Orionis will leverage its Allo-Glue platform for the discovery of small-molecule monovalent glues

May 21st, 2025, BOSTON, MA and GHENT, Belgium – Orionis Biosciences, a privately held, clinical-stage life sciences company focused on the rational discovery and development of drug modalities with induced proximity mode of action, today announced a second multi-year collaboration with Genentech, a member of the Roche Group, to discover small-molecule monovalent glue medicines for novel and challenging targets in oncology. Orionis announced its first collaboration with Genentech, to discover novel small-molecule medicines for challenging targets in major disease areas, including oncology and neurodegeneration, in September 2023.

Orionis’s small-molecule Allo-Glue platform integrates multiple proprietary technologies to advance the
discovery and design of molecular glues for highly challenging disease targets. It combines advanced
chemical biology tools, engineered cellular assay systems, custom-built high-throughput robotic
automation and specialized artificial intelligence infrastructure, and enables the generation and analysis of hundreds of millions of in-cell protein interaction events. The AI-driven chemistry stack integrates
predictive modeling, generative design, and a compound interrogation engine operating across a vast
chemical space. Collectively, these capabilities accelerate the systematic discovery and simultaneous
optimization for potency, selectivity, and synthetic accessibility of monovalent molecular glue modalities.

Under the terms of the agreement, Orionis will be responsible for the discovery and optimization of
molecular glues, while Genentech will be responsible for subsequent later-stage preclinical and clinical
development, regulatory filing, and commercialization of such small molecules. Orionis will receive an
upfront payment of $105 million and is eligible for potential research, development, commercial and net
sales milestone payments, whose total could exceed $2 billion as well as potential tiered royalties upon sale of collaboration products.

“We are thrilled about this second collaboration with Genentech, which expands our collaborative efforts
in applying induced proximity concepts to include molecular glue types beyond targeted protein degraders,” said Niko Kley, Co-Founder and CEO of Orionis Biosciences. “The expansion of our existing strategic alliance underlines a strong alignment in vision for molecular glues, and the excellent work by both teams during the past year”.

“By integrating advanced cellular sensing technologies, large-scale robotic automation and specialized
artificial intelligence, at Orionis we have built a unique capability for discovery of new drug modalities to
rationally reprogram protein networks,” said Riccardo Sabatini, Orionis Chief Data Scientist. “It’s an
exciting time in small-molecule drug development”.

“Molecular glues, including protein degraders and non-degraders, are an exciting therapeutic modality,
providing access to disease-related proteins that have proven challenging and elusive to more traditional
treatment modalities,” said Boris L. Zaïtra, Head of Roche Corporate Business Development. “This new collaboration with Orionis has the potential to significantly enhance our innovation to bring transformative cancer medicines to patients”.

About Orionis Biosciences
Orionis Biosciences is a clinical-stage life sciences company pioneering the systematic discovery and
rational design of therapeutic modalities that invoke molecular proximity-based mechanisms of action to
impact challenging and traditionally elusive disease targets. The company’s Allo-Glue platform enables
unprecedented target-centric and target-agnostic discovery and design of small molecule glues for any
induced proximity applications. Its A-Kine biologics platform comprises an array of engineered
cytokines that exhibit exquisite cell-target selectivity, and novel types of multifunctional immune cell
engagers. The company is advancing a deep and diversified pipeline of oncology programs and cancer
immunotherapies. It leverages its disruptive technologies across multiple disease targets and therapeutic
indications in collaboration with industry partners.

Orionis Media Contact:
Matt Crenson
Ten Bridge Communications
[email protected]

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Dose-escalation study to evaluate ORB-011 as single agent, with initial safety, pharmacokinetic and mechanism-based pharmacodynamic readouts.

Tony Fadell, inventor of the iPod, co-inventor of the iPhone, founder of Nest, and Principal at Build Collective, joins Orionis Board of Directors.

November 15, 2023, BOSTON, MA, and GHENT, Belgium – Orionis Biosciences, a life sciences company pioneering the creation of highly selective and tunable therapeutics for cancer and other diseases, today announced that the first patient has been dosed in a Phase 1 clinical trial of ORB-011, an attenuated, cis-targeted interferon immunotherapy based on the company’s A-Kine® platform. ORB-011 is the first clinical candidate to emerge from the platform, which engineers cytokines to be highly selective for specific cellular targets while avoiding the broad systemic activity and associated toxicities observed with traditional cytokine therapies. The company is also announcing the appointment of Tony Fadell to its Board of Directors.

ORB-011 is a first-in-class modified interferon designed to act with a high level of precision on cDC1 dendritic immune cells, potent activators of tumor cell killing CD8+ T cells. Preclinical research has shown that selective activation of cDC1s with such conditionally active interferon molecules translates into effective antitumor activity. Targeted activation of cDC1 was also well tolerated in non-human primate studies.

“The beginning of this clinical study represents a major milestone for Orionis and our A-Kine® protein engineering platform, which combines a range of redesigned immune-modulatory cytokines with targeting modules aimed at cell types of therapeutic relevance. ORB-011 has the potential to harness the therapeutic activity of interferon in a new way,” said Nikolai Kley, Ph.D., Founder, President, and Chief Executive Officer of Orionis Biosciences. “Interferons and other cytokines in our pipeline are powerful immune-activating agents. By localizing their activity to specific target cells, and exploiting communication networks across immune cells, we are evolving immunotherapies with unique translational potential.”

Tony Fadell, Principal at Build Collective has joined the Orionis Board of Directors. He is the founder and former CEO of Nest, the company that pioneered the “Internet of Things.” Tony was the SVP of Apple’s iPod Division and led the team that created the first 18 generations of the iPod and the first three generations of the iPhone. Tony holds more than 300 patents and is the author of the New York Times Best-Seller “BUILD – An Unorthodox Guide to Making Things Worth Making.”

“Tony is a tremendously supportive and collaborative investor, bringing a broad range of expertise and insights to countless topics important to the strategic growth and vision of our business,” said Dr. Kley. “His increased involvement will help us take Orionis to the next level and execute on our mission to bring new breakthrough medicines to patients in need.”

“Orionis deploys the most powerful new foundational technologies available: Robotics plus Assay-on-Chip for high-throughput screening, generative AI for structure-based drug design…to name only a few,” said Fadell. “This is what’s needed to combat the toughest, currently undruggable diseases. I’m excited about Orionis’s focus on immunotherapies: activating and directing our natural immune system to go after cancer. I can’t think of a more worthwhile endeavor.”

About ORB-011
ORB-011 is a clinical-stage, targeted interferon that is designed to specifically activate cDC1 dendritic cells, immune cells that are specialized in presenting tumor antigens to, and activating, tumor cytotoxic CD8 T cells. It achieves localized activity by a unique mechanism of induced proximity on the cell surface of cDC1s. Orionis is evaluating ORB-011 in a Phase 1 open-label dose-escalation study (NCT05947474) for patients with recurrent or refractory solid tumors amenable to medically safe serial biopsies, including, but not limited to, colorectal cancer, HR+ or triple-negative breast cancer, non-small cell lung cancer, pancreatic cancer, head and neck squamous cell carcinoma, metastatic melanoma, bladder/urothelial, gastric cancers, esophageal, renal cell, hepatic and ovarian cancers. The Phase 1 clinical trial will provide initial safety, pharmacokinetic and pharmacodynamic readouts, and identify a dose of ORB-011 for use in future studies. It is being conducted at this time at the M.D. Anderson Cancer Center in Houston, Texas and at Honor Health Research Institute in Scottsdale, Arizona.

About the A-Kine® Platform
Orionis’s A-Kine® platform is designed to harness the intrinsic function and therapeutic potential of cytokines as key immune system regulators and natural defenders against cancer and infections. A-Kines® are designed to be highly selective for intended cell targets, such as immune cells, and to avoid broad systemic activity and associated toxicities observed with traditional cytokine therapies. The platform covers multiple cytokine classes, including interferons, interleukins, and tumor necrosis factors, to generate a diversified pipeline of targeted immunotherapy candidates. These redesigned cytokines are leveraged to restart a stalled Cancer Immunity Cycle at multiple different positions to elicit natural mechanisms of immune attack against a variety of cancers.

About Orionis Biosciences
Orionis Biosciences is a life sciences company pioneering the discovery of conditionally active drug modalities for life threatening diseases. These operate by leveraging induced molecular proximity and cooperativity mechanisms in unique fashion to gain novel target access, drug potency and precision. The company applies its design concepts and technological innovations to the discovery of small molecules, with a focus on monovalent molecular glues with its Allo-Glue platform, and to the design and engineering of novel classes of precision biologics and cytokine-based immunotherapies with its A-Kine® platform. The company is advancing a deep and diversified pipeline of drug modalities, including agents that engage components of the adaptive and innate immune systems, creating new avenues for the development of single agent-effective therapies for patients with cancer or other diseases. To learn more, please visit www.orionisbio.com.

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Orionis will leverage its Allo-Glue platform for discovery of small molecule monovalent glues.

September 20, 2023, BOSTON, MA and GHENT, Belgium – Orionis Biosciences, a privately held life sciences company with an integrated drug discovery and chemical biology platform, announced today a multi-year collaboration with Genentech, a member of the Roche Group, to discover novel small molecule medicines for challenging targets in major disease areas, including oncology and neurodegeneration.

Orionis’s Allo-Glue platform utilizes multiple unique approaches to discover drug-like small molecules against disease targets that have remained elusive to traditional discovery approaches. The platform integrates a suite of proprietary chemical biology technologies, including biological assays, computational analyses, chemical libraries and automated processes for high throughput discovery, rational design and optimization of small molecules that promote or induce interactions of proteins in living cells. This includes molecular glues that can promote interactions leading to either target degradation (through virtually any ligase) or modulation of target function, via either direct or allosteric mechanisms. Both target-centric and ligase-driven discovery paradigms are enabled and leveraged in a synergistic manner in the company’s overall approaches to molecular glue discovery.

Under the terms of the agreement, Orionis will be responsible for the discovery and optimization of molecular glues for Genentech’s designated targets, while Genentech will be responsible for subsequent later-stage preclinical, clinical development, regulatory filing, and commercialization of such small molecules. Orionis will receive an upfront payment of $47 million and is eligible for development milestone payments, as well as commercial and net sales milestone payments that could exceed $2 billion and a tiered royalty upon sale of collaboration products.

“Molecular glues represent one of the most exciting recent developments in small-molecule drug discovery. We are thrilled to collaborate with Genentech, a company long known for its world-class science and trailblazing medicines, to make use of technological innovations that we have systematically evolved over the past years to unlock novel target space with such drug modalities” said Nikolai Kley, Co-Founder and CEO of Orionis Biosciences. “We could not be more excited about the potential for this pioneering collaboration to lead to impactful new treatment paradigms.”

Riccardo Sabatini, Orionis Chief Data Scientist, added, “It is exciting to see how synergies created by the integration of our biological, chemical and computational technologies are being leveraged for the discovery and design of molecular glues.”

“Molecular glue degraders are an exciting modality to target disease-related proteins that have proven challenging with more traditional treatment modalities,” said James Sabry, Global Head, Roche Pharma Partnering. “For patients with unmet needs, this offers a new therapeutic approach to modulate major disease drivers. This collaboration enables us to apply the concept of targeted protein degradation to discover and develop medicines for patients with serious and life-threatening diseases.”

About Orionis Biosciences

Orionis Biosciences is a life sciences company pioneering the discovery of conditionally active drug modalities for life threatening diseases. These operate by leveraging induced molecular proximity and cooperativity mechanisms in unique fashion to gain novel target access, potency and precision. The company applies its design concepts and technological innovations to the discovery of small molecules, with a focus on monovalent molecular glues with its Allo-Glue platform, and to the design and engineering of novel classes of precision biologics and cytokine-based immunotherapies with its A-Kine platform. The company is advancing a deep and diversified pipeline of drug modalities, including agents that engage components of the adaptive and innate immune systems with high precision, creating new avenues for the development of single agent-effective therapies for patients with cancer and other diseases. To learn more, please visit www.orionisbio.com.

Orionis Media Contact:

Olivia Durr, Ten Bridge Communications
[email protected]

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Cytokines are powerful regulators of the immune system and attractive therapeutic effector candidates. However, their sites of action must be restricted to avoid systemic toxicity. To achieve spatial control of cytokine bioactivity, Orionis has developed a proprietary biologics platform that integrates a strategic “plug-and-play” assembly of modular biomolecular building blocks into therapeutic agents with unique conditional effector functions and cell-target selectivity. These conditionally active, cis-acting cytokines aim to trigger anti-tumor immune responses even in cold tumors that lack prevalent immune involvement and are refractory to checkpoint inhibitor and other therapies.

“Today we shared preclinical data that represent exciting progress for our proprietary A-Kine platform. Our R&D engine, inspired by nature’s intrinsic mechanisms for disease control, has the potential to address some of the biggest challenges in oncology drug discovery and beyond,” said Nikolai Kley, Ph.D., Founder, President and Chief Executive Officer of Orionis Biosciences. “As we look ahead, we anticipate IND submission and the start of a conditionally active cytokine Phase 1 trial in 2023.”

Orionis’ deep and diversified A-Kine pipeline comprises multiple cytokine classes, including re-engineered interferons (IFNs), interleukins (ILs) and tumor necrosis factors (TNFs). In conjunction with an arsenal of cell-targeting strategies, Orionis is harnessing the therapeutic potential of these cytokines to reprogram immune cells and reactivate the cancer immunity cycle, and thereby the immune system’s natural mechanisms of disease control.

The company presented its advances and breakthroughs in design, engineering and development of exquisitely target-selective A-Kines incorporating:

• Cis-acting Interferons to promote immune system recognition and infiltration of tumors
• Cis-acting Interleukin-2 to directly activate CD8+ tumor cytotoxic T cells

These unique agents exhibit potent, single agent anti-tumor activity in multiple preclinical cancer models, mediated by targeting of key immune cells, including subtypes of myeloid cells and tumor cytotoxic CD8+ T cells, and PD-1/PD-L1 checkpoint mechanisms. Orionis’ A-Kine pipeline reflects multiple protein engineering innovations and contains an array of programs in lead optimization and IND-enabling phases.

Details of today’s presentation are as follows:

14th Annual PEGS Europe Protein & Antibody Engineering Summit, November 14–16, 2022, Barcelona, Spain

• Title: A-Kine Platform: On-Target Cytokines to Reprogram Cell Targets for Immuno-Oncology
• Date and Time: Monday, November 14, 11:45 a.m. CET
• Presenter: Erik Depla, Ph.D., Director of Biology, Orionis Bio

Orionis recently announced a $55 million financing to support entry of its lead A-Kine cancer immunotherapy programs into the clinic. The company anticipates IND submission and start of a Phase 1 study of a conditionally active cytokine in 2023. In addition to the A-Kine platform, Orionis has developed the Allo-Glue protein degradation platform for discovery and rational design of small molecule molecular glues. These types of conditionally active small molecules are designed to tackle traditionally undruggable or elusive drug targets by harnessing nature’s cellular machinery to degrade and dispose of proteins that cause and/or promote disease.

About Orionis Biosciences
Orionis Biosciences is a life sciences company pioneering technological innovations in genome-scale drug discovery to develop novel, highly specific and tunable therapeutics for cancer and beyond. The company utilizes its proprietary A-Kine biologics and Allo-Glue small molecule platforms to target core disease vulnerabilities and reach previously intractable targets. Orionis has multiple first-in-class immunotherapies in development for the treatment of cancer. Learn more at www.orionisbio.com.

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“Molecular glues have the potential to greatly extend the treatment of challenging diseases like cancer, and there is vast untapped power in this modality. A lack of systematic, scalable discovery and design approaches to molecular glues has, however, limited the field,” said Riccardo Sabatini, Ph.D., Chief Data Scientist at Orionis. “Today we are presenting new data that demonstrate the ability of Orionis’ proprietary Allo-GlueTM platform to transform glue discovery into a genome-scale, high throughput and rational discovery paradigm. Our large-scale interrogation of small molecule-triggered protein-protein interactions makes it abundantly clear that molecular glue mechanisms are more common than previously appreciated. Clearly, this presents a large and exciting space for chemistry innovation.”

The Allo-Glue platform can interrogate more than 18,000 target proteins simultaneously — virtually the entire human proteome — as well as diverse and privileged chemical libraries, at scale and in an unprecedented, unbiased manner across large number of targets and target classes, including traditionally intractable disease targets. To date, Orionis has mapped more than 150 million molecular glue interactions. This growing data set will provide the company with unique opportunities to further evolve and apply its novel numerical modelling approaches to the rational design of molecular glues.

To date, Orionis’ Allo-Glue platform has:

• Identified multiple monovalent glues and targets for new ligases beyond the E3 ligase cereblon: A series of molecules have demonstrated strong and highly selective target recruitment and degradation in preclinical studies, further validating the concept that drug-induced, selective degradation of proteins is achievable with multiple types of E3 ligases and targets
• Established the feasibility of target-centric approaches to glue discovery, as exemplified by discovery of drug-like molecules for traditionally intractable oncology targets
• Evolved and applied computational methods and machine learning models to rational expansion and design of new molecular glues

Details of today’s presentation are as follows:

5th Annual Targeted Protein Degradation, October 25-28, 2022, Boston, Massachusetts

• Title: Monovalent Molecular Glues: Cereblon and Beyond
• Date and Time: Wednesday, October 26, 5:00 p.m. ET
• Presenter: Riccardo Sabatini, Chief Data Scientist, Orionis Bio

Last week Orionis announced a $55 million financing to support entry of its lead cancer immunotherapy programs into the clinic. In addition to its Allo-Glue molecules, Orionis is rapidly advancing a deep pipeline of biologics for the treatment of cancer based on its A-KineTM platform, which engineers target-selective, conditionally active cytokines designed to trigger anti-tumor immune responses even in cold tumors that lack prevalent immune involvement and are refractory to checkpoint inhibitor therapies. A-Kines aim to avoid the systemic toxicities observed with traditional cytokine therapies. The company anticipates IND submission and start of a Phase 1 study of a conditionally active cytokine, driven by its proprietary A-Kine platform, in 2023.

“We are all very excited about the continued progress the company is making with its multipronged technology and therapeutic approaches to currently hard to treat cancers. Our R&D engine has the potential to address some of the biggest challenges in drug discovery, including diseases beyond cancer,” said Nikolai Kley, co-founder, President and Chief Executive Officer of Orionis Biosciences.

About Orionis Biosciences

Orionis Biosciences is a life sciences company pioneering technological innovations in genome-scale drug discovery to develop novel, highly specific and tunable therapeutics for cancer and beyond. The company utilizes its proprietary A-KineTM biologics and Allo-GlueTM small molecule platforms to target core disease vulnerabilities and reach previously intractable targets. Orionis has multiple first-in-class immunotherapies in development for the treatment of cancer. Learn more at www.orionisbio.com.

Media contact:

Lisa Qu Ten Bridge Communications
[email protected]

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Orionis Biosciences announced Wednesday morning that it finished a Series C round and secured $55 million. That infusion gives Orionis flexibility to expand its R&D operations, increase its pipeline and bring assets into human trials. The biotech plans to introduce its lead candidate, a conditionally active cytokine therapy, into the clinic sometime next year.

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