In a blockbuster agreement, Guangzhou’s Akeso (HK: 9926) out-licensed ex-China rights to its bispecific PD-1/VEGF candidate in a deal worth up to $5 billion. Summit Therapeutics (NSDQ: SMMT) of Menlo Park, CA will pay $500 million upfront and up to $4.5 billion in milestones, plus single digit royalties for rights to develop ivonescimab in the US, Canada, Europe and Japan. Akeso, which is developing ivonescimab in Phase III trials for various lung cancer indications, believes its candidate is the most advanced PD-1/VEGF candidate in the world.  

Akeso says ivonescimab combines the power of immunotherapy via a blockade of PD-1 with the anti-angiogenesis benefits of an anti-VEGF in a single molecule. The company believes the novel design has the potential to reduce side effects and improve safety.

In data presented at ASCO 2022, ivonescimab produced an overall response rate of 68% in a Phase II study in patients with NSCLC who had failed EGFR-TKI therapy. The median Progression-Free Survival time was 8.2 months. Ivonescimab patients also received chemotherapy (pemetrexed and carboplatin) as part of the regimen. Chemotherapy (pemetrexed and platinum-based chemotherapy), the current standard of care, has a historical mPFS of 4.3 months.

In a separate cohort, ivonescimab combined with docetaxel in patients who have failed PD-L1 and chemotherapies demonstrated a mPFS of 6.6 months as compared to a historical mPFS of 4.5 months with docetaxel alone.

Currently, Akeso is conducting several Phase III clinical trials:

• Ivonescimab monotherapy versus pembrolizumab monotherapy as a first-line treatment for NSCLC patients with positive PD-L1 expression;
• Ivonescimab plus chemotherapy versus chemotherapy in EGFR mutated advanced non-squamous NSCLC that failed in prior EGFR-TKI therapy.

Ivonescimab has received breakthrough therapy designation status in China from the NMPA for three indications: the two indications, plus a combination with docetaxel to treat locally advanced or metastatic NSCLC patients who failed a regimen of a PD-(L)1 inhibitor combined with platinum-based doublet chemotherapy.

"Ivonescimab has demonstrated the potential to deliver superior clinical benefit for patients." said Dr. Michelle Xia, co-founder, Chairwoman, CEO, and President of Akeso, "The Akeso team has been dedicated to the development of ivonescimab in the past 8 years and advanced the molecule to the clinical Phase III stage. We are so pleased to partner with the world-class Summit team, which has the track record of successfully bringing over a dozen indications to market for the first-in-class blockbuster drug IMBRUVICA® (ibrutinib)."

"The partnership between Summit and Akeso is a strategically compelling opportunity," stated Robert W. Duggan, Chairman and Chief Executive Officer of Summit. "It represents bringing together Akeso's extraordinary team and the talented members of team Summit with their proven track record of success of global clinical development, regulatory approvals, and commercialization, particularly in oncology. We believe the potential exists for enormous creation through this partnership."

"After reviewing a substantial number of opportunities, much of which was focused on potential treatments for solid tumors, we have found the ideal partnership with the potential to change the paradigm for treating patients facing difficult odds with devastating diagnoses," added Dr. Maky Zanganeh, Co-CEO, President, and a member of Summit's Board of Directors. "Ten years ago, metastatic lung cancer patients rarely survived for more than ten to twelve months from diagnosis. Today, survival can be measured in years. Our goal is to improve the quality of life of a patient facing immeasurable odds while extending the duration of that patient's life."

Akeso’s Dr. Michelle Xia will be appointed to the board of directors of Summit.

Akeso was founded in 2012. The company has established a comprehensive in-house drug development platform to build a pipeline of over 30 innovative assets in the fields of cancer, autoimmune disease, inflammation, metabolic disease, and other major therapeutic areas. 17 assets have entered clinical stage. Using an in-house bispecific platform (Tetrabody technology), the company has advanced four potential first-in-class bispecific antibody drugs into the market or clinical development, including cadonilimab (PD-1/CTLA-4), ivonescimab (PD-1/VEGF), PD-1/LAG-3, and TIGIT/TGF-Beta bispecific antibodies.

In June 2022, cadonilimab was approved by the NMPA and became the first commercialized PD-1 based bispecific drug globally. Another oncology product, penpulimab (a PD-1 antibody), was granted marketing approval in China in August 2021.

See our other articles on Akeso.

Disclosure: none.