Gone for good.
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.
Dr Reddy's Labs has a biosimilar business. They sell a biosimilar version of rituximab in India,
and three other biologics. They also have a generics business and sell generic docetaxel.
Maybe a deal would involve Dr. Reddy's Labs producing enough bavituximab for world-wide distribution.
"A WHO certified cGMP manufacturing facility, which includes E.coli and mammalian cell culture facilities."
http://www.drreddys.com/products/biosimilars.html
Probably nothing to it and the overall market will go down and take PPHM with it.
My guess is it goes under $4 because of the overall market decline in the next month.
Then it will be time to buy before good news sends the PPS back over $5. Patience will be rewarded.
I think it is all going on at UTSW.I have been waiting to hear something, but nothing so far.
Maybe at this year's AACR meeting we will get an update.
Betabodies are not mysterious. Here is the poster from the 2013 AACR meeting
http://www.peregrineinc.com/images/stories/pdfs/xianming_2013.pdf
Here is a diagram of a betabody. It is the Fc part of the mab fused to
domains I/V of beta2-GPI. So it is like a combination of PGN635 and beta2-GPI
into one entity. The Fc part binds to macrophages and DCs using their Fc-gamma
receptors, while domain V binds to PS. One of Thorpe's patents from 2006
describes an earlier version of a betabody.
There is no reason to expect a betabody to work any better than
the full mab attached to beta2-GPI, except for the fact that the half-life
in the blood is 5 times longer (~125 hrs vs. 25 hrs), and that could make
a big difference, but yet to be shown.
Here is Bavi/2aG4/1N11 binding to beta2-GPI
I am suspicious because the run up from $5 to $6.50 (30%)
essentially occurred from Tuesday Jan 14th until Friday Jan 17th.
From Thursday to Friday it jumped a dollar from $5.50 to $6.50 (18%).
That seems like too short of a time for the offering to be put together.
What bothers me is the run up from $5 to $6.50 in the four days before the
announcement of the direct offering on the 21st. Then the PPS collapses back to under $5.
In the previous 3 weeks the PPS was about $5, or less. This is just too much of a coincidence.
It just looks like blatant manipulation using insider information.
Sorry, I guess I jumped to conclusions and assumed that whoever was buying
on margin were institutional investors. Do you have any idea how much of the
stock is bought on margin? That would be a key thing to know for understanding
the behavior of the PPS.
Thanks for clearing that up. So now when the price drops below $5 some
institutional holders will be forced to sell, and below $4.62 the remaining
institutional holders will be forced to sell? However, if you look at
the major holders of the stock the 7 institutions listed account for
142300 shares (<0.3%) of the stock as of Dec 31, 2013 (see link below).
So how is it that they are driving the PPS?
I am just trying to understand what is going on here.
It would seem that the insiders and 5% holders are driving the PPS since
they control 28% of the stock.
http://finance.yahoo.com/q/mh?s=NNVC+Major+Holders
Breakdown
% of Shares Held by All Insider and 5% Owners: 28%
% of Shares Held by Institutional & Mutual Fund Owners: 0%
% of Float Held by Institutional & Mutual Fund Owners: 0%
Number of Institutions Holding Shares: 7
The slow down is in the trial using the combination of anti-CTLA4 (Yervoy)
and anti-PD1 (novolumab). I have also read that this is believed to be side effect
problems from Yervoy. This is why they do clinical trials. It is rare that
something doesn't come up, but that doesn't mean it is the end.
I can't put any confidence in a second-hand report like this. If BMS were doing this
they would have to announce something. There are many clinical trials using nivolumab
ongoing with hundreds of patients enrolled.
I don't have any doubt that anti-PD1 will work well with bavi.
I think better than anti-CTLA4, with fewer side effects. I hope
that data turns up soon. I like the slides. Slide 17 is very interesting.
I would like more info about it. If you look at the poster from the
annual SITC meeting in October there is some info about the numbers
of mice etc. The immunohistochemistry (IHC) stuff is new.
http://www.peregrineinc.com/images/stories/pdfs/sitc_172_gong.pdf
Okay, I was thinking about the drive from Vancouver.
I really want to visit Banff one day.
I was living in Victoria, BC and flew from there to Edmonton. That was spring of 1999.
I moved to Colorado in 2000. I like Canada and would consider moving back to Victoria again.
The Keystone conferences started out here in Colorado at the Keystone ski resort.
Yes, they are too expensive to attend unless someone else is paying.
The Immune Evolution in Cancer meeting is in Whistler,BC. I went to a conference there once. It is about 2 hours north of Vancouver, BC. The HIV Pathogenesis meeting is in Banff, Alberta, much farther north deep in the Canadian Rockies. I flew over that once on the way to Edmonton to give a talk. Might be pretty cold in March!
http://www.banff.ca/
I have no idea. I was surprised too.
I own shares. It is none of your business how many.
The file is here. It is under the additional information link for the archived event.
http://www.peregrineinc.com/images/stories/pdfs/gtc.pdf
I asked Jay Carlson about this very point. He replied
"We will report other preclinical data when we have it."
I take this to mean that the preclinical studies of bavi + anti-PD1
are not under their control. Maybe the studies are being done at UTSW,
or another place. The data may be being held back while papers are being
written and submitted to a journal or meeting. The titles of the abstracts
accepted at the annual AACR meeting will be online Feb 19th, maybe that will give us a clue.
I would agree with that. I think the crash will be coming soon.
That will be the time to buy some biotechs with long-term potential on the cheap.
Try this. Oops, doesn't seem to work either.
http://vimeo.com/84073332
I am a recent convert to NanoViricides. I was doing some DD on it when the price collapsed.
I quickly bought some at $4.86. The pps is now at the level seen on Sept 17, 2013.
The day before, Sept 16th, the pps was $3.65. If the overall market keeps going down,
and no new data is released, the pps may drop back to that $3.40-3.70 level seen just after
the 3.5:1 reverse split. I am waiting to see if that happens, at which time I will buy more.
The technology of nanoviricides has tremendous potential. Although I think the anti-viral uses
will be huge, there are even more possibilites. Here is this patent application for anti-cancer uses.
Sorry, I don't have private message capability for a reply. I really appreciate your message and intel.
Slides from Dr. Freimarks's talk at GTC Summit yesterday.
http://www.peregrineinc.com/images/stories/pdfs/gtc.pdf
Hi Doc,
Duramycin is very specific for phosphatidylethanolamine.
Hope you are doing well. I was in Sonoma over Christmas
but it looked and felt like June. No rain at all. How is SR?
Mark
Why is there so little activity on this board? Nanoviricides has much more going on.
How easily we forget. The "Duke paper" came out in 2010. Available online:
http://jem.rupress.org/content/207/4/763.full.pdf+html
Interesting that this will be resurfacing at the Keystone meeting in Banff. In case you also forgot that
Dr. Empig coauthored a poster at the 2010 CBDST meeting
I have been thinking about the future uses for nanoviricides beyond viruses. If you think of a nanoviricide as a large antibody you can see other uses. A ligand for a glycoprotein specific for a bacterial family could be encoded into the nanoviricide then the NVs could attach to that glycoprotein all over the surface of the bacterium. This would be like an antibody opsonizing the bacterium. There could be a cytotoxic agent inside the NV which is released into the bacterium once the NV has fused with the bacterium. Not sure if this would work, but it is an idea.
On another note, it would seem that once the phase 1 is completed that NanoViricides could be a prime candidate for Breakthrough Therapy Designation from the FDA.
1) betabodies are still too large to get through the blood brain barrier.
2) I don't think so, what matters is that PS is the target.
3) There should be plenty of beta2-GPI around for bavi. I think Thorpe
addressed this question at the NYAS talk last year. A betabody still need two
PS molecules for binding. It might be possible for more of the betabodies to
bind within a given space because they are smaller.
4) This is what I think will make all the difference. This might allow more betabodies
to find PS targets. Perhaps it will also allow the betabodies to have a greater
effect on the repolarization of the tumor microenvironment.
We'll have to see preclinical data to know.
It is interesting. I wonder how long it would take the tumor cells to evolve so that the surface proteins targeted would be
changed just enough so that the targeting fails.
Yes, I have listened to the CC several times. I don't know what he means by an "upstream checkpoint inhibitor".
It is not at all that simple. What I think he means here is what Thorpe stated in the past, that is for bavi to be
able to mediate the destruction of the tumor vasculature the macrophages (TAMs) would have to be of the anti-tumor
M1 type. For that to be true, the tumor microenvironment must have been repolarized so that M2-like
macrophages became M1-like macrophages, and this is what bavi has done. This is where the thinking about
the MOA has changed since it is now recognized that the effect on the tumor vasculature is in reality a
manifestation of the change in the tumor microenvironment brought about by using bavi. As such there is
really no such thing as the "upstream checkpoint" since the tumor microenvironment is a very complicated
system of feedback loops between all the immune cells and the cytokines and chemokines which they produce
to influence each other. The "downstream checkpoint inhibitors" are the PD-L1 and PD-L2/PD-1 and the CD80
and CD86/CTLA-4 interactions between antigen presenting cells and activated T cells which are ways the
natural immune response to pathogens is controlled apart from the tumor microenvironment.
Betabodies. I don't understand where people are getting the idea that betabodies are the savior.
So far we have seen one poster from this year's AACR meeting.
Phosphatidylserine-Targeting ‘Betabodies’ for the Treatment of Cancer
http://www.peregrineinc.com/images/stories/pdfs/xianming_2013.pdf
They were first mentioned in the 2006 patent, but since then nothing. They should work well considering that
they have a half-life in mouse blood about 5 times longer than 2aG4 (mouse version of bavi). However, the
poster contained no efficacy data in mice, never mind humans. I do expect them to work well, but so far we
just have unfounded expectations as to how well. In addition, their MOA should be no different than bavi.
The betabody is functionally the same as the bavi mab it is just a different construct which removes
the necessity of binding to beta2-glycoprotein I. In that sense it is more like the PGN632 mab which binds
PS directly. The Fc end of the betabody (the "body" part) actually comes from the 2aG4 mab, and in the
human version probably from PGN635. I think they might use an optimized Fc end as shown in this poster from the 2012 AACR meeting.
Increased Fc-FcR Interaction of Human Phosphatidylserine Targeting Antibody Enhances Pro-Inflammatory and ADCC Mechanisms
http://www.peregrineinc.com/images/stories/pdfs/aacr_2012_fc.pdf
I look forward to seeing some survival data from the mouse studies.
The evolution of the MOA. It is ridiculous to think that suddenly a new understanding of the MOA has occurred,
the understanding has evolved and matured as more was learned. You can easily track how the thinking about the
MOA has evolved over at least the last 4 years by looking at posters which are on Peregrine's website.
http://www.peregrineinc.com/technology/bavituximab-oncology/mechanism-of-action.html
2010
Phosphatidylserine (PS) on dying tumor cells suppresses dendritic cell activation and inhibits tumor immunity: reversal with PS-targeting antibody
http://www.peregrineinc.com/images/stories/pdfs/2010_AACR_Poster_PS_Reversal.pdf
2011
Phosphatidylserine-Targeting Antibody Induces Differentiation of Myeloid-Derived Suppressor Cells into M1-like Macrophages
http://www.peregrineinc.com/images/stories/pdfs/aacr_moa.pdf
2012
Targeting of Phosphatidylserine by Monoclonal Antibodies Induces Innate and Specific Anti-tumor Responses
http://www.peregrineinc.com/images/stories/pdfs/sitc_2012.pdf
2013
Phosphatidylserine-targeting antibody reactivates tumor immunity and destroys tumor vasculature in mice
http://www.peregrineinc.com/images/stories/pdfs/yin_aacr.pdf
I don't think that is an entirely fair characterization of how the new immunotherapy agents will be used.
WIth all the excitement about anti-PD1/PDL1/CTLA4 mabs they still do not work on the majority of patients.
In addition, at ASCO there were several posters about trials combining these mabs with chemotherapy. Here are three:
1) A Phase 1 Study of Nivolumab (Anti-PD-1; BMS-936558, ONO-4538) Plus Platinum-based Doublet Chemotherapy
in Chemotherapy-naïve Non-small Cell Lung Cancer (NSCLC) Patients.
2) A Phase 1 Study of BMS-936558 Plus Sunitinib or Pazopanib in Patients With Metastatic Renal Cell Carcinoma.
3) A Phase 1 Study of BMS-936558 in Combination With Gemcitabine/Cisplatin, Pemetrexed/Cisplatin,
or Carboplatin/Paclitaxel in Patients With Treatment-Naïve, Stage IIIB/IV Non-Small Cell Lung Cancer.
Fire Fox, I certainly agree with you on this.
FTM
It is from this paper from which I posted the KM plot.
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=89290443
I think the complete discussion section of this paper is worth reading.
4. Discussion
We demonstrate that 2aG4-IL2 treatment of irradiated 4T1
tumor cells significantly increases their ability to function as a vaccine.
The enhancement in immunogenicity is attributable to three
mechanisms. First, the improvement is antigen-specific indicating
that 2aG4-IL2 blocks PS-dependent immunosuppressive signals.
Second, the improvement is greater with 2aG4-IL2 than with 2aG4
alone, indicating that immunostimulatory cytokine-IL2 contributes
to the vaccination. IL-2 is a potent T-cell growth factor that has been
demonstrated in several prior studies to function as a vaccine adjuvant
[30–32]. Third, although not formally demonstrated here, we
expect that the Fc portion of 2aG4-IL2 enhances presentation of
tumor antigens by stimulating Fc receptor mediated phagocytosis
by antigen presenting cells, as demonstrated previously in other
systems [33,34].
A few PS blocking strategies to restore the immunogenicity of
tumor cell vaccines have been reported. Masking PS on cancer cell
vaccines with the PS-binding protein annexin 5A has been reported
to reverse PS mediated immunosuppression and improve antitumor
immune responses [15,16]. Injection of annexin 5A coated
tumor cells in combination with radiotherapy resulted in a strong
anti-tumor effect, with 90% of the mice rejecting the tumor after
challenge as opposed to only 25% of control animals. Similarly,
blockade of PS-dependent phagocytosis through the MFG-E8 pathway
significantly increased the antitumor immunity induced by
a GM-CSF-secreting tumor cell vaccine [35]. However, given that
multiple receptors exist for PS on APC [36–39], interfering with
MFG-E8 pathway alone may not be sufficient to block PS mediated
suppression completely. The anti-PS antibody strategy for
masking PS has an advantage over the annexin 5A and MFG-E8
strategies in that it promotes efficient antigen uptake and processing
through Fc receptor-mediated phagocytosis, which favors the
cross-priming pathway that preferentially activates CD8+ cytotoxic
T cells responses in vivo [40,41].
We recently reported that treatment of rats bearing established
F98 gliomas in their brains with unconjugated 2aG4 and
local irradiation cured 15% of the animals. Surviving animals were
immune to rechallenge with viable F98 tumor cells[10]. In vitro,
2aG4 enhanced the ability of dendritic cells to generate F98-specific
cytotoxic T-cells in an antigen-specific manner. Consistent with
these findings, our current study shows that masking PS on irradiated
4T1 cells with unconjugated 2aG4 enhanced antitumor CTL
immunity, and reduced spontaneous metastasis, although, no survival
benefit was observed. However, when the 2aG4 was fused
to IL-2 and used to coat 4T1, a powerful immune response to 4T1
tumor cells was induced. Immunostimulatory cytokines, such as
IL-2, have been extensively used to boost the antitumor immune
response of cancer vaccines in other studies [42–45].
IL-2 stimulates the expansion of antigen-activated T-cells, but
also stimulates the expansion of regulatory T-cells (Tregs) which
can be detrimental to a vaccine. It has been reported that brief
low-dose IL-2 treatment favors expansion of Treg [46]. The balance
of effects on helper T-cells and NK cells versus Tregs is probably
determined by the concentration of IL-2, timing and duration of
exposure. Indeed, superior antitumor effects with cancer cell vaccines
have been observed when IL-2 adjuvant is formulated as a
slowly IL-2-releasing cytokine depot rather than as free IL-2 [47].
Our 2aG4-IL-2 fusion has a longer in vivo half life than does free IL-
2 and would therefore persist at higher concentrations for longer,
which may explain its beneficial immune activating properties. An
alternative strategy to avoid the detrimental effects of IL-2 on Tregs
would be to fuse 2aG4 to a cytokine that is free from this property,
such as IL-15 or IL-21.
In summary, we have shown that a whole cell vaccine created
by coating irradiated tumor cells with anti-PS-IL2 fusion protein
can generate robust anti-tumor immunity. While this study was in
a prophylactic setting, future studies will address the therapeutic
efficacy of this approach in animals from which the primary tumor
has been removed surgically. This treatment setting could begin to
address whether patients who have residual diseases and who are
at high-risk to develop cancer might benefit from immunization
with their own killed tumor cells coated with anti-PS-IL2 [48,49].
Given the broad action of PS-dependent immunosuppression, and
the fact that all killed whole cell vaccines strongly express PS, the
current approach could be generally applicable. It might also be
applicable in a so-called in situ vaccine setting in which a patient’s
tumor is treated with irradiation or other local therapy and anti-
PS-IL2 then injected into the dead tumor tissue [50,51]. Since most
chemotherapeutic drugs and radiation elicit apoptotic cell death, PS
exposed on dead and dying tumor cells would be expected to abrogate
local immunity; if so, intra-tumoral injection of anti-PS-IL2
might simultaneously overcome the immunosuppressive environment
while adding IL-2 to activate immunity