Fairytale ending? Mythic flags new approach to improving ADC performance

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December 2021 saw the launch of a new US based biotech, Mythic Therapeutics, with an oversubscribed Series B financing round of US$103m.

The company says it is pioneering a protein engineering-focused approach to improving the effectiveness of antibody-drug conjugates (ADCs) and other antibody-based therapeutics.

The Series B proceeds will finance the biotech’s lead program through first-in-human clinical studies in lung cancer and will also go towards development of its pipeline. 

Viking Global Investors led the round, with Venrock Healthcare Capital Partners, Foresite Capital, Perceptive Advisors, and Highside Capital, among others, also participating in the fundraising exercise.

Unlocking the potential of targeted therapies

Although the development history of ADCs spans more than four decades, the clinical benefit of the technology has so far remained limited to a subset of diseases and targets with optimal biological characteristics, such as high levels of target expression, said Mythic. 

The biotech claims to have developed a breakthrough approach to expand the role of ADCs in precision medicine.

It outlined how its technology “dramatically increases therapeutic potency without compromising safety”, thereby unlocking the full potential of targeted therapies against a broad array of tumor targets.

ADCs are designed to specifically deliver a therapeutic payload to a target tissue or disease site. However, studies have demonstrated that the vast majority of payload is ultimately released non-specifically throughout the body, causing systemic toxicity and reducing efficacy, said Mythic. 

Its FateControl technology is designed to increase the amount of ADC that is internalized by the target tissue while reducing payload release in non-targeted tissues, thereby improving therapeutic index independent of the linker and payload.

To date, approaches to improve the performance of ADCs have focused primarily on innovation in one of three dimensions: linker and payload chemistries, conjugation technology, and new target biology,” said Brian Fiske, co-founder and chief scientific officer (CSO) at the newly launched biotech. “Mythic seeks to improve the clinical performance of ADCs by introducing a new dimension of ADC technology focused on manipulating the fate of ADCs within the cell.”

The company added that its lead program in lung cancer has the potential to drive a multi-fold expansion of the number of lung cancer patients eligible for treatment using ADCs.

Adagene hits key milestone in ADC alliance  

Meanwhile, late last month saw Chinese headquartered company, Adagene, announce the achievement of a key milestone in its ongoing collaboration with US developer, Exelixis, for the development of novel masked ADC candidates leveraging its proprietary SAFEbody precision masking technology.

Exelixis selected lead SAFEbody candidates, and, in doing so, triggered a US$3m milestone payment for Adagene.

Under the terms of the agreement between those companies, Adagene received an upfront payment of US$11m, with Exelixis permitted to nominate two targets for development of SAFEbody candidates during the collaboration. Adagene is eligible for development and commercialization milestones, as well as royalties on net sales of products developed around each of these targets.

Adagene said its SAFEbody technology is designed to overcome safety and tolerability challenges associated with many antibody therapeutics by using precision masking technology to shield the binding domain of the biologic therapy. “This allows for improved tumor-specific targeting of antibodies, while minimizing on-target off-tumor toxicity in healthy tissues, a longstanding challenge with many antibody therapeutics.”