LONDON – Amphista Ltd. becomes the latest to join the growing band of proteolysis targeting chimera (Protac) specialists, arriving on the scene with a $7.5 million series A and what it says is a new approach to targeted protein degradation (TPD).
Its technology will expand the range of TPD targets and should overcome recently identified Protac resistance mechanisms, according to Nicola Thompson, CEO. “We have gained novel insights and can access untapped areas of TPD,” she said.
Early leaders in this field of chemistry are developing double-headed molecules composed of a ligand for a target protein and a ligand for an E3 ubiquitin ligase, chemically joined by a flexible linker. As the two are brought together, the E3 ligase tags the target protein for programmed degradation within the cell, through the ubiquitin-proteosome pathway.
Thompson did not want to go into detail at this stage of the company’s development, but said, “We have identified novel warheads to target protein degradation machines. We don’t target traditional E3 ligases, and that has a number of advantages. We are coming in via a different mechanism,” she told BioWorld.
As a technology, Thompson said TPD is a “therapeutically agnostic modality,” harnessing the body’s natural processes to selectively and efficiently degrade and remove disease-causing proteins. Glasgow, U.K.-based Amphista initially will focus on oncology, though Thompson said it is too early to say what cancer indications the company will pursue.
Amphista’s technology comes from the lab of the company’s co-founder and chief scientific officer (CSO), Alessio Ciulli, professor of chemical and structural biology at Dundee University, acknowledged as one of the leading academics in the field.
In a previous posting, Ciulli worked with Craig Crews, CSO and founder of the most advanced Protac company, Arvinas Inc., of New Haven, Conn. While at Crews’ lab at Yale University, Ciulli is credited with solving the first crystal structure of a Protec ternary complex.
As yet, Amphista’s programs are in early preclinical development, but following the spin-out of the company from Dundee University, Thompson is hopeful this first round of funding will advance things to the point where investors will back a series B round before the end of the year.
The field is attracting significant private capital, and there are precedents for Amphista’s early stage counterparts raising large private rounds. Most recently, last month Kymera Inc., of Cambridge, Mass, which has five preclinical TPD programs, raised $102 million in a series C.
There also have been big money pharma partnerships struck around preclinical research. Kymera, for example, received $70 million up front in a four-year research and development agreement with Vertex Pharmaceuticals Inc. in May 2019.
Arvinas has completed a string of high-value deals. In July 2019, it received $100 million in cash, committed funding and an equity investment, when it signed an agreement to apply its Protac platform to cardiovascular, oncology and gynecological targets nominated by Bayer AG.
Dundee University was a pioneer in forming collaborations with multiple pharma partners in early stage research, and Ciulli’s lab has funding from Ono Pharmaceutical Co. Ltd., Boehringer Ingelheim GmbH, Nurix Inc. and Eisai Co. Ltd.
In the collaboration with Boehringer, which started in 2016 and was extended in 2018, the partners have developed a structure-based design approach to designing Protac molecules. The new approach yielded the first Protac that can shred the protein SMARC2, expression of which is associated with poor prognosis in many types of tumors, including liver hepatocellular carcinoma and kidney renal clear cell carcinoma.
In the deal with Eisai, signed in July 2019, the Japanese pharma has options to develop and commercialize Protac molecules directed at oncology targets, discovered by Ciulli. There will be up-front and milestone payments and royalties on sales of any programs Eisai takes in-house.
Thompson said Amphista has exclusive rights to the TPD small molecules it has spun out of Ciulli’s lab.
The series A round was led by Advent Life Sciences, with new investor Biomotiv. The seed round backers Scottish Investment Bank and the European Investment Bank followed on.
Raj Parekh, general partner of Advent, said Amphista’s differentiated and proprietary technology has the scope to address previously undruggable targets. “The company has a potentially unique approach to targeted protein degradation when compared to traditional Protac platforms,” he said.