The new collaboration between BioNTech and Cambridge, UK-based clinical stage immuno-oncology specialist Crescendo Biologics will leverage both companies’ expertise to develop precision immunotherapies to treat cancer and other diseases. In the second project, which has already led to a commercial joint venture, BioNTech collaborated with London-headquartered InstaDeep on the model of an early warning system (EWS) for new Covid variants.

Crescendo collaboration focused on cancer therapy

The partnership with Crescendo just getting under way will leverage BioNTech’s proprietary multimodal immunotherapy expertise and the British biotech’s proprietary Humabody V_H platform to develop precision immunotherapies to treat cancer and other diseases, including mRNA-based antibodies and engineered cell therapies.

During the discovery phase, initially set for three years, the German partner will hold exclusive worldwide development and commercialization rights to all immunotherapies arising from the collaboration. Crescendo will receive $40 million upfront, including a cash payment and an equity investment from BioNTech, plus research funding.

The Cambridge firm, which is backed by blue-chip investors including Sofinnova Partners, Andera Partners, IP Group, Takeda Ventures, Quan Capital and Astellas, also will be eligible for development, regulatory and commercial milestone payments potentially exceeding $750 million, plus tiered royalties on global net sales.

Humabodies are a novel class of therapeutics that retain the high-affinity binding and specificity of conventional therapeutic antibodies while providing additional advantages such as small size, enhanced tissue and tumor penetration, stability and molecular simplicity. Due to their modular nature, they are thought to be ideally suited for development of multi-target immunotherapies.

Crescendo’s platform provides “excellent properties for exploiting novel targets and target combinations with great potential for the development of multi-specific mRNA and engineered cell-based therapies in a variety of disease areas,” said BioNTech CEO Ugur Sahin.

InstaDeepProject Develops EWS for Virus Variants

A new computational method developed by BioNTech and InstaDeep to identify new Covid variants uses artificial intelligence (AI) to calculate immune escape and fitness metrics. The Early Warning System (EWS) the companies jointly developed analyzes worldwide available sequencing data to predict the behavior of the high-risk variants.

The companies’ new method developed in a project begun in 2020, combines structural modeling of the viral spike protein and AI algorithms to flag potential high-risk variants in less than a day. The system is based on fitness metrics that score the variants’ ACE2 and variant spike protein interaction as well as their immune escape properties. BioNTech said the predictions were validated using experimental data generated in-house and publicly available data.

During the trial period, the EWS is said to have identified more than 90% of the World Health Organization’s designated Variants of Concern, Variants of Interest, and Variants Under Monitoring, on average two months ahead of the WHO. The system was able to detect the variants Alpha, Beta, Gamma, Theta, Eta and Omicron, for instance, in the same week the sequence was first uploaded.

BioNTech said the new monitoring methods ranked the Omicron variant as high-risk on the same day its sequence became available and also detected the new IHU variant recently observed in France. The latter has immune escape properties relatively similar to those of Omicron but with significantly lower fitness, making this variant “less of a concern,” given current data, the Mainz-based biotech added.

Results from the study underscore that the new EWS is capable of evaluating new variants in minutes and can risk-monitor variant lineages almost in real-time, BioNTech CEO Sahin said. What’s more, it is also fully scalable as new variant data becomes available. “Early flagging of potential high-risk variants could be an effective tool to alert researchers, vaccine developers, health authorities and policy makers and provide more time to respond to new variants of concern,” he stressed.

Karim Beguir, co-founder and CEO of InstaDeep, said the collaboration addressed the challenge of more than 10,000 novel variant sequences currently being discovered every week by exploiting the powerful AI capabilities of the London- based company’s DeepChain platform combined with BioNTech’s Covid-related knowhow and technology.

A major advantage of the EWS system, the collaborators believe, is that it was able to distinguish the WHO-designated variants from those that had had no designation over a 11-month period. For variants Alpha to Mu, only around 25 cases on average had been recorded at the time the variants were being flagged by the international health watchdog, they noted.

While the WHO warnings were issued only after more than 1,500 cases had been recorded, BioNTech said the new EWS detected Omicron on the day its sequence was first uploaded as the highest immune-escaping variant among more than 70,000 others discovered between early October 2021 and late November 2021 and also assigned it a high fitness score.

The data published from the sequencing work has been issued as a pre-print on the BioRxiV server.

Author: Dede Williams, Freelance Journalist