Korea Drug Development Fund (KDDF) is helping turn cutting-edge science into breakthrough cancer treatments. With a budget of $1 billion, KDDF has funded 162 drug development projects, helping its portfolio companies strike licensing deals worth $9.1billion and bring a medicine to the global market. KDDF, a government-funded organization, has spent the past 9years supporting people at each step of the drug development process, from academics aiming to translate scientific advances into clinical candidates to established biopharma companies seeking global partners. Along the way, KDDF has reviewed 590 proposals and backed 162 programs.
Of those programs, 46 have been the subject of licensing deals, including 18 agreements involving global companies. KDDF success stories include the 2018 oncology deal that granted Janssen global rights to Yuhan’s lazertinib and a 2019 deal for the European rights to SKBiopharmaceutical’s antiepileptic drug cenobamate.
Fifty-one KDDF-backed anti-cancer programs are in development in Korea. Here, we look at three cancer programs in KDDF’s portfolio.
IntoCell has improved two key components of antibody–drug conjugates (ADCs) to create new, better treatments for solid tumors such as breast and lung cancer.
The first breakthrough involved the linker that connects targeting antibodies to cytotoxic payloads. Through the discovery of a new self-immolative group, IntoCell created a linker that can be attached to toxins with phenolic and non-phenolic functional groups. That advance led to the development of benzodiazepines that are much more soluble than molecules that share similar chemical structures.
IntoCell has combined its linker and payload in an anti-B7-H3 ADC. B7-H3 is an immune checkpoint. Notably, B7-H3 expression inversely correlates with that of PD-1, the most commonly targeted immune checkpoint, creating the potential for dual therapy.
Preclinical tests show that the ADC binds to B7-H3 on cancer cells with high affinity and rapidly releases its payload, resulting in antitumour activity in mouse models of breast, colon and non-small-cell lung cancer. IntoCell is now running investigational new drug (IND)-enabling studies while looking for partners interested in licensing its B7-H3 ADC and other technologies with different cell binding modalities such as fusion albumins.
KDDF’s achievements. Through its portfolio of companies KDDF has achieved a number of major milestones in its evolving history. FDA, Food and DrugAdministration;MFDS,Ministry of Food and Drug Safety; ODD, orphan drug designation.
CellBion is applying linker technology to a different modality, namely radiopharmaceuticals that target prostate-specific membrane antigen (PSMA).
Anti-PSMA radiopharmaceuticals typically use amide bonds and a long linker to connect the ligand and chelator. However, enzymes can break the bonds, causing side effects.
Those problems led CellBion to create a shorter linker that connects the ligand and chelator with- out the use of amide bonds. These diagnostic and therapeutic radiopharmaceuticals, 177Lu-DGUL and 68Ga-NGUL, appear to have better drug-like proper- ties than other anti-PSMA products.
In tests in mice, CellBion’s diagnostic PET imaging compound, 68Ga-NGUL, was stable in blood, readily taken up into tumors and quickly excreted. A preliminary clinical trial in metastatic castration- resistant prostate cancer provided early evidence of safety and efficacy in humans.
CellBion plans to build on its progress by filing an IND with the Korean FDA. Based on data generated to date, CellBion thinks 177Lu-DGUL may have superior efficacy and fewer side effects, resulting in improved survival and quality of life for cancer patients.
ImmuneOncia also aims to improve on a promising but flawed class of cancer candidates, anti-CD47 antibodies. Cancer cells use CD47 to protect them- selves from immune attack. By blocking the signal, researchers hypothesized that they could help the immune system destroy tumors.
However, the presence of CD47 on normal host cells including red blood cells has caused antibodies against the target to trigger adverse events such as anemia. To avoid side effects, ImmuneOncia developed a CD47-targeting drug that has affinity that does not cause hemagglutination, while keeping the efficacy profile.
That therapy, IMC-002, showed a similar effi- cacy profile and superior safety/pharmacokinetic profiles in preclinical tests to competitor agents. ImmuneOncia is planning an IND filing to test the drug in humans in the first half of 2020 in the USA. IMC-002 is part of ImmuneOncia’s pipeline of immune checkpoint modulators. Lead asset IMC- 001, an anti-PD-L1 therapy, is entering a multi- regional phase 2 study. Other candidates, including bispecific antibodies, are in earlier development. ImmuneOncia sees synergies in its pipeline and is open to partnering opportunities, including R&D collaborations and business alliances.
A track record of success
KDDF thinks IntoCell, CellBion and ImmuneOncia are poised to join its list of successes. That list now includes an approval from the US FDA, which cleared SK Biopharmaceuticals’ anti-epileptic drug cenobamate in 2019. The approval further validated Korean science and KDDF’s model, which collec- tively are making innovative, first-in-class rugs available for licensing by global companies.
Business Development Team
Korea Drug Development Fund
Tel: +82 2 6379 3069