Hanmi-MSD collaborate for R&D

Conducting licensing out·clinical trials

Hanmi entered into a clinical trial collaboration agreement with MSD for its combination therapy containing Keytruda to develop the next-generation IL-2

They have expanded collaboration deals for Keytruda combination therapies to three cases, including BH3120·Tivumecirnon

Trials for efpeglenatide, a MASH candidate licensed-out in 2020, 'going well'

Hanmi Pharmaceutical entered into a clinical trial collaboration agreement with the U.S.-based Merck (MSD) for developing an immune anticancer drug candidate.

 

The clinical collaboration between Hanmi Pharmaceutical (hereafter, Hanmi) and Merck has expanded to three cases.

 

In addition to clinical trial collaboration, Hanmi continues to collaborate with MSD for efforts such as technology transfers.

 

According to pharmaceutical sources on May 20, Hanmi recently signed a clinical collaboration and distribution agreement with MSD to evaluate the combination therapy containing 'HM16390,' a next-generation anticancer drug that is "LAPS interleukin-2 (IL-2) analog," and MSD's anti-PD-1 anticancer drug 'Keytruda (active ingredient name: pembrolizumab).

 

According to the agreement, Hanmi will be responsible for conducting the Phase 1 trial to assess the safety and efficacy of HM16390+Keytruda combination therapy as a clinical trial sponsor.

 

MSD will supply Keytruda used in clinical trials.

 

HM16390 is a next-generation interleukin-based immuno-oncology candidate that activates immune cells.

 

HM16390 induces T-cell proliferation and activation to enhance immune responses within the tumor microenvironment.

 

By increasing the number of tumor-infiltrating lymphocytes (TIL) that respond to immune checkpoint inhibitors in the tumor microenvironment, it is designed to convert 'cold tumors' (with low immune activity) into 'hot tumors' (infiltrated by immune cells) and to maximize efficacy when used in combination with checkpoint inhibitors.

 

'Proleukin' is the only recombinant IL-2 therapy approved by the U.S.

 

Food and Drug Administration (FDA).

 

Still, its use is limited due to the risk of adverse events at high doses.

 

Most IL-2 analogs in development focus on enhancing binding affinity to the IL-2 β-receptor to boost anti-tumor effects, which can trigger excessive systemic immune responses and lead to severe side effects such as cytokine release syndrome.

 

(source: Hanmi Pharmaceutical)

Hanmi has addressed these limitations by finely adjusting HM16390's binding affinity to the IL-2 α-receptor.

 

According to Hanmi, this approach secures safety while maximizing efficacy.

 

In particular, Hanmi is developing HM16390 as a long-acting therapeutic using its proprietary Labsccovery platform technology, enabling once-per-cycle subcutaneous (SC) administration alongside chemotherapy.

 

HM16390 is currently in a multinational Phase 1 clinical trial.

 

Earlier, Hanmi announced at the Society for Immunotherapy of Cancer (SITC) last November that preclinical studies of HM16390 demonstrated complete remission.

 

Keytruda, MSD's immuno-oncology agent, is the world's top-selling pharmaceutical.

 

It is an immune checkpoint inhibitor that blocks the interaction between PD-1 on T cells and PD-L1 on cancer cells, enabling immune cells to attack tumor cells.

 

First approved by the U.S.

 

FDA in September 2014 for malignant melanoma, Keytruda has continuously added new indications.

 

It has over 40 indications to date, including breast, gastric, and lung cancers, making it the checkpoint inhibitor with the broadest range of cancer uses.

 

However, the efficacy of Keytruda is limited to patients whose tumors express high levels of PD-L1.

 

It is known that those with low PD-L1 expression derive minimal benefit.

 

To address this, MSD is actively developing combination therapies to expand the responsive patient population and enhance efficacy.

 

Hanmi expects that combining HM16390 with Keytruda will further improve treatment outcomes.

 

Hanmi and MSD have expanded collaboration deals to three in total.

 

Hanmi also conducts Keytruda combination therapy clinical trials with MSD's PD-L1/4-1BB bispecific antibody candidate 'BH3120' in combination with its oral CCR4 antagonist, 'Tivumecirnon.' BH3120, which is being co-developed by Hanmi and Beijing Hanmi Pharm, is a bispecific antibody immuno-oncology candidate in which a single antibody simultaneously binds to two different targets.

 

It features Hanmi's proprietary Pentambody platform technology, combining an immuno-oncology mechanism that activates immune cells with the target-oncology characteristic of selectively attacking only cancer cells.

 

In particular, Hanmi explains that BH3120 is designed to respond differently to each target, PD-L1 and 4-1BB, thereby enhancing therapeutic efficacy while reducing side effects.

 

Hanmi plans to present the interim results of the Phase 1 clinical trial evaluating the BH3120 and Keytruda combination therapy in the second half of this year.

 

Previously, Hanmi Pharmaceutical reported that in tumor-bearing mouse models refractory to immune-oncology agents, the combination of BH3120 and Keytruda demonstrated tumor growth inhibition that was at least comparable to that observed with a competing pipeline agent (GEN1046).

 

R&D new pipeline: Preclinical trials, Phase 1 Trials, Phase 2 Trials, Phase 3 Trials, Approved (source: Hanmi Pharmaceutical)

Tivumecirnon is an oral immuno-oncology candidate Hanmi acquired from RAPT Therapeutics in 2019.

 

It blocks the CCR4 receptor protein, thereby inhibiting the migration of regulatory T cells that suppress immune responses into tumors.

 

In January, at the ASCO Gastrointestinal Cancers Symposium held in San Francisco, Hanmi presented a poster on the Phase 2, Part 1 results for Tivumecirnon.

 

In collaboration with RAPT and MSD, this trial treated ten Epstein-Barr virus (EBV)-positive gastric cancer patients and achieved an objective response rate (ORR) of 60%.

 

ORR is a key efficacy metric representing the proportion of patients whose tumors have either disappeared entirely or shrunk by a defined amount following cancer treatment.

 

Among these responses, there was one complete response and five partial responses.

 

The median time to response (mTTR) was 2.7 months.

 

The median duration of response (mDOR) was 17.3 months.

 

In Cohort 2, the median progression-free survival (PFS) was 10.4 months.

 

Hanmi explained that the treatment-related adverse events observed among the 20 patients enrolled in the trial were mostly manageable.

 

In addition to its clinical collaboration with MSD, which is focused on Keytruda combination therapy, Hanmi is also maintaining partnerships via technology licensing agreements.

 

For instance, it includes 'efpeglenatide,' which Hanmi licensed to MSD in 2020 in a deal valued at USD 860 million.

 

Efpeglenatide is a dual-action agent that activates the glucagon-like peptide-1 (GLP-1) receptor, which enhances insulin secretion and suppresses appetite, and the glucagon receptor, which increases energy metabolism.

 

Hanmi previously licensed efpeglenatid to Janssen in 2015 for obesity and diabetes indications, regained the rights in 2019, repurposed it for metabolic-associated steatohepatitis (MASH), and successfully licensed it again to MSD.

 

MSD is currently conducting a Phase 2 clinical trial of efpeglenatide.

 

The trial compares efpeglenatide with the comparator treatment, semaglutide from Novo Nordisk, and a placebo.

 

According to a 2023 presentation at the European Association for the Study of the Liver (EASL) in Vienna, data from the Phase 2a analysis showed that at week 24 of treatment, efpeglenatide reduced liver stiffness by 72.7% compared to baseline.

 

This result markedly outperformed semaglutide, which achieved a 42.3% reduction over the same period.

 

Resolution of steatosis without fibrosis worsening and improvement of fibrosis without steatosis worsening are key evaluation endpoints defined by the FDA for NASH therapies.

 

MSD aims to complete the Phase 2 trial of efpeglenatide by December of this year.