Innate's Cancer Therapeutics are Reaching New Clinical Heights
Yannis Morel, Ph.D./courtesy of Innate Pharma
Many of Innate Pharma’s cancer-fighting products have recently made clinical progress. BioSpace connected with Yannis Morel, Ph.D., executive board member and head of product portfolio strategy and business development, to get an inside look at the science behind a few of the Marseille, France-based company’s therapeutics.
“We specialize in immuno-oncology, and particularly in the development of new therapeutic antibodies that harness the innate immune system,” Morel said.
Innate has developed several blocking and therapeutic antibodies that trigger the immune system to fight cancer. “We started out working with NK (natural killer) cell checkpoint inhibitors, and more recently have moved into the field of multispecific antibodies, also called NK cell engagers (NKCEs),” he continued.
Morel has been with the company for more than two decades and started out on the immunology team as a scientist in 2001. He shared that he earned his Ph.D. in the early days of immuno-oncology. “I was a researcher in academia and was really excited by the innovative possibilities and the pathways to make potential new drugs that would contribute to improved cancer patient outcomes. Next door to my lab, this biotech company, Innate Pharma, was just starting. I was so excited by the project that I joined.”
T-cell Lymphoma Therapy Sees Encouraging Phase II Data
One of the very first products the company developed, lacutamab (IPH4102), targets KIR3DL2, a tumor-associated antigen related to T-cell lymphoma. Morel said the product “depletes cells that express the KIR3DL2 antigen.”
Lacutamab was first examined in a Phase 1 clinical trial from 2015 to 2017 that involved 44 patients with Sézary syndrome, mycosis fungoides, a type of cutaneous T-cell lymphoma and primary cutaneous T-cell lymphoma (CTCL). Findings from the trial were published in The Lancet Oncology, with the authors stating that “if confirmed in future trials, IPH4102 could become a novel treatment option for these patients.”
“We had very encouraging data at the end of Phase I with strong monotherapy activity even in late-stage patients after multiple lines of treatment,” Morel said.
Lacutamab continues to be investigated clinically today. “In our ongoing Phase II trial, we have cohorts addressing patients who are suffering from mycosis fungoides. Some patients are KIR3DL2 negative, and some are KIR3DL2 positive. We recently presented some very encouraging preliminary data supporting our biological hypothesis,” Morel said. The company expects to present more data later this year on both tumor activity and longer periods of follow-up with patients.
Key Late-Stage Asset Reaches Phase III
Another of Innate’s products, co-developed with AstraZeneca, is monalizumab. The blocking antibody also provokes an anti-tumor response. “This product targets a checkpoint molecule called NKG2A. NKG2A is an inhibitory checkpoint, like PD-1, that is expressed both on NK cells, and very interestingly, on tumor-infiltrating CD8 T cells,” Morel explained.
He added that “the last six to nine months have been very rich for monalizumab.” The product is currently in two Phase III trials. One trial, INTERLINK-1, utilizes the product in combination with cetuximab to treat head and neck cancer patients.
The other, PACIFIC-9, is investigating the product in combination with durvalumab in patients suffering from unresectable, Stage III non-small cell lung cancer (NSCLC). “There is a biological hypothesis that by blocking NKG2A, we can increase the efficacy of the PD-L1 blockade,” Morel said.
After the first patient in this trial was dosed earlier this year, Chief Executive Officer Mondher Mahjoubi commented in a press release that the company is “very pleased that our key late-stage asset, monalizumab, has progressed into a second Phase III trial with our partner, AstraZeneca. The launch of PACIFIC-9 represents an important financial milestone for Innate, as it triggers a $50 million milestone payment that reinforces our cash position.”
The company announced in early June that another of its products, a blocking monoclonal antibody known as IPH5201, will be moving forward in a Phase II study. Developed in collaboration with AstraZeneca, this product intends to trigger anti-tumor functions in lung cancer patients.
ANKET Platform Potently Activates NK Cells Against Tumors
In a 2021 interview with BioSpace, Innate CSO Eric Vivier, Ph.D., DVM highlighted the company’s proprietary ANKET (Antibody-based NK cell Engager Therapeutics) platform, which serves as an alternative to T-cell therapy and works to safely eradicate tumors.
The platform creates multispecific synthetic molecules that bind receptors on tumors and associated antigens. Morel explained that the first project using ANKET in partnership with Sanofi targeted CD123, a tumor antigen for acute myeloid leukemia. “Our first-generation molecule is highly specific. It binds on one end of the tumor, and on the other end, the molecule activates NK cells via NKp46 and CD16, which yields very potent activation of NK cells against the tumor,” he said.
Today, the platform’s new generation molecules are even more efficient. “In our latest innovation, we further improved these molecules by adding a cytokine in the engager molecule. Now, we can increase the number of NK cells significantly, causing even more anti-tumor effects,” Morel continued.
In addition to these products, the company has many others in various stages of development. “We have assets that are targeting several mechanisms of action,” he shared. “We also have a next wave of innovations with our ANKET platform, which is very modular. Based on the binder we incorporate into our molecules, we can replicate this product on any kind of tumor antigen.”
Morel added that, in addition to the Sanofi program, Innate is working on other so-far undisclosed tumor antigens. “This will lead to multiple products in various disease areas,” he said.