Cullinan Oncology and Taiho Pharmaceutical have announced a strategic collaboration worth up to $405 million to jointly develop and commercialize CLN-081/TAS6417, an orally available, irreversible EGFR inhibitor targeting cells with exon 20 insertion mutations in non-small cell lung cancer (NSCLC).
Under the agreement, Taiho will acquire Cullinan Pearl Corp., Cullinan Oncology's subsidiary that holds worldwide rights to CLN-081/TAS6417 outside Japan. The deal includes an upfront payment of $275 million to Cullinan Oncology, with potential for an additional $130 million in regulatory-based milestone payments.
The transaction, expected to close in the second quarter of 2022 subject to customary conditions, represents a significant development for both companies and for patients with this rare form of lung cancer.
A Targeted Approach for an Underserved Patient Population
CLN-081/TAS6417 was specifically engineered to selectively target EGFR exon 20 insertion mutations while sparing wild-type EGFR. This selectivity profile aims to deliver effective treatment with potentially fewer side effects compared to less selective EGFR inhibitors.
EGFR exon 20 insertion mutations affect approximately 2-3% of all NSCLC patients, representing about 38,000 patients worldwide annually. These mutations are associated with poorer outcomes compared to more common EGFR mutations such as exon 19 deletions.
The drug has already received Breakthrough Therapy Designation from the FDA in early 2022, highlighting its potential to address significant unmet needs in this patient population. Currently in Phase I/IIa development, the companies expect to initiate a pivotal study in the second half of 2022.
Strategic Collaboration Structure
The collaboration features a unique structure that benefits both companies:
- Taiho gains exclusive global rights to CLN-081/TAS6417 outside the United States
- Cullinan Oncology retains the option to co-commercialize the drug in the U.S. alongside Taiho Oncology, Inc. (Taiho's U.S. subsidiary)
- Both companies will equally contribute to future clinical development in the U.S.
- Each company will receive 50% of profits from potential U.S. sales
- Taiho will commercialize the drug in territories outside the U.S. and China
"We are excited to embark on this collaboration with Taiho. Taiho is an ideal partner with whom to advance CLN-081/TAS6417 into later stage development and commercialization, given their deep understanding of the molecule and strategic focus on targeted therapies, existing stake in Cullinan Pearl, and strong oncology-focused commercial capabilities in the U.S.," said Nadim Ahmed, Chief Executive Officer of Cullinan Oncology.
Financial Impact and Future Outlook
For Cullinan Oncology, the deal provides substantial financial benefits. The company anticipates its cash runway will extend through 2026 based on current operating plans, considering the upfront payment and reduction in development and pre-commercialization costs.
"Importantly, the structure of the agreement provides the opportunity to efficiently establish our own commercial infrastructure, which will also be leveraged for our future programs," Ahmed noted. "The transaction payments, reduced development expense, and potential ongoing revenue stream upon future commercialization will help us to devote greater resources to advance our robust pipeline of assets across a wide range of modalities."
The deal represents a homecoming of sorts for the molecule. Masayuki Kobayashi, President and Representative Director of Taiho Pharmaceutical, commented, "We are pleased to bring CLN-081/TAS6417 back into our pipeline and move it towards commercialization with Cullinan Oncology. Cullinan Oncology has carried CLN-081/TAS6417 from pre-IND to planned pivotal study in approximately three years."
Rapid Clinical Development
The speed of development for CLN-081/TAS6417 has been notable. Following the original licensing agreement in 2019, Cullinan Pearl rapidly advanced the program, opening an Investigational New Drug application and initiating a global Phase I/IIa study in NSCLC patients harboring EGFR exon 20 mutations.
The FDA's Breakthrough Therapy Designation, granted in early 2022, further validates the drug's potential and may accelerate its path to market. Data from the ongoing clinical trials are expected to be presented at upcoming medical conferences.
Market Context
The collaboration comes at a time of increasing focus on precision medicine approaches in oncology. Targeted therapies for specific genetic mutations have shown promise in improving outcomes while potentially reducing side effects compared to traditional chemotherapy.
In the EGFR exon 20 insertion mutation space, the companies will be competing with Takeda's Exkivity (mobocertinib), which received FDA approval in September 2021 for adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations.
However, Cullinan and Taiho believe CLN-081/TAS6417 has the potential to be best-in-class, with a differentiated profile that could provide advantages in efficacy and tolerability.
Growing Cullinan's Ambitions
The substantial upfront payment structure of this deal is somewhat unusual in the biotech industry, where licensing agreements typically feature smaller upfront payments with larger milestone-based "biobucks" that may never materialize.
Ahmed explained that the drug's Breakthrough designation has "derisked" the asset to some degree, justifying the larger upfront payment. The deal pushes Cullinan's cash reserves past $600 million and enables the company to pursue ambitious growth plans, including potentially doubling its workforce this year.
"As we evolve into a late-stage oncology company, and then ultimately, our aspiration to become an end-to-end fully integrated biotech company, we're going to need those funds to kind of do some of these programs," Ahmed said.
With four additional oncology assets either just launched into the clinic or planned for 2023 entry, Cullinan is positioning itself as an emerging force in targeted oncology therapeutics.
The market responded positively to the announcement, with Cullinan's shares jumping 24% following the news.
