Hanmi Using Proprietary mRNA Platform to Develop New Drugs for Refractory Cancer and Rare Diseases


Hanmi Pharmaceutical Group, which declared “Sustainable Innovation Management for a Pharmaceutical Powerhouse” as its management slogan for 2022, recently unveiled a new R&D strategy for this year.

At the 40th JP Morgan Healthcare Conference, Kwon Se-chang, who is in charge of the New Drug Development Division at Hanmi Pharm (co-CEOs Kwon Se-chang and Woo Jong-soo), detailed new R&D plans, which include about 30 new drug pipelines currently under development, on the 13th of January.

During the presentation, President Kwon introduced various pipelines, including Rolontis, a new biologic for treatment of neutropenia, and poziotinib, a first-in-class anticancer drug, which plan to file for marketing approval from the US Food and Drug Administration (FDA) this year. He also presented various new drugs based on the mRNA platform that Hanmi has successfully secured.

Hanmi Pharm is currently working on 30 first-in-class drugs, including 13 for cancer, 8 for metabolic and cardiovascular and renal (CVRM) diseases, 5 for rare diseases, and 4 in other areas. About 600 R&D personnel, accounting for more than 25% of all employees, have been concentrating on these projects.

Hanmi Pharm is pursuing open innovation in partnership with global pharmaceutical companies as well as startups, research institutes, and universities. Four areas with unmet medical needs, such as immuno-oncology, inflammation and fibrosis, rare diseases of the central nervous system (CNS), and novel modalities, have been designated as the focused areas for open innovation.

President Kwon said, “Hanmi Pharm, which has built more than 30 first-in-class drug pipelines in the fields of oncology and rare diseases, will build greater value in the future based on the recently successfully secured mRNA platform. [...] We will do our best so that the R&D results gained by the company over the years will bear fruit in 2022.”

Expect FDA approval for Rolontis and poziotinib in 2022

Hanmi Pharm said that Rolontis and poziotinib are expected to receive FDA marketing approval this year. Spectrum Pharmaceuticals plans to resubmit the Biologics License Application (BLA) for Rolontis to the FDA in the first quarter, and has submitted marketing approval for pozionitib. Hanmi Pharm recently made a large equity investment in Spectrum in expectation of its successful commercialization of the two new drugs.

A clinical trial of HM43239, myeloid kinome inhibitor, which was licensed to Aptose Biosciences, a NASDAQ-listed pharmaceutical company specializing in blood diseases, for KRW 500 billion, is set to kick off this year. HM43239 was designated as an orphan drug by the US FDA in 2018 and by the Ministry of Food and Drug Safety of Korea in 2019. Following that, Phase 1 clinical trials are currently underway in the two countries. Based on the results of these clinical studies, Aptose plans to continue its follow-up studies as soon as possible.

HM43239 was found to be effective in inducing a complete response (CR), characterized by a decrease of bone marrow (BM) blasts to less than 5% and normalization of blood cell counts, in patients who had not responded to existing treatments. Some patients even recovered to a state where autologous hematopoietic stem cell transplantation became possible.

There has also been a steady rise in the potential value of belvarafenib, an anticancer drug for targeted therapy licensed to Genentech in 2016. Currently, Genentech is conducting a global Phase 1b clinical trial to examine the effectiveness of belvarafenibin treating NRAS melanoma.

Its parent company, Roche, has included belvarafenib in a large-scale clinical research project (TPISTRY) that conduct on its selective pipelines. Also, it has been examining its safety and effectiveness as a single agent in 50 solid cancer patients with BRAF mutation 2, 3 and fusion.

During the presentation at the conference, the clinical strategy for the EZH1/2 dual inhibitor (HM97662) was also introduced. Hanmi Pharm has been developing HM97662 for new target anticancer drugs for refractory malignant hematologic cancer and solid cancer. Hanmi Pharm plans to apply for approval of a Phase 1 clinical trial in the next six months, to progress dose escalation and expansion studies within this year.

In the preclinical research, HM97662 have shown promise in inhibiting multiple mutations in relapsed or refractory cancer, EZH2, which is an overexpressed oncogene, as well as EZH1 that complementarily activates.

At the same time, Hanmi Pharm kicks off its spurs in development of new drugs using PENTAMBODY, a bispecific antibody platform developed by Beijing Hanmi Pharmaceuticals. PENTAMBODY is a next-generation antibody technology allowing a single antibody to simultaneously bind to two different targets. It has excellent immunogenicity, stability as well as high productivity, as it is structurally similar to immunoglobulin G.

Currently, Beijing Hanmi Pharm has been conducting research on five bispecific antibody drugs using PENTAMBODY. A Phase 1 dose escalation study on BH2950 (PD-1/Her2 bispecific antibody) with solid cancer patients has been completed based on a joint development partnership with Innovent. Neither dose-limiting toxicity (DLT) nor maximum tolerated dose (MTD) was appeared, and a dose expansion study is currently underway based on the data from the Phase 1 study.

First-in-class drugs for NASH, obesity, diabetes, and other metabolic disorders

LAPSTriple Agonist (HM15211), which simultaneously activates the GLP-1, glucagon, and GIP receptors, has shown powerful effectiveness against fatty liver in NASH patients with liver fibrosis diagnosed by biopsy,in a global Phase 2 clinical trial (P2b). It is expected to lead to the development of a first-in-class drug in the offing.

LAPSTriple Agonist (HM15211) simultaneously activates the GLP-1, glucagon, and GIP receptors. HM15211 has shown its powerful effectiveness against fatty liver in NASH patients with liver fibrosis diagnosed by biopsy in a global Phase 2 clinical trial (P2b). The development of a first-in-class drug is in the offing.

The US FDA has granted HM15211 the fast track status so that it can be developed as a treatment of NASH. HM15211 has also been designated as an orphan drug for the treatment of NASH and other rare diseases such as primary biliary cholangitis, primary sclerosing cholangitis, and idiopathic pulmonary fibrosis. It has also been designated as an orphan drug by the European Medicines Agency (EMA) for the treatment of primary sclerosing cholangitis more recently.

Efinopegdutide, a dual agonist that was licensed to US firm MSD in 2020, is currently being examined in regard to its effectiveness against NASH in a Phase 2a clinical trial. Efinopegdutide is said to have a weight loss effect by simultaneously activating GLP-1 receptors, which facilitate insulin secretion and appetite suppression, and glucagon receptors, which boost energy metabolism.

Efpeglenatide, a GLP-1 receptor agonist, is a new biologic for treatment of diabetes that only needs to be administered once a week. It has been shown to reduce blood sugar, blood pressure, and weight in both low- and high-risk patients with type 2 diabetes.

In AMPLITUDE-O, a large-scale global Phase 3 study carried out in 344 regions in 28 countries, 4,076 patients with type 2 diabetes or cardiovascular disease were administered either 4 or 6 mg of efpeglenatide. Compared to the control group (administered a placebo), the incidence of cardiovascular events and the incidence of kidney disease were 27% and 32% lower, respectively.

It also has proven excellence in reducing the risk for a major adverse cardiovascular event (MACE) and outstanding safety in the renal system. Moreover, it was proven to be the first extendin-4-based GLP-1 receptor agonist to reduce the risk of classical 3-point MACE (nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death). It also exhibited similar glycemic control and superior gastrointestinal (GI) safety to other GLP-1 formulations. Based on the results of the large-scale global Phase 3 clinical trial, Hanmi Pharm is making multi-faceted efforts to develop a first-in-class drug.

First-in-class drugs for rare diseases as new growth engines

Receiving the most orphan drug designations among domestic pharmaceutical companies this year, Hanmi Pharm expects to obtain further achievements in the field of refractory and rare diseases this year.

The company, which has received 18 orphan drug designations from the US FDA, EMA, and MFDS of Korea, is endeavoring to develop treatments for rare diseases such as the short bowel syndrome, congenital hyperinsulinemia, and lysosomal storage diseases.

LAPSGlucagon Analog (HM15136) is being developed as a therapeutic agent for congenital hyperinsulinemia, which occurs in one in 50,000.

It is the world’s first glucagon candidate that needs to be administered just once a week, and addresses the short half-life of glucagon, which promotes glucose synthesisin the body, and its solubility and stability in a bio-similar environment. Currently, its global Phase 2 clinical trial is underway. LAPSGLP-2 Analog (HM15912) is being developed with the aim of dosing frequency of once-monthly, based on excellent stability in the body and effectiveness in promoting the growth of villus cells. A global Phase 2 clinical trial has recently kicked off to check its effectiveness against the short bowel syndrome.

Global open innovation: joint research with universities and new businesses

Last December, Hanmi Pharm signed a license agreement with AffaMed Therapeutics to transfer the rights to sell risuteganib (product name: Luminate) in China. Risuteganib is a new drug for retinal disease developed by Allegro Ophthalmics LLC, an American R&D company specializing in ophthalmology. Hanmi Pharmaceutical made a strategic investment in Allegro Ophthalmics back in 2015. At the time, Hanmi Pharm held the exclusive sales and development rights to the drug in Korea and China.

Hanmi Pharm also started joint research with Dankook University in last June for a new drug targeting resistant lung cancer and established a research center on campus to work together on discovering next-generation lung cancer targets. The company has even signed an agreement with LegoChem Biosciences to jointly research and develop next-generation antibody-drug conjugates (ADC) with the application of the bispecific antibody platform, PENTAMBODY, developed by Beijing Hanmi Pharm.

Not only that, but the company is dedicating itself to global R&D cooperation and to building an R&D network as a means to discover future growth engines.

Expanding areas of development with the proprietary mRNA platform

During his presentation at the conference, Co-CEO/President Kwon revealed that Hanmi Pharm had successfully developed an mRNA platform based on its own R&D capabilities. He explained that the mRNA platform will be used to develop not only a COVID-19 vaccine but also drugs for cancer, metabolic disorders, cardiovascular and renal diseases, and enzyme replacement therapy.

The Hanmi Pharmaceutical R&D Center secured the mRNA platform using raw materials produced by Hanmi Fine Chemical and developed candidate materials that are effective against the recently emerged variants of COVID-19. The company has confirmed that its COVID-19 vaccine candidate (HM72524) has excellent neutralizing effects even against the variants, and it plans to apply for clinical research approval as soon as possible.

Hanmi Pharmaceutical has also begun research on anticancer vaccines and drugs for metabolic diseases, and lysosomal storage diseases based on the mRNA platform.

To expand into the contract development and manufacturing company (CDMO) business, Hanmi Pharm is currently diversifying its Bio Plant in Pyeongtaek into a facility capable of mass-producing mRNA- and DNA-based biopharmaceuticals as well as existing LAPSCOVERY products. The company even concluded a licensing and facility establishment agreement with Zydus Cadila based in India.

Last June, Hanmi Pharm commenced a project to develop next-generation mRNA vaccine platform technology to gain vaccine sovereignty together with ST Pharm, Green Cross and KIMCo (Korea Innovative Medicines Consortium).

The pharmaceutical giant expects that the expertise in mRNA will lead to the development of a wide range of therapeutic agents even after the end of the COVID-19. It also emphasized that mRNA-based therapeutics will become an important pillar of Hanmi Pharm’s new drug pipelines, along with new synthetic drugs and biologic drugs.

“I expect that this year Hanmi Pharm will gain groundbreaking achievements in R&D,” said Co-CEO/President Kwon. He also added, “We will make a leap forward this year by building strong new growth engines for Hanmi Pharmaceutical Group in new fields of innovation, such as mRNA, in addition to obtaining achievements in cancer, rare diseases, and metabolic diseases, through in-house research and open innovation.”

Source: Yageop Sinmun (Pharmaceutical Newspaper)