A novel drug developed by University of Colorado Anschutz Cancer Center researchers to treat certain types of breast cancer — including “postpartum” breast cancer diagnosed within 10 years after a woman gives birth — is one step closer to being evaluated in humans.
For the past two decades, cancer center members Traci Lyons, PhD, and Virginia Borges, MD, MMSc, have worked to better understand why some breast cancers become resistant to treatment and continue to spread despite advances in therapy. That work has been especially important for women diagnosed with postpartum breast cancer, an aggressive form of the disease that can develop in the years following childbirth, often while patients are raising infants, toddlers, or early elementary-aged children. The cancer center researchers are hopeful that a future clinical trial will help determine whether their experimental therapy can address that unmet need.
With funding and commercialization support from CU Anschutz Innovations, the Chancellor's Development Initiative Fund, the Gates Grubstake Fund, SPARK Colorado, American Cancer Society BrightEdge, the National Cancer Institute, and other sources, Lyons and Borges have co-founded their own company, Pearl Scientific, to produce Pearl-01, the drug that targets semaphorin 7A, a protein Lyons discovered as highly relevant to breast cancer.
Lyons discovered semaphorin 7A as a promising target while studying immunosuppression in breast cancer and during postpartum mammary involution — the post-lactation period when the mammary gland returns to its pre-pregnancy state.
The work builds on decades of research through the Young Women's Breast Cancer Translational Program, led by Borges since 2004 to provide specialized clinical care and research on why breast cancers in younger women often behave more aggressively than those diagnosed later in life. Through this work, Borges identified postpartum breast cancer as a uniquely aggressive subset of the disease.
Working with animal models of triple-negative and estrogen receptor positive breast cancer with high expression of semaphorin 7A, the researchers are now testing humanized antibodies of the new drug that could target the protein in humans.
“We have 30 product candidates, and so far, we've tested 13,” Lyons says. “All 13 show good binding to the target, and a handful of them, in a very preliminary study, actually reduced tumor growth. The results are promising.”
Lyons likens the discovery of semaphorin 7A to that of the HER2 protein in the early 1990s, which led to the development of the drug Herceptin (trastuzumab) to target it.
“One comment we often get is, ‘If this is so important for breast cancer, why has no one ever heard of it?’” she says. “My answer is, ‘Because they weren't looking in the right place.’”
Through their experiments, the cancer center researchers have found that the mouse prototype of Pearl-01 not only binds to semaphorin 7A on the tumor cell, preventing the signaling that allows it to survive and divide, but it also acts as immunotherapy, reactivating the immune system to attack the tumor.
“It has a double modality where it can turn off pro-survival signaling in the tumor itself, so the tumor cell dies, but can also activate the cytotoxic T cells to come in and kill the tumor,” Lyons says. Supporting studies are published in Cell Reports (2025) and Molecular Cancer Therapeutics (2026).
Lyons, founder, CSO, and president, and Pearl Scientific’s newly elected CEO, Ted Haack, are now traveling the country pitching to investors, while also applying for funding from the NCI in order to get the $10-$20 million necessary to move the project to its next big goal: a phase 1 clinical trial that will identify the drug’s optimal dose for further trials and gather preliminary safety and efficacy data.
Based on Lyons’ and Borges’ original research showing that semaphorin 7A is high in postpartum patients and can predict for recurrence, the researchers hope that postpartum patients will ultimately benefit from the drug, achieving a longstanding goal for the Young Women's Breast Cancer Translational Program. Their ongoing research also suggests that most breast cancers express some semaphorin 7A, which is why the initial Phase I trial is broadly targeting breast cancer, not just those diagnosed postpartum.
“The clinical trial will first be for patients with relapsed metastatic breast cancer whose tumors are not responding to their current treatment,” Lyons says. “We need to identify the safety of targeting semaphorin 7A in humans and also hope to see a clear signal that it is very active in killing breast cancer.”
For Lyons and Borges, the ultimate goal is to determine whether targeting semaphorin 7A can provide a new treatment option for breast cancer. If successful, the first-in-human Phase I trial would be the first step toward bringing a potentially new class of targeted therapy that could benefit any subtype of breast cancer. While significant preclinical work remains before a clinical trial could launch, each milestone brings them closer to this goal. Progress on this journey will be fueled by the team finding further investments for Pearl Scientific.