Innovation Pharmaceuticals Inc (IPIX)

[olden_grumpini]

What is your opinion of the IC50 values for brilacidin in Calu-3 cells in the Wang paper? “Our results showed that brilacidin inhibited SARS-CoV-2 pseudovirus entry into all cell lines tested with IC50 values ranging from 12.0 ± 1.7 to 23.0 ± 1.6 µM (Figure 1).” In figure 1, Calu-3 cells have an IC50 of 18.28 ± 1.87 µM. This is more than 32X the IC50 value in the Bakovic paper that was published in viruses.

As to dosing, these are the doses Polymedix used in their P2 trial:
1.6 mg/kg (0.4 mg/kg on day one followed by 0.30 mg/kg daily for four days)
2.15 mg/kg (0.75 mg/kg on day one followed by 0.35 mg/kg daily for four days)
2.4 mg/kg (1.0 mg/kg on day one followed by 0.35 mg/kg daily for four days) 

This is what they wrote about the safety of that trial (emphasis added):

The most common adverse event experienced by patients in the study was numbness and tingling, felt by 65%-87% of treated patients. The majority of the cases were rated as mild and no patient discontinued due to just numbness and tingling. Excluding the numbness and tingling, the treatment-related adverse events were 9.6%, 5.6%, and 7.4% for the low, medium and high dose of brilacidin vs. 10.9% for daptomycin. Eight patients discontinued treatment due to treatment-related adverse events. Three patients that received brilacidin experienced a treatment-related serious adverse event Two of these patients discontinued treatment due to hypertension (one medium dose and one high dose).

My opinion is that the dose given in the P2 COVID trial was below those of the Polymedix P2 trial. The DMC would have been provided with all safety data for brilacidin which would include the Polymedix results. The fact that they allowed the trial to increase to 5 days of dosing from 3 reinforces my opinion since that decision was made without any efficacy data.

I too am interested to see whether brilacidin reduced the viral load in the subjects with moderate disease, but I am not optimistic that it did.