Pasadena-based pharmaceutical company Lixte Biotechnology Holdings Inc.’s new chief executive is also charting a new course for the company and its cancer treatment drug.

Bas van der Baan, a veteran biotech executive, took over as chief executive last fall as the company founder and longtime chief executive, John Kovach, retired and then passed away at age 87. Baan has taken the helm as the company is embarking on clinical trials of its main drug candidate.

But Lixte’s drug is not designed to be administered as a standalone treatment against cancer; rather, the aim is to have it work in tandem with more established chemotherapy and immunotherapy regimens.

It’s an unusual course for the nearly 20-year-old company. Most biotech companies – including Lixte itself for its first 15 years – have developed drugs that act on a standalone basis to treat cancers or other diseases.

“We have pivoted from a monotherapy approach to helping other therapies – namely immunotherapy and chemotherapy – to kill cancer cells,” Baan said.

But that’s not Lixte’s only unusual feature. Unlike most biotech companies, Lixte doesn’t have in-house research and development staff. Instead, the company farms that basic work out, along with just about everything else. The only full-time employees are four executives who oversee all the outsourced work.

This of course minimizes overhead, but it also makes the company dependent on the research goals of others.

As a result, while Lixte’s technical global headquarters is in Pasadena, the research and clinical trial work have been dispersed around the globe. Baan’s home base is at the Netherlands Cancer Institute in Amsterdam, where much of the research work is taking place. Other work for Lixte – including clinical trials – is being done at the University of Texas’ MD Anderson Cancer Center in Houston.

City of Hope roots

Lixte Biotechnology began in 2005 as the late Kovach, then a researcher at Duarte-based City of Hope, was looking into a molecular compound that acts as an inhibitor of an enzyme – called PP2A phosphatase – that regulates cell replication and plays a role in the transformation of regular cells into cancer cells. Sensing the commercial possibilities of this compound that inhibits this enzyme, Kovach left City of Hope to launch Lixte.

For the next 15 years, Kovach and a small team he recruited researched this molecular compound to gauge both its safety and its effectiveness. They took the drug – with the placeholder name of LB-100 – through preclinical trials (including animal testing) on certain types of cancers and determined it was both safe enough and effective enough to warrant clinical trials in human cancer patients.

But then came an unexpected twist.

Lixte’s molecular compound caught the attention of researchers at the Netherlands Cancer Institute and the two entities began collaborating on their research. According to Baan, around the year 2020, the idea came up that the same molecular compound could be added to existing chemotherapy and immunology treatments to make those treatments more effective.

This has been a long-sought goal of many in the cancer-treatment sector. Chemotherapy and immunotherapy are typically the first line of treatment against cancerous tumors. The goal is to shrink the tumors – ideally to the point where the cancer is regarded as in remission – without having to surgically remove them.

But both chemotherapy and immunotherapy have severe side effects (including intense nausea, hair loss, anemia and loss of immunity) and low success rates – often as low as 20%. That means most patients who undergo chemotherapy and immunotherapy go through all that pain and suffering – ultimately for naught.

“It’s all about making chemotherapy and immunotherapy more effective by keeping the inhibitor going,” said Winson Ho, a former Lixte board member who is currently an assistant professor in the department of neurosurgery at UC San Francisco and an expert in the treatment of brain cancers.

“It’s not about reducing the side effects of chemo and immunotherapy – at least not at this stage,” he added.

Lixte is one of several companies pursuing this combination therapy approach. The concept of combination therapy has been around for decades, but only in the last 15 to 20 years has the scientific research developed to enable the use of enzyme inhibitors such as what Lixte is doing. Each of the drugs developed to be used in tandem with chemotherapy and immunotherapy targets a different pathway to block the transformation of regular cells into cancer cells.

For Lixte, this change in application strategy meant that more research had to be done to see how its drug interacted with the drugs used in chemotherapy and immunotherapy. That preclinical research was mostly completed as of last year, and now the company – through its partners – is launching the clinical trial phase.

Late last month, Lixte announced that the first patient had received its drug in combination with immunotherapy as part of an early-phase clinical trial of ovarian clear cell carcinoma patients. The driving force and funding behind the clinical trial is actually Middlesex, United Kingdom-based pharmaceutical giant GSK (formerly GlaxosmithKline), which is seeking to test the effectiveness of a new monoclonal antibody. The clinical trial was initiated by – and is being conducted at – MD Anderson Cancer Center in Houston.

Baan noted that this is the most recent of three clinical trials to get underway involving Lixte’s LB-100 molecular compound. The other two trials are targeting different types of cancers.

All the trials are very narrow at this stage, involving only about a couple dozen patients.

“Going forward, we need to get a larger base to see how effective the combination therapy really is against different cancer targets,” Baan said.

Lixte’s challenge will be to see if its specific drug boosts the effectiveness of chemotherapy and immunotherapy more than other combination therapies being developed by other pharmaceutical companies, especially those companies with deep pockets like GSK or Rahway, New Jersey-based Merck & Co.

“There has been some progress by other companies in the treatment of melanomas and colon cancer, but otherwise, progress has been quite slow,” Baan said.

Lixte is at somewhat of a disadvantage, especially when competing against similar combination therapy drugs being developed by pharma giants.

“The company’s approach of farming out of its R&D means it doesn’t have as much control over the direction of research,” former board member Ho said. “So far, though, that has not been an issue at all with Lixte.”