Manifold Bio’s molecular ‘barcode’ could break Pharma’s Vivo bottleneck – TechCrunch

Manifold Bio’s molecular ‘barcode’ could break Pharma’s Vivo bottleneck – TechCrunch

In creating a new drug, there comes a point where you will eventually have to put molecules in a real animal – one at a time – and see if it actually does what you think. Manifold Bio’s molecular machinery can allow one hundred molecules to be tested simultaneously in a single living system, potentially advancing the whole process.

The space for drug discovery has advanced a lot in the last few years, first through fast and inexpensive gene transcription, then through CRISPR, then through AI-powered protomics. However, in order to finally understand that no matter how much they accelerate basic research, you don’t need to know. In vivo The test remains a major obstacle.

In vivo means “in life”, as opposed to in vitro (glass) or silico (simulated), and rats are common critters who receive dubious respect for testing the safety and efficacy of a new drug. And the general equation is: a drug, a mouse. Since this is a logically challenging and time-consuming part of drug testing, it is usually left until the company or lab is confident that it will work fairly well with only a handful of molecules. But it is also the first – and often the last – of any of these drugs to actually work in the body and the result is a lot of wastage.

Enter the manifold bio. The startup, equipped with $ 40 million in Series A funding, aims to make mouse experiments a hundred times more efficient and effective, changing that equation and enabling in vivo testing that verifies the effectiveness of a molecule. Before You throw millions of dollars worth of assets into it.

Gleb Kuznetsov, founder and CEO of Manifold Bio, explained, “The best testing environment is reality.” “But as you go further into the drug development program, you’re investing more, more expensive testing and working. We’ve been optimizing for a long time, so once we get to the final gate to the clinical trial, we’re moving forward with a drug that has already been optimized. If you can be more confident that this is the right investment drug, you can tackle the underlying risk of your investment. ”

Currently, at the mouse testing stage, you usually have a target condition and a few candidate drug molecules. One goes into each mouse and you observe what is happening – and at this critical juncture they all have a real chance of being flanked.

Manifold’s invention is becoming parallel to in vivo testing, with up to a hundred simultaneous tests on a single mouse. To make this happen, it has developed a “protein barcoding” technology that you can think of as a molecular RFID tag.

Images of multiple “barcodes” attached to proteins for testing in vivo.

“The way it works is that we add an extra bit of protein, our protein barcode and it makes the protein trackable and we can track it wherever it goes,” Kuznetsov said. Instead of verifying lab tests, “it’s more to inform design information. Computers have a lot of AI and machine learning driven development, lots of designs. We focus on a specific cancer goal, something on the surface of the cancer cell that really flags it as a cancer cell, and find drug designs that specifically target those cancer cells – and nowhere else. “

The problem here is that at this stage, you may see a thousand different proteins, each of which can be distinguished from the others by just a few amino acids, the building blocks that give proteins their shape and function.

That’s where the manifold barcodes come in Each protein, though similar, receives a tag that is completely unique and identifiable when performed through a proprietary DNA conversion process. An equal amount of 100 molecules goes into the mouse, probably 95 does nothing, 3 connects decently with the cancer and 2 connects at a much higher rate. These are 98 molecules that you don’t have to take through further testing.

This screening process takes a lot of uncertainty out of the equation, since you know for sure that this protein actually does what you designed it to do in a living mammalian system. And it is relatively inexpensive and early part of the process, after design and low volume synthesis.

From left, Manifold co-founders Gleb Kuznetsov, Shane Lofgren and Pierce Ogden.

The hard part was designing the tags themselves. If you think about it, every little protein barcode must meet a really high bar.

“There are elements of a molecular biology here but there are also many computational aspects to making these things identifiable. They don’t have to affect drug behavior either and they must be stable, identifiable, unique and productive,” Kuznetsov said. Designing one will be a challenge – designing 100 can be the foundation of a completely new drug development path. He compared it to the changes that took place in computing when we went from serial processing in the CPU to parallel processing in the GPU.

To be clear, it’s not about supercharging testing at other companies – Manifold’s goal is to create a completely vertical integrated pharmaceutical company based on this biotech-infused method.

A manifold bio employee works in their wet lab.

“We’re going end-to-end internally,” Kuznetsov said. “The drugs that we have in our house, we made those molecules from scratch, we have pooled them in vivo testing and soon they will be at the level of clinical trials.”

Their seed was to create a round foundation and show off the technical work – which it has now. $ The 40MA round is to start the process of more expensive and standardized clinical trials. The company is currently focusing on cancer, as it is not only a huge threat, it is also a good match for the types of drugs used to detect the process.

The company was run by Kuznetsov and his co-founders, but Genetics pioneer George Church helped start and build the company. He is currently an advisor.

The new funding round was led by Triatomic Capital, with new investors participating in Section 32, FPV Ventures, Horizons Ventures and Tencent and existing investors Playground Global, Fifty Years and Fast by GETTYLAB.

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