In late November, affected by the news of the commercialization rights of ** core products, Conrad Biologics (CNTBUS) was hit hard in the secondary market, closing down nearly 40% in a single day. After that, Conrad, who was "seriously injured", has also been fluctuating**, and it has not taken a turn for the better until recently.
Zhitong Financial APP observed that on December 15, Conrad Biotech opened high and went high, with a rise of more than 15% throughout the day, and continued to rise at the end of the day, and finally closed up 2336%。The readout of the topline results of the 2B clinical trial of Rademikibart*** in the indication of moderate to severe persistent asthma is an important reason for the positive response in the secondary market. However, the company's stock price did not continue to rise, and on December 18, the share price of Conrad Biotechnology opened low again and closed down 778%, the company's stock price fell below $1 again.
In fact, in addition to atopic dermatitis (AD), asthma is also one of the indications worth paying attention to in IL-4R, and there are relatively few players in the current IL-4R asthma field, so the market has great expectations for the commercialization prospect of Conrad Biotech in this indication track.
The top line turned out to be positive, but it was difficult to support a valuation reversal.
As mentioned above, in addition to atopic dermatitis (AD), asthma is also one of the indications worth focusing on for IL-4R, because IL-4R is a potential target for both asthma and atopic dermatitis.
Specifically, the use of IL-4R (IL-4R) antagonists has the effect of blocking IL-4 mediation. The development of antagonistic antibodies (AB) against the interleukin 4 receptor (IL-4R) subunit of the IL-4 IL-13 receptor is a potential strategy for T helper cell 2 (Th2)-mediated allergic diseases such as asthma and atopic dermatitis. Dupilumab, for example, has been widely approved for adult patients with moderate to severe atopic dermatitis (AD) since 2018 and for asthma control in 2019, highlighting the promising clinical efficacy of IL-4R in eosinophilic asthma.
The key data of Phase 2B clinical trial of the core product Rademikibart*** for the indication of moderate to severe persistent asthma disclosed by Conrad Biotech this time are also the key data of the Phase 2B clinical trial.
The results showed that in terms of primary endpoints, the study found a significant improvement from baseline in pre-bronchodilator** FEV1 in the rademikibart group compared to the placebo group. At week 12, lung function was significantly improved in the rademikibart group compared to placebo (see table below). Compared with placebo, the 150 mg and 300 mg trial groups showed significant improvement as early as week 1 (both p < 0.).001) and continued until Week 24 (p = 0.).001 and p < 0001)。In addition, the ACQ-5 score was reduced at week 24 in the Rademikibart group.
Although the study did not examine the difference in the rate of severe exacerbations per year between the test and control groups, the results showed a strong trend towards a decrease in the rate of severe exacerbations per year after the rademikibart group**, with more than half of the exacerbations occurring in the placebo group during the 24-week study. Compared with the control group, there was a strong trend of prolonging the time to first exacerbation in both rademikibart groups, indicating that the patients had a more obvious benefit from reducing severe exacerbations after treatment.
In terms of safety, the two rademikibart groups were well tolerated, and the proportion of related adverse events was similar across the groups.
In terms of horizontal non-head-to-head data comparison, the effectiveness data of Conrad Biologics rademikibart in asthma indications is better than that of current global competitors, especially dupilumab, which is also an important reason for Conrad's stock price to rise on the 15th.
However, even if the clinical data is excellent, it is difficult for Conrad Biotech to achieve a valuation reversal in the secondary market based on this data alone.
As the largest competitor of rademikibart in the field of asthma indications, dupilumab has been approved in China on November 17 this year for the maintenance of adolescents aged 12 years and above and **asthma patients**.
According to the previous annual report of Conrad Biologics, Conrad is expected to complete a 36-week phase 2 maintenance trial of moderate to severe atopic dermatitis (AD) in the second half of this year. Based on feedback received from the Center for Drug Evaluation (CDE) of the China Food and Drug Administration, the company plans to submit a new drug application (NDA) in the first quarter of 2024 for approval in 2025. Judging from the current R&D progress, AD will become the first indication to be declared by Rademikibart, and in comparison, the application progress of asthma indication will be slower, and the commercialization time will be slower, so it will not continue to affect the valuation of the secondary market in the short term.
Can it achieve a breakthrough under the pressure of competing products?
From a commercial point of view, even if Conrad's rademikibart is successfully launched in 2025, it will face a strong competitive team led by dupilumab.
In terms of asthma indications, as mentioned above, the asthma indication of dupilumab has been approved in China, and the key lies in the data of the Chinese subgroup of the Asia-Pacific study of dupilumab released this year.
According to Zhitong Financial APP, this subgroup data comes from the multicenter, double-blind, parallel-group, phase trial of dupilumab conducted in the Asia-Pacific region, and the total population of the study is a 12-year-old patient with asthma who is still poorly controlled after using medium-high dose ICS combined with at least one control drug [with or without oral glucocorticoid (OCS) maintenance]**.
The results of the study showed that in terms of primary endpoints, pre-bronchodilator** FEV1 was significantly improved from baseline in Chinese patients with type 2 asthma who did not receive OCS maintenance ** in the dupilumab group compared with placebo, and the pre-bronchodilator FEV1 was significantly improved by 460 mL, which is consistent with the results of the global population.
In terms of secondary endpoints, ACQ-5 scores were also reduced at week 24 in the dupilumab group, and the annual rate of severe exacerbations in Chinese patients with type 2 asthma was significantly reduced by 74% compared with placebo in the dupilumab group.
In addition, the proportion of **related adverse events in the overall safety population (n = 484) was similar in both groups. It can be said that it is based on the above sufficient evidence, including the analysis of Chinese population subgroups, that has promoted the approval of dupilumab in China.
From the perspective of competing products, although the rademikibart and dupilumab of Conrad Biologics are not head-to-head studies, from the perspective of efficacy and safety, both have significant efficacy in improving asthma patients, and the real gap between the two may lie in their commercial sales capabilities.
According to Sanofi's annual report and quarterly report, dupilumab's sales revenue in 2018 reached 78.8 billion euros;In 2019, it reached 207.4 billion euros (about 22.2 billionUS$4.9 billion), a year-on-year increase of 152%;In 2020, the global sales volume was 353.4 billion euros;In 2021, global sales reached 524.9 billion euros, up 4853%。In the first quarter of last year, dupilumab sales reached 1.6 billion euros, a year-on-year increase of 45.57%。
According to the 2023 semi-annual report released by Sanofi, the sales of its star product dupilumab reached 231.6 billion euros, reaching 25.5 billion euros in the second quarter6.2 billion euros, with sales of 48.8 billion euros in the first half of the year7.8 billion euros, full-year sales are expected to exceed the 10 billion euro mark.
In addition, dupilumab was included in the National Medical Insurance Catalogue only 5 months after its marketing in China, and became the only targeted biologic agent for moderate to severe atopic dermatitis in the new version of the Medical Insurance Catalogue, which is enough to show that the product is leading at the commercial level.
In contrast, according to the previous licensing transaction, the domestic commercialization rights of Rademikibart have been sold to a domestic manufacturer, and the company currently only owns the overseas rights and interests of the product.
But currently, the global asthma COPD drug market is dominated by GSK, AstraZeneca, and Sanofi. In 2019, GSK's product sales revenue for this segment was 85US$3.4 billion, although a slight decline, still accounts for 37% of the global market, firmly in the top spot. AstraZeneca and Sanofi each achieved growth in total sales revenue in the asthma segment with their two monoclonal antibodies. Sanofi, with dupilumab, has advanced to the top three as early as 2019.
Such a competitive environment in the market meant that Conrad Biotech could hardly roll out the overseas sales of Rademikibart on its own, and cooperation with MNC seemed to be the only way. Now, it seems that the good clinical data of Rademikibart has laid a good foundation for its possible overseas licensing transactions in the future.