Core views

Kangfang Biotech released the results of the Cardonil 1L stage III cervical cancer study in IGCS 2024. The entire population had significant benefits for PFS and OS. At the same time, it has excellent clinical efficacy regardless of whether it is combined with bevacizumab, filling the clinical gap in the treatment of cervical cancer patients unsuitable for bevacizumab. The COMPASSION-16 study demonstrated the significant clinical value and commercialization potential of the Cardonil protocol as a complete iteration of the standard treatment for advanced cervical cancer. Follow-up attention can be paid to: (1) continuous release of AK104, approval of 1L of cervical cancer; (2) reading of 2L data from AK112 overseas; (3) completion of related studies in AK112; (4) new Phase III clinical launch of AK112 overseas; (5) reading of other relevant data, etc.

occurrences

In IGCS 2024, Kang Fang Biotech released the results of the Cardonil 1L stage III cervical cancer study. COMPASSION-16/AK104-303 is a phase III clinical trial evaluating all patients (regardless of PD-L1 expression status) with or without cardonil combined with chemotherapy and first-line treatment with or without bevacizumab. The main study endpoints were P FS and OS. The main study endpoints were P FS and OS. A total of 445 participants with PD-L1 CPS<1 accounted for about 26% of the patients.

Cardonil has remarkable curative effects in all first-line cervical cancer patients and those with low PD-L1 expression/negative expression. It has excellent clinical efficacy regardless of whether it is combined with bevacizumab, filling the clinical gap in the treatment of cervical cancer patients unsuitable for using bevacizumab, and has great clinical value and commercialization potential for iterating standard treatment for advanced cervical cancer.

Brief review

1. Cardonil significantly lengthens the PFS and OS of 1L cervical cancer and reduces the risk of disease progression and death. In COMPASSION-16/AK104-303, a randomized, double-blind, multicenter, placebo-controlled phase 3 trial, female patients with untreated persistent, recurrent, or metastatic cervical cancer between the ages of 18 and 75 in 59 clinical centers in China were randomly assigned (1:1) to receive cardonilizumab (10 mg/kg) or placebo plus platinum chemotherapy, with or without bevacizumab, every 3 weeks Total Six cycles followed by maintenance treatment every 3 weeks for up to 2 years. Randomization is carried out through an interactive network response system center. Stratification factors include the use of bevacizumab (yes or no) and previous concurrent chemotherapy (yes or no). The main study endpoints were progression-free survival (PFS) and overall survival (OS) assessed by independent center imaging assessment (BICR) based on recistv1.1.

A total of 445 eligible women were recruited between September 11, 2021 and June 23, 2022. Of the enrolled patients, 100% were of Chinese origin, 370 (83%) had squamous cell carcinoma, 215 (48%) had previous concurrent chemotherapy, and 323 (73%) had metastatic disease at baseline. Bevacizumab was used by 265 (60%) participants. 116 (26%) participants had PD-L1 CPS <1, 312 (70%) participants had a PD-L1 CPS≥1, and 180 (40%) had a PD-L1 CPS≥10.

As of April 30, 2024, median follow-up time was 25.6 months, mPFs in the cardonilizumab group was 13.3 months (95% CI 11.6—17.1), and 8.2 months (7.7-9.6) in the placebo group (HR 0.62 [95% CI 0.49—0.79], p <0.0001); MoS was not achieved (27.0 months to cannot be estimated) compared to 22.8 months (17.6—29.0) (HR 0.64 [0.48—0.86) ], p=0.0011). The ORR cardonilizumab group and placebo group of BICR were 82.9% and 68.6%, respectively; DCR was 93.7% and 91.9%, respectively; and MDO R was 13.2 months (10.5,18.7) and 8.2 months (6.6,11.7).

2. Regardless of PD-L1 expression status or whether it is combined with bevacizumab, the beneficial performance in all subgroups was consistent. In all subgroup mPFs analysis, cardonilizumab was superior to the placebo group. In people with CPS <1, the Cardonil regimen reduced the risk of death by 35% (OS HR 0.65); in people with CPS≥1, the Cardonil regimen reduced the risk of death by 39% (OS HR 0.62); in people with CPS≥10, the Cardonil regimen reduced the risk of death by 45% (OS HR 0.54). For participants using bevacizumab, the cardonil regimen reduced the risk of death by 22% (OS HR 0.78); for participants not using bevacizumab, the cardonil regimen reduced the risk of death by 56% (OS HR 0.44).

In all subgroup MoS analyses, cardonilizumab was superior to the placebo group. In people with CPS <1, the Cardonil regimen reduced the risk of death by 23% (OS HR 0.77); in people with CPS≥1, the Cardonil regimen reduced the risk of death by 31% (OS HR 0.69); in people with CPS≥10, the Cardonil regimen reduced the risk of death by 32% (OS HR 0.68). For participants using bevacizumab, the cardonil regimen reduced the risk of death by 16% (OS HR 0.84); for participants not using bevacizumab, the cardonil regimen reduced the risk of death by 50% (OS HR 0.50).

Unlike pabolizumab, cardonilizumab targets PD-L1 CPS<1 negative patients with a lower HR. The HR for MPFs is 0.65, and the HR for MoS is 0.77. Cardonilizumab has been approved by the NMPA for second-line or late-line treatment of advanced cervical cancer regardless of PD-L1 status.

Also, as a PD-1 and CT LA-4 dual-target drug, its clinical benefits without bevacizumab are superior to those combined with bevacizumab. When not combined with bevacizumab, the cardonil regimen reduced the risk of death by 50% compared to the control group (OS HR 0.5), and the cardonil regimen filled the clinical gap in the treatment of cervical cancer patients unsuitable for bevacizumab. The GOG 240 trial confirmed the use of bevacizumab in first-line treatment of cervical cancer, and bevacizumab is still part of standard treatment. However, adverse effects of bevacizumab, including vascular and gastrointestinal complications, limit use in some patients. In clinical studies, about 40% of cervical cancer participants were ineligible for bevacizumab treatment, while real-world retrospective studies reported lower application rates for bevacizumab, and the most common adverse reaction was vaginal bleeding.

3. Security is easy to manage, and no new safety signals have been found

193 (85%) patients in the cardonilizumab group had grade 3 or higher adverse events, compared with 176 (80%) in the placebo group; 186 (82%) participants in the cardonilimab group had grade 3 or higher treatment-related adverse events, and 173 (79%) in the placebo group; the most common adverse events at all levels and grade 3 or above were decreased neutrophil count, decreased white blood cell count, and anemia in both groups. Adverse events led 63 (28%) participants in the cardonil group and 23 (11%) participants in the placebo group to discontinue any trial drug. Adverse events resulted in the death of 12 (5%) participants in the cardonil group, of which 9 (4%) were treatment-related; the placebo group had 7 (3%) participants, of whom 6 (3%) were treatment-related.

4. The R&D and innovation pipeline is progressing smoothly, and the harvest period is about to be ushered in

New indications for chetanil (cardonilizumab, PD-1/CTLA-4) continue to expand. Cardonil has adopted a combination of 19 indications. More than 20 clinical trials have been carried out on lung cancer, liver cancer, gastric cancer, cervical cancer, kidney cancer, esophageal squamous cell carcinoma, colorectal cancer, etc. Clinical data on all indications have been published in international academic conferences and journals, and continue to be included in authoritative guidelines and expert consensus. On September 30, 2024, Ketanil combined chemotherapy for first-line treatment of gastric cancer or NMPA was approved for marketing. Up to now, it has entered 13 clinical guidelines, including the “CSCO Guidelines for the Diagnosis and Treatment of Gastric Cancer” and “CSCO Guidelines for the Diagnosis and Treatment of Nasopharyngeal Cancer”. As of October 2024, 4 phase III clinical trials are progressing smoothly in the NDA review for 1 first-line treatment indication of Ketanil.

5. Prospects for future milestones

In June 2022, cardonil monotherapy for recurrent or metastatic cervical cancer that previously failed platinum-containing chemotherapy was approved for marketing, filling the gap in immunotherapy for advanced cervical cancer in China. On September 26, 2024, the CDE approved cardonil combined with the standard treatment plan for first-line treatment of advanced gastric cancer. With positive results in various major indications of cardonil, especially in registered studies of first-line treatments, the number of people who are indicated for cardonil will expand rapidly. This time, for 1L cervical cancer indications, regardless of PD-L1 expression and whether bevacizumab was used in combination, PFS and OS in the entire population had significant benefits, filling the clinical gap in the treatment of cervical cancer patients unsuitable for bevacizumab. In the future, I am optimistic about the great clinical value and commercialization potential of the Cardonil protocol to iterate standard treatment for advanced cervical cancer.

6. Profit forecast and valuation

The company's revenue for 2024, 2025, and 2026 is estimated to be 2.655, 4.102, and 6.207 billion yuan, respectively, with corresponding growth rates of -41.33%, 54.49%, and 51.32%; net profit to mother is -0.425, 0.173, and 0.878 billion yuan, respectively, with corresponding growth rates of -120.95%, 140.81%, and 406.22%, respectively.

In terms of research pipelines, the company's various products and indications are about to be approved for sale. At the same time, the existing R&D pipeline is constantly being expanded and enriched, and the early research pipeline is rich in reserves, and has long-term sustainable development capabilities. In terms of product sales, IDA's approval to go public contributed to the increase in the company's product sales. Kaitani grew steadily, and the company's product sales revenue increased year by year. Considering the excellent efficacy and broad market space of the company's innovative drug products, it was given a “buy” rating.