NeuClone Developing Biosimilars of PD-1 Inhibitors

Sydney, Australia-based NeuClone Pharmaceuticals disclosed that it is actively developing 2 biosimilars that will reference 2 blockbuster programmed death-1 (PD-1) immune checkpoint inhibitors: nivolumab (Opdivo) and pembrolizumab (Keytruda), produced by Bristol Myers Squibb and Merck, respectively.

Pembrolizumab and nivolumab are both used to treat melanoma, lung cancer, head and neck cancer, Hodgkin lymphoma, stomach cancer, liver cancer, and gastric cancers, among others.

PD-1 inhibitors are considered targeted therapies in cancer because they directly address one of the mechanisms of cancer development. When the PD-1 ligand (L) attaches to PD-1 on the surface of cancer cells, it prevents the immune system from destroying the cell. PD-1 inhibitors function by blocking PD-1/PD-L1 interaction and allowing the cell-signaling process to alert the immune system to the presence of the cancer cell, which is then attacked.

The success of treatment with PD-1 inhibitors has led to FDA approvals of their use in multiple types of cancer and has significantly improved outcomes for patients.

"These 2 medicines have helped reshape previous standard-of-care approaches for many cancer patients. Providing affordable biosimilar alternatives is crucial to allow many more patients around the world access to these life changing treatments,” Noelle Sunstrom, CEO and founder of NeuClone, said in a statement.

“Combined global sales of the 2 reference products in 2019 were $19.2 billion and are forecast to reach over $32 billion in 2024,” NeuClone said, citing data from EvaluatePharma.

NeuClone did not announce a timeline for bringing these products to market, nor did it say which markets it would seek for regulatory review and approval. The pembrolizumab and nivolumab biosimilar candidates are currently in advanced preclinical development and are being co-developed by NeuClone and Serum Institute of India, NeuClone’s strategic manufacturing partner. The main patents on both drugs will not expire until at least 2026.

The 2 companies joined forces in June 2014 to develop 10 biosimilar monoclonal antibodies for the treatment of several cancers and autoimmune diseases.

NeuClone’s Other Biosimilars

In addition to its nivolumab and pembrolizumab molecules, NeuClone has disclosed information on 6 biosimilars, including biosimilars for trastuzumab (Herceptin), ustekinumab (Stelara), denosumab (Prolia/Xgeva), palivizumab (Synagis), adalimumab (Humira), and pertuzumab (Perjeta).

NeuClone’s trastuzumab, ustekinumab, denosumab, and pertuzumab molecules are all being developed in conjunction with the Serum Institute.

NeuClone has completed phase 1 testing for its ustekinumab biosimilar (NeuLara) and published the results in April 2020 after beginning the trial in 2019. Ustekinumab is used for the treatment of plaque psoriasis and psoriatic arthritis.

Its trastuzumab biosimilar, used to treat patients with breast, stomach, and esophageal cancers, met primary and secondary end points in a phase 1 trial completed in 2019.

According to NeuClone’s website, its denosumab biosimilar, whose development was announced in 2018, was entered into a phase 1 clinical trial in 2019. Denosumab is used to treat osteoporosis, hypercalcemia, bone cancer, and bone problems in patients with cancer.

Its palivizumab and adalimumab molecules are both in late preclinical development. Palivizumab is used to in the prevention of respiratory syncytial virus infections and adalimumab is used to treat several inflammatory conditions including arthritis, plaque psoriasis, ankylosing spondylitis, Crohn's disease, and ulcerative colitis.

The company announced the development of its pertuzumab candidate in December 2018 but have not disclosed any new information on its progress since then. Pertuzumab is used to treat patients with metastatic HER2-positive breast cancer and neoadjuvant in early HER2-positive breast cancer.