GT-005

External view of Novartis’ office in Canada iStock, JHVEPhoto For $80 million upfront and the promise of more than $1.2 billion in milestones, Novartis has bought the global rights to develop an oral HDAC6 inhibitor from Chong Kun Dang Pharmaceutical. Pictured: Novartis’ head office in Canada/iStock, JHVEPhoto Novartis on Monday inked a technology export contract with Korean biotech company Chong Kun Dang Pharmaceutical for an early-stage HDAC6 Inhibitor, according to Korea Biomedical Review . Under the agreement, Novartis will make an upfront payment of $80 million and pledge up to nearly $1.23 billion more in development and regulatory milestones. The Korean biotech will also remain eligible to future sales-based royalties, as well as an ongoing technology fee depending on net sales. In return, Novartis will gain the exclusive global rights—except in Korea—to develop and commercialize the investigational small-molecule HDAC inhibitor CKD-510. The candidate in 2021 cleared a Phase I first-in-human study in 87 healthy volunteers and the Korean company appears to be positioning the drug candidate as a potential treatment for Charcot-Marie-Tooth disease , a rare and heritable disease that afflicts the nerves in the limbs. However, a Chong Kun Dang (CKD) official told Korea Biomedical Review that the indication for CKD-510 “has not been specified yet.” In preclinical studies, the candidate has also shown potential against atrial fibrillation, leading to an increase in acetylated alpha-tubulin and better action potential duration, among other key markers of the disease. “Efficacy for various diseases has been confirmed through many clinical and non-clinical studies, and indications will be confirmed through partners in the development process,” according to the company official. Novartis’ contract with CKD comes as the Swiss pharma sheds assets and franchises in an effort to streamline its business. Most notably, Novartis announced in September 2023 that its shareholders had approved the spin-off of the company’s generics and biosimilars division Sandoz—more than a year after plans of the spinout were finalized . The same month, Novartis turned its back on a 2021 partnership with BeiGene to develop the investigational anti-PD-1 antibody tislelizumab for esophageal squamous cell carcinoma and other oncology indications, including hepatocellular carcinoma and non-small cell lung cancer. Novartis in September also discontinued the development of the mid-stage gene therapy GT005, which was being trialed for geographic atrophy secondary to dry age-related macular degeneration. The candidate originally belonged to Gyroscope Therapeutics, which Novartis acquired in December 2021 for $800 million upfront. A month earlier, Novartis dropped another candidate —the anti-TGFβ antibody NIS793 that it was advancing in partnership with Xoma Corporation. Not all of Novartis’ partnerships end in a discontinued drug, however. Last week, the Swiss pharma reported that the endothelin A receptor antagonist atrasentan met its primary efficacy endpoint in the Phase III ALIGN study in IgA nephropathy. Novartis got access to atrasentan when it bought Chinook Therapeutics for $3.2 billion upfront in June 2023. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com .

Novartis inked the acquisition of gene therapy startup Gyroscope Therapeutics in 2021 for up to $1.5 billion to take control of GT005. As Novartis looks to sell off its eye disease unit, a geographic atrophy (GA) program is being discontinued on weak data, shutting down a pipeline of milestone payments related to the 2021 acquisition of Gyroscope Therapeutics. Development of GT005 will be shut down in GA secondary to dry age-related macular degeneration after the independent data monitoring committee conducted an initial benefit-risk assessment on the phase 2 HORIZON program. The committee determined that the overall data did not support continuation of the program. That means a lucrative pipeline of milestone payments will be shut down for Syncona, an investment firm that previously owned Gyroscope Holdings before Novartis’ 2021 buyout. Novartis inked the acquisition of gene therapy startup Gyroscope Therapeutics for up to $1.5 billion to take control of GT005. The deal included $800 million upfront and $700 million in milestone payments. The milestone tap has been turned off with the discontinuation of GT005, according to Syncona. The firm received $442 million when Gyroscope was acquired and had milestone payments valued at 54.5 million pounds sterling ($68.2 million) as of June 30 still outstanding. Syncona will now write off the potential milestone. The decision to discontinue GT005 is “naturally disappointing,” the firm’s CEO Chris Hollowood said, “but we respect Novartis’ decision.” While data were the impetus for this decision, Novartis is looking to offload its larger eye disease ambitions amid a major restructuring that will claim 8,000 staffers. The Swiss pharma is also spinning off its generics unit Sandoz and could sell the ophthalmology and respiratory disease businesses. Besides GT005, Novartis is also working on meds in glaucoma and ocular surface disease. The company divested its “front of eye” ophthalmology assets to Bausch + Lomb in June for $2.5 billion, including approved dry eye disease therapy Xiidra.