Core views
The company published two clinical data on the core product SKB264 on ASCO. Among them, the combination with A167 showed excellent efficacy and good safety in first-line treatment of advanced NSCLC without driving gene mutations; the single drug was also used to treat TNBC in phase III clinical results were also positive, and it is expected that this indication will be approved in the second half of the year. Partner MSD is actively deploying SKB264 global clinical trials. Currently, it has deployed 9 phase III clinical trials, covering various types of lung cancer, breast cancer, and endometrial cancer. The company currently has 5 products that have entered the NDA stage. We believe that with the clinical advancement of various subsequent products, the company's R&D capabilities in the ADC field will be further recognized.
occurrences
The company announced SKB264 clinical trial data at the ASCO conference
Colombotech announced on May 24 that it will announce the ASCO (American Society of Clinical Oncology) at the ASCO (American Society of Clinical Oncology) annual meeting two clinical study data: 1) SKB264 combined with KL-A167 for phase II clinical trials for patients with advanced undriven gene mutations NSCLC who have not received treatment; 2) SKB264 monotherapy for the end of TNBC. SKB264
Brief review
First-line NSCLC data is positive, showing BIC potential
The phase II clinical trial (NCT05351788) disclosed by the company this time selected patients with advanced NSCLC who had not received treatment and were genetically negative. Among them, group 1A received “SKB264 5 mg/kg + KL-A167 1200 mg” every 3 weeks, and group 1B received “SKB264 5 mg/kg + KL-A167 900 mg” every 2 weeks. until the disease progresses or becomes unacceptably toxic.
Clinical results showed positive efficacy and controlled safety. As of January 2, 2024, a total of 40 patients in Group 1A and 63 patients in Group 1B were recruited. For group 1A, median follow-up of 14 months in 37 patients with evaluable efficacy had an ORR of 48.6%, DCR of 94.6%, mPFS of 15.4 months, and a 6-month PFS rate of 69.2%. For group 1B, ORR reached 77.6% and 100% DCR at 6.9 months of follow-up in 58 patients with evaluable efficacy. mPFS was not yet achieved, but the 6-month PFS rate was 84.6%. The most common grade 3 treatment-related TRAEs in the two groups include decreased neutrophil count (30.0%/30.2%), decreased white blood cell count (5.0%/17.5%), anemia (5.0%/15.9%), rash (5.0%/6.3%), and drug rash (7.5% /0). Due to drug hypersensitivity, 1 patient in cohort 1B had TRAE that caused SKB264 withdrawal. There were no treatment-related deaths, and overall safety was manageable.
Shows BIC potential compared to similar treatments. Previously, MSD K drugs had been approved as advanced driver gene-negative NSCLC 1L therapy. For non-squamous non-small cell lung cancer (NCT02578680), when compared with pemetrexe/platinum chemotherapy, when followed for 21 months, ORR was 47.6% VS 18.9%, and MPFs was 8.8 months vs. 4.9 months; for squamous non-small cell lung cancer (NCT02775435), K pharmaco-carboplatin and paclitaxel compared to carboplatin and paclitaxel, when followed for 19 months, ORR was 57.9% VS 38.4%, MPFs was 6.4 months VS 4.8 months; in similar Trop-2 ADCs, Gilead updated the SG+K drug phase II data on ASCO, with an ORR of 67% in the 30-person sample, MPFS13.1m in non-squamous cell carcinoma patients, and MPFS not achieved in patients with squamous cell carcinoma; AstraZeneca/Daiichi Sankyo updated phase Ib tropion-LUNG02 clinical data, ORR 52 in people treated with DATO-DXD+K combination therapy %, mPFS reached 11.1m. On this basis, the ORR for the triple chemotherapy combination therapy was 56% and mPFs 6.8m; in addition, AstraZeneca/Daiichi Sanso also announced some clinical results of phase Ib with or without DATO-DXD + Imfinzi at the WCLC conference in September 23. The ORR for the double and triple therapy was 50% and 76.9%, respectively, and the DCR for the double treatment was 92.9%, and there was no PFS or OS related data. Compared to approved treatments and some ongoing clinical trials, the data disclosed by SKB264 showed better clinical results. Although direct head-to-head comparisons cannot be made due to the number of clinical samples and patient baselines, SKB264's outstanding data in current phase II clinical trials still shows the BIC potential of this combination therapy.
Phase III of TNBC reached the main end point, and it is expected that phase III of the terminal indications will be approved for marketing by the end of the year to reach the main end of progression-free survival (PFS). The study (NCT05347134) is a multicenter, randomized, open-label clinical trial (n=263) that assessed the efficacy and safety of SKB264 compared to third-line chemotherapy in patients with locally advanced, recurrent, or metastatic TNBC that cannot be surgically resected. As of June 21, 2023, the study had reached a major PFS endpoint. Compared to the chemotherapy group, patients in the SKB264 group had a 69% lower risk of disease progression or death (HR=0.31, 95% CI: 0.22-0.45, P<0.00001). According to the results of the BICR assessment, the median PFS for SKB264 and chemotherapy was 5.7 months and 2.3 months, respectively, and the 6-month PFS rate was 43.4% and 11.1%, respectively.
As of November 30, 2023, the study reached the secondary end of overall survival (OS). Compared with the chemotherapy group, the OS of patients in the SKB264 group showed significant statistically significant advantages (HR = 0.53, 95% CI: 0.36-0.78, P = 0.0005), but the median OS was not yet achieved (95% CI: 11.2-NE), while the median OS of patients in the chemotherapy group was 9.4 months (95% CI: 8.5-11.7). The SKB264 group had an ORR of 43.8% as assessed by BICR and 12.8% in the chemotherapy group.
The most common grade 3 or higher TRAE in the SKB264 group was reduced neutrophil count (32.3%), anemia (27.7%), and decreased white blood cell count (25.4%), and overall safety was good.
In December 2023, SKB264 was accepted by the NMPA for an unresectable locally advanced or metastatic TNBC indication NDA that has received at least two previous treatments (at least one of which is for advanced or metastatic stages). The NDA has been included in the priority review and approval process and is expected to be approved in the second half of the year.
MSD actively lays out multiple indications, and the potential for internationalization gradually highlights MSD's active layout of the ADC sector. In 2022, Colombotech and MSD signed three licensing and cooperation agreements to develop up to nine ADC assets for cancer treatment, including three ADC assets (SKB264, SKB315, and SKB410) and up to six pre-clinical ADC assets that have advanced to the clinical stage. In the future, 6 ADC products, including SKB264, will be the focus of MSD's R&D.
SKB264 is the product with the fastest progress in cooperation, and the Phase III clinical layout is being accelerated. SKB264 is currently the fastest progressing product in the company's cooperation pipeline with MSD.
In May 2022, the company reached an agreement with MSD for the first time to authorize its SKB264 overseas interest, and the company received a total one-time payment of US$102 million and a potential milestone payment of US$1.16 billion. SKB264 is being promoted using MK-2870 as the MSD pipeline. Since the second half of '23, MSD has carried out 9 phase 3 clinical trials. MSD's planning and rapid layout of the MK2870 single drug or combination indications also further demonstrated MSD's confidence in the product.
24-year outlook: Catalyst events are abundant, and MSD continues to drive clinical progress. The company's A167 (RM-NPC), A166 (3L advanced HER2+BC), and SKB264 (3L advanced TNBC) are expected to be approved for listing in 2024; SKB264 3L eGFRMT NSCLC indications are expected to submit an NDA, and A400 for advanced RET+ NSCLC indications are expected to submit an NDA; SKB264 is expected to have data this year for 1L of TNBC treatment Read it out. Up to now, MSD has initiated 9 global phase III clinical trials, covering other indications such as lung cancer, breast cancer, and endometrial cancer. It is expected that more phase III clinical trials will be carried out this year.
Profit forecasts and investment advice
We expect Collombott's 2024-2026 revenue to be 1,358 billion yuan, 1,523 billion yuan, and 2,484 billion yuan, respectively. The company's three R&D platforms are actively deploying various types of drugs. Among them, the ADC platform is technologically advanced. It has completed external licensing of MSD three times, accelerated the global layout of the product, broad potential market space, excellent competitive pattern, and gave it a “buy” rating.
Risk analysis
Industry policy risks: Risks such as changes in research design requirements, price changes, volume procurement policy changes, and changes in the scope and ratio of medical insurance reimbursement due to industry policy adjustments (major changes in government procurement, health insurance policies, and innovative drug marketing review policies).
Risk of R&D falling short of expectations: In the product development process, there is a risk that the R&D cycle will be extended, costs will rise, or R&D will fail due to mistakes in design, planning, organization, coordination, and control. In the process of developing new drugs, there are risks such as uncertain clinical enrollment progress and uncertain efficacy results and safety outcome data.
Risk that approval falls short of expectations: In the approval process, there are risks such as additional data and lengthening of the approval cycle due to factors such as additional data and changes in the approval process.
Risk of sales falling short of expectations: Newly launched drugs face risks such as market entry, market acceptance, product competitiveness, product competition pattern, and changes in market demand, and there is a risk that sales of marketed products fall short of expectations.