In the eight years since Berg Pharma LLC was co-founded by billionaire businessman, venture capitalist and real estate mogul Carl Berg, scientist Niven R. Narain, who serves as the company’s president and chief technology officer, and Berg LLC managing director and investor Mitch Gray, the company has quietly amassed an enormous portfolio of early stage drug candidates and diagnostics across multiple indications, with the largest concentration in cancer. Using Berg’s interrogative biology drug discovery platform, the Boston-based biotech is starting to move those assets forward.

Berg Pharma – the company’s co-founder and namesake also serves as chairman – is using its enabling technologies to incorporate changes in drug development farther upstream, at the discovery level, rather than tweaking molecules later in the process, according to Narain. In traditional drug development, damaging side effects may not appear until late in clinical development or even after approval and marketing, he pointed out.

“What we did was develop a platform that gets back to fundamental biology,” Narain said.

Human tissue samples are the starting materials for Berg’s drug discovery platform – in cancer, which is “not a neat disease,” samples from a variety of types of cancer patients.

“We go much deeper than the genome,” Narain explained. “We feel the genome is the template of the human system, but the gene produces RNA, which produces proteins and metabolites and lipids. Berg’s created the technologies that drive a much more robust understanding of the conversation within the cellular process.”

Berg seeks to use that “conversation” within the cells to understand how metabolic alterations relate to the onset of disease. The biological platform is agnostic, Narain said, so the company doesn’t start its drug discovery process with any bias.

“It’s all data-driven,” he told BioWorld Today. “We take the human tissue samples, we run them through the instrument-based platforms and we subject the data to a Bayesian artificial intelligence system.”

Berg’s health care analytics approach is designed to identify the pressure points that govern the breakdown of healthy biological processes, leading to disease. The company then develops therapeutic candidates based on organic compounds found in the human body that “normalize” the disease microenvironment.

“Where others call that a drug target, Berg actually uses that as the drug,” Narain explained. “All of our drugs are based on internal proteins and peptides.” The approach precludes the need for screening of chemical libraries or use of synthetic compounds, dramatically compressing the drug development timetable and reducing or altogether eliminating the risk of toxicity.

“What we’re doing is essentially using the body’s own machinery to fix itself,” he said.

‘WE'VE BUILT THE PIPELINE IN A VERY DYNAMIC MANNER’

Berg’s lead program is cancer candidate BPM 31510, which has been formulated in a topical cream for skin cancer and intravenously for solid tumors, potentially including pancreatic, triple-negative breast, liver and brain cancer. BPM 31510 targets the metabolism of cancer cells by reversing the Warburg phenotype. The endogenous small molecule, which resides in mitochondria, restores oxidative phosphorylation and confers re-capitulation of the BCL-2 protein family potential to induce cell death, a process cancer evades.

The FDA recently approved the company’s plans to begin a phase IIb trial of BPM 31510 in skin cancer. In the meantime, Berg is expanding a phase Ib study into four arms, comparing BPM 31510 alone against a variety of combinations and controls. The program will make use of Berg’s artificial intelligence to characterize a molecular and metabolic footprint for each patient, based on multiple tissue samples, enabling investigators to compare responders and non-responders. One arm of the trial will evaluate the effect of mitochondrial priming – therapy with BPM 31510 followed by chemotherapy.

In diabetes, the company has two lead molecules that act through an insulin-independent mechanism. The internal proteins, designed to drive glucose into skeletal muscle and decrease localized inflammation, are preparing to enter investigational new drug-enabling studies.

Berg has four additional diabetes targets that are entering early validation studies and other early stage assets that may be expanded into neurology indications, such as Parkinson’s disease and Alzheimer’s disease.

Of course, Berg enjoys the luxury of exploration without counting the pennies. The company is privately held and self-funded – mostly by Carl Berg. But even with 200 employees, the company’s burn rate is lower than some of its peers, Narain insisted.

“We’ve spent a significant amount of capital but nowhere near what a comparator company would have spent,” he said. “Because our process is data-driven, we do things differently. We’ve built the pipeline in a very dynamic manner.”

The company is seeking to build and scale based on the big pharma model but also plans to partner or license its assets following proof-of-concept studies.

“We want to discover and develop, then look to big pharma for what they do very well, which is late-stage clinical development, sales and marketing,” Narain said.

Berg is more interested in co-development deals than out-licensing, he added. The company’s desire to keep “skin in the game” for a lower up-front and higher back-end royalties “sends a message that we believe in our technologies,” Narain said.

The public markets aren’t completely off the table, either – perhaps, even, for a piece of the company.

“We’re getting a lot of free advice from various outfits right now,” Narain admitted.

Ultimately, Berg’s drug development process is a hallmark of the personalized medicine movement, designed to provide patient-specific treatment options that lead to optimal clinical outcomes.

“We envision our company as a sustainable model for changing the health care system,” Narain said. “We’re showing that if you can stratify patients and build drugs based on understanding patient biology through their phenotype, that’s going to lead to a better health care reimbursement model and also provide our country with more funds to create innovative medicines.”