Congruence Therapeutics — The AI platform targeting protein misfolding

Written Feb 8, 2022. Wrote the blog post describing Amplitude Ventures' investment in Congruence Therapeutics. You can find the original here.

This week, Congruence announced the close of a $50M US Series A financing. This is a great example of Amplitude’s strategy to support early-stage companies from a concept to a well-financed business with a diverse and experienced management team and a great group of investors. Congruence is tackling rare diseases of protein misfolding through leveraging the power of AI and machine learning through their Revenir platform and combining it with experienced drug developers. Congruence perfectly fits our precision medicine strategy with its unique AI platform and experienced management team led by an exceptional entrepreneur, Clarissa Desjardins.

Clarissa is the former CEO of Clementia Pharmaceuticals, which was sold to Ipsen in 2019 for $1.3 billion dollars. Clementia’s lead product, SohonosTM (palovarotene), was recently approved in Canada and is under review at the FDA as the first treatment for Fibrodysplasia Ossificans Progressiva, a debilitating and progressive rare bone disorder.

After the sale of Clementia, Clarissa’s passion for curing rare diseases remained intact and it was a natural decision for Amplitude to work with her to support the creation of Congruence. Our team has worked with Clarissa several times over the last few decades. She brings a renowned blend of team building, scientific knowledge, business acumen, and focus on the patients to her companies. That’s why she’s such a great entrepreneur and is another example of the outstanding women in science that Amplitude is supporting. It is an honour to have the opportunity to celebrate the upcoming International Day of Women and Girls in Science by announcing the launch of Congruence Therapeutics.

What is protein misfolding?

Proteins are the workhorse of the cell and each expertly performs a specific task. Some are structural like those found in membranes while others bind to specific molecules and shuttle them to different locations. The wealth and specificity in function are made possible by how proteins fold.

Proteins start off as amino acids and as they’re created in our cells, the order of amino acids determines how the protein chain will fold upon itself. By folding into distinct shapes, proteins can perform different roles despite being composed of the same building blocks. To think about it a different way, all vehicles are made from steel but a race car’s sleek shape allows it to go fast, while a bus or Zamboni are shaped to perform their own unique tasks.

Folding allows a protein to adopt a specific shape but the complex process sometimes fails for several reasons such as a mutation in the amino acid chain, incorrect sequence order or simply not folding properly due to external factors. Misfolded proteins thus can impact the health of the cell as they can contort into shapes that are unfavourable to the cellular environment, such as those aggregates found in neurological diseases like Alzheimer’s, Parkinson’s and ALS.

How is Congruence solving the problem?

Solving the protein misfolding problem has long been considered one of the great biological mysteries that scientists have been trying to solve for generations. Now with the acceleration of AI, machine learning and big data, multiple groups are working on this problem, including AlphaFold, Google’s AI engine, which recently had exceptional results that excited scientists around the world.

Congruence is building their own proprietary AI engine, Revenir, using publicly available and unique datasets by incorporating computational biophysics to tackle the protein misfolding problem in rare diseases. This purpose-built technology uses mathematical modeling, physics, and machine learning to characterize the biophysical defects of misfolded proteins that cause disease, then designs compounds to rescue the mutated proteins by correcting these defects in silico.

Clarissa recently hired Ken Valenzano, an experienced drug hunter and 17-year veteran of Amicus who was involved in the discovery and development of Galafold (migalastat), the only FDA-approved small molecule therapy for Fabry’s. Ken has spent his entire career studying diseases of protein misfolding and did his PhD studying lysosomal storage disorders. Ken joins the initial team at Congruence which has expertise and experience in these areas and we’re confident in the team’s ability to execute on their plan.

Why we’re excited:

Clarissa is an amazing entrepreneur and leader and we are extremely excited to back her again in her new venture. When you combine that with a clearly defined business scope and a great tech platform, it was a quick decision for Amplitude to support Congruence. Congruence is focused on two very interesting and “hot” areas: the use of machine learning for structural biology and the development of therapies for rare diseases. We are excited to back Clarissa and the team at Congruence in their mission. In many ways we’re excited to get to work with the team again.

Congruence is a great fit with Amplitude’s vision of creating, building, and growing world-class companies that meaningfully impact patients’ lives. With a diverse and stellar management team led by an exceptional entrepreneur, a unique AI platform and a stellar group of investors, we’re excited to see Congruence tackle the protein misfolding problem in rare diseases and bring new medicines to patients.

-Amplitude team

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