Trendy Medicine Bar: The second curve is established, and deep divers enter the deep sea without fear

The most fortunate thing for a Biotech is to make a good drug; the more difficult thing is to prove that the success of the first drug can be copied to the entire platform. This is what we have been emphasizing for so long.

In the past few years, it has not been difficult for the market to understand InnoCare Pharmaceutical Co., Ltd. Orelabrutinib is the clearest anchor: look at the expansion of indications for hematoma, look at medical insurance coverage, look at hospital penetration, look at sales volume, and then hand over part of the valuation to the follow-up pipeline. This framework was once effective enough because the company's business value, R&D resources, and capital market attention revolved around BTK for a long time.

By 2026, this single-line framework is starting to get crowded. Orelabrutinib is still growing, and the depth of hematological tumors has not stopped, but the company's real new amount of information has increasingly appeared outside of hematological tumors.

Soficitinib (ICP-332) met the primary endpoint in the Phase III registration for moderate to severe atopic dermatitis, and subsequently the Phase II part of the Phase II/III study in vitiligo also met the primary endpoint; Fadeucravacitinib (ICP-488) met the primary endpoint in the Phase III psoriasis, while advancing to cutaneous lupus erythematosus and Sjogren's syndrome. On the other hand, the domestic marketing application for orelabrutinib for primary immune thrombocytopenia (ITP) has been accepted, and the global autoimmune development has entered the global Phase III of PPMS and SPMS through Zenas. In the past few years, investments dispersed in different pipelines and different diseases have begun to enter the mid- to late-stage cash-out window at the same time for the first time.

This is also what this semi-annual report is really worth writing about.

In the first half of 2026, the company's total revenue reached 1.14 billion yuan, a year-on-year increase of 55.5%; drug sales revenue was 920 million yuan, a year-on-year increase of 43.2%; in the first half of 2026, the net profit was 240 million yuan, turning a loss into a profit year-on-year. Operating cash flow continued to become positive, and the cash reserve at the end of the period reached 8.43 billion yuan. These numbers ultimately determine how quickly a company can turn R&D into commercialization, but they serve as a "pedestal."

What is more worth asking is: after establishing the basic base of hematoma, whether InnoCare Pharmaceutical Co., Ltd. can develop an independent self-immune product system.

If the answer holds true, the meaning of 2026 will change. It is no longer just a year when orbutinib continues to increase its volume, nor is it just a year when two TYK2s happen to read data at the same time. The company has begun to move from a "Biotech driven by hematoma" to a Biopharma stage "driven by hematoma cash flow, self-immune product group and global clinical development".

The term second growth curve is used so frequently in the pharmaceutical industry that it often loses its meaning. A true second curve must meet at least three conditions: it has clinical value independent of the first product, can form an independent source of income, and is backed by repeatable R&D capabilities. Looking back at InnoCare Pharmaceutical Co., Ltd. according to this standard, dual TYK2 may be more worthy of attention than simply adding another indication for orelabrutinib.

1. Only those who can make their own blood are qualified to talk about the second growth curve.

The R&D ambitions of innovative drug companies ultimately return to cash flow.

In the past, Chinese Biotech could rely on financing to cover research and development. When the primary market flourished, cash consumption did not immediately become a strategic constraint. After the environment changes, there are more and more late-stage clinical trials, larger and larger registration trials, and an increasingly heavy commercialization team. Whether a company can continue to advance multiple Phase III projects increasingly depends on whether it has its own hematopoietic system.

InnoCare Pharmaceutical Co., Ltd. has crossed the most dangerous road. The company will achieve annual profitability for the first time in 2025 and will continue to remain profitable in the first half of 2026. It can be seen that InnoCare Pharmaceutical Co., Ltd.'s revenue does not rely solely on one-time BD revenue, but on recurring product sales. The former can amplify current profits, but the latter determines whether the R&D machine can operate in the long term.

Orelabrutinib remains the most important cash flow generator here. Indications such as first-line CLL/SLL and MZL continue to expand the treatable population. Hospital coverage and sinking capabilities determine how much more mature products can be released. After tanxituzumab and zolecitinib entered commercialization, another change began to occur: the same commercial team no longer only serves one product. For Biopharma, only by sharing market access, medical and sales networks for multiple products can it be possible to gradually turn sales expenses from a mere cost item into a platform asset.

Hematoma research and development itself has not stopped. The BTK+BCL2 regimen composed of orelabrutinib and Mesutoclax is pushing the company from single-drug competition to fixed treatment courses and deep remission. The general direction of global hematoma treatment is already clear: after long-term treatment with single drugs, the industry is looking for deeper remissions, lower MRD and limited treatment courses. InnoCare Pharmaceutical Co., Ltd. owns both BTK and BCL2 assets, which means it has the opportunity to design combination sequencing, ramping methods, MRD assessment and discontinuation strategies within its own system. More importantly, Mesutoclax's head-to-head venetoclax treatment for newly diagnosed AML makes the market more hopeful and full of imagination.

The line of blood remains important, but its meaning in this article has changed. Hematoma is responsible for guarding the first growth curve, and immunity is responsible for finding the second growth curve. The more stable the former, the more qualified the latter is for long-term investment.

Therefore, the final answer to the financial part of the semi-annual report is not "how much money" the company made in the first half of the year, but another question: whether the cash brought in by drug sales and BD, as well as the cash reserves currently held by the company, are enough to support more and more late-stage clinical trials, turning external financing from a survival necessity into a capital allocation tool.

InnoCare Pharmaceutical Co., Ltd. has built this cycle. InnoCare Pharmaceutical Co., Ltd.'s next biggest constraint will slowly shift from "whether there is money to do it" to "which projects are most worth doing." For a company moving from biotech to biopharma, this is often the starting point for real change in the business model.

2. Orelabrutinib gets rid of hematoma, and BTK begins to assume the second role

The value of orelabrutinib is undergoing a migration that is easily underestimated.

BTK's most mature commercial history comes from B-cell malignancies, but BTK has never only existed in tumor cells. B cell receptor signaling, myeloid cells, and part of the innate immune response are all related to BTK, which determines that BTK has the natural possibility of spillover from hematological tumors to autoimmune diseases. In the past few years, many companies around the world have tried this approach, but the selectivity, tissue distribution, central penetration and clinical strategies of different molecules ultimately took them in different directions.

Therefore, when discussing the self-immunization value of orelabrutinib, there is no need to repeatedly compare it one-to-one with a certain BTK company. A more appropriate frame of reference is the overall BTK inhibitors that have established a commercial foundation in the field of lymphoma. Viewed within this framework, orelabrutinib is one of the few mature BTK assets that still puts large-scale autonomous development at its core and has reached the registration or global Phase III stage.

Domestic development has given some anchors. Orelabrutinib continues to accumulate clinical evidence in autoimmune diseases such as SLE, and its marketing application for primary immune thrombocytopenia has also entered the regulatory process. Overseas development is even more radical: multiple sclerosis was handed over to Zenas to promote global development, with the target directly targeting the two progressive diseases of PPMS and SPMS.

What is most worthy of study here is not “a few more indications”, but the change in the role of Orelabrutinib within the company.

During the period of hematoma, it proved that InnoCare Pharmaceutical Co., Ltd. could produce a commercially competitive kinase inhibitor; after entering self-immunity, it began to verify whether the same set of molecular design, translational medicine and clinical development capabilities could be reused across diseases. When a molecule moves from malignant B cells to a chronic immune disease, the treatment goal will shift from rapid suppression of tumor clones to multi-year immune regulation; in addition to efficacy, long-term safety, tissue distribution, patient compliance and chronic disease payment all become more important.

Orelabrutinib is therefore like a bridge. One end is connected to InnoCare Pharmaceutical Co., Ltd.'s most mature hematoma capabilities, and the other end is connected to the company's emerging self-immunization platform.

The importance of this bridge is also that it reduces the difficulty of starting the second growth curve from scratch. The company does not need to wait until the first TYK2 is launched to learn for the first time how to conduct autoimmune clinical trials, how to build an autoimmune medical team, and how to understand the endpoints of chronic diseases. Orelabrutinib has already completed part of its organizational learning ahead of schedule.

If you zoom in further, you will find that self-immunization itself is also becoming the capital center of the global pharmaceutical industry again. In the past decade or so, oncology has absorbed the most innovation resources, and in recent years, large pharmaceutical companies have re-increased their investment in mergers and acquisitions, BD, and internal R&D in the field of immune inflammation. The reason is not complicated: the patient base of autoimmune diseases is large and the treatment courses for chronic diseases are long. Once a drug establishes advantages in safety and convenience, the product life cycle is often longer than that of oncology drugs; at the same time, precision immunology is breaking down the past extensive immune suppression into increasingly clear cells, cytokines and signaling pathways.

This is why InnoCare Pharmaceutical Co., Ltd.’s self-immunity story cannot be limited to orelabrutinib.

BTK is more like the first stepping stone. What really determines whether a company can establish a second product platform is whether it can complete molecular differentiation again on another target and turn this differentiation into indication selection and clinical results.

This brings us to the two TYK2 models.

3. The same TYK2, two structural answers

The double TYK2 of InnoCare Pharmaceutical Co., Ltd. is the most worth unpacking section of the whole article.

The easiest thing to see in the market is the surface: Soficitinib (ICP-332) and Fadeucravacitinib (ICP-488) are both called TYK2 inhibitors, so it is natural to ask why a company wants to produce two small molecules with the same target, and whether there will be internal competition.

The real answer lies in the protein structure.

TYK2 belongs to the JAK family. Simplifying it into a two-stage switch, JH1 near the C-terminal is a catalytically active kinase domain, responsible for the real phosphorylation output; JH2 next to it is a pseudokinase domain, more like a regulator, which determines the conformation of JH1 to enter the working state. Although both pills suppress the TYK2 signal, their impact points are completely different: ICP-332 hits JH1, and ICP-488 hits JH2.

The JH1 route is a direct entry into the "engine". The small molecule occupies the ATP-binding region of the catalytic domain, directly suppressing the kinase activity. Its advantage is that the inhibition can be very strong and the effect can be very direct; the difficulty also comes from this. JAK1, JAK2, JAK3 and TYK2 belong to the same family, and their catalytic domains are relatively conserved. Therefore, when making drugs on JH1, medicinal chemistry must solve a long-term problem: it must be strong enough without suppressing other JAKs too deeply.

The design of ICP-332 falls right on this balance point. In the company's early public pharmaceutical data, ICP-332's inhibitory activity against TYK2 JH1 reaches sub-nanomolar levels, and it still retains a certain activity against JAK1, but its inhibition against JAK2 and JAK3 is significantly weaker; the company has also disclosed that it has about 400 times selectivity relative to JAK2. The 2024 AAD research title even directly describes ICP-332 as a "highly selective oral TYK2/JAK1 inhibitor." Putting these pieces of information together, it can explain its pharmacological properties better than simply writing "highly selective TYK2": it does not pursue the complete elimination of all JAK family signals, but retains a certain JAK1 pathway coverage based on TYK2 as the mainstay, while trying to distance itself from JAK2/JAK3 as much as possible.

This is important for indication selection.

The inflammatory network of atopic dermatitis is not only driven by IL-4 and IL-13; instead, multiple signals related to itch are intertwined with each other, and a considerable part of them are related to both JAK1 and TYK2. For moderate to severe AD, patients and doctors often have very realistic requirements for drugs: skin lesions must be rapid, itching must be rapid, and long-term safety cannot be reduced to the price of traditional pan-JAK. A JH1 molecule that is dominated by TYK2 while retaining a certain amount of JAK1 coverage is theoretically more likely to form a "potent + fast" pharmacological profile.

The current human body data is basically in the same direction as this outline. The AD phase II of ICP-332 was only treated for 4 weeks. The EASI improvement from baseline in the 80mg and 120mg groups reached 78.2% and 72.5% respectively, EASI-75 both reached 64%, and the placebo was 8%; previously disclosed, itching improvement appeared very early. In July 2026, the Phase III registration for moderate to severe AD reached the primary endpoint and multiple secondary endpoints, and the complete effect size still needs to be disclosed later. Vitiligo gave the second PoC: at 24 weeks, the F-VASI improvement from baseline in the 80mg and 120mg groups was 38.8% and 41.2% respectively, while the placebo group was only 2.2%.

If you only look at these two data, it is easy to define ICP-332 as "an AD drug." What is more noteworthy is the company's indication portfolio: AD, vitiligo, prurigo nodularis, chronic spontaneous urticaria, psoriasis, etc., which are obviously concentrated in diseases with a high burden of skin inflammation and itching and which require strong clinical symptom control. The structure does not mechanically determine the indications, but the pharmacological coverage brought by JH1 is obviously isomorphic with the clinical needs of this group of diseases.

Of course, the JH1 route also means that safety must be taken more seriously. The Phase III topline disclosed that no new safety signals emerged, and the market is highly concerned about the safety data released in the future.

ICP-488 takes a different path.

JH2 is a pseudokinase regulatory domain. Compared with the highly conserved JH1 ATP pocket of the JAK family, JH2 provides a space for easier family selection. ICP-488 does not directly compete with JH1's ATP, but specifically binds to the TYK2 JH2 domain and allosterically locks TYK2 in a state that is more difficult to activate. The company's public information shows that ICP-488 has nanomolar inhibitory activity against JH2, but is very weak against JH1. The values here are not in the same experimental system as the JH1 assay. We cannot simply compare "whose IC50 is lower." What is really valuable is that the selection spectra of the two drugs are almost in opposite directions.

This is the most important asset of the JH2 route: cleanliness.

It more intensively cuts off the classic downstream of TYK2, including IL-23, IL-12 and type I interferon signals, while minimizing contact with JAK1, JAK2 and JAK3. For chronic autoimmune diseases that require years or even long-term treatment, this high selectivity has the opportunity to exchange for a wider safety window.

Looking again at the indications for ICP-488, the correspondence between structure and clinical strategy becomes clear.

Psoriasis is one of the most typical IL-23/Th17 axis diseases, and TYK2 is a very direct node on this pathway, so highly selective JH2 inhibition has the most mature biological validation here. At 12 weeks of ICP-488 Phase II, PASI-75 in the 6 mg and 9 mg groups reached 77.3% and 78.6%, PASI-90 reached 36.4% and 50.0%, respectively, and sPGA 0/1 reached 70.5% and 71.4% respectively. In July 2026, the registration phase III further reached the primary endpoint and multiple secondary endpoints, and no new safety signals were disclosed.

More interesting are the second batch of indications: cutaneous lupus erythematosus and Sjogren's syndrome.

Significant type I interferon-related immune abnormalities are present in both diseases. TYK2 happens to be at a critical position for type I IFN signaling. Therefore, the expansion of ICP-488 from psoriasis to CLE and Sjogren's syndrome is not simply copying the business logic of "dermatology sales teams can share". There is also a stronger pathway logic behind it: using a JH2 allosteric inhibitor that is as clean as possible to continuously suppress the IL-12/IL-23/type I IFN group of TYK2-dependent signals to deal with diseases that require long-term immune regulation.

This also explains why the two TYK2s can coexist.

Soficitinib is more like a "bordered broad-spectrum anti-inflammatory small molecule": JH1 strongly inhibits TYK2 while retaining a certain amount of JAK1 coverage. The development focus is naturally closer to AD, vitiligo, PN, CSU and other diseases that require rapid control of skin lesions, itching and multi-pathway inflammation.

Fadeucravacitinib is more like an "extremely selective pathway drug": JH2 allosteric inhibition puts the pharmacological focus on TYK2 itself, and the development focus is more likely to extend to psoriasis, CLE, and Sjögren's syndrome where IL-23 and type I IFN drive are obvious and the long-term treatment safety window is more important.

This boundary cannot be drawn to death. Psoriasis itself is the intersection of two routes, and Soficitinib is also advancing psoriasis research. Disease biology is never a single-target textbook, and drug exposure, dosage, safety window, and clinical positioning will all change the final answer. This article prefers to understand the two drugs as a "pharmacological stratification experiment" conducted by InnoCare Pharmaceutical Co., Ltd. using the same target: first use the structure to make the two molecules have different personalities, and then let the clinic find the most suitable diseases for each.

The significance of this event is greater than the peak sales of each of the two pills.

Orelabrutinib has proven that InnoCare Pharmaceutical Co., Ltd. can make a successful small molecule; dual TYK2 has begun to prove that the company can make two structural routes around the same mature target, and then reversely allocate indications based on selectivity, signal coverage, and safety windows. The former is closer to "asset capabilities", while the latter is beginning to develop "platform capabilities".

Imagine that both Soficitinib and Fadeucravacitinib have moved from Phase III to registration, and the self-immunity story of InnoCare Pharmaceutical Co., Ltd. has truly separated from Orelabrutinib. At that time, the core asset of the second growth curve will no longer be a BTK that crossed over from hematoma, but a self-immune small molecule system that can grow its own products, including VAV1 and oral IL-17 and more undisclosed self-immune molecules.

4. After Zenas, global phase III progresses

In the cooperation between InnoCare Pharmaceutical Co., Ltd. and Zenas, after 2026, the focus of observation has shifted from transaction amount to execution.

When signing a contract, what the market is most likely to remember is the potential total transaction value, cash and equity consideration, milestones, and tiered sales commissions of up to a dozen percentage points. Those numbers determine how big a deal looks on signing day, but not how much cash it turns into at the end. What really changes the value of assets is whether overseas partners can advance a Chinese-sourced small molecule to global Phase III, complete regulatory filings, and ultimately establish commercialization capabilities.

Zenas' latest second quarter 2026 update gives a relatively clear answer: both orelabrutinib progressive multiple sclerosis phase III are already ongoing.

For PPMS, PriMroSe plans to enroll approximately 705 patients globally and randomly receive orbrutinib 80 mg once daily or placebo in a 2:1 ratio. The primary endpoint is the time to composite confirmed disability progression at 12 weeks. For inactive SPMS, Monarch plans to enroll approximately 990 patients worldwide. They will also be randomized on a 2:1 basis. Orelabrutinib 80 mg once daily is compared with placebo. The primary endpoint is the time to confirm disability progression at 24 weeks. Zenas disclosed that Monarch was launched in March 2026, and both studies are currently in progress.

For multiple sclerosis, the success of these two trials does not come solely from the number of patients.

There are many effective drugs for the treatment of relapsing MS, but there is still a lack of sufficiently effective treatment options for progressive MS, especially inactive SPMS. After the disease reaches this stage, the problem gradually shifts from peripheral immune cells repeatedly entering the central nervous system to persistent chronic inflammation within the CNS. Microglia, macrophages, and central B cell-related immune activities are thought to be related to the continued progression of disability.

The pharmacological label of orelabrutinib becomes very important here: oral administration, high selectivity, and can enter the CNS. Zenas's positioning is also very clear, hoping to simultaneously affect peripheral pathogenic B cells and B cells, macrophages and microglia in the center, thereby touching the "compartmentalized inflammation" that is difficult to cover with traditional peripheral immunotherapy.

The latest semi-annual report also revealed a signal worth tracking. Zenas has had four orelabrutinib-related abstracts accepted by MSToronto 2026, including the 24-week efficacy and safety data of the previous RRMS phase II, pharmacokinetic analysis, and the design of two phase III studies of Monarch and PriMroSe. This means that in the second half of this year, the market will receive more clinical information than simply "Phase III is enrolling".

A more realistic point is that cooperation has begun to enter new payment nodes. Zenas disclosed in its 10-Q that it recognized a $20 million regulatory milestone payment obligation in the first half of the year related to the InnoCare agreement; the company subsequently disclosed that it reached a proximal milestone in August 2026, which requires a payment of $25 million to InnoCare Pharmaceutical Co., Ltd. and the issuance of 2 million Zenas common shares. From the perspective of cooperation execution, clinical advancement is gradually turning paper milestones into real economic rights and interests.

Zenas' own status is also worthy of attention. Its core asset, obexelimab, has a BLA for the treatment of IgG4-related diseases that has been accepted by the FDA, with a PDUFA target date of May 27, 2027. For InnoCare Pharmaceutical Co., Ltd., this seemingly unrelated development is actually very important: the partners are migrating from clinical stage Biotech to US commercialization organization. The long-term value that a partner that starts to build registration, market access and commercialization capabilities can bring to orelabrutinib is completely different from a licensee that is only responsible for completing the trial.

Therefore, Zenas does not need to rush to give an overly accurate peak sales figure for orelabrutinib.

Zenas previously estimated the combined business opportunities of U.S. PPMS and inactive SPMS at more than $12 billion. Using 10%, 20%, and 30% share for scenario calculation, you can get potential sales ranging from billions of dollars to billions of dollars. In addition to calculations, the market needs to pay more attention to three variables: whether the two phase III trials can complete high-quality enrollment; whether the disease progression endpoint can replicate early pharmacological and imaging signals; and whether Zenas can establish a sufficiently mature neuroimmune commercialization system before the product is launched.

If these three things are accomplished, InnoCare Pharmaceutical Co., Ltd. will be worth much more than just one BD.

It will run through a chain that China's innovative drug industry has always wanted to prove: China completes discovery and early verification, overseas partners undertake global registration clinical trials, FDA and EMA systems complete registration, products are sold overseas, and milestones, equity and royalties continue to flow back.

For a Chinese Biopharma that is still expanding its overseas capabilities, this globalization path is very realistic. The company does not need to bear hundreds of millions of dollars in global phase III and commercialization costs at the earliest stages, and can retain long-term upside through its equity structure.

Now that internationalization has reached this point, the size of the contract has taken a backseat to the second place. Whether partners can truly push the medicine to patients around the world will be the ultimate fulfillment.

Conclusion: The real second breaking point is to replicate success a second time

InnoCare Pharmaceutical Co., Ltd.’s most important achievement in the past decade is certainly orelabrutinib.

It proves that the company can go from drug discovery to registration and commercialization, establish a hematoma sales system, form hematopoietic function, and open up profit channels. For most biotechs, completing this step is difficult enough.

What comes next is even harder.

For a Biotech to truly become a company, it needs to prove that the success of the first drug can be replicated. It needs second and third products, different mechanisms, cash flow independent of the founding assets, and reusable medicinal chemistry, translational medicine, clinical development and commercialization capabilities within the company.

Looking back at InnoCare Pharmaceutical Co., Ltd. now, several lines are approaching this proposition at the same time for the first time.

On the commercial side, drug revenue in the semi-annual report surged 43.2% year-on-year, proving that internal hematopoiesis is still strengthening; on the hematological tumor side, Orbutinib and Mesutoclax continue to extend the value of single drugs to combinations and fixed courses of treatment; on the autoimmune side, Soficitinib and Fad Eucravacitinib uses two completely different structural solutions, JH1 and JH2, and has begun to form a product system independent of BTK; overseas, Zenas has brought orelabrutinib into two global Phase III, and the cooperation milestones have begun to be gradually realized.

Among these four lines, the one that may really change the company's valuation structure is still free.

The reason is simple. Orelabrutinib's continued growth proves how far the first drug can go; if dual TYK2 is successful, it proves what the company can do further.

The most interesting thing about Soficitinib and Fadeucravacitinib is never just that "InnoCare Pharmaceutical Co., Ltd. has two TYK2s." The difference between JH1 and JH2 allows the two molecules to have different selectivity spectra starting from the protein structure, and then from different signal coverage to different clinical needs. Medicinal chemistry, disease biology and indication strategies form a complete chain here.

If this chain finally runs through, InnoCare Pharmaceutical Co., Ltd.'s second growth curve will be more strictly defined.

Hematoma has laid the foundation of the company and will determine the next step of the company.