Yuhan Strikes Long-Awaited Lung Cancer Deal Through Huge Janssen Alliance
Executive Summary
Yuhan inks long-awaited, major global license agreement for its novel third-generation EGFR TKI with Janssen, in a $1.2bn deal poised to boost the South Korean firm's ongoing R&D efforts in key therapeutic areas, while Janssen will further beef up its oncology portfolio. But competition with entrenched rival Tagrisso awaits.
Yuhan Corp. has reached a license and co-development agreement with Janssen Biotech Inc. for the South Korean company's novel third-generation EGFR tyrosine kinase inhibitor (TKI) lazertinib, in a massive deal worth as much as $1.25bn in total plus double-digit sales royalties to Yuhan along with the drug's originators.
The move marks another long-awaited mega licensing alliance between South Korean and global pharma firms, and adds to the increasing international recognition of the Korean pharma industry's rising innovative R&D strength.
It comes after a more than two-year absence in large out-licensing agreements by Korean pharma companies, since Hanmi Pharmaceutical Co. Ltd.'s tie-up with Roche in 2016 for the pan-RAF inhibitor HM95573, and is being seen as good news for Yuhan - which had been seeking a global partner for the compound - and the wider Korean pharma industry.
Reflecting longer term upside from the deal, shares of Yuhan surged by their daily limit of 30% in Seoul to close at KRW231,000 ($205) on Nov. 5.
Deal Structure
Under the agreement, Yuhan will receive $50m upfront and milestone payments of up to $1.205bn, plus double-digit sales royalties after commercialization of the drug.
In return, Janssen gains exclusive worldwide rights, excluding South Korea, to develop, manufacture and commercialize lazertinib, with Yuhan retaining development and commercialization rights at home, Yuhan said in a statement.
Korean biotech Oscotec Inc. and its US subsidiary Genosco will also be major beneficiaries, receiving 40% of the proceeds of the new license agreement, including royalties, given that Yuhan originally licensed in the compound from the companies in 2015. Development has also been supported by the Korea Drug Development Fund.
Trial Plans
Janssen and Yuhan now plan to jointly proceed with global clinical trials of lazertinib beginning in 2019, both as a monotherapy and combination therapy for non-small cell lung cancer (NSCLC). Janssen will lead the global clinical trial programs, while Yuhan will conduct the studies in South Korea.
Lazertinib (YH25448/GNS-1480), an oral, potent, highly mutant-selective and irreversible third-generation EGFR-TKI, is able to penetrate the blood-brain barrier (BBB). It specifically targets the activating EGFR mutations Del19 and L858R, as well as the T790M mutation, while sparing wild type; various EGFR mutations are present in about 10-15% of NSCLCs.
The molecule is already being evaluated by Yuhan in a Phase I/II trial as both a first- and second-line therapy in advanced NSCLC, and the hope is to develop it into the best-in-class third-generation EGFR-TKI for patients with advanced T790M mutant NSCLC including brain metastasis.
ASCO Data
At this year's American Society of Clinical Oncology (ASCO) annual meeting, Genosco announced data from the Phase I/II open label, dose-escalation study in advanced EGFR-TKI-resistant NSCLC with or without CNS metastasis, which concluded that lazertinib was well-tolerated with low rates of Grade 3 or higher adverse events, and exhibited robust activity in patients with NSCLC with acquired resistance to EGFR-TKIs, with or without brain metastasis.
“These data are impressive and underscore the potential of lazertinib to be the best-in-class third-generation EGFR-TKI for patients with advanced EGFR T790M mutant NSCLC, including brain metastasis. And importantly, the treatment was well-tolerated with no dose-limiting toxic effects,” said the study's principal investigator Dr Byoung Chul Cho at the time.
“Results indicate that lazertinib compares favorably with results from a similar Phase I/II [AURA1] clinical trial of osimertinib, a currently marketed 3rd generation EGFR-TKI.”
A total of 118 patients (38 in the dose-escalation cohort and 80 in the expansion cohort) with EGFRm advanced NSCLC with acquired resistance to EGFR-TKIs with or without brain metastasis were enrolled in the lazertinib Phase I/II study as of April 20, 2018.
No dose-limiting toxicities were observed up to 320mg and there were no dose-dependent increases in treatment-emergent adverse events. Of the evaluable patients (n=110) with a confirmed response at the date of data cutoff, lazertinib demonstrated promising anti-tumor efficacy signals with a confirmed objective response rate (ORR) of 61% across all dose levels.
Of note, the confirmed ORR in patients with T790M+ was 86% at the lazertinib 240mg dose level and in patients with brain metastasis, the intracranial ORR was 55% across all dose levels
'Promising Complement' To Janssen Portfolio
For Janssen, the new deal marks a continuing beefing-up of its pipeline in oncology, which is becoming an increasingly important priority therapeutic area for Johnson & Johnson along with its more established immunology business, still seen as its top franchise globally. (Also see "J&J Growth Plans Heavy On Line Extensions, Sticking With Immunology And Oncology" - Scrip, 14 Sep, 2018.)
"As a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for patients with EGFR mutations, lazertinib is a promising complement to the Janssen Oncology portfolio. We look forward to studying the potential of this novel agent in both combination and monotherapy approaches as we continue to advance the development of targeted therapies for patients with non-small cell lung cancer," Johnson & Johnson told Scrip in a statement.
According to its website, lung cancer appears to be an area of focus for Janssen. The company is already advancing JNJ-61186372 through clinical development, encouraged by early data from a Phase I trial in advanced NSCLC with the bispecific antibody, which targets EGFR and cMET.
“Further, Janssen continues to progress a pipeline of novel early assets and therapeutic approaches as we are committed to developing innovative treatments that may improve and prolong the lives of people diagnosed with lung cancer, the leading cause of cancer mortality in the world,” added J&J in the statement.
Facing Up To Tagrisso
In terms of the competitive landscape in EGFR mutation-positive NSCLC, the overall segment is fairly crowded, with five EGFR-targeted TKIs now approved across the major markets. A number of generic competitors are also on the way, Hardik Patel, Therapeutic Area Director, Oncology, at Informa's Datamonitor Healthcare told Scrip.
“However, in terms of EGFR-positive patients who also have the T790M mutation, there is really only one product available for these patients, which is Tagrisso [AstraZeneca PLC's osimertinib, as referenced in the ASCO results]. It's estimated that about half of EGFR-positive patients will have the T790M mutation, so there is still an opportunity to gain market share within this segment,” Patel commented.
“But Tagrisso is a very effective drug, and it has been approved for EGFR T790M mutation-positive patients since 2015, so lazertinib will need to demonstrate strong clinical efficacy in order to successfully compete with Tagrisso,” given it is a relative late-comer, he added.
Tagrisso is also being moved into the first-line setting in major markets, most recently in Japan. (Also see "Japan Approval Another Boost For Tagrisso in 1L NSCLC" - Scrip, 21 Aug, 2018.)
While only around 10-15% of NSCLC patients in the US and Europe have EGFRm NSCLC, this proportion rises to 30-40% in Asia, and the secondary EGFR T790M resistance mutation – against which osimertinib is also active – causes resistance to standard EGFR inhibitors in around two-thirds of these.
Such patients are particularly sensitive to treatment with EGFR-TKIs, which act to block the cell signalling pathways that drive tumor growth. About 25% of patients with EGFRm NSCLC also have brain metastases at diagnosis (increasing to approximately 40% within two years of diagnosis),
Yuhan R&D To Speed Up?
Helped by the latest deal, Yuhan should be able to speed up its R&D efforts in key therapeutic areas, including oncology and immuno-oncology. At present, six of the firm's 11 strategic investment projects in new drug development are in oncology, including four in immuno-oncology.
At a recent meeting in Seoul, Moo Young Song, a research scientist at Yuhan, cited the lazertinib lung cancer program as a successful example of external open innovation. (Also see "Korean Pharma Finds Own Way To Collaborative And Open Innovation" - Scrip, 2 Oct, 2018.)
"For us, early stage partnership is the key," he said at the time. "We bring in early-stage compounds from bioventures and add value using our know-how and then license them out to third parties."
Lazertinib was seen as Yuhan's leading novel oncology drug asset with potential to be licensed out to a global pharma partner, and expectations had been increasing since the positive clinical trial results were unveiled at international conferences including ASCO.
From the editors of PharmAsia News.