Four Questions with Serengulam Govindan: Welcoming the Immunomedics Team to Gilead

Today, with the completion of the acquisition of Immunomedics, Gilead is expanding its presence in the area of solid tumors, adding a first-in-class treatment for patients with metastatic triple-negative breast cancer (mTNBC). The medicine is an antibody-drug conjugate – or ADC – that is designed to carry the active cancer medicine, or payload, on an antibody directly to cancer cells.

One especially important component of ADCs is the linker that connects the antibody and the payload. Release and delivery of the payload too soon can or too late could potentially make the treatment less effective.

Serengulam Govindan, a chemist at Immunomedics who is called Govi by his colleagues, was part of the team at Immunomedics that spent more than a year trying to create the right linker.

“We needed to find a linker that would drop the payload at the right speed,” he explains. “The goal of the linker that we created was to be like a Goldilocks – not too fast and not too slow.”

We sat down with Govi to talk about antibody-drug conjugates.

Q: What is the advantage of an antibody drug-conjugate?
These medicines are designed to deposit the drug at tumor sites, with the goal of improving efficacy, sparing as many normal cells as possible, while trying to manage systemic toxicity.

Q: ADCs have been around for the last 30 years and many of the drug candidates over the years have failed. Can you talk about how the field has evolved?
The first generation of ADCs utilized clinically-used chemotherapy drugs as the payloads. These failed in the clinic because they weren’t potent enough for ADC delivery. Based on those results, researchers realized that they needed to use drugs that were orders of magnitude more potent compared to chemotherapy.

Working with highly potent drugs is also a challenge because the linkers that deliver the payload need to be stable enough to carry it to cancer cells without releasing the payload too early. The field has had to evolve to produce medicines that balance the components to allow a therapeutically significant dose of the medicine to reach cancer cells while minimizing any potential off-target effects.

Q: Gilead and Immunomedics share a common purpose of working to advance medicines for people with some of the toughest-to-treat diseases – and this certainly includes triple-negative breast cancer. What makes it “triple-negative” and why is it so hard to treat?
This form of breast cancer is called triple-negative because it tests negative for estrogen receptors, progesterone receptors and excess HER2 protein. What this means for patients is that this form of breast cancer doesn’t respond to hormone therapy medicines or to drugs that target HER2, limiting treatment options.

Triple-negative breast cancer accounts for approximately 15-20% of all breast cancers and tends to be among the most aggressive forms of breast cancer. Metastatic disease occurs when the cancer has spread to other parts of the body.

When you look at all of this together, it really points to the urgent need for people with mTNBC.

Q: Today is a significant milestone for you and the team at Immunomedics. Can you share some closing thoughts with us?
I am really proud that the work we have done over the years at Immunomedics has always centered on patients. Working here has brought sheer joy – it’s a great feeling to be part of something that could have a big impact on patients. I look forward to the next chapter, as we work together with the team at Gilead to continue to bring forward scientific innovation to benefit people with cancer.