Punit's decision to invest in a 'pot' company......Incredibly insensitive move. Many physicians equate smoking weed with cigarettes - Long term harmful effects. I have no doubt he lost the respect of some of his peers.
I got a kick out of the last question .....Punit slipped that in Ha
What we don't know is the dosing schedule for the combo trial .....the original melanoma trial schedule or will it be the extension trial schedule that began last Mar. If this combo works, 1B mc =$4 a share.
"Why is it selling for 30 cents a share?" - The current share price is proof that an inexperienced CEO can single handedly convince wall street the science is as worthless as him.
With good ph2b results, wall street and Oncs investors will know his ineptness could not stop the science from being a success.
Buy 10k shares ($3k) ......sell 10k at 3. ($30k) .......welcome to the lottery. GL
From the Jan 12 pr announcing the pilot study of TNBC -
This pilot study is designed to assess whether IL-12 ImmunoPulse increases TNBC tumor immunogenicity by driving a pro-inflammatory cascade of events that leads to increases in cytotoxic tumor-infiltrating lymphocytes (TILs). The presence and number of TILs is thought to be a key requirement for promoting the anti-tumor activity of antibodies like anti-PD-1/PD-L1. By driving cytotoxic immune cells into the tumor, IL-12 ImmunoPulse may be an ideal candidate to combine with checkpoint blockade therapies which reported some activity in TNBC
Dr. Pierce, Dr. Le- CMO, and Dr. Telli - Lead investigator of TNBC at Stanford U ......Their medical/scientist experience is telling them ...IL-12 + PD-1 will work in this indication.
In triple-negative breast cancer, the presence of CD8 tumor-infiltrating lymphocytes not only correlates with response to PD-1/PD-L1 therapeutics, but to response to certain chemotherapeutic regimens as well. In breast cancer, as well as other solid tumor types, I think we are going to find that maximally effective therapy involves a rational combination of immunogenic chemotherapies with immunotherapy, which is really exciting.
One of the emerging areas that I predict will become “hot” is the development of intratumoral cancer immunotherapies, in which we “take the fight to the tumor,” deploying immunostimulatory molecules directly into the tumor to combat the local immunosuppressive microenvironment to drive a systemic antitumor response. I think we are beginning to see this approach as a real opportunity in the treatment of solid tumors such as triple-negative breast cancer. ■
3 pr's wall street will react favorably to --- announcement(s) of first patient enrolled.
- the HNCC trail (listed on clin. trials)
- the TNBC trial ............and the biggie ,
- the PD-1 combo trial , detailing all the trial parameters ; maybe Oncs goes 1st class with planned look at safety and futility/efficacy by the DSMC. ......including a footnote the DMC can recommend an early stop leading to a Ph III based on the statistical analysis.
"a strong correlation between the density of CD8+ T cells, located at invasive edge of melanoma lesions and the probability of response to ..... (Keytruda)."
- we know EP/IL12 increases TIL's (density of CD8+ T cells)
The upcoming melanoma combo trial , if this doesn't work, I'll never buy another bio. (liar)
con't . . . .
Association with BRCA1/2 mutation status was not significant. In a multivariate model, each 10% increase in iTILs (OR 2.62 [95% CI 1.08 – 6.35]; p=0.03), but not sTILs (OR 1.17 [95% CI 0.87 – 1.58];p=0.28) was independently associated with pCR (RCB=0). However, both sTILs (p=0.02) and iTILs (p=0.009) were significantly associated with continuous RCB value. Conclusions: Both sTILs and iTILs are predictive of response to platinum-based neoadjuvant therapy and are significantly associated with TNBC subtypes, with the highest frequency in the IM subtype. Clinical trial information
- the p value found with intratumoral tils p=0.009 ... now I can see why Oncs was asked by experts in the field of TNBC to enroll patients in a EP/IL-12 Trial.
- "Both sTILS and iTILS are predictive of response to "chemo."
.Furbush......this is an excellent find, thnks. If this 'increase in tils" proves out (clinically) - $$$$
Found this from ASCO last year http://meetinglibrary.asco.org/content/131689-144 The association of TIL and TNBC response.
Background: Increased TILs are prognostic and predictive of therapy response in TNBC. PrECOG 0105, a neoadjuvant trial of carboplatin, gemcitabine and iniparib, enrolled 80 pts with clinical stage I-IIIA TN or BRCA1/2 mutation-associated BC. This correlative study was designed to assess the association of pre-therapy TILs in PrECOG 0105 with pathologic response, germline BRCA1/2 genotype & gene expression profiles, including TNBC subtypes. Methods: Evaluable pts had TNBC and completed at least 4 of 6 planned cycles of therapy. H and E stained tumor sections from pre-therapy biopsies were evaluated by a central pathologist for density of stromal (sTILs) and intratumoral (iTILs) lymphocytes. Pathologic response was assessed by the residual cancer burden (RCB) index. All patients had comprehensive BRCA1/2 genotyping. TNBC subtypes were derived from Affymetrix U133 plus 2.0 arrays. Results: 70 pts were included in this analysis. Median age = 47 yrs, median T size = 3.2 cm, 20% BRCA1/2 mutant & 48% node positive. 76% of tumors had at least 10% sTILs (range 10-80%) & 31% at least 10% iTILs (range 10-40%). Lymphocyte-predominant BC (LPBC), defined as ≥50% sTILs, was seen in 13%. pCR rate was highest (56%) in LPBC, though not significantly different from the non-LPBC group (38%, p=0.47). sTILs were significantly associated with TNBC subtype; median sTIL = 40% in the IM subtype, 15% in BL1, 20% in BL2, 10% in LAR, 0% in M, and 10% in MSL (p=0.0005). iTILs were also significantly associated with TNBC subtypes (p=0.0003); iTIL 0 for 10/14 (71%) in IM subtype, 1/7 (14%) in BL1, and 0 in others. Association with BRCA1/2 mutation status was not significant. In a multivariate model, each 10% increase in iTILs (OR 2.62 [95% CI 1.08 – 6.35]; p=0.
......to see 'phase 2' is nice surprise . .. . . .
Head and Neck Squamous Cell Carcinoma
Biological: Plasmid interleukin-12
Device: Intratumoral electroporation
andre....your 2015 pick, Aeri - 3rd qtr IO was 81% , today showing 93% !! - - final 4th qtr update next week , .... - 2 things I like, your bio stocks and you get some 'all riled up' ! Lol - keep posting : )
The full abstract , long. I've read it several times......some sentences 5 consecutive times .....in an attempt to understand what is being said.- My opinion does not make this a stat sig miss ......will leave it at that.
" . ...Taken together, our data show that SUMOylation is a critical post-translational modification that regulates SERCA2a function and provides a platform for the design of novel therapeutic strategies for HF."
SUMO1-dependent modulation of SERCA2a in heart failure
Jae Gyun Oh,
Antoine H. Chaanine,
Woo Jin Park
& Roger J. Hajjar
Nature 477, 601–605 (29 September 2011) doi:10.1038/nature10407 Received 18 February 2011 Accepted 01 August 2011 Published online 07 September 2011
The calcium-transporting ATPase ATP2A2, also known as SERCA2a, is a critical ATPase responsible for Ca2+ re-uptake during excitation–contraction coupling. Impaired Ca2+ uptake resulting from decreased expression and reduced activity of SERCA2a is a hallmark of heart failure1. Accordingly, restoration of SERCA2a expression by gene transfer has proved to be effective in improving cardiac function in heart-failure patients2, as well as in animal models3. The small ubiquitin-related modifier (SUMO) can be conjugated to lysine residues of target proteins4, and is involved in many cellular processes5. Here we show that SERCA2a is SUMOylated at lysines 480 and 585 and that this SUMOylation is essential for preserving SERCA2a ATPase activity and stability in mouse and human cells. The levels of SUMO1 and the SUMOylation of SERCA2a itself were greatly reduced in failing hearts. SUMO1 restitution by adeno-associated-virus-mediated gene delivery maintained the protein abundance of SERCA2a and markedly improved cardiac function in mice with heart failure. This effect was comparable to SERCA2A gene delivery. Moreover, SUMO1 overexpression in isolated cardiomyocytes augmented contractility and accelerated Ca2+ decay. Transgene-mediated SUMO1 overexpression rescued cardiac dysfunction induced by pressure overload concomitantly with increased SERCA2a function. By contrast, downregulation of SUMO1 using small hairpin RNA (shRNA) accelerated pressure-overload-induced deterioration of cardiac function and was accompanied by decreased SERCA2a function. / . . .. . . . . . . ...
Too many investors do not understand. The impending r/s is not to uplist. Sure, Oncs will be eligible and they will move to nasdaq or nyse.....Punit knows he has 5 yrs of money raises ahead. He will put the question of r/s in the annual proxy this spring and it will pass and it will be enacted soon thereafter. Probably 1 for 10, with 25M shares outstanding...... Punit, the pro when it comes to dilution will go to town- At $5 a share (.50 pre-split) He can begin again. 10M here, 10M there....this company will be around for 20 yrs, and he knows it.
My grasp of the obvious has always been lacking (ha) You raise a valid point. Thnks, . .. .. . Qure was the first, next up . . ..Cldn.
$5,148,998 +28% 4.2% Low
Heights Capital ...
$4,306,835 +24% 3.6% Low
..these are the only institutional holdings I could find on the big,bad, web - total 7.8% of S/O
from CNBC site.
craigakess, I wanted to get back to you last week re: downlist .....got distracted : (
"buy orders w/ volume is the only way this moves" usually brought on by substantial news. Can the mm's cause the volume to jump to 14 million in a day ? I don't know.......
Guarantee # 7 ? (I've lost count, lol) ---The pr of first patient enrolled , vol. and price.
sal, - we'll agree to disagree .Oncs has had 1 pr in 4 months that coincided with volume.
Nov. 25th , pre market was the announcement of the combo trial. The volume that day , 4 million shares.
A 20% increase in share price during trading. The mm's are not 'holding us down' - that is a red herring argument.- Buy orders w/ volume is the only way this will move. - Last year it was 14M shares in one day, moving price up 50% ....from around .50 to .75 -The 1st enrollment p.r. will bring volume, price+, while waiting for that.......we stay right here. ......and watch all the other bio's .. . . . ..
In that trial, a gene known as SERCA2 is delivered via an inert virus — a modified virus without infectious particles. SERCA2 is a gene that produces an enzyme critical to the proper pumping of calcium out of cells. In heart failure, SERCA2 is dysfunctional, forcing the heart to work harder and in the process, to grow larger.
The virus carrying SERCA2 is delivered through the coronary arteries into the heart during a cardiac catheterization procedure. Studies show only a one-time gene therapy dose is needed to restore healthy SERCA2a gene production of its beneficial enzyme.
But previous research by Mount Sinai discovered SERCA2 is not the only enzyme that is missing in action in heart failure. A study published in Nature in 2011 by Dr. Hajjar and his research group showed that the SUMO-1 gene is also decreased in failing human hearts. But SUMO-1 regulates SERCA2a's activity, suggesting that it can enhance the function of SERCA2a without altering its levels. A follow-up study in a mouse model of heart failure demonstrated that SUMO-1 gene therapy substantially improved cardiac function.
This new study tested delivery of SUMO-1 gene therapy alone, SERCA2 gene therapy alone, and a combination of SUMO-1 and SERCA2.
In large animal models of heart failure, the researchers found that gene therapy delivery of high dose SUMO-1 alone, as well as SUMO-1 and SERCA2 together, result in stronger heart contractions, better blood flow, and reduced heart volumes, compared to just SERCA2 gene therapy alone.
"These new study findings support the critical role SUMO-1 plays for SERCA2 function, and underlie the therapeutic potential of SUMO-1 gene replacement therapy for heart failure patients," reports Dr. Hajjar.
Also, according to Dr. Hajjar, the time it took investigators to translate their basic laboratory findings to successful preclinical studies was very short.
this 'p.r' from Mount Sinai ...dated nov. 13 ........a long cut and paste.
Researchers at the Cardiovascular Research Center at Icahn School of Medicine at Mount Sinai have successfully tested a powerful gene therapy, delivered directly into the heart, to reverse heart failure in large animal models.
The new research study findings, published in November 13 issue of Science Translational Medicine, is the final study phase before human clinical trials can begin testing SUMO-1 gene therapy. SUMO-1 is a gene that is "missing in action" in heart failure patients.
"SUMO-1 gene therapy may be one of the first treatments that can actually shrink enlarged hearts and significantly improve a damaged heart's life-sustaining function," says the study's senior investigator Roger J. Hajjar, MD, Director of the Cardiovascular Research Center at Icahn School of Medicine at Mount Sinai and the Arthur & Janet C. Ross Professor of Medicine at Mount Sinai. "We are very eager to test this gene therapy in our patients suffering from severe heart failure."
Heart failure remains a leading cause of hospitalization in the elderly. It accounts for about 300,000 deaths each year in the United States. Heart failure occurs when a person's heart is too weak to properly pump and circulate blood throughout their body.
Dr. Hajjar is already on a path toward approval from the Food and Drug Administration to test the novel SUMO-1 gene therapy in heart failure patients. When it begins, the clinical trial will be the second gene therapy treatment designed to reverse heart failure launched by Dr. Hajjar and his Cardiovascular Research Center at Icahn School of Medicine at Mount Sinai.
The first trial, named CUPID, is in its final phases of testing SERCA2 gene therapy. Phase 1 and phase 2a trial results were positive, demonstrating substantial improvement in clinical events.