HM16390 / Hanmi - LARVOL DELTA

Hanmi Pharmaceutical also presented the clinical research background, design, and progress of HM16390. (Chosun Biz) - "The global phase 1 trial is currently in the dose-escalation part of the monotherapy cohort, and the company plans to expand to a combination cohort with Keytruda in the first half of next year."

Trial status • Oncology • Solid Tumor

Hanmi Pharmaceutical presents HM16390 data showing enhanced efficacy and safety (Chosun Biz) - "Hanmi Pharmaceutical said at the conference that it identified a mechanism by which HM16390, based on its optimized IL-2 alpha receptor binding affinity, temporarily and selectively increases regulatory T cells (Treg) in the blood rather than in tumor tissue. Through this, it said it confirmed in a Treg-deficient model the action of mitigating excessive immune responses to reduce systemic toxicity. In another study, compared with a variant lacking IL-2 alpha receptor binding affinity, only HM16390 showed a significant increase in tumor-specific CD8+ T cells (TST), most of which were activated and characterized by PD-1 expression."

Preclinical • Triple Negative Breast Cancer

Phase I Study of HM16390 as a Single Agent and in Combination With Pembrolizumab in Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=292 | Recruiting | Sponsor: Hanmi Pharmaceutical Company Limited | N=215 ➔ 292 | Trial completion date: Mar 2030 ➔ Jul 2031 | Trial primary completion date: Mar 2030 ➔ Jul 2031

Enrollment change • Trial completion date • Trial primary completion date • Solid Tumor

HM16390, a long-acting IL-2 analog with enhanced IL-2Rβ binding and optimal IL-2Rα binding, selectively expands tumor-specific T cells, resulting in potent anti-tumor immunity in murine tumor models (SITC 2025) - "Treatment with anti-PD-1 alone or its combination with paclitaxel, a standard-of-care for TNBC, resulted in only marginal tumor control (<40% TGI) without achieving CR. Since these TSTs are key mediators of PD-1 blockade response, combining HM16390 with anti-PD-1 is expected to elicit a synergistic anti-tumor effect. These findings support the potential of HM16390 both as a monotherapy or combined with CPIs, particularly for immunotherapy-resistant tumors."

IO biomarker • Preclinical • Oncology • Triple Negative Breast Cancer • CD8 • IL2

HM16390, a long-acting IL-2 analog with enhanced IL-2Rβ and optimal IL-2Rα bindings, promotes peripheral Treg expansion to mitigate systemic toxicity while preserving potent anti-tumor immunity (SITC 2025) - "In contrast, HM16390 induced a dose-dependent increase in Tregs, which appeared to support a gradual and sustained expansion of CD8+ T cells with improved tolerability.Conclusions Unlike non-alpha variants, HM16390 preserves Treg activation while expanding CD8+ T cells, leading to improved safety and tolerability in both murine and primate models. These findings support fine-tuned CD25 binding as a promising approach to enhance the therapeutic index of IL-2-based cancer immunotherapy."

Oncology • CD8 • IL2

A Phase I, Open-Label, Multicenter, Dose Escalation and Expansion Study of HM16390, as a Single Agent and in Combination with pembrolizumab, in Patients with Advanced or Metastatic Solid Tumors (SITC 2025) - P1 | "The Dose-Expansion Part is designed to evaluate the safety, efficacy, pharmacokinetics, and pharmacodynamics in specific indications informed by preclinical and emerging clinical data. ClinicalTrials.gov Identifier: NCT06724016.BackgroundzTrial Registration ClinicalTrials.gov Identifier: NCT06724016.Ethics Approval This study has been approved by the Institutional Review Board at each investigational site."

Clinical • Combination therapy • Metastases • Oncology • Solid Tumor • IL2 • IL2RA

Identifying predictive biomarkers for HM16390, a novel long-acting IL-2 analog, by analyzing single-cell and bulk transcriptomic data of immune checkpoint inhibitors treated patients (SITC 2025) - "Interestingly, both markers reflect the critical role of IL-2 binding to the CD25 receptor on T cells, these findings suggest the importance of CD25 engagement in immunotherapy. Their clinical utility will be further evaluated in a clinical trial of HM16390, whose defining feature is its optimal affinity for IL2Rα, along with a strong enhancement in IL-2Rβ binding."

Biomarker • Checkpoint inhibition • Clinical • IO biomarker • Hematological Malignancies • Oncology • IL2 • PD-1 • STAT5

Hanmi Pharm, MSD to test immune-activating Keytruda combo in phase 1 (Korea Biomedical Review) - "Hanmi Pharmaceutical is teaming up with MSD (Merck & Co. in the U.S. and Canada) to launch a phase 1 trial testing its experimental immune-activating drug HM16390 alongside Keytruda (pembrolizumab) in patients with solid tumors, including metastatic melanoma and renal cell carcinoma."

Commercial • Melanoma • Renal Cell Carcinoma

Hanmi Pharmaceuticals, Next-Generation IL-2 Anticancer Drug Clinical Trial Patient Recruitment…Phase 1 to be Completed in 2030 [Google translation] (Nate) - "According to the industry on the 24th, Hanmi Pharmaceutical has started recruiting patients for the HM16390 phase 1 clinical trial....This clinical trial is the first to administer HM16390 to humans, targeting 215 patients with solid cancer. The primary evaluation index is the occurrence and characteristics of dose-limiting toxicity (DLT) according to the first cycle of drug administration....The phase 1 clinical trial to administer HM16390 to humans for the first time is expected to be completed in 2030."

Enrollment open • Trial completion date • Solid Tumor

Dose Escalation and Expansion Study of HM16390 in Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=215 | Recruiting | Sponsor: Hanmi Pharmaceutical Company Limited | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Oncology • Solid Tumor

Dose Escalation and Expansion Study of HM16390 in Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=215 | Not yet recruiting | Sponsor: Hanmi Pharmaceutical Company Limited

Metastases • New P1 trial • Oncology • Solid Tumor

Synergistic tumor clearing effect of a novel long-acting IL-2 analog, HM16390, in combination with immune checkpoint inhibitors in a cold tumor syngeneic animal models (SITC 2024) - "In contrast, daily aldesleukin did not induce significant immune infiltration compared to HM16390, and TIL infiltration on day 8 was similar to that of vehicle...Anti-PD-1 as monotherapy or in combination with paclitaxel exerted only marginal tumor growth inhibition (TGI) against 4T1 tumor...The limited anti-tumor efficacy of another major CPI, anti-CTLA4 (TGI 50% without cured mice), also demonstrated synergism when combined with HM16390 (TGI 90%, more than 40% of mice cured) in 4T1 mice. Conclusions These studies support that HM16390 could be an ideal combination partner for both anti-PD-1 and anti-CTLA4 antibodies, whose mode of actions are considered different, through significant modulation of the TME toward an immune favorable state."

Checkpoint inhibition • Combination therapy • Preclinical • Oncology • Solid Tumor • Triple Negative Breast Cancer • IL2

Favorable safety profile of a novel long-acting IL-2, HM16390, with effective control of systemic toxicities via fine-tuned CD25 engagement in animal models (SITC 2024) - "Conclusions The CD25 binding characteristics within HM16390 was finely tuned to mitigate unwanted toxicity derived from uncontrolled immune cell expansion. The crucial role of CD25 in terms of safety has been demonstrated in rodents and non-human primates, and these findings support HM16390 as a safe and effective immuno-oncology agent."

Preclinical • Oncology • CD8 • IL2 • IL2RA • ISG20

[SITC 2024] Hanmi Pharmaceuticals Confirms Possibility of Combination Use of 'HM16390' for Melanoma and Breast Cancer [Google translation] (Hankyung) - "Hanmi Pharmaceutical presented the results of a study that proved the efficacy of HM16390 using a cold tumor animal model that is no longer effective against immunotherapy...As a result, the TIL CD8 cell ratio in the aldesleukin administration group dropped from 25% on the first day of treatment to 12% on the 8th day of treatment, but the HM16390 administration group increased from 22% to 41% during the same period...In a study that administered HM16390 together with anti-PD-1 immunosuppressants, anti-CTLA4 immunosuppressants, and the cancer killing effect of the combination administration model was more prominent than that of single administration....The survival rate in the CTLA4 monotherapy group was 14.3%, and the HM16390 high-dose monotherapy group was 57.1%."

Preclinical • Breast Cancer • Melanoma • Oncology • Skin Cancer • Solid Tumor

Hanmi Pharmaceuticals, New Drug Clinical Trial to Overcome Limitations of Immune Checkpoint Inhibitors [Google translation] (Health Korea News) - "On the 7th, Hanmi Pharmaceutical received approval for the Phase 1 clinical trial plan (IND) for 'HM16390' from the Ministry of Food and Drug Safety. The trial is to evaluate the dose increase and expansion of 'HM16390' in patients with advanced or metastatic solid cancer."

New P1 trial • Solid Tumor

Hanmi Pharmaceutical applies for US phase 1 IND for innovative anticancer drug ‘HM16390’ [Google translation] (docdocdoc.co.kr) - "Hanmi Pharmaceutical announced on the 3rd that it applied for an clinical trial (IND) to the U.S. Food and Drug Administration (FDA) at the end of last month to enter phase 1 clinical trials for an innovative new immunomodulating anticancer drug (LAPS IL-2 analog, code name HM16390). This is a clinical trial plan to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic characteristics of HM16390 in patients with advanced or metastatic solid cancer."

New P1 trial • Solid Tumor

Hanmi Pharmaceutical “Applies for clinical trials of immunotherapy anti-cancer drugs in the U.S. this month” [Google translation] (Korea Medicare) - "This month, Hanmi Pharmaceutical will apply for a clinical trial with the U.S. Food and Drug Administration (FDA) for 'HM16390', an immunotherapy candidate being developed in-house....'This is Hanmi Pharmaceutical’s second immunotherapy pipeline, which is receiving much anticipation,' and added, 'We plan to submit an clinical trial protocol (IND) to the U.S. this month.'"

IND • New trial • Oncology

[AACR 2024] Hanmi Pharmaceutical HM16390 shows potential in various cancer types (Newsmp) - "Among these, the first abstract of the two posters released on the 8th showed that HM16930 showed 14 times more powerful activity on NK cells and CD8+ T cells than aldesleuki....In addition, in the melanoma (B16F10) mouse model, it showed longer-lasting characteristics after injection, and CD8+ T cells in peripheral blood increased significantly and regulatory T cells increased transiently, which suggests that HM16390 was effective in the expansion of CD8+ T cells....For example, in a renal cell carcinoma mouse model transplanted with RENCA-luc cells, HM16390 was injected at weekly intervals for 4 weeks, resulting in complete tumor regression in 40% to 80% of all treatment groups in a dose-dependent manner....The panc02 tumor synthesis (pancreatic ductal adenocarcinoma) mouse model showed excellent tolerability and dose-dependent antitumor effects, and a complete response was reported in mice administered the highest dose."

Preclinical • Melanoma • Pancreatic Ductal Adenocarcinoma • Renal Cell Carcinoma

The immune-modulation of HM16390, firing up the poor tumor microenvironment to induce a potent anti-tumor efficacy (AACR 2024) - "These modulations culminate in a significant anti-tumor effect and synergies with PD-1 blockade in the B16F10 and PDAC model. Given that both B16F10 melanoma and Panc02 PDAC are recognized as poor immunogenic murine models with low TIL frequency, HM16390 shows promise in modifying the immunogenicity of the TME, thereby activating proper immune responses in preclinical models."

Biomarker • Clinical • IO biomarker • Late-breaking abstract • Tumor microenvironment • Gastrointestinal Cancer • Melanoma • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD8 • GZMB • IFNG • IL2 • IL2RA

HM16390, a novel long-acting IL-2 analog with fine-tuned binding affinities to IL-2 receptor subunits for favorable safety profile, exhibits potent tumor killing effect in the various tumor syngeneic models (AACR 2024) - "Although recombinant human IL-2 (rhIL-2, aldesleukin) produced approximately a 15% objective response rate in patients with renal cell carcinoma (RCC) and metastatic melanoma, its IL-2Rα (CD25)-biased binding and short half-life (t1/2 in human: 13-85 min) require a high dose and frequent dosing interval, leading to systemic toxicity such as vascular leak syndrome (VLS) and cytokine release syndrome (CRS). This indicates a long-term immunological memory response of generated memory cells by treatment of HM16390. In conclusion, HM16390 demonstrates potent and durable anti-tumor activity in various murine tumor models via its enhanced CD122 binding affinity, and incorporated optimal CD25 binding affinity may alleviate systemic toxicity by immunomodulatory role of peripheral Tregs."

Clinical • Late-breaking abstract • Genito-urinary Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Solid Tumor • CD8 • IL2 • ISG20 • STAT5

Hanmi Pharmaceutical seeks to secure exclusive U.S. technology for new non-immune tumor treatment drugs [Google translation] (Health Korea News) - "Hanmi Pharmaceutical is seeking to register a U.S. patent for a new drug for the treatment of non-immune tumors (cold tumors) that do not respond to immune checkpoint inhibitors....As a result of coverage by Health Korea News, Hanmi Pharmaceutical is filing a patent registration process with the United States Patent and Trademark Office (USPTO) for ‘Novel conjugate of immune-stimulating IL-2 analog and preparation method thereof’. It has been confirmed that is in progress....The 'novel immune-activating interleukin 2 analog conjugate' mentioned is presumed to be 'HM16390'..."

Patent • Oncology

Hanmi Pharmaceutical confirms complete response with immunotherapy ‘HM16390’…Enter phase 1 clinical trial next year [Google translation] (Newdaily) - "Hanmi Pharmaceutical announced on the 7th that it participated in the Society of Immunotherapy and Oncology (SITC) held in San Diego, USA from the 1st to the 5th (local time) and presented two research results confirming the differentiated development strategy and efficacy of HM16390 as posters....Based on these research results, Hanmi Pharmaceutical is currently preparing to apply for an investigational new drug (IND) and plans to begin phase 1 clinical trials as early as the first half of next year."

New P1 trial • Preclinical • Oncology

Durable anti-tumor effect induced by a long-acting and ‘beta-intensified’ IL-2 mutein, HM16390, in various immunological conditions (SITC 2023) - "The animals were given once a week of HM16390 via SC or 5 consequence days per week of aldesleukin via intraperitoneal, and monitored tumor growth and survival rate. The mOS was prolonged up to 38 days compared to vehicle (14 days) and CR was observed in up to 22% of the mice at doses ≥17 mg/kg. Conclusions HM16390 demonstrated potent and durable anti-tumor activity in murine models with a wide range of immunogenic states through its IL-2R beta intensified IL-2 agonism."

Genito-urinary Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Solid Tumor • IL2 • IL2RA

A long-acting and Beta-intensified IL-2 analog, HM16390, significantly alters tumors to an immune favorable environment to potentiate PD-1 blockade (SITC 2023) - "Methods B16F10 mice were sacrificed on days 1, 3, and 8 after a single subcutaneous administration of HM16390 or 5 consecutive days via intraperitoneal injections of aldesleukin. Conclusions HM16390 efficiently inhibited tumor growth and prolonged survival rate through the significant increase of tumor-infiltrating cytotoxic lymphocytes. This favorable immune alteration in tumors by HM16390 potentiates anti-tumor effect of PD-1 blockade."

IO biomarker • Oncology • CD8 • IFNG • IL2

Hanmi Pharm to unveil new drug pipelines at AACR 2023 (Korea Biomedical Review) - "Hanmi Pharmaceutical said it would disclose new drug research projects at the upcoming annual meeting of the American Association for Cancer Research (AACR 2023) in the U.S....The new pipelines that Hanmi Pharmaceutical will unveil at the AACR include LAPSIL-2analog (HM16390), EZH1/2 dual inhibitor (HM97662), SOS1 inhibitor (HM99462), YAP/TAZ-TEAD inhibitor, mRNA anti-cancer vaccine, and PD-L1/4-1BB BsAb (BH3120)....On April 17, Hanmi is to disclose the results of its preclinical candidate BH3120....Beijing Hanmi Pharmaceutical and Hanmi plan to submit a phase 1 investigational new drug application to the U.S. FDA within this month."

Clinical data • IND • Preclinical • Oncology