Immunotherapy Candidate Enters Clinical Trials
Since 2008, Alligator Bioscience has been building a pipeline of antibodies for immunotherapy of cancer. By the end of 2014, their first drug candidate is expected to enter clinical trials.
Ever since Bristol-Myers Squibb’s immunotherapy anti-cancer treatment Ipilimumab, marketed as Yervoy®, was approved by the FDA in 2011, immunotherapy has been extremely hot. This is not surprising since it’s the first type of therapy that actually presents a cure for cancer, a market of astronomical proportions.
In short, immunotherapy works by activating the body’s own immune system to fight the cancer cells, by targeting certain receptors. By combining different immunotherapies, it may be possible to obtain even better treatment effects, than what is known today.
”At the end of the day, all anti-cancer treatments will be combination treatments” says Sibylle Lenz, CEO of Alligator Bioscience, a biotech company in Medicon Village, Lund, which develops antibody-based drug development candidates for immunotherapy of cancer.
”It has been groundbreaking to see patients survive for years, instead of months, after treatment with antibody based immunotherapies,” she adds.
Since 2008, Alligator Bioscience has been building a pipeline of antibodies for immunotherapy of cancer. The company focuses on the discovery and early development phases. Their first project, the fully human CD40 activating antibody ADC-1013, is entering clinical trials in late 2014.
”ADC-1013 induces powerful anti-tumour immune effects through the activation of the receptor CD40 on dendritic cells. We are currently preparing the clinical trial application package for submission later this autumn,” Sibylle Lenz tells.
In addition to a dramatic increase in the number of immune cells attacking the tumour, a tumour-specific memory is established leading to long-term immunity to the cancer. However, systemic administration of CD40 activating antibodies has previously been associated with severe toxicity related to systemic immune activation.
”Therefore, we’re developing ADC-1013 for intratumoral administration. Locally administered ADC-1013 has been shown to induce a strong anti-tumour immune response resulting in eradication of the tumours in different mouse models. In addition, mice cured from a certain tumour by ADC-1013 were subsequently resistant to this tumour even if no further treatment was administered. This confirms that ADC-1013 is able to evoke a long-term immunological memory that protects from new metastases for several months after treatment,” says Sibylle Lenz.
The two other projects in the company’s pipeline, ADC-1015 (local administration) and ADC-1016 (systemic administration), are bispecific antibodies meaning that they target two receptors instead of one. By incorporating two immune activating entities, superior efficacy is obtained.
”In fact, ADC-1015 can induce better effect than the two corresponding immune activators given in combination!,” states Sibylle Lenz.
By binding to two cells simultaneously, ADC-1015 also promotes cell-to-cell interactions resulting in strong co-stimulatory signalling and massive immune activation, leading to superior anti-tumour efficacy. Being administered locally, ADC-1015 is likely to restrict the immune activation to the tumour microenvironment thereby reducing systemic side effects. The compound is currently in preclinical development.
Although intratumoral administration is the most straightforward way to localise a therapeutic antibody to the tumour area, it’s not always feasible. Therefore, Alligator Bioscience is running a bispecific drug development project that combines systemic administration with local immune activation, ADC-1016.
”Even though ADC-1016 is administered systemically, the pharmacological effects are localised to the tumours. This is achieved by the fusion of a tumour targeting antibody with an immune activating antibody,” says Sibylle Lenz.
In growing their pipeline Alligator uses its proprietary technology platforms: ALLIGATOR-GOLD, a unique fully human antibody library, and FIND® (Fragment INduced Diversity), a powerful in vitro based antibody optimisation technology.
”We also have extensive research collaborations with groups in the USA, UK and other countries. And, a long-standing scientific collaboration with Uppsala University Professor Thomas Tötterman, an internationally recognised pioneer in the field of cancer immunotherapy,” Sibylle Lenz concludes.