Moleculin’s New STAT3 Inhibitor Attacks Cancer from Inside the Cell


Wally Klemp Moleculin

Walter Klemp, Chairman and CEO of Moleculin Biotech

The death of Sen. John McCain helped raise awareness about the plight of brain tumor patients and the lack of movement on developing new therapies for this disease over the past several years. But now, Houston-based Moleculin Biotech has launched a clinical trial that could be a game-changer if all goes well.

Working in conjunction with University of Texas MD Anderson Cancer Center, Moleculin has initiated a Phase I trial for WP1066, a molecule that Walter Klemp, chairman and chief executive officer of Moleculin, said is an entirely new approach to treating brain tumors. The first patient has been dosed in the early trial, the company announced.

“We’re excited about opening a new chapter in the development of brain tumor treatments,” Klemp told BioSpace Wednesday afternoon.

Moleculin’s WP1066, a first in class drug candidate, is built from the chemical backbone of the active ingredient in propolis and is the first anticancer agent with drug-like properties that consistently inhibits the activated form of STAT3 within cancer cells. STAT3 is a target that has been long-sought because of its broad range of tumor-promoting effects. When activated, STAT3 proliferates the growth of tumor cells and supports the “evasion of the immune response and metastasis to distant organs,” the company said. Because of its importance in supporting the growth of cancer cells in the brain, it’s a significant target for therapies.

“This represents a major milestone for Moleculin. Being able to say we finally have a druggable STAT3 inhibitor gets people’s attention,” Klemp said.

Moleculin Chief Medical Officer Sandra Silberman said WP1066 inhibits STAT3, which controls not just proliferation, but also some immunologic function including cytokine release and T-cell infiltration. By inhibiting STAT3, it will allow the T-cell to penetrate the tumor, Silberman said. In animal and preclinical studies, Silberman said WP1066 has shown “extremely promising results.”

The Phase I study at MD Anderson will not only include the standard dose escalation and tolerability studies, but adds a surgical aspect, which is standard of care when it comes to glioblastoma. When the time is right, MD Anderson will attempt to remove the tumors from patients’ brains and see the effects of WP1066 and determine if the T-cells are penetrating and if they get a cytokine response.

“We’re going to get a lot of information out of this,” Silberman said.

Kemp added that is it indicative the community understands the importance of STAT3 as a target and that until now, it’s been “difficult to find an agent that can do that.”

Moleculin is eying dosing 15 patients in the Phase I trial. While the first patient has already been dosed, Klemp said the study will depend on the rate of trial recruitment, which could be slow. Practically speaking, Klemp said he anticipates a data readout in 2019.

“Given the significant unmet need, if they see encouraging data, they believe this is an undertaking that could ultimately receive fast-track handling from the FDA,” Klemp said.

Klemp also noted that MD Anderson isn’t the only research facility interested in exploring the abilities of WP1066. The Mayo Clinic and Emory University have also reached out to the company to form collaborative efforts to test WP1066 in their labs. Those institutes have their eyes on using the STAT3 inhibitor in into pediatric brain tumor trials, Klemp said.

While Moleculin is excited about the potential of WP1066 in brain tumors, the company has several other irons in the fire. Klemp noted that unlike other small biotechs with a central focus around one molecule or therapeutic theme, Moleculin has three distinct core technologies. In addition to WP1066, the company has a suite of molecules that inhibit glycolysis, a primary source of energy for tumors, and annamycin, a second generation anthracycline for the treatment of relapsed or refractory acute myeloid leukemia. Klemp said the company is driving these molecules into the clinic as part of a broad-based scope of research.

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