Hope Medicine Announces Positive Phase 2 Results for HMI-115, a First-in-Class PRLR Monoclonal Antibody for Endometriosis Pain in 190 Million Affected Women Worldwide

A Novel Solution for the Health Woes of 190 Million People.

Recently, Herui Medicine (Nanjing) Co., Ltd. (“Herui”) announced positive interim analysis results from a Phase 2 study of HMI-115 in female patients with moderate-to-severe endometriosis-associated pain. HMI-115 is a monoclonal antibody targeting the prolactin receptor (PRLR) and features a first-in-class mechanism of action. The company plans to rapidly advance global Phase 3 trials to enable patients to benefit from HMI-115 treatment as soon as possible.

Endometriosis, also known as "endo." The endometrium normally grows within the uterine cavity and is shed from the body each month with menstrual blood. Endometriosis occurs when endometrial tissue fails to be expelled normally during menstruation and instead implants in other parts of the body. This is a chronic condition associated with severe, life-disrupting dysmenorrhea, pain during defecation and/or urination, chronic pelvic pain, bloating, nausea, and fatigue, and may also be accompanied by depression, anxiety, and infertility.

However, there is currently no known complete cure for endometriosis, and treatment typically aims to control symptoms. Furthermore, while early diagnosis and effective treatment of endometriosis are crucial, patients often struggle to obtain them due to limitations in healthcare resources, patient education, and social awareness. In China, for example, some patients only receive a definitive diagnosis when they discover they are infertile; younger patients, meanwhile, endure long-term pain and are prone to delayed treatment due to misdiagnosis.

And the population affected by endometriosis—according to the latest statistics from the World Health Organization (WHO)—is approximately 10% (about 190 million) of women and girls of reproductive age worldwide.According to the latest data from McKinsey’s 2024 report, the global market size for endometriosis is approximately $200 billion.

Over the past decade, the number of young women diagnosed with endometriosis in hospitals across China has been steadily increasing. The reasons for this trend remain as unclear as the etiology of the disease itself; it is merely hypothesized to be associated with the delayed childbearing age among women overall, changes in dietary patterns, and the pressures of modern society. However, despite new insights into the diagnosis and treatment of endometriosis both domestically and internationally—emphasizing its nature as a chronic condition that requires early diagnosis and intervention, comprehensive treatment, and long-term management—key questions remain unresolved. Specifically, there is still no definitive consensus in the academic community on why endometrial tissue, which should be expelled from the body with menstrual blood, becomes ectopically implanted in extrauterine sites, and precisely how this ectopic implantation occurs.

This has also become a major challenge in the development of new therapies for endometriosis.

Current theories can only explain the mechanisms underlying a subset of lesions. The implantation theory has long dominated the scientific literature, proposing that certain lesions may be associated with the retrograde flow of menstrual blood through the fallopian tubes. In patients with endometriosis, endometrial cells attach to the peritoneum in an abnormal state. However, this theory currently fails to account for endometriosis in women with congenital absence of the uterus, adolescent girls, or the rare cases observed in males. Clearly, endometriotic cells are not merely uterine cells transplanted to the abdominal cavity; the development of endometriotic lesions involves additional mechanisms.

Others may result from the transformation of normal cells (transitional cells) into endometriotic cells. This theory can explain the occurrence of endometriotic cysts in the ovaries and lesions in the pelvis.

According to Müllerianosis theory, other lesions may originate from embryonic remnants. This theory can explain why endometriotic lesions have a high incidence in the posterior uterus and uterosacral ligaments, whereas their incidence is lower on the ovaries, sigmoid colon, appendix, or diaphragm. Furthermore, a recent theory emphasizes epigenetic changes occurring in normal endometrial cells, positing that such changes are responsible for the development of intraperitoneal endometriotic lesions.

In recent years, one of the most significant advancements in the global treatment landscape for endometriosis has been the development of GnRH (gonadotropin-releasing hormone) antagonists. A representative drug in this class is AbbVie’s elagolix, the first GnRH antagonist approved for the treatment of moderate-to-severe endometriosis, which received FDA approval in the United States in 2018. Additionally, Pfizer/Myovant’s oral GnRH receptor antagonist, relugolix, has achieved notable commercial success. However, in the progestin segment, Visanne (dienogest), although approved in China, Japan, and certain European countries, has not yet obtained FDA approval.

Despite these advances, current treatment regimens still face numerous challenges. First-line therapy primarily consists of inexpensive oral contraceptives, which offer only modest efficacy, with approximately one-third of patients showing no response (possibly due to progesterone receptor variants). Furthermore, although oral contraceptives have relatively fewer side effects, they still have limitations. Similarly, glucocorticoids used in the treatment of lupus erythematosus, while inexpensive, are associated with significant adverse effects, thereby driving the industry to develop more advanced biologics.

Another commonly used older medication is GnRH agonists, such as leuprorelin; however, these drugs also have side effects and cause infertility during treatment. Furthermore, existing hormonal therapies are associated with other adverse effects, including cardiovascular risks, breakthrough bleeding, osteoporosis, and depression—particularly osteoporosis and depression. Osteoporosis recovery is slow and in some cases irreversible, while depression can severely impair patients’ quality of life, contradicting the principles of chronic disease management.

Although the latest GnRH antagonists can effectively alleviate pain, they also suppress estrogen more severely, leading to more severe depression. Therefore, despite pain relief, patients’ mood does not show significant improvement. Meanwhile, due to a range of side effects, these drugs cannot be used long-term and are not covered by medical insurance.

In light of these limitations, leading experts in China—including Academician Lang Jinghe, an authority in endometriosis research, Academician of the Chinese Academy of Engineering and Honorary Director of the Department of Obstetrics and Gynecology at Peking Union Medical College Hospital; Academician Chen Zijiang; and Dr. Zhu Lan, Director at Peking Union Medical College Hospital—have all emphasized the urgent need for an innovative non-hormonal therapy. Meanwhile, infertility remains a significant challenge in China, making it particularly crucial to adopt treatment regimens that do not impair fertility.

Herui was founded in 2018 by Professor Xiao Ruiping, Director of the Institute of Molecular Medicine at Peking University and Dean of the School of Future Technology at Peking University. On April 8, 2019, Herui and Bayer signed a global exclusive license agreement for the development and commercialization of HMI-115, a monoclonal antibody targeting the prolactin (PRL) receptor. Under the license agreement, Herui Pharma will develop and commercialize novel antibodies targeting the prolactin receptor worldwide, based on Bayer’s intellectual property. Notably, this marks the only time in Bayer’s 160-year history that it has granted global rights to a Chinese biotech company.

Prolactin (PRL), also known as lactotropic hormone or luteotropic hormone, is a protein hormone secreted by the acidophilic cells of the anterior pituitary gland. Its primary functions include promoting mammary gland development and growth, stimulating and maintaining lactation, and stimulating the generation of LH receptors in ovarian follicles.

From a clinical perspective, prolactin, as a hormone, has relatively clear and limited primary functions, the most significant of which is to promote lactation. However, since the period during which lactation is required is relatively short, taking patients with endometriosis-associated pain as an example, once pregnancy occurs, the maternal body naturally secretes large amounts of progesterone, causing the patient’s pain to subside. This pain relief persists through childbirth and until weaning. This means that patients do not experience pain during the lactation period.

From a molecular biology perspective, activation of the prolactin pathway promotes the proliferation of ectopic endometrial cells, leading to lesion expansion and triggering inflammation through immune system activation. Furthermore, prolactin activation sensitizes nociceptive nerves, rendering previously non-painful stimuli intolerably painful. Therefore, blocking prolactin receptors can inhibit these three activation pathways, thereby reversing the pathological process of endometriosis.

Current research has revealed numerous novel functions of prolactin. Although initially thought to be unrelated to certain physiological processes, prolactin is now recognized to act similarly to inflammatory cytokines, particularly under conditions of significant physiological stress, during which the prolactin signaling pathway is activated. For instance, the effects of prolactin become pronounced in scenarios such as intense physical exercise, negative mood states, or psychological stress, earning it the designation of a "stress hormone." However, excessively elevated prolactin levels can lead to a range of complications, including amenorrhea and depression in women, and sexual dysfunction in men. Therefore, blocking prolactin receptors is more advantageous than allowing its overactivity.

The primary mechanism of action of HMI-115 lies in blocking the prolactin receptor, thereby inhibiting the prolactin signaling pathway. It is worth noting that HMI-115 is not required during pregnancy and lactation. If pain recurs after the lactation period (i.e., after weaning), treatment with this medication can be initiated, thus perfectly avoiding the periods of lactation and most of the pregnancy.

This is also why HMI-115 demonstrated few side effects in clinical trials, as it does not interfere with normal physiological activities. In October 2024, HMI-115 was included in the Breakthrough Therapy Designation (BTD) list by the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA), with a proposed indication for the treatment of moderate-to-severe pain associated with endometriosis.

This mechanism of source innovation has yielded positive clinical data.

Recently, Herui announced the interim analysis results of a Phase 2 study evaluating HMI-115 in female patients with moderate-to-severe endometriosis-associated pain.

This Phase 2 study is an international, multicenter, randomized, double-blind, placebo-controlled trial designed to evaluate the safety and efficacy of HMI-115 in women with moderate-to-severe endometriosis-associated pain over a 12-week treatment period. The study was conducted in 142 female patients from the United States, Poland, and China. Interim results showed:

Mr. Chen Xi, CEO of Herui, also shared other positive feedback from the clinical trials. He noted that researchers in China, Poland, and the United States all expressed high recognition for HMI-115. Among the 102 subjects, only two withdrew due to personal reasons, a rate far lower than the up to 25% dropout rate seen with other drugs in the same class. This result further demonstrates the efficacy and patient acceptability of HMI-115.

Mr. Chen Xi particularly emphasized that in the clinical trials of HMI-115, patients did not report any depression-related adverse events, indicating that they were able to maintain a favorable psychological state following treatment. This is precisely one of the most critical criteria for successful disease management, particularly in the context of chronic conditions.

Furthermore, HMI-115 supports biweekly subcutaneous administration. On one hand, similar to insulin, this more sophisticated route of administration avoids “pill burden” (the excessive number of oral tablets patients are required to take daily); on the other hand, the biweekly dosing frequency makes HMI-115 more akin to long-acting medications, aligning with the broader trend in the development of chronic disease therapies.

Thus, the emergence of HMI-115 has not only addressed the pain points of existing medications but also gained favor among physicians and patients due to its significant efficacy and lower side effects, further underscoring the critical role of source innovation in driving the development of the pharmaceutical industry.

Compared with other fields, women’s diseases—particularly the treatment of chronic conditions in women—have received less attention. There remains a substantial amount of unmet clinical need, and the challenges encountered in advancing clinical trials are more complex than anticipated.

Patient recruitment emerged as a major challenge in the early stages. In China, for instance, the team devoted substantial time during the initial months to both activating numerous research centers and persuading investigators to accept this novel mechanistic drug. Due to the high degree of innovation associated with HMI-115, patient enrollment progressed relatively slowly at the outset.

Furthermore, clinical trials involving female participants are significantly more complex than those involving males. For instance, patients with a predisposition to keloid formation may experience injection-site reactions that compromise cosmetic appearance, thereby deterring some potential candidates from participating. Additionally, married patients often consult their spouses when deciding whether to enroll in a trial; out of concern for their family’s well-being, spouses may discourage them from participation.

Fortunately, patient recruitment has made initial progress, with researchers beginning to leverage their social network influence to encourage patients to join clinical trials. The trust relationship between gynecological patients and physicians is particularly critical; once such trust and a sense of security are established, they attract more patients to participate in the trials. As research centers successfully enroll suitable patients and these patients perceive therapeutic benefits, researchers’ confidence grows, further drawing in additional participants. Commenting on this phenomenon, Mr. Chen Xi stated, “This effect is akin to the flywheel effect: initially slow to turn, but with sustained effort, the flywheel accelerates on its own.”

With the disclosure of positive Phase II data, the Phase III clinical trial of HMI-115 is progressing in an orderly manner, bringing it one step closer to official market launch and offering new hope for the 190 million patients suffering from this condition.