Replies to post #350929 on Innovation Pharmaceuticals Inc (IPIX)

[Here Today]

So based on you deduction, this is what I am thinking could be looked at eventually as well:

Possibly giving a 1 course IV treatment to newly diagnosed patients (defined as patients being diagnosed and treated within 1 - 3 days of onset of symptoms) as an outpatient procedure so that the 1 dose can eliminate the Viral load in the infected patient in cohesion with the patients own immune system. This will be due in part to the antiviral aspect of Brilacidin.


Then for patients in the severe to critical, follow the current CT for all 3 MOA’s that Brilacidin has shown.

[LilyGDog]

Great post biodoc!

Go Leo & IPIX!

farrell90, I'm more focused on Brilacidin's anti-inflammatory properties for the treatment population since it's likely that the viral load has greatly decreased from its peak by the time patients are actually dosed.

Bear with me:
(1)The time from onset of symptoms to hospitalization is between 3 and 10 days.
(2)The median time from onset of Covid symptoms to dyspnea is 5-8 days.
(3)The median time to ICU admission from onset of symptoms is 10 days as reported by the CDC.
(4)The virus can no longer be cultured from patient specimens 10 days after onset of symptoms (according to the CDC).

So most of the patients in the clinical trial have likely been symptomatic for at least five days and some even 10 days before they are considered moderate or severe.

The viral load is already decreasing by the time patients are really sick in the ICU and the problem isn't viral replication but the uncontrolled cytokine cascade which is the inflammatory response gone haywire. I am definitely not objecting or minimizing the potential benefit of anti-virals on the back end of the infectious process but I think anti-inflammatories will prove to play a much bigger role in patient improvement for mod/severe Covid.

IMO, Brilacidin's anti-inflammatory properties may be more important for patient recovery than its anti-viral properties. Dexamethasone is more effective than Remdesivir in the moderate/severe Covid population. Earlier in the disease, Remdesivir may prove more effective as limiting the viral load may limit the cytokine cascade.

I know that the argument for Brilacidin has been built on its anti-viral properties but the course of disease changes therapeutic intervention strategy from anti-viral to anti-inflammatory. Brilacidin is incredibly intriguing because it has both potent anti-viral and anti-inflammatory properties.

As a potential Covid therapy for moderate/severe patients, I am more focused on Brilacin's anti-inflammatory potential. For patients earlier in the disease process (pre-hospitalization or minimally symptomatic) I'd probably focus more on the anti-viral properties.

It may be a little out there but I hope it's food for thought.

[To infinity and beyond!]

your timeline is helpful. have said over and over that the trial we need for B is prophylaxis or very early in its course- an ED study with IV would have been good, when people are not very ill and not sick long at all- earlier in the course of illness. Or prophylaxis with a spray or inhaler - but these may never get developed.

The problem of course is that there is no data about the antiinflammatory impact of B v C- NONE. It is being discovered right now as we speak, mostly in Russia.

We can only hope there will be some benefit in patients who are hospitalized and quite ill. It is totally undiscovered country.

[To infinity and beyond!]

Trial then based on completely untested mechanism - the anti inflamm properties of B. lab data all about antiviral and that led to approval.

Cross your fingers- it is all we can do.

Anti inflamm benefits B for C- not known at all, NOT tested even until now

Anti inflamm ideal dosing? B for C? Not known even at all, not a clue.

[TheWayISeeIt]

Excellent post. Thank you. Worthy of a sticky.

[farrell90]

Great post.

In the NHS dexamethasone trial its anti-inflammatory effect was judged by the clinical response. Inflammatory markers are only briefly mentioned.

https://www.nejm.org/doi/full/10.1056/NEJMoa2021436

Now we have Brilacidin with 3 possible antiviral MOA's plus being a proven broad spectrum antibiotic and with anti-inflammatory properties.

It seems it would be difficult to tell which MOA was primarily improving clinical response except as you outlined by correlating the time from the first infectious symptoms and following inflammatory markers serially.

The other question I have is the 3 or 5 day dosing. Obviously the current planned dosing is for the antiviral effect. The long half life of Brilacidin will extend its biologic effects several days.

If the Brilacidin's primary MOA is anti inflammatory and not anti viral should the dosing be adjusted for that effect? In the NHS study Dexamethasone was given for up to 10 days. Will monitoring inflammatory markers as planned be helpful in adjusting the Brilacidin treatment course from 3 to 5 days?

In this short Phase 2 trial it is not likely additional adjustments will be made in the trial parameters. If the inflammatory markers show a response to Brilacidin, how would you design the Phase 3 trial?

TIA

GLTA Farrell

[To infinity and beyond!]

Hey folks do you all grasp this? The lab studies which were the foundation for FDA approval for the trial were about antiviral impact, esp viral spread, as we have been repeatedly told. Bakovic et al in the Viruses paper describes antiviral data

Biodoc describes the following problem- as the disease progresses the virus has already spread and done its direct damage. Can you make a difference if you start treatment on Day 3? or 5? Or 7? Or 10?

Next to no one would be hospitalized on Day 3 of symptoms and some would be on Day 5. As the disease progresses the CT scans and CXRs will tell you- the virus is very widespread.

Again, The data put forth by IP so far talks about mechanisms of action whose relevance is not clearly beneficial by the time the drug will be given to actual patients. That is why I have advocate from the very start a trial done on people whose symptoms were at the earliest identifiable point. Lots of those patients come to emergency depts- they want to know if they have COVID and how sick they are. Great time for a study of B for C- if you want to impact the virus very early.

The antiinflammatory and immunomodulating impact of B may play a role in COVID patients but THERE IS NO DATA TO SUPPORT IT. The GMU lab and the paper that came out have nothing to do with antiinflammatory or antibacterial(3in 1) role in B v C treatment. It is known that B has some antiinflamm impact but those are not COVID studies. B may have had some antiinflamm benefit in the distal colons of some patients with ulcerative colitis, based on the preliminary study done a few years back now. Recall that there were no controls and obv mechanism not comparable. Also B OM data does not apply

So: antiinflammatory mechanism in B v C? Nothing at all known. All guesswork. No direct studies to point to. Nothing done at GMU to support use in the current trial with respect to immunomodulation.The high SI that everyone is excited about? The 426 reference? It tells you NOTHNG about antiinflammatory benefit. Nothing at all. Because no one has a clue about what level of B is needed to mitigate COVID inflammation.

So the trial is proceeding and there may be benefit from an antiviral mechanism. And there may not be.

B is not in the lab with preincubation. B is in hospitals with patients with many days of illness with COVID already. How relevant will the SI 426 be? We can hope for some antiviral benefit .

But the antiinflammatory impact has no relevant COVID lab data no SI # and NO DOSING INFO AT ALL to support it

Cross your fingers and pray for a miracle- that is where things stand in this pivotal trial. Recall the reassurance of those who said there was a "very good" chance of success? That was just blather.