Oncology and
Immuno-oncology Drug Discovery
Modern cancer medicines that target precise mutations or boost the immune system have greatly improved the prospects of many patients. But cures remain rare, despite significant ongoing research to improve patient outcomes. Sygnature Discovery’s scientists work across the entire span of oncology drug discovery, from target identification and lead optimisation to candidate nomination and clinical positioning. Medicinal chemists, DMPK experts, bioscientists and in vivo specialists in our translational oncology department work in integrated teams to deliver tailored services for clients.
Dedicated Oncology Drug Discovery Leadership Team
With an extensive track record of delivering novel therapeutics from target validation to clinical studies, our oncology leadership team draws on experience from pharma, biotech, non-for-profit and academic backgrounds to deliver deep critical thinking to your drug discovery project. This expertise spans the entire drug discovery process from target validation, through to clinical trials, patient stratification and biomarker alignment. We unite considerable early discovery expertise with our experiences in the clinical setting, which allows us to think more holistically about your project and deliver a seamless and efficient path from idea to candidate and beyond.
Our Oncology Drug Discovery Philosophy
Patients remain at the heart of every project. Since cancer is no longer considered a single disease driven by unregulated cell proliferation, our scientists also work alongside expert colleagues in inflammation, the immune system and neurological disorders. This wider expertise accelerates the delivery of candidates, particularly for immuno-oncology and CNS cancer projects.
Our bioscientists are skilled in creating robust, tailored in vitro screening cascades. What’s more, state-of-the-art technologies and orthogonal biophysics platforms allow decision-enabling data to be delivered rapidly. A variety of cell culture formats enable focused experiments to be carried out to help in the lead triage process. And in the immuno-oncology setting, our in-house Human Blood Donor Panel gives easy access to immune and inflammatory cells from volunteer blood.
What sets us apart? The deep experience that our scientists have gained across the breadth of oncology drug discovery and a collective knowledge base that informs decisions.
Over recent years, this detailed expertise has directly led to the delivery of twelve clinical candidates in the oncology arena (spanning Phase 1-3 clinical trials), with a further four in pre-clinical development.
Antibody Drug Conjugates (ADCs)
Sygnature Discovery applies decades of small molecule drug discovery expertise to transform antibody-drug conjugates (ADCs) into safer, more effective therapies. Traditionally, ADC development has followed more closely that of antibody therapies, with conjugation and payload selection being undertaken towards the later stages of lead optimization. Yet by engineering precision payloads, optimizing conjugation strategies and refining DMPK properties, we drive the development of antibody drug conjugates for a substantial positive impact on stability, selectivity, and a significantly wider therapeutic window. This novel, chemistry-first payload approach ensures better-targeted delivery, reduced off-target toxicity, and improved patient outcomes—shaping the next generation of safer, more targeted antibody drug conjugates.
Molecular Glues & Degraders
Given that many oncology processes are driven by proteins with disordered structures or a lack of functional activity, it’s not surprising that most of the research activity in both heterobifunctional degraders and molecular glues remains focused upon the delivery of novel oncology therapeutics. However, this expanding field of research often relies on empirical experimentation to deliver start points for optimization.
At Sygnature Discovery, we have developed multiple platforms to expedite proof-of-concept in this area, including our CHARMED platform for the discovery of novel heterobifunctional degraders. We also offer both cell-free and live-cell high-throughput assays for the unbiassed discovery of molecular glues, allowing exploration beyond the commonly exploited Cereblon/IMID molecular glues.
We have significant expertise in the wider field of protein degradation, while our computational and medicinal chemistry capabilities enable rapid optimization, transforming early hits into in vivo capable leads. Delivering these leads involves the complexities of DMPK and pharmacokinetics, particularly in the Beyond Rule-of-Five space, as it is essential to fully understand the effects of protein degraders on the human body as early as possible. Our skills in these areas can pay dividends in your oncology drug discovery programme.
Translational Oncology
At Sygnature Discovery, our translational oncology team designs and delivers tailored preclinical studies to support oncology drug discovery across a wide range of therapeutic modalities – including small molecules, biologics, ADCs, RNA/DNA therapeutics, viral and cell therapies, and radiotherapy.
We offer a comprehensive portfolio of validated and bespoke tumour models, including xenograft, syngeneic, orthotopic and humanized systems, with capabilities spanning monotherapy, combination therapy, resistance modelling and dose/schedule optimization. These in vivo studies are supported by ex vivo platforms for detailed biomarker analysis, target engagement and immune cell profiling. In addition, we can also enrich these studies with in vivo imaging, or deliver combinations in vitro and in vivo with ionizing radiation.
By combining efficacy, pharmacokinetics, pharmacodynamics and biomarker data, we establish clear PK/PD/efficacy relationships that drive decision-making and de-risk your oncology pipeline.
The team includes oncology specialists with extensive pharma experience and a considerable track record of delivering clinical candidates. This depth of expertise enables us to tailor customized, mechanism-informed study designs that move your oncology program forward efficiently and effectively.
Success Stories in Oncology Drug Discovery
These case studies highlight some of Sygnature’s successes in the oncology field:
- Corcept Therapeutics – Glucocorticoid receptor antagonists
- CellCentric – EP300/CBP inhibitors
- Fragment-based hit discovery – Optimization against BRD3
