When asked why he founded Unnatural Products (UNP), a developer of oral macrocyclic peptide therapeutics, Cameron Pye, PhD, attributes the decision at least in part to “being in the right place at the right time.” Pye and his co-founder Joshua Schwochert, PhD, met as doctoral students in the laboratory of Scott Lokey, PhD, at the University of California, Santa Cruz. Their research there exposed them to pre-competitive collaborations with pharmaceutical companies interested in macroyclic peptides.
Research in the Lokey lab has led to the launch of Circle Pharma, a company developing macrocycle therapies for cancer and other illnesses using a rational design approach. In founding UNP, Pye and Schwochert opted for a more data-driven approach to making synthetic molecules from non-canonical amino acids using nature as inspiration, Pye told GEN in an interview. From the beginning, “the goal was to build a platform technology” that was “target agnostic and therapeutic area agnostic” and to use it for internal projects as well as in collaborative partnerships.
The company’s most recent partnership is with immunology company argenx. UNP announced the multi-target deal earlier this week, noting that it will focus on discovering and developing synthetic oral macrocyclic peptide drugs that target “undruggable” disease targets. Under the terms of the agreement, the partners will utilize UNP’s platform for drug discovery, which combines AI-guided compound design, massively parallel synthesis, and direct-to-biology screening capabilities. UNP will conduct research and development until IND-enabling studies, and argenx will have the exclusive option to develop and commercialize products against these targets across multiple indications.
Pye declined to disclose specifics about the targets that UNP and argenx will be pursuing, except to say that it will be in the immunology field. Commenting on the partnership with argenx, Pye noted that the company was “interested in other modalities” beyond antibodies. The partnership is really an “opportunity to put our heads together” and combine both companies’ expertise in biology and chemistry.
UNP’s process starts by screening candidate molecules against a protein target using technologies and established approaches for testing macrocyclics like phage display or mRNA display. The hits are then fed into the company’s computational drug platform, where they are modified and optimized. There is no black box algorithm in the process, Pye told GEN. “What the platform’s about is being able to take smart shots on goal” in order to “find a successful hypothesis to weave your way through that chemical landscape to a development candidate.”
Internally, UNP is focused on drugs for chronic conditions like obesity, where an oral therapy could be a desirable option for patients. Its efforts are focused mostly on the activin type 2 receptor, which is implicated in muscle preservation and cardiac-related conditions. The goal for these drugs would be “higher quality weight loss” and “not just chasing the magnitude and the speed of that weight loss, but preserving functional muscle and really improving downstream outcomes for patients,” Pye said.
Besides its molecule discovery and optimization capabilities, UNP also has some in-house manufacturing capabilities. “Once you’ve identified the molecule of interest, the beauty is that this is predominantly solid phase peptide chemistry at its core, though with a lot of bells and whistles that we’ve added to it,” Pye said. Internally, “we’ll scale up to the gram scale” and beyond that, they work with third parties to help with synthesis at higher scales.
As part of the deal with argenx, UNP will receive upfront, near-term payments and R&D funding. They are also eligible to receive up to approximately $1.5 billion in potential research, development, regulatory, and commercial milestones and option payments as well as tiered royalties on net sales. Additionally, argenx will make an equity investment in UNP.
In 2023, UNP raised $32 million in a Series A funding round led by Merck Global Health Innovation Fund and TechBio-focused ARTIS Ventures. New investors in the round included First Spark Ventures, The Venture Collective, Humain Ventures, LongeVC, and Not Boring Capital. Previously, UNP inked a deal with BridgeBio Pharma to generate drug-like macrocycles for intracellular targets associated with rare fibrotic diseases and potential oncology applications. It signed another deal last year with Merck & Co. to use the UNP platform to develop macrocyclic peptides for an undisclosed oncology target.
The post Unnatural Products, Argenx Partner on Macrocyclic Peptides for Immune Disease appeared first on GEN - Genetic Engineering and Biotechnology News.
Research in the Lokey lab has led to the launch of Circle Pharma, a company developing macrocycle therapies for cancer and other illnesses using a rational design approach. In founding UNP, Pye and Schwochert opted for a more data-driven approach to making synthetic molecules from non-canonical amino acids using nature as inspiration, Pye told GEN in an interview. From the beginning, “the goal was to build a platform technology” that was “target agnostic and therapeutic area agnostic” and to use it for internal projects as well as in collaborative partnerships.
The company’s most recent partnership is with immunology company argenx. UNP announced the multi-target deal earlier this week, noting that it will focus on discovering and developing synthetic oral macrocyclic peptide drugs that target “undruggable” disease targets. Under the terms of the agreement, the partners will utilize UNP’s platform for drug discovery, which combines AI-guided compound design, massively parallel synthesis, and direct-to-biology screening capabilities. UNP will conduct research and development until IND-enabling studies, and argenx will have the exclusive option to develop and commercialize products against these targets across multiple indications.
Pye declined to disclose specifics about the targets that UNP and argenx will be pursuing, except to say that it will be in the immunology field. Commenting on the partnership with argenx, Pye noted that the company was “interested in other modalities” beyond antibodies. The partnership is really an “opportunity to put our heads together” and combine both companies’ expertise in biology and chemistry.
UNP’s process starts by screening candidate molecules against a protein target using technologies and established approaches for testing macrocyclics like phage display or mRNA display. The hits are then fed into the company’s computational drug platform, where they are modified and optimized. There is no black box algorithm in the process, Pye told GEN. “What the platform’s about is being able to take smart shots on goal” in order to “find a successful hypothesis to weave your way through that chemical landscape to a development candidate.”
Internally, UNP is focused on drugs for chronic conditions like obesity, where an oral therapy could be a desirable option for patients. Its efforts are focused mostly on the activin type 2 receptor, which is implicated in muscle preservation and cardiac-related conditions. The goal for these drugs would be “higher quality weight loss” and “not just chasing the magnitude and the speed of that weight loss, but preserving functional muscle and really improving downstream outcomes for patients,” Pye said.
Besides its molecule discovery and optimization capabilities, UNP also has some in-house manufacturing capabilities. “Once you’ve identified the molecule of interest, the beauty is that this is predominantly solid phase peptide chemistry at its core, though with a lot of bells and whistles that we’ve added to it,” Pye said. Internally, “we’ll scale up to the gram scale” and beyond that, they work with third parties to help with synthesis at higher scales.
As part of the deal with argenx, UNP will receive upfront, near-term payments and R&D funding. They are also eligible to receive up to approximately $1.5 billion in potential research, development, regulatory, and commercial milestones and option payments as well as tiered royalties on net sales. Additionally, argenx will make an equity investment in UNP.
In 2023, UNP raised $32 million in a Series A funding round led by Merck Global Health Innovation Fund and TechBio-focused ARTIS Ventures. New investors in the round included First Spark Ventures, The Venture Collective, Humain Ventures, LongeVC, and Not Boring Capital. Previously, UNP inked a deal with BridgeBio Pharma to generate drug-like macrocycles for intracellular targets associated with rare fibrotic diseases and potential oncology applications. It signed another deal last year with Merck & Co. to use the UNP platform to develop macrocyclic peptides for an undisclosed oncology target.
The post Unnatural Products, Argenx Partner on Macrocyclic Peptides for Immune Disease appeared first on GEN - Genetic Engineering and Biotechnology News.