Cyrus Biotechnology to Present its Protein Engineering Capability, Immunogenicity Risk Mitigation, and Best-in-Class IgG Protease Candidate at Hit ID Summit

SEATTLE--(BUSINESS WIRE)--Nov 11, 2024--

Cyrus Biotechnology, Inc., a Seattle-based biotechnology company with a novel hybrid AI/screening platform for biologics discovery, will present the company’s capabilities in protein engineering and therapeutics risk mitigation at the inaugural Hit ID Summit in Boston, Tuesday November 12 at 1pm at the Boston Back Bay Hilton. The presentation by Dr. Yifan Song, Chief Science Officer (CSO) and Cyrus Co-founder will also include preclinical work validating a next generation IgG-degrader (Immunoglobulin degrading enzyme from S. pyogenes, IdeS) for autoimmune disease and gene therapy pre-treatment. The IdeS program demonstrates the utility of Cyrus’s protein engineering platform for optimizing biologics to build validated, derisked, and readily manufacturable development candidates.

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In the presentation, Dr. Song will demonstrate Cyrus’s capabilities in developing a best-in-class IdeS using in silico AI, protein design algorithms from the 2024 Nobel Prize winning Baker Lab, and high-throughput laboratory screening. These have been used by Cyrus for dozens of collaborations including with Genentech, Janssen, and Selecta Bio. Cyrus’s IdeS candidate has been optimized for all the key therapeutic features, including serum half-life, enzymatic activity, stability, and B cell and T cell immunogenicity.

The presentation will show Cyrus’s IdeS candidate has substantially extended half-life and pharmacodynamics compared to the wild type IdeS, rapidly reducing serum IgG level and maintaining low IgG titers for at least 14 days in rabbits, compared to a duration of less than 7 days for the wild type.

Cyrus’s candidate which demonstrates near-wild-type IgG degrading activity in vitro and in vivo, can be titrated to achieve different degrees of IgG reduction, and is effective at very low doses.

Cyrus employs a proprietary platform for reducing the immunogenicity of protein therapeutics. The approved WT IdeS enzyme therapeutic elicits a very strong anti-IdeS antibody response upon first dose and is not redosable in the clinic. Cyrus has substantially reduced the binding of pre-existing anti-IdeS antibodies - by orders of magnitude in one assay format - and even in human sera with high anti-IdeS antibody titers.

Novel data generated in rabbits exhibits that Cyrus's reduced immunogenicity IdeS does not elicit anti-IdeS antibodies for a minimum of two weeks after administration, while wild type IdeS induces strong anti-IdeS antibodies under the same conditions (see figure below). In a multi-dose study, low doses of Cyrus’s IdeS retain strong activity upon repeat dosing while the WT IdeS loses efficacy after a first dose.

“These newly generated data, combined with titratable potency at very low doses, will permit Cyrus's IdeS to be administered via convenient subcutaneous injection at a frequency suitable for chronic indications such as autoimmune Immune Thrombocytopenia (ITP) and generalized Myasthenia Gravis (gMG),” said Lucas Nivon, Cyrus Biotechnology CEO and Co-founder. “The efficacy of IgG reduction has been shown by the FcRn inhibitor class in the clinic for gMG. Cyrus’s IdeS has more rapid IgG reduction, better IgG-lowering potency, and likely more convenient administration than the anti-FcRn class, with the potential for best-in-disease performance.”

Hit ID Summit

The Hit ID Summit provides the ideal environment for medicinal chemistry, computational chemists & drug discovery experts from both large pharma and biotechs to unite, share experiences & reach conclusions to be applied in hit screening strategies.

About Cyrus Biotechnology

Cyrus Biotechnology is a pre-clinical-stage AI-driven therapeutics company with an internal pipeline of novel biologics primarily in autoimmune indications. Cyrus is advancing a next generation IdeS IgG protease with half-life extension and immunogenicity optimization, for treatment of IgG-mediated autoimmune indications, into IND-enabling studies, as well as advancing multiple discovery stage cytokine programs. Cyrus was co-founded with Prof. David Baker, 2024 Nobel Laureate in Chemistry, inventor of Rosetta and numerous protein design AI tools, and has worked with dozens of Pharma firms on protein redesign for novel therapeutics, including Genentech and Janssen, and has contributed to cytokine optimization with half a dozen partners. In 2021 Cyrus started to develop its own therapeutics.

For more information about Cyrus please visit https://cyrusbio.com/

NOTICE: The information contained in this document is dated as of November 11, 2024. Cyrus Biotechnology, Inc. (the Company) disclaims any obligation to update such information after such date. This document contains forward–looking statements reflecting the Company’s current expectations that necessarily involve risks and uncertainties. Actual results and the timing of events may differ materially from those contained in such forward-looking statements due to a number of factors and the Company undertakes no obligation to revise or update any forward-looking statement to reflect events or circumstances after the issuance of this press release.

Figure shows anti-IdeS antibody formation in rabbits after dosing with 1 mg/kg of WT IdeS (left) compared to 1 mg/kg of Cyrus reduced immunogenicity IdeS (right). (Graphic: Business Wire)

The Native American Church is considered the most widespread religious movement among the Indigenous people of North America. It holds sacred the peyote cactus, which grows naturally only in some parts of southern Texas and northern Mexico. Peyote has been used spiritually in ceremonies, and as a medicine by Native American people for millennia.

It contains several psychoactive compounds, primarily mescaline, which is a hallucinogen. Different tribes of peyote people have their own name for the cactus. While it is still a controlled substance, U.S. laws passed in 1978 and 1994 allow Native Americans to use, harvest and transport peyote. However, these laws only allow federally recognized Native American tribes to use the substance and don't apply to the broader group of Indigenous people in the US.

The Native American Church developed into a distinct way of life around 1885 among the Kiowa and Comanche of Oklahoma. After 1891, it began to spread as far north as Canada. Now, more than 50 tribes and 400,000 people practice it. In general, the peyotist doctrine espouses belief in one supreme God who deals with humans through various spirits that then carry prayers to God. In many tribes, the peyote plant itself is a deity, personified as Peyote Spirit.

The Native American Church is not one unified entity like, say, the Catholic Church. It contains a diversity of tribes, beliefs and practices. Peyote is what unifies them. After peyote was banned by U.S. government agents in 1888 and later by 15 states, Native American tribes began incorporating as individual Native American Churches in 1918. In order to preserve the peyote ceremony, the federal and state governments encouraged Native American people to organize as a church, said Darrell Red Cloud, the great-great grandson of Chief Red Cloud of the Lakota Nation and vice president of the Native American Church of North America.

In the following decades, the religion grew significantly, with several churches bringing Jesus Christ’s name and image into the church so their congregations and worship would be accepted, said Steve Moore, who is non-Native and was formerly a staff attorney at the Native American Rights Fund.

“Local religious leaders in communities would see the image of Jesus, a Bible or cross on the wall of the meeting house or tipi and they would hear references to Jesus in the prayers or songs,” he said. “That probably helped persuade the authorities that the Native people were in the process of transformation to Christianity.”

This persecution of peyote people continued even after the formation of the Native American Church, said Frank Dayish Jr. a former Navajo Nation vice president and chairperson for the Council of the Peyote Way of Life Coalition.

In the 1960s, there were laws prohibiting peyote in the Navajo Nation, he said. Dayish remembers a time during that period when police confiscated peyote from his church, poured gasoline on the plants and set them on fire.

“I remember my dad and other relatives went over and saved the green peyote that didn’t burn,” he said, adding that it took decades of lobbying until an amendment to the American Indian Religious Freedom Act in 1994 permitted members of federally recognized Native American tribes to use peyote for religious purposes.

Peyote is the central part of a ceremony that takes place in a tipi around a crescent-shaped earthen altar mound and a sacred fire. The ceremony typically lasts all night and includes prayer, singing, the sacramental eating of peyote, water rites and spiritual contemplation.

Morgan Tosee, a member of the Comanche Nation who leads ceremonies within the Comanche Native American Church, said peyote is utilized in the context of prayer — not smoked — as many tend to imagine.

“When we use it, we either eat it dry or grind it up,” he said. “Sometimes, we make tea out of it. But, we don’t drink it like regular tea. You pray with it and take little sips, like you would take medicine."

Tosee echoes the belief that pervades the church: "If you take care of the peyote, it will take care of you.”

“And if you believe in it, it will heal you,” he said, adding that he has seen the medicine work, healing people with various ailments.

People treat the trip to harvest peyote as a pilgrimage, said Red Cloud. Typically, prayers and ceremonies take place before the pilgrimage to seek blessings for a good journey. Once they get to the peyote gardens, they would touch the ground and thank the Creator before harvesting the medicine. The partaking of peyote is also accompanied by prayer and ceremony. The mescaline in the peyote plant is viewed as God's spirit, Red Cloud said.

“Once we eat it, the sacredness of the medicine is inside of us and it opens the spiritual eye,” he said. “From there, we start to see where the medicine is growing. It shows itself to us. Once we complete the harvest, we bring it back home and have another ceremony to the medicine and give thanks to the Creator.”

Associated Press religion coverage receives support through the AP’s collaboration with The Conversation US, with funding from Lilly Endowment Inc. The AP is solely responsible for this content.

The property of the late Amada Cardenas, who was one of the first federally licensed peyote dealers, alongside her husband, to harvest and sell the sacramental plant to followers of the Native American Church, in Mirando City, Texas, Monday, March 25, 2024. (AP Photo/Jessie Wardarski)