Alumis Files for Nasdaq IPO with $529M Raised in 3 Years on China-Originated TYK2 Inhibitor ESK-001

On June 7, 2024, Alumis’s Nasdaq IPO application was accepted.

Alumis, based in California, USA, was incubated and established by Forsite Labs in 2021. Its investors include prominent firms such as Foresite Capital, AyurMaya, Samsara BioCapital, venBio Partners, Lilly Asia Ventures, and BridgeBio Capital.

Just three months ago, Alumis completed a $259 million Series C financing round, setting a new record for the largest funding amount raised by a biotech startup in 2024. The proceeds will support the research and development of its pipeline of oral therapies targeting immune dysfunction and help initiate the Phase 3 clinical trial of its core asset, ESK-001, for psoriasis.

ESK-001 is a highly selective TYK2 inhibitor with best-in-class potential, which Alumis licensed from the Chinese innovative pharmaceutical company Haisco. Notably, at the time Haisco out-licensed TYK2 to Alumis, its global R&D progress ranked third worldwide, trailing only Bristol Myers Squibb (BMS) and Takeda.

By licensing HaiSiKe’s differentiated TYK2 inhibitor, Alumis has raised a cumulative total of $529 million over three years, including a $70 million Series A financing completed in May 2021, a $200 million Series B financing completed in January 2022, and a $259 million Series C financing completed in March 2024, and is poised to enter the capital markets soon. In terms of amount, Alumis’s gains have far exceeded the potential total cost of acquiring the licensed asset.

In March 2021, FL2021-001 (the predecessor of Alumis) acquired the patents and rights to Haisco’s TYK2 inhibitor for an upfront payment of $60 million, with potential milestone payments totaling $120 million.

Alumis considers ESK-001 a TYK2 inhibitor with differentiated advantages, as evidenced by its selectivity, optimized molecular properties/pharmacokinetics, maximized target inhibition, and improved tolerability.

Alumis recently announced the results of the Phase 2 STRIDE trial of ESK001 in patients with moderate-to-severe plaque psoriasis, demonstrating excellent efficacy.

In terms of efficacy, after 228 patients with psoriasis were randomly assigned to receive one of five doses of ESK-001 or placebo for 12 weeks, all treatment groups achieved the primary endpoint of PASI 75 and key secondary efficacy endpoints, demonstrating a clear dose-dependent response.

In terms of safety, no treatment-related serious adverse events occurred in the treatment group, and the incidence of adverse events (AEs) was comparable to that in the placebo group.

Furthermore, open-label extension (OLE) studies demonstrated that 80–90% of patients in the ESK001 maximum dose group (40 mg twice daily) achieved PASI 75 response at Week 16.

Alumis plans to advance the Phase 3 trial of ESK-001 for the treatment of moderate-to-severe plaque psoriasis in the second half of 2024, while supporting two ongoing Phase 2 clinical trials for systemic lupus erythematosus and non-infectious uveitis.

Currently, Haisco has received a $60 million upfront payment and the first milestone payment ($20.66 million out of $37 million; the listed company holds approximately 55.84% equity in FT Group). In addition, with the initiation of Phase III clinical trials for ESK-001 in the second half of this year, Haisco is expected to receive the second milestone payment (approximately $12.8432 million).

Alumis’ second drug candidate, A-005, is a CNS-penetrant allosteric TYK2 inhibitor for the treatment of neuroinflammatory and neurodegenerative diseases. The company initiated the Phase 1 program for A-005 in healthy volunteers in April 2024 and expects to report preliminary results by the end of this year.

TYK2 can be described as one of the hottest targets in the field of autoimmune diseases today.

In addition to Alumis’s substantial financing, Sudo Biosciences, a TYK2-focused developer, announced in January 2024 that it had raised $147 million in its Series B funding round. Myrobalan Therapeutics, another company targeting TYK2, secured $24 million in Series A financing in January 2023.

TYK2 is a member of the JAK kinase family. The JAK family comprises four members: JAK1, JAK2, JAK3, and TYK2. As core components of the JAK-STAT signaling pathway, JAK inhibitors have long been a key focus of intense competition among major pharmaceutical companies.

Currently, more than ten JAK inhibitors have been approved for marketing worldwide. Based on selectivity, marketed products can be broadly categorized into two generations: pan-JAK inhibitors and highly selective JAK inhibitors. While the former offers a broader therapeutic window by inhibiting multiple targets, it is associated with significant off-target effects and unavoidable toxicity. The latter generation features enhanced selectivity; compared to first-generation JAK inhibitors, it demonstrates significantly reduced risks of cardiovascular events and infections, yet it remains subject to the FDA’s boxed warning.

Developing JAK inhibitors with higher selectivity and reduced off-target toxicity has become a new frontier for pharmaceutical companies to compete in R&D capabilities, with TYK2 emerging as a key breakthrough target.

From a target perspective, unlike the other three members of the JAK family, TYK2 has minimal impact on other cytokines when regulating cytokines such as IL-23, IL-12, and type I interferons (IFNs). Therefore, inhibiting TYK2 can reduce the side effects associated with the inhibition of other JAK family members.

Currently, there is only one TYK2 inhibitor on the market: Sotyktu (deucravacitinib) from Bristol Myers Squibb (BMS), which was approved by the FDA in September 2022 for the treatment of patients with moderate-to-severe plaque psoriasis. Notably, deucravacitinib is the first JAK inhibitor without a black box warning, offering a new solution to the toxicity concerns associated with JAK inhibitors. Sotyktu generated $170 million in revenue in 2023, and BMS projects that its annual sales will exceed $4 billion by 2030.

The market launch and rapid uptake of deucravacitinib have also spurred enthusiasm within the industry and among major pharmaceutical companies for TYK2 inhibitors.

In December 2022, the TYK2 therapeutic arena witnessed a blockbuster deal: Takeda and Nimbus Therapeutics entered into a collaboration worth up to $6 billion for TAK-279 (formerly known as NDI-034858), sending shockwaves through the industry. The development of TAK-279 was informed by BMS’s deucravacitinib, demonstrating superior in vitro selectivity.

The initial commercial success of BMS’s Sotyktu and Takeda’s substantial investment have endowed TYK2 with significant financial promise. The blue-ocean market for TYK2 is gradually unfolding. The global psoriasis drug market is projected to expand further to approximately $40 billion by 2028. If TYK2 inhibitors can continue to demonstrate efficacy, long-term safety, and sustained clinical benefits through large-scale clinical trials, the existing psoriasis indication alone would suffice to position TYK2 as a potential golden target.

References:

“The Next Lucrative Target Emerges: Could the Best-in-Class Come from China?” – VCBeat

"Chinese-Made Molecules Go Global: $529 Million in Financing and IPOs" — VCBeat