“I want to put together cures for AstraZeneca and patients,” Matthew Ellis, the company’s new SVP of early oncology told BioSpace in an interview.
AstraZeneca SVP of Early Oncology Matthew Ellis/Courtesy AstraZeneca
With an eye on becoming a leading oncology company, AstraZeneca made a splash at the American Association for Cancer Research meeting in New Orleans with 60 different presentations highlighting the cancer programs that will bolster its three biggest assets: Enhertu, Lynparza and Tagrisso.
At the annual oncology conference, AstraZeneca’s team, led by Susan Galbraith, executive vice president of oncology research and development, highlighted several of its developmental programs. Prior to the start of AACR, Galbraith said the company is serious about pioneering new approaches to cancer treatment through the development of therapies that can target cancer at earlier stages and with greater precision. The first efforts of that goal were on display at the oncology conference where the company focused on MEDI5752, a novel bispecific antibody, and AZD5305, a next-generation PARP1-selective inhibitor.
AstraZeneca highlighted those two assets as well as AZD8205, a novel ADC that targets B7-H4, a protein that is overexpressed in multiple solid tumors. AZD8205 is the first ADC that uses the company’s proprietary linker technology.
The U.K.-based pharma company has high hopes for these three assets. MEDI5752 is designed to simultaneously target the immune checkpoint proteins PD-1 and CTLA-4. AstraZeneca believes that the use of a bispecific antibody-like MEDI5752 is a promising immuno-oncology approach precisely because of the way it was engineered to block both proteins. MEDI5752 is designed to bind to CTLA-4 only in the presence of PD-1.
With that specific bit of engineering, it reduces the chances of off-target toxicities. The drug will bind only to those activated T-cells and broaden the therapeutic window for the medication. MEDI5752 is currently being assessed in a Phase I study, and the company presented data from the first 86 patients who were dosed with different levels in order to find the right level of efficacy and durability.
With its next-generation PARP1 inhibitor, AstraZeneca believes it has a new approach to killing cancer cells by targeting their DNA repair mechanisms. Not only that, but AstraZeneca also has early evidence that one of its experimental PARP1 inhibitors is capable of crossing the blood-brain barrier, which will potentially allow for new approaches to treating malignancies of the brain.
Galbraith is now supported by Matthew Ellis, senior vice president of early oncology. Ellis joined the big pharma in March after spending a year in academic research. He told BioSpace from AACR that after years of academic research focused on the tumor profiles of patients, he wants to close out his career by helping AstraZeneca develop new therapies for multiple cancer types.
“I want to put together cures for AstraZeneca and patients,” he said in an interview.
Ellis joined AstraZeneca from the Lester and Sue Smith Breast Center at Baylor College of Medicine, where he was the director who oversaw efforts to better understand the molecular profile of breast cancer in order to improve treatment. He was also the co-lead of The Cancer Genome Atlas Breast Cancer project, which revealed that the loss of the NF1 gene is an important driver of breast cancer resistance to hormone therapy.
As AstraZeneca’s assets were on display at AACR, he said he was excited about the potential of these therapies and how they can potentially improve patient care and, one day, help lead to an eradication of cancer. As a cancer survivor himself, Ellis said he’s well aware of the needs of patients and keeps them at the forefront of what he intends to do at the pharma giant.
As a breast cancer physician, Ellis said he’s prescribed PARP inhibitors on multiple occasions and expressed particular excitement about AZD5305, the next-generation PARP1 inhibitor. He noted that this particular asset has been designed to target PARP1, while engineering out PARP2. Current PARP inhibitors that include PARP2 have some off-target issues, he said.
“This has improved the off-target profile,” Ellis said, referring to AZD5305. “The preclinical profile of it is remarkable… the hematological toxicity is gone.”
Ellis added that without the toxicity concerns from PARP2, there is a potential for using higher doses in patients. That could ultimately lead to its use as a medication that could prevent breast cancer patients from having to have a mastectomy and prevent prostate cancer patients from having invasive procedures.
“We’re still in early days with this molecule with early data, but it’s captured everyone’s imagination. This is something we intend to take advantage of,” Ellis said.
He also expressed excitement about the ADC AZD8205, saying that early data suggests the therapy is a “remarkable opportunity to replace chemotherapy.” As an oncologist, Ellis said chemotherapy is a double-edged sword of treatment.
Replacing that with an ADC approach could be transformative. AZD8205 targets B7-H4, a protein overexpressed in a range of solid tumors. He said B7-H4 was carefully selected because of its overexpression and the current understanding of its role in the tumor. AstraZeneca plans to drive this into human testing next year, “coming to a patient near you, soon,” Ellis quipped.
As Ellis looked ahead at his future with AstraZeneca, he said he is excited about exploring new hypotheses in oncology drug research, and will also conduct a top-to-bottom review of the company’s compounds in order to prioritize and accelerate development.
Ellis also said he intends to promote equity in clinical trials. He said ethnic minorities have been overlooked as participants in trials, and that is something that has to change. He expressed hope that some barriers to trials will be addressed in order to open them up to more people from all races.
“The one thing I’ve learned is the value of diversity. It creates an amazing environment, but we have to honor that diversity to make sure that everyone can get a drug and they won’t be overlooked,” Ellis said.
He added that he also hopes to become a champion for trial participation, pointing out that participation levels in the United States are at about 5% of patients. He would like to see that increase to 25%, which would help achieve those higher levels of minority participation.
“There’s a societal responsibility to mitigate cancer in our different populations,” he said.
