Orogen Therapeutics, Inc. (“Orogen” or the “Company”) today announced the selection of two development candidates (DCs), ORO-110 and ORO-210, potential best-in-class oral small molecule inhibitors of IL-17 and JAK1/TYK2, respectively. Both DCs have completed extensive nonclinical studies to demonstrate attractive pharmacokinetic and pharmacodynamic characteristics, including nanomolar potency, exposure, and half-life attributes.

In a preclinical joint inflammation model, oral administration of the ORO-110 IL-17 small molecule inhibitor achieved reductions in inflammation as good as a leading anti-IL-17 antibody with corresponding mitigation of underlying disease pathology similar to positive-control antibody and reduction of downstream cytokine mediators of inflammation. ORO-110 administration also reduced inflammation better than a leading competitor small molecule at a substantially lower dose than the competitor compound. No adverse events were noted in the model, nor have any safety concerns been observed in pilot toxicity work. ORO-110 is targeted for inhibition of the IL-17 AA homodimer and IL-17 AF heterodimer while sparing activity against IL-17 FF, a key component of mucosal immunity the preservation of which is important in preventing opportunistic infections such as candidiasis.

In preclinical models of atopic dermatitis, oral administration of ORO-210, a next-generation JAK1/TYK2 dual-target small molecule inhibitor, showed broader coverage of key downstream inflammatory cytokines with a better hematologic/immunologic molecular safety profile than a leading JAK1/TYK2 competitor small molecule compound. The ORO-210 DC product profile is aimed at enhancing inhibition of downstream cytokine mediators of inflammation such as IL-6, with improved JAK2-sparing and safety.

“Oral options represent an important frontier in the treatment of a range of inflammatory disorders where treatment with biologic antibodies has room for improvement. As next-generation oral medicines, ORO-110 and ORO-210 show strong promise in addressing unmet needs in a broad range of patients for whom treatment options to date are suboptimal and where effective oral therapies could expand treatment options and support earlier intervention, subject to clinical evidence,” stated Percio Gulko, MD, Professor of Medicine and former Chief of Rheumatology at the Icahn School of Medicine, Mt. Sinai, and medical advisor to Orogen. “The attributes exhibited by ORO-110 in inhibiting IL-17 AA and AF while avoiding compromise of IL-17 FF activity, and by ORO-210 in more broadly covering the inflammatory cascade mediated via JAK1 and TYK2 signaling, are important in balancing potent efficacy and important safety considerations in immunological disorders.”

IND-enabling studies and cGMP manufacturing activities are underway to support planned clinical development, including initial assessments in patients, with first-in-human dosing targeted to start for ORO-110 in late 2027 and for ORO-210 in early 2028. Candidate indications potentially to be explored for ORO-110 in diseases mediated by IL-17 include psoriasis, hidradenitis suppurativa, psoriatic arthritis, axial spondyloarthritis, and juvenile idiopathic arthritis, among others. Conditions potentially to be evaluated for ORO-210 in disorders driven by cytokine pathways involving JAK1 and TYK2 include atopic dermatitis, Sjogren’s disease, sclerotic disease, sarcoidosis and lupus.

“Advancing ORO-110 and ORO-210 to development candidate status are important milestones for Orogen. We are encouraged by the rapid progress the company has made on these programs, culminating in nomination of our first drug candidates in only two years since company inception,” said Mark Pykett, Orogen CEO. “The rigorous datasets generated to date for our two development candidates provide a strong foundation to advance toward clinical studies.”

About ORO-110

Orogen’s oral small molecule IL-17 inhibitor development candidate, ORO-110, exhibits potential best-in-class properties with promising in vivo efficacy demonstrated in model systems, including inhibition of the IL-17 AA homodimer and IL-17 AF heterodimer while sparing activity against IL-17 FF, a key component of mucosal immunity the compromise of which can lead to opportunistic infections.

About ORO-210

Orogen’s oral small molecule JAK1/TYK2 dual-target inhibitor development candidate, ORO-210, exhibits next-generation properties that optimize coverage of downstream cytokine-mediators of inflammation while enhancing hematologic/immunologic safety.

About Orogen Therapeutics

Orogen Therapeutics’ mission is to deliver groundbreaking clinical solutions to patients with serious unmet medical needs. Our vision is rooted in redefining small molecule medicines using our innovative drug discovery platform that integrates robust DNA-encoded libraries (DEL) unique and proprietary, target-specific DEL (FocusDEL™) powered by AI to rapidly and effectively develop novel medicines. We have assembled proprietary on-DNA assets consisting of billions of compounds across nearly 200 libraries and more than 55,000 building blocks, supporting screening efforts that have provided over 1 trillion data points for AI training to date. With a primary focus on immuno-inflammatory diseases, the company is advancing a portfolio of novel oral inhibitors for a range of cytokine targets, including IL-17, JAK1/TYK2, TL1A, FcRn, TNF-alpha, and other targets.

Forward-Looking Statements

“Forward-looking statements” that may be contained in this communication are made within the meaning of federal securities laws, including Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. In this context, forward-looking statements often address expected future performance, and often contain words such as “expect,” “anticipate,” “should,” “hope,” “project,” “estimate,” “predict,” “goals,” “intend,” “plan,” “believe,” “seek,” “will,” “would,” “target,” “outlook,” and similar expressions and variations or negatives of these words. All statements, other than those of historical fact, are forward-looking statements, including statements regarding outlook, expectations and guidance. Forward-looking statements address matters that are uncertain and subject to risks, uncertainties, and assumptions that could cause actual results to differ materially from those expressed in any forward-looking statements.

For more information, please visit our website at www.orogentx.com.

Media gallery

About The Author
Business Wire