CNS Pharma turns to crowdfunding to advance glioblastoma drug

CNS Pharma has launched a fundraising drive for a phase 2 study of a drug for glioblastoma, the form of brain cancer that has claimed the lives of Senator Ted Kennedy and Vice President Joe Biden's son Beau.

The program is notable because it involves a drug in the well-established anthracycline class of cytotoxic chemotherapy agents that differs from its predecessors in one crucial aspect: It can cross the blood-brain barrier (BBB) designed to protect the central nervous system from toxic attack.

With so much attention on cancer immunotherapies at the moment, it’s easy to gloss over the valuable role played by conventional chemotherapy over the decades. And CNS Pharma’s drug berubicin—licensed from Reata Pharmaceuticals last year—has already shown its potential in glioblastoma with a 44% response rate in a phase 1 study.

No anthracycline has ever been able to show anything like these results because of their inability to cross the BBB, said CNS Pharma’s CEO John Climaco, who told us berubicin “could be the most important advancement in treating this type of cancer in over a century.”

Despite decades of research into the disease, there have not been any significant therapies that have impacted overall survival in glioblastoma, which is expected to be diagnosed in around 12,500 people in the U.S. this year. The disease is almost uniformly fatal, with a median survival remaining unchanged for years at less than 15 months.

Berubicin grew out of a screening process in the lab of medicinal chemist Waldemar Priebe, Ph.D., of MD Anderson Cancer Center, aimed at finding DNA-binding drugs that could sidestep cellular systems such as Pgp and MRP1 receptor pathways designed to block compounds from being able to penetrate the brain, Sandra Silberman, CNS Pharma’s chief medical officer and a practicing physician at Duke University Medical Center, told FierceBiotech.

Those receptors are doubly interesting in cancer as they are also thought to play a role in the development of resistance in tumor cells after prior exposure to cancer drugs.

“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,” according to Silberman.

The company is still working through the process of developing the protocol for its phase 2 trial in a patient population refractory to first-line therapy, including surgery, radiation and chemotherapy, and for whom additional surgical intervention is not an option.

“We may recruit an initial cohort of up to six patients to re-establish the dose, schedule and safety of berubicin, following which we will be enrolling 40-50 patients for the phase 2 clinical trial with primary endpoints of progression-free survival and overall survival, and secondary endpoints of response rates, safety and quality of life,” continued Silberman 

Silberman thinks the full enrollment could take around two years, with a follow up of around one year from the last patient enrolled, giving a three-year timeline for the data readout.

“If the initial results in this open-label, non-randomized study can reiterate the excellent and unprecedented activity [in phase 1], we plan to discuss with the FDA whether we can use this study for registration under 21 CFR Part 314, Subpart H for accelerated approval.”

The company is estimating that around $8 million would be needed to run the study, but the added personnel needed to run it—plus the potential for patients to continue on study or an increase in sample size due to activity—could raise the total tally for study completion of the preparation for FDA filing to $15 million or so.

With that as a target, CNS Pharma is hoping to raise at least that amount in the coming months to finish the phase 2 trial and—if all goes according to plan—be ready for a submission to the FDA.

The first fundraising through the Republic site has a maximum of just over $1 million, and CNS has to date raised around $148,000—which it said is higher than its target of $100,000. A Regulation A+ crowd-funding via Sprout Equity with a ceiling of $15 million is also in the pipeline, and the company is also considering an IPO and NASDAQ listing later this year, with an offering of up to $15 million.

Climaco explains that the decision to turn to crowdfunding was driven by a desire to “democratize” the fundraising process and “give ordinary people who had an interest in the disease a chance to help advance research while making a good investment.” The approach will no doubt be helped by the high-profile figures affected by glioblastoma, including Senator John McCain who was diagnosed with the disease last year.

“Collectively the CNS team has raised well over $100 million from traditional early stage sources such as venture capital,” said Climaco. “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. We … felt that a broader shareholder base would be a good thing for the company.”

Along with progressing berubicin, the additional funding will be used to swell CNS Pharma’s headcount and potentially add to its pipeline via additional licensing deals.