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"Giving a drug which has a poor AE profile when given systemically is always a poor strategy in OM where the ulceration can result in first pass metabolism being bypassed"
So why do you mention first pass metabolism being bypassed? Brilacidin is used as a swish and spit applied directly to the affected areas, so there is no significant first pass metabolism loss of drug through the administration process.There is a paucity of systemic OM treatments. In fact, the most effective treatment for OM is ceasing the chem/rad treatment, which presents a different set of problems We can play word games, but until there is an FDA PH3 there will be no useful determination regarding efficacy and safety.
You're missing the point about OM. It can be so severe that folks sometimes stop chem/radiation and face the cancer w/o treatment. If B for OM is at all useful, it will be sold by the barrelful, perhaps as an adjuvant treatment.. Especially as it is a nonimmunologic and can be administered non systemically.
Re the dapto comparison, there are journal citations summarizing and categorizing the data as I did, citing #14 in in my previous post. Of course there are side effects, we've seen that chart for years, but what is needed is a PH3 to verify both efficacy and safety at various use levels, and perhaps also in a nonIV treatment mode. Do I think we will see that, probably not. But casting it all off on side effects is premature, and substitutes your judgement for facts as yet unobtained.
Daptomycin's side effects were listed on the Mayo cite as extensive.”
And yet brilacidin had almost twice the last incidence of adverse events in this study than daptomycin.
Not sure where you got this from? Check this below, covered many times on this mb, from all perspectives.
Biochemical Pharmacology
Volume 133, 1 June 2017, Pages 152-163 has a quite different take:
Go to the bottom of item #14. They are referring to the Brilaciding vs Dapto study
14. Defensin-mimetic peptides
(14) "Antibacterial peptides are innate antibacterial compounds found in human and animal tissues and cells, especially white cells. These peptides help in defending the body against bacterial infections. The first molecule that entered clinical development was magainin, which was derived from frog skin. However, this molecule dropped out of development due to manufacturing, stability, and potency issues. Many antibacterial peptides have been described since the discovery of the magainin peptide. Brilacidin (Cellceutix Corp/Polymedix/U.Penn) is a defensin-mimetic, non-peptidic molecule that was designed by chemists to mimic the amphiphilic properties of antimicrobial peptides and is being developed to treat ABSSSI. Brilacidin is bactericidal for Gram-positive and Gram-negative bacteria and is extraordinary in that it is also bactericidal even for non-replicating bacteria [49]. It targets the bacterial cell membrane and has been demonstrated to have low mammalian membrane disruptive properties along with low mammalian cell cytotoxicity. Two Phase 2 studies (NCT02052388) were completed successfully in 430 subjects with ABSSSI comparing three dosing regimens of brilacidin to daptomycin for the treatment of ABSSSI. All brilacidin treatment regimens were shown to be well tolerated."
"That’s probably why this particular development program was abandoned." (i.e. Brilacidin for ABSSSI )
I also listed below a journal article recounting a study where Brilacidin proved as effective as Vancomycin in treating MRSAS keratitis.
My point with this is that Briladidin has some proven bacterial effectiveness, and finishing the FDA 3 for ABSSSI would provide some indication of value, but at a then-estimated cost of 34 million (no doubt more now) this will not likely happen.
You probably saw it proved as effective as daptomycin, also an iv, but used for a day to get the same effects as Daptomycin did in one week. Daptomycin's side effects were listed on the Mayo cite as extensive. See bellow:
More common
Bloating or swelling of the face, arms, hands, lower legs, or feet
fever
tingling of the hands or feet
unusual weight gain or loss
Less common
Agitation
black, tarry stools
bladder pain
bloody or cloudy urine
blurred vision
chest pain, discomfort, or tightness
chills
confusion
cough
decreased awareness or responsiveness
decreased frequency or amount of urine
depression
diarrhea
difficult, burning, or painful urination
dilated neck veins
dizziness
dry mouth
dryness and peeling of the skin
fainting
faintness or lightheadedness when getting up suddenly from a lying or sitting position
fast heartbeat
frequent urge to urinate
headache
hostility
increased blood pressure
increased thirst
irregular breathing
irregular heartbeat
irritability
itching in the genital or other skin areas
itching, pain, redness, swelling, tenderness, or warmth on the skin
lightheadedness
loss of appetite
loss of consciousness
lower back or side pain
mood changes
muscle pain, cramps, or twitching
nausea
nervousness
numbness or tingling in the hands, feet, or lips
pale skin
pounding in the ears
rapid, shallow breathing
seizures
severe sleepiness
skin rash
slow or fast heartbeat
sneezing
sores, ulcers, or white spots on the lips or in the mouth
sore throat
stomach pain
sweating
swollen glands
trouble breathing
unusual bleeding or bruising
unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness
vomiting of blood or material that looks like coffee grounds
Rare
Bleeding gums
blistering, peeling, or loosening of the skin
blood in the urine or stools
burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
clay-colored stools
dark urine
difficulty with moving
drowsiness
eye pain
feeling of warmth
feeling unusually cold
general feeling of illness
hives
hoarseness
increase in bone pain
irritation
joint pain, stiffness, or swelling
loss of appetite
mood or mental changes
no blood pressure or pulse
pinpoint red spots on the skin
rapid heartbeat
redness of the face, neck, arms, and occasionally, upper chest
shivering
skin rash, encrusted, scaly, and oozing
stopping of the heart
swollen, painful, or tender lymph glands in the neck, armpit, or groin
trembling
trouble swallowing
twitching, twisting, uncontrolled repetitive movements of the tongue, lips, face, arms, or legs
unpleasant breath odor
yellow eyes or skin
Incidence not known
Diarrhea, watery, and severe, which may also be bloody
dry cough
puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
stomach cramps or tenderness
Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
Less common
Anxiety
back pain
blurred vision
cold sweats
cool, pale skin
depression
flushed, dry skin
fruit-like breath odor
increased hunger
increased urination
itching of the vagina or outside genitals
lack or loss of strength
limb pain
nervousness
nightmares
pain during sexual intercourse
shakiness
slurred speech
sweating
thick, white, curd-like vaginal discharge without odor or with mild odor
trouble sleeping
Rare
Bad, unusual, or unpleasant (after) taste
belching
change in taste
continuing ringing or buzzing or other unexplained noise in the ears
excess air or gas in the stomach or intestines
feeling of constant movement of self or surroundings
feeling of fullness
hearing loss
heartburn
indigestion
pain or discomfort in the chest, upper stomach, or throat
passing gas
pressure in the stomach
red, sore eyes
seeing, hearing, or feeling things that are not there
sensation of spinning
sore mouth or tongue
swelling of the stomach area
swelling or inflammation of the mouth
white patches in the mouth or on the tongue
Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.
Just caught this. Pretty much a generic comment.
Could not agree more. LR is quite an asset, though when he is devastating one of my bogus facts or arguments, smiling about it can sometimes be not so easy.
I know I sound simplistic Hound but errors are really easy with a shell company that has no real staff, no office, no little lab (I know sunspotter, animal experiment capacity is out) and not even a post doc or two. We have Leo and another well paid friend.
I don't have a paid subscription, as I bet most on the board don't. I don't recall ever seeing IPIX in the free edition in one of the modestly in-depth, covered items. Then again, most have to do with testing progress, and there is very little of that for IPIX, sadly.
I don't have a paid subscription, as I bet most on the board don't. I don't recall seeming IPIX in the free edition.
FirstWord Pharma <newsletters@firstwordpharma.com>
When IPIX gets mentioned here, we are in the mix. Not until then.
Really glad that BARDA is in the mix, but why would a company with a failed covid trial (IPIX) be considered worth a shot. Even our compassionate use was a bust. Our best bet remains with NIH, BARDA, etc. for other bacterial and virals, etc. Nothing much has changed for IPIX, imo, with the new covid funding; and with Leo as our point, well it is not the best place to be. It's why I keep mentioning board members with good creds to alert some of these agencies/corporations/institutes to some of the IPIX potentials (Of course hoping they really exist).
Not really, but why do you think so. Cheer me up.
It would be more appropriate for the SEC to do investigations re shady little bios leaders skirting the law, then doj can become involved, again, if it choose. But there is virtually no chance of that. The SEC staff/budget is small, as I recall when I looked at it a few years ago, and little guys do not seem to be on their screen; this is, after all, the good ole US. Also, more than a few times, you have indicated your professional involvement in the pharma field, or at least that's something I recall you writing. So why not approach NIH or some others re the potentials of Brilacidin, unless you have now evolved to the point you think there is little product potential. This is something I can not really shouldn't do.
"That loan payback, when we have no real avenue for raising cash, at a time when we desperately need cash to run B-OM Phase 3 was the moment I realized we're finished. If he truly believed in the pipeline I'm not sure why he would do that"
How can I not agree? Also, why can't Leo and shell company spring a few bucks for a post doc or two (annual salaries in the 40s to 70s or so) who could do grant requests at NIH, BARDA, many institutes, private bios. There is no staff of competent bio folks for IPIX, just salaries. And the worst part is that the 1,000 (but I haven't checked the numbers in months and months) or so board members and other holders and not even occasional board participants were to pool their shares and try and vote some changes, Leo and company has it locked, as I see it. And here we are. No surprise hardly anyone checks the board frequently except for a few, not sure what to call us.
Still lots of room for a non steroidal, non immuno therapy, especially if it is administered by non IV modes. Of course that does not mean that I am expecting anything to pop here.
Alfasigma is the first and only recognition (with money) by any company of any IPIX/CTIX product. It can net IPIX something (better than nothing) if the trial is successful, and could even entice the company to want to buy all or part of IPIX. At least in my view. All else is even more speculative, imo.
It's called depression.
I do hope someone with some science creds calls or emails BARDA to see if they would give a look see at B for bad bacterials/virals. I just don't trust Leo to do the deal. In fairness, he got us a cheapie Alfasigma deal, which though small could still lead to good things. But getting a more specific time perspective has been really difficult. So WTFKs.
Great post. Summing the article up, to some extent, with a Bobbie Dylan quote, "Money doesn't talk, it swears."
Professionals and professional societies always take care of themselves, the client/patient or whatever we call them, do get taken care of, but insider interests are always well addressed. This article could have been written about the legal profession, judges, lawyers and all the rest, using many of the same points and even the same words.
Dr. Farrell, it occurs to me why don't you and sunspotter and any other scientific, medical and/or pharmacological SMEs that still post, approach BARDA about Brilacidin for ABSSSI and other antibiotic uses. The IV would not be a deal breaker as they have upwards of a Billion to develop additional treatment modes (especially now that they are not wasting $650,000,000 annually on a useless vaccine contract with a former contractor). I just don't have confidence in Leo approaching them, and the need for meds like Brilacidin is, at least potentially, a big deal which fits within their missions. Having been a former employee (of the parent agency) I am not allowed to become involved or I would do it myself (In fact I would have done it a few years ago).
"Why do you think this team will be able to get government money for an ACTIV clinical trial after being unable/unwilling to get BARDA money for Brilacidin as a novel antibiotic?"
After working in the other part of the agency BARDA is housed in, and, after you subtract more than a bit for incompetence and probable fraudulent perspectives, a failure at BARDA may not be a total dead issue. But Leo coming back, successfully, is just not something I see him doing. And he'd have to be a better salesman than he was before (If he even made a pitch, we'll never know). In honesty, I have not kept up with the new BARDA leadership, we can hope they will relook at Brilacidin, and so many other things of merit they overlooked, and they could; but usually only if the CEO makes a new pitch based on BARDA's past and huge failures to conduct its mission with integrity and competence. Is Leo slick and competent enough? He is at fleecing the longs, but not sure of much else.
I much appreciate the thoughtful analysis and discussion. Very good to read.
"Secondary endpoints and data from the Compassionate Use has been really encouraging. Without doubt, a fair trial of many people and not just a handful will be really meaningful."
Really, Monroe1, don't you think anything of value in compassionate use would have been front page/major cable news blockbuster. If Brilacid had any merit it would have been sucked up by a BP by now, at least the coivd piece. Also, recall, we are still dealing with an IV, so the population of those treated is limited to those hospitalized and often sicker. There may be some beneficial effect from the growing number of out of facility, IV infusion "businesses." Just not sure how that will play out.
And a few human uses, but not for covid, not for covid at all.
https://www.beckershospitalreview.com/pharmacy/ivermectin-didn-t-curb-covid-19-hospitalizations-in-largest-study-to-date.html
When you mean effectiveness you do mean in farm or animal use, right?
The problem we have is Leo not making the deals manyh here would like him too. We want pps and company testing and growth. He wants a nice salary, and no personal debts (recall he owns the company for all intents and purposes, and its debt is his debt). So knows what is on his mind. I sure don't. The covid test most of his reluctantly bought into (by not selling at 4o cents or more) was a dumb move. Testing some folks at death's door, with an iv, and utterly devoid of the potential benefits of early treatment or prophylaxis. Dumb. But he's not dumb, anything else would have cost more money, so he didn't want to try. As I've said before, every time I think of Leo not selling lots at over 40 cents to get some money for finishing some 2bs, maybe with some partners, it continues to fry me. But Fme. I bought on and bought it.
Yes, I said I "believe" almost like the prayer. But I am not sure, no one around here is, as far as I can tell.
I agree, I think he just went out and did a bio very quickly, not paying much attention. I came to that conclusion after I researched the issue more myself. As he is apparently a very busy guy, along with the other luminaries on the Board and the scientific advisory group.
Right you are, the $16 was from their website.
Pliant is $16 a share, a little bio with real ambitions and products. Degrado is a scientific advisor, listed on the cite. among others. It is his bio, so I am betting he did it himself, probably a little too fast and with not much thought. I more or less answered my own questions. Still, it was a nice pull by Williams, lots of us have enough on the table to justify reading any dd we can grab on to. Even when some of it was obviously quickly, and sloppily done by a brilliant scientist (Degrado). I guess I would rather have Degrado overly optimistic re Brilacidin than pessimistic.
"Brilacidin, currently licensed to Cellceutix, is now in Phase 3 clinical trials for drug-resistant Staphylococcal aureus infections."
Uhhh, what does this mean? It sounds great, but how is it real. I found nothing in clinicatriasl.gov. But the bio write up is real, and Degrado is no liar, for sure. The bottom of the post lists a 2022 date. What is missing here?
Nothing, I believe they are underway with their 2b, and later, we can hope, a 3. If the 2b is successful, and we find out, I'll double down more. If not, then I'll just watch for a while. When Leo did not sell 50 to a 100 million or more shares when the pps was in the 40/50 range (though that would no doubt tanked the pps), we were kind of assured that the 2bs for ABSSSI and OM were not his major concern. In honestly, I am not sure what is, with the exception of using IPIX as his piggy bank.
there is a lot going on behind the scenes.
How do you know this?
PJ, so you are buying at a really low pps. Can I ask what event or events are you expecting to justify even this low pps purchase. At first I was tempted to double down a bit more myself, and have done that in dribs and drabs, but it is really getting hard for me to justify that. Really hard.
Nice analysis. Sad.
I don't have much to add and agree with your major premises. I'm hoping that the AF test could spur Leo to move in response to an offer we have no idea will come, and even that could be a year or more away. And, really, no solid way to get any decent info re AF progress or lack of it. And I have near zero faith that the gov/institute invitro testing will lead to anything of value for IPIX.
Good question. What do you see, in the near and longer term?
"someone on this board could buy the whole company and then run it."
Lots of dough to put up for a company that probably needs 75 to 100 million or more to conduct its remaining tests. I am not counting the tests that could pop up if gov invitro studies unearth something. But we have no way of knowing what. And the whole time, the time value of the IPIX products wanes.
I'd go a buck a share, though it really sounds like a pipe dream from this level. Sad, really, Because if B were played a lot smarter that would be the minimum, including kevetrin.
Yep, zandant, as it has been run it is a bad business, but it still has some decent products that may never see the light of day. But still generates income for the insiders, so to speak.
A wise leader might try and sell all or part of B for ABSSSI and other bacterial infections to alfasigma, yes alfasigma. They have an interest in pathogens as they related to the many forms of IBD. But I said "wise," not greedy. I still think if we see a successful IBD test we may get an offer for the whole Brilacidin franchise. AF, while not a huge BP, if easily big enough to make a decent offer for the whole of IPIX. But just my opinion