Recently disclosed initiations of first-in-human studies include assets in development by four private US biotechs – Eikon Therapeutics, ArsenalBio, Iambic Therapeutics and Strand Therapeutics – that together raised nearly $1bn from venture financiers over the past two years.
Elsewhere, the latest clinicaltrials.gov listings reveal cell therapies using monocytes, NK cells and an armed Car-T approach, as well as SpringWorks’ Hippo pathway inhibitor. The list is also notable for including two assets that use small molecules to hit PD-L1 and HER2, targets usually associated with monoclonal antibody approaches.
The HER2 inhibitor is Iambic’s lead asset, and is coded IAM1363. Iambic closed a $100m series B round last October, and its first-in-human study, in patients with HER2-positive cancers, is scheduled to begin this month.
The oral PD-L1 inhibitor, meanwhile, is CS2346, and belongs to the Chinese company Chipscreen. Small-molecule PD-(L)1 blockade is an intriguing area but progress has proved elusive. One of the key current players is Incyte, whose pipeline includes the PD-L1 inhibitors INCB99280 and INCB99318; Evercore ISI analysts say investors ascribe minimal value to this programme.
Private
The other private company-owned assets going into first-in-human studies are Strand’s IL-12-expressing mRNA STX-001, ArsenalBio’s bispecific Car-T AB-2100, and Eikon’s PARP1 inhibitor EIK1003.
Selective PARP1 blockade has attracted Gilead, AstraZeneca and Merck KGaA; Eikon pulled off a spectacular $518m series B round in January 2022, before recruiting as chief executive Roger Perlmutter, the head of Merck & Co’s research lab, the following year.
ArsenalBio, the recipient of $220m of private investor money in September 2022, reckons it can increase Car-T cells’ specificity and potency by “and” logic gating. Thus AB-2100 is activated on binding to PSMA only in the presence of CA9 (carbonic anhydrase IX), which it says is expressed at a high level in renal cell carcinoma.
Four other cell therapies appear in the latest list of clinical entrants. Carisma Therapeutics’ lead focus is on Car-engineered macrophages, but it’s now going clinical with CT-0525, a Car-monocyte that targets HER2. Nuwacell is progressing unmodified NK cells, while Zhongke Qiyuan has a T-cell receptor approach targeting HBV,
And ASP2802 is an anti-CD20 Car being developed by Astellas’s Xyphos subsidiary. This project’s special feature is the expression of an inert form of NKG2D, allowing its activation only in the presence of a so-called bispecific Micabody comprising an NKG2D-exclusive ULBP2-based ligand fused to an antigen-targeting MAb, and Astellas calls this approach Convertible Car.
Hippo
Targeting the Hippo signalling pathway has proved disappointing for Ikena, but nevertheless SpringWorks is pressing ahead with its contender, the pan-Tead inhibitor SW-682.
Finally, now that Pfizer’s $43bn takeover of Seagen has closed, and some early castoffs have been revealed, one asset that is going forward is SGN-35C. Like Seagen’s blockbuster Adcetris this targets CD30, but instead of monomethyl auristatin E it uses a topoisomerase I inhibitor payload.
Recently disclosed first-in-human studies*
