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Strange so many longs worry about a "missing" P1 milestone. Does it make future milestones less likely? If NEO works, 450 mil is coming in sooner or later before or after "possible" dilution.
Hot-spot peptide vaccine targeting 1 mutation in gliomas and other tumors (IDH1R132H)
12/32 (37.5%) patients displayed pseudoprogressions, not too shabby
https://meetinglibrary.asco.org/record/159095/abstract
AMGN needs to control NEO manufacturing. Will they want another pharma making ammo for their IO arsenal or micro biotech mishap?
Neon MC upon IPO will be valued 5X - 10X ADXS
conversion of all outstanding shares of our preferred stock into an aggregate of 93,222,418 shares of our common stock upon the completion of this offering
HOT is also 1 year ahead of competition timewise. 1st construct target KRAS mutants in NSCLC, PDAC ...
NEO-SV-01, is a neoantigen vaccine for the treatment of estrogen-receptor-positive, or ER+, breast cancer, for which we expect to file an Investigational New Drug application, or IND, in the first half of 2019.
HOT is also the first in class off the shelf neoantigen vaccine to enter clinic targeting NSCLC pts with KRAS mutants. Will Construct include EGFR mutant, frame shift mut...?
30 targets in HOT for NSCLC in clinic soon. Neon PV01 max out at 20. I believe HOT is the off the shelf hidden gem in IO.
ADXS finally becomes a neoantigen company too. unlike Neon, Lm can handle longer frame shift mutations, carry more payload......
ADXS more like AMGN subsidary without Aim2cerv or P3...
Is Blackrock the smarter ADXS holder managing R/R?
FMR suffered 900 mil paper loss on NKTR today. It increased NKTR holding by 114% while Blackrock cut their NKTR position by 32%.
Only 4/62 mutations are req'd. Seems NEO MOA will help make this ACT possible for pts with little TILs to begin with.
62 different mutations were identified in her tumor cells. The researchers then tested different TILs from the patient to find those that recognized one or more of these mutated proteins. TILs recognized four of the mutant proteins, and the TILs then were expanded and infused back into the patient.
https://www.nih.gov/news-events/news-releases/new-approach-immunotherapy-leads-complete-response-breast-cancer-patient-unresponsive-other-treatments
But Melcher points out that the therapy is complex and expensive and more importantly, requires doctors to find enough infiltrating immune cells in a patient’s tumour to make the treatment effective. “The case with other TIL therapies in the past is that they’ve not been able to expand enough T cells in many patients, there aren’t enough to start with.”
Should have said tumor biopsy. pls excuse newbie posting.
If NEO dosing has started, we should know how well it works compared to other RNA and peptide vaccines in 12 months. Will ADXS find TILS targetting "non-immunogenic" neoantigens in PB after NEO treatment is the billion $ question.
I am here for NEO and HOT. If it's up to me, I would slow spending on other programs until AMGN cash payments come in.
Applying your logic, IDO should have been a big win for INCY. High ORR is meaningless in pts with lots of non-measurable mets. PSA combo showed a OS tail, no ORR. I am buying more shares as I believe OS is the ultimate ORR.
P53 is a cancer suppressor gene. In most cases, the p53 gene is mutated, giving rise to a stable mutant protein whose accumulation is regarded as a hallmark of cancer cells
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135636/
Bigger than KRAS? TP53 "hotspot" mutations and unique neoantigens expressed by human ovarian cancers.
http://clincancerres.aacrjournals.org/content/early/2018/05/31/1078-0432.CCR-18-0573
Will EXEL be interested in cabozantinib + PSA combo? Cabo showed some interesting data in bone mets a few years ago, it can use a few good TILs and EXEL needs to grow.
medium OS = 8 months for 23 pts with measurable disease per RECIST v1.1, ECOG PS 0-1, and PD-L1 expression in ≥1%. MSI is the key for PD1.
Median OS is 18.4 months for patients on enzalutamide
https://academic.oup.com/annonc/article/27/suppl_6/725PD/2799463
5/14 pts with non-measurable disease still alive 6/1, 79% (11/14) had disease stabilization. I think this is the best target as a salvage therapy. Will someone explain to me why AR+PSA is not a viable combo? It makes more sense to me compared to AR+PD1 unless AR can raise # of TILs.
Bidding 2K more at $1.8 to add to my pile. 13 months median OS is tempting.
I think the ones still alive probably had non measurable disease, less M2 to grow the tumor.
What is the incremental benefit for the patients on combo?
Median OS was 18.4 months among patients receiving enzalutamide and 13.6 months among patients receiving placebo, an incremental benefit of 4.8 months
Better raise cash before ADXS/AMGN present data to show NEO can control tumor growth and generate neoantigen-specific CD8+ T cells by targeting neoantigens that fail to elicit immunogenicity when immunized as peptide + CpG adjuvant. P1 data on Metastatic Microsatellite Stable Colon Cancer will be interesting.
From AMGN's IO arsenal:
ADXS-NEO can be engineered to carry a payload of numerous tumor antigens—up to 100 or more if needed. This feature of the vaccine is designed to address the genetic diversity found in tumors. “The cancer cells in a patient’s body don’t all express the same number or kinds of antigens,” said Roger Sidhu, a global product general manager at Amgen who chairs the Amgen-Advaxis Joint Steering Committee. “This new approach could generate antitumor T cells that target a broad spectrum of the cells present in a tumor. We see that as an exciting potential advantage.”
https://www.amgenscience.com/immuno-oncology-research/
According to AFFIRM study, median PSA progression and PFS are identical at 8.3 months for mCRPC pts treated with Enzalutamide. Additionally, when comparing enzalutamide and placebo, PSA-level response rate (54% versus 2%, p < 0.001)
53% ADXS PSA combo pts were on Enzalutamide. 16/37 pts (43%) had a decreased PSA post-BL. Of these, 8(22%) achieved a PSA reduction ≥50% from BL.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3721441/
Combo seems to work well where TME not well established. I expect more confirmed response in addition to the 2 mentioned in abstract.
9 PA and 14 PB pts had non-measurable disease at BL; 33% (3/9) and 79% (11/14) had disease stabilization (non-CR/non-PD)
Non-measurable disease. All other lesions (or sites of disease), including small lesions (longest diameter <10 mm or pathological lymph nodes with ≥ 10 to <15 mm short axis), are considered non-measurable disease
This looks like NEO done ex vivo - tLLO.
Another personalized vaccine composed of the patient’s dendritic cells, harvested from serum samples (steps 4-6). The cells are then exposed to a material previously gathered from the tumor (steps 1-3) before being injected back into the patient in vaccine form
http://ccgynonc.com/a-new-personalized-vaccine-may-increase-ovarian-cancer-survival-rates/
Frameshift mutation can also be a hotspot
ABCA7 frameshift deletion associated with Alzheimer disease
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4871806/
I like MOAs that targets APC, like TTI621, AXAL, NEO etc. Looking at the recent failed big trials of MEK and IDO, MOAs target tumors, TME, even CART have high relapse rates.
Can mRNA vaccines target frameshift mutations ≥150 aa?
Neo w/ Lm is better than NeoVax w/ Poly-ICLC.
ADXS-NEO can control tumor growth and generate neoantigen-specific CD8+ T cells by targeting neoantigens that fail to elicit immunogenicity when immunized as peptide + CpG adjuvant
Merck paid $125 mil. for hotspot vaccine
mRNA-5671 encodes for the four most commonly found KRAS mutations, and is designed to target most of the KRAS mutations that occur in NSCLC, colorectal cancer and pancreatic cancer.
https://www.businesswire.com/news/home/20180503006100/en
It would be interesting to see how many patients experienced antigen spreading after PSA vaccine are still alive w/ SD. PSA may just behave like AXAL in cancers with low mutation load.
May be the elephants sitting on ADXS have moved on with the end of month cleansing and share holders can breathe a little. Now shorts will have to deal with coming attractions:
1. clinical hold
2. PSA abstract
3. NEO dosed
4. EMA conditional approval
Is Fidelity done with garage sale? PSA abstract and NEO dosed soon.
There is a 3 month wait at NYU sleep center for the emotional investors.
$1.60 for personalized heteroclitic immunization to treat cancers.
The effectiveness of the Lm platform is demonstrated by the generation of neoantigen-specific T cells to peptide sequences that were identified as “non-immunogenic” using a conventional peptide-adjuvant immunization.
EDIS is the first automated algorithm-driven platform to speed up the design of heteroclitic peptides that can be publicly queried online.
https://www.ncbi.nlm.nih.gov/pubmed/28932628