Programming Medicine to Send the Right Information to the Right Cell

In the first of four features on Senda Biosciences, Big4Bio spoke with CEO Guillaume Pfefer and Chief Platform Officer Stuart Milstein about how and why the company was founded, and how molecular connections among different kingdoms of life that have co-evolved over millennia may hold the key to addressing the challenges of delivering nucleic acid therapeutics to patients. The second feature will provide an in-depth focus on its technology and plans moving forward.

Companies to Watch – Senda Biosciences

by Marie Daghlian

What if we could program an information molecule—mRNA, siRNA, gene editors—to go directly into any cell we choose and so multiply the number of approved medicines to treat diseases anywhere in the body?

Stuart Milstein, Chief Platform Officer, Senda

Senda Biosciences says it believes it has found the key to doing that and is buzzing with passion and energy.

“Senda has the opportunity to solve a problem that our industry has been trying to overcome for a long time in this space of nucleic acid therapeutics,” says Chief Platform Officer Stuart Milstein. “And that problem is that we’ve been able to continuously optimize many different types of innovative information molecules such as siRNAs or mRNAs and we’ve been able to really harness our understanding of biology to co-opt endogenous biological processes in ways that have never been done before in drug development. But we’ve been challenged to get these molecules to where they need to be, and that’s what Senda is all about: developing fully programmable medicines.”

The idea originated at Flagship Pioneering to try to overcome the limitations that have prevented the explosion of advancements of nucleic acids programming molecules from rapidly turning into an abundance of medicines to treat patients. They were looking for a way to extend the notion of programmability beyond information molecules, or programming in the cell, to also program to the cell of interest.

“How do we program sending the right molecule to the right cell – and thinking that if we can do that,” says Senda CEO and Flagship Partner Guillaume Pfefer, “our industry could bring more medicines to more patients, faster.”

Pfefer says the original team was studying other mechanisms in nature, specifically in plants, and thought that the natural world might hold the solution to this challenge, too. Soon the team moved from plants to bacteria, then aggregated several Flagship companies to unveil Senda in October 2020.

Senda CEO Guillaume Pfefer

“As our name suggests, Senda is all about sending the right information to the right cell,” says Pfefer. The company decodes the natural chemical routing language of interspecies’ molecular connections for natural nanoparticles that evolved to shuttle information biomolecules into human cells, displaying tropism, potency, and repeatability in their interactions.

The foundation of the platform is the Senda Atlas, which was developed by systematically surveying many species across five kingdoms of life to unpack the molecular composition of natural nanoparticles involved in interspecies communication. It is a library of 75,000 molecular features that Senda is using to program nanoparticles for therapeutic use.

“We’re using various types of machine learning models to integrate that information and drive us toward the programmability,” Milstein says. “The basis is this interspecies communication that we are beginning to understand—that there is communication within species and between species, and it’s harnessing that information to build these nanoparticles.”

Starting with a species, for example, the company uses analytical methods to first characterize the molecular composition of the natural nanoparticles secreted by that species to communicate with other cells in its surrounding. Part of its “secret sauce” is establishing proprietary analytical methods to characterize the molecular components. Then it uses modeling to help understand which molecules from natural nanoparticles can be brought together through a combination of empirical experiments that lead to information that can be used for programming. That programming then can feed algorithms that help improve the platform through iterative cycles.

“One of the main things we’re trying to address here is a bit of a frustration in this field – we’ve done a very good job of making different types of effector molecules, mRNAs, sRNAs,” says Milstein, “but where we’ve done a very poor job, and where we’ve faced a lot of challenges, is getting them where we need then to act within the body. What we’re trying to iterate on is making nanoparticles that do something specific—generate different tropism or targeting to different cells or tissues than have normally been accessible by traditional lipid nanoparticles, which have found most of their success targeting the liver. That’s really where the programming comes into this. We want to drive these programmable medicines to other tissues and cell types, beyond the liver, so we can address unmet needs, in things that haven’t been accessible before.”

Senda has a patient-centric strategy dedicated to finding solutions for the patient, says Pfefer. Before joining Senda as chief executive officer, he was at GSK when the readouts from a phase 3 study of the shingles vaccine that would become known as Shingrix came out and he was excited that within two years it would become available to patients – but he realized that it had taken 20 years to get to that point. His mission is to shorten that time to make more medicines available to patients sooner.

The company raised $123 million in a series C financing in August 2022, during a difficult time for raising capital. Pfefer says the company is in good shape to advance the platform and build a pipeline.

“We’re in a good place. I can tell you the smile of the Senda employees at the office is bright, and there’s a ton of energy and we have confidence that we have enough time to move forward and advance our platform and programs toward making medicine and finding solutions for patients,” he says.

Senda’s business model includes partnering, which will be critical to making this technology available to patients faster, says Pfefer. The company is starting with several programs in the immunotherapy space, mainly because there is tremendous opportunity to make a difference in the life of patients. Senda is also working on programs that it intends to partner relatively rapidly to expand the breadth of impact to the patient. “It doesn’t have to be Senda 100 percent. It has to be the whole industry that moves to the next level of bringing medicines to the patient,” says Pfefer.

“It’s a duality of the company we’re building,” says Pfefer. “It’s a multi-product platform company and we are investing as much to the programs we are on the platform at this stage. The platform is really created in a self-learning and an amplification of learning way to explore the space. It’s like moving into a new planet where nobody has been before and exploring and learning to explore faster and faster. We’re not excluding any tissue or cell, we’re just learning to get there in an efficient way, while starting to move into creating, hopefully, future medicines for patients.”

This is part of the Big4Bio Company to Watch program for April 2023: Senda Biosciences
For more information on the series, click here.