Carmine Therapeutics Inc. said Tuesday that Takeda Pharmaceutical Co. Ltd. has engaged it in a research collaboration aimed at the discovery, development and commercialization of new nonviral gene therapies for two rare disease targets. Terms of the deal included an up-front payment of undisclosed value for Carmine, plus research funding, and more than $900 million in potential milestone payments. Tiered royalties would be paid on potential marketed products.

Takeda will also provide Carmine with a $5 million convertible loan to support development of its red blood cell extracellular vesicles (RBCEV) platform, called Regent.

While the deal's focus is very early stage, it speaks to the heart of what Takeda is trying to achieve with gene therapy, the company's rare diseases drug discovery chief, Madhu Natarajan, told BioWorld. Gene therapies for rare disease can't just seek to provide a missing or deficient protein to patients who need it. Rather, he said, they should "put enough functionality back in such that you can arrest disease progression in as many cells as can be reached."

To make that happen, he said he envisions enlisting the best-performing technologies from across the gene therapy landscape, something a large company like Takeda is well-positioned to do. "To steal a phrase from The Princess Bride, you make 'the good parts version' of everything, and you stick it together. I think that could be magical," he said.

Carmine's part of the puzzle is expertise in using RBCEVs as nucleic acid delivery vehicles, thus providing an avenue that has the potential to overcome the current limitations of adeno-associated virus (AAV) therapies, such as immunogenicity, small transgene capacity and manufacturing challenges.

XQ Lin, CEO, Carmine

The advantage of the approach, Carmine's founding CEO, XQ Lin, told BioWorld, is that "these extracellular vesicles derived from red blood cells are extremely homogenous and quite easily loaded with large DNA plasmids and transgenes." Furthermore, compared to AAV-based gene therapy, he said, RBCEV-based gene therapy has the potential for repeat dosing, a significantly larger transgene payload capacity in excess of 11 KB, and enhanced biodistribution in selected tissues through RBCEV surface modification. "There's a potential here for next-generation curative gene therapies" that can be dosed again and again, he said. "That's the reason why Takeda, despite our early stage, decided to partner with us," he said.

Working with Takeda – one of many big biopharma players to express interest in the company – will provide Carmine's team with significant funding to further develop its platform, and advance the company's wholly owned programs. Evidencing that, in December 2019 the company won Bristol Myers Squibb’s Co.'s 2019 Golden Ticket, winning that company's sponsorship of a year of space at Labcentral's Kendall Square facility.

Carmine Therapeutics was founded in 2019 by Esco Ventures X, a Cambridge, Mass., and Singapore-based biotech incubator, as well as Harvey Lodish (Whitehead, MIT) and Singaporean professors Minh Le and Jiahai Shi. Lin, in addition to being managing partner of the incubator and Esco Ventures, has developed significant experience managing R&D teams and developing products, initially in the medical device space as part of his family's business, Singapore-based Esco Group (Esco Micro Pte. Ltd.).

Lodish has been a founding member of companies, including Genzyme Corp., Arris Pharmaceutical Corp. (now Axys Pharmaceuticals Inc.), Millennium Pharmaceuticals Inc. and Rubius Therapeutics Inc., the latter another company genetically engineering red blood cells to create a new class of cellular medicines. Lodish is also chair of Carmine's scientific advisory board.

In addition to Carmine, Esco Ventures has backed companies including Hummingbird Bioscience Pte. Ltd., a startup led by former Axovant Sciences Inc. executive Shankar Ramaswamy, and Nanoview Biosciences Inc., among others. The company-building aspect of Esco’s operation is still fairly new, but Lin said, “I think we bring a unique flavor” with a trans-Pacific model well positioned to develop science from under-ventured areas of Asia.

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