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Well, here you go folks. The abstract body from the AACR conf. This was submitted by Dec 3. Doesn't really dive in to efficacy much. I wouldn't be surprised to see a pr in the morning about it.
Introduction: Preclinical models have shown that activated DC’s can effectively clear both injected (local) and non-injected (distal) inoperable tumor lesions. Based on this strong rationale a Phase I trial was designed to exploit this finding in late stage solid tumors.
Methods: We designed a phase I study to determine the safety of intratumoral injection of activated DC by administering the product repeatedly until disease progression or unacceptable toxicity, in advanced cancers. Endpoints included maximum tolerated (MTD), dose limiting toxicities (DLT), safety, and immune response criteria (iRC) and RECIST. The treatment consisted of image-guided intratumoral (IT) injections of autologous, activated dendritic cells (DCVax-Direct,). Injections were given on days 0, 7 and 14, followed by booster immunizations at weeks 4, 8 and 16. Three dose levels, at 2 million, 6 million or 15 million DC per injection, were tested. Concomitant, serial biopsies were performed at the time of the vaccination in the absence of toxicity /progression. Systemic immune responses were tracked through evaluation of T cell subsets and cytokines in circulation, and through T cell receptor (TCR) sequencing in the tumor tissue and in the periphery.
Results: To date, 40 patients (men, n=18; women, n=22), median age 53.7 (range 30 - 73) years, median of 3.1 (1 - 6) prior therapies (including 1 patient with prior immune therapy) were enrolled. Seventeen patients were treated at the 2 million dose level, 19 at the 6 million dose level, and 3 at 15 million. The MTD has not been reached and there were no dose limiting toxicities. Two patients experienced Grade 3/4 drug related toxicities : one case of fever and dehydration and one case of systemic inflammatory response syndrome. Patterns of immunological reactivity were assessed by pathological scoring on tumor biopsies for 29 patients, and included increasing necrosis in 62% of patients and emergence or amplification of infiltrating T cells in 55%. In-depth study was carried out in a patient with therapy-refractory, de-differentiated liposarcoma whose imaging at 12 weeks post initial injection revealed necrosis in the primary tumor and stable lung metastases. Biopsies demonstrated an intra-tumoral inflammatory response consisting of lymphocytes, macrophages and TIA-1 expressing cells, suggesting cytolytic activity. TCR sequencing revealed the presence of shared TCR sequences in the tumor as well as in circulation, demonstrating a systemic anti-tumor response. Analysis of T cell subsets in circulation demonstrated normalization of the CD4/CD8ratio.
Conclusion:
Immunotherapy with partially activated DC’s injected IT demonstrate early signals of immune reactivity even in late stage patients with cancer. Preliminary data support the generation of anti-tumor effects following IT injection of the partially activated, autologous DC’s.
Time will tell. But stable disease is not a typical characteristic of a stage IV cancer patient that's failed all other treatment. I think the FDA will get creative or at least be somewhat flexible in how they evaluate this patient population. If you had all 40 patients tumors shrink 28% but since it didn't meet the 30% threshold of recist, do you think the FDA would just say oh well too bad? Especially since there is considerable variability in measurements. No I don't think so. That response rate with that amount of shrinkage is a dramatic effect. That may be a stretch in terms of expected results but the point is the FDA guidelines often use words as may, should, can, generally etc. There is some flexibility in the language.
CI and CAR-T's are "killing" it but have also killed patients and we have no data on durability. Exciting nonetheless, but overall benefit may not be more than what Northwest provides.
Yes this is true "generally" but the FDA will not ignore, nor will the market, that the patients are seeing a clinical benefit for majority of patients who have stage IV cancer. And I wouldn't be surprised to see the FDA use a different criteria going forward when evaluating this.
No prob Doc. Again, we already know they met the recist criteria for stable disease. That is considered a response. Some patients, at the time they released that, had up to 28 percent shrinkage and they weren't done with their treatments. So for all those that were at or near 28 percent shrinkage only needed another 2 percent to meet the partial response criteria for recist. I would expect a pr to have been met by several patients.
We should all recall Northwest refute to AF, in particular the part about the recist criteria(below). Even if the majority of patients are seeing stable disease this is a very big deal and is considered a response using recist. Also keep in mind that this phase I is to assess safety primarily and we will easily meet this endpoint. There will be no failure to meet endpoints so the stock has absolutely no reason to tank as some here have suggested.
Actual facts: While still only part way through treatment, more than 50% of these patients (11 of the 19) have already shown tumor shrinkage of up to 28%, substantial tumor cell death and substantial accumulation of immune cells in the tumors. These data were shown in imaging scans and biopsies provided by the world-renowned cancer centers conducting this clinical trial, as the Company made clear in its announcement and conference call.
Feuerstein claim: “Under the globally accepted definition of tumor response known as RECIST (Response Evaluation Criteria in Solid Tumors), a partial response requires a 30% reduction in the size of the target lesion.”
Feuerstein claim: “DCVax-Direct: 0% response rate.”
Actual facts: There are numerous types of established measures of patient responses to treatments.
The measures reported in the Company’s announcement (partial tumor shrinkage, substantial tumor cell death and substantial accumulation of immune cells in the tumors) are considered clinically significant and are regularly the focus of peer reviewed scientific and medical publications in oncology, particularly for late stage disease which is the focus of the Company’s DCVax-Direct trial.
The RECIST criteria are just one set of measures, and the Company has made no claims about these measures. Further, the RECIST criteria themselves include multiple categories: they recognize not only a “Partial Response” of 30% or more — they also recognize “Stable Disease” (which includes tumor shrinkage of up to 28% as has been seen among the early responses in the Company’s DCVax-Direct trial).
No doubt its coming very soon. I would love to see it done around 12 per share after some great data. I am hoping Woodford does the next round as well. And we should also assume that it will be favorable financing. Once you do a deal like the last one with Woodford, there is no going back to neg terms.
Maybe slightly over but they will want a solid cash position as the start, up to 3 phase II trials. They will likely want to do it before they report for the quarter as to not show such a weak cash position.
Which is what I was saying on here several days ago. A capital raise is definitely on the way. I believe it happens right after the data and I believe the data will be very positive and elicit a run over 10. I think Linda is as a point where she/cognate have substantial ownership and are now comfortable letting the price rise. Evidenced by the new and significant investor Woodford. He will work with Linda to raise money at a higher and less dilutive price, given he also has vested interest.
Let us not forget the world vaccine congress 2015 conf Northwest will be attending on the 9th of April.
http://www.terrapinn.com/conference/world-vaccine-congress-washington/C53403.stm
Seems like a lot of possibilities for some data on direct but I still have to assume she will stick by her statement that it will be delivered at the end of March. Now all we know for sure is that they will have a presence at ITOC on the 26th, but the paper Dr. Bosch is speaking to is not that of Direct. Is there another way they can still present the data at this conference? I don't think LP would change her mind on this as she likely prepared people at the conf that data was coming and would like to release such important data in a country that has been very supportive of the company.
Ahhh, good catch. Sounds like a very strong possibility that she was hinting at the combination trial for the third. So now we just need to fund the phase II trials. I don't believe we hear about phase II start until after the next financing deal. I suspect this will be a fairly substantial raise but it will be from a price north of 10 dollars and won't be too dilutive. Well, sounds like we have it all figured out. Now we can just sit back and watch it unfold.
I agree. This is the one. We just may get a little more than just Direct Data. Perhaps we will get the partner for a combination trial here as well. As LP stated that was coming soon as well and its one of the topics addressed at this conf.
Combination Themes:What combination will convert non-responders to responders? What combination will improve response among responders?
Didn't LP say it was going to be presented at a conf in Germany? I don't recall her exact words. Maybe we were just assuming that?
Right. It wont be the complete data set but it will be just as LP stated, A substantial picture of the 40 patients. Which will be good enough for a strong rise in share price. I'm not sure exactly how she will PR it, but its coming. I believe her delivering this news in Germany is very deliberate and is the result of the enormous amount of support they have received in Europe. I believe she is providing this news then because she is planning her next capital raise. I will be interested to see if Woodford is the one to finance the next one as well.
Wait a minute....So you don't believe Linda will follow through with what she stated last conference? That she will present most the data at a conference in Germany at the end of March?
I disagree, I believe she will follow through. The large options activity for April also thinks so. I also believe she will do the next round of financing with the elevated share price. 12 or so is my near term target.
So your suggesting that the coming PH I Direct data will have no impact on the near term stock price? The recent move higher and the large April Open Interest on calls suggest otherwise.
Long, I have also been watching that April activity closely. I was wondering what the catalyst would be to justify that large open interest and now we are seeing why. Absolutely not a coincidence. There will be a major move in this stock by April. My guess is north of 10. However, I have also noted the 6 dollar April puts with some decent volume, but i'm not sure if that position was opened at the same time. They could be selling the puts to go long the calls.
Good points,I like how Linda is positioning the company to be the answer for the low response rates from CI's and attaching us to a hot immunotherapy trend. Even though its true that they will likely work well together, it is a good time to start pointing that out to investors. In the near future I believe we will see the vaccine and CI's as the SOC followed by salvage chemo if those don't work, yet still taking advantage of the chemosensitization effect produced by the CI's. Not really sure where the car-t tech will fit in yet.
Yes the CI collaboration is by far the biggest news coming out of this conference. I was speaking to this a couple weeks ago about how CI should not be viewed as competition as they likely have synergy. People may want to go back and review that post. I provided a link to another company that speaks on this potential. Its worth a listen if your into DD. Anyway, this is exciting stuff.
There is one CI company I'm aware of that has a GBM trial going on albeit an early trial. https://clinicaltrials.gov/ct2/show/NCT02052648?term=indoximod&rank=5
Ok Long, now we have some significant options activity to discuss. 5k+ at the same april2015 7 dollar strike. These were going through at .45. Here we do not see the collapse in premium as we seen the other day. Looks like a clear buy. Tomorrow's Open interest will tell us if its a buy to open or a buy to close. Somethings going on for sure prior to April with this recent purchase, I would say.
Flip, thanks for following up. That is helpful information. Newlink is ultimately looking to use their own vaccine(hyperacute) in combination with their CI's. Interim analysis coming shortly on their IMPRESS trial which will also help us understand survival rates for pancreatic cancer patient(resected). It will be important as we look at survival among the pancreatic cancer patients in the direct trial.
Additionally what has been pointed out in many of these early studies is the chemosensitization effect that some of these immunotherapies are showing. Some CR's have happened with follow on Chemo, which is quite remarkable.
All this to say that one way or another BP will be looking at NWBO whether its because its a major threat or because they have combination potential with their vaccine. It's my belief that the vaccine will be accepted as playing a major role in conjunction with CI's in fighting cancer and will become the SOC. With chemo as a backup considering the chemosensitization effects.
I don't think you can read into that. All we really know by the increase in open interest is that nobody closed a position with those 3k contracts. You can increase open interest whether you buy to open or you sell to open. My belief is still that the volume was a sell to open thus creating more open interest. The price they were being sold for was a good indicator of that. However, I will say this, 75k hardly seems worth it for a tute unless they know they can keep the share price under 7.
Here you go Study
The CI used is from Newlink Genetics.
To correct my previous post about another DC Vaccine being developed. It is actually from MEDVAX technologies INC.A private company. They have a DC vaccine in a phase I/II trial in combination with a checkpoint inhibitor. Primary completion date was DEC 2014.
Perhaps Flipper can tell us how their vaccine differs better than I but it will be an important trial to get data from in terms of the performance of combination therapy. Lets hope we here about this trial soon. This could be quite significant.
I don't have the details but its only approx 75,000 dollars worth. The same thing happened a month ago or so around the 50-60 cent level and it looked like a seller of calls then as well. A buyer coming in to purchase those calls is likely going to push up the price. With this latest transaction the price was dropping. Appears to me to be seller initiated.
Looks to me like someone was selling the calls at .25 cents. If it was a buyer, I would think it would push up the ask. That was the first time I seen a 25 cent ask on those calls. Its usually 50-60 cents. Given the discount It looks like a seller of calls and someone that does not expect the price to be above 7.
I don't think, as of right now, we should view CI's as competition but rather should view them as a synergistic treatment with immunotherapy vaccines. These combination treatments have shown, in pre-clinicals, to be far more effective than just checkpoint blockade alone. I encourage everyone to listen to the last CC of Newlink Genetics were they speak to this. The combination of the two is really the premise of the company's strategy. If you mobilize the immune system first with the vaccine and then introduce checkpoint blockade (pre-clinically speaking)you can really get some incredible results. But I will let them speak on it. Listen to the Nov 6th CC at around the 21,22 minute mark.Newlink CC
They also have their CI (indoximod) in a phase 1 GBM trial that's ending in March2015. There may be a potential for a partnership down the road to combine the vaccine and CI.
John, the question concerning dosage has not been answered and will not be answered until we see the Phase II trial design. There we can conclude what dose they see as being most effective. The only thing LP has said was with regards to -L where she stated more is not always better.
No problem, and no doubt there are still many things to consider. LP's response caught me by surprise so I was not prepared to follow that up with additional questions plus we were well over the time allotted. Anyway, it has been helpful to have a thorough discussion on the matter to help flush out various possibilities.
Unfortunately an ASM is sometimes the only way to get some additional details, such as these, as we are not usually in the position to ask the questions face to face. Nor is it the kind of information that would be included in a PR. And as we all know, there is rarely a Q & A session.
Glad everyone could come on-board. But lets be clear about where the "lost in translation" occurred. It was not from LP's mouth to my ears, nor was it from my finger tips to this board. It was all from board members that had a hard time coming to terms with the idea.
My original post:
I hear you but keep in mind, the flow of information is a delicate thing. Just as the water flowing from a spigot, it can be turned off abruptly. If everything LP says is questioned and requires clarity because it doesn't align with other message board poster predictions then future communications will provide less. Remember, just as Ready just pointed out, she(Linda) and the company have been very consistent in their message and have yet to bring up or discuss a halt at interim look.
I am in another company where the analysts following the company and the CEO both are very vocal about a possible halt at second interim look. That has not been the case here.
No problem at all Highway. I just don't understand this "lost in translation" stuff. What she said lines up with her guidance very well. There is no reason to believe what I reported is not accurate.
No I am not saying that, LP is saying that, repeatedly. Perhaps her estimates are conservative but that's the guidance she is giving us.
Let me add a little more color to the discussion we had. When I asked "what about a halt" LP looked at me in surprise and wasn't sure what I meant. Then another shareholder chimed in, "for efficacy" I guess because she was thinking I meant for futility and clearly wasn't thinking along the lines of any type of halt. She responded. "Why would we want to do that when were so close to the end."
Anyway, I am simply here to share information that I learned at the meeting because people here have been so generous to share the information they have. You can assign any value you want to what I've stated. However, I am disappointed people are running back to LP to get clarification. It was not my intention have LP inundated with emails about info I shared from the meeting. It definitely makes me a bit apprehensive about doing so in the future.
I walked away from that meeting very comfortable with her strategy and could see the burning desire to bring these products to market. She has a plan that she is executing quite well.
I have not researched any examples. I am simply telling you and everyone here what LP said. I provided context around the discussion to help understand what we were talking about when it came up.
LP has not once indicated that the trial could have the chance of stopping at the first interim. As far as I know any such talk has only came from the message board. Thus there should be no high expectation from large investors that the trial will be stopped early. Consequently, there won't be a big sell off for a "continue".Additionally, DIRECT will have developed far enough to bring substantial value and provide share price support if -L drags on.
I really am not sure. She has stated her expectation several times. Everyone seems to think that something was "lost in translation" because the timing doesn't agree with their personal projections of when 248 is going to hit.
I prefer to stick with LP's projections rather than the posters here. No offense. She has stated several time when she expects to hit primary endpoint of 248 in the trial 3-5 months after enrollment and she expects enrollment to complete in 09/15.
From the last conference she stated "We expect to finish enrollment, in the Phase III trial, hopefully in around September time frame, it depends a little bit on how fast, how many more of the European sites come on. But, we expect to finish about then. And we expect topline results to be about 3 to 5 months after full enrollment. So around the end of next year or slightly after, we expect to be reaching the finish line on that Phase III trial."
So if the first interim hit around April-May2015 then 10 months later she is expecting topline data. This is the point that she was saying she would prefer to wait for. She has now expressed that view twice within the last two weeks that topline data will be early 2016. That was also stated when they announce the trial enhancements.
That is 8-10 months after the first IA, not from now. I provided a little additional context to that discussion in an earlier post.
I am aware. But if you look at the past financing deals over the last year, they have pretty much raised money at the 5 dollar level anyway. My question was really geared towards trying to understand whether or not they had the option to do more long term financing. Which would give us a hint at investor appetite for Northwest stock. I completely understand their strategy, but given you can't predict the stock price for 4 or 6 months out, I think I would rather have more than a quarters worth of cash on hand. Just my preference. Again, as they de-risk the platform will continue to see more favorable terms and probably larger deals. That's why Direct is so important in terms of de-risking the stock. If it continues to perform well it will limit any downside and remove focus from the Phase 3 trial.
Its really hard to say. I can kind of see her point about waiting an extra 8-10 months or so to de-risk the trial even further. I think it been such a long trial that she just want to make sure she gets to the finish line without tripping or getting disqualified. As Flip said, Direct will take center stage and become the driver of the share price while we await the outcome of -L. It was a little discouraging but I'm thinking with the data coming from Direct it won't really matter.