about one-third of patients.
Checkpoint inhibitors work by releasing the brake on the immune system, so these drugs are most effective against “hot” tumors already studded with T cells and other immune cells.
“Cold” tumors are largely resistant to checkpoint inhibitors because they lack significant engagement by immune cells. To extend the analogy, releasing the brakes on a car that’s missing an engine still doesn’t travel very far.
How to turn “cold” tumors into “hot” tumors? OncoSec’s approach is to inject “cold” melanoma lesions with DNA-based interleukin-12 (IL-12), a protein that activates components of the immune system. OncoSec then uses a short series of electric shocks (delivered with needles) to open the membrane of the tumor cells and help the IL-12 to enter.
Related Story: The investor euphoria for Incyte’s experimental cancer drug is hard to rationalize
The company’s phase 2 study enrolled 22 patients with melanoma predicted to be unresponsive to checkpoint inhibitors based on findings from two biomarker assays. All the patients were treated with a series of electrically pulsed injections of OncoSec’s ImmunoPulse IL-12 directly into their melanoma lesions followed by standard intravenous delivery of Keytruda.
The results: Nine of the 21 evaluable patients, or 43 percent, responded to the IL-12/Keytruda combination treatment. Eight patients, or 38 percent, had a complete response.
After 15 months of follow-up, 57 percent of the patients have not experienced regrowth of their tumors, with a handful of patients followed for 18-24 months without progression.
OncoSec also analyzed samples of tumor taken from patients before and after treatment with the IL-12/Keytruda treatment, which showed increases in types of immune cells suggesting the tumors were being turned “hot.”
With the important caveat that cross-trial comparisons are challenging, the OncoSec IL-12 results presented Wednesday are not all that different from previously released results from Incyte’s phase 2 clinical trial of melanoma patients treated with epacadostat and Keytruda: an overall response rate of 56 percent, including complete response in 14 percent of patients. The median progression-free survival for the Incyte study was 12 months, with 49 percent of patients progression free at 18 months.
“From a clinical perspective, both drugs look very promising,” said Dr. Howard Kaufman, an oncologist at Massachusetts General Hospital and immediate past president of the SITC, when asked to make comparisons between OncoSec’s IL-12 therapy and Incyte’s epacadostat.
“What’s missing with both of these drugs, of course, are data from randomized controlled trials using a survival endpoint. We need to see those data first before drawing any conclusions, but there is potentially a role for both of these drugs in different patients,” he added. [Kaufman did not participate in OncoSec’s clinical trial but he was recently hired as the chief medical officer at a private biotech company developing engineered viruses to activate the immune system to fight cancer.]
Without a control arm, it’s impossible to determine precisely if OncoSec’s IL-12 therapy was responsible to the tumor shrinkage reported, or if the patients were simply responding to Keytruda alone. That is a fundamental weakness in the study results presented at the SITC meeting, although in fairness, the same criticism can be leveled against Incyte and its clinical trial.
However, OncoSec did enroll a handful of melanoma patients with tumors that continued to grow after prior treatment with a checkpoint inhibitor. The tumors in some of these patients later shrank when IL-12 was administered in combination with Keytruda, including a single patient with a complete response — a hint that OncoSec’s therapy was working as designed.
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OncoSec CEO Punit Dhillon described another important patient in the study: A pig farmer who was treated with IL-12/Keytruda after his melanoma lesions had already failed to respond to Keytruda, Opdivo, and Yervoy. Three months after the combination treatment began, the patient’s tumors stabilized, then started to shrink. He’s been followed for two years, still in partial response, said Dhillon.
The only way to know for sure if OncoSec’s therapy is working as designed is to test the combination of IL-12 and Keytruda in patients with melanoma confirmed to be unresponsive to Keytruda (or any checkpoint inhibitor) on its own.
OncoSec is enrolling just such a clinical trial, in collaboration with Merck. Study results are expected to read out in the middle of next year.
On Tuesday, Dhillon ceded the CEO role at OncoSec to Daniel O’Connor, the former CEO of Advaxis. Dhillon remains with OncoSec as president and retain his board seat.
Adam Feuerstein
Senior Writer, Biotech
Adam Feuerstein is STAT’s national biotech columnist, reporting on the intersection of biotech and Wall Street.
subscription to STATNEWS required for adam f. article, BUT, he does equate ImmunoPulse stats with those of Epacadostat by Incyte. Thought I would post Epacadostat results--Note the side effects!
Early Keytruda combo data paint Incyte’s epacadostat as a threat to Bristol-Myers’ I-O melanoma franchise
by Nick Paul Taylor | Aug 31, 2017 8:18am
Incyte has presented data suggesting its IDO1 enzyme inhibitor dials up the effect Keytruda has on advanced melanoma patients. The interim phase 1/2 readout paints the Incyte-Merck combination as a potential improvement over Bristol-Myers Squibb’s incumbent CTLA-4-PD-1 cocktail.
As of late February, 54 patients in the advanced melanoma group of the epacadostat-Keytruda trial were evaluable. The overall response rate clocked in at 56%—which broke up into eight complete and 22 partial responses—and the median progression-free survival (PFS) was 12.4 months. The responses occurred regardless of the PD-L1 and BRAF mutation status of the patients.
Incyte also has evidence the responses are durable. All bar two of the 30 responses to the drug combination are still ongoing.
The data lend credence to Incyte’s belief in the mechanism of action of epacadostat. Tumors upregulate the IDO1 enzyme to evade the immune system. Epacadostat inhibits this enzyme to dial down this evasion, helping the immune system to hit the tumor with its full force. While more data are needed to confirm the hypothesis, that could have implications for the tussle for the immuno-oncology market.
Incyte’s data stack up well against the combination of Bristol-Myers’ Opdivo and Yervoy, which won FDA approval at the start of last year on the strength of a PFS of 11.5 months in patients with advanced melanoma.
There are reasons to think the slight difference between the PFS results from the clinical trials will ultimately translate into an edge for Incyte. Bristol-Myers’ trial enrolled treatment-naive patients, whereas some subjects in the Incyte study have previously been treated. Incyte’s treatment-naive subpopulation is yet to reach a median PFS but the rates achieved at six, 12 and 18 months suggest it is on track to better the Opdivo-Yervoy result.
Incyte can also point to safety data to argue its combination could better that of Bristol-Myers. The latest update reported 17% of patients suffered grade three or worse treatment-related adverse events. That compares favorably to results generated by Bristol-Myers’ combination, which, in an update earlier this year, was linked to a 58% rate of grade three or four adverse events.
Hey chick, I believe they made their last payment a few years back
Things are going good titan, thank you for the well wishing! I got to say my excitement and enthusiasm is picking back up. I was a little nervous for a while thinking that they were going to drop immuno pulse for it’s mediocre showing in place of the new multigene approach which would then push everything away back as far as timeline for marketing or Buy out. But once they revised the BORR to 50%, it really changes what’s going to go down this week. I don’t feel like a investor here I feel more like a capital venturerist, With all that I have in this little company – – but I really think it is a great opportunity here for the next 6 to 8 years of doing something great in oncology.
yep TJ, just picked up more, 2.5k for the pop I hope ;)