eFFECTOR takes the roads less traveled to maximize cancer treatment

Therapeutic EFFECTOR is at the forefront of the development of Selective Translational Regulation Inhibitors (STRIs), a class of therapies that block the production of common pathogenic proteins in cancer.

Interim results from studies of STRI therapies in breast cancer patients have shown that the therapies are safe, work as expected and indeed show signs of clinical activity.

In an interview with BioSpaceSteve Worland, President and CEO of eFFECTOR, said he was particularly excited about STRIs because of the history they are already creating.

“This is the first agent in this class that has ever entered clinical development,” Worland said. “So it’s very exciting.”

Steve Worland_EFFECTOR 2How do STRs work?

Cancer cells depend on protein synthesis to multiply and spread. When STRIs are used, this protein synthesis is blocked at the central node, also called eukaryotic initiation factor 4F (elF4F), where two cancerous pathways would normally converge, causing cancer to multiply and spread. Blocking this production would inhibit the creation of disease-causing proteins while preserving the normal, healthy state of the cell.

STRIs can work alongside existing therapies and potentially other drugs still in development. If STRIs prove largely safe and effective for cancer patients, they could be used before a patient has to undergo chemotherapy.

According to Worland, once breast cancer progresses to a certain point, there are limited options for patients until they undergo chemotherapy.

“What we hope is, with a well-tolerated regimen, we can develop a second chemotherapy-free regimen that patients could follow before switching to chemotherapy,” he said.

Country of the world present data on early STRI studies at the American Society of Clinical Oncology (ASCO) annual meeting in early June. eFFECTOR reported that STRIs were shown to be safe for patients tested while working to block the production of cancer-related proteins without harming other non-dangerous cells.

Worland said clinicians involved with the data were “very pleasantly surprised that it was as safe as it was while still having the effects it did.”

To look closer

Until now, most STRI studies have focused on ER-positive or estrogen-responsive breast cancer. This means that patients with this type of cancer have cancer cells that grow in response to the hormone estrogen. The majority of breast cancers are considered ER-positive, according to National Library of Medicine.

Worland said the studies began with these breast cancer patients because there is already a large amount of research to support the importance of protein production in this type of cancer. He said he knew it was a “timely area to explore” and that, if successful, it could make a difference to the way breast cancer is treated.

The experimental group in the Phase I/II clinical trial of eFFECTOR is heterogeneous – among the women involved, each is at a different place in their breast cancer treatment regimen. Although many patients were already on other therapies, the STRI drug in question, called zotatifine or “zota” for short, was still noticeable.

In a press release, Wordland said zota was “generally well tolerated” in clinical trials and shows “very convincing preclinical activity, including in combination with palbociclib for breast cancer.”

The first two phases of the clinical trial focused on dose escalation. As doses of zota slowly increased, clinicians measured patient responses and monitored outcomes. So far, zota has been shown to be not only safe, but also effective in some patients in slowing protein production in ER-positive breast cancer cells.

What happens afterwards?

Now that the appropriate zota dosage has been determined for a varying group of women, Worland explained that it’s important to identify the genetics that work best with how zota works. Even just looking at ER-positive breast cancer, there’s an assortment of genetics that come into play that would affect how zota works with a person’s cells.

“The hope would be that we could refine that and identify the group that responds the most to our drug,” he said.

New data about how Zota works in people with ER-positive breast cancer will be available by the first quarter of next year. Worland also thinks STRIs might be effective in other forms of cancer.

“One of the exciting things about the drug is that it hits networks that are very important for cancer cells, but again it’s quite selective, so we think we can go into a few other areas as well.” , did he declare.

There is currently a KICKSTART study for patients with non-small cell lung cancer. The study will measure the productivity of adding STRI therapy to existing immunotherapy for patients with lung cancer. The STRI drug, called tomivosertib, is an immunotherapy treatment that will stop the production of these specific cancer cells in the body, thus protecting the immune system.

More data regarding how these STRI drugs work can be expected later this year and early 2023.

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