Gilead Sciences to Acquire PepStar’s Oral IL-23R Inhibitor Program for $1.275 Billion
Gilead Sciences, Inc. has entered into a definitive agreement to acquire an oral interleukin-23 receptor (IL-23R) inhibitor program, including its lead investigational candidate HCXT-2001, from PepStar Therapeutics Limited, a privately held, clinical-stage biotechnology company. The transaction, valued at $1.275 billion in upfront cash consideration, is expected to strengthen Gilead’s inflammation and immunology portfolio and expand its development opportunities in immune-mediated inflammatory diseases.
HCXT-2001 is an investigational, clinical-stage oral macrocyclic peptide designed to inhibit IL-23R. The candidate has an extended half-life and represents a potentially differentiated approach to targeting the IL-23 pathway through an oral medicine. The pathway is an established therapeutic target in several immune-mediated inflammatory conditions, including inflammatory bowel diseases (IBD), with potential applications in psoriasis.
Through the acquisition, Gilead will obtain worldwide rights to the IL-23R inhibitor program, including HCXT-2001. The agreement aligns with the company’s broader strategy to develop innovative medicines for people living with chronic inflammatory and autoimmune conditions. By adding another oral therapeutic candidate to its pipeline, Gilead aims to broaden its options for developing treatments that could be administered alone or in combination with other medicines.
The company has identified inflammatory bowel disease as a key potential application for HCXT-2001. Gilead is also exploring the possibility of combining the candidate with emvistegrast, with the longer-term objective of developing an oral treatment approach for patients who require ongoing management of inflammatory disease.
The transaction is expected to close in the fourth quarter of 2026, subject to customary closing conditions. Gilead anticipates that the acquisition will reduce its generally accepted accounting principles (GAAP) and non-GAAP earnings per share (EPS) by approximately $0.79 to $0.83 in the fourth quarter of 2026.
HCXT-2001 Expands Gilead’s Oral Inflammation Pipeline
HCXT-2001 is the lead asset in PepStar’s oral IL-23R inhibitor program. It is an investigational macrocyclic peptide designed to block signaling through the interleukin-23 receptor, a component of the immune system involved in regulating inflammatory responses.
Interleukin-23, commonly referred to as IL-23, is a cytokine that plays an important role in immune regulation and inflammatory processes. Its signaling activity contributes to the development and maintenance of certain immune responses associated with chronic inflammatory diseases. When these processes become dysregulated, they can contribute to persistent inflammation and tissue damage.
IL-23 pathway inhibition has become an established therapeutic strategy in several immune-mediated diseases. Treatments targeting this pathway have demonstrated clinical relevance in conditions such as psoriasis and inflammatory bowel disease, supporting continued research into approaches that modulate IL-23 signaling.
HCXT-2001 is intended to target IL-23R through an oral macrocyclic peptide. Its extended half-life is a potentially important feature of its pharmacological profile, although further clinical development will be needed to determine how this characteristic affects dosing, treatment convenience, safety, and efficacy.
The oral formulation is also relevant to Gilead’s interest in developing precision medicines for chronic inflammatory conditions. Oral therapies can offer an alternative to injectable treatments and may provide additional flexibility for patients who need long-term disease management.
However, HCXT-2001 remains investigational, and its potential benefits have yet to be established through the clinical evidence required for regulatory approval. Its eventual place in treatment will depend on future studies assessing its performance against relevant clinical endpoints and available therapies.
The acquisition provides Gilead with an opportunity to advance the program using its research, clinical development, and global commercialization capabilities. It also adds another mechanism to the company’s inflammation portfolio, allowing it to pursue additional approaches to immune-mediated diseases.
Potential Applications in Inflammatory Bowel Disease
Inflammatory bowel disease is a major area of interest for the acquisition. IBD primarily includes Crohn’s disease and ulcerative colitis, two chronic conditions characterized by inflammation of the gastrointestinal tract.
Crohn’s disease can affect different sections of the digestive tract and may involve inflammation extending through multiple layers of the intestinal wall. Ulcerative colitis primarily affects the colon and rectum, with inflammation involving the intestinal lining. Both conditions can cause symptoms such as abdominal pain, diarrhea, fatigue, and periods of disease activity followed by remission.
Treatment strategies aim to control inflammation, reduce symptoms, maintain remission, and limit complications associated with ongoing disease. Despite advances in treatment, some patients do not respond adequately to existing medicines, lose response over time, or experience adverse effects that complicate long-term management.
These challenges have created continued demand for treatments that act through different biological mechanisms and offer additional administration options.
By acquiring HCXT-2001, Gilead is expanding its potential to investigate oral inhibition of IL-23R as an approach to IBD. The candidate’s mechanism could provide an additional option for targeting inflammatory pathways involved in these diseases, subject to successful clinical development.
Gilead Chief Medical Officer Dietmar Berger, MD, PhD, highlighted the potential role of HCXT-2001 in the company’s expanding inflammation pipeline.
“HCXT-2001 adds a potentially differentiated oral approach to our growing inflammation pipeline, reflecting our commitment to addressing significant unmet patient needs,” Berger said.
He added that the company sees potential for HCXT-2001 to be developed either as a standalone treatment or in combination with other therapies, including emvistegrast, as a daily oral treatment for people living with IBD.
The proposed combination strategy reflects Gilead’s interest in evaluating complementary mechanisms that could potentially address different aspects of disease biology. Combining therapies can sometimes offer opportunities to improve disease control, particularly when individual treatments act on distinct pathways. Nevertheless, the suitability and benefits of any HCXT-2001 combination will need to be demonstrated through appropriately designed clinical studies.
The company has not established a final clinical role for HCXT-2001, and further development will determine which IBD populations, treatment settings, or combination strategies may be appropriate.
Potential Opportunities Beyond IBD
In addition to inflammatory bowel disease, HCXT-2001 may have potential applications in psoriasis, an immune-mediated inflammatory condition that primarily affects the skin.
Psoriasis is associated with abnormal immune activity that accelerates skin-cell turnover and contributes to the development of inflamed, scaly skin lesions. IL-23 signaling is an important component of the inflammatory processes involved in the disease, making the pathway a target for established therapeutic approaches.
The acquisition could therefore provide Gilead with an opportunity to explore whether oral IL-23R inhibition may have applications beyond gastrointestinal inflammation.
Any expansion into psoriasis or other immune-mediated diseases would require additional research to establish the candidate’s effectiveness, safety, and suitability for the relevant patient populations. The company’s stated rationale for the acquisition emphasizes the broader potential of the IL-23R inhibitor program, but the future development strategy will depend on clinical findings and commercial considerations.
More broadly, the addition of HCXT-2001 supports Gilead’s efforts to build a portfolio that includes multiple mechanisms and therapeutic modalities. Such a portfolio can give drug developers greater flexibility when responding to differences in disease biology, patient characteristics, treatment preferences, and unmet medical needs.
The acquisition also adds a clinical-stage asset to Gilead’s inflammation pipeline, potentially creating opportunities to assess oral treatment approaches alongside other medicines being developed by the company.
Gilead Strengthens Its Inflammation and Immunology Strategy
Gilead has been building a differentiated inflammation and immunology portfolio focused on chronic conditions where additional treatment options may be needed. The company’s strategy combines immunology research, precision oral medicines, and an internal development pipeline spanning complementary scientific approaches.
The objective is to develop treatments that address underlying disease mechanisms and improve outcomes that matter to patients. Gilead’s areas of focus include inflammatory bowel disease, type 2 inflammatory diseases, lupus, and B-cell-mediated autoimmune diseases.
These conditions differ in their biological drivers and clinical manifestations, making a range of therapeutic mechanisms important to the development of a broad immunology portfolio.
The addition of HCXT-2001 provides Gilead with another opportunity to investigate targeted immune modulation through an oral therapy. The program may also support future development strategies that evaluate monotherapy and combination approaches.
For chronic inflammatory conditions, treatment decisions often involve balancing disease control, safety, convenience, durability of response, and the patient’s ability to maintain therapy over time. Oral medicines can be an important component of this treatment landscape, although the clinical value of any individual candidate depends on its demonstrated performance relative to existing options.
Gilead’s acquisition of the PepStar program is therefore both a pipeline expansion and a strategic investment in the continued development of oral medicines for immune-mediated disease.
PepStar Highlights Its Oral Peptide Platform
The transaction represents a significant milestone for PepStar Therapeutics, which developed the oral IL-23R inhibitor program and its lead candidate, HCXT-2001.
Haibing Guo, Founder and Chief Executive Officer of PepStar, expressed confidence in Gilead’s ability to advance the candidate through subsequent stages of development.
“We are excited for Gilead to take HCXT-2001 forward and believe their scientific expertise and global development capabilities can help realize the full potential of this novel oral IL-23R inhibitor,” Guo said.
He described the agreement as a major milestone for the company and said it underscored the strength of PepStar’s proprietary oral peptide platform.
Guo also highlighted the progress made by PepStar’s team during the company’s first three years and expressed enthusiasm about its continued efforts to develop innovative medicines for patients worldwide.
The agreement provides PepStar with a transaction through which its IL-23R inhibitor program can be advanced by a larger biopharmaceutical company with global development capabilities. For Gilead, it offers access to the candidate and associated program rights without having to develop the asset entirely through internal discovery.
The deal also illustrates the role that biotechnology partnerships and acquisitions can play in advancing clinical-stage drug candidates. Smaller biotechnology companies may concentrate on developing specific scientific platforms or drug candidates, while larger pharmaceutical companies can provide additional resources for clinical development, regulatory engagement, and eventual commercialization.
Transaction Value, Financial Impact and Advisory Teams
Under the definitive agreement, Gilead will acquire the oral IL-23R inhibitor program, including HCXT-2001, for $1.275 billion in upfront cash consideration, subject to customary adjustments.
The payment is payable at closing. Completion of the transaction remains subject to customary closing conditions, and the companies expect the acquisition to close in the fourth quarter of 2026.
Gilead expects the transaction to reduce both GAAP and non-GAAP EPS by approximately $0.79 to $0.83 in the fourth quarter of 2026. The projected impact reflects the anticipated financial effect of the acquisition during that period.
Lazard is serving as Gilead’s exclusive financial advisor, while Centerview Partners LLC is acting as PepStar’s exclusive financial advisor.
Covington & Burling LLP and Mayer Brown LLP are serving as legal counsel to Gilead. Sidley Austin LLP is representing PepStar, with Wilson Sonsini Goodrich & Rosati LLP serving as patent counsel to PepStar.
The transaction gives Gilead worldwide rights to the IL-23R inhibitor program, positioning the company to determine the future development and commercialization strategy for HCXT-2001.
Outlook for HCXT-2001 Development
The acquisition of PepStar’s oral IL-23R inhibitor program expands Gilead’s opportunities in inflammation and immunology, particularly in inflammatory bowel disease. HCXT-2001 offers a potentially differentiated oral approach to a clinically validated immune target, with an extended half-life that may be relevant to its future development.
The company’s interest in evaluating HCXT-2001 alone or in combination with emvistegrast also points to a broader strategy of exploring complementary treatment mechanisms for chronic inflammatory diseases.
Future research will need to establish the candidate’s safety, efficacy, dosing profile, and potential advantages over existing therapies. Additional studies will also determine whether its mechanism can be applied successfully across IBD, psoriasis, or other immune-mediated conditions.
For PepStar, the agreement marks the next stage in the development of a program built on its proprietary oral peptide platform. For Gilead, it strengthens the company’s inflammation pipeline and adds another potential treatment approach to its efforts to address significant unmet needs in chronic inflammatory disease.
With the transaction expected to close in the fourth quarter of 2026, HCXT-2001 will become part of Gilead’s broader strategy to develop oral and combination therapies targeting the underlying drivers of immune-mediated inflammation.
About HCXT-2001
HCXT-2001 is an investigational oral macrocyclic peptide inhibitor of IL-23R with an extended half-life currently in Phase 1 clinical trials, originally developed by PepStar Therapeutics Limited. Its safety and efficacy have not been established, and it has not been approved by any regulatory authority.
About Gilead Sciences
Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis, COVID-19, cancer, and inflammation. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, Calif.