Fill in the blank for the treatment of squamous cell carcinoma, accelerate innovation and realize innovation, IMMUNEONCO-B(01541) enters a critical ball-hitting area.

At this year's ASCO conference, China's innovation power has achieved a milestone breakthrough in both "quantity explosion" and "quality breakthrough": 94 studies were selected for oral presentations at the conference, including 13 innovative studies from 12 Chinese pharmaceutical companies selected for the latest breakthrough abstracts (LBA). Research related to PD-(L)1/VEGF dual blockade is undoubtedly a major focus of this year's ASCO conference. Among them, AKESO's HARMONi-6 study confirmed that the combination of Imvozi (PD-1VEGF dual-target) with chemotherapy in first-line advanced squamous non-small cell lung cancer significantly outperformed the combination of Torleyzelumab with chemotherapy in terms of overall survival (OS). This is the first time that a PD-1VEGF dual-specific antibody has demonstrated double significant positive results in OS+PFS in 1L NSCLC. The importance of the above-mentioned studies is undeniable: as traditional PD-1 monotherapy has limited benefit in PD-L1 low-expression/negative squamous cell carcinoma, the addition of VEGF can effectively "broaden" the benefits of immunotherapy. This was also confirmed in the IMMUNEONCO-B (01541) meeting where the IMM2510 (PD-L1/VEGF dual-specific fusion protein, ADCC-enhanced) in later-line lung squamous cell carcinoma data was equally validated. As another major breakthrough in the field of lung cancer for a Chinese pharmaceutical company, Yimeng Angke's innovative value was highly recognized by the global academic community at this year's ASCO conference. Filling the clinical gap in the treatment of late-stage squamous lung cancer In the past twenty years, the wave of targeted therapy and immunotherapy has significantly improved the overall survival curve of NSCLC. However, due to factors such as lack of functional validation, high intratumor heterogeneity, and complex alternative escape pathways, squamous non-small cell lung cancer (SqNSCLC) has become a "target desert". At this year's ASCO conference, Chinese innovative pharmaceutical companies such as AKESO and Yimeng Angke collectively showcased their research results, demonstrating that China's innovation strength is taking on the "toughest bone to chew" in lung cancer, SqNSCLC, and launching a comprehensive offensive in the field of multi-line therapy. The research results of AKESO and Yimeng Angke have attracted widespread attention from the global academic community at this year's ASCO conference for their potential to redefine the gold standard of first-line treatment for sq-NSCLC with AKESO's HARMONi-6 hardcore Phase III head-to-head clinical research data. Yimeng Angke, on the other hand, with its outstanding IMM2510 data for later-line squamous cell carcinoma, has the potential to fill the clinical gap in IO-resistant lung squamous cell carcinoma. From a market perspective, lung cancer, as the malignant tumor with the highest incidence and mortality worldwide, has always been a focus of the oncology community. Squamous cell carcinoma of the lung (Squamous cell carcinoma) accounts for about 25%-30% of NSCLC. In the field of later-line treatment, for patients with lung squamous cell carcinoma who have progressed after receiving PD-1 inhibitors and platinum-based chemotherapy, the prognosis is very poor. Docetaxel as the standard treatment for this group of patients has limited efficacy and significant toxicity. In addition, in recent years, several Phase III studies exploring new treatment strategies have ended in failure: such as the CONTACT-01 study (atezolizumab combined with cabozantinib vs. docetaxel), the LEAP-008 study (lenvatinib combined with pembrolizumab vs. docetaxel), etc., these studies have failed to demonstrate a survival benefit over docetaxel, highlighting the huge unmet treatment needs in this area and the significant importance of the key data readout of IMM2510 in later-line squamous cell carcinoma. According to the research data disclosed by Yimeng Angke, in the dose escalation and expansion stages, among the total of 22 evaluable patients, 15 patients received the recommended dose of 20mg/kg Q2W. The efficacy data shows: ORR was 27.3% (6/22), DCR was as high as 81.8% (18/22), median DOR reached 11.1 months; median follow-up time was 8.31 months, median PFS was 9.4 months; median overall survival has not been reached (95% CI: 7.786, NR). The key point of this data is the early positive signals of mPFS and OS. In particular, the data of mPFS of 9.4 months is significantly higher than the historical data of mPFS of 2.9-3.5 months for docetaxel. Regarding safety data, IMM2510 shows significant scarcity: the permanent discontinuation rate due to adverse events is only 3.1% (1/32); Grade 3 TEAE is 53.1% (17/32), Grade 3 TRAE is 37.5% (12/32); mainly hematological toxicity is observed, and Grade 3 irAE is not observed. It is worth noting that, in comparison with other drugs undergoing Phase III clinical studies in the same indication track, for example, ONC-392 (anti-CTLA-4 antibody) has an irAE incidence rate as high as 60%, and a discontinuation rate of 22.2% due adverse events; while another drug, IBI363, has a discontinuation rate due to adverse events also at 22.2%, and high irAE toxicity such as joint pain, rash, etc. It is not difficult to see that the groundbreaking data readout of IMM2510 effectively addresses a key pain point in the treatment of later-line squamous cell lung cancer, namely achieving precise efficacy while realizing "chemotherapy-free and low toxicity" in the face of patients with poor physical condition and extremely limited tolerance to toxicity in later-line squamous cell lung cancer. This feature is expected to make IMM2510 the best option in the chronic treatment scenario of SqNSCLC, filling the clinical gap in the treatment of later-line squamous cell lung cancer. Innovative achievements are being released intensively, and internal value awaits reevaluation The current development of innovative drugs in China is no longer simply Me-too/Me-better, but is transitioning towards higher-end BIC/FIC. The innovative achievements in PD-(L)1/VEGF dual blockade mentioned above are just a glimpse of Yimeng Angke's deep cultivation in the BIC/FIC track. As a platform-based innovative pharmaceutical company focused on immune regulation and bispecific antibody fields, Yimeng Angke has built an integrated research and development platform from target screening, molecular design to process development and production (CMC) in recent years. With the support of the innovative platform, the company has obtained over 30 NMPA/FDA IND approvals, covering multiple treatment areas such as oncology, autoimmune diseases, and metabolism, establishing a core product matrix including IMM01, IMM0306, and IMM2510, and holds the global commercialization rights for these products, driving the company to gradually form an international development pattern of "independent research and development + global commercialization". In recent years, Yimeng Angke has released a series of innovative achievements. In addition to the complete data on IMM2510 in later-line lung squamous cell carcinoma presented by the company at the ASCO conference mentioned above, Yimeng Angke has also initiated clinical studies on the combination therapy of IMM2510 for solid tumors. Among them, the combination of IMM2510 with IMM27M is highly anticipated. It is understood that IMM27M is an lgG1 antibody targeting the CTLA-4 target, which has been significantly enhanced in ADCC activity through genetic engineering modification. It has shown significantly better in vivo efficacy than the same class of drug ipilimumab at the same dose. Multiple repeated in vivo studies have proven that IMM27M has strong anti-tumor activity and can be combined with a variety of drugs in the company's pipeline for clinical research. The combination research of IMM27M with IMM2510 is referred to by Yimeng Angke as the "diamond scheme", and its Ib/IIa phase clinical trial is progressing smoothly. Yimeng Angke has also presented several major research achievements at multiple international academic conferences. For example, excellent remission data for the core drug IMM0306 in R/RFL was presented at last year's ASCO and ASH meetings, and the latest preliminary results of the phase Ib/II clinical trial of this drug for patients with moderate to severe active systemic lupus erythematosus (SLE) were announced at this year's EULAR meeting. It is worth mentioning that on June 18th this year, AKESO's research results on the HARMONi-A study for the indication of EGFR-TKI-resistant nsq-NSCLC were published in the main journal of the top international medical journal "Journal of American Medical Association (JAMA)". The HARMONi-A study achieved positive results in both PFS and OS, sufficient evidence from evidence-based medicine has proved the outstanding clinical value of PD-(L)1/VEGF dual therapy over traditional PD-1 therapy, paving the way for promising expectations from the industry and the market for drugs targeting the same pathway including IMM2510. However, against the backdrop of a decline in the healthcare sector in the Hong Kong stock market, many fundamental favorable factors of Yimeng Angke have not been accurately reflected in the secondary market. It can be observed that since September last year, the innovative drug sector of the Hong Kong stock market has changed from its previous bull market state, showing a trend of volatility and decline, especially after mid-April this year, the decline continued. This directly led to the continuous decline of the Hang Seng Healthcare Index after mid-April this year. From April 16th to the present, the index has fallen by more than 25%. In fact, behind the downward trend of the healthcare sector in the Hong Kong stock market are multiple resonating factors such as funding, market sentiment, and geopolitics, but the result has led to many fundamentally sound innovative pharmaceutical companies, including Yimeng Angke, being unfairly affected in their stock prices. Despite facing uncertainties within the industry, the management of Yimeng Angke has continued to use stock buyback as a way to further convey a positive signal that the internal value of the company urgently needs to be reevaluated by the market. Since June this year, Yimeng Angke has repurchased shares six times, totaling 923,400 shares, with a repurchase amount of nearly 3 million Hong Kong dollars, fully demonstrating the company's commitment to shareholder responsibility and returns, and reflecting the management's greater confidence in the company's future development. With the dual logic of buyback benefits and valuation repair, the feedback from the secondary market is significant. It can be observed that since June this year, Yimeng Angke's stock price has risen by over 20%, significantly outperforming the index, indicating that the company's stock price is likely to be the first to rebound. Conclusion With the disclosure of the groundbreaking data of IMM2510, Yimeng Angke's certainty in differential original innovation has been further confirmed, and the company is expected to open up more valuation imagination space through multiple potential FIC/BIC products in its pipeline. Referring to the current valuation of the top innovative pharmaceutical companies in the Hong Kong stock market, such as ASCENTAGE PS with a valuation of 18.72 times and AKESO PS with a valuation of 22.85 times. In comparison, Yimeng Angke, which holds over 1 billion yuan in cash and has a similar differentiated innovative pipeline, and also rewards shareholders through stock buybacks, currently has a PS valuation of only 8.69 times. This valuation level is clearly in the bottom "strike zone", and the internal value of the company urgently needs to be reevaluated by the secondary market, and it is worth investors' attention.