Innate challenges Pfizer in Nectin-4

The crowded field of Nectin-4 ADCs just got even busier, with the entrance into the clinic of Innate Pharma’s IPH4502. The company claims its project is differentiated from Pfizer’s approved drug Padcev, but now needs to prove this.

The latest listings on clinicaltrials.gov also reveal first-in-human trials for Cogent’s FGFR2/3 inhibitor CGT4859, and Jiangsu HengRui’s mystery CDK inhibitor, among other projects.

Nectin-4

According to OncologyPipeline IPH4502 will become the 10th clinical-stage Nectin-4 ADC when it starts phase 1 at the end of this month. So far the only approved drug of this class is Padcev, which is marketed for urothelial cancer.

However, Innate has its eye on other tumour types including oesophageal, triple negative breast, and non-small cell lung cancers, its latest corporate presentation suggests. The company says IPH4502 hits a different epitope than Padcev, and has a higher bystander effect, which it says could lead to stronger activity in Nectin-4-low tumours.

The Innate project also uses a more fashionable payload, a topoisomerase 1 inhibitor, while Padcev employs an MMAE payload. Still, the most advanced topo1-based Nectin-4 ADC is Jiangsu HengRui’s SHR-A2102, which recently went into phase 3.

CDK and FGFR inhibition

This Chinese group also features in the new clinical listings, in the ever-popular CDK arena. CDK4/6 inhibitors such as Novartis’s Kisqali and Pfizer’s Ibrance are approved, while some groups are looking to selective CDK4 and CDK2 inhibitors, and the likes of Pfizer and Roche are evaluating CDK2/4 combinations. However, Blueprint recently deprioritised its CDK2-specific project, BLU-222.

HengRui isn’t going into specifics about its latest asset, HRS-3802, but it’s notable that the group already has a CDK4 contender, HRS-6209, in phase 2.

Selective FGFR inhibition has also seen activity recently, with Elevar licensing Relay’s FGFR2 inhibitor lirafugratinib in December. Two FGFR inhibitors, Incyte’s Pemazyre and Taiho’s Lytgobi, have US accelerated approvals for cholangiocarcinoma, but are associated with high levels of toxicity – it’s thought these adverse events are associated with hitting the 1 and 4 receptor subtypes.

The latest contender, Cogent’s CGT4859, could therefore avoid these problems by being an FGFR2/3 inhibitor. Tyra Biosciences, meanwhile, has impressed with an FGFR3-specific project, TYRA-300. And a big readout in selective FGFR inhibition is approaching, with phase 3 data on Amgen/Zai Lab’s anti-FGFR2b antibody bemarituzumab in first-line gastric cancer expected in early 2025.

Cytokines continue

Despite various cytokine disappointments, some companies haven't given up here. One is the private Swiss group Bright Peak Therapeutics, which last year dosed the first patient with its PD1/IL18 immunoconjugate BPT567; this study has only just been listed on clinicaltrials.gov.

Another private company, Trutino, has just gone into the clinic with a conditionally activated IL-2 project, ODC-IL2, which it hopes could overcome the toxicity linked with recombinant human IL-2, Proleukin. Boehringer Ingelheim has an option to acquire that company, via a deal signed in 2022.

Meanwhile, there are few details about Solve Therapeutics' SLV-154, but it's notable that the private group was founded by the same team that ran VelosBio and sold it to Merck & Co in 2020. 

Recently disclosed first-in-human studies*

Note: *projects newly listed on the clinicaltrials.gov database between 13 and 17 Jan 2025.