HOUSTON—Cancer specialists have been historically frustrated by the inability of anticancer drugs to penetrate the blood-brain barrier (BBB) and fight glioblastoma multiforme (GBM). Now, for the first time, a drug is being developed which has clinically been shown to cross this barrier and attack the tumor directly. Berubicin was created in the lab of world-renowned cancer therapeutics expert Dr. Waldemar Priebe, a professor of medicinal chemistry in the Department of Experimental Therapeutics at the MD Anderson Cancer Center.
Berubicin belongs to the anthracycline class of drugs, which are considered to be among the most effective anticancer treatments ever developed and has shown promising results in its Phase 1 clinical trials, in which 44 percent of brain cancer patients treated demonstrated significant antitumor activity. In April, CNS Pharmaceuticals announced that it is working to develop this compound, which is expected to enter Phase 2 clinical trials. CNS expects the funding to be raised in part by an equity crowdfunding campaign.
“Dr. Waldemar Priebe at the MDACC developed an innovative, modular approach to create a library of high-affinity and sequence-selective DNA-binding agents based on the structure and mechanism of action of anthracyclines. This approach combined molecular modeling and structure-based rational design with combinatorial chemistry, and led to the creation of libraries of DNA base pair binding agents that also had features of being impervious to Pgp- and MRP1-overexpressing cells, which are receptors that not only dynamically block compounds from being able to penetrate the brain, but are also generated to provide tumor cells resistance after previous exposure,” says Dr. Sandra Silberman, chief medical officer of CNS Pharmaceuticals. “In-vitro screening of compounds from this library against these cell lines allowed selection of the most potent and active compounds, from which berubicin was identified.
“The major mechanisms of action of berubicin are based on its derivation from an anthracycline, and that is inhibition of DNA and RNA synthesis by intercalating (essentially ‘entwining’) between base pairs of the DNA/RNA strand, thus preventing the replication of rapidly-growing cancer cells; inhibition of the topoiosomerase II enzyme, which prevents the relaxing of supercoiled DNA and blocks DNA transcription and replication; and creating iron-mediated free oxygen radicals that damage the DNA and cell membranes.”
Silberman also notes that “Because anthracyclines have never been able to cross the blood-brain barrier before, the unique properties of berubicin are extremely encouraging and exciting with the potential to fight and perhaps finally conquer this terrible disease. The results of the Phase 1 clinical trial suggest that berubicin may change the way glioblastoma is treated worldwide.
“Berubicin ... was developed specifically for its ability to overcome the BBB, and be able to target these cells as tumors within the brain. Moreover, there is already clinical information from an initial study of patients with GBM receiving berubicin showing not only safety of administration, but a significant signal of efficacy inasmuch as several patients had reduction in the size of their brain tumors, with one patient having a complete response that has been durable for over 10 years,” she continues.
“No anthracycline—the class of anticancer drugs to which berubicin belongs—has ever been able to show anything like these results [before], based on this class of drugs’ inability to get into the brain,” remarks John M. Climaco, CNS Pharmaceuticals’ CEO. “This disease does not discriminate. Should our future clinical trials demonstrate that berubicin has this unique capability and unprecedented effectiveness, this could be the most important advancement in treating this type of cancer in over a century. Despite decades of research into glioblastoma, there have not been any significant therapies that impacted overall survival.”
In a step toward democratizing the financing of this important cancer drug technology, CNS Pharmaceuticals is running an equity crowdfunding campaign on Republic, utilizing new equity crowdfunding securities laws called regulation CF or Reg CF for short, to support the development of berubicin. A portion of this capital will fund early work in preparing for the Phase 2 clinical trial.
“Collectively, the CNS team has raised well over $100 million from traditional early-stage sources, such as venture capital. Our feeling was that there is nothing magic about that process—sometimes you net great board members with terrific experience and tremendous value add, and sometimes you just don’t,” says Climaco. “With a devastating disease like cancer that has touched so many people, we felt that democratizing the fundraising process would give ordinary people who had an interest in the disease a chance to help advance research while making a good investment. We also felt that a broader shareholder base would be a good thing for the company.”
“After looking at various platforms, we decided on Republic because they seemed to have the strongest and most engaged community as well as a very solid and knowledgeable team,” he adds. “In addition, the fact that all but a couple of their prior campaigns were successful was a good sign that we would likely reach a community of highly active investors.”
Additional funds are expected to be raised through a planned initial public offering and NASDAQ listing later this year, with an offering of up to $15 million. “Going forward after the crowdfunding phase, we will raise $8 million to $15 million,” Silberman tells DDNews. “Based on the current estimates of sample size, duration of the study, requiring six to seven sites participating in the trial, $8 million would be sufficient to initiate the study; however, with additional personnel needed to conduct this study, as well as the potential for patients to continue on study or increase in sample size due to activity, up to $15 million could be required for study completion and possible FDA filing.”