Shareholder Alert
I want to address my fellow shareholders who have been writing me about today’s event concerning another company’s Phase 3 results and why Cellceutix is very different.
Today Cempra’s stock declined dramatically over what was described as “potential safety concerns” related to the company's drug in a Phase 3 trial to treat community-acquired bacterial pneumonia (CABP). As for efficacy, it seems to me that Cempra met its main goal of non-inferiority to moxifloxacin in this study.
Cempra’s drug solithromycin is a next-generation version of a class of antibiotics called macrolides. Bacteria have developed resistance to prior-generation macrolides, including Sanofi SA's telithromycin and Pfizer Inc.'s azithromycin, and solithromycin was developed, in part, to deal with this issue.
For the Cempra Phase 3 study, the drugs were given for 7 days, as described below:
Cempra initiated the second Phase 3 trial of solithromycin, Solitaire-IV, in December 2013. This study was a double-blind, active-controlled, global, multi-center trial that enrolled 863 adult patients with moderate to moderately severe CABP and could include up to 25% PORT Class II and 75% PORT Class III/IV (with at least 25% PORT Class IV CABP patients). Patients initially received IV administration of either 400 mg of solithromycin or 400 mg of moxifloxacin. Patients could switch to oral dosing of their assigned drug based on investigator assessment of clinical stability. For solithromycin, the oral dose was an 800 mg loading dose followed by 400 mg once daily resulting in a total of 7 days of treatment with IV or IV and oral dosing. For moxifloxacin, the oral dose was 400 mg once daily for a total treatment duration of 7 days with IV or IV and oral dosing.
Although solithermycin seems like an excellent drug it may have the disadvantage that moxifloxacin is expected to go off patent in 2019, and generics will likely be available then or shortly thereafter.
We are not competing with Cempra and I wish them success.
Regarding Cellceutix’s Brilacidin for ABSSSI
This week Cellceutix issued a press release in which I issued the following comment:
"As the manufacturing process of Brilacidin for the phase 3 trial is the final product that would be used for commercialization, should the trial be successful and all regulatory marketing approvals be obtained in the future, we are conscientious to ensure it is exactly what we want it to be," commented Leo Ehrlich, Chief Executive Officer at Cellceutix. "We know of companies that failed to be meticulous in this matter heading into a pivotal trial and it has come back on them; that's a mistake we don't intend to make."
Obviously, we want to de-risk the planned Phase 3 program as much as possible. We have improved the manufacturing process of Brilacidin and have engaged in other phase 3-enabling activities. Regarding safety, we have studied the data from our previous clinical trials and have determined that a low single-dose can minimize adverse events while maintaining effectiveness. In the recent phase 2b study, there were zero serious adverse events (SAEs) that were deemed by the principal investigator (PI) as related to study drug. For patients receiving the lowest single-dose of brilacidin—the dose most likely to be used in phase 3—there was no observed increase in blood pressure-related adverse events, relative to the active comparator, daptomycin. Regarding our adverse event of numbness and tingling, that is not an issue that much concerns us. These events were extensively studied, were mild, transient, self-resolving, and without any complications. Moreover, because brilacidin is given as a single dose, the patient has already been treated for his or her infection before numbness and tingling occurs. That's it. We all have taken medicines when after ingestion you feel something and then it’s gone.
Regarding competition with generics: There are no generics that can be given a single time for treating ABSSSI.
Regarding resistance to our drug: Brilacidin is the first in a new class of antibiotics known as Host Defense Protein (HDP) mimics. As such, there is no expected cross-resistance. In contrast, all of the newly approved ABSSSI drugs have come from existing classes of antibiotics that have been marketed for years, if not decades. This means resistance has already developed to older members of that class, and when bacteria are exposed to the new members of the same class, cross-resistance is likely to occur.
Other advantages: Brilacidin is also effective against the stationary phase of bacteria. Most bactericidal antibiotics require bacteria to be in an "active growth phase" in order for rapid killing to occur. However, in endocarditis, catheter tip infections, prosthetic joint infections, and other biofilm-related infections, the bacteria divide slowly or not at all. This is called the “stationary phase”. Brilacidin is active against bacteria in both the rapid growth phase and the stationary phase, and it has been shown to disrupt biofilms. This means that brilacidin, unlike other ABSSI drugs, has the potential to be used for biofilm-related infections caused by Staph aureus. In addition, by killing bacteria in both phases (rapid growth and stationary), this decreases the opportunity for persistent bacteria to evolve into resistant bacteria. This is yet another way that brilacidin can reduce the burden of resistance
In addition: Brilacidin has immunomodulatory activity, including anti-inflammatory activity. This is not surprising, as brilacidin was created to mimic the molecules (HDPs) that comprise our innate immune system. This is the immune system that protects our barriers surfaces, such as skin and mucous membranes. These immunomodulatory properties may promote the clinical resolution of infections. This is in addition to brilacidin’s ability to directly kill bacteria. These immunomodulatory properties allow us to also use brilacidin for inflammatory conditions. For example, brilacidin is in a phase 2 study as an oral rinse for the prevention of oral mucositis in patients undergoing chemoradiation for head and neck cancer.
I want to address my fellow shareholders who have been writing me about today’s event concerning another company’s Phase 3 results and why Cellceutix is very different.
Today Cempra’s stock declined dramatically over what was described as “potential safety concerns” related to the company's drug in a Phase 3 trial to treat community-acquired bacterial pneumonia (CABP). As for efficacy, it seems to me that Cempra met its main goal of non-inferiority to moxifloxacin in this study.
Cempra’s drug solithromycin is a next-generation version of a class of antibiotics called macrolides. Bacteria have developed resistance to prior-generation macrolides, including Sanofi SA's telithromycin and Pfizer Inc.'s azithromycin, and solithromycin was developed, in part, to deal with this issue.
For the Cempra Phase 3 study, the drugs were given for 7 days, as described below:
Cempra initiated the second Phase 3 trial of solithromycin, Solitaire-IV, in December 2013. This study was a double-blind, active-controlled, global, multi-center trial that enrolled 863 adult patients with moderate to moderately severe CABP and could include up to 25% PORT Class II and 75% PORT Class III/IV (with at least 25% PORT Class IV CABP patients). Patients initially received IV administration of either 400 mg of solithromycin or 400 mg of moxifloxacin. Patients could switch to oral dosing of their assigned drug based on investigator assessment of clinical stability. For solithromycin, the oral dose was an 800 mg loading dose followed by 400 mg once daily resulting in a total of 7 days of treatment with IV or IV and oral dosing. For moxifloxacin, the oral dose was 400 mg once daily for a total treatment duration of 7 days with IV or IV and oral dosing.
Although solithermycin seems like an excellent drug it may have the disadvantage that moxifloxacin is expected to go off patent in 2019, and generics will likely be available then or shortly thereafter.
We are not competing with Cempra and I wish them success.
Regarding Cellceutix’s Brilacidin for ABSSSI
This week Cellceutix issued a press release in which I issued the following comment:
"As the manufacturing process of Brilacidin for the phase 3 trial is the final product that would be used for commercialization, should the trial be successful and all regulatory marketing approvals be obtained in the future, we are conscientious to ensure it is exactly what we want it to be," commented Leo Ehrlich, Chief Executive Officer at Cellceutix. "We know of companies that failed to be meticulous in this matter heading into a pivotal trial and it has come back on them; that's a mistake we don't intend to make."
Obviously, we want to de-risk the planned Phase 3 program as much as possible. We have improved the manufacturing process of Brilacidin and have engaged in other phase 3-enabling activities. Regarding safety, we have studied the data from our previous clinical trials and have determined that a low single-dose can minimize adverse events while maintaining effectiveness. In the recent phase 2b study, there were zero serious adverse events (SAEs) that were deemed by the principal investigator (PI) as related to study drug. For patients receiving the lowest single-dose of brilacidin—the dose most likely to be used in phase 3—there was no observed increase in blood pressure-related adverse events, relative to the active comparator, daptomycin. Regarding our adverse event of numbness and tingling, that is not an issue that much concerns us. These events were extensively studied, were mild, transient, self-resolving, and without any complications. Moreover, because brilacidin is given as a single dose, the patient has already been treated for his or her infection before numbness and tingling occurs. That's it. We all have taken medicines when after ingestion you feel something and then it’s gone.
Regarding competition with generics: There are no generics that can be given a single time for treating ABSSSI.
Regarding resistance to our drug: Brilacidin is the first in a new class of antibiotics known as Host Defense Protein (HDP) mimics. As such, there is no expected cross-resistance. In contrast, all of the newly approved ABSSSI drugs have come from existing classes of antibiotics that have been marketed for years, if not decades. This means resistance has already developed to older members of that class, and when bacteria are exposed to the new members of the same class, cross-resistance is likely to occur.
Other advantages: Brilacidin is also effective against the stationary phase of bacteria. Most bactericidal antibiotics require bacteria to be in an "active growth phase" in order for rapid killing to occur. However, in endocarditis, catheter tip infections, prosthetic joint infections, and other biofilm-related infections, the bacteria divide slowly or not at all. This is called the “stationary phase”. Brilacidin is active against bacteria in both the rapid growth phase and the stationary phase, and it has been shown to disrupt biofilms. This means that brilacidin, unlike other ABSSI drugs, has the potential to be used for biofilm-related infections caused by Staph aureus. In addition, by killing bacteria in both phases (rapid growth and stationary), this decreases the opportunity for persistent bacteria to evolve into resistant bacteria. This is yet another way that brilacidin can reduce the burden of resistance
In addition: Brilacidin has immunomodulatory activity, including anti-inflammatory activity. This is not surprising, as brilacidin was created to mimic the molecules (HDPs) that comprise our innate immune system. This is the immune system that protects our barriers surfaces, such as skin and mucous membranes. These immunomodulatory properties may promote the clinical resolution of infections. This is in addition to brilacidin’s ability to directly kill bacteria. These immunomodulatory properties allow us to also use brilacidin for inflammatory conditions. For example, brilacidin is in a phase 2 study as an oral rinse for the prevention of oral mucositis in patients undergoing chemoradiation for head and neck cancer.
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