Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Adding some historical info as well.
The last two FDA approved drugs for pancreatic cancer were Onivyde and Abraxane, which are new formulations of old chemotherapeutics.
Onivyde was tested in metastic patients who already failed gemcitabine treatment and the ORR (complete + partial response) was 7.7%. Not sure if any were complete response.
Abraxane (protein-bound paclitaxel) was tested with gemcitabine and had an ORR of 23%. I think there was only 1 CR out of 431 patients. Also, this was for first line treatment of metastic patients.
There will be a PARP inhibitor likely approved for pancreatic cancer, but this would be in the maintenance setting, also only a smaller percentage of patients would be eligible.
A quick search for what's going on with PD-1 and pancreatic cancer yielded the below: The data is from a phase 1 study of Opdivo and another investigational medicine.
"Preliminary efficacy data, collected from 31 patients with pancreatic cancer, found that three experienced a partial response and one had stable disease. Also, one patient with disease progression — and so not considered among those responding to treatment — saw a reduction in target lesions by over 40 percent.
The six-month disease control rate was 13 percent, and objective response rate was 10 percent."
so 3/31, or ~10% ORR and no CR.
More on the other category. Amgen recently announced good data from their BiTE platform at ASH, where most others were showing CAR-T data. They bought the BiTE platform for quite a bit of money a few years back so they could be doubling down on that, just look at their phase 1 pipeline. Also with a change in R&D head I’m sure there will be Some shuffling.
If you look at the aacr neo poster. The more senior author from Amgen is at another biotech now. Maybe they lost their Amgen stakeholder.
actually, the PSA trial now says "Actual Enrollment: 51 participants", so I think this is "active, not recruiting" due to full enrollment.
Adxs neo now recruiting per clinical trials.gov
Adxs psa no longer recruiting but still active
Both changes were last week. Any thoughts?
Now they committed the capital expenses to their own manufacturing facility, there is a lot of headcount that goes with it (operations, quality, microbiology, manufacturing, analytical testing, etc). If they laid everyone off they would have to outsource these activities which still cost a lot, and then waste the investment they put in.
It's difficult for them to undo this at this point. I hope they get a permanent CEO soon, but Tony is likely doing the best he can, which is focusing the clinical development programs. Lot of large Pharmas are going through this process as well and out-licensing programs, doesn't necessarily mean the drug is a poor performer.
Hmm, I think a good move. This is more similar to AZ's Lynparza SOLO trials. One of them read out successfully earlier this year. Lynparza is only for 15-20% of ovarian cancer patients, so there is room for TPIV200.
Did they ever say how many patients have been enrolled so far? It may be why they needed to increase the number of patients, since the PFS would likely be different between the patient populations.
There's still a lot unknown regarding versus different PD-1/PD-L1 mAbs, just b/c it didn't work in Lung does not mean it will not work in others.
For example, Durva worked in bladder, but Genentech's PD-L1 drug failed recently.
Opdivo (BMS) worked in H&N, but Keytruda (Merck) just reported a failure.
Keytruda worked in NSCLC first line, but Opdivo failed.
He could not realistically give any guidance on this situation.
Gotcha. Thanks.
What did they say in the presentation about EU approval?
Is this based on the GOG study? Thanks.
Not really.
JnJ and Amgen have vetted listeria as a immunotherapy platform through Aduro and ADXS now.
Just need to see combo results in November. The CR we saw early in the trial is encouraging, but would like to see results without impact of clinical hold.
Also I like that they are building up their own manufacturing capability. A lot of start ups just contract this out, even in the late phase and commercial. This shows good long term investment to grow.
Depends how you view ADXS. Those looking at it like a catalyst driven play have probably been disappointed for a long time. We definitely lost a few years because of the former management, but I think we're starting to see the inflection.
It takes awhile to build and refine the platform. If you look at some of the companies that have become bigger players, like Regeneron, you'll see an abysmal stock price for many years while they developed their platform.
Same for Medarex, their platform developed BMS's CLTA-4 and PD-1 drugs, Medarex was around for a long time (founded in 1980s), and only recently those drugs have taken off.
CAR-T is really hot, but those technologies have been incubated in the academic hospitals for many years to become what it is today.
It might seem like everyone is passing ADXS by, but relatively speaking, ADXS has not been working on it as long. And maybe a good thing, because people have learned a lot on clinical trial design for immunotherapy. There have been tons of failures in cancer vaccines, and even in check point inhibitors (look up Pfizer's development of a CLTA-4 drug).
I'm eagerly awaiting more clinical results as you are, but just a bit of perspective.
I guess my message was not clear. Let me rephrase.
TPIV has shown to provide an immune response, but we don't know efficacy b/c it has not been tested yet as you pointed out.
However, Immunogen has shown preliminary efficacy correlation between Folate receptor alpha expression and response with their ADC.
Thus, although TPIV has not shown efficacy, if Immunogen can show efficacy against that target, and TPIV has shown ability to generate immune response against that target, it is favorable that TPIV can show good efficacy. Obviously, ADC mechanism and immunotherapy is different, but with immunotherapy you typically see a long lasting effect compared to cytotoxic therapies. If you look at the PD-1 data, you see very long term survivors. Thus I had said in my original post "I think this bodes well for the TPIV/Astra combo study"
I pointed out the Immunogen study, b/c it is encouraging data for the Folate receptor alpha target.
If you go a few years back, the picture was not as good, look up Vintafolide and farletuzumab. Both phase 3 failures with big pharma backing. Vintafolide was licensed by Merck. Farletuzumab was acquired by Eisai.
So in summary, my message was that I am optimistic regarding the TPIV/Astra combination study.
Some clinical evidence that FRa is a viable target in ovarian cancer.
Immunogen reported phase 1 results for their FRa targeted ADC in May.
The median PFS and ORR in patients with high/medium FRa expression was 6.7 mo and 44% compared to 4.2 mo and 17% in pateints with low FRa.
I think this bodes well for the TPIV/Astra combo study since Immunogen showed some correlation between FRa expression level and response rate. TPIV has only shown immune response in their trials so far, and no efficacy, but this is helpful data to show the target may work.
What the bar is in platinum resistant ovarian cancer.
Since it looks like the we'd most likely get data from the PD-1 combo trial first, I did a short search to see at what recent results there have been for ovarian cancer. Overall, there does not seem to have been much activity, but in 2014, Avastin was approved for platinum resistant ovarian cancer. If you know of any others, please share.
You can look on pubmed for the Aurelia trial for Avastin, but here is a summary:
"The PFS hazard ratio (HR) after PFS events in 301 of 361 patients was 0.48 (95% CI, 0.38 to 0.60; unstratified log-rank P < .001). Median PFS was 3.4 months with chemotherapy alone versus 6.7 months with bevacizumab-containing therapy. RECIST ORR was 11.8% versus 27.3%, respectively (P = .001). The OS HR was 0.85 (95% CI, 0.66 to 1.08; P < .174; median OS, 13.3 v 16.6 months, respectively). Grade ≥ 2 hypertension and proteinuria were more common with bevacizumab. GI perforation occurred in 2.2% of bevacizumab-treated patients.
Conclusion Adding bevacizumab to chemotherapy statistically significantly improved PFS and ORR; the OS trend was not significant. No new safety signals were observed."
It got approved and there does not seem to be an OS benefit. If TPIV200 can show survival benefit, then this would be a huge boost for patients.
Also, immunotherapy takes a bit of time to kick in. In a recent talk I saw, it was mentioned that for checkpoint inhibitors, the early part of the survival curve looks similar to the control arm. Hopefully a combo can help patients see benefit sooner.
Cool. We have similar taste. TPIV and ADXS are my biggest holdings. I've seen you over on CYDY board too.
Yeah I'd hope we stay in the 100-200 million market cap range once the trials get going. So cheap right now for the pipeline they have.
Check out ADXS and ADRO for other cancer vaccine companies with PD-1 combos too. They both fell in price recently and are holding a lot of cash. Good opportunity as well.
I agree, very positive. The fact that they are splitting trial cost is a help as well. Many of these PD-1 combo studies make the smaller the company pay.
They're also looking for CR and PFS at 6 mo for the end points, so hopefully we can get some interim data by year's end. I think one thing that has been holding this back, is no true efficacy data yet, just immune response. Will be great once we get some prelim results.
Thanks for posting. A bit overly optimistic, but good information.
Will be interesting to see the reaction after June.
Yeah I would not think it'd be a huge inconvenience, but for whatever reason, that is the blame in literature on the slow adoption of Maraviroc. It was approved in 2007, so possible diagnostic testing is cheaper/faster today.
Yeah it's a high percentage, but patients still need to take a test.
That's where the issue came up for Maraviroc. Not saying it's insurmountable but something for them to think about strategy wise.
The market value is low for a few reasons. One being it's on OTC.
The other reason the market is likely hesitant because PRO140 only treats patients with the HIV tropism CCR5. Big pharma's past experience with CCR5 has not been a great success. Pfizer got approval for Maraviroc (Selzentry) in 2007 to treat patients with CCR5 tropism. Pfizer and now ViiV, has not been successful commercially with the drug (sales only a few hundred million) because patients need a test to determine if they would benefit from the drug, where as other HIV treatments do not require this. Also, it was not for first-line treatment.
I think the data will be fine. We will see how the potential for more convenient dosing schedule can impact the adoption if it's approved.
From FierceBiotech
AZ and VentiRx team up for PDL1-oncology vax trial in ovarian cancer
Ovarian cancer has few treatments and suffers from poor diagnosis, although AZ already markets Lynparza, an ADP-ribose polymerase (PARP) inhibitor, that's licensed for ovarian cancer patients who have BRCA gene mutations identified through a genetic test. This combo trial is seeking to expand on this and treat more women who do not have the BRCA gene.
There are currently a number of pharma and biotechs also researching this area, including GamaMabs' immune-activating cancer candidate and Clovis Oncology's ($CLVS) rucaparib.
Wow. Are they going to do this every year...
We've probably got 3 more years to go before anything is approved and the CEO already has >10 million worth of stock?
The revenue is promising, good to see growth back on track. The market cap has come down quite a bit, so valuation is a bit more rationale.
I am still puzzled by their stubbornness not to run a sepsis trial. The payer situation has only gotten tougher in the last year, so I don't know why they thought they could get away with a hard endpoint. Especially since reducing IL-6 level has never been correlated with improved survivals. Increased IL-6 level is seen with worse survival, but reducing it may not necessarily be the key.
Up and down. Not much to do but wait for data. It's the strategy they chose that will likely pay out more in the long term to get 100% revenue from the asset versus what ADRO did.
If you look at the agreement for Aduro and Janssen, they are only getting single digit to mid-teens royalties for ADU-741. Same with ADU-214. They get 10-30 million upfront, and more back loaded milestones.
They are likely only getting low-teens for royalty on the portion of sales exceeding a certain milestone, which is probably greater than 1 billion. So if the drug sells 1 billion, which is pretty decent, they'd likely get 50-90 million. I have not done the EPS calculation, but not sure that would support a huge market cap, and they are already at a few billion.
From ADRO's 10Q.
"The Company is eligible to receive royalties on net sales of licensed products by Janssen, its affiliates and
sublicensees at a rate ranging from mid-single digits to low teens based on aggregate annual net sales and based on the country of sale."
Can't believe it's going this low...I'm just going to watch for now
Any update when they expect to return to sales growth? Do we still think Q3?
Also, what do you mean they cannot get mortality data? Was the dosing study mentioned? Thanks.
Reading through the document:
"Whether a surrogate endpoint is reasonably likely to predict clinical benefit is a function of the scientific plausibility of the relationship between the disease, endpoint, and the expected device
effect, and the empirical evidence to support that relationship. The empirical evidence may include epidemiological, pathophysiological, therapeutic, or other scientific evidence. When considering evidence of a predictive relationship between the endpoint and clinical benefit, it is important to do so in the context of the nature of the disease as well as the mechanism of action of the device.
Use of a surrogate endpoint depends on the quality of data and strength of evidence supporting the measure, and on the context in which it is applied (“context of use”).32 When there is strong evidence demonstrating a predictive relationship between a measure and clinical benefit, it may be accepted for use as a “well-established” surrogate endpoint in a clinical study which will serve as the basis for approval. A measure which is reasonably likely to predict clinical benefit
could be used as a basis for regulatory approval in some instances such as for an EAP Device"
I don't think there's been any trials that have shown IL-6 reduction does indeed lead to better survival outcome. When I searched, I did not see any trials done in sepsis with the IL-6 antibodies, though they are being used in same cases with CAR-T therapy. Thus, I have a harder time believing that reduction of IL-6 will be accepted as a surrogate endpoint. Though there is clinical evidence pointing that high IL-6 leads to more mortality, reducing that does not guarantee increased survival.
Ic. I think I'm misunderstanding the process of EAP. Will need to read more into it.
I would not compare XON to CTSO. Very different fields. They make chemical tools to control gene expression, which has impact in many fields beyond medical only.
They also recently had a large deal with Merck KGaA (not the US based Merck). They got $115 million up front split with ZIOP, with a lot of other milestones.
Don't follow too many other medical device stocks, but AMDA is one that is trying to adopt a new device/implant. They are valued very cheaply compared to CTSO with much more sales.
Where are you getting approval by US authority this June/July?
FDA approval is 1H 2017 at earliest. For cardiac surgery, the initial trial is 20 treated patients, 20 untreated, and plans to be be completed later this year. Expansion and completion of that trial could start end of this year, but would still likely require most of 2016 to complete. Then submission, I think even 510k requires 90 days for FDA to review. PMA probably longer (not as familiar with devices).
Even if they pursue EAP with a small sepsis trial. It would take time to select sites, start up, so probably Q4 2015.
Just guesses, but they have not historically moved very quickly on clinical trials.
so many posts today. trying to catch up...
I'd just be unsure if FDA would deem IL-6 reduction meaningful enough. I think a lot of people agree that high IL-6 correlates with increased mortality, but it is more unknown if reduction of that would actually decrease mortality. There are a lot of other things going on besides just cytokines in sepsis as the cause of sepsis could be from many things. Hence, I'm not sure it'd be an acceptable surrogate endpoint.
Also, let's say it got approved through EAP based on cytokines alone. Without more data, I'd think adoption rate would be similar to what we are seeing now.
surprised you feel that strongly about EAP. You think cytokine reduction will be an acceptable endpoint? I'm not sure there's clear guidance that reduction is a predictor of reduced mortality.
usually he posts links and stuff and that's fine, but he posted a message from another anonymous message board claiming they talked to multiple CTSO representatives who said acceptance is growing and everything is fine. Those are not facts to me. I follow this board b/c there is not nearly as much crap as yahoo.
more anecdotes.
going to buy in under $7?
I may consider it.
Thanks.
Quite a bit of time to hold the data. I would think they would release ASAP to better provide guidance for usage?
Thanks. At least he acknowledged they are a bit short in clinical data.
I do hope the EAP process makes them move a bit faster on sepsis. I just pray they do not go after a soft-endpoint like IL-6 reduction, but at least something like days in ICU, since that would greatly appeal to the payer side of the healthcare.
I think the fact remains that sales will not be factor for awhile, or the cardiac surgery partnership. They are just now getting to training Fresenius, so sales probably won't be until late q2 or q3. They have not started evaluations with cardiac partner, so I'm assuming it will take a few months to do that, few months to review data and come up with a potential deal.
I think only near-term catalyst is the dosing study results. My guess is it would show some positive sub-group analysis. Even though they have stated it was not supposed to show statistical significance, I am afraid of how the market will react.
get any questions in?