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gandolph, can we make you the "go to" for getting together for the night before the PPHM stockholder's meeting since you have been kind enough to include your email? mndague@hotmail.com. I'll send you my email address tonite so we can plan place and time. thanks!
gandolph, can we make you the "go to", at least at first, since you have been kind enough to include your email? mndague@hotmail.com. Perhaps everyone going to the stockholders meeting who want to get together the night before can send you an email, and then with that list we can make a decision about what time and where. I checked w. several restaurants, and Bucca di Beppo, close-by, has a room which accomodates 12+, with no up front deposit. None of the others: BJ, Opah, Calif. Pizza Kitchen have separate meeting/eating rooms, which is not absolutely necessary. I'll send you an email tonight, and hope this gets the ball rolling. Cheers, and thanks in advance.
freethemice, do we know whether or not Thorpe is speaking at stockholder meeting? I'm trying to shoehorn that meeting within trips between Houston and Honolulu, originating in SF. Then CJ serves up that Thorpe-chaired San Diego immunology meeting which I would really like to attend too...and then, and then... Any after-meeting get together planned?
DD for newbies.AllUneed2know: cjgaddy post 92740. If you read the following you probably do not need to research PPHM much further;
Philip Thorpe,PhD., Pharmacology professor at U.TexasSW, is the inventer of Bavituximab, "BAVI", PPHM's lead product, a monoclonal antibody. Thorpe will be chairing the IBC Antibody Therapeutics Conference to be held in December: see post 9270 for the program brochure.
12-5-2012: Philip Thorpe & Joe Shan to speak about Bavi at IBC’s Antibody Therapeutics Conf. in San Diego…
Dr. Phil Thorpe is Chair for session, ”Dev. Status of Immunomodulatory Therapeutic Antibodies” - 6 speakers:
• Dario Neri (Swiss Federal Inst. of Tech.) - immunocytokines delivering IL-2, TNF-A, IL-12
• Bruce Cree (UCSF) - B cell-depleting mabs that deplete dysregulated Bcells that contribute to MS
• Erik Fedyk (Millennium Pharm) – mab vedolizumab [MLN0002] vs. inflammatory bowel disease
• Gens Volkmer (Stanford Univ) - CD47-blocking antibodies that inhibit of tumor growth & Mets
• Philip Thorpe (UTSW, PPHM SAB) - Bavituximab reactivates innate & adaptive tumor immunity and induces an immune cell-mediated shutdown of tumor vasculature
• Joseph Shan (Peregrine’s VP/Clin+RegAffairs) – an update on the perf. of Bavi in cancer clinical trials
Dec5 2012: IBC’s 23rd Annual Intl. Conf – Antibody Eng. & Therapeutics (SDiego) http://tinyurl.com/bv3usce
...11:00am Dr. Philip Thorpe (Chair) “Overcoming Immune Suppression in Tumors with Bavituximab: Preclin. Studies”
…11:30am Joe Shan, “Clinical Dev. of Bavituximab, a PS-Targeting Mab”
Dec2-6 2012: “IBC’s 23rd Annual Intl. Conf – Antibody Engineering & Therapeutics Conf.”, SanDiego
”Cutting-Edge Basic Science Combined with Updates on Clinical Progress”
http://www.ibclifesciences.com/antibodyeng
Comprised of 2 sub-conferences:
• Antibody Engineering Agenda (Dec3-5): http://www.ibclifesciences.com/antibodyeng/agenda.xml
• Antibody Therapeutics Agenda (Dec4-5): http://www.ibclifesciences.com/antibodyeng/agenda-ther.xml
2012 ANTIBODY THERAPEUTICS SCIENTIFIC ADVISORY BOARD
• Rathin C. Das, PhD, CEO, Synergys Biotherapeutics, Inc.
• Mark R. Alfenito, PhD, CEO, EnGen Bio, Inc.
• Benjamin P. Chen, PhD, Managing Partner, Ignatius Transaction Partners, LLC
• Philip E. Thorpe, PhD, Professor of Pharmacology & Serena S. Simmons Distinguished Chair, Univ. of Texas SW
• Trudi Veldman, PhD, Director, Biologics Generation, Abbott Laboratories
OVERVIEW http://www.ibclifesciences.com/antibodyeng/overview.xml
• Leading Academic Research – MIT, UCSF, Cambridge Univ., Scripps
• Innovative Emerging Science – Chugai, Cell-Signal, Zyngenia, Los Alamos Natl Lab
• Proven Clinical Results – Seattle-Gen, Pfizer, Amgen, “UTSW examines clinical studies of Bavituximab used to overcome immune suppression in tumors”
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Antibody Therapeutics Conference – Wed. Dec. 5, 2012
Track: ”Development Status of Immunomodulatory Therapeutic Antibodies”
12-5-12 8:00am: Chairperson’s Opening Remarks - Philip E. Thorpe, Ph.D., Professor of Pharmacology, Serena S. Simmons Distinguished Chair, Univ. of Texas SW
- - - - - - -
SESSION CHAIR: Philip E. Thorpe, Univ, of Texas SW Medical Center
Session Overview: The development of immunomodulatory antibodies is one of the most significant advances in cancer therapy in the 10 years that IBC’s Antibody Therapeutics Conference has been held. The best known antibodies of this category are anti-CTLA4 (e.g., ipilimumab), anti-PD1, and anti-PD1L mAbs, which have shown meaningful clinical activity in melanoma, renal cell cancer, and non-small cell lung carcinoma (NSCLC). These antibodies act by suppressing the downregulation of activated T cells, thereby maintaining and enhancing immune responses to tumor antigens. This session will focus on new and alternative approaches to creating immunomodulatory antibodies for the treatment of cancer & non-malignant diseases, including rheumatoid arthritis (RA) and multiple sclerosis (MS).
SPEAKERS:
Dario Neri (Swiss Federal Inst. of Technology) will deliver the keynote presentation in which he will discuss immunocytokines for the treatment of cancer & RA. Immunocytokines are fusions of antibody-binding domains with cytokines that activate or suppress immune activity. The strategy is to create fusion proteins that target fibronectin and tenascin isoforms that are selectively present in the extracellular matrix surrounding angiogenic and remodeling blood vessels. For cancer, the immunocytokines deliver IL-2, TNF-A, or IL-12 to stimulate immune cell attack on the tumor vasculature. For RA, IL-10 is delivered to suppress immune reactivity around inflamed vessels.
Bruce Cree (Univ. of California, SanFran) will describe how B cell-depleting monoclonal antibodies can be used to deplete dysregulated B cells that contribute to MS pathogenesis. Clinical studies have shown promising efficacy with > 90% reductions in markers of disease and excellent tolerability; Phase 3 clinical trials are in progress.
Erik Fedyk (Millennium Pharm.) will discuss vedolizumab [MLN0002], a humanized monoclonal antibody for treating inflammatory bowel disease. Vedolizumab binds to the gut-tropic A4B7 integrin on vascular endothelium, thereby blocking the homing of MAdCAM-1 positive leukocytes into mucosal & inflamed tissues. Vedolizumab is in Phase 3 trials in patients with moderate to severe Crohn disease.
Gens Volkmer (Stanford Univ.) will discuss pre-clinical evidence that CD47, which is overexpressed in numerous tumor types, transmits a “don’t eat me” signal to macrophages and dendritic cells. Treatment with CD47-blocking antibodies enables immune cells to phagocytose tumor cells in vitro. This results in inhibition of tumor growth and prevention of metastases in xenograft tumor models.
Philip Thorpe (Univ. of Texas SW Medical Ctr) will give an update on the mechanism of anti-tumor action of bavituximab, an immunostimulatory chimeric monoclonal antibody that is showing promising activity in clinical trials in patients with various types of cancer. Bavituximab targets the immunosuppressive lipid phosphatidylserine (PS) that becomes exposed on tumor blood vessels and tumor cells. Tumors externalize PS and secrete PS-expressing exosomes that impose quiescence on immune cells, thereby creating a tumor microenvironment that supports tumor growth. Bavituximab causes myeloid-derived suppressor cells in tumors to differentiate into tumoricidal M1 macrophages that destroy tumor vasculature and tumor cells by antibody-dependent cell-mediated cytotoxicity. It also causes immature dendritic cells in tumors to mature and present tumor antigens that result in the generation of tumor-specific cytotoxic T cells. Thus, bavituximab reactivates innate & adaptive tumor immunity, and induces an immune cell-mediated shutdown of tumor vasculature. Joseph Shan (Peregrine Pharm.) will then give an update on the performance of bavituximab in clinical trials in patients with cancer. Bavituximab has been shown to be well-tolerated both as a single agent and in combination with approved therapies. Bavituximab has demonstrated promising anti-tumor activity as an adjunct to std. chemotherapy, and is advancing to late stage clinical development in NSCLC.
- - - - - - - - - - - - - - - -
Session wrapup: “Given that several of the new agents being described in this session have already been established as safe & effective in clinical trials, there is a high likelihood that some will become approved drugs. This is therefore a timely session that will give a glimpse of what is around the corner.”
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12-5-12 11:00am Philip E. Thorpe, Ph.D., Professor of Pharmacology, Serena S. Simmons Distinguished Chair, Univ. of Texas SW
“Overcoming Immune Suppression in Tumors with Bavituximab: Preclinical Studies”
Bavituximab is a monoclonal antibody that is proving safe & effective as a 2nd-Line therapy in advanced lung cancer patients. It targets the immunosuppressive lipid, phosphatidylserine [PS], which becomes exposed on tumor blood vessels & tumor cells. Bavituximab causes MDSCs to differentiate into tumoricidal M1 macrophages that destroy the tumor vasculature and tumor cells by ADCC. It also causes immature dendritic cells in tumors to mature and present tumor antigens, resulting in the generation of tumor-specific cytotoxic T-cells.
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12-5-12 11:30am Joseph Shan, MPH, VP, Clinical & Regulatory Affairs, Peregrine Pharmaceuticals, Inc.
“Clinical Development of Bavituximab, a Phosphatidylserine (PS)-Targeting Monoclonal Antibody”
Bavituximab, an investigational monoclonal antibody, localizes selectively on tumor vasculature, synergizes with chemotherapy, causes vascular shut down in tumors and reactivates innate and adaptive tumor immunity. In clinical trials to date, bavituximab has been well-tolerated both as a single agent and in combination with approved therapies. Bavituximab has demonstrated promising anti-tumor activity as an adjunct to standard chemotherapy in several solid tumor indications and is advancing to late-stage clinical development in NSCLC.
cj, thanks. Thorpe chairing the tumor immunology confab is evidence of how far PPHM's anti-PS platform has come under the insight and stewardship of Dr. Philip Thorpe, PPHM's lead science (UTSW Prof., Dept.Pharm). I'll keep my money on Thorpe, UTSW, and PPHM. Remember the naysayers? Years ago I said Thorpe's work was Nobel quality, and echoes of that are beginning to be audible. The value Bavi, even the spin-offs from the aniti-PS platform, grow apace with each new report and discovery. Great stuff. Thorpe chairing a the tumor immunology conference speaks volumes. Fab.
cj, thanks. It is SO gratifying to see how far this anti-PS platform has come under the insight and stewardship of Dr. Philip Thorpe, our intrepid science helmsman (no offence FTM). Many of us vividly remember the naysayers who cast dispersions on his ability and knowledge. Years ago I said his was Nobel quality work, and there are echoes of that here now, and the many spin-offs from that platform continue to grow apace. Great stuff. Thorpe chairing a conference of that quality speaks volumes.
dia, MerckKGaA has always been on my shortlist of suspects (along w. DNA/Roche, BI) since they did a deal with PPHM years ago
SceneI: PPHMstockholder meeting, PPHM Corporate Hdqs. Tustin, Cal.
"This is a business meeting," PPHM CEO says, "Let us put aside for the moment all altruistic goals of fighting disease, and focus on our sacred duty as trustees and administrators, that of maximizing stockholder value."
"Partner quickly," someone from PPHM-IHub-Blog blurts. "It's our only chance."
"Go it alone." another says, a demented physician.
"We've already announced our plans," the CEO says. "Regional partnerships. We can't keep it all." He spread his hands expansively. "That said, we really can't take any scenario off the table, especially as we get further and further into favorable results..."
"Partnership. PIII is way too costly," the same blogger blurted again.
"ImClone went it alone all the way to production and distribution, and succeeded," the balding MD muttered, "And had squat compared to PPHM".
"But Bristol-Meyer got ImCL in the end."
"BMY got coldturded. That hurt PPHM and every MAB producer immensely. If there's another ImCL everyone from the FDA to industry will lose it.."
PPHM CEO continued, "Negotiations are now 24-7 instead of all day. We can no longer do our daytime jobs even at night."
"Maximizing shareholder value..." a RB poster shouted, fisting the CEO.
"Let's take a vote," the CEO says. "And for the first time in history, retail stockholdsers' votes will be counted. I confess. I read IHUB on the can... there are laptops in all the executive toilets ...someone on your website...Loof, I think...is having a contest about how much per share you're going to get, and how anxious everyone is to partner..so we know youlong suffering retailer's bottom line...we definitely don't want a lawsuit...but fight if we must. Listen, the banks want in on it now, and might be willing to offer the same amount BP is offering, on more favorable terms. That is, you stockholders could continue owning the entire company."
"Is Bavi really THAT good...?" the blogger asks, voice quavering.
"This has been going on for years," another IHubber says. "We just want to get our money back."
"At this point Bavi is not a cure," the CEO said. "But it looks like we have a shot at having MAB Bavi used with every form of current therapy for solid cancers, including chemo, irraidiation, and surgery...terrific adjunct treatment. That's worth something."
.
OMG CP, the road to scientific progressand inquiry is littered with "right for the wrong reasons" and spin-off insights more important than the original target. Believe me, if you are an oncologist; if you're shown the numbers; shown a schematic of the strategy; and both make sense, combined with FDA approval and advanced clinical trials, you are not going to be looking for quarks, god particles, or pi zoo-ons. You're going to ask how much it costs, and how soon can you get some...much like swarms of patients will be aking soon about Bavi. We're still a "monkey see, monkey doo-doo" people, and the leaders of scientific thought and investigation have yet to weigh in with any negatives on Bavi, DewDiligence notwithstanding. Cheers!
dukesboy,there are many types of "brain tumors", some of which are benign. If it is a malignant glioblastoma multiforme the outlook is not good, and PPHM's Cotara is a reasonable strategy, but would require a compassionate use application obtained through his oncologist since it is not through clinical trials yet.
cj, thanks. that's a "keeper" reference for understanding MOA.
dia, CP, and wook, good thinking and great researching. IMO the most important concept is understanding "apoptosis", or the normal arc of cellular degeneration and death. The cell membrane structure is composed of many different phospholipids in different ratios, and many of them are in play, or could be in play in this therapeutic strategy. Phosphatidylserine, PS, is one of the more plentiful. Think of a revolving door and an AAA battery with a positive and negative terminal. During normal apoptosis the PS polarity switches and the molecule "flips" or revolve its inside pole to the outside. That PS polarity change is a normal event along the way to cellular death, and is a sign to the garbageman cells of the immmune system that its a routine scavenger job, not an emergency. However, the externalized PS in this case is masking an emergency. Bavi- unmasks the situation. A true whistle-blower. Without going further into the following scenario, which has been done here so many times, suffice it to say that specialized body immune cell are called to the scene to investigate, are able to penetrate to tumor and sample,"photograph/read" its blueprint, determine that it and is not truly "self", and begin to build and reproduce immune cell clones that will fight and reproduce and fight that cancer cell line.
biopharm, agreed. If Bavi- is 1/2 as good as many of us thinks, there is every reason to think that a loan from Credit Suise is as good as an infusion from a biotech partner. PPHM has the production capabilities. I'm not sure how important a sales staff or distribution network is going to be. ImClone did it with a dud...and therein probably lies our greatest handicap!
biopharm, if the historical trend continues IMO it is likely that AA would occur.
mojo,thurly,drragmop:doesn't whynotpphm post 92494 cap the discussion of the credibility of Garnick's statement, that he did not seen a statistically significant PII result at Genentec?
rrdog, may be a small difference in side-effect profile in the two dosage levels.p we'll have to see how that plays out
geo and rrd, additionally: who would in their right mind would not want Bavi in their tea with a disease like advanced metastatic cancer? Mark my work, the rush for compassionate use, and all the paperwork it involves will be an added impetus to rapid review and accelerated approval.
pacemaker, nice!
biopharm, you're the greatest. nice post.
"Compassionate use": PPHM will soon have its hands full (Who needs a partner?!) I would prescribe or use Bavituximab today: Single patient access
Patients who don’t qualify for either clinical trials or an expanded access program (if one exists) may be able to get the unapproved new drug by applying for single patient access.
In this case, the patient’s doctor must first ask the drug company if the drug can be used for the patient and see if the drug company will supply it. If the company agrees, the patient’s doctor works with the drug company to ask the FDA to approve the drug for use by this one patient.
The FDA requires the doctor to send information about the patient, why the request is being made, the proposed treatment plan, and a signed informed consent from the patient (see our document Informed Consent for more information). The length of time it takes to get single patient access varies. But if it is an emergency, the FDA can complete the paperwork in 24 hours.
Why use drugs that aren’t approved?
According to guidelines from the National Cancer Institute, most compassionate drug use is for patients who meet all of these conditions:
• Have advanced disease
• Have used standard treatments and they have not worked
• Are not eligible for any clinical trial that’s in progress
• Have no other treatment options
• Have a type of cancer for which there is reason to expect the investigational drug will help
• Are likely to have benefits that outweigh the risks involved
In a case like this, the doctor may consider trying to get a new, unapproved drug for a patient to see if it will help.
Cancer surgeons understand this stuff because the wrestle gnarly tumors out of bodies all the time. Oncologists do "the standard of care" for the most part, and seldom touch cancer. Anything new to them is a potential lawsuit, lost income, threatening, or a hassle. That applies to many (NOT ALL). Radiation therapists seldom handle tumor or see patients. All the triumvirate (surgeons, oncologists, radiation therapists)understand the ramifications of Bavi treatment. A syllogism(Greeks??????sµ??syllogismos "conclusion," "inference") a kind of logical argument in which one proposition [the conclusion] is inferred from two or more others [the premises] of a specific form): If Bavituximab extends life > 2x in advanced lung ca
jims,silly question for you or others...I've never quite understood why PPHM goes to these conferences if there is, in fact, a "beard" for the party...that is, if we already have a silent partner in the wings, or even seriously interested companies. Is it simply to keep up appearances? Does it provide leverage against suitors? Indicate we're still thinking about going it on our own? Keeping options open? Shopping loans? All the above? None? Thanks.
OMG FTM you don't miss anything. FTM for vacant board seat!@
For those non-statisticians (that would be me too): In the latest super results for advanced lung cancer using Bavi + Chemotherapy, the odds are 1.5 chances in 100 that the results could be from chance or test design alone. That is, if 100 identical trials were run, only once in 100 times would these results be seen from faulty trial design, patient selection, etc. Another approach: If you are going to bet on a result, what is your comfort level with 98.5 chances out of 100 of drawing a winning card from two decks of cards.
spanky, actually Dr. Thorpe DID say Bavi + irradiation therapy probably works better than Bavi + chemotherapy. See RRDog post #91886. Bavi + Irradiation makes a lot of sense. Also, with Bavi surgeons will be able to "debulk" tumor mass with increasing confidence that micrometastases can be controlled and patient will have a longer life. cheers!
chey, thanks for Seeking Alpha article 9/12/12. Now that is reporting! And thank you for the other many contributions here.
FTM, you ask, "Any other ideas?" Lots. Start with Bavituximab + irradiation therapy. This is an indication that should have been the beginning...the opening salvo...of Bavi ued in combination therapy. IMO it was an error to have begun clinical trials with chemo + Bavi, and nothing short of a miracle that it shows significant activity against horrendous disease (metastatic lung cancer). But at the time, with its desperate fiancial situation, chemo trials in India and Russia were the only straw we could grasp. There are so many advancements in specific targeted irradiation now. What an opportunity in virtually every cancer treated with irradiation. Next? Bavi plus surgery. Bavi in less advanced cases? Bavi w. radioactive iodine (as in PPHM's RAI bearing MAB Cotara). And as mentioned before this week, since Bavi can cross the nasal mucosa, a preventive in the form of a nose spray? The price drop today speaks volumes for what the wall street crowd must do to put food on the table.
porkchop, I've agreed for years with what you said, "I think our partner is running the show now..."
spankyvol, agreed, the biggest "short-term driver" is the MOS(months of survival in advanced cancer patients using Bavituximab) which has not yet been reached when it was reached in [previous!]standard of care therapy months ago. What newcomers are not aware of is all the criticism of PPHM execs for their underspoken approach to accomplishments. That criticism here has been muted for about 6 weeks now, but will undoubtedly start once again. Once upon a time there were so-called "ethical pharmaceutical houses"...Parke-Davis, Lily, Merck...before Pfizer, BW, etc. existed--ethical because of their studied restraint re. unfounded claims. I consider PPHM's executive suite to be guided by ethical considerations and restraints, and respect them for it. The past two weeks have seen the only glimse of well-deserved and rational exuberance.
thanks carltun and clonepone. Here's the deal: Erbitux/SamWaxsal/MarthaSteward/CarlIcahn/ImClone was a different era, and ImClone went it on its own with a not very efficacious product, to be kind. Let's focus on PPHM, a different era, and an enormous advance in the science and art. I have been sensitive to the "dead money" concerns here in the past...and it was worse than dead money as it turned out...but the several clinical trials of MAB Bavi for several different types of solid tumors; viral applications; imaging applications; PPHM's better-than-avastin antiVEGF; PPHM's antiTNT Cotara which was mentioned by Garnick today as being set to begin PIII...on and on. Most important of all is going to be the effect of the dawning of awareness in the scientific and then the public sector of exactly what is going on here. It's major. The only downside I can think of is the float.
exwannabe, fast answer: yes. There is going to be such a clamor for using Bavi on a compassionate-use basis that they might not even need regulatory approval (how's that for hype?!!). I am already advising patients in that direction.
carltun123,couldn't disagree more, but couldn't care less either, about "short-term catalysts" since I don't trade that much (don't have time). However, being a veteran of the ImClone run-up with Erbitux, this particular stage of developmentwith that MAB witnessed the greatest price run-up. And the upside and the certainty here is infinitely greater than with Erbitux. So it strikes me that anyone distracted by a dearth of "short-term catalysts" does not have an appreciation of the true long-term potential here. And by-the-way, there were enormous trading opportunities during that run-up with IMCL. There will always be those out there trying to stir the pot. What a way to make a living.
BKT thanksamillion. Terrific information. eom
clone, we've been through a lot more intellectual(or non-intellectual) rigors than Cramer can muster, and I could care less what he says if it is negative. If it is positive I might start watching his show because it would tell me a lot about the people he listens to...and maybe even his candor.
thurly, I agree w. Co3..and management: genetics would not be in play here for a number of reasons, and I can see how it would be dismissed as a non-issue. From a professional point of view the results reported Fri. and today are nothing short of profound, and Garnick said it all when he said he has never (repeat, never) seen a PII trial reach statistical significance as this one has. Sit tight and watch the clown antics trying to trick you out of your money. Buy low and....whatever.
free the mice, "another outstanding person...", another outstanding post. You're the cream in our coffeee here, and have raised the bar on this board spectacularly. cheers for your labors here, and for labor day weekend. When are you going to get that vacation?!
lanoosk, nice post. thanks eom
thanks for the last two papers FTM. The last from Bristol Myers Squibb researcher.
biochica,we rock and roll when the big money players have their ducks in a row...and not until.
geo,yes,and it's happening (it's happening!) It is a tragedy (literally)that PPHM was forced into combo-chemotherapy trials rather than combo-irradiation therapy trials first. Short answer, the entire field of anti-phospholipid therapy that is opening up is mind-boggling, and to have this amount of experience in human trials at this stage of development is a rarity. Bavi-today is very much like JohnGlenn's suborbital ride was to space exploration. With genetic engineering advances the sky is not even the limit with this technology.
koman, good question. all of us have backgrounds that allow us to (or not to) connect the dots. That is true at this moment regarding the upcoming PPHM presentation at the thoracic cancer conclave in Chicago on September 7, and will continue to be true after the presentation. it is inconceivable that the message will be other than "very" interesting...but still anecdotal, possibly not statistically significant, and unpublished in the peer-reviewed literature. That will give rise to continued need for guesswork, reality checks, and wishful thinking. We re not dealing with a cure here...at least in this set of advanced disease. We have to again connect the dots and say, "OMG, if it shows evidence of activity against this stage disease, what could it do for the earliest stages of the disease. That's where we're going with all this. Prevention...early detection...early intervention.