This year's ASCO annual meeting marked a milestone for Chinese innovation, achieving both a "quantity explosion" and a "quality breakthrough": 94 studies were selected for oral presentations, with 13 innovative studies from 12 Chinese pharmaceutical companies included in the latest Late-Breaking Abstracts (LBA).

Research related to PD-(L)1/VEGF bispecific antibodies was undoubtedly a major focus at this ASCO meeting. Among them, the HARMONi-6 study by Akeso Inc. (09926) confirmed that Ivonescimab (PD-1×VEGF dual-target) combined with chemotherapy demonstrated significantly superior overall survival (OS) compared to tislelizumab combined with chemotherapy in first-line advanced squamous non-small cell lung cancer.

This is the first time a PD-1×VEGF bispecific antibody has shown dual significant positive results for both OS and PFS in 1L NSCLC. The importance of the above research is undeniable: as traditional PD-1 monoclonal antibodies offer limited benefit in PD-L1 low/negative squamous carcinoma, the addition of VEGF can effectively "broaden" the benefit boundary of immunotherapy.

This point was also validated in the later-line lung squamous carcinoma data for IMM2510 (a PD-L1/VEGF bispecific fusion protein with enhanced ADCC) presented by IMMUNEONCO-B (01541) at the meeting. As another significant breakthrough by a Chinese pharmaceutical company in the field of lung cancer, IMMUNEONCO-B's innovative value also received high recognition from the global academic community at this ASCO meeting.

Filling a Critical Clinical Gap in Later-Line Treatment

Over the past two decades, the waves of targeted and immunotherapy have sharply raised the overall survival curve for NSCLC. However, due to factors such as a lack of functional validation, high intratumor heterogeneity, and complex escape pathways, squamous non-small cell lung cancer (SqNSCLC) has become a "target desert."

The collective appearance of Chinese innovative pharmaceutical companies like Akeso and IMMUNEONCO-B with their respective research results at the ASCO meeting demonstrates that Chinese innovative forces are launching a comprehensive offensive against SqNSCLC, the "toughest nut to crack" in lung cancer, across multiple lines of therapy.

The reason the research achievements of Akeso and IMMUNEONCO-B garnered widespread attention from the global academic community at this ASCO meeting lies in the fact that Akeso, with the robust Phase III head-to-head clinical data from HARMONi-6, has the potential to redefine the gold standard for first-line treatment of sq-NSCLC.

Meanwhile, IMMUNEONCO-B, with its outstanding IMM2510 data in later-line squamous carcinoma, has the potential to fill the clinical gap for IO-resistant lung squamous carcinoma.

From a market perspective, lung cancer, as the malignancy with the highest global incidence and mortality rates, has always been a focus in oncology. Among them, lung squamous cell carcinoma accounts for approximately 25%-30% of NSCLC cases.

In the later-line treatment setting, the prognosis is extremely poor for lung squamous carcinoma patients who have progressed after receiving PD-1 inhibitors and platinum-based chemotherapy. Docetaxel, as the standard treatment for this population, has limited efficacy and significant toxicity.

Furthermore, over the past several years, multiple Phase III studies exploring new treatment strategies have ended in failure, such as the CONTACT-01 study (atezolizumab combined with cabozantinib vs. docetaxel) and the LEAP-008 study (lenvatinib combined with pembrolizumab vs. docetaxel).

These studies failed to show superior OS benefit compared to docetaxel, highlighting the significant unmet treatment needs in this field and underscoring the importance of the key IMM2510 later-line squamous carcinoma data readout.

According to the research data disclosed by IMMUNEONCO-B, in the dose-escalation and expansion phases, among a total of 22 efficacy-evaluable patients, 15 received the recommended dose of 20mg/kg Q2W.

The efficacy data showed: an ORR of 27.3% (6/22), a DCR as high as 81.8% (18/22), a median DOR of 11.1 months; with a median follow-up time of 8.31 months, the median PFS was 9.4 months; the median overall survival has not yet been reached (95% CI: 7.786, NR).

The core highlight of this data set lies in the positive early signals for mPFS and OS. In particular, the mPFS of 9.4 months is significantly higher than the historical mPFS data of 2.9-3.5 months for docetaxel.

In terms of safety data, IMM2510 further demonstrates clear scarcity: the permanent discontinuation rate due to AEs was only 3.1% (1/32); ≥Grade 3 TEAEs were 53.1% (17/32), and ≥Grade 3 TRAEs were 37.5% (12/32).

The overall toxicity profile was primarily hematological, with no ≥Grade 3 irAEs observed. It is important to note that, comparing horizontally with other agents in the same indication pipeline undergoing Phase III clinical studies: the irAE incidence for ONC-392 (anti-CTLA-4 antibody) is as high as 60%, with an AE-related discontinuation rate of 22.2%.

Another agent, IBI363, also has an AE-related discontinuation rate of 22.2%, with high irAE toxicities such as arthralgia and rash. It is not difficult to see that the significant data readout for IMM2510 addresses a key pain point in later-line lung squamous carcinoma treatment.

Specifically, for later-line lung squamous carcinoma patients with poor performance status and extremely limited tolerance to toxicity, achieving confirmed efficacy while realizing "chemotherapy-free and low toxicity" is crucial. This characteristic positions IMM2510 to potentially become the optimal regimen in the chronic disease management scenario for SqNSCLC, filling the clinical gap in later-line lung squamous carcinoma treatment.

Intensive Release of Innovations and Underlying Value Awaiting Recognition

The frontier of domestic innovative drug development is no longer merely about Me-too/Me-better, but is transitioning towards higher-end BIC/FIC transformations. The aforementioned innovative achievements in PD-(L)1/VEGF bispecific antibodies are just a microcosm of IMMUNEONCO-B's deep cultivation in the BIC/FIC track.

As a platform-based innovative pharmaceutical company focused on immune regulation and bispecific antibodies, IMMUNEONCO-B has in recent years built an integrated R&D platform covering everything from target screening and molecular design to process development and manufacturing (CMC).

Supported by this innovative platform, the company has obtained over 30 NMPA/FDA IND approvals, covering multiple therapeutic areas including oncology, autoimmune diseases, and metabolism. It has established a core product matrix including IMM01, IMM0306, and IMM2510, and holds global commercialization rights, propelling the company towards forming an international development pattern of "independent R&D + global commercialization."

In recent years, IMMUNEONCO-B has intensively released its innovative achievements. Beyond presenting the latest complete data for IMM2510 in later-line lung squamous carcinoma at the ASCO meeting mentioned above, the company has also initiated clinical studies of IMM2510 combination therapies for solid tumors.

Among these, the combination of IMM2510 with IMM27M holds great promise. IMM27M is an IgG1 antibody targeting CTLA-4, engineered to significantly enhance ADCC activity. Compared to the similar drug Ipilimumab, it showed significantly superior in vivo efficacy at equivalent doses in animal studies.

Multiple repeated in vivo studies have demonstrated that IMM27M possesses potent anti-tumor activity and can be combined with various drugs in the company's pipeline for clinical research. Its combination study with IMM2510 is referred to by IMMUNEONCO-B as the "Diamond Regimen," and its Ib/IIa phase clinical trial is currently proceeding smoothly.

IMMUNEONCO-B has also presented several significant research findings at multiple international academic conferences. For example, at last year's ASCO and ASH annual meetings, it presented excellent response data for its core product IMM0306 in R/R FL, and at this year's EULAR meeting, it announced the latest preliminary results from the Ib/II phase clinical trial of this drug for patients with moderate to severe active systemic lupus erythematosus (SLE).

Additionally, it is worth noting that on June 18 this year, the HARMONi-A research results for Akeso's Ivonescimab in the EGFR-TKI resistant nsq-NSCLC indication were published in the main journal of the top-tier international medical publication JAMA (Journal of the American Medical Association).

The HARMONi-A study, achieving dual positive results in PFS and OS, provides robust evidence-based medical proof of the outstanding clinical value of PD-(L)1/VEGF dual-targeting over traditional PD-1 therapies. This has also heightened industry and market anticipation for the development of drugs targeting the same pathway, including IMM2510, in this field.

However, against the backdrop of a correction in the Hong Kong stock pharmaceutical sector, many of IMMUNEONCO-B's fundamental positives have not been accurately reflected in its secondary market performance.

It has been observed that since last September, the Hong Kong stock innovative drug sector has shifted from its previous bull market state to a volatile downtrend, particularly experiencing a sustained decline since mid-April this year. This directly led to the Hang Seng Healthcare Index falling continuously after mid-April.

From April 16 to the present, the index has dropped by over 25%. In reality, the decline in the Hong Kong stock pharmaceutical sector is the result of a confluence of multiple factors including capital flows, market sentiment, and geopolitics.

This outcome, however, has led to the mispricing of stocks for many fundamentally sound innovative pharmaceutical companies, including IMMUNEONCO-B. Despite facing uncertainties in the market, IMMUNEONCO-B's management continues to send a positive signal to the market about the urgent need to reassess the company's intrinsic value through share repurchases.

Since June this year, IMMUNEONCO-B has conducted a cumulative total of 6 repurchases, buying back 923.4 thousand shares with an amount nearing HK$3 million. This fully demonstrates the company's sincere attitude towards being responsible to and rewarding shareholders, reflecting greater confidence from management in the company's future development.

Supported by the dual logic of repurchase benefits and valuation repair, the secondary market feedback has been noticeable. It has been observed that since June this year, IMMUNEONCO-B's stock price has accumulated a gain of over 20% within the period, significantly outperforming the index.

This also suggests that the company's stock price may be among the first to see a rebound.

Concluding Remarks

With the disclosure of significant IMM2510 data, the certainty of IMMUNEONCO-B's differentiated original innovation has been further confirmed. The company also has the potential to unlock more valuation imagination through multiple pipeline products with potential FIC/BIC profiles.

Referring to the current valuations of leading innovative pharmaceutical companies in Hong Kong, for instance, Ascentage Pharma has a PS valuation of 18.72x, and Akeso Inc. has a PS valuation of 22.85x. In contrast, IMMUNEONCO-B, which holds over CNY 1 billion in cash, also possesses a differentiated innovative pipeline, and can return value to shareholders through share repurchases, currently has a PS valuation of only 8.69x.

This valuation level is clearly already at a bottom "sweet spot" position. The company's intrinsic value urgently awaits reassessment by the secondary market, making it worthy of investor attention.