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Blushwood Tree fruit kills some cancers in 48hrs

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#31 jondoeuk

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Posted 01 June 2017 - 07:22 PM

Aduro Biotech Announces FDA Clearance of Investigational New Drug Application to Evaluate the Combination of ADU-S100 with PDR001 for the Treatment of Solid Tumors and Lymphomas http://investors.adu...icle&ID=2278048

 

The company also plan to give an update on the Phase Ia which has now been completed http://investors.adu...icle&ID=2276846



#32 mag1

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Posted 01 June 2017 - 08:21 PM

Sorry.

 

PMID: 28342934



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#33 jondoeuk

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Posted 02 November 2017 - 03:37 AM

Data from a randomized, 26-patient, Phase 2 study evaluating G100, (novel, synthetic TLR4 agonist injected intratumorally), and low-dose radiation (XTR), versus G100 and XRT with the systemic administration of Merck's anti-PD-1 antibody, Keytruda (pembrolizumab) will be presented at ASH https://ash.confex.c...aper104167.html
 
 
The data in the submitted abstract show: A 31% ORR for patients receiving G100+XRT+pembrolizumab (G+P), as compared to a 15% ORR for patients receiving G100+XRT (G); and shrinkage of untreated (abscopal) tumours in 62% of patients receiving G+P and 46% of patients receiving G. These abstract data are earlier (June 2017) than the data that will be presented in the planned presentation. The updated data appear to demonstrate a stronger clinical response and biomarker profile for those patients receiving G100, XRT and pembrolizumab, as compared to those patients receiving G100 and XRT alone.


#34 jondoeuk

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Posted 14 November 2017 - 07:25 AM

Some posters from SITC

 

IMO-2125 (TLR9 agonist) will be ongoing into a PhIII next year for advanced melanoma patients who are refractory to PD(L)-1 blockade http://www.ideraphar...te-immunity.pdf

 

A PhI will happen using NKTR-262 (TLR 7/8 agonist) and they will then combine it with NKTR-214 (CD122-biased agonisthttp://www.nektar.co...er-P275.pdf.pdf

 

Another PhI will test ZVex-IL12 http://www.immunedes...12_v4_FINAL.pdf Immune Design who are behind that should also be testing the combo of G100 and CMB305 in subtypes of STS. In another poster they presented they showed the latter two have a synergist effect http://www.immunedesign.com/wp-content/uploads/2017/11/2017-SITC_Poster_GBM_v2_FINAL.pdf

 

Analyses of a PhII of pIL-12 plus pembrolizumab in stage III/IV melanoma patients predicted to not respond to anti-PD-1 http://oncosec.com/w...TER-2017_-1.pdf Depending on the outcome of the next trial then it could be approved early by the FDA.


Edited by jondoeuk, 14 November 2017 - 07:37 AM.


#35 mag1

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Posted 14 November 2017 - 07:47 AM

Would NKTR214 combine well with alpha-c-galactosylceramide?

alpha-c-galactosylceramide turbo charges NK T cells because it fits right into their receptors.



#36 jondoeuk

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Posted 28 March 2018 - 01:43 AM

Would NKTR214 combine well with alpha-c-galactosylceramide?

alpha-c-galactosylceramide turbo charges NK T cells because it fits right into their receptors.

 

It could. The only data in humans I could find was this http://clincancerres.../8/12/3702.long Toxicity was minimal and included a case of grade 3 fever with headache, vomiting, chills and malaise 2-3 hours after the first injection and a case of transient flush. There were no partial or complete tumour responses observed, but disease stabilisations was observed in 7 patients (median time 123 days).


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#37 jondoeuk

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Posted 28 March 2018 - 01:55 AM

IMO-2125 is now in a PhIII https://clinicaltria...how/NCT03445533 They will present some preclinical data at AACR http://www.abstracts...esentation/8178
 
 
NKTR-262 is in a PhI https://clinicaltria...how/NCT03435640 Again, some preclinical data at AACR http://www.abstracts...esentation/8235
 
 
AACR data on pIL-12 in patients with pre-treated inoperable locally advanced or recurrent triple-negative breast cancer http://www.abstracts...sentation/11173
 
 
AACR human data on another TLR9 agonist http://www.abstracts...sentation/11133
 
 
AACR on an IT delivered oncolytic virus http://www.abstracts...sentation/11188
 
 
 
 
ADU-S100 monotherapy data will be presented at either ESMO or STIC. After this they will discuss the combo with anti-PD1. They plan to do another with Yervoy too. (AACR preclinical http://www.abstracts...esentation/8369)

Edited by jondoeuk, 28 March 2018 - 02:07 AM.


#38 mag1

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Posted 28 March 2018 - 02:41 AM

Wow! I heard word last year about the next wave of immunooncology products approaching, though I was not sure which ones they meant.

It looks like OX40, TLR7/8/9 and others are now moving forward. It was startling when I went to clinicaltrials.gov and downloaded the phase 1

trials for cancer to see how many IO drugs were loading up hundreds of patients. Very impressive! Pharma is making a very very large commitment to this

research.

 

http://www.alpha-galcer.net/index.html


Edited by mag1, 28 March 2018 - 02:54 AM.


#39 jondoeuk

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Posted 28 March 2018 - 05:51 PM

Wow! I heard word last year about the next wave of immunooncology products approaching, though I was not sure which ones they meant.

It looks like OX40, TLR7/8/9 and others are now moving forward. It was startling when I went to clinicaltrials.gov and downloaded the phase 1

trials for cancer to see how many IO drugs were loading up hundreds of patients. Very impressive! Pharma is making a very very large commitment to this

research.

 

http://www.alpha-galcer.net/index.html

 

Thanks for the link. From this https://endpts.com/t...eline-now-what/ John Carroll states: 

 
Among the highlights of the CRI report:
 
— There are 2,004 immunotherapy agents in development.
 
— 940 of these I/O therapies are in clinical-stage development, with 1,064 in the preclinical stage.
 
— There are 164 PD-1/L1 agents in development, with 50 in the clinic and 5 on the market. They have inspired 1,502 trials with 1,105 combos.
 
— 344 are cancer vaccines in human studies, and 224 are clinical-stage cell therapies.
 
— There are 69 oncolytic viruses in clinical development, all in the second wave behind Amgen’s T-Vec; 95 are preclinical.
 
— There are 99 T cell targeted immunomodulators in clinical development, 199 in preclinical development.
 
— There are 165 different targets being combined in checkpoint studies, with 251 including an anti-CTLA-4 and 170 involving chemotherapies.
 
— 0f 1,105 PD-1/L1 drug studies CRI examined, 60% are smaller, non-industry supported trials.
 
 
The key is to make ''cold'' tumours ''hot'' https://cen.acs.org/...ugh-cancer.html


#40 mag1

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Posted 28 March 2018 - 10:20 PM

Amazing!

 

NK-214 looks like it has staying power!

So many times with cancer drugs, patients have a short term response and then they relapse.  

After the SITC presentation I was afraid something similar would happen with NK-214-- it has happened with

essentially ever other cancer therapy. But no. In the presentation below, they are updating the November results till

this month. Most of the responders are still responding and some of them have actually demonstrated enhanced

later response versus their initial response. This is remarkable. The patients involved were stage IV treatment

naive (e.g. in melanoma). Looks like they are set to go with a large phase III trial soon.  

 

http://ir.nektar.com...3e-3f3dd5fd1484

 

Of course, NK-214 is targets the Il-2 pathway. This has substantial implications for it being applied in ACT. Nektar seems to be still

at an early stage in advancing this line of the research.

 

I hope that the FDA will allow for NK-214 to move rapidly through the clinical trial process now. The numbers that have been posted to

date are startling. The responses have resulted in clinically meaningful benefits to patients. It should not take long for this to be clearly seen

in the clinical results.

 

One thing that I am not sure about is whether there is a biomarker for response for NK-214. Calitheria's drug had a biomarker screen that could predict

response prospectively. Does Nektar have a way of selecting for responders? That would completely uncork this one! If they select those patients who

are likely responders and average time to first response is 2-3 months then this could indeed to be on the way to a rapid trip to the market. 

 

 

 

 



#41 mag1

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Posted 07 May 2018 - 04:20 AM

Is CpG (i.e. CpG 7909, Promune, CpG ODN) an available product?

Appears that they are now working on another generation of TLR9s, wonder if any first generation products made it to market.

This one seems to have been in development for decades and then it never seemed to have made it to the market.

Do pharmas have to redo everything when a product runs out of its patent clock just to have a protected product?

This would seem so wasteful of resources and would compromise patient well-being.

 

The rule probably should be that the patent clock only starts once a product makes it to market.

This way if something crops up along the way and it is found that a product does actually help for patients

(though possibly in an unexpected way) these patients could benefit without having to wait for the next generation to arrive.


Edited by mag1, 07 May 2018 - 04:21 AM.


#42 jondoeuk

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Posted 07 May 2018 - 07:07 PM

Is CpG (i.e. CpG 7909, Promune, CpG ODN) an available product?

Appears that they are now working on another generation of TLR9s, wonder if any first generation products made it to market.

This one seems to have been in development for decades and then it never seemed to have made it to the market.

Do pharmas have to redo everything when a product runs out of its patent clock just to have a protected product?

This would seem so wasteful of resources and would compromise patient well-being.

 

The rule probably should be that the patent clock only starts once a product makes it to market.

This way if something crops up along the way and it is found that a product does actually help for patients

(though possibly in an unexpected way) these patients could benefit without having to wait for the next generation to arrive.

 

No. It was taken into a PhIII in NSCLC thanks to Pfizer. Sadly the DSMC concluded that the risk-benefit profile didn't justify continuation of the trial. Data was published showing no improvements in either OS or PFS and it added toxicities when used with chemo.

 

Dynavax have got an inhaled TLR9 (DV281) in a PhIb trial (NCT03326752) and the PhII will start early next year.



#43 jondoeuk

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Posted 07 May 2018 - 07:14 PM

CMP-001 was one of the main winners of AACR https://twitter.com/...270307702001664

A PhIb will start in patients with PD-1/PD-L1 resistant NSCLC soon.

 

 

A PhI/II of IMO-2125 (another TLR9 agonist given via IT injections) in France will open to multiple tumour types including: NSCLC, melanoma, HNSCC, urothelial carcinoma, etc. It will be combined with IT injections of ipilimumab and IV nivolumab. Also a Phase II in combo with IV pembrolizumab in patients with NSCLC.

 

 

Early data from G100 (a TLR4 agonist) given at 20mcg shows a two-fold increase in TILs in patients with iNHL (follicular lymphoma). Data should be presented in the next few months and the company (Immune Design) is in talks with the FDA and hope they will grant them a PhIII trial in that indication.


Edited by jondoeuk, 07 May 2018 - 07:16 PM.


#44 mag1

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Posted 08 May 2018 - 02:26 PM

jondoeuk, how close are we to a true breakthrough in cancer (i.e., large declines in reported cancer mortality)?

You are highly informed about what is now happening in cancer research.

 

I would love to know when a substantial decline in cancer mortality might occur.

My best guess is that we are now perhaps within a year or two from that happening.

It is always difficult to estimate timelines in medicine because there are times when

progress in advancing even what appear to be potentially very promising candidates

can stop for years at a time.

 

However, given current results with TLR9, OX40, NKTR214, liquid biopsies (allowing

for very early diagnosis) etc. one has the impression that we are now finally

close to effective treatments.

 

 

 



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#45 mag1

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Posted 08 July 2018 - 04:49 AM

Combining CpG,α-Galactosylceramide (GalCer), melanoma-associated peptide antigens and monophosphoryl lipid A (MPLA) in melanoma   PMID:29940370





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