At the 25th World Lung Cancer Conference (WCLC) held in Santiago on Sunday, highly anticipated phase III clinical data was announced.

A head-to-head comparison between Akeso/Summit's bispecific antibody, Ivonescimab (PD-1/VEGF), and the blockbuster drug Keytruda in the treatment of non-small cell lung cancer (NSCLC) showcased impressive results.

Patients treated with Ivonescimab showed a progression-free survival (PFS) of 11.1 months, while the Keytruda group had a PFS of only 5.8 months. The head-to-head study results demonstrated a 49% reduction in the risk of progression or death compared to Keytruda (HR=0.51, P<0.0001), achieving a median improvement of 5.3 months in progression-free survival, meeting the primary endpoint of the study.

The HARMONi-2 study enrolled 398 Chinese patients who received either Ivonescimab or Keytruda as initial treatment following diagnosis. These patients had no EGFR mutations or ALK rearrangements and had a PD-L1 tumor proportion score of at least 1%.

Professor Zhou Caicun from Shanghai Eastern Hospital, the leading investigator of the study, stated, "The results of HARMONi-2 support Ivonescimab as a first-line treatment option for PD-L1 positive advanced non-small cell lung cancer patients."

Akeso also held a teleconference immediately to interpret the data and express confidence in the future market prospects for Ivonescimab.

The capital markets have shown great interest in this data, and analysts have used terms such as "unprecedented," "far exceeding expectations," and "a new benchmark in first-line NSCLC PFS" to describe the achievements of the HARMONi-2 clinical study.

However, from the stock price performance, the market seems to have anticipated the company's success in obtaining the data this time. Summit's stock price has fluctuated by over 270% in the past four months.

The twists and turns of the evusiranib data.

This year, investors have had a thrilling experience with Akeso/Summit, and the story of evusiranib begins in May.

On May 24th, due to market concerns about the poor clinical data performance of evusiranib, which differed significantly from the previous Phase II data, Akeso's share price plummeted, with an intraday drop of over 40%.

On the same day, the management urgently held a conference call to clarify that everyone should focus on the HR data, stating, "Our HR data is the best, which is the key to the clinical aspect."

Almost at the same time, Akeso announced that evusiranib had obtained approval from the Chinese National Medical Products Administration for the treatment of locally advanced or metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) with EGFR mutations after EGFR tyrosine kinase inhibitor (TKI) therapy.

However, the market reaction was still sluggish and the stock price did not stop falling.

Until May 31, the situation finally reversed. Akeso announced that its drug, Ivosidenib, had defeated the drug king Keytruda in a head-to-head clinical trial, just days before the CSCO, the largest cancer conference in the United States, opened in Chicago. Although specific data was not disclosed at the time, the results were described as "historic" and "unprecedented".

As a result, Akeso's stock price soared 37% that day, and Summit's stock price skyrocketed 272%.

At the WCLC conference, Professor Zhou Caicun presented detailed final data from this trial, confirming this groundbreaking result. Ivosidenib became the star of the conference, shocking the field of oncology.

Defeating Keytruda is the dream of every oncology drug developer.

Defeating Keytruda is the dream of every oncology drug developer.

As the revenue pillar of Merck, Keytruda has not only opened a new era of cancer immunotherapy, but also become the cornerstone of cancer treatment, gradually becoming one of the highest-selling drugs globally.

In the first half of 2024, Keytruda's global sales reached $14.2 billion, and it is expected to exceed $30 billion for the full year, accounting for 45% of Merck's total revenue. Keytruda's success is due to its expanding indications, with approximately 40 indications approved so far.

However, despite the excellent performance of Ivosidenib shown in the HARMONi-2 clinical trial data, there may still be a critical data gap before obtaining approval for marketing by the US FDA.

Citi analyst pointed out that investors' main concern is whether the good PFS results of Akeso's ivosidenib in HARMONi-2 can translate into significant OS benefits, and the FDA generally relies on OS data in the approval of related indications.

Dr. Xia Yu, CEO of Akeso, said in a conference call that based on historical data of immunotherapy, the advantage of ivosidenib in PFS (5.3 months) is likely to translate into OS benefit, and the company is confident about it. Even before obtaining the final OS data, ivosidenib may be approved through the priority review pathway.

According to Citi's analysis, a good PFS HR (HR=0.51 announced this time) is likely to bring clinically meaningful OS benefits (OS HR < 0.8). Positive OS data will also enhance market confidence in the ongoing global phase III HARMONi-3 study (first-line squamous non-small cell lung cancer).

It is worth noting that the market has previously expressed doubts about the performance of the Keytruda combination with lenvatinib in the LEAP-007 study. Although the combination improved PFS by 2.4 months (6.6 months vs 4.2 months, HR 0.78), the OS deteriorated instead (14.1 months vs 16.4 months, HR 1.10).

Dr. Xia Yu explained why ivosidenib is able to translate PFS into OS data.

She said: "Ivosidenib has shown extremely high safety in all patient groups. Akeso's dual antibody platform effectively addresses the hemoptysis and thrombotic side effects induced by VEGF in central squamous cell carcinoma, thereby improving patient tolerance and allowing the drug to fully exert its efficacy on tumors. This is why, in the head-to-head trial with Keytruda, ivosidenib has shown better results and there is great hope to translate PFS into OS."

Another factor to consider is that the HARMONi-2 trial has only recruited Chinese patients, which may lead to differences in the FDA's data requirements in multi-ethnic populations, so Akeso's global clinical trials need to continue to progress.

Another victory for capital and technology?

By the end of 2022, Akeso's Ivo single antibody was licensed to Summit for an upfront payment of $0.5 billion and milestone payments of $5 billion, marking the beginning of Akeso's entry into the international market and opening another capital myth for Summit's CEO Bob Duggan.

Bob Duggan has previously invested in promoting the research and commercialization of the blockbuster drug Imbruvica in the field of hematological malignancies (with sales of $9.8 billion in 2021).

He previously served as CEO of Pharmacyclics, under his leadership, Imbruvica achieved commercial success and was eventually acquired by AbbVie for over $20 billion. Duggan's personal investment return also exceeded $3 billion, and the success of Pharmacyclics made him a billionaire. Now he is trying to replicate this successful model at Summit.

Since 2018, Duggan has gradually purchased Summit shares and became the largest shareholder of the company in 2020, assuming the role of CEO.

After the original drug of Summit failed in phase 3 clinical trials, Summit paid Akeso $0.5 billion in December 2022 to obtain the commercialization rights for Ivo single antibody in the United States and Europe.

Following the release of HARMONi-2 clinical data, Bob Duggan is one step closer to hatching another blockbuster oncology drug.

The success of Ivo single antibody has made Summit one of the best performing biotech companies in the US stock market in 2024, with its stock price rising by 365% year to date and a market cap exceeding $8.8 billion.

Ivo single antibody has also attracted the attention of a top biotech hedge fund, Baker Bros, which disclosed a new position of 23.2 million shares in Summit last month.

Conclusion

The success of innovative drugs is not only a technological breakthrough, but also can achieve better development of innovative drugs by synchronously achieving success in capital.

As a representative of innovative drugs in China, Akeso is likely to be at the peak of the field of tumor drugs, achieving dual success in technology and capital.