As part of WuXi AppTec’s ongoing efforts to collaboratively foster new thinking and actionable approaches in advancing breakthroughs for patients, we have launched a new interview series in 2022 – “Delivering on the Promise of New Modalities” – so leading voices of R&D can share how their approaches are addressing the barriers standing in the way of breakthroughs.

Our next instalment of our interview series features Reagan Jarvis, Co-Founder & CEO of Anocca AB, an innovative therapeutic biotechnology company developing next-generation immunotherapies that precisely leverage the immune system of each patient. Their technology platform deploys proprietary cellular, genetic and molecular tools to rapidly and accurately interrogate the adaptive immune system so as to develop and manufacture T-cell therapies and reagents. Last year, the company raised $47 million in Series B Financing to further advance the company’s industrialised cellular biology platform and progress its pipeline of TCR-T cellular therapies towards Phase I/IIa clinical trials.

Thanks for joining us. Anocca focuses on developing novel T-cell therapies. In your opinion, what are the top industry-wide challenges in this field? What are the solutions?

Reagan: Chimeric antigen receptor (CAR) T-cell therapies have revolutionised the treatment of some haematological cancers. However, CAR-T therapies have shown little promise in the treatment of solid tumours, due in part to the small number of suitable cell surface targets in the solid tumour setting.
There is a natural solution to the targeting limitation of CAR-Ts, namely, in T-cell receptor (TCR) targeting. TCRs are the native targeting system of T-cells and detect ‘HLA-presented peptides’ that are derived from processed protein targets from all parts of a cancer cell. The promise of TCR-equipped cellular therapeutics is in unlocking this cancer-specific target space that has been inaccessible to CAR-equipped cell therapies.

A fundamental challenge in the TCR-T therapies is technological – platforms for more precise mapping and validation of the complex and extensive target space and efficient generation of optimal targeting TCRs are needed to deliver potent and safe T-cell therapies for solid tumours.

What is your TCR-T approach helping to address the challenges? How differentiated is it from existing approaches?

Reagan: Anocca’s platform has been purpose-built to systematically work through the complexity of T-cell biology. We have assembled a range of high-precision cell-based assay systems to conduct the necessary cellular analyses to build potent cellular therapies.

The key to this approach is that at every layer of our systematic TCR-T pipeline, we account for the genuine biology in high-precision and rapidly formatted cellular assays. We don’t rely on computational predictions and indirect analyses that poorly approximate the biology or make it difficult to distil critical information.

Beyond precision biology, addressing the TCR target space requires efficiency and scalability. The biology of HLA-presented peptide targets means that different patient segments require different TCR assets, even when we are considering the same tumour target, such as a KRAS mutation. Our technology enables the rapid construction of TCR asset franchises with deep HLA and target coverage to maximise patient reach.

What are critical challenges in realizing the full potential of your new TCR-T system? What are the future solutions?

Reagan: Anocca has addressed the challenges with respect to target and population coverage in addition to targeting quality and specificity of TCR-based cellular therapies, but substantial challenges remain across the space for mobilising CAR and TCR targeting receptors in cost-effective and efficacious cell manufacturing platforms.

The approved CAR-T products today are autologous, meaning manufactured from the patient’s own T-cells. The success of these CAR-T products has fuelled a massive amount of investment in enhanced autologous manufacturing and novel allogeneic, or ‘off-the-shelf’, cellular therapy manufacturing platforms.

Improved manufacturing platforms, whether autologous or allogeneic, is acknowledged as a key challenge across the industry. Targeting lower costs, shorter cycle times and reduced operational complexity. This is important for CAR-Ts with high competition around a handful of targets – but is critical to the future of the TCR-T field that will see deployment of multi-asset product families that truly address the natural T-cell target space.

Novel data technologies, AI, or machine learning can also play a role in Anocca?

Reagan: Anocca has built a range of tools within our proprietary software platform. Data analysis, visualisation and machine learning tools are used to conduct quality control and other post-hoc assessments on the systematic biological data we generate. Machine learning for hypothesis generation will undoubtedly be rolled into the platform as our outcome-based datasets grow.

Generally, there is emerging value in developmental areas where the number of unique variables is more manageable, such as small molecule drug discovery. We think this is down the line for TCR-T therapies, where the combinatorial complexity of TCR-target interactions will take time to sample, even with Anocca’s platform, requiring a truly staggering number of curated datapoints to make meaningful progress.

In the coming years, we will see value in a closer marriage of systematic biological assay platforms that feed machine learning models and in turn functionally test the hypotheses generated by such models.

Where you think Anocca will go over the next 5 or 10 years in thinking about collaboration?

Reagan: Anocca’s TCR-T product development is underpinned by our technologies to precisely identify targets and generate high-quality TCRs. Ultimately, these assets must be mobilised in quality effector cell platforms. The amount of technology and expertise required to build a cell therapy product is a key challenge across the space, where innovations and innovators span the globe.

We are building a global network of collaborations to access technologies and expertise to ensure we are at the leading edge of cell therapy manufacture to mobilise our TCR asset libraries now and in the future. Importantly, cellular platforms are highly amenable to stepwise refinement and enhancement, independent of the targets or targeting receptors.

With Anocca’s ability to precisely and efficiently analyse T-cell biology we are also building collaborations to move beyond oncology into new modalities and disease areas. Stable long-term collaboration will be key to delivering transformative therapies and vaccines that harness T-cell immunity.

Thanks Reagan. Any closing remarks?

Reagan: During the next decade, therapeutic approaches that precisely recruit or re-target T-cell immunity will achieve a giant leap forward in the treatment and prevention of serious illnesses like cancer. Having built a unique R&D engine from the ground up to harness T-cell immunity, the team at Anocca is excited to next deliver multiple products into clinical development and contribute to a new era of precision immunotherapies.

 

 

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Reagan Jarvis, Ph.D.

Co-Founder & CEO, Anocca AB

Reagan Jarvis is CEO and co-founder at Anocca. Previously holding the CSO post from the company’s founding in 2014 until 2018, Jarvis guided the in-house development of technological and manufacturing capabilities at the company and is co-inventor for all Anocca’s proprietary technologies. Jarvis was educated in his native New Zealand and holds a BSc(hons) and PhD from Department of Biochemistry, University of Otago. Jarvis conducted post-doctoral research in then Department of Surgical Sciences at University of Otago, and subsequently the German Cancer Research Center (DKFZ), Heidelberg.