Gandeeva Therapeutics — unlocking the power of cryo-EM

Written Jan 31, 2022. Wrote blog post describing Amplitude Ventures' investment in Gandeeva Therapeutics. You can find the original here.

Gandeeva recently announced a $40M US round of financing. We are extremely excited to join the other syndicate members in building another world-leading company in Canada. By continuing to invest in the great scientific innovation coming out of Canadian universities, we are excited about Gandeeva’s capability of revolutionizing the drug discovery paradigm through cryo-EM.

Led by Sriram Subramaniam, a world-leading researcher in the cryo-EM space, Gandeeva is poised to industrialize the cryo-EM process for efficient use in drug discovery and drug development. We first met Sriram when he was recruited by the University of British Columbia to build a world-class cryo-EM facility in Vancouver. We’ve closely followed and worked with Sriram over the last several years to refine the story and help him in building Gandeeva to what it is today.

What is cryo-EM?

Cryo-EM, or cryogenic electron microscopy, is an electron microscopy technique involving flash-freezing solutions of proteins or other biomolecules and shooting them with electrons to produce microscopic images of individual molecules. These are used to reconstruct the 3D shape, or structure, of the molecule, as well as different conformations. These structures are extremely useful for uncovering how proteins work, how they malfunction in disease, and how to target them with drugs.

For decades, scientists preferred to use other imaging techniques, including X-ray crystallography, a process that involves crystallizing proteins, blasting them with X-rays and reconstructing their shape from the resulting patterns of diffracted light. X-ray crystallography produces high-quality structures, but it’s not easy to use with all proteins — some can take months or years to crystallize, and others never crystallize at all.

Cryo-EM doesn’t require protein crystals, but the technique stalled for a long time because it was arduous, expensive and tended to produce low-resolution structures. However, due to breakthroughs in software and hardware in the last decade, electron microscopes and sophisticated software have allowed scientists to transform the images they captured into sharper molecular structures, gaining unique insights into the structure and behaviour of many molecules. This innovation led Richard Henderson, a structural biologist based out of Cambridge university, to share the Nobel Prize in Chemistry in 2017 for his work on developing the technique. Since that time, cryo-EM structures are being used more often by scientists while X-ray crystallography techniques have slowed, as presented in the image below

How is Gandeeva solving this problem?

Sriram Subramaniam, the CEO of Gandeeva, is one of the world leaders in the cryo-EM space. He was the first to demonstrate atomic resolution cryo-EM of proteins, first to demonstrate atomic resolution small molecule drug mapping and first to demonstrate the use of cryo-EM in precision medicine with a structure of a drug bound to a patient mutant in cancer.

His work demonstrated the structures of a variety of protein targets in numerous diseases could be determined at high resolution using cryo-EM. One example occurred recently as his lab demonstrated the atomic structure of the Omicron variant weeks after it was announced by the WHO.

As a world-leader in the cryo-EM space, Sriram and his team have significantly advanced Gandeeva’s AI-driven cryo-EM imaging platform that combines breakthrough technologies across chemistry, biology, imaging, and machine learning to visualize, measure and capture protein-drug interactions at atomic resolution, providing new insights into how proteins function and how they can be targeted.

Currently, the cryo-EM process is limited by several different factors including sample preparation, data processing, atomic building, and collection of high-quality cryo-EM data. Gandeeva is industrializing this process to make it more efficient for use in drug discovery and drug development.

When developing a new drug, there are several issues that kill a lot of drugs in development such as toxicity, low effectiveness and binding to unwanted tissues. Through Gandeeva’s cryo-EM platform, they’re able to combine prediction and experimentation to visualize and optimize drug design at an atomic scale with unprecedented speed and more intentionality. This allows them to design ‘better’ drugs and test these problems earlier on in the process, thereby leading to a higher chance of success for the drug in clinical trials.

Another win for Canadian life sciences

As we’ve demonstrated several times in the past with our investments in Repare Therapeutics, Notch Therapeutics, and Deep Genomics, Amplitude is incredibly bullish on the potential and performance of life sciences companies in Canada.

Gandeeva is another fantastic example of a company at the bleeding edge of its field with global ambitions and access to local resources such as the world-class cryo-EM facility built at UBC. We know that with a great team, a world leader in the field, a shift in the drug discovery industry towards cryo-EM, and a solid group of investors, Gandeeva is poised to become a leader in the years to come.

Canadian biotech is showcasing itself on the world stage and now we’re excited to watch it grow.

-Amplitude team

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