eFFECTOR Takes Road Less Traveled to Maximize Cancer Treatment

eFFECTOR Therapeutics is pioneering the development of selective translation regulation inhibitors (STRIs), a class of therapies that block the production of disease-driving proteins common in cancer.  

Interim results from studies of STRI therapies in breast cancer patients have shown that the therapies are safe, operate as designed and are effectively showing signs of clinical activity.  

In an interview with BioSpace, Steve Worland, president and CEO of eFFECTOR, said he is especially excited about STRIs because of the history they are already making.  

"This is the first agent of this class that's ever gone into clinical development," Worland said. "So it's very exciting."  

How Do STRIs Work?

Cancer cells rely on the synthesis of proteins 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 cancer pathways would normally converge, causing cancer to multiply and spread. Blocking this production would inhibit further creation of disease-driving proteins while still preserving the cell's normal and healthy state.  

STRIs can work alongside existing therapies and potentially other drugs still in development. If STRIs are found to be widely safe and effective for cancer patients, they could be put to use before a patient has to undergo chemotherapy.  

According to Worland, once breast cancer progresses to a certain point, there is a limited number of options for patients until undergoing chemotherapy.  

"What we're hoping is, with a well-tolerated regimen, to be able to craft a second non-chemotherapy regimen that patients could take before moving on to chemotherapy," he said. 

Worland presented data about the first studies on STRIs at the American Society of Clinical Oncology (ASCO) annual meeting in early June. eFFECTOR reported that its drug, zotatifin, or "zota" for short, seemed to be safe for the patients tested while working to block the production of cancer-related proteins without harming other non-dangerous cells.  

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

A Closer Look

Most of the studies on zota so far have focused on ER-positive or estrogen-receptive breast cancer. This means that patients with this type of cancer have cancer cells that grow in response to the hormone estrogen. A majority of breast cancers are considered ER-positive, according to the National Library of Medicine. 

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

The experimental group comprising eFFECTOR's Phase I/II clinical trial is heterogeneous – of the women involved, each is in a different place in their breast cancer treatment regimen. Despite many patients already undergoing other therapies, the impact of zota was still noticeable. 

In a press release, Wordland said zota has been "generally well-tolerated" in the clinical trials and shows "very compelling preclinical activity, including in combination with palbociclib for breast cancer."  

The first two phases of the clinical trial focused on dose escalation. As the doses of zota slowly increased over time, clinicians measured reactions among the patients and monitored the results. So far, the therapy has proven to not only be safe but also effective among certain patients in slowing the protein production of ER-positive breast cancer cells.  

What Comes Next?

Now that the proper dosage of zota has been determined for a varying group of women, Worland explained that it's important to pinpoint the genetics that work best with the way zota operates. Even looking at just ER-positive breast cancer, there is an assortment of genetics that comes into play that would have an effect on the way zota works with a person's cells. 

"The hope would be that we could further refine that and identify the group that is most responsive to our drug," he said. 

New data regarding the way zota works in individuals with ER-positive breast cancer will be available by the first quarter of next year. Worland also believes that STRIs could be effective in other forms of cancer. 

"One of the exciting things about the drug is it hits networks that are very important for cancer cells, but again, it's quite selective so we think we can go in a couple of other areas as well," he said. 

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 lung cancer patients. The STRI drug, called tomivosertib, is an immunotherapy treatment that will halt the production of these specific cancer cells in the body, therefore protecting the immune system.  

More data regarding the way these STRI drugs work can be expected at the end of this year and early in 2023.