An unfamiliar name goes after familiar targets

According to OncologyPipeline there are around 35 clinical-stage HER2-targeting ADCs, but this hasn’t put off Baili Pharmaceutical. The Chinese group is about to see its contender, BL-M17D1, enter the clinic.

The company is also beginning human trials of an ADC against another increasingly popular target, DLL3, according to the latest listings on clinicaltrials.gov. Other new entrants include a mystery project from Kumquat Biosciences, a rare oncology foray from Novo Nordisk, and a Car-T therapy from UTC against a novel target, CDH17.

Baili's parent company, Sichuan Biokin Pharmaceutical, filed to float on the Hong Kong stock exchange earlier this month; Baili also has a US subsidiary, SystImmune, which is probably most famous for snagging Bristol Myers Squibb as a partner for its EGFR and HER3-targeting ADC, izalontamab brengitecan.

Now the group is going after HER2, a space dominated by AstraZeneca and Daiichi’s Enhertu. Two Chinese studies of BL-M17D1 are listed on clinicaltrials.gov, one focused on breast cancer and the other on gastrointestinal tumours.

Baili could see less competition for it DLL3 project, BL-M14D1. While interest here has ramped up since the success of Amgen’s T-cell engager Imdelltra, Baili is one of only three players with a DLL3-targeting ADC in the clinic, according to OncologyPipeline.

KRAS crowd

KRAS G12D is another popular target, but Genfleet and Verastem – which partnered last year – reckon they’re doing something different. Their asset, GFH375 (VS-7375), is said to hit GTP-bound (active) and GDP-bound (inactive) forms of KRAS G12D, also known as its “on” and “off” states.

This approach is analogous to that being taken by BridgeBio Oncology Therapeutics in KRAS G12C and pan-KRAS inhibition; that group spun out of its parent company in May. Others, like Revolution Medicines, are targeting the “on” states of KRAS proteins; the currently approved KRAS drugs, Amgen’s Lumakras and Bristol Myers Squibb’s Krazati, target the inactive form of KRAS G12C.

Other companies are looking for less crowded areas. China’s UTC Therapeutics has joined a handful of players aiming at Cadherin-17 (CDH17), with an unnamed Car-T contender. CDH17 is found in the gastrointestinal tract; indeed, the only other clinical-stage Car-T asset against this target, Chimeric Therapeutics’ CHM 2101, is being tested in colorectal and gastric cancers.

Other projects hitting CDH17 include ADCs from Multitude and Torl, and a T-cell engager from Arbele.

Novo’s cancer conundrum

Novo Nordisk is better known for its diabetes and obesity drugs, but its 2021 acquisition of the RNA interference player Dicerna gave it an oncology wildcard: a small interfering RNA against a familiar target, PD-L1.

One question is whether this will provide any advantages over conventional anti-PD-(L)1 MAbs. One advantage could be dosing frequency: siRNAs in other diseases, such as Novartis’s Leqvio, are given just twice a year. Merck & Co’s Keytruda, meanwhile, is dosed IV every three or six weeks, though a subcutaneous version is in the works.

PD-L1 isn’t the only oncology project in Novo’s pipeline: the Danish group is also studying an siRNA against STAT3, but whether it will want to take these assets all the way is another question.

Kumquat mystery

Finally, a mystery project from the private US biotech Kumquat Biosciences could be the result of an April 2024 tie-up with Takeda. No details have been given about KQB198’s mechanism – only that it’s a small molecule being studied in NSCLC and other solid tumours, and is being tested as monotherapy and in combination with Tagrisso.

The Takeda deal covered a “novel” immuno-oncology small molecule. Kumquat is to lead development into phase 1, and Takeda could take over afterwards. Kumquat will receive $130m in “near-term payments”, but the up-front fee wasn’t broken out.

Recently disclosed first-in-human studies*

Note: *projects newly listed on the clinicaltrials.gov database between 15 and 18 Jul 2024.