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12 November, 2019 - 13:06 By Kate Sweeney

PhoreMost – Drugging the Undruggable

The company bringing a systematic pipeline of first-in-class drugs to market – Cambridge-based PhoreMost – is at the forefront of discovering and developing the next generation of therapies. 

The company’s team of expert scientists and biotechnology professionals is putting to work its proprietary phenotypic screening platform, SITESEEKER®, to support first-in-class drug discovery programmes. 

PhoreMost is operating a novel business model, generating an early revenue stream through strategic partnerships with pharmaceutical organisations, and is developing an internal asset pipeline covering the core therapeutic areas of oncology, targeted protein degradation, and diseases of ageing. 

The company collaborates with industry leading pharma and biotechs to develop first-in-class drugs to treat previously untreatable diseases. These programmes serve to bring specialist expertise together, to rationally progress a diverse target portfolio. 

For example, PhoreMost recently expanded its collaboration agreement with Sentinel Oncology to accelerate progression of a novel allosteric PLK1 inhibitor through IND enabling studies, and named the lead development candidate as a potential glioma (brain and spinal cord tumour) therapeutic. 

In 2017 PhoreMost established its first spin-out, NeoPhore, to progress a novel target for cancer immunotherapy to the small-molecule development stage. 

NeoPhore aims to take advantage of novel biological mechanisms to boost cancer immunity in patients with unresponsive tumours, as well as improve responses in patients already eligible for cancer immunotherapy treatments.

SITESEEKER, based on PROTEINi® (protein interference) technology, exploits the inherent shape diversity of proteins in the search for novel drug targets. 

It is a fully validated platform that can systematically scan the entire proteome in a live cell environment to identify the best new targets for drug development and, crucially, how to drug them.

Origins and progress

PhoreMost was founded in 2015 from a Cambridge University spin-out by a core team of leading scientists, including CEO Dr Chris Torrance, with early proof-of-concept data from a drug discovery platform developed by the lab of Ashok Venkitaraman. The company raised initial seed financing from Cambridge-based Angel Investors including Jonathan Milner, Amadeus Capital, Sunil and Prashant Shah of o2h Ventures, and Cambridge Enterprise. 

The company has grown rapidly through its validation phase building a diverse team of passionate scientists and experienced management personnel and announced the completion of an £11 million Series-A funding round in May 2018, with Parkwalk Advisors and Morningside Ventures investing. 

This has enabled PhoreMost to expand its operations at the Babraham Research Campus and progress novel targets through its internal drug discovery programme.


The PhoreMost team

Technology

Although advances in research, and especially in genomics, are opening the door to many potential new and improved targeted therapies, there is often no obvious point of attack when disease targets are viewed in isolation outside of a cell. 

In reality targets are dynamic entities and their interactions with the cell environment open up pockets of druggable space. However, as it is difficult to routinely look inside a cell, many potential drug targets are unattainable with conventional methods. 

PhoreMost is able to remove these barriers with its SITESEEKER live-cell screening platform, offering significant advantages over other drug discovery methods. 

The PROTEINi libraries on which SITESEEKER is based are used alongside pooled phenotypic screening to rapidly identify key peptide-target interactions of therapeutic interest. Critically, using SITESEEKER PhoreMost is also able to use this information as a basis to design small-molecule drugs in a highly time-efficient process.  

Focus areas 

The SITESEEKER platform can be deployed across any therapeutic area and PhoreMost is actively seeking collaborations with both academic and industrial partners. Earlier in the year the company announced a research partnership with Vernalis, a subsidiary of Ligand Pharmaceuticals, to design small molecule inhibitors against a novel oncology target identified and validated by the SITESEEKER platform. PhoreMost has also been working with C4X Discovery since June on a neurodegeneration drug discovery collaboration with the initial focus on Parkinson’s disease. 

This partnership demonstrates the strength of PhoreMost’s collaborative business model as insights from C4X Discovery’s analysis of patient-based genetic data will be incorporated alongside SITESEEKER to reveal novel drug targets.

The recent expansion of PhoreMost’s relationship with Sentinel Oncology also exemplifies the value of PhoreMost’s strategy to use functional protein-protein interactions to drive the development of novel therapies.

Internally, the company has an emerging asset pipeline across key therapeutic areas - oncology (targets against the cell-signalling gene, KRAS), immuno-oncology (neoantigen generation), and ageing (autophagy & senescence modulating targets) – and is extending this portfolio to targeted protein degradation.

Future development

PhoreMost is now set for a transformative expansion phase. The company will continue to develop its internal drug target programmes and additional high-profile collaborations are in the pipeline to expand the applications of SITESEEKER-based drug discovery. 

The progression of any drug discovery assets towards clinical development will be aided by further investment. The company is planning a Series B fundraise and the formation of several more spin-outs to target specific therapeutic areas. 

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