HCW9302, HCW Biologics’ IL-2Rα-Biased Fusion Immunotherapeutic, Shows Preliminary Clinical Activity in Phase 1 Alopecia Areata Trial with Favorable Early Safety Profile

HCW Biologics, a US-based clinical-stage biopharmaceutical company focusing on fusion immunotherapeutics, announced preliminary phase 1 clinical data for HCW9302, an investigational interleukin-2 (IL-2)–based fusion immunotherapeutic designed to selectively expand regulatory T cells (T_regs), in patients with alopecia areata. In the second dose cohort (3 µg/kg), the 3 enrolled participants demonstrated at least a 25% reduction in Severity of Alopecia Tool (SALT) scores from baseline at 4 and/or 9 weeks following a single subcutaneous dose.¹

No dose-limiting toxicities, capillary leak syndrome, cytokine release syndrome, or increases in blood eosinophil counts were observed across the first 2 dose cohorts, the company reported.¹ Enrollment in the third cohort (8 µg/kg) is underway, with the recommended phase 2 dose expected to be established by year-end 2026.

"The positive preliminary human data readout from the first [2] cohorts of the [p]hase 1 clinical study of HCW9302 monotherapy for alopecia areata is highly encouraging, showing potential benefit along with a well-tolerated safety profile even with a single, subcutaneous low-dose regimen," said Hing C. Wong, PhD, founder and CEO of HCW Biologics, in a company press release.¹ “The results are consistent with our preclinical studies, which demonstrated that HCW9302 exhibits a strong IL-2 receptor α bias, a unique and novel mechanism of action, while preferentially expanding and stimulating T_reg cells to reduce pro-inflammatory and autoimmune responses in animal disease models, including alopecia and atherosclerosis.”

What did the dose-escalation trial design and preliminary efficacy results show?

The phase 1 multi-center, dose-escalation study (NCT07049328) is designed to enroll up to 30 patients with alopecia areata across multiple dose cohorts receiving a single subcutaneous dose of HCW9302 monotherapy. The study’s primary objectives include evaluation of safety and determination of the recommended phase 2 dose. Secondary objectives include assessment of disease response and pharmacodynamic effects on T_reg proliferation and function.

Two active clinical sites are enrolling: The Ohio State University Wexner Medical Center and the James A. Haley Veterans' Hospital in Tampa, Fla. In the first cohort (1 µg/kg), no clinical response data were reported in the current readout. As mentioned, the second cohort (3 µg/kg) with three participants having mild alopecia showed ≥25% SALT score reduction in all 3 patients at 4 and/or 9 weeks post-dose. Adverse events across both cohorts were mild, self-limiting, and resolved without medical intervention with the most common event being temporary injection-site reaction, according to the company.

What unmet need exists in alopecia areata?

Alopecia areata is a T-cell–mediated autoimmune condition in which autoreactive immune cells attack the hair follicle, causing non-scarring hair loss that may affect localized areas, the entire scalp, or the whole body.² The condition affects approximately 1 in 1000 individuals globally, with a lifetime incidence of approximately 2%, and disproportionately presents in those under 30 years of age.²

While Janus kinase inhibitors, including baricitinib and ritlecitinib, have received FDA approval for alopecia areata in recent years and represent a significant advance, these agents act through broad immunosuppression of downstream cytokine signaling rather than targeted restoration of immune tolerance. Long-term safety considerations, including infection risk and potential cardiovascular effects, may warrant ongoing monitoring.³ Currently, curative therapies do not exist, and patients commonly experience relapsing disease throughout their lives.³

What is HCW9302's mechanism of action, and how does IL-2Rα bias differentiate it from other IL-2–based agents?

HCW9302 is a subcutaneously injectable fusion immunotherapeutic constructed with a proprietary tissue factor scaffold that confers high-affinity binding to the IL-2 receptor α chain (IL-2Rα, CD25), which is constitutively expressed at high levels on T_regs.⁴ This IL-2Rα–biased binding is designed to preferentially stimulate T_reg proliferation and activation relative to CD4+ and CD8+ effector T cells and natural killer cells, which are cell populations that express IL-2 receptor β and γ chains but lower levels of IL-2Rα, and whose activation by conventional high-dose IL-2 therapy produces the capillary leak syndrome and cytokine release that limit clinical utility of recombinant IL-2.⁴

This mechanism is distinct from other IL-2 engineering strategies including PEGylated IL-2 conjugates and IL-2 muteins with attenuated IL-2Rβγ binding. The latter generally reduce affinity across receptor subunits rather than selectively enhancing IL-2Rα engagement.⁵ Preclinical studies have demonstrated HCW9302-induced T^reg accumulation and suppression of autoimmune responses in alopecia and atherosclerosis models.¹

What are the next steps and planned expansions of the HCW9302 clinical program?

HCW Biologics anticipates establishing the recommended phase 2 dose by year-end 2026 following completion of the third and any subsequent dose escalation cohorts. Upon phase 2 dose selection, the company intends to evaluate multi-dose HCW9302 monotherapy in expanded alopecia areata cohorts and in other inflammatory dermatological conditions, including vitiligo and atopic dermatitis. The company has also indicated interest in exploring HCW9302 in amyotrophic lateral sclerosis based on emerging evidence implicating T_reg dysfunction in neuroinflammatory disease pathogenesis. However, the company has to date not initiated clinical studies in that indication.¹

References

1. HCW Biologics. HCW Biologics announces positive results for preliminary human data readout for phase 1 clinical trial evaluating IL-2 based fusion immunotherapeutic, HCW9302 monotherapy, in alopecia areata. Published June 16, 2026. Accessed June 16, 2026. https://investors.hcwbiologics.com/news-releases/news-release-details/hcw-biologics-announces-positive-results-preliminary-human-data
2. Pratt CH, King LE Jr, Messenger AG, Christiano AM, Sundberg JP. Alopecia areata. Nat Rev Dis Primers. 2017;3:17011. doi:10.1038/nrdp.2017.11
3. King B, Ohyama M, Kwon O, et al. Two phase 3 trials of baricitinib for alopecia areata. N Engl J Med. 2022;386(18):1687-1699. doi:10.1056/NEJMoa2110343
4. Arenas-Ramirez N, Woytschak J, Boyman O. Interleukin-2: biology, design and application. Trends Immunol. 2015;36(12):763-777. doi:10.1016/j.it.2015.10.003
5. Trotta E, Bessette PH, Silveria SL, et al. A human anti-IL-2 antibody that potentiates regulatory T cells by a structure-based mechanism. Nat Med. 2018;24(7):1005-1014. doi:10.1038/s41591-018-0070-2