RMB 9.9 Billion: Two Small-Molecule New Drugs from Chengdu Go Global

On June 23, Haisco announced that it had entered into an exclusive licensing agreement with Nuvectis, granting Nuvectis the exclusive rights to develop, manufacture, and commercialize the HSK42360 project (a BRAF inhibitor) worldwide, excluding the Greater China region, as well as the exclusive rights to develop, manufacture, and commercialize the HSK39297 project (a CFB inhibitor) globally, excluding Greater China, Southeast Asia, and India.

As part of the consideration for the out-licensing transaction, Haisco will receive licensing fees from Nuvectis for the HSK42360 and HSK39297 projects (including a $40 million upfront payment and near-term milestone payments, plus up to $1.421 billion in additional milestone payments) as well as sales royalties (with a total collaboration value of $1.461 billion, approximately RMB 9.907 billion).

In the first half of this year, licensing activities among domestic pharmaceutical companies were intensive. Leading enterprises continued to roll out differentiated, source-innovative pipelines, while homogeneous follow-on molecules gradually lost their appeal to overseas buyers. In this transaction, Haisco bundled its next-generation BRAF-targeted therapy and late-stage complement factor B inhibitor, targeting two blue-ocean markets: central nervous system solid tumors and complement-mediated kidney diseases, respectively.

This dual-track licensing deal covering both oncology and autoimmune indications serves as direct proof that domestically developed small-molecule drugs, distinguished by unique molecular mechanisms and robust clinical data, are continuing to attract bets from overseas listed biotech firms and global capital.

HSK42360, one of the assets in this transaction, is Haisco's self-developed next-generation small-molecule BRAF paradoxical breaker.

Traditional dabrafenib and encorafenib inhibit BRAF monomers, which readily leads to the formation of BRAF dimers post-administration, resulting in paradoxical sustained pathway activation and rapid induction of acquired resistance. Consequently, long-term combination with MEK inhibitors is required in clinical practice, yet adverse effects such as cutaneous squamous cell carcinoma cannot be completely eliminated.

HSK42360's innovative molecular design simultaneously inhibits BRAF V600X mutations and blocks BRAF dimerization, thereby overcoming acquired resistance to first-generation BRAF inhibitors in various tumors. It also demonstrates superior blood-brain barrier penetration, addressing unmet clinical needs in primary gliomas and brain metastases.

In terms of clinical progress, Phase I dose-escalation data for HSK42360 demonstrated that monotherapy achieved durable tumor shrinkage in patients with relapsed disease following prior failure of BRAF/MEK inhibitor therapy. The objective response rate exceeded 40% in high- and low-grade gliomas, and broad-spectrum antitumor activity was observed across BRAF-mutant solid tumors, including non-small cell lung cancer (NSCLC), thyroid cancer, and colorectal cancer.

In terms of the market, currently approved products fail to effectively cover central nervous system (CNS) tumors, and there has long been a lack of effective monotherapy regimens for BRAF-mutant solid tumors in the CNS. HSK42360 carves out a niche incremental market by leveraging its dual differentiated advantages.

Another pipeline asset, HSK39297, is a selective small-molecule inhibitor of complement factor B (FB), targeting the mechanism of excessive activation of the alternative complement pathway for the treatment of complement-mediated autoimmune diseases such as paroxysmal nocturnal hemoglobinuria (PNH), IgA nephropathy, and lupus nephritis.

Currently, the mainstream global treatment for PNH primarily relies on injectable C5 inhibitors, which require frequent administration and result in poor patient adherence. Novartis' iptacopan is the only approved oral CFB inhibitor, but it requires twice-daily dosing, imposing a higher long-term medication burden. HSK39297 enables once-daily oral administration, offering a clear clinical advantage in terms of dosing convenience.

More importantly, two pivotal Phase III clinical trials in PNH have fully validated the efficacy advantages: in treatment-naïve patients, the therapy significantly increased baseline hemoglobin levels and substantially reduced transfusion requirements compared with eculizumab; in the refractory patient cohort who had failed C5 inhibitor therapy, it also consistently improved anemia-related parameters.

Currently, this pipeline is leading domestic competitors in progress. The New Drug Application (NDA) for the PNH indication has been submitted to the NMPA, while Phase III trials for IgA nephropathy and Phase II trials for lupus nephritis are advancing concurrently. Industry analysts project that the combined global market size for PNH and IgAN will exceed $20 billion over the next decade. Long-acting oral CFB inhibitors are poised to gradually replace injectable formulations, becoming the mainstream therapeutic regimen.

Overall, the simultaneous overseas licensing of the HSK42360 and HSK39297 pipelines represents a bundled deal. As these two pipelines belong to distinct therapeutic areas—oncology and autoimmune diseases, respectively—they do not compete for R&D or commercial resources. This bundled divestment model creates mutual benefits for both parties involved.

For Nuvectis, the two pipelines align with its dual-track strategy in oncology and immunology, addressing gaps in its existing portfolio. For Haisco, the regional rights retention strategy allows it to secure emerging markets with large populations, such as Greater China and Southeast Asia. Leveraging its comprehensive domestic clinical and commercialization teams, Haisco can independently drive local launches, while overseas clinical development and capital operations are handled by specialized international biotech firms, thereby achieving efficient division of R&D resources between domestic and global markets.

The companies involved in this collaboration are complementary in terms of resources and market focus.

Nuvectis, the transferee, is a NASDAQ-listed clinical-stage biotech company whose core strategy focuses on two precision therapy sectors: oncology and complement immunology. It boasts a comprehensive team dedicated to overseas clinical registration, multi-center trial operations, and commercialization preparation.

The company's current pipeline is primarily composed of early-stage targeted oncology drugs and lacks mature clinical assets in the complement immunology sector. The simultaneous introduction of two candidate molecules from distinct disease areas will rapidly enhance the pipeline's therapeutic coverage. Meanwhile, as a publicly listed company with robust access to secondary market fundraising, it has secured financing provisions within the agreement to ensure adequate funding for large-scale overseas clinical development of both pipelines.

Haisco, the licensor, started as a specialty generic drug company and has undergone a comprehensive transformation into an innovative drug developer over the past decade. It has established five complete pipeline matrices in anesthesia and analgesia, oncology, autoimmune diseases, metabolism, and respiratory diseases. Haisco possesses full-chain independent R&D capabilities, from hit compound screening, molecular optimization, and formulation development to Phase III clinical trials, eliminating the need for heavy reliance on external CROs for core molecular modification.

More notably, since the beginning of this year, Haisco has completed four major overseas licensing deals:

In January, Haisco licensed its respiratory pipeline HSK39004 to AirNexis, with a total collaboration value of up to $1.063 billion; in April, it reached a partnership with AbbVie for its analgesic Nav1.8 pipeline, worth up to $745 million; in early June, it entered into an innovative drug R&D collaboration with Eli Lilly across multiple disease areas, with a potential total consideration of up to $3.054 billion; coupled with the current $1.461 billion dual-pipeline transaction with Nuvectis, the potential total value of its cross-border collaborations within the year exceeds $6 billion.

Haisco's high-frequency licensing activity is no accident; it is fundamentally underpinned by three core R&D advantages.

First, its pipeline strategy avoids homogenized competition around crowded, high-profile targets, prioritizing less competitive niche segments such as central nervous system (CNS) tumors and long-acting complement inhibitors. Each candidate molecule is assigned clear clinical differentiation metrics, thereby enhancing valuation for overseas licensing deals from the outset.

Second, it has established a comprehensive supporting technology system for small molecules, with in-house capabilities in crystallography, oral formulation development, and pharmacokinetic optimization, resulting in molecule iteration speed and clinical translation efficiency that lead the industry.

Third, its licensing team employs a tiered strategy to precisely match partners: collaborating with large multinational pharmaceutical companies on multi-target platform joint development, and bundling mature clinical pipelines for mid-sized overseas Biotech firms, thereby maximizing both the upfront consideration per deal and long-term returns.

Furthermore, Haisco's ability to execute high-frequency licensing deals stems not only from the aforementioned R&D and licensing advantages, but also from its intensive R&D investment (with R&D expenses accounting for 24.72% of revenue in 2025), robust pipeline reserves (53 projects under development, including 29 Class 1 innovative drugs), and the financial reinvestment enabled by the steady commercialization of core products such as ciprofol.

From a macro-industry perspective, Haisco's intensive overseas expansion exemplifies the transformation of Chinese pharmaceutical companies. The industry has evolved from early-stage generic manufacturing and follow-on innovation to independent R&D of source-differentiated small molecules. Chinese-made small-molecule drugs are gradually acquiring the core competitiveness to compete on equal footing with global cutting-edge pipelines. Meanwhile, licensing collaborations have upgraded from simple cash-flow generation to long-term strategic partnerships featuring synergistic development through domestic and international clinical and capital resources.

Overall, the licensing landscape for innovative drugs in China has entered a period of concentrated deal realization in recent years, with small molecules, bispecific antibodies, and ADCs advancing in parallel across multiple tracks. The logic employed by overseas pharmaceutical companies for asset selection has undergone a significant shift; pipelines that merely follow existing innovations are no longer sufficient to secure large-scale partnerships. Instead, differentiated pipelines featuring novel mechanisms of action and robust data support have become the preferred acquisition targets for buyers.