A Novel Approach to Drug Discovery: Tapping Into the Unexplored 98% of Genomic Space

2 Jun 2017

Proteorex Therapeutics Inc. is a startup biotechnology company, headquartered at JLABS @ Toronto (Canada) with an office in San Francisco, (USA). This blog post is written by Dr. Aman Iqbal, CEO and Co-Founder of Proteorex Therapeutics.

Our mission is to attack the toughest diseases in a powerful way previously thought to be impossible.

Proteorex Therapeutics is discovering small-molecule drugs to treat diseases with the greatest unmet medical need. Our award-winning drug discovery platform uniquely integrates a novel synthesis design strategy, neural network computational technology, and patient-derived cell-based screening to rapidly and cost-effectively unlock targets considered undruggable using existing approaches.

THE BACK STORY

The beginnings

Back in 2012, I was at a leading biotechnology company in the UK that was developing drugs for solid tumors and other hematological malignancies using an industry leading drug design and discovery platform technology. There I discovered that the success rate against some of the tougher drug targets like the intracellular protein-protein interactions (PPIs) was very low. PPIs are extremely tough targets to develop small molecule drugs against and unfortunately, there is not a single technology or a combination of different approaches that can tackle the entire PPome (Protein-Protein interaction proteome). After declining a job offer from a Fortune 500 Biotech, I decided to pursue solving this super challenging problem and building my concept into a reality.

The move

The trans-Atlantic move to Toronto, Canada, was strategic. Toronto is currently building a thriving healthcare ecosystem, with a growing number of startups from digital health to therapeutics. This is happening when some of the world’s leading biotech sectors are saturated in terms of ideas as well as talent pool.

The start

I approached Dr. Michael Anstey (now co-founder and COO) through my Oxford Alumni network, while Michael was a Principal at Boston Consulting Group (BCG). Mike was blown away by the idea and the impact the technology can have not just on the industry but the patients most importantly. Michael came on board as a partner and we went on a hunt to find a technical co-founder who can start plugging away on the concept.

The setbacks

Proteorex started with three co-founders on their own; not being a spin out, we had no support from a parent organization and no technology transfer support. After multiple setbacks of not being able to raise non-dilutive capital through grants, the co-founders decided to pivot to a different business model that would generate revenues to support the core technology development. However, the idea did not work due to high competition and we pivoted back to our original plan of technology development. This series of events exposed divergent visions of the company and created internal conflict, leading to one of the co-founders leaving the company.

The revival

With dwindling capital, I was very strategic in designing some key experiments against a challenging drug target complex implicated in a rare form of leukemia. The resulting data provided the first glimmer of hope of great things to come.

In the late summer of 2015, Proteorex brought on board an outstanding academic, Prof. Robert Batey, currently Chair of the Department of Chemistry at the University of Toronto and a leading and well-respected figure in peptide-based medicinal chemistry. Prof. Batey and his lab have been instrumental in driving all of the chemistry for Proteorex and generating some really exciting data.

Around this time, Dr. Marc Adler also joined the team. An Oxford-Yale organic chemist who previously worked with leading PPI expert Prof. Andrew Hamilton, Marc had just moved to Toronto and was looking for opportunities to get involved in the medicinal chemistry space.

With two chemistry stalwarts on the team, we pulled off two major successes in less than 6 months:

  • Proteorex won a game-changing award for the best technology and pitch at BioPharm America in Boston; this competition was judged by some of the leading corporate venture groups of the world. We were suddenly in the limelight.
  • Proteorex, along with Prof. Robert Batey/UofT, were successful in securing one of the most prestigious drug discovery grants in Canada: the CQDM-OCE Explore grant. The grant is co-funded by 8 pharmaceutical companies, CQDM, and OCE.
  • Although still very early stage, with this new-found stardom we were soon chased by some investors locally in Toronto.

First experience of saying NO

As much as money is important for any startup to grow, iterate on technology, and deliver results rapidly, it is also equally important to choose the right investor who is aligned with your vision. Unfortunately, after 3 months of ‘dating’ a high net worth private investor, the Proteorex founding team decided not to accept their lucrative offer. The decision was taken due to an improper fit between the two entitles. It was hard, but all major decisions in life are hard!

ONWARDS & UPWARDS

The problem

In spite of billions of dollars invested in cancer research, the current survival rate is still below 5 years for 65% of global cancer patients. For 1.5 million cancer patients, there are no treatment options at all. (Source: NCI)

For other rare and orphan diseases the situation is even worse: more than 500,000 patients with 145 orphan diseases (annual patient population <100,000/year) have no treatment options; for 1.5 million patients with CNS disorders like neuroinflammation and glioblastoma, there are no treatment options; and so on.

We are facing a crisis point: the number of ‘low-hanging fruit’ (easy-to-drug targets) will be exhausted by 2025.

The current opportunistic mentality within the Pharma industry has led to billions of early stage R&D discovery dollars being invested in only a handful of easy-to-drug targets — resulting in fewer new treatment options for patients.

This leaves the biomedical industry with only the more challenging targets — the ‘high-hanging fruit’ — to have any chance of keeping the healthcare system going with new medicines and better patient survival outcomes.

The Proteorex solution — and the potential impact

The most challenging drug targets are intracellular protein complexes. However, they are also likely to have the greatest impact because:

PPIs are a part of the 98% of the genome that has not been tapped for developing new drugs.
33% of all diseases (with more than 650,000 associated protein complexes) could be treated using drugs against PPI targets.
There is only one FDA approved PPI-targeting drug, and it offers only 25% efficacy.
There are zero technologies that can target all intracellular protein complexes.
Proteorex has developed and commercialized an award winning proprietary chemistry platform to discover non-peptidic small molecule inhibitors of PPIs. These can then be optimized further to become potent drugs in the form of oral pills, which will eliminate the need for taking drugs through IV, thereby benefiting patients in both treatment and care. We employ neural network computational tools to better optimize our lead candidates.

Proof of concept

Advantages

  • Medium throughput BUT targeted and intelligent design approach vs. brute force
  • Fewer shots on more targets, i.e. accuracy
  • Time- and cost-efficient
  • Conjugates can be used as probes to study disease biology as a small molecule drug is being developed in parallel
  • Commercial validation achieved through a revenue generating business deal

Validation

We achieved commercial validation of our innovative chemistry platform through the following awards and partnerships:

  • Revenue-generating R&D partnership with Corbin Therapeutics in Montreal, Canada
  • R&D partnership and co-development opportunity with multiple pharmaceutical companies through a public-private grant investment
  • Lab space, mentorship, and R&D (Target ID) collaboration with Johnson & Johnson
  • Funding and incubation by the world’s largest biotechnology accelerator, Indiebio in San Francisco, USA

The plan ahead

After having proven our award winning synthetic chemistry platform in real patient-derived samples, Proteorex is on an ambitious mission to combine our proprietary targeted drug design chemistry platform, deep neural network computational technology, and cutting edge patient-derived cell-based screening to design and develop new and effective treatment options that will improve patient survivability and drug efficacy.

Proteorex is evaluating a partnership with a world leading informatics company, Oxford Drug Discovery in the UK. In addition, Proteorex is looking for partners with automated or semi-automated patient-derived diseased cell-based screening platforms. Together, the three units will collaborate to develop and bring new treatment options for patients.

The Proteorex team is excited to bring new, powerful drugs to the world to treat diseases. Each day we are motivated by the thought that every idea, every breakthrough we have can make a tangible and unsurpassed positive impact on a person’s life. We will continue to pursue new targets, innovate our technology, and pursue partnerships to carry out our mission to attack the toughest diseases in a powerful way previously thought to be impossible, and in this manner help to prolong and improve the quality of human life.

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