Med tech

Houston biotech company aims to enhance oncology treatment of highly resistant cancers

Houston-based Moleculin has three different oncology technologies currently in trials. Getty Images

Immunotherapy and personalized medicine get all the headlines lately, but in the fight against cancer, a natural compound created by bees could beat them in winning one battle.

In 2007, chairman and CEO Walter Klemp founded Moleculin Biotech Inc. as a private company. The former CPA had found success in life sciences with a company that sold devices for the treatment of acne. That introduction into the field of medical technology pushed him toward more profound issues than spotty skin.

"Coincidentally, the inventor of that technology had a brother who was a neuro-oncologist at MD Anderson," Klemp recalls.

The since-deceased Dr. Charles Conrad slowly lured Klemp into what he calls the "cancer ecosphere" of MD Anderson. In 2016, the company went public. And it looks like sooner rather than later, it could make major inroads against some of the toughest cancers to beat.

Klemp observed that while Houston has the world's largest medical center, "the tragic irony" is that other cities have far more biotech money ready to be invested.

"The Third Coast is really starved for capital," he says. "What drew me into this was I was one of the few entrepreneurs that lived here that knew the ropes in terms of tapping into East and West Coast capital structures and could make that connection for them."

The company has three core technologies currently being tested with some success, but the most promising is called WP1066, named for researcher Waldemar Priebe, "a rock star" in his native Poland, according to Klemp, who works at MD Anderson. Though Priebe came to the U.S. in the 1980s, he is still an adjunct professor at the University of Warsaw and conducts some of his trials in Poland because it's easier to get grant money there.

WP1066 uses propolis, a compound of beeswax, sap and saliva that bees produce to seal small areas of their hives, as a base. The molecular compound that Priebe discovered affects STAT3 (signal transducer and activator of transcription), a transcription factor that encourages tumor development. In short, the active compound in WP1066 both downregulates the STAT3, a long-time Holy Grail in the cancer research world, and directly attacking the tumor, but also quieting T Cells, which allows the body's own immune system to fight the cancer itself. Essentially, it works both as chemotherapy and immunotherapy.

WP1066 is demonstrating drug-like properties in trials at MD Anderson on glioblastoma, the aggressive brain cancer that recently took the life of the hospital's former president, John Mendelsohn, as well as John McCain and Beau Biden. It is also being tested against pancreatic cancer, one of the most virulent killers cancer doctors combat.

Priebe also created Annamycin, named for his oldest daughter, a first-line chemotherapy drug that fights Acute Myeloid Leukemia without the cardiotoxicity that can damage patients' hearts even as they beat their cancer.

WP1122 uses yet another mechanism to fight cancer.

"Most people don't know that morphine is essentially a modified version of heroin," Klemp explains.

The difference between the poppy-based drugs? Heroin can cross the blood-brain barrier. It's described as the dicetyl ester of morphine. WP1122 is the dicetyl ester of 2DG (2-Deoxyglucose), a glycolysis inhibitor, which works by overfilling tumor cells with fake glucose so that they can't consume the real glucose that makes them grow.

"The theory is, we could feed you so full of junk food that eventually you'd starve to death," Klemp elucidates. It can cross the blood-brain barrier and is metabolized slowly, meaning that it can be made into a drug in a way that 2DG cannot.

What's impressive about Moleculin is its diversity of drugs. Most companies have one drug that gets all or most of the attention. Moleculin has strong hopes for all three currently in trials.

"It's essentially multiple shots on the goal," says executive vice president and CFO Jonathan Foster.

Moleculin has 13 total employees, five of whom are based in Houston. An office in the Memorial Park area serves as a landing pad for employees and collaborators from around the world to get their work done when in Space City. The virtual office set-up works for the company because experts can stay in their home cities to get their work done. And that work is on its way to saving scores of lives.

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This UH engineer is hoping to make his mark on cancer detection. Photo via UH.edu

Early stage cancer is hard to detect, mostly because traditional diagnostic imaging cannot detect tumors smaller than a certain size. One Houston innovator is looking to change that.

Wei-Chuan Shih, professor of electrical and computer engineering at the University of Houston's Cullen College of Engineering, recently published his findings in IEEE Sensors journal. According to a news release from UH, the cells around cancer tumors are small — ~30-150nm in diameter — and complex, and the precise detection of these exosome-carried biomarkers with molecular specificity has been elusive, until now.

"This work demonstrates, for the first time, that the strong synergy of arrayed radiative coupling and substrate undercut can enable high-performance biosensing in the visible light spectrum where high-quality, low-cost silicon detectors are readily available for point-of-care application," says Shih in the release. "The result is a remarkable sensitivity improvement, with a refractive index sensitivity increase from 207 nm/RIU to 578 nm/RIU."

Wei-Chuan Shih is a professor of electrical and computer engineering at the University of Houston's Cullen College of Engineering. Photo via UH.edu

What Shih has done is essentially restored the electric field around nanodisks, providing accessibility to an otherwise buried enhanced electric field. Nanodisks are antibody-functionalized artificial nanostructures which help capture exosomes with molecular specificity.

"We report radiatively coupled arrayed gold nanodisks on invisible substrate (AGNIS) as a label-free (no need for fluorescent labels), cost-effective, and high-performance platform for molecularly specific exosome biosensing. The AGNIS substrate has been fabricated by wafer-scale nanosphere lithography without the need for costly lithography," says Shih in the release.

This process speeds up screening of the surface proteins of exosomes for diagnostics and biomarker discovery. Current exosome profiling — which relies primarily on DNA sequencing technology, fluorescent techniques such as flow cytometry, or enzyme-linked immunosorbent assay (ELISA) — is labor-intensive and costly. Shih's goal is to amplify the signal by developing the label-free technique, lowering the cost and making diagnosis easier and equitable.

"By decorating the gold nanodisks surface with different antibodies (e.g., CD9, CD63, and CD81), label-free exosome profiling has shown increased expression of all three surface proteins in cancer-derived exosomes," said Shih. "The sensitivity for detecting exosomes is within 112-600 (exosomes/μL), which would be sufficient in many clinical applications."

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