Core views
Cinda Biotech released the latest IBI363 solid tumor data. Overall, the product showed excellent initial efficacy and good safety in patients with solid tumors. In the ≥0.1 mg/kg dose range, ORR was 35.1%, DCR was 75.7%, and mPFS was 5.5 months in SqnsCLC subjects. In terms of safety, only 13.2% of the 38 subjects in the 3mg/kg Q3W dose group developed grade 3 or above TRAE, and none stopped treatment due to AE.
Overall, IBI363 has shown outstanding efficacy and safety, and is expected to become the second-generation IO leading drug.
occurrences
On June 14, 2024, at the 2024 European Society of Medical Oncology (ESMO) June General Conference, Cinda Biotech presented the clinical data of the world's first (first-in-class) PD-1/IL-2α-Bias bispecific antibody fusion protein IBI363 for the treatment of various advanced solid tumors (study registration number: NCT05460767).
reviews
IBI363 solid tumor data has excellent efficacy and can be expected in the future
Most patients enrolled in lung cancer and melanoma were immunotreated, and those enrolled in colorectal cancer were not sensitive to immunotherapy. As of April 16, 2024, a total of 347 advanced solid tumor subjects received IBI363 monotherapy at different doses (0.2 μg/kg QW~3 mg/kg Q3W). This included 100 cases of non-small cell lung cancer, 89 cases of melanoma, 102 cases of colorectal cancer, and 56 cases of other tumors. 81.8% of the subjects had previously received 2 or more systematic treatments. Of the 245 subjects other than colorectal cancer, 84.1% of the subjects had received immunotherapy before enrolling.
The single drug showed excellent initial efficacy. Within the dose range of ≥0.1 mg/kg, 300 patients had 3 cases of complete remission (CR) and 49 cases of partial remission (PR), with an ORR of 17.3% and a DCR of 56.3%. As of the data cut-off date, the mDOR was 8.1 months [4.2, NR], and the overall mDOR was not mature. Among 204 subjects who had previously received immunotherapy, the ORR was 17.6%. In the 3 mg/kg dose group, a total of 15 subjects underwent at least one post-baseline tumor evaluation, with an ORR of 46.7% and a DCR of 80.0%.
IBI363 monotherapy has shown outstanding efficacy in patients with squamous non-small cell lung (SqnsCLC) cancer with negative driver genes. After 70 cases of NSCLC (only 1 case not previously treated with PD-1 but treated with TCE) were treated with ≥0.3 mg/kg of IBI363, the overall ORR was 27.1% and DCR 72.9%. Among 37 subjects receiving ≥0.3 mg/kg of IBI363, ORR was 35.1% and DCR was 75.7%. At cut-off date, patients with sqnsCLC had a median follow-up time of 5.7 months and a median PFS of 5.5 months (95% CI, 3.2-6.9). Eleven of the 13 PR patients were still in remission and are expected to have a longer DOR. Among the 9 NSCLC patients receiving 3 mg/kg, the ORR of 6 patients with sqnsCLC was 100%, the ORR of 3 patients with adNSCLC was 33.3%, and the DCR was 100%. The curative effect of sqnsCLC was amazing. Currently, only a small number of patients enrolled in adNSCLC are expected, and further enrollment evaluations are expected. Consider: ① sqnsCLC accounts for about 35% to 40% of NSCLC patients, of which 70%-80% of patients are genetically negative, so they are an important NSCLC population; ② Currently, there is a large number of immunotreated patients with sQnsCLC that do not meet clinical needs.
IBI363 therefore has important clinical value.
The IBI363 single agent has shown excellent efficacy in melanoma patients, and the future can be expected. Thirty-seven patients with melanoma who had previously received immunotherapy were treated with 1 mg/kg of IBI363, and ORR and DCR were 29.7% and 73.0%, respectively. Among the 8 subjects with mucosal melanoma who had not undergone previous immunotherapy, the overall ORR was 75.0% and the DCR was 100%. Overall, IBI363 has shown excellent initial efficacy in patients treated with IO and patients with IO “cold tumors”. The product has excellent results and is expected to become the leading drug for second-generation IO.
IBI363 has excellent safety and shows potential for combined use
Among all patients, the most common treatment-related adverse events (TRAEs) were joint pain, anemia, and abnormal thyroid function. The overall incidence of grade 3 or above TRAE was 23.9%, the overall incidence of immune-related adverse events (iRAE) of grade 3 or above was 10.4%, and the proportion of all patients who stopped treatment due to side effects was 3.2%. In the 3 mg/kg Q3W dose group, 13.2% of patients developed grade 3 or above TRAE, and none of the subjects discontinued or died due to side effects. Overall, IBI363 has shown good safety. The product has now been undergoing clinical trials with drug combinations with different mechanisms, and the potential for future combined use can be expected.
The new mechanism breaks through IL2 safety limitations. IBI363 shows outstanding clinical efficacy. IL2 receptors are divided into three types, namely IL-2Rα (IL2RA coding, CD25), IL-2Rβ (IL2RB coding, CD122), and IL-2Rγ (IL2RG coding, CD132). Traditional IL2 drug designs focus on natural IL2 and IL2 designs that are biased towards beta-gamma, but overall, because the product activates lymphocytes in the blood, causing strong toxicity problems, it is impossible to achieve the desired target dosage. The drug design of IBI363 is based on Cinda Biotech's new understanding and explanation of the biological function of the IL2 subunit (related article published in the top journal Nature Cancer). The PD-1/IL-2 design uses an innovative IL-2α-Biased form, mainly because specific T cells (TST) within tumors express high CD25, so the drug can bind to TST within tumors and further promote TST proliferation and differentiation, thereby further killing tumors. Outside of tumors, IBI363 is more likely to bind to Treg cells, so overall safety is controllable while ensuring efficacy. In human clinical practice, IBI363 has shown good safety data. The clinical dose is as high as 40-200 times that of other IL-2 drugs. At the same time, it has also shown outstanding efficacy in tumors, and is excellent overall.
IBI343 (CLDN18.2 ADC) showed outstanding efficacy in pancreatic cancer patients. Subsequent population data is worth expecting IBI343 as an innovative CLDN18.2 ADC drug developed by the company. It showed outstanding efficacy in pancreatic cancer patients: in 10 patients with backline CLDN18.2 expression ≥ 60% (1+/2+/3+), the overall ORR was as high as 40%, and the curative effect was outstanding. At the same time, it is worth noting that the company's products avoided ADCC-mediated digestive tract toxicity after clever design. The overall probability of nausea and vomiting in patients was 25.7%, and gastrointestinal safety was good. At the same time, only 2.9% of patients stopped treatment due to adverse reactions, and safety was manageable. Overall, the company's IBI343 showed excellent efficacy and safety data in pancreatic cancer. The company will update more data at the ESMO GI conference in the future, which is worth looking forward to.
The company's core pipeline continues to advance, and it is expected to usher in a number of catalytic non-tumor pipelines before the first half of next year: ① Weight loss indications for the 6mg standard of mast peptides are expected to be approved. ② Marshidopeptide diabetes indications are expected to be submitted for marketing.
③ Indications for IBI-112 moderate to severe psoriasis are expected to be submitted for marketing. In the cancer product pipeline: ① More data on IBI-343 (CLDN 18.2 ADC) in gastric cancer and other indications is expected to be read in June. ② More POC data on IBI-363 (PD-1/IL-2) in solid tumor patients is expected to continue to be disclosed in June.
We believe that based on Cinda Biotech's strong R&D capabilities and the efficient advancement of clinical progress in oncology and non-oncology pipelines, the company's catalytic incidents will continue to occur for some time to come, and the company's value is expected to be further enhanced.
Profit forecasts and investment advice
The company's extensive layout on the oncology circuit has begun to take shape, and high-value clinical products are expected to further increase the revenue of the company's oncology circuit and continue to reduce marginal costs. In the non-oncology circuit, the company has carried out an extensive layout in the fields of metabolism, self-immunity, and ophthalmology, and the products already on the market and under development are highly competitive and leading in progress. We expect Cinda Biotech's 2024-2026 revenue to be $7.70 billion, $11.65 billion, and $15.31 billion. Using DCF valuation, the company's reasonable market value is HK$108.1 billion, maintaining the target price at HK$66.58. Maintain a “buy” rating.
Risk analysis
The risk of uncertainty in the development of new drugs. As a technological innovation, new drug research and development has the characteristics of a long R&D cycle, high investment, high risk, and low success rate. From laboratory research to approval of a new drug for marketing, it has to go through many complex steps such as pre-clinical research, clinical trials, new drug registration and marketing, and after-sales supervision. Every step may face the risk of failure. There is also a risk that existing products or treatments will be replaced by new treatments and technologies.
Commercialization risks. Health insurance fees have exceeded expectations, causing the pricing of innovative drugs to fall short of expectations; although the company has exclusive varieties in the release stage, competition in the PD1 and biosimilar markets is fierce, which may lead to a risk that the sales share falls short of expectations or that the sales expense ratio is higher than expected.