Pharma tries to flip the returned out-licensing of new drugs

Hanmi's Poseltinib secures positive results through the Phase 2 study on lymphoma

Yuhan·Daewoong·TiumBio, and Others continue developing…strengthening competitiveness

New drug candidates from Korean pharmaceutical companies, which were previously returned after technology transfer, are now re-entering the clinical stage and proving their potential.

 

Attention is focused on whether these candidates will re-label their past failures and demonstrate technological potential.

 

According to industry sources on July 2, NOBO Medicine and Hanmi Pharmaceutical disclosed the Phase 2 clinical trial results for Poseltinib, a hematological cancer treatment under co-development.

 

These results were presented last month at the International Conference on Malignant Lymphoma (ICML) held in Lugano, Switzerland.

 

Poseltinib Revives after Technology Transfer Return...Targets Unmet Needs in Lymphoma Poseltinib is a Bruton's tyrosine kinase (BTK) inhibitor initially developed by Hanmi Pharmaceutical in 2010 and subsequently out-licensed to Eli Lilly in 2015 for up to US$690 million (approximately KRW 893 billion).

 

BTK inhibitors are drugs that reversibly bind to the protein binding site of the BTK enzyme, which regulates the function of B cells and myeloid cells, thereby inhibiting its catalytic reaction.

 

After in-licensing Poseltinib from Hanmi Pharmaceutical, Eli Lilly conducted a Phase 2 clinical trial in patients with rheumatoid arthritis but discontinued it due to a lack of confirmed efficacy.

 

Poseltinib failed to demonstrate efficacy in clinical trials where key endpoints included improvement in rheumatoid arthritis symptoms and the incidence of drug-related adverse events.

 

Consequently, Lilly returned the technology transfer rights to Hanmi Pharmaceutical in 2019.

 

Hanmi Pharmaceutical signed a joint development agreement for Poseltinib with domestic biotech venture NOBO Medicine (formerly Genome Opinion) in October 2021, entering the hematological cancer treatment market.

 

NOBO Medicine has been conducting investigator-initiated clinical trials for patients with relapsed and refractory Diffuse Large B-cell Lymphoma (DLBCL) using a triple combination therapy combining Poseltinib with Roche's Columvi and BMS's Revlimid at Seoul National University Hospital.

 

The industry discussed the possibility of transitioning Poseltinib and developing it for hematological cancers, such as lymphoma and leukemia.

 

It is because Janssen's BTK inhibitor Imbruvica was already launched as a treatment for mantle cell lymphoma, and sufficient safety and tolerability results had been confirmed for Poseltinib.

 

The recently announced clinical results are from two studies: ▲Relapsed and refractory Diffuse Large B-cell Lymphoma (DLBCL) ▲Relapsed and refractory Primary Central Nervous System Lymphoma (PCNSL).

 

DLBCL is the most common type of aggressive lymphoma, accounting for approximately 30-40% of all non-Hodgkin lymphoma patients.

 

While the remission rate for first-line treatment is high, the prognosis is poor for relapsed or refractory patients who do not respond to existing therapies.

 

Therefore, it has led to a continuous demand for treatments with new mechanisms of action.

 

In the DLBCL trial, the Poseltinib combination therapy with Columvi and Revlimid achieved an objective response rate (ORR), measuring the proportion of patients who had a treatment response, such as tumor size reduction, of 84.1%.

 

The complete response rate (CRR), representing the proportion of patients whose cancer completely disappeared, was 58.5%.

 

In terms of safety, significant adverse events reported included Grade 3 or higher neutropenia (68.7%), cytokine release syndrome (4.8%), and cardiac arrhythmia (3.6%).

 

Roche

For the PCNSL trial, the two companies replaced Columvi with Roche's antibody-drug conjugate (ADC) drug Polivy, an anti-cancer agent.

 

PCNSL is a rare type of non-Hodgkin lymphoma that originates in the central nervous system, specifically in the brain and spinal cord, accounting for the majority of CNS lymphomas.

 

This disease is difficult to treat, has a high recurrence rate, and treatment options are particularly limited in elderly patients.

 

As it frequently recurs even after conventional chemotherapy or radiation therapy, there is a significant unmet medical need for new drug candidates with superior brain penetrability.

 

Clinical results showed that the Poseltinib + Polivy + Revlimid combination therapy had an ORR of 55.6% and a CRR of 33.3%.

 

The median progression-free survival (PFS), the period patients lived without their disease worsening, was 6.3 months.

 

Although the number of enrolled patients was small at 10, these results are considered significant given the challenging indication of central nervous system lymphoma.

 

The median overall survival (OS) has not yet been reached, and the 6-month survival rate was 88.9%.

 

Patients were tracked without treatment discontinuation, and only one case of severe adverse event, neutropenia (11%), occurred.

 

NOBO Medicine explains that Poseltinib, which works by selecting multiple kinases including BTK and TEC, demonstrates blockade of bypass pathways, high brain penetrability, and a low side effect profile.

 

Yuhan·Daewoong·TiumBio, and Others Continue New Drug Clinical Trials

Yuhan Corp, Daewoong Pharmaceutical, and TiumBio are also continuing clinical trials for their returned drug candidates, aiming for re-licensing or in-house commercialization.

 

Yuhan Corp announced in March that it had received notification of termination of its technology transfer agreement and return of rights for 'YH25724', a MASH (Metabolic Dysfunction-Associated Steatohepatitis) new drug candidate, from Boehringer Ingelheim.

 

In July 2019, Yuhan Corp signed a technology transfer agreement for YH25724 with Boehringer Ingelheim.

 

YH25724 is a dual agonist that simultaneously targets GLP-1 and FGF21, and a technology transfer agreement was signed at the preclinical stage.

 

Yuhan Corp announced its intention to continue developing its MASH new drug.

 

Yuhan Corp stated, "Based on the potential to address unmet medical needs of patients and positive safety results from clinical trials, we are considering continuing the development of this candidate." Daewoong Pharmaceutical is continuing the development of 'Bersiporocin', an idiopathic pulmonary fibrosis (IPF)treatment, which was previously out-licensed to China's CS Pharmaceutical.

 

In March, CS Pharmaceutical notified Daewoong Pharmaceutical of its intent to terminate the contract.

 

Bersiporocin is an anti-fibrotic new drug candidate that inhibits PRS, affecting collagen production, and works by suppressing the excessive production of collagen that causes fibrosis.

 

IPF is a type of interstitial pneumonia characterized by progressive fibrosis of the lung parenchyma.

 

Currently, available treatments offer only limited therapeutic effects, capable only of delaying the disease, thus leaving significant unmet needs.

 

Bersiporocin's Phase 1 clinical trial, conducted in 2022 in Korea and Australia with a total of 162 healthy adults, confirmed its safety and characterized its pharmacokinetic properties, including absorption, distribution, and metabolism in the body.

 

The following year, Daewoong Pharmaceutical received approval for a multinational Phase 2 clinical trial and is evaluating the efficacy and safety of Bersiporocin in IPF patients aged 40 and above.

 

This trial includes patients who are currently receiving or have discontinued approved treatments.

 

TiumBio was notified in March this year by the Italian pharmaceutical company Chiesi of the termination of their contract and return of rights for the respiratory disease treatment development program 'NCE401'.

 

In 2018, TiumBio signed an agreement to transfer NCE401 to Chiesi, along with an upfront payment of US$1 million.

 

NCE401 was being developed as a new drug candidate for respiratory diseases designed to target transforming growth factor-beta (TGF-ß).

 

However, Chiesi reportedly failed to identify a suitable candidate molecule.

 

TiumBio's clinical trials for TU2218, which is produced using the same platform and developed as an anti-cancer drug, are progressing smoothly.

 

TU2218 simultaneously blocks the pathways of TGF-ß and vascular endothelial growth factor (VEGF), both known to hinder immunotherapy activity.

 

This mechanism aims to maximize the efficacy of immunotherapies.

 

TiumBio unveiled the results of its Phase 2 clinical trial for TU2218 in combination with MSD's immunotherapy 'Keytruda' at the American Society of Clinical Oncology (ASCO) meeting held in Chicago last month.

 

The recently disclosed trial represents early cohort results from an ongoing study in patients with head and neck cancer and biliary tract cancer.

 

Clinical results showed that the TU2218 + Keytruda combination therapy resulted in a partial response (PR), where tumor size decreased beyond a certain standard, in 7 out of 11 patients with head and neck cancer.

 

Stable disease (SD), characterized by no significant change in tumor size or condition, was observed in one patient.

 

In the biliary tract cancer cohort, 4 out of 23 patients showed PR, and 7 showed SD.