Accurate treatment of lung cancer! Redding Pharmaceuticals/Cullinan Oncology achieves exclusive authorization: Next-generation EGFR inhibitor CLN-081 introduced to China!

Zai Lab and Cullinan Oncology recently jointly announced that they have reached an exclusive authorized partnership to promote the development, production and commercialization of CLN-081 in Greater China, including Chinese mainland, Hong Kong, Macau and Taiwan.
Cullinan Oncology is a U.S.-based biopharmaceutical company focused on developing diverse pipelines of transformative tumor-targeted therapies and immuno-oncology therapies for cancer patients.
CLN-081 (formerly TAS6417) is an oral small molecule tyrosine kinase inhibitor (TKI), a next-generation irreversible EGFR inhibitor that selectively targets cells that express EGFR mutations.
currently conducting a phase 1/2a dose increment and expansion study (NCT04036682) is evaluating CLN-081 in different doses (2 oral doses per day) in patients with EGFR exon 20 insertion mutation non-small cell lung cancer (NSCLC) who have previously received platinum-containing chemotherapy or another approved standard therapy.
currently, there are no approved treatment options worldwide for patients with the EGFR Ex20ins mutation.
in this area, the fastest-growing is Johnson and Johnson's dual-specific antibody amivantamab, which filed for listing in the US and EU earlier this month and at the end of the month.
other areas of focus include poziotinib (poziotini, green leaf pharmaceutical rights in China) and TAK-788 (mobocertinib, Takeda), which has been included in the "breakthrough treatment drug variety" by the National Drug Administration's Drug Review Center (CDE) for the treatment of patients with localized advanced or metastasis non-small cell lung cancer (NCLC) who have received at least one systemic chemotherapy in the past.
CLN-081 Chemical Structure (Photo: medchemexpress.com) Under the terms of the agreement, Cullinan Oncology subsidiary Cullinan Pearl will receive an advance payment of $20 million and will be eligible for development, regulatory, sales-based milestone payments of up to $211 million.
addition, Reding Pharmaceuticals will pay Cullinan royalties based on CLN-081's annual net sales in Greater China.
Will be awarded exclusive rights to develop, manufacture and commercialize CLN-081 in Greater China. Dr. Ying Du, founder, chairman and CEO of
Redding Pharmaceuticals, said, "This EGFR exon 20 insertion mutation (Ex20ins) targeted drug in collaboration with Cullinan has the potential to be the best-in-class drug, creating synergies with Reding Pharmaceuticals' existing lung cancer product pipelines and further strengthening our layout in this disease area."
china has one of the highest rates of EGFR mutations in lung cancer, while non-small cell lung cancer with Ex20ins mutations still has a huge unsolvent demand.
looking forward to working closely with Cullinan to bring new hope to these patients at an early time.
, Chief Executive Officer of Cullinan Oncology, said: "Reding Pharmaceuticals is the ideal partner for clinical development and commercialization in Greater China and we are delighted to be working with them to develop CLN-081.
EGFR inhibitors currently on the market have not yet been able to adequately solve the problem of exon 20 insertion mutation.
believe that CLN-081, with its available effectiveness and safety data, can meet the huge untreated treatment needs of patients with this mutation.
look forward to working with Reding to start the development of CLN-081 in China as soon as possible.
" currently, TKI targeted at EGFR mutations has been developed and approved, but these TKIs are largely ineffective for EGFR exon 20 insertion mutations (Ex20ins).
patients with advanced NSCLC who carried EGFR Ex20ins had a medium total lifetime (mOS) of about 9 months, compared with about 40 months for patients with advanced NSCLC with sensitive mutations such as Ex19del and L858R.
, there is an urgent clinical need to develop a new EGFR-TKI that targets Ex20ins mutations but does not affect wild type (WT) EGFR to maximize efficacy and strengthen treatment windows by reducing WT-driven toxicity.
CLN-081 is a new type of oral EGFR inhibitor with activity for Ex20ins mutations.
the drug is a powerful Ex20ins mutation inhibitor that is more selective than WT-EGFR, indicating that its clinical treatment window may be wider than most approved/developing EGFR-TKI.
results of the first human, Phase 1/2a clinical trials presented at the ESMO Virtual Conference 2020 in September (click: Preliminary Safety and Activity of CLN-081 in NSCLC with EGFR Exon 2 0 Insertion Mutations (Ins20) includes data on 22 patients in the Phase 1 dose increment study as of the data cut-off date (September 1, 2020), with a dose range of 30-150 mg and 2 oral doses per day.
data show that CLN-081 has acceptable safety, dose-free toxicity (DLT), no class 3 or above drug-related adverse events, the most common drug-related adverse events include rash and dry skin, and only one case of level 1 drug-related diarrhea was observed.
In this group of EGFR Ex20ins NSCLC patients treated (more than 80% of patients received 2 or more systemic treatment options, including immuno-oncology therapy and targeted therapy), encouraging initial anti-tumor activity was observed at multiple dose levels, including an initial dose level of 30 mg.
22 patients treated, 17 had objective reactions assessed by data cut-off and 5 had not yet reached the initial scan time.
Of the 17 patients with assessable reactions, 6 experienced objective remission (total remission rate ORR-35%), of which 2 confirmed partial remission (PR), 3 partial remissions did not reach confirmed scan time, and 1 case did not have partial remission.
the remaining 11 cases of efficacy were assessed to be stable (disease control rate of DCR -65%), with a range of changes in target lesions ranging from 3% to -21%.
9 of the 11 patients were in stable condition at the data cutoff.
In particular, in 4 patients who had previously received poziotinib and/or TAK-788 (mobocertinib), 2 achieved partial remission (PR, 1 confirmed case, 1 unconfirmed case) and the medium time for treatment in these 2 patients was 5 months (range: 3-8 months).
Poziotinib chemical structure (Photo: selleck.cn) poziotinib is a pan-HER tyrosine kinase inhibitor developed by Korean-American medicine that can effectively inhibit EGFR Ex20ins, which owns the Chinese market.
TAK-788 (mobocertinib) is the next-generation, powerful, selective small molecule TKI developed by Takeda, which targets EGFR and HER2 exon 20 insertion mutations.
notable, TAK-788 (mobocertinib) was awarded breakthrough drug qualification (BTD) by the FDA in April this year and included in the "breakthrough treatment drug variety" by the National Drug Administration (NMPA) Drug Review Center (CDE) in October this year to treat patients with localized advanced or metastasis non-small cell lung cancer (NSCL) who have received at least one systemic chemotherapy in the past.
mobocertinib chemical structure (Photo: medchemexpress.cn) Currently, there is no approved treatment for this particular type of NSCLC.
in Phase 1/2 clinical trials, TAK-788 (mobocertinib, 160mg, oral once daily) showed strong results: the medium progression-free lifetime (PFS) was 7.3 months and the total remission rate (ORR) was 43% (n=12/28).
study, the safety of TAK-788 (mobocertinib) was controlled (n-72), and the most common treatment-related adverse events were diarrhea (85%), nausea (43%), rash (36%), vomiting (29%) and decreased appetite (25%).
In addition, earlier this month and at the end of the month, Johnson and Johnson submitted to the FDA and the European Union EMA, respectively, a listing application for the dual-specific antibody amivantamab (JNJ-61186372, JNJ-6372) for the treatment of metastasis NSCCL patients with EGFR Ex20ins mutations after the failure of platinum-containing chemotherapy.
this marks the first regulatory filing by the European Union and the United States for the treatment of patients with EGFR Ex20ins mutation NSCLC.
approved, amivantamab would be the first treatment specifically targeted at EGFR Ex20ins mutation NSCLC.
amivantamab was also granted breakthrough drug eligibility (BTD) by the FDA in March.
data from the 1st CHRYSALIS Study (NCT02609776) show that in patients with advanced NSCLC with EGFR Ex20ins mutations, amivantamab treatment showed lasting remission: (1) in all assessable patients, the total remission rate (ORR) was 36%, The medium duration of remission (DOR) was 10 months, the clinical benefit rate (≥ partial remission of the disease stabilization ≥12 weeks) was 67% ;(2) and the ORR was 41%, the mesodor was 7 months, and the clinical benefit rate was 72% among the assessable patients who had previously received platinum-containing chemotherapy.